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Sökning: WFRF:(Holmäng Agneta 1959)

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1.
  • Alexanderson, Camilla, 1978, et al. (författare)
  • A single early postnatal estradiol injection affects morphology and gene expression of the ovary and parametrial adipose tissue in adult female rats.
  • 2010
  • Ingår i: The Journal of steroid biochemistry and molecular biology. - : Elsevier BV. - 1879-1220 .- 0960-0760. ; 122:1-3, s. 82-90
  • Tidskriftsartikel (refereegranskat)abstract
    • Events during early life can affect reproductive and metabolic functions in adulthood. We evaluated the programming effects of a single early postnatal estradiol injection (within 3h after birth) in female rats. We assessed ovarian and parametrial adipose tissue morphology, evaluated gene expression related to follicular development and adipose tissue metabolism, and developed a non-invasive volumetric estimation of parametrial adipose tissue by magnetic resonance imaging. Estradiol reduced ovarian weight, increased antral follicle size and number of atretic antral follicles, and decreased theca interna thickness in atretic antral follicles. Adult estradiol-injected rats also had malformed vaginal openings and lacked corpora lutea, confirming anovulation. Estradiol markedly reduced parametrial adipose tissue mass. Adipocyte size was unchanged, suggesting reduced adipocyte number. Parametrial adipose tissue lipoprotein lipase activity was increased. In ovaries, estradiol increased mRNA expression of adiponectin, complement component 3, estrogen receptor alpha, and glucose transporter 3 and 4; in parametrial adipose tissue, expression of complement component 3 was increased, expression of estrogen receptor alpha was decreased, and expression of leptin, lipoprotein lipase, and hormone-sensitive lipase was unaffected. These findings suggest that early postnatal estradiol exposure of female rats result in long-lasting effects on the ovary and parametrial adipose tissue at adult age.
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2.
  • Alexanderson, Camilla, 1978, et al. (författare)
  • Early postnatal oestradiol exposure causes insulin resistance and signs of inflammation in circulation and skeletal muscle.
  • 2009
  • Ingår i: The Journal of endocrinology. - 1479-6805. ; 201:1, s. 49-58
  • Tidskriftsartikel (refereegranskat)abstract
    • Early postnatal events can predispose to metabolic and endocrine disease in adulthood. In this study, we evaluated the programming effects of a single early postnatal oestradiol injection on insulin sensitivity in adult female rats. We also assessed the expression of genes involved in inflammation and glucose metabolism in skeletal muscle and adipose tissue and analysed circulating inflammation markers as possible mediators of insulin resistance. Neonatal oestradiol exposure reduced insulin sensitivity and increased plasma levels of monocyte chemoattractant protein-1 (MCP-1) and soluble intercellular adhesion molecule-1. In skeletal muscle, oestradiol increased the expression of genes encoding complement component 3 (C3), Mcp-1, retinol binding protein-4 (Rbp4) and transforming growth factor beta1 (Tgfbeta1). C3 and MCP-1 are both related to insulin resistance, and C3, MCP-1 and TGFbeta1 are also involved in inflammation. Expression of genes encoding glucose transporter-4 (Glut 4), carnitine-palmitoyl transferase 1b (Cpt1b), peroxisome proliferator-activated receptor delta (Ppard) and uncoupling protein 3 (Ucp3), which are connected to glucose uptake, lipid oxidation, and energy uncoupling, was down regulated. Expression of several inflammatory genes in skeletal muscle correlated negatively with whole-body insulin sensitivity. In s.c. inguinal adipose tissue, expression of Tgfbeta1, Ppard and C3 was decreased, while expression of Rbp4 and Cpt1b was increased. Inguinal adipose tissue weight was increased but adipocyte size was unaltered, suggesting an increased number of adipocytes. We suggest that early neonatal oestrogen exposure may reduce insulin sensitivity by inducing chronic, low-grade systemic and skeletal muscle inflammation and disturbances of glucose and lipid metabolism in skeletal muscle in adulthood.
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3.
  • Alexanderson, Camilla, 1978, et al. (författare)
  • Postnatal testosterone exposure results in insulin resistance, enlarged mesenteric adipocytes, and an atherogenic lipid profile in adult female rats: comparisons with estradiol and dihydrotestosterone.
  • 2007
  • Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 148:11, s. 5369-76
  • Tidskriftsartikel (refereegranskat)abstract
    • Postnatal events contribute to features of the metabolic syndrome in adulthood. In this study, postnatally administered testosterone reduced insulin sensitivity and increased the mesenteric fat depot, the size of mesenteric adipocytes, serum levels of total cholesterol, low-density lipoprotein cholesterol, and triglycerides, and the atherogenic index in adult female rats. To assess the involvement of estrogen and androgen receptors in these programming effects, we compared testosterone-exposed rats to rats exposed to estradiol or dihydrotestosterone (DHT). Estradiol-treated rats had lower insulin sensitivity than testosterone-treated rats and, like those rats, had enlarged mesenteric adipocytes and increased triglyceride levels. DHT also reduced insulin sensitivity but did not mimic the other metabolic effects of testosterone. All treated rats were probably anovulatory, but only those treated with testosterone had reduced testosterone levels. This study confirms our previous finding that postnatal administration of testosterone reduces insulin sensitivity in adult female rats and shows that this effect is accompanied by unfavorable changes in mesenteric fat tissue and in serum lipid levels. The findings in the estradiol and DHT groups suggest that estrogen receptors exert stronger metabolic programming effects than androgen receptors. Thus, insults such as sex hormone exposure in early life may have long-lasting effects, thereby creating a predisposition to disturbances in insulin sensitivity, adipose tissue, and lipid profile in adulthood.
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4.
  • Améen, Caroline, 1975, et al. (författare)
  • Effects of gender and GH secretory pattern on sterol regulatory element-binding protein-1c and its target genes in rat liver.
  • 2004
  • Ingår i: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 287:6
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigated whether the sexually dimorphic secretory pattern of growth hormone (GH) in the rat regulates hepatic gene expression of sterol regulatory element-binding protein-1c (SREBP-1c) and its target genes. SREBP-1c, fatty acid synthase (FAS), and glycerol-3-phosphate acyltransferase (GPAT) mRNA were more abundant in female than in male livers, whereas acetyl-CoA carboxylase-1 (ACC1) and stearoyl-CoA desaturase-1 (SCD-1) were similarly expressed in both sexes. Hypophysectomized female rats were given GH as a continuous infusion or as two daily injections for 7 days to mimic the female- and male-specific GH secretory patterns, respectively. The female pattern of GH administration increased the expression of SREBP-1c, ACC1, FAS, SCD-1, and GPAT mRNA, whereas the male pattern of GH administration increased only SCD-1 mRNA. FAS and SCD-1 protein levels were regulated in a similar manner by GH. Incubation of primary rat hepatocytes with GH increased SCD-1 mRNA levels and decreased FAS and GPAT mRNA levels but had no effect on SREBP-1c mRNA. GH decreased hepatic liver X receptor-alpha (LXRalpha) mRNA levels both in vivo and in vitro. Feminization of the GH plasma pattern in male rats by administration of GH as a continuous infusion decreased insulin sensitivity and increased expression of FAS and GPAT mRNA but had no effect on SREBP-1c, ACC1, SCD-1, or LXRalpha mRNA. In conclusion, FAS and GPAT are specifically upregulated by the female secretory pattern of GH. This regulation is not a direct effect of GH on hepatocytes and does not involve changed expression of SREBP-1c or LXRalpha mRNA but is associated with decreased insulin sensitivity.
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5.
  • Gabrielsson, Britt, 1957, et al. (författare)
  • Dietary herring improves plasma lipid profiles and reduces atherosclerosis in obese low-density lipoprotein receptor-deficient mice
  • 2012
  • Ingår i: International Journal of Molecular Medicine. - : Spandidos Publications. - 1107-3756 .- 1791-244X. ; 29:3, s. 331-37
  • Tidskriftsartikel (refereegranskat)abstract
    • Diet is a significant modifiable risk factor for cardiovascular disease and high fish intake has been associated with vascular health in population studies. However, intervention studies have been inconclusive. In this study, male low-density lipoprotein receptor-deficient mice were given 16-week high fat/high sucrose diets, supplemented with either minced herring fillets or minced beef. The diets were matched in total fat and cholesterol content; taurine content and fatty acid composition was analysed. Body weights were recorded throughout the study; plasma lipids were analysed at week 8 and 16. Body composition and adipocyte size were evaluated at study end. Atherosclerosis was evaluated at week 12 (ultrasound) and at termination (en face histology). Herring-fed mice had a higher proportion of long-chain n-3 polyunsaturated fatty acids in the hepatic triacylglycerides (TAG) and phospholipid fractions. The herring-fed mice had increased body weight (P=0.007), and reduced epididymal adipocyte size (P=0.009), despite similar food intake and body composition as the beef-fed mice. The herring-fed mice had lower plasma TAG and very-low-density lipoprotein (VLDL)-cholesterol concentrations throughout the study (TAG; P=0.0012 and 0.004, VLDL-cholesterol; P=0.006 and 0.041, week 8 and 16, respectively). At week 16, the herring-fed had higher plasma concentrations of HDL-cholesterol (P=0.004) and less atherosclerotic lesions in the aortic arch (P=0.007) compared with the beef-fed mice. In conclusion, dietary herring in comparison to beef markedly improved vascular health in this mouse model, suggesting that herring provides an added value beyond its content of macronutrients.
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6.
  • Hall, Ulrika Andersson, et al. (författare)
  • Longitudinal changes in adipokines and free leptin index during and after pregnancy in women with obesity.
  • 2020
  • Ingår i: International journal of obesity. - : Springer Science and Business Media LLC. - 1476-5497 .- 0307-0565. ; 44, s. 675-683
  • Tidskriftsartikel (refereegranskat)abstract
    • Detailed data on adipokines and body composition during and after pregnancy in women of different BMI categories are lacking. Furthermore, adipokine regulation during pregnancy and the factors contributing to gestational insulin resistance are not completely understood. The objective was to longitudinally determine adipokine levels, body composition, and insulin sensitivity during and after pregnancy in women of healthy weight (HW) and with obesity (OB), and identify factors associated with insulin resistance.Women (30 HW, 19 OB) underwent blood sampling and body composition examination, by air-displacement plethysmography, longitudinally during pregnancy (trimesters 1, 2, 3) and after pregnancy (6, 12, 18 months postpartum). Serum leptin, soluble leptin receptor (sOB-R), and adiponectin levels were measured and free leptin index (FLI) and homeostatic model assessment of insulin resistance (HOMA-IR) determined.Fat mass and leptin increased during pregnancy in the HW (p<0.01) but not in the OB group. sOB-R increased during pregnancy in both groups (p<0.001). Thus, FLI was unchanged in HW throughout pregnancy but reduced in OB (p=0.001), although consistently higher in OB. Adiponectin decreased in both groups during pregnancy (p<0.001 for HW, p=0.01 for OB). After pregnancy, adiponectin increased in both groups, but more markedly in OB where it reached trimester 1 levels. Multivariable regression identified FLI as the variable most strongly associated with HOMA-IR in all trimesters, but not after pregnancy.Leptin, sOB-R, adiponectin, and FLI undergo marked changes during and after pregnancy with differences in women of different BMI. We suggest that leptin activity is regulated by its soluble receptor and that this is an important factor for optimizing fat mass and insulin sensitivity during pregnancy.
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7.
  • Lager, Susanne, 1978, et al. (författare)
  • Perinatal lack of maternal IL-6 promotes increased adiposity during adulthood in mice.
  • 2011
  • Ingår i: Endocrinology. - : The Endocrine Society. - 1945-7170 .- 0013-7227. ; 152:4, s. 1336-46
  • Tidskriftsartikel (refereegranskat)abstract
    • The perinatal environment appears important in establishing metabolic phenotypes in adulthood. Mice deficient in IL-6 (IL-6(-/-)) tend to develop mature-onset obesity, but it is unknown whether perinatal exposure to IL-6 produced by the dam influences the metabolism of adult offspring. To address this issue, we monitored IL-6(-/-) offspring of IL-6(-/-) or IL-6(+/-) dams, as well as wild-type (WT) mice. At adult age, IL-6(-/-) mice weighed significantly more and had more body fat than WT mice, regardless of maternal genotype, and had lower insulin sensitivity. This phenotype was more pronounced in IL-6(-/-) offspring of IL-6(-/-) dams, because they gained weight significantly faster than IL-6(-/-) offspring of IL-6(+/-) dams and had more body fat and higher serum leptin levels at an earlier age. The leptin content was 2-fold higher in milk from IL-6(-/-) than WT dams. However, cross-fostering IL-6(-/-) mice with WT dams did not alter body weight, body composition, or adipocyte size at adult age compared with IL-6(-/-) mice fostered by IL-6(-/-) dams. Conversely, WT mice fostered by IL-6(-/-) dams weighed significantly more than those fostered by WT dams and had more body fat, larger adipocytes, and altered hypothalamic gene expression. We conclude that body fat of adult mice can be increased by perinatal exposure to factors affected by lack of maternal IL-6.
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8.
  • Lindqvist, Helen, 1977, et al. (författare)
  • Influence of herring (Clupea harengus) and herring fractions on metabolic status in rats fed a high energy diet.
  • 2009
  • Ingår i: Acta physiologica (Oxford, England). - : Wiley. - 1748-1716 .- 1748-1708. ; 196:3, s. 303-14
  • Tidskriftsartikel (refereegranskat)abstract
    • AIM: Few dietary studies have looked beyond fish oil to explain the beneficial metabolic effects of a fish-containing diet. Our aim was to study whether addition of herring, or sub-fractions of herring, could counteract negative metabolic effects known to be induced by a high-fat, high-sugar diet. METHODS: Rats were given six different diets: standard pellets; high energy diet with chicken mince (HiE control); high energy diet with herring mince (HiE herring); and high energy diet with chicken mince and either herring oil (HiE herring oil), herring press juice, PJ (HiE PJ) or herring low molecular weight PJ (HiE LMW-PJ). Factors associated with the metabolic syndrome were measured. RESULTS: There were no differences in energy intake or body weight between the groups, but animals fed high energy diets had a higher body fat content compared with the pellet group, although not statistically significant in all groups. Mesenteric adipocyte size was smaller in the HiE herring oil group compared with the HiE control. Glucose clamp studies showed that, compared with the pellet group, the HiE control and HiE herring diets, but not the HiE herring oil diet, induced insulin resistance. Addition of herring or herring oil to the high energy diet decreased total cholesterol levels, triacylglycerols and the atherogenic index compared with the HiE control group. CONCLUSIONS: The results suggest that addition of herring or herring oil counteracts negative effects on blood lipids induced by a high energy diet. The lipid component of herring thus seems to be responsible for these beneficial effects.
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9.
  • Malmberg, Per, 1974, et al. (författare)
  • A new approach to measuring vitamin D in human adipose tissue using time-of-flight secondary ion mass spectrometry: A pilot study
  • 2014
  • Ingår i: Journal of Photochemistry and Photobiology. B: Biology. - : Elsevier BV. - 1011-1344. ; 138, s. 295-301
  • Tidskriftsartikel (refereegranskat)abstract
    • Circulating concentrations of vitamin D, 25(OH)D, and 1,25(OH)2D are lower in obese than lean individuals, but little is known about the adipose tissue content of these molecules. The aim of this study was to explore the possibility to use time-of-flight secondary ion mass spectrometry (TOF-SIMS) to measure vitamin D and its metabolites in fat tissue in obese and lean subjects. Abdominal subcutaneous adipose tissue (SAT) biopsies were obtained from three lean and three obese women, and paired biopsies SAT and visceral adipose tissue (VAT) were obtained from three obese subjects during gastric bypass surgery. TOF-SIMS was used to measure vitamin D3, 25(OH)D3, and 1,25(OH)2D3 in adipose tissue. We found that vitamin D3, 25(OH)D3, and 1,25(OH)2D3 in adipose tissue can be measured with TOF-SIMS. In adipose tissue, vitamin D3 and its metabolites were located in adipocyte lipid droplets. The content of vitamin D3 (P = 0.006) and 25(OH)D3 (P = 0.018) were lower in SAT in obese compared with lean women. TOF-SIMS has the potential to semi-quantitatively measure vitamin D metabolites in adipose tissue, and offers a possibility to compare vitamin D levels in different depots and groups of individuals. It also gives the opportunity to explore the localization of vitamin D metabolites at a cellular level.
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10.
  • Mannerås, Louise, 1980, et al. (författare)
  • A new rat model exhibiting both ovarian and metabolic characteristics of polycystic ovary syndrome.
  • 2007
  • Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 148:8, s. 3781-91
  • Tidskriftsartikel (refereegranskat)abstract
    • Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder associated with ovulatory dysfunction, hyperandrogenism, abdominal obesity, and insulin resistance. However, its etiology is unclear, and its management is often unsatisfactory or requires a diversified approach. Here, we describe a new rat PCOS model, the first to exhibit both ovarian and metabolic characteristics of the syndrome. Female rats received the nonaromatizable androgen dihydrotestosterone (DHT) or the aromatase inhibitor letrozole by continuous administration, beginning before puberty, to activate androgen receptors. Adult DHT rats had irregular cycles, polycystic ovaries characterized by cysts formed from atretic follicles, and a diminished granulosa layer. They also displayed metabolic features, including increased body weight, increased body fat, and enlarged mesenteric adipocytes, as well as elevated leptin levels and insulin resistance. All letrozole rats were anovulatory and developed polycystic ovaries with structural changes strikingly similar to those in human PCOS. Our findings suggest that the formation of a "hyperplastic" theca interna reflects the inclusion of luteinized granulosa cells in the cyst wall rather than true hyperplasia. We conclude that the letrozole model is suitable for studies of the ovarian features of human PCOS, while the DHT model is suitable for studies of both ovarian and metabolic features of the syndrome.
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11.
  • Mannerås, Louise, 1980, et al. (författare)
  • Low-frequency electro-acupuncture and physical exercise improve metabolic disturbances and modulate gene expression in adipose tissue in rats with dihydrotestosterone-induced polycystic ovary syndrome.
  • 2008
  • Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 149:7, s. 3559-68
  • Tidskriftsartikel (refereegranskat)abstract
    • Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder associated with ovulatory dysfunction, hyperandrogenism, abdominal obesity, and insulin resistance. Pharmacotherapy is often unsatisfactory. This study evaluates the effects of low-frequency electro-acupuncture (EA) and physical exercise on metabolic disturbances and adipose tissue mRNA expression of selected genes in a rat PCOS model characterized by insulin resistance and adiposity. Dihydrotestosterone (inducing PCOS) or vehicle (control) was administrated continuously, beginning before puberty. At age 10 wk, PCOS rats were randomly divided into three groups; PCOS, PCOS EA, and PCOS exercise. PCOS EA rats received 2-Hz EA (evoking muscle twitches) three times/wk during 4-5 wk. PCOS exercise rats had free access to a running wheel for 4-5 wk. EA and exercise improved insulin sensitivity, measured by clamp, in PCOS rats. Exercise also reduced adiposity, visceral adipocyte size, and plasma leptin. EA increased plasma IGF-I. Real-time RT-PCR revealed increased expression of leptin and IL-6 and decreased expression of uncoupling protein 2 in visceral adipose tissue of PCOS rats compared with controls. EA restored the expression of leptin and uncoupling protein 2, whereas exercise normalized adipose tissue leptin and IL-6 expression in PCOS rats. Thus, EA and exercise ameliorate insulin resistance in rats with PCOS. This effect may involve regulation of adipose tissue metabolism and production because EA and exercise each partly restore divergent adipose tissue gene expression associated with insulin resistance, obesity, and inflammation. In contrast to exercise, EA improves insulin sensitivity and modulates adipose tissue gene expression without influencing adipose tissue mass and cellularity.
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12.
  • Svensson, Henrik, 1982, et al. (författare)
  • Adipose tissue and body composition in women six years after gestational diabetes: factors associated with development of type 2 diabetes.
  • 2018
  • Ingår i: Adipocyte. - : Informa UK Limited. - 2162-397X .- 2162-3945. ; 7:4, s. 229-237
  • Tidskriftsartikel (refereegranskat)abstract
    • Factors differentiating women at highest risk of progression to type 2 diabetes mellitus (T2DM) after gestational diabetes mellitus (GDM) are incompletely known. Our aim was to characterize adipose tissue and body composition in relation to glucose metabolism in women with a history of GDM and to identify factors associated with development of T2DM. We examined glucose tolerance (OGTT), insulin sensitivity (HOMA-IR), body composition (anthropometry, air displacement plethysmography), and blood chemistry in 39 women 6years after GDM. An adipose tissue biopsy was obtained to assess the size, number, and lipolytic activity of adipocytes, and adipokine release and density of immune cells and blood vessels in adipose tissue. Normal glucose tolerance (NGT) was identified in 31 women and impaired glucose metabolism (IGM) in 8. Women with IGM had higher BMI/fat mass, and related expected adipose tissue features, than women with NGT. Ethnicity was similar in the groups, but numerically there was a higher proportion of European women in the NGT group and a higher proportion of non-European women in the IGM group. BMI was the best discriminator of NGT versus IGM (multivariable logistic regression: OR=1.34, P<0.01). Waist-to-height ratio and adipocyte volume were most strongly associated with HOMA-IR (multivariable linear regression: R2=0.656, P<0.001). After adjustment for BMI/ethnicity, women with IGM had increased serum adipocyte fatty acid-binding protein, weight gain after index pregnancy, and a lower proportion of fat-free mass. These factors, together with high BMI, abdominal fat distribution, and enlarged adipocytes, may increase the risk of progression to T2DM after GDM.
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13.
  • Svensson, Henrik, 1982, et al. (författare)
  • Body fat mass and the proportion of very large adipocytes in pregnant women are associated with gestational insulin resistance.
  • 2016
  • Ingår i: International journal of obesity (2005). - : Springer Science and Business Media LLC. - 1476-5497 .- 0307-0565. ; 40, s. 646-653
  • Tidskriftsartikel (refereegranskat)abstract
    • Pregnancy is accompanied by fat gain and insulin resistance. Changes in adipose tissue morphology and function during pregnancy and factors contributing to gestational insulin resistance are incompletely known. We sought to characterize adipose tissue in trimesters 1 and 3 (T1/T3) in normal weight (NW) and obese pregnant women, and identify adipose tissue-related factors associated with gestational insulin resistance.
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14.
  • Svensson, Henrik, 1982, et al. (författare)
  • Free lipid and computerized determination of adipocyte size.
  • 2018
  • Ingår i: Adipocyte. - : Informa UK Limited. - 2162-397X .- 2162-3945. ; 7:3, s. 180-182
  • Tidskriftsartikel (refereegranskat)abstract
    • The size distribution of adipocytes in a suspension, after collagenase digestion of adipose tissue, can be determined by computerized image analysis. Free lipid, forming droplets, in such suspensions implicates a bias since droplets present in the images may be identified as adipocytes. This problem is not always adjusted for and some reports state that distinguishing droplets and cells is a considerable problem. In addition, if the droplets originate mainly from rupture of large adipocytes, as often described, this will also bias size analysis. We here confirm that our ordinary manual means of distinguishing droplets and adipocytes in the images ensure correct and rapid identification before exclusion of the droplets. Further, in our suspensions, prepared with focus on gentle handling of tissue and cells, we find no association between the amount of free lipid and mean adipocyte size or proportion of large adipocytes.
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15.
  • Alexanderson, Camilla, 1978, et al. (författare)
  • Influence of having a male twin on body mass index and risk for dyslipidemia in middle-aged and old women.
  • 2011
  • Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 35, s. 1466-1469
  • Tidskriftsartikel (refereegranskat)abstract
    • Background:Animal experiments suggest that exposure to elevated levels of androgens during development by means of so-called hormonal programming causes metabolic aberrations at adulthood. An indirect strategy to address the possible importance of such an influence also in humans would be to study female dizygotic twins, presuming that those with a twin brother-due to diffusion of testosterone-have been exposed to higher androgen levels prenatally.Design:We have compared 8409 women with a male twin with 9166 women with a dizygotic female twin with respect to self-reported indices of anthropometry and metabolic aberrations at age 42 or older.Results:Body mass index (BMI), body weight and rate of dyslipidemia were moderately, but significantly, higher in women from opposite-sexed (OS) twin pairs; splitting for age revealed this difference to be present in those 60 years of age only.Conclusion:The results (i) support the notion that comparisons of women with a twin brother with women from same-sexed twin pairs may be used to shed light on possible long-term effects of interindividual variations in early androgen exposure, and (ii) suggest that the effects of early androgen exposure on metabolism previously observed in animal experiments are of relevance also for humans.International Journal of Obesity advance online publication, 8 March 2011; doi:10.1038/ijo.2011.18.
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16.
  • Andersen, E., et al. (författare)
  • Environmental factors influence the epigenetic signature of newborns from mothers with gestational diabetes
  • 2019
  • Ingår i: Epigenomics. - : Future Medicine Ltd. - 1750-1911 .- 1750-192X. ; 11:8, s. 861-873
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: To investigate the degree by which epigenetic signatures in children from mothers with gestational diabetes mellitus (GDM) are influenced by environmental factors. Methods: We profiled the DNA methylation signature of blood from lean, obese and GDM mothers and their respective newborns. Results: DNA methylation profiles of mothers showed high similarity across groups, while newborns from GDM mothers showed a marked distinct epigenetic profile compared with newborns of both lean and obese mothers. Analysis of variance in DNA methylation levels between newborns showed higher variance in the GDM group. Conclusion: Our results suggest that environmental factors, rather than direct transmission of epigenetic marks from the mother, are involved in establishing the epigenetic signature associated with GDM. © 2019 Romain Barrès.
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17.
  • Andersson Hall, Ulrica, et al. (författare)
  • Growth differentiation factor 15 increases in both cerebrospinal fluid and serum during pregnancy
  • 2021
  • Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 16:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim Growth differentiation factor 15 (GDF15) increases in serum during pregnancy to levels not seen in any other physiological state and is suggested to be involved in pregnancy-induced nausea, weight regulation and glucose metabolism. The main action of GDF15 is regulated through a receptor of the brainstem, i.e., through exposure of GDF15 in both blood and cerebrospinal fluid (CSF). The aim of the current study was to measure GDF15 in both CSF and serum during pregnancy, and to compare it longitudinally to non-pregnant levels. Methods Women were sampled at elective caesarean section (n = 45, BMI = 28.15.0) and were followed up 5 years after pregnancy (n = 25). GDF15, insulin and leptin were measured in CSF and serum. Additional measurements included plasma glucose, and serum adiponectin and Hs-CRP. Results GDF15 levels were higher during pregnancy compared with follow-up in both CSF (385 +/- 128 vs. 115 +/- 32 ng/l, P<0.001) and serum (7378929198 vs. 404 +/- 102 ng/l, P<0.001). CSF levels correlated with serum levels during pregnancy (P<0.001), but not in the non-pregnant state (P = 0.98). Both CSF and serum GDF15 were highest in women carrying a female fetus (P<0.001). Serum GDF15 correlated with the homeostatic model assessment for beta-cell function and placental weight, and CSF GDF15 correlated inversely with CSF insulin levels. Conclusion This, the first study to measure CSF GDF15 during pregnancy, demonstrated increased GDF15 levels in both serum and CSF during pregnancy. The results suggest that effects of GDF15 during pregnancy can be mediated by increases in both CSF and serum levels.
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18.
  • Andersson Hall, Ulrica, et al. (författare)
  • Growth-differentiation-factor 15 levels in obese and healthy pregnancies: Relation to insulin resistance and insulin secretory function
  • 2021
  • Ingår i: Clinical Endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 95:1, s. 92-100
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective/Aim: Growth-differentiation-factor 15 (GDF15) has been suggested to improve or protect beta cell function. During pregnancy, beta cell numbers and function increase to overcome the natural rise in insulin resistance during gestation. In this study, we longitudinally measured serum GDF15 levels during and after pregnancy in women of normal weight (NW) and in women with obesity (OB) and explored associations between GDF15 and changes in beta cell function by homeostatic model assessment (HOMA). Methods: The cohort participants were 38 NW (BMI 22.3 +/- 1.7) and 35 OB (BMI 35.8 +/- 4.2). Blood was sampled and body composition measured at each trimester (T1, T2, and T3) and at 6, 12 and 18 months postpartum. Fasting glucose, insulin and GDF15 were measured, and HOMA for insulin resistance (HOMA-IR) and beta cell function (HOMA-B) determined. Results: GDF15 levels increased significantly each trimester and were similar to 200-fold higher at T3 than in the nonpregnant postpartum state. GDF15 was higher in NW than OB during pregnancy, but was reversed after pregnancy with a significant interaction effect. GDF15 correlated inversely with BMI and fat-free mass at T3. Low GDF15 was associated with lower incidence of nausea and with carrying a male foetus. The pregnancy induced increase in GDF15 associated with increased HOMA-B in OB and with reduced fasting glucose in all women. Conclusion: Large gestational upregulation of GDF15 levels may help increase insulin secretory function to overcome pregnancy-induced insulin resistance.
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19.
  • Andersson Hall, Ulrica, et al. (författare)
  • Physical activity during pregnancy and association with changes in fat mass and adipokines in women of normal-weight or with obesity
  • 2021
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Adipose tissue and adipokine concentrations change markedly during pregnancy, but the effects of physical activity on these changes are rarely studied. We aimed to assess physical activity levels in pregnant women of normal-weight (NW) or with obesity (OB), and to determine the relation with changes in fat mass and adipokines. In each trimester, pregnant women (136 NW, 51 OB) were interviewed about their physical activity and had their body composition, leptin, soluble leptin receptor (sOB-R) and adiponectin determined. NW reported higher activity and more aerobic exercise than OB during early pregnancy. Both groups maintained training frequency but reduced overall activity as pregnancy progressed. NW women reporting aerobic and/or resistance exercise and OB women reporting aerobic exercise had greater sOB-R increases (independent of BMI or gestational weight gain). In NW, exercise also associated with lower fat mass and leptin increases. Higher activity levels associated with lower gestational weight gain in both groups. The relationship between physical activity and adiponectin differed between NW and OB. Maternal exercise may partly mediate its beneficial effects through regulation of leptin bioavailability, by enhancing pregnancy-induced increases in sOB-R. This could be of particular importance in OB with pre-gestational hyperleptinemia and leptin resistance.
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20.
  • Bosaeus, Marja, et al. (författare)
  • A randomized longitudinal dietary intervention study during pregnancy: effects on fish intake, phospholipids, and body composition
  • 2015
  • Ingår i: Nutrition Journal. - : Springer Science and Business Media LLC. - 1475-2891. ; 14:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Fish and meat intake may affect gestational weight gain, body composition and serum fatty acids. We aimed to determine whether a longitudinal dietary intervention during pregnancy could increase fish intake, affect serum phospholipid fatty acids, gestational weight gain and body composition changes during pregnancy in women of normal weight participating in the Pregnancy Obesity Nutrition and Child Health study. A second aim was to study possible effects in early pregnancy of fish intake and meat intake, respectively, on serum phospholipid fatty acids, gestational weight gain, and body composition changes during pregnancy. Methods In this prospective, randomized controlled study, women were allocated to a control group or to a dietary counseling group that focused on increasing fish intake. Fat mass and fat-free mass were measured by air-displacement plethysmography. Reported intake of fish and meat was collected from a baseline population and from a subgroup of women who participated in each trimester of their pregnancies. Serum levels of phospholipid arachidonic acid (s-ARA), eicosapentaenoic acid (s-EPA), and docosahexaenoic acid (s-DHA) were measured during each trimester. Results Weekly fish intake increased only in the intervention group (n=18) from the first to the second trimester (median difference 113 g, p=0.03) and from the first to the third trimester (median difference 75 g, p=0.01). In the first trimester, fish intake correlated with s-EPA (r=0.36, p=0.002, n=69) and s-DHA (r=0.34, p=0.005, n=69), and meat intake correlated with s-ARA (r=0.28, p=0.02, n=69). Fat-free mass gain correlated with reported meat intake in the first trimester (r=0.39, p=0.01, n=45). Conclusions Dietary counseling throughout pregnancy could help women increase their fish intake. Intake of meat in early pregnancy may increase the gain in fat-free mass during pregnancy.
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21.
  • Bosaeus, Marja, et al. (författare)
  • Accuracy of quantitative magnetic resonance and eight-electrode bioelectrical impedance analysis in normal weight and obese women.
  • 2014
  • Ingår i: Clinical Nutrition. - : Elsevier BV. - 0261-5614. ; 33:3, s. 471-477
  • Tidskriftsartikel (refereegranskat)abstract
    • Background & aims Quantitative magnetic resonance (QMR) has previously been shown to both overestimate and underestimate average fat mass (FM) in humans. Eight-electrode bioelectrical impedance analysis (BIA) has previously been found biased as well as successfully validated. We report cross-sectional accuracy of QMR and eight-electrode BIA evaluated with air displacement plethysmography (ADP) as reference method. Methods Fat mass and fat free mass (FFM) by QMR and eight-electrode BIA were evaluated against ADP as reference in 38 normal weight and 30 obese women. Total body water estimates by QMR and eight-electrode BIA were compared. Results Fat mass was overestimated by QMR (1 ± 2 kg, p < 0.001) and was underestimated by eight-electrode BIA (1 ± 3 kg, p = 0.03, Bonferroni adjusted p = 0.29) in normal weight women. Fat mass was underestimated by both QMR (2 ± 2 kg, p < 0.001) and eight-electrode BIA (9 ± 3 kg, p < 0.001) in obese women. Fat free mass biases were of similar magnitude but in opposite direction to FM biases. Total body water estimates were larger by eight-electrode BIA compared to QMR (1–10 kg). Conclusions Fat mass and FFM by QMR were both biased but in opposite directions in both normal weight and obese women. Eight-electrode BIA FM and FFM estimates were imprecise and biased in obese women. Thus, QMR is more precise and more accurate than eight-electrode BIA for estimating body composition in women, but is not accurate enough to be used for individual single assessment of body composition.
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22.
  • Bosaeus, Marja, et al. (författare)
  • Body Composition During Pregnancy: Longitudinal Changes and Method Comparisons
  • 2020
  • Ingår i: Reproductive Sciences. - : Springer Science and Business Media LLC. - 1933-7191 .- 1933-7205. ; :27, s. 1477-1489
  • Tidskriftsartikel (refereegranskat)abstract
    • The Pregnancy Obesity Nutrition and Child Health study is a longitudinal study of reproductive health. Here we analyzed body composition of normal-weight and obese Swedish women by three methods during each trimester of pregnancy. Cross-sectional and longitudinal fat mass estimates using quantitative magnetic resonance (QMR) and bioelectrical impedance analysis (BIA) (Tanita MC-180MA-III) were compared with fat mass determined by air displacement plethysmography (ADP) in pregnancy weeks 8-12, 24-26, and 35-37 in normal-weight women (n = 122, BMI = 22.1 +/- 1.6 kg/m(2)) and obese women (n = 29, BMI = 34.6 +/- 3.6 kg/m(2)). ADP results were calculated from pregnancy-adjusted fat-free mass densities. Mean fat mass by QMR and ADP were similar in obese women, although with wide limits of agreement. In normal-weight women, QMR overestimated mean fat mass in all trimesters, with systematic overestimation at low fat mass values in trimesters 1 and 3. In obese women, fat mass by BIA was grossly underestimated and imprecise in all trimesters, especially at higher values in trimester 2. In normal-weight women, fat mass by BIA was moderately lower than by ADP in trimester 1, similar in trimester 2, and moderately higher in trimester 3. QMR and ADP assessed fat mass changes similarly in obese women, whereas BIA overestimated fat mass changes in normal-weight women. Mean fat mass and fat mass changes by QMR and pregnancy-adjusted ADP were similar in pregnant obese women. Mean fat mass by QMR and fat mass changes by BIA were higher than corresponding values determined by pregnancy-adjusted ADP in normal-weight women.
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23.
  • Brackmann, Christian, 1973, et al. (författare)
  • Nonlinear microscopy of lipid storage and fibrosis in muscle and liver tissues of mice fed high-fat diets
  • 2010
  • Ingår i: Journal of Biomedical Optics. - : SPIE-Intl Soc Optical Eng. - 1083-3668 .- 1560-2281. ; 15:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Hallmarks of high-fat Western diet intake, such as excessive lipid accumulation in skeletal muscle and liver as well as liver fibrosis, are investigated in tissues from mice using nonlinear microscopy, second harmonic generation (SHG), and coherent anti-Stokes Raman scattering (CARS), supported by conventional analysis methods. Two aspects are presented; intake of standard chow versus Western diet, and a comparison between two high-fat Western diets of different polyunsaturated lipid content. CARS microscopy images of intramyocellular lipid droplets in muscle tissue show an increased amount for Western diet compared to standard diet samples. Even stronger diet impact is found for liver samples, where combined CARS and SHG microscopy visualize clear differences in lipid content and collagen fiber development, the latter indicating nonalcoholic fatty liver disease (NAFLD) and steatohepatitis induced at a relatively early stage for Western diet. Characteristic for NAFLD, the fibrous tissue-containing lipids accumulate in larger structures. This is also observed in CARS images of liver samples from two Western-type diets of different polyunsaturated lipid contents. In summary, nonlinear microscopy has strong potential (further promoted by technical advances toward clinical use) for detection and characterization of steatohepatitis already in its early stages.
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24.
  • Bromander, Sara, et al. (författare)
  • Cerebrospinal fluid insulin during non-neurological surgery.
  • 2010
  • Ingår i: J Neural Transm (Vienna, Austria:1996). - : Springer Science and Business Media LLC. - 1435-1463 .- 0300-9564. ; 20, s. 328-329
  • Tidskriftsartikel (refereegranskat)abstract
    • Insulin plays an important metabolic and transmitter role in the central nervous system, but few studies have investigated the relationship between central and peripheral insulin concentrations. 35 patients undergoing knee surgery had cerebrospinal fluid (CSF) samples drawn before, 3 h after, and in the morning following surgery. Serum insulin concentrations increased after surgery and CSF insulin concentrations changed in the same direction with far smaller amplitude. These results indicate that the blood-brain barrier protects the brain from stress-induced peripheral hormonal fluctuations.
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25.
  • Chorell, Elin, et al. (författare)
  • Pregnancy to postpartum transition of serum metabolites in women with gestational diabetes
  • 2017
  • Ingår i: Metabolism-Clinical and Experimental. - : Elsevier BV. - 0026-0495 .- 1532-8600. ; 72, s. 27-36
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. Gestational diabetes is commonly linked to development of type 2 diabetes mellitus (T2DM). There is a need to characterize metabolic changes associated with gestational diabetes in order to find novel biomarkers for T2DM. Objective. To find potential pathophysiological mechanisms and markers for progression from gestational diabetes mellitus to T2DM by studying the metabolic transition from pregnancy to postpartum. Design. The metabolic transition profile from pregnancy to postpartum was characterized in 56 women by mass spectrometry-based metabolomics; 11 women had gestational diabetes mellitus, 24 had normal glucose tolerance, and 21 were normoglycaemic but at increased risk for gestational diabetes mellitus. Fasting serum samples collected during trimester 3 (gestational week 32 +/- 0.6) and postpartum (10.5 +/- 0.4 months) were compared in diagnosis-specific multivariate models (orthogonal partial least squares analysis). Clinical measurements (e.g., insulin, glucose, lipid levels) were compared and models of insulin sensitivity and resistance were calculated for the same time period. Results. Women with gestational diabetes had significantly increased postpartum levels of the branched-chain amino acids (BCAAs) leucine, isoleucine, and valine, and their circulating lipids did not return to normal levels after pregnancy. The increase in BCAAs occurred postpartum since the BCAAs did not differ during pregnancy, as compared to normoglycemic women. Conclusions. Postpartum levels of specific BCAAs, notably valine, are related to gestational diabetes during pregnancy. (C) 2017 Elsevier Inc. All rights reserved.
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26.
  • Dahlgren, Jovanna, 1964, et al. (författare)
  • Interleukin-6 in the maternal circulation reaches the rat fetus in mid-gestation
  • 2006
  • Ingår i: Pediatric Research. - 0031-3998 .- 1530-0447. ; 60:2, s. 147-51
  • Tidskriftsartikel (refereegranskat)abstract
    • Maternal systemic infection during pregnancy may expose the fetus to infectious agents and high levels of mediators of the resulting inflammatory response, such as IL-6 (IL-6). Increased fetal and maternal levels of IL-6 have been associated with adverse neonatal outcome but might also stress the fetus and contribute to cardiovascular and neuroendocrine dysfunction in adulthood. It is unclear whether interleukins cross the placental barrier, although this matter has been little studied. The aim of this study was therefore to investigate if IL-6 administered to pregnant rats in vivo is transferred to the fetus. We injected 125I IL-6 i.v. to pregnant dams at gestation day 11-13 (mid-gestation) or 17-19 (late gestation). We found 125I-IL-6 in the exposed fetuses as well as in amniotic fluids. Fetal 125I-IL-6 levels were markedly higher in animals injected in mid-gestation compared with late pregnancy (p < 0.01). This difference was mirrored in a 15-fold higher unidirectional materno-fetal clearance for 125I-IL-6 in mid-gestation (p < 0.01). We conclude that the permeability of the rat placental barrier to IL-6 is much higher in mid-gestation than in late pregnancy. Maternally derived IL-6 may directly induce fetal injury but also stimulate the release of fetal stress hormones resulting in stimuli or insults in neuroendocrine structures and hormonal axes which might lead to disease at adult age.
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27.
  • Dahlgren, Jovanna, 1964, et al. (författare)
  • Prenatal cytokine exposure results in obesity and gender-specific programming.
  • 2001
  • Ingår i: American journal of physiology. Endocrinology and metabolism. - 0193-1849. ; 281:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Prenatal events appear to program hormonal homeostasis, contributing to the development of somatic disorders at an adult age. The aim of this study was to examine whether maternal exposure to cytokines or to dexamethasone (Dxm) would be followed by hormonal consequences in the offspring at adult age. Pregnant rats were injected on days 8, 10, and 12 of gestation with either human interleukin-6 (IL-6) or tumor necrosis factor-alpha (TNF-alpha) or with Dxm. Control dams were injected with vehicle. All exposed offspring developed increased body weight (P < 0.05--0.001), apparently due to an increase of 30--40% in adipose tissue weight (P < 0.05--0.01). Corticosterone response to stress was increased in the IL-6 group (P < 0.05-0.01). Dxm-treated male rats exhibited blunted Dexamethasone suppression test results. In male rats, insulin sensitivity was decreased after IL-6 exposure (P < 0.01), whereas basal insulin was elevated in the TNF-alpha group (P < 0.01). In female rats, plasma testosterone levels were higher in all exposed groups compared with controls (P < 0.01--0.001), with the exception of Dxm-exposed offspring. Males in the TNF-alpha group showed decreased locomotor activity (P < 0.05), and females in the IL-6 group showed increased locomotor activity (P < 0.05). These results indicate that prenatal exposure to cytokines or Dxm leads to increased fat depots in both genders. In females, cytokine exposure was followed by a state of hyperandrogenicity. The results suggest that prenatal exposure to cytokines or Dxm can induce gender-specific programming of neuroendocrine regulation with consequences in adult life.
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28.
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29.
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30.
  • Fagman, Johan Bourghardt, 1980, et al. (författare)
  • The androgen receptor confers protection against diet-induced atherosclerosis, obesity, and dyslipidemia in female mice.
  • 2015
  • Ingår i: FASEB journal : official publication of the Federation of American Societies for Experimental Biology. - : Wiley. - 1530-6860 .- 0892-6638. ; 29:4, s. 1540-1550
  • Tidskriftsartikel (refereegranskat)abstract
    • Androgens have important cardiometabolic actions in males, but their metabolic role in females is unclear. To determine the physiologic androgen receptor (AR)-dependent actions of androgens on atherogenesis in female mice, we generated female AR-knockout (ARKO) mice on an atherosclerosis-prone apolipoprotein E (apoE)-deficient background. After 8 weeks on a high-fat diet, but not on a normal chow diet, atherosclerosis in aorta was increased in ARKO females (+59% vs. control apoE-deficient mice with intact AR gene). They also displayed increased body weight (+18%), body fat percentage (+62%), and hepatic triglyceride levels, reduced insulin sensitivity, and a marked atherogenic dyslipidemia (serum cholesterol, +52%). Differences in atherosclerosis, body weight, and lipid levels between ARKO and control mice were abolished in mice that were ovariectomized before puberty, consistent with a protective action of ovarian androgens mediated via the AR. Furthermore, the AR agonist dihydrotestosterone reduced atherosclerosis (-41%; thoracic aorta), subcutaneous fat mass (-44%), and cholesterol levels (-35%) in ovariectomized mice, reduced hepatocyte lipid accumulation in hepatoma cells in vitro, and regulated mRNA expression of hepatic genes pivotal for lipid homeostasis. In conclusion, we demonstrate that the AR protects against diet-induced atherosclerosis in female mice and propose that this is mediated by modulation of body composition and lipid metabolism.-Fagman, J. B., Wilhelmson, A. S., Motta, B. M., Pirazzi, C., Alexanderson, C., De Gendt, K., Verhoeven, G., Holmäng, A., Anesten, F., Jansson, J. -O., Levin, M., Borén, J., Ohlsson, C., Krettek, A., Romeo, S., Tivesten, A. The androgen receptor confers protection against diet-induced atherosclerosis, obesity, and dyslipidemia in female mice.
  •  
31.
  • Gustavsson, Carolina, et al. (författare)
  • Cerebrospinal fluid levels of insulin, leptin, and agouti-related protein in relation to BMI in pregnant women
  • 2016
  • Ingår i: Obesity. - : Wiley. - 1930-7381. ; 24:6, s. 1299-1304
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveDuring pregnancy, metabolic interactions must be adapted, though neuroendocrine mechanisms for increased food intake are poorly understood. The objective of this study was to characterize differences in insulin, leptin, and agouti-related protein (AgRP) levels in serum and cerebrospinal fluid (CSF) in pregnant women with normal weight (NW) and pregnant women with overweight (OW) or obesity (OB). Placenta as a source for increased peripheral AgRP levels during pregnancy was also investigated. MethodsWomen were recruited at admission for elective cesarean section. Insulin, AgRP, and leptin were measured in serum and CSF from 30 NW, 25 OW, and 21 OB at term. Serum during pregnancy and placenta at term were collected for further AgRP analysis. ResultsImmunohistology showed placental production of AgRP and serum AgRP levels increased throughout pregnancy. CSF AgRP, leptin, and insulin levels were higher in OW and OB than NW. Serum leptin and insulin levels were higher and AgRP lower in OB than NW. ConclusionsHigh serum AgRP levels might protect from the suppressive effects of leptin during pregnancy. Pregnant women with OB and OW might further be protected from the suppressive effect of leptin by high CSF AgRP levels. Evidence was found, for the first time, of human placental AgRP production mirrored by levels in the circulation.
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32.
  • Hall, Ulrika Andersson, et al. (författare)
  • Central and Peripheral Leptin and Agouti-Related Protein during and after Pregnancy in Relation to Weight Change.
  • 2018
  • Ingår i: Clinical endocrinology. - : Wiley. - 1365-2265 .- 0300-0664. ; 88:2, s. 263-271
  • Tidskriftsartikel (refereegranskat)abstract
    • To study changes of neuropeptides and adipokines in cerebrospinal fluid (CSF) and serum from pregnancy to post-pregnancy in relation to weight changes, fat mass and glucose metabolism.With high postpartum weight retention being a risk factor in future pregnancies and of life-long obesity we evaluated neuropeptide and adipokine changes in women who either gained weight or were weight stable.Women were followed for 5±1 years after pregnancy and divided into two groups, Weight-Stable and Weight-Gain, by weight change from start of pregnancy.Twenty-five women (BMI 27±5kg/m2 ) recruited at admission for elective caesarean section.CSF and serum levels of agouti-related protein (AgRP), leptin, and insulin, and serum levels of adiponectin and soluble leptin receptor were measured during and after pregnancy. These measurements were further related to fat mass and insulin sensitivity (HOMA-IR).S-AgRP levels during pregnancy were lower in the Weight-Stable group and a 1 unit increase in s-AgRP was associated with 24% higher odds of pertaining to the Weight-Gain group. After pregnancy, s-AgRP increased in the Weight-Stable group but decreased in the Weight-Gain group. Decreased transport of leptin into CSF during pregnancy was reversed by an increased CSF:serum leptin ratio after pregnancy. In women who returned to their pre-pregnancy weight, serum adiponectin increased after pregnancy and correlated negatively with HOMA-IR.S-AgRP concentration in late pregnancy may be one factor predicting weight change after pregnancy, and circulating AgRP may be physiologically important in the long-term regulation of body weight. This article is protected by copyright. All rights reserved.
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33.
  • Hall, Ulrika Andersson, et al. (författare)
  • Circulating Linoleic Acid is Associated with Improved Glucose Tolerance in Women after Gestational Diabetes
  • 2018
  • Ingår i: Nutrients. - : MDPI AG. - 2072-6643 .- 2072-6643. ; 10:11, s. 1629-
  • Tidskriftsartikel (refereegranskat)abstract
    • Abstract: Women with previously diagnosed gestational diabetes mellitus (GDM) are at increased risk of type-2-diabetes mellitus (T2D).We aimed to establish links between glucose tolerance (GT) and serum fatty acid (FA) profile in the transition from GDM to T2D. Six years after GDM, 221 women were grouped as having normal GT (NGT), impaired GT (IGT), or T2D based on oral GT test results. Fasting serum FAs were profiled, anthropometric measures taken, and dietary intake determined. Linoleic acid (LA) was significantly higher in NGT women (p < 0.001) compared with IGT and T2D, and emerged as a strong predictor of low glucose and insulin levels, independently of BMI. Self-reported vegetable oil consumption correlated with LA serum levels and glucose levels. Delta-6-, delta-9-, and stearoyl-CoA-desaturase activities were associated with decreased GT, and delta-5-desaturase activities with increased GT. In a subgroup of women at high risk of diabetes, low LA and high palmitic acid levels were seen in those that developed T2D, with no differences in other FAs or metabolic measurements. Results suggest that proportions of LA and palmitic acid are of particular interest in the transition from GDM to T2D. Interconversions between individual FAs regulated by desaturases appear to be relevant to glucose metabolism
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34.
  • Hall, Ulrika Andersson, et al. (författare)
  • Exercise, aerobic fitness, and muscle strength in relation to glucose tolerance 6 to 10 years after gestational diabetes
  • 2022
  • Ingår i: Diabetes Research and Clinical Practice. - : Elsevier BV. - 0168-8227. ; 191
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: We sought to identify self-reported exercise and objectively measured fitness variables associated with glucose tolerance and metabolic health 6–10 years after gestational diabetes (GDM) Methods: Women (n = 84) underwent oral glucose tolerance testing (OGTT), body composition measurements, and lifestyle questionnaires 6 and 10 years after GDM. In a subset (n = 45), peak oxygen uptake (VO2peak), peak fat oxidation, and maximal isometric strength of five muscle groups were tested. Results: At 10 years, 41 women (49%) had impaired glucose metabolism or type 2 diabetes (T2D). VO2peak and muscle strength were lowest in the T2D group. In a regression analysis, VO2peak and all strength measurements were associated negatively with HbA1c and waist-hip ratio and positively with high-density lipoprotein cholesterol. However, only muscle strength was associated with fasting and area-under-the-curve glucose. For changes between the 6- and 10-year follow-ups, only muscle strength was associated with HbA1c change, whereas both VO2peak and strength were associated with high-density lipoprotein level and changes in waist-hip ratio. Peak fat oxidation and self-reported physical activity showed no or weak relationships with glycemic variables. Conclusion: Objectively measured fitness variables, particularly muscle strength, were strongly associated with glycemic and other metabolic outcomes in a high-risk group after GDM.
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35.
  • Hall, Ulrika Andersson, et al. (författare)
  • Higher Concentrations of BCAAs and 3-HIB Are Associated with Insulin Resistance in the Transition from Gestational Diabetes to Type 2 Diabetes
  • 2018
  • Ingår i: Journal of Diabetes Research. - : Hindawi Limited. - 2314-6745 .- 2314-6753.
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim. Determine the metabolic profile and identify risk factors of women transitioning from gestational diabetes mellitus (GDM) to type 2 diabetes mellitus (T2DM). Methods. 237 women diagnosed with GDM underwent an oral glucose tolerance test (OGTT), anthropometrics assessment, and completed lifestyle questionnaires six years after pregnancy. Blood was analysed for clinical variables (e.g., insulin, glucose, HbA1c, adiponectin, leptin, and lipid levels) and NMR metabolomics. Based on the OGTT, women were divided into three groups: normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and T2DM. Results. Six years after GDM, 19% of subjects had T2DM and 19% IGT. After BMI adjustment, the IGT group had lower HDL, higher leptin, and higher free fatty acid (FFA) levels, and the T2DM group higher triglyceride, FFA, and C-reactive protein levels than the NGT group. IGT and T2DM groups reported lower physical activity. NMR measurements revealed that levels of branched-chain amino acids (BCAAs) and the valine metabolite 3-hydroxyisobyturate were higher in T2DM and IGT groups and correlated with measures of insulin resistance and lipid metabolism. Conclusion. In addition to well-known clinical risk factors, BCAAs and 3-hydroxyisobyturate are potential markers to be evaluated as predictors of metabolic risk after pregnancy complicated by GDM.
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36.
  • Hall, Ulrika Andersson, et al. (författare)
  • Infant body composition relationship to maternal adipokines and fat mass: the PONCH study
  • 2021
  • Ingår i: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 89, s. 1756-1764
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Infant adiposity is linked to both high maternal fat mass (FM) and excessive gestational FM gain, whereas the association with maternal adipokines is less clear. The aim was to determine how levels of maternal leptin, the soluble leptin receptor (sOB-R), adiponectin, and FM during pregnancy were linked to infant FM in normal-weight (NW) women and women with obesity (OB). Methods Body composition and serum levels of leptin, adiponectin, and sOB-R were determined three times during pregnancy in 80 NW and 46 OB women. For infants, body composition was measured at 1 and 12 weeks of age. Results Maternal leptin and sOB-R levels increased during pregnancy. For NW women, infant FM at 1 week was inversely associated with changes in maternal leptin and at 12 weeks inversely associated with absolute maternal sOB-R levels throughout pregnancy, as well as changes in sOB-R levels in early pregnancy. For OB women, infant FM at both 1 and 12 weeks were best explained by maternal FM. Conclusions Leptin and sOB-R, thought to regulate leptin bioavailability, are associated with fat accumulation in infants born to NW women. In OB women, maternal FM in early pregnancy is more important than leptin in determining infant fat accumulation. Impact In normal-weight women, the regulation of maternal leptin bioavailability during pregnancy has a role in infant fat mass accumulation. In women with obesity, however, pre-pregnancy maternal fat mass seems more important for infant fat mass. This is the first study of maternal adipokines and fat mass including longitudinal measurements in both mothers and their children. Understanding the relationship between maternal factors and infant fat mass is of great importance as obesity is programmed over the generations, and it is important to learn what regulates this programming.
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37.
  • Hall, Ulrika Andersson, et al. (författare)
  • Maternal obesity and gestational diabetes mellitus affect body composition through infancy: the PONCH study
  • 2019
  • Ingår i: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 85:3, s. 369-377
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: To determine how maternal obesity or gestational diabetes mellitus (GDM) affect infant body size and body composition during the first year of life. METHODS: Eighty three normal-weight (NW) women, 26 obese (OB) women, and 26 women with GDM were recruited during pregnancy. Infant body composition was determined by air-displacement plethysmography at 1 and 12 weeks, and anthropometric measurements made until 1 year of age. RESULTS: Girl infants born to OB women and women with GDM had a higher body-fat percentage (BF%) at 1 and 12 weeks of age than girls born to NW women. Girls had higher BF% than boys in OB and GDM groups only. Maternal HbA1c and fasting plasma glucose correlated with girl infant BF% at 1 week of age. Maternal weight at start of pregnancy correlated with birthweight in NW and OB groups, but not the GDM group. OB group infants showed greater BMI increases from 1 week to 1 year than both NW and GDM group infants. CONCLUSION: Results show that both maternal glycaemia and obesity are determinants of increased early life adiposity, especially in girls, with glycaemic levels being more influential than maternal weight for infants born to women with GDM.
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38.
  • Hultman, Karin, 1980, et al. (författare)
  • Maternal taurine supplementation in the late pregnant rat stimulates postnatal growth and induces obesity and insulin resistance in adult offspring
  • 2007
  • Ingår i: J Physiol. ; 579(Pt 3):Jan 11, s. 823-33
  • Tidskriftsartikel (refereegranskat)abstract
    • An adequate supply of taurine during foetal life is important for normal beta-cell development and insulin action and an altered availability of taurine may program glucose metabolism in utero and result in type 2 diabetes in adult age. We examined whether maternal taurine supplementation in late pregnant rats affects postnatal growth, adult body composition, insulin sensitivity and endogenous insulin secretion in intra-uterine growth restricted (IUGR) and normal offspring. Uterine artery ligation or sham operations were performed on gestational day (GD) 19. Taurine supplementation was given to half of the dams from GD 18 until term resulting in four groups of offspring: sham (n= 22), sham/taurine (n= 22), IUGR (n= 22) and IUGR/taurine (n= 24). The offspring were studied at 12 wks of age. In offspring with normal birth weight, foetal taurine supplementation markedly stimulated postnatal growth. In sham/taurine females, fat depots, plasma free fatty acid and leptin concentrations were increased and insulin sensitivity was reduced. Insulin sensitivity was unaltered in IUGR and IUGR/taurine offspring. However, whereas IUGR offspring showed little catch-up growth, 50 % of IUGR/taurine animals displayed complete catch-up at 12 wks of age and these animals had increased fat depots and reduced insulin sensitivity. In conclusion, taurine supplementation in late gestation results in accelerated postnatal growth, which was associated with adult obesity and insulin resistance both in IUGR and normal offspring. This effect was particularly evident in females. These data suggest that foetal taurine availability is an important determinant for postnatal growth, insulin sensitivity and fat accumulation.
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39.
  • Hussain, Ahmed, 1985, et al. (författare)
  • A maternal diet of fatty fish reduces body fat of offspring compared with a maternal diet of beef and a post-weaning diet of fish improves insulin sensitivity and lipid profile in adult C57BL/6 male mice.
  • 2013
  • Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 209:3, s. 220-234
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim The maternal diet during pregnancy and lactation may affect the long-term health of the offspring. Our aim was to study how a fish or meat diet perinatal and after weaning affects body composition, insulin sensitivity and the profile of n-3 and n-6 polyunsaturated fatty acids (PUFAs) in breast milk, fat depots, skeletal muscle and liver in male adult mice offspring. Methods During gestation and lactation, C57BL/6 dams were fed a herring- or beef-based diet. Half of the pups in each group changed diets after weaning. In offspring, body composition measured by DEXA, plasma lipid profile and insulin sensitivity measured by euglycemic clamp or QUICKI were monitored to adulthood. Analysis of total FAs by GC-MS were performed in the diet, breast milk and in different tissues. Results At 9 week of age, offspring of herring-fed dams had less body fat than offspring of beef-fed dams. Mice fed herring after weaning had increased insulin sensitivity at 15 week of age, reduced total plasma cholesterol and triglyceride levels, and compared with beef-fed mice, larger interscapular brown adipose tissue depots. The FA composition of the maternal diet was mirrored in breast milk, and the herring diet significantly affected the FA profile of different tissues, leading to an increased content of n-3 PUFAs. Conclusion A herring-based maternal diet reduces body fat in the offspring, but the insulin sensitivity, plasma lipids and amount of brown adipose tissue are affected by the offspring's own diet; the herring diet is more beneficial than the beef diet.
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40.
  • Hussain, Ays, et al. (författare)
  • Maternal beef and postweaning herring diets increase bone mineral density and strength in mouse offspring.
  • 2013
  • Ingår i: Experimental biology and medicine (Maywood, N.J.). - : SAGE Publications. - 1535-3699 .- 1535-3702. ; 238:12, s. 1362-9
  • Tidskriftsartikel (refereegranskat)abstract
    • The maternal diet during gestation and lactation affects the long-term health of the offspring. We sought to determine whether maternal and postweaning crossover isocaloric diets based on fish or meat affect the geometry, mineral density, and biomechanical properties of bone in mouse offspring in adulthood. During gestation and lactation, C57BL/6 dams were fed a herring- or beef-based diet. After weaning, half of the pups in each group were fed the same diet as their dams, and half were fed the other diet. Areal bone mineral density (aBMD) and bone mineral content (BMC) of the whole body and lumbar spine were measured in the offspring by dual X-ray absorptiometry at 9 and 21 weeks of age. At 22-26 weeks, tibia bone geometry (length, cortical volumetric (v) BMD, BMC, area and thickness) was analyzed by peripheral quantitative computed tomography, and the biomechanical properties of the tibia were analyzed by the three-point bending test. Plasma insulin-like growth factor-1 was analyzed at 12 weeks. In comparison to the maternal herring diet, the maternal beef diet increased aBMD and BMC in the whole body and lumbar spine of adult offspring, as well as cortical vBMD, BMC, bone area, and thickness at the mid-diaphyseal region of the tibia and the biomechanical properties of tibia strength. In contrast, a postweaning beef diet decreased aBMD in the lumbar spine and BMC in the whole body and lumbar spine compared with a postweaning herring diet, which instead increased plasma insulin-like growth factor-1 levels. The change from a maternal beef diet before weaning to a herring diet after weaning decreased body weight and increased the cortical area, vBMD, BMC, thickness, and strength of the tibia. These significant crossover effects indicate that a preweaning maternal beef diet and a postweaning herring diet are optimal for increasing BMC and bone strength in offspring in adulthood.
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41.
  • Johansson, Maria E, 1977, et al. (författare)
  • Hyperinsulinemic rats are normotensive but sensitized to angiotensin II.
  • 2008
  • Ingår i: American Journal of Physiology. Regulatory Integrative and Comparative Physiology (USA). - : American Physiological Society. - 0363-6119 .- 0363-6119 .- 1522-1490. ; 294:4
  • Tidskriftsartikel (refereegranskat)abstract
    • The effect of insulin on blood pressure (BP) is debated, and an involvement of an activated renin-angiotensin aldosterone system (RAAS) has been suggested. We studied the effect of chronic insulin infusion on telemetry BP and assessed sympathetic activity and dependence of the RAAS. Female Sprague-Dawley rats received insulin (2 units/day, INS group, n = 12) or insulin combined with losartan (30 mg.kg(-1).day(-1), INS+LOS group, n = 10), the angiotensin II receptor antagonist, for 6 wk. Losartan-treated (LOS group, n = 10) and untreated rats served as controls (n = 11). We used telemetry to measure BP and heart rate (HR), and acute ganglion blockade and air-jet stress to investigate possible control of BP by the sympathetic nervous system. In addition, we used myograph technique to study vascular function ex vivo. The INS and INS+LOS groups developed euglycemic hyperinsulinemia. Insulin did not affect BP but increased HR (27 beats/min on average). Ganglion blockade reduced mean arterial pressure (MAP) similarly in all groups. Air-jet stress did not increase sympathetic reactivity but rather revealed possible blunting of the stress response in hyperinsulinemia. Chronic losartan markedly reduced 24-h-MAP in the INS+LOS group (-38 +/- 1 mmHg P < 0.001) compared with the LOS group (-18 +/- 1 mmHg, P
  •  
42.
  • Karlsson, Therese, 1979, et al. (författare)
  • Increased vitamin D-binding protein and decreased free 25(OH)D in obese women of reproductive age.
  • 2014
  • Ingår i: European journal of nutrition. - : Springer Science and Business Media LLC. - 1436-6215 .- 1436-6207. ; 53:1, s. 259-267
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: Obese subjects have lower circulating 25-hydroxyvitamin D (25(OH)D) than normal-weight subjects. Knowledge is scarce regarding differences in vitamin D-binding protein (DBP), free 25(OH)D, and intake of vitamin D between normal-weight and obese subjects. The purpose of this study was to examine intake and vitamin D status in obese compared with normal-weight women. METHODS: Between September 2009 and October 2011, 43 obese and 43 normal-weight women, 22-45years of age, mean BMI of 39.1±4.6 and 21.6±1.8kg/m(2), respectively, were recruited in the western Sweden region (latitude 57°N). Blood samples, data regarding diet, and sun exposure were collected. RESULTS: DBP concentrations were 320±121 and 266±104μg/mL (P=0.02) in obese and normal-weight women, respectively. Calculated free 25(OH)D was 13.3±5.5 (obese) and 23.7±10.7 (normal-weight) (P<0.001). The obese women had a 20.1nmol/L lower mean 25(HO)D concentration compared to normal-weight women (P<0.001). 56% of obese women and 12% of normal-weight women had 25(OH)D concentrations ≤50nmol/L. There was no statistically significant difference in total vitamin D intake between the groups. 39% of the women had a total vitamin D intake <7.5μg/day, the current national recommendation for vitamin D in Sweden. CONCLUSIONS: Obese women had higher DBP concentrations compared with normal-weight women and lower free 25(OH)D. The obese women were more likely to have 25(OH)D concentrations that could be considered suboptimal. Vitamin D intake was generally low in normal-weight and obese women of childbearing age.
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43.
  •  
44.
  • Korotkova, Marina, 1954, et al. (författare)
  • Gender-related long-term effects in adult rats by perinatal dietary ratio of n-6/n-3 fatty acids.
  • 2005
  • Ingår i: American journal of physiology. Regulatory, integrative and comparative physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 288:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Epidemiological studies in humans have shown that perinatal nutrition affects health later in life. We have previously shown that the ratio of n-6 to n-3 polyunsaturated fatty acids (PUFA) in the maternal diet affects serum leptin levels and growth of the suckling pups. The aim of the present study was to investigate the long-term effects of various ratios of the dietary n-6 and n-3 PUFA during the perinatal period on serum leptin, insulin, and triacylglycerol, as well as body growth in the adult offspring. During late gestation and throughout lactation, rats were fed an isocaloric diet containing 7 wt% fat, either as linseed oil (n-3 diet), soybean oil (n-6/n-3 diet), or sunflower oil (n-6 diet). At 3 wk of age, the n-6/n-3 PUFA ratios in the serum phospholipids of the offspring were 2.5, 8.3, and 17.5, respectively. After weaning, all pups were given a standard chow. At the 28th postnatal wk, mean body weight and fasting insulin levels were significantly increased in the rats fed the n-6/n-3 diet perinatally compared with the other groups. The systolic blood pressure and serum triacylglycerol levels were only increased in adult male rats of the same group. These data suggest that the balance between n-6 and n-3 PUFA during perinatal development affects several metabolic parameters in adulthood, especially in the male animals.
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45.
  • Kristiansson, Emilia, 1994, et al. (författare)
  • Validation of Oura ring energy expenditure and steps in laboratory and free-living
  • 2023
  • Ingår i: BMC Medical Research Methodology. - : Springer Science and Business Media LLC. - 1471-2288. ; 23
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundCommercial activity trackers are increasingly used in research and compared with research-based accelerometers are often less intrusive, cheaper, with improved storage and battery capacity, although typically less validated. The present study aimed to determine the validity of Oura Ring step-count and energy expenditure (EE) in both laboratory and free-living.MethodsOura Ring EE was compared against indirect calorimetry in the laboratory, followed by a 14-day free-living study with 32 participants wearing an Oura Ring and reference monitors (three accelerometers positioned at hip, thigh, and wrist, and pedometer) to evaluate Oura EE variables and step count.ResultsStrong correlations were shown for Oura versus indirect calorimetry in the laboratory (r = 0.93), and versus reference monitors for all variables in free-living (r >= 0.76). Significant (p < 0.05) mean differences for Oura versus reference methods were found for laboratory measured sitting (- 0.12 +/- 0.28 MET), standing (- 0.27 +/- 0.33 MET), fast walk (- 0.82 +/- 1.92 MET) and very fast run (- 3.49 +/- 3.94 MET), and for free-living step-count (2124 +/- 4256 steps) and EE variables (MET: - 0.34-0.26; TEE: 362-494 kcal; AEE: - 487-259 kcal). In the laboratory, Oura tended to underestimate EE with increasing discrepancy as intensity increased. The combined activities and slow running in the laboratory, and all MET placements, TEE hip and wrist, and step count in free-living had acceptable measurement errors (< 10% MAPE), whereas the remaining free-living variables showed close to (<= 13.2%) acceptable limits.ConclusionThis is the first study investigating the validity of Oura Ring EE against gold standard methods. Oura successfully identified major changes between activities and/or intensities but was less responsive to detailed deviations within activities. In free-living, Oura step-count and EE variables tightly correlated with reference monitors, though with systemic over- or underestimations indicating somewhat low intra-individual validity of the ring versus the reference monitors. However, the correlations between the devices were high, suggesting that the Oura can detect differences at group-level for active and total energy expenditure, as well as step count.
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46.
  • Källner, Kristin, et al. (författare)
  • Interaction of Iron Homeostasis and Fatty Acid Metabolism in the Development of Glucose Intolerance in Women with Previous Gestational Diabetes Mellitus
  • 2023
  • Ingår i: Nutrients. - 2072-6643. ; 15:14
  • Tidskriftsartikel (refereegranskat)abstract
    • A gestational diabetes mellitus (GDM) diagnosis during pregnancy means an increased risk of developing type 2 diabetes later in life. By following up with women after GDM we aimed to examine the relationship between iron parameters, individual fatty acids (FAs) and desaturases in the development of impaired glucose metabolism (IGM). Based on an oral glucose tolerance test (OGTT), six years after GDM, 157 women were grouped as having normal glucose tolerance (NGT) or IGM. Fasting serum FAs, activity of desaturases and iron parameters (ferritin, transferrin, iron, soluble transferrin receptor, total iron binding capacity, hepcidin) were measured, and clinical and anthropometric measurements taken. Soluble transferrin receptor was higher in the IGM group compared to the NGT group (3.87 vs. 3.29 mg/L, p-value = 0.023) and associated positively with saturated FAs and negatively with monounsaturated FAs in the IGM group (adjusted for BMI, age and high sensitivity C-reactive protein; p-value < 0.05). Iron, as well as transferrin saturation, showed a positive association with MUFAs and desaturase activity. These associations were not seen in the NGT group. These results suggest that iron homeostasis and FA metabolism interact in the development of glucose intolerance in women with previous GDM.
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47.
  • Manni, Luigi, 1962, et al. (författare)
  • Effect of anti-NGF on ovarian expression of alpha1- and beta2-adrenoceptors, TrkA, p75NTR, and tyrosine hydroxylase in rats with steroid-induced polycystic ovaries.
  • 2006
  • Ingår i: American journal of physiology. Regulatory, integrative and comparative physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 290:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Estradiol valerate (EV)-induced polycystic ovaries (PCO) in rats are associated with higher ovarian release and content of norepinephrine, decreased beta2-adrenoceptors (ARs), and dysregulated expression of alpha1-AR subtypes, all preceded by an increase in the production of ovarian NGF. The aim of this study was to further elucidate the role of NGF in the ovaries by blocking the action of NGF during development of EV-induced PCO in rats. Control and EV-injected rats were treated with intraperitoneal injections of IgG (control and PCO groups) or with anti-NGF antibodies (anti-NGF and PCO anti-NGF groups) every third day for 5 wk starting from the day of PCO induction. Rat weight, estrous cyclicity, ovarian morphology, ovarian mRNA, and protein expression of alpha1-AR subtypes, beta2-AR, the NGF receptor tyrosine kinase A (TrkA), p75 neurotrophin receptor (p75NTR), and tyrosine hydroxylase (TH) were analyzed. Ovaries in both PCO and PCO anti-NGF groups decreased in size as well as in number and size of corpora lutea. mRNA expression of alpha1a-AR and TrkA in the ovaries was lower, whereas expression of alpha1b- and alpha1d-AR and TH was higher, in the PCO group than in controls. Protein quantities of alpha1-ARs, TrkA, p75NTR, and TH were higher in the PCO group compared with controls, whereas the protein content of beta2-AR was lower. Anti-NGF treatment in the PCO group restored all changes in mRNA and protein content, except that of alpha1b-AR and TrkA mRNAs, to control levels. The results indicate that the NGF/NGF receptor system plays a role in the pathogenesis of EV-induced PCO in rats.
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48.
  • Manni, Luigi, 1962, et al. (författare)
  • Effect of electro-acupuncture on ovarian expression of alpha (1)- and beta (2)-adrenoceptors, and p75 neurotrophin receptors in rats with steroid-induced polycystic ovaries.
  • 2005
  • Ingår i: Reproductive biology and endocrinology : RB&E. - : Springer Science and Business Media LLC. - 1477-7827. ; 3
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Estradiol valerate (EV)-induced polycystic ovaries (PCO) in rats is associated with an increase in ovarian sympathetic outflow. Low-frequency (2 Hz) electro-acupuncture (EA) has been shown to modulate sympathetic markers as well as ovarian blood flow as a reflex response via the ovarian sympathetic nerves, in rats with EV-induced PCO. METHODS: In the present study, we further tested the hypothesis that repeated 2 Hz EA treatments modulate ovarian sympathetic outflow in rats with PCO, induced by a single i.m. injection of EV, by investigating the mRNA expression, the amount and distribution of proteins of alpha1a-, alpha1b-, alpha1d-, and beta2-adrenoceptors (ARs), as well as the low-affinity neurotrophin receptor (p75NTR). RESULTS: It was found that EV injection results in significantly higher mRNA expression of ovarian alpha1b- and alpha1d-AR in PCO rats compared to control rats. The p75NTR and beta2-ARs mRNA expression were unchanged in the PCO ovary. Low-frequency EA resulted in a significantly lower expression of beta2-ARs mRNA expression in PCO rats. The p75NTR mRNA was unaffected in both PCO and control rats. PCO ovaries displayed significantly higher amount of protein of alpha1a-, alpha1b- and alpha1d-ARs, and of p75NTR, compared to control rats, that were all counteracted by repeated low-frequency EA treatments, except for alpha1b-AR. CONCLUSION: The present study shows that EA normalizes most of the EV-induced changes in ovarian ARs. Furthermore, EA was able to prevent the EV-induced up regulation of p75NTR, probably by normalizing the sympathetic ovarian response to NGF action. Our data indicate a possible role of EA in the regulation of ovarian responsiveness to sympathetic inputs and depict a possible complementary therapeutic approach to overcoming sympathetic-related anovulation in women with PCOS.
  •  
49.
  • Manni, Luigi, 1962, et al. (författare)
  • Effect of exercise on ovarian morphology and expression of nerve growth factor and alpha(1)- and beta(2)-adrenergic receptors in rats with steroid-induced polycystic ovaries
  • 2005
  • Ingår i: J Neuroendocrinol. ; 17:12, s. 846-58
  • Tidskriftsartikel (refereegranskat)abstract
    • Oestadiol valerate (EV)-induced polycystic ovaries (PCO) in rats cause anovulation and cystic ovarian morphology. Denervation of ovarian sympathetic nerves restores ovulatory disruption. In the present study, we determined whether 5 weeks of voluntary exercise influence ovarian morphology and the expression of sympathetic markers in the EV-induced PCO rat model. The effect of exercise on (i) ovarian morphology; (ii) mRNA and protein expression of nerve growth factor (NGF); and (iii) mRNA and number of ovarian-expressing cells for the NGF receptor (p75 neurotrophin receptor) and the alpha(1a)-, alpha(1b)-, alpha(1d)- and beta(2)-adrenergic receptors (ARs) in rats with EV-induced PCO was evaluated. PCO was induced by a single i.m. injection of EV, and controls were injected with oil alone in adult cycling rats. The rats were divided into four groups: (i) control (oil); (ii) exercise group (oil + exercise); (iii) a PCO group (EV); and (iv) a PCO exercise group (EV + exercise). The exercise and PCO exercise groups ran voluntarily for 5 weeks in computer-monitored wheels placed in the cages where they were housed. The results obtained indicated that ovarian morphology was almost normalised in the PCO exercise group; NGF mRNA and protein concentrations were normalised in the PCO exercise group; high numbers of NGF receptor expressing cells in PCO ovaries were lowered by exercise; and the number of immunopositive cells of the different AR subtypes were all reduced after exercise in the PCO group, except for the alpha(1b)- and beta(2)-AR whereas the mRNA levels were unaffected, indicating transcriptional regulation. In conclusion, our data indicate a beneficial effect of regular exercise, as a modulator of ovarian sympathetic innervation, in the prevention and treatment of human PCOS.
  •  
50.
  • Manni, Luigi, 1962, et al. (författare)
  • Ovarian expression of alpha (1)- and beta (2)-adrenoceptors and p75 neurotrophin receptors in rats with steroid-induced polycystic ovaries.
  • 2005
  • Ingår i: Autonomic neuroscience : basic & clinical. - : Elsevier BV. - 1566-0702. ; 118:1-2, s. 79-87
  • Tidskriftsartikel (refereegranskat)abstract
    • Polycystic ovary syndrome (PCOS) is the main cause of infertility in women. Despite extensive research aimed at identifying the pathogenetic mechanism underlying this condition, the aetiology of the disease is still unknown. Evidence from studies on women with PCOS and on an experimental rat polycystic ovary (PCO) model suggests that the sympathetic regulatory drive to the ovary may be unbalanced. The present study was designed to investigate this hypothesis. Accordingly, we used the well-defined rat PCO model, where PCO is induced by a single intramuscular (i.m.) injection of estradiol valerate (EV), and compared the model with oil-injected controls. We studied the ovarian expression of the alpha1- and beta2-adrenoceptors (ARs), the neurotrophin receptor p75 (p75NTR), and the sympathetic marker tyrosine hydroxylase (TH) at two time points: 30 and 60 days after EV injection. Our data demonstrate for the first time that all of the alpha1-AR subtypes are expressed in normal rat ovaries at both the mRNA and the protein levels. Furthermore, the expression of the alpha1-AR subtypes was differentially modulated in a time- and subtype-dependent manner in rats with EV-induced PCO. The ovaries in rats with steroid-induced PCO are characterised by an early overexpression of these molecules and p75NTR, while the beta2-AR was downregulated. An increase in the expression of ovarian TH after EV injection was also detected, suggesting a structural and functional remodelling of ovarian sympathetic innervation in PCO rats. Our evidence strongly indicates that the role of the sympathetic nervous system is crucial in the pathogenesis of EV-induced PCO. Overall, our findings suggest that therapeutical approaches aimed at down-regulating the sympathetic tone to the ovary could be useful in the prevention and clinical treatment of PCOS.
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