| 1. |
- Ling, Charlotte, et al.
(författare)
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Identification of Functional Prolactin (PRL) Receptor Gene Expression: PRL Inhibits Lipoprotein Lipase Activity in Human White Adipose Tissue
- 2003
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Ingår i: The Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0013-7227 .- 1945-7197 .- 0021-972X. ; 88:4, s. 1804-1808
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Tidskriftsartikel (refereegranskat)abstract
- During lactation serum levels of prolactin (PRL) are elevated, and the activity of lipoprotein lipase (LPL) is decreased in the adipose tissue and increased in the mammary gland. However, PRL has been suggested to affect the adipose tissue in an indirect fashion during lactation. In the present study, we demonstrated expression of four PRL receptor (PRLR)mRNA isoforms (L, I, S1a, and S1b) in human sc abdominal adipose tissue and breast adipose tissue using RT-PCR/Southern blot analysis. In addition, L-PRLR [relative molecular mass (Mr) 90,000] and I-PRLR (Mr 50,000) protein expression was detected in human sc abdominal adipose tissue and breast adipose tissue using immunoblot analysis. Two additional protein bands with the molecular weight Mr 40–35,000 were also detected. The direct effect of PRL on the regulation of LPL activity in human abdominal adipose tissue cultured in vitro was investigated. PRL (500 ng/ml) reduced the LPL activity in human adipose tissue to 31 +/- 7.7%, compared with control.GH (100 ng/ml) also reduced the LPL activity, to 45 +/- 8.6%, compared with control. In agreement with previous studies, cortisol increased the LPL activity and GH inhibited cortisolinduced LPL activity. Furthermore, we found that PRL also inhibited the cortisol-induced LPL activity. Taken together, these results demonstrate a direct effect of PRL, via functional PRLRs, in reducing the LPL activity in human adipose tissue, and these results suggest that LPL might also be regulated in this fashion during lactation.
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| 2. |
- Svensson, Henrik, 1982, et al.
(författare)
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Adipose tissue and body composition in women six years after gestational diabetes: factors associated with development of type 2 diabetes.
- 2018
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Ingår i: Adipocyte. - : Informa UK Limited. - 2162-397X .- 2162-3945. ; 7:4, s. 229-237
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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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| 3. |
- Svensson, Henrik, 1982, et al.
(författare)
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Body fat mass and the proportion of very large adipocytes in pregnant women are associated with gestational insulin resistance.
- 2016
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Ingår i: International journal of obesity (2005). - : Springer Science and Business Media LLC. - 1476-5497 .- 0307-0565. ; 40, s. 646-653
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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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| 4. |
- Svensson, Henrik, 1982, et al.
(författare)
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Free lipid and computerized determination of adipocyte size.
- 2018
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Ingår i: Adipocyte. - : Informa UK Limited. - 2162-397X .- 2162-3945. ; 7:3, s. 180-182
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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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| 5. |
- Björnheden, Tom, 1945, et al.
(författare)
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Computerized determination of adipocyte size.
- 2004
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Ingår i: Obesity research. - 1071-7323. ; 12:1, s. 95-105
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Fat cell size is a fundamental parameter in the study of adipose tissue metabolism, because it markedly influences the cellular rates of metabolism. Previous techniques for the sizing of adipocytes are often complicated or time-consuming. The aim of this study was to develop a new, computerized method for rapid and accurate determination of adipocyte size in a cell suspension obtained by incubating human or rat adipose tissue biopsies with collagenase. RESEARCH METHODS AND PROCEDURES: The cell suspension was placed between a siliconized glass slide and a cover slip. Using the reference method [designated as (R)], the cell diameters were determined manually using a microscope with a calibrated ocular. The new method presented here [designated as (C)] was based on computerized image analysis. RESULTS: After two well-defined corrective adjustments, measurements with (R) and (C) agreed very well. The small remaining differences seemed, in fact, to depend on inconsistencies in (R). DISCUSSION: We propose that (C) constitutes a valuable tool to study fat cell size, because this method is fast and allows the assessment of a sufficient number of cells to get reliable data on size distribution. Furthermore, images of cell preparations may be stored for future reference.
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| 6. |
- Carlsson, Björn, 1958, et al.
(författare)
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Expression and physiological significance of growth hormone receptors and growth hormone binding proteins in rat and man.
- 1991
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Ingår i: Acta paediatrica Scandinavica. Supplement. - 0300-8843. ; 379
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Tidskriftsartikel (refereegranskat)abstract
- The molecular structure of the GH receptor has recently been characterized and the receptor identified as a member of a new receptor superfamily that includes the prolactin receptor and several cytokine receptors. No obvious signal transducing domain has been identified on any of these related receptors. One possible signalling mechanism involves receptor interaction with other membrane-associated proteins that function as mediators of signal transduction. Whether such a mechanism is involved in signal transduction of the GH receptor is not known. Another common feature of these receptors is the presence of soluble forms such as the GHBP. The functions of these proteins in the circulation and at the level of the target cell remain to be resolved.
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| 7. |
- De Pergola, G, et al.
(författare)
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Amount of G-protein alpha-subunit in rat white adipocytes: lack of difference between subcutaneous and visceral fat.
- 1993
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Ingår i: Acta endocrinologica. - 0001-5598. ; 129:4, s. 366-70
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Tidskriftsartikel (refereegranskat)abstract
- It has been the purpose of this study to examine possible differences in the amount of stimulatory (Gs) and inhibitory (Gi) G-protein alpha-subunits (measured with a quantitative enzyme-linked immunosorbent assay in fat cell membrane preparation) between subcutaneous and intra-abdominal regions in rats. The lipolytic response to isoproterenol and the number of beta-adrenergic binding sites were also examined. These parameters were all evaluated simultaneously in subcutaneous (inguinal), epididymal and perirenal fat samples collected from six male Sprague-Dawley rats. The membrane contents of the Gs and Gi alpha-subunits were similar in the three depots. Moreover, no difference was found among the different regions with regard to isoproterenol-stimulated glycerol release and beta-adrenoceptor number, expressed per cell number. In conclusion, the present study shows for the first time in rats that the abundance of inhibitory and stimulatory G-protein alpha-subunits is similar in subcutaneous and in visceral adipocytes. Moreover, the number of beta-adrenoceptors and the lipolytic response to isoproterenol do not show significant variations with the anatomical site. As the present results are apparently in contrast with those obtained previously in human adipocytes, there is a possibility that the different results observed in rat and in human fat cells could be explained by species differences.
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| 8. |
- Edén, Arvid, 1975, et al.
(författare)
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Asymptomatic Cerebrospinal Fluid HIV-1 Viral Blips and Viral Escape During Antiretroviral Therapy: A Longitudinal Study.
- 2016
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Ingår i: The Journal of infectious diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 214:12, s. 1822-1825
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Tidskriftsartikel (refereegranskat)abstract
- We examined longitudinal cerebrospinal fluid (CSF) samples (median, 5 samples/patients; interquartile range [IQR], 3-8 samples/patient) in 75 neurologically asymptomatic human immunodeficiency virus (HIV)-infected patients receiving antiretroviral therapy. Twenty-seven patients (36%) had ≥1 CSF HIV RNA load of >20 copies/mL (23% had ≥1 load of >50 copies/mL), with a median HIV RNA load of 50 copies/mL (IQR, 32-77 copies/mL). In plasma, 42 subjects (52%) and 22 subjects (29%) had an HIV RNA load of >20 and >50 copies/mL, respectively. Two subjects had an increasing virus load in consecutive CSF samples, representing possible CSF escape. Of 418 samples, 9% had a CSF HIV RNA load of >20 copies/mL (5% had a load of >50 copies/mL) and 19% had a plasma HIV RNA load of >20 copies/mL (8% had a load of >50 copies/mL). A CSF-associated virus load of >20 copies/mL was associated with higher CSF level of neopterin. In conclusion, CSF escape was rare, and increased CSF HIV RNA loads usually represented CSF virus load blips.
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| 9. |
- Edén, Arvid, 1975, et al.
(författare)
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HIV-1 viral escape in cerebrospinal fluid of subjects on suppressive antiretroviral treatment.
- 2010
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Ingår i: The Journal of infectious diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 202:12, s. 1819-25
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Tidskriftsartikel (refereegranskat)abstract
- Occasional cases of viral escape in cerebrospinal fluid (CSF) despite suppression of plasma human immunodeficiency virus type 1 (HIV-1) RNA have been reported. We investigated CSF viral escape in subjects treated with commonly used antiretroviral therapy regimens in relation to intrathecal immune activation and central nervous system penetration effectiveness (CPE) rank.
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| 10. |
- Edén, Arvid, 1975, et al.
(författare)
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Reply to Seligman
- 2011
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Ingår i: J Infect Dis. ; 2011:1, s. 174-175
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 11. |
- Ekman, Inger, 1952, et al.
(författare)
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The person-centred approach to an ageing society
- 2013
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Ingår i: European Journal for Person Centered Healthcare. - : University of Buckingham Press. - 2052-5656 .- 2052-5648. ; 1:1, s. 132-137
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Tidskriftsartikel (refereegranskat)abstract
- Modern care is often based on investigations such as laboratory markers and imaging - for example, x-ray or ultrasound. The results contribute to a diagnosis and, if judged necessary, treatment is initiated. This diseased-oriented approach is the prevailing mode of management in modern medicine. In contrast, person-centered care (PCC) takes the point of departure from each person´s subjective experience of illness and its impact on daily life. A patient is considered as a person with emotions and feelings. PCC is considered present within clinical care according to a definition articulated by the Centre for Person Centred Care at the University of Gothenburg (GPCC) when three core components are present: elicitation of a detailed patient narrative; formulated partnership between caregiver and patient and documentation of the partnership in the patient record. Accordingly, when there is an illness requiring care and the person is attended using these components, PCC is being applied. In most situations today, PCC is not applied as the narrative is not fully elicited or the partnership and/or the documentation are not included. It is proposed that the challenge to Society arising from changing demographics can be addressed by implementing PCC and creating an alternative to existing healthcare. The importance and benefits of such an approach on a wider scale is not yet clear as research has been limited to date. Studies in selected patient populations (heart failure and hip fractures), however, have shown promising results. As the population ages, there will be a dramatic increase in healthcare consumption. Even with technological developments, there will be a need for tremendous resources to be dedicated to care. A new organization and attitude from healthcare policymakers and providers above and beyond the present model appears required in order to respond to this demand. As part of such change, person-centred care, with the interaction between healthcare providers and the person of the patient, can facilitate, compensate and develop more effective healthcare services for the future.
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| 12. |
- Frick, Fredrik, 1973, et al.
(författare)
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Different effects of IGF-I on insulin-stimulated glucose uptake in adipose tissue and skeletal muscle.
- 2000
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Ingår i: American journal of physiology. Endocrinology and metabolism. - 0193-1849. ; 278:4
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Tidskriftsartikel (refereegranskat)abstract
- The effect of insulin-like growth factor I (IGF-I) on insulin-stimulated glucose uptake was studied in adipose and muscle tissues of hypophysectomized female rats. IGF-I was given as a subcutaneous infusion via osmotic minipumps for 6 or 20 days. All hypophysectomized rats received L-thyroxine and cortisol replacement therapy. IGF-I treatment increased body weight gain but had no effect on serum glucose or free fatty acid levels. Serum insulin and C-peptide concentrations decreased. Basal and insulin-stimulated glucose incorporation into lipids was reduced in adipose tissue segments and isolated adipocytes from the IGF-I-treated rats. In contrast, insulin treatment of hypophysectomized rats for 7 days increased basal and insulin-stimulated glucose incorporation into lipids in isolated adipocytes. Pretreatment of isolated adipocytes in vitro with IGF-I increased basal and insulin-stimulated glucose incorporation into lipids. These results indicate that the effect of IGF-I on lipogenesis in adipose tissue is not direct but via decreased serum insulin levels, which reduce the capacity of adipocytes to metabolize glucose. Isoproterenol-stimulated lipolysis, but not basal lipolysis, was enhanced in adipocytes from IGF-I-treated animals. In the soleus muscle, the glycogen content and insulin-stimulated glucose incorporation into glycogen were increased in IGF-I-treated rats. In summary, IGF-I has opposite effects on glucose uptake in adipose tissue and skeletal muscle, findings which at least partly explain previous reports of reduced body fat mass, increased body cell mass, and increased insulin responsiveness after IGF-I treatment.
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| 13. |
- Frick, Fredrik, 1973, et al.
(författare)
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Hepatic and adipose tissue depot-specific changes in lipid metabolism in Late-onset Obese (LOB) rats.
- 2008
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Ingår i: Lipids. - : Wiley. - 0024-4201 .- 1558-9307. ; 43:4, s. 313-24
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Tidskriftsartikel (refereegranskat)abstract
- Transgenic Late-onset OBesity (LOB) rats slowly develop a male-specific, autosomal dominant, obesity phenotype with a specific increase in peri-renal white adipose tissue (WAT) depot and preserved insulin sensitivity (Bains et al. in Endocrinology 145:2666-2679, 2004). To better understand the remarkable phenotype of these rats, the lipid metabolism was investigated in male LOB and non-transgenic (NT) littermates. Total plasma cholesterol (C) levels were normal but total plasma triacylglycerol (TAG) (2.8-fold) and hepatic TAG content (25%) was elevated in LOB males. Plasma VLDL-C and VLDL-TAG levels were higher while plasma apoB levels were 60% lower in LOB males. Increased hepatic TAG secretion explained the increased VLDL levels in LOB males. The hepatic gene expression of FAS, SCD-1, mitochondrial (mt)GPAT, and DGAT2 was up-regulated in both old obese and young non-obese LOB rats. Lipoprotein lipase (LPL) activity in heart and epididymal white adipose tissue (WAT) was unchanged, while LPL activity was increased in peri-renal WAT (30%) and decreased in soleus muscle (40%). Moreover, FAS, SCD-1 and DGAT2 gene expression was increased in peri-renal, but not in epididymal WAT. Basal lipolysis was reduced or unchanged and beta-adrenergic stimulated lipolysis was reduced in WAT from both old obese and young non-obese LOB rats. To summarize, the obese phenotype of LOB male rats is associated with increased hepatic TAG production and secretion, a shift in LPL activity from skeletal muscle to WAT, reduced lipolytic response in WAT depots and a specific increase in expression of genes responsible for fatty acid and TAG synthesis in the peri-renal depot.
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| 14. |
- Gabrielsson, Britt, 1957, et al.
(författare)
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Molecular characterization of a local sulfonylurea system in human adipose tissue.
- 2004
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Ingår i: Molecular and cellular biochemistry. - 0300-8177 .- 1573-4919. ; 258:1-2, s. 65-71
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Tidskriftsartikel (refereegranskat)abstract
- ATP-sensitive potassium (KATP) channels are present in many cell types and link cellular metabolism to the membrane potential. These channels are heterooctamers composed of two subunits. The sulfonylurea receptor (SUR) subunits are targets for drugs that are inhibitors or openers of the KATP channels, while the inwardly rectifying K+ (Kir) subunits form the ion channel. Two different SUR genes (SUR1 and SUR2) and two different Kir6.x genes (Kir6.1 and Kir6.2) have been identified. In addition, isoforms of SUR2, SUR2A and SUR2B, have been described. We have previously performed expression profiling on pooled human adipose tissue and found high expression of SUR2. Others have reported expression of SUR1 in human adipocytes. The aim of this study was to characterize the expression of the sulfonylurea receptor complex components in human adipose tissue. RT-PCR analysis, verified by restriction enzyme digestions and DNA sequencing, showed that SUR2B, Kir6.1 and alpha-endosulfine, but not SUR1, SUR2A or Kir6.2, are expressed in human adipose tissue. Real-time RT-PCR showed that SUR2B was expressed at higher levels in subcutaneous compared with omental adipose tissue in paired biopsies obtained from seven obese men (p < 0.05). Analysis of tissue distribution showed that SUR2B expression in adipose tissue was lower than that in muscle, similar to that in heart and liver, while the expression in pancreas was lower. The effect of caloric restriction was tested in obese men (n = 10) treated with very low calorie diet for 16 weeks, followed by a gradual reintroduction of ordinary food for 2 weeks. Biopsies were taken at week 0, 8 and 18. There was no consistent effect of weight reduction on SUR2B or Kir6.1 expression. We conclude that the necessary components for a local sulfonylurea system are expressed in human adipose tissue and that the sulfonylurea receptor complex in this tissue is composed of SUR2B and Kir6.1. The expression of SUR2B was higher in subcutaneous compared with omental adipose tissue and was not affected by weight loss.
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| 15. |
- Lindkvist, Annica, et al.
(författare)
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Reduction of the HIV-1 reservoir in resting CD4+ T-lymphocytes by high dosage intravenous immunoglobulin treatment: a proof-of-concept study
- 2009
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Ingår i: AIDS research and therapy. - : Springer Science and Business Media LLC. - 1742-6405. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The latency of HIV-1 in resting CD4+ T-lymphocytes constitutes a major obstacle for the eradication of virus in patients on antiretroviral therapy (ART). As yet, no approach to reduce this viral reservoir has proven effective. METHODS: Nine subjects on effective ART were included in the study and treated with high dosage intravenous immunoglobulin (IVIG) for five consecutive days. Seven of those had detectable levels of replication-competent virus in the latent reservoir and were thus possible to evaluate. Highly purified resting memory CD4+ T-cells were activated and cells containing replication-competent HIV-1 were quantified. HIV-1 from plasma and activated memory CD4+ T-cells were compared with single genome sequencing (SGS) of the gag region. T-lymphocyte activation markers and serum interleukins were measured. RESULTS: The latent HIV-1 pool decreased with in median 68% after IVIG was added to effective ART. The reservoir decreased in five, whereas no decrease was found in two subjects with detectable virus. Plasma HIV-1 RNA >or= 2 copies/mL was detected in five of seven subjects at baseline, but in only one at follow-up after 8-12 weeks. The decrease of the latent HIV-1 pool and the residual plasma viremia was preceded by a transitory low-level increase in plasma HIV-1 RNA and serum interleukin 7 (IL-7) levels, and followed by an expansion of T regulatory cells. The magnitude of the viral increase in plasma correlated to the size of the latent HIV-1 pool and SGS of the gag region showed that viral clones from plasma clustered together with virus from activated memory T-cells, pointing to the latent reservoir as the source of HIV-1 RNA in plasma. CONCLUSION: The findings from this uncontrolled proof-of-concept study suggest that the reservoir became accessible by IVIG treatment through activation of HIV-1 gene expression in latently-infected resting CD4+ T-cells. We propose that IVIG should be further evaluated as an adjuvant to effective ART.
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| 16. |
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| 17. |
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| 18. |
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| 19. |
- Ljung, Thomas, 1961-, et al.
(författare)
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Central and peripheral glucocorticoid receptor function in abdominal obesity.
- 2002
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Ingår i: Journal of endocrinological investigation. - 0391-4097 .- 1720-8386. ; 25:3, s. 229-35
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Tidskriftsartikel (refereegranskat)abstract
- Abdominal obesity seems to be associated with a moderately deranged feedback regulation of the hypothalamic-pituitary-adrenal (HPA) axis where central glucocorticoid receptors (GR) are involved. Therefore, functions of central and peripheral GR were compared in this study. Furthermore, since trinucleotide repeats in early exons of steroid hormone receptor genes influence transcription, and therefore may influence receptor density, this was also studied. Ten middle-aged men, 5 with abdominal obesity and 5 controls, were studied. The suppression of dexamethasone (dex) on serum cortisol was used in dose-response tests to assess the function of central GR. Abdominal adipose tissue biopsies were incubated and exposed to cortisol in different concentrations, and the function of the peripheral GR assayed as induction of lipoprotein lipase (LPL) activity. Aberrant expansion of exonic trinucleotide repeats in the first coding exon of the GR gene was studied by sequencing of genomic DNA. Results showed that men with abdominal obesity showed less inhibition of serum cortisol by dex, particularly at lower concentrations, while in the controls cortisol secretion was inhibited in an apparent dose-response manner. LPL activity in adipose tissue was lower in abdominal obese men than in controls. However, the sensitivity to cortisol was not different between the groups. There was no evidence for expansion of trinucleotide repeats. These results suggest that the central GR and the peripheral GR in adipose tissue exhibit functional differences in abdominal obesity.
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| 20. |
- Oscarsson, Jan, 1960, et al.
(författare)
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Effects of growth hormone on lipoprotein lipase and hepatic lipase.
- 1999
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Ingår i: Journal of endocrinological investigation. - 0391-4097. ; 22:5 Suppl, s. 2-9
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Forskningsöversikt (refereegranskat)abstract
- Lipoprotein lipase (LPL) is a key enzyme in the regulation of the flux of fatty acids. LPL hydrolyses triglycerides in chylomicrons and very-low-density lipoproteins (VLDL), forming intermediate- (IDL) and low-density lipoproteins (LDL). Hepatic lipase (HL) is a related enzyme with a more restricted tissue distribution than LPL; HL is mainly engaged in the turnover of IDL and of high-density lipoproteins (HDL). Both enzymes can be released from their endothelial sites by heparin and their activities measured separately in post-heparin plasma (PHP). The PHP-LPL activity decreases in hypophysectomized rats and this effect is reversed by growth hormone (GH) therapy. However, GH seems to have no effect, or an inhibitory effect, on PHP-LPL activity in humans. Muscle and adipose tissues are the main sources of PHP-LPL activity. One week of GH therapy of hypophysectomized rats increases skeletal muscle and heart LPL activity. In this model, GH has little or no effect on LPL activity in adipose tissue. However, GH has been shown to decrease LPL activity in isolated rat adipose tissue. Insulin-like growth factor-I therapy decreases and insulin therapy increases LPL activity in adipose tissue of hypophysectomized rats, whereas these therapies have no effect on LPL activity in muscle tissue. The LPL activity in human adipose tissue is reduced both in vivo and in vitro after administration of GH while the LPL mRNA level is unchanged. The effect of GH on HL activity has been studied in PHP and liver. Several studies in the rat indicate that GH increases PHP-HL and liver HL activity, at least partly at the level of mRNA expression. In humans, GH has been shown to have variable effects on PHP-HL activity; this variability is probably to some extent dependent on different experimental set-ups. Although GH therapy increases hepatic secretion of VLDL, serum triglyceride levels decrease as a result of GH therapy in the hypophysectomized rat. An increase in HL and LPL activity by GH therapy is in line with these findings. In summary, GH is involved in the regulation of both LPL and HL activity but the effects and mechanisms of action of GH in the regulation of LPL and HL activity in different tissues are not yet fully elucidated.
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| 21. |
- Oscarsson, Jan, 1960, et al.
(författare)
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GH but not IGF-I or insulin increases lipoprotein lipase activity in muscle tissues of hypophysectomised rats.
- 1999
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Ingår i: The Journal of endocrinology. - 0022-0795. ; 160:2, s. 247-55
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Tidskriftsartikel (refereegranskat)abstract
- Changes in GH secretion are associated with changes in serum lipoproteins, utilisation of fuels and body composition. Since lipoprotein lipase (LPL) is a key enzyme in the regulation of lipid and lipoprotein metabolism, changes in LPL activity may contribute to these effects of GH. The present study was undertaken to investigate the role of GH and the GH-dependent growth factor, IGF-I, in the regulation of LPL in heart, skeletal muscle and adipose tissue. Female rats were hypophysectomised at 50 days of age. One week later, hormonal therapy was commenced. All hypophysectomised rats received l-thyroxine and cortisol. Adipose tissue, the heart, soleus and gastrocnemius muscles were excised after 1 week of hormonal therapy. The effect of insulin injections on adipose tissue and heart LPL activity was also studied. In separate experiments, LPL activity in post-heparin plasma was measured. Hypophysectomy had no effect on adipose tissue LPL activity, whereas activity was reduced in heart, soleus and gastrocnemius muscle tissues. GH treatment had no significant effect on LPL activity in adipose tissue or soleus muscle, but increased the LPL activity in heart and gastrocnemius muscle. GH treatment increased post-heparin plasma LPL activity. Recombinant human IGF-I treatment (1.25 mg/kg per day) markedly reduced LPL activity in adipose tissue, but had no effect in muscle tissues. The effect of IGF-I treatment on adipose tissue LPL was not reflected by a decrease in post-heparin plasma LPL activity. Daily injections of insulin for 7 days increased LPL activity in adipose tissue but had no effect on heart LPL activity. In adipose tissue, LPL mRNA levels tended to decrease as a result of IGF-I treatment. In the muscle tissues, no significant effects of hypophysectomy, GH or IGF-I treatment on LPL mRNA levels were observed.%It is concluded that GH increases heart and skeletal muscle tissue LPL activity, which probably contributes to an increased post-heparin plasma LPL activity. The effect of GH on muscle LPL activity is probably not mediated by IGF-I or insulin. Insulin and IGF-I have opposite effects on LPL activity in adipose tissue.
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| 22. |
- Oscarsson, Jan, 1960, et al.
(författare)
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Low dose continuously infused growth hormone results in increased lipoprotein(a) and decreased low density lipoprotein cholesterol concentrations in middle-aged men.
- 1994
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Ingår i: Clinical endocrinology. - 0300-0664. ; 41:1, s. 109-16
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Tidskriftsartikel (refereegranskat)abstract
- Animal studies have shown that slight increases in basal GH concentrations may result in changes in lipoprotein metabolism. Such changes in GH secretion have been observed in physiological and pathophysiological states such as fasting, uncontrolled diabetes and during oestrogen treatment. The aim of this study was to investigate the possible effects of increases in basal plasma GH concentrations on lipoprotein concentrations.Recombinant human growth hormone (rhGH) was given as a continuous subcutaneous infusion in a low dose (0.02 U/kg/day) in an open study.Eight middle-aged (42-59 years) overweight (body mass index: 26.1-33.8 kg/m2) but otherwise healthy men were studied over a period of 14 days.Blood samples were obtained after an over-night fast before and after 2, 7 and 14 days of treatment. Plasma and serum were separated and used for subsequent measurements of hormone and lipoprotein concentrations. On days 0, 7 and 14 of treatment, post-heparin plasma was also obtained for determinations of plasma lipoprotein lipase and hepatic lipase activities. In addition, a hyperinsulinaemic euglycaemic glucose clamp was performed on days 0 and 13 of the study. Fat biopsies from abdominal and gluteal fat depots were obtained for measurement of lipoprotein lipase activities on days 0 and 14 of the study.Serum GH concentrations increased to a steady level of 2-4 mU/l during treatment. Serum insulin-like growth factor-I (IGF-I) concentrations increased throughout the treatment period to twice the pretreatment levels. Plasma insulin and blood glucose concentrations increased on day 2 of treatment. After 7 and 14 days of treatment blood glucose concentrations were not different from pretreatment levels, but plasma insulin concentrations were still elevated. Serum cholesterol and low density lipoprotein (LDL) cholesterol concentrations had decreased after 7 and 14 days of treatment. High density lipoprotein (HDL) cholesterol concentrations were not affected, but very low density lipoprotein (VLDL) cholesterol and triglyceride concentrations increased transiently at day 2 of treatment. Serum apolipoprotein (apo) A-I, apoB and apoE concentrations were not significantly affected. Serum lipoprotein(a) concentrations had increased by days 7 and 14 to 147 and 142% of pretreatment concentrations, respectively. Lipoprotein lipase and hepatic lipase activities in post-heparin plasma, as well as abdominal and gluteal adipose tissue lipoprotein lipase activities, were not affected. There was no significant change in glucose disposal rate estimated from the glucose clamp studies.A low dose infusion of GH results in marked changes in lipoprotein concentrations with a transient increase in VLDL cholesterol and thereafter in a decrease in LDL cholesterol. In addition, this low dose of GH resulted in marked increases in lipoprotein(a) concentrations. The observed effects of GH may partly involve changes in IGF-I and insulin secretion.
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| 23. |
- Ottosson, Malin, 1959, et al.
(författare)
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Effects of cortisol and growth hormone on lipolysis in human adipose tissue.
- 2000
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 85:2, s. 799-803
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Tidskriftsartikel (refereegranskat)abstract
- The in vitro effects of cortisol and GH on basal and stimulated lipolysis in human adipose tissue were studied using a tissue incubation technique. After preincubation for 3 days in control medium containing insulin, adipose tissue pieces were exposed to cortisol for 3 days. GH was added to the cortisol-containing medium during the last 24 h (day 6). Adipocytes were then isolated, and lipolysis was studied in the absence and presence of isoprenaline, noradrenaline, forskolin, and N-6-monobutyryl-cAMP. Cortisol reduced the basal rate of lipolysis (P < 0.01) and the sensitivity to isoprenaline compared to the control values (P < 0.01). Addition of GH to the cortisol-containing medium increased the basal rate of lipolysis (P < 0.01) and the sensitivity to isoprenaline (P < 0.01) to the control level and increased the maximum isoprenaline-induced lipolytic activity (P < 0.01). Similar effects were obtained in the presence of noradrenaline. Maximum forskolin-induced lipolytic activity was reduced after exposure of the tissue to cortisol (P < 0.05), whereas addition of GH antagonized this effect (P < 0.01). Induction of the maximum lipolytic activity with N-6-monobutyryl-cAMP was not influenced by the preceding hormone exposure. Addition of GH alone during the last 24 h of incubation increased the basal rate of lipolysis (P < 0.05) and resulted in a borderline significant increase in the maximum isoprenaline-induced lipolytic activity (P = 0.055), suggesting that GH induces lipolysis also in the absence of glucocorticoids. Thus, cortisol and GH have opposite effects on the basal lipolytic activity in human adipose tissue in vitro as well as on the sensitivity to catecholamines, GH being the lipolytic and cortisol the antilipolytic agent. The present findings are in agreement with in vivo observations.
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| 24. |
- Ottosson, Malin, 1959, et al.
(författare)
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Growth hormone inhibits lipoprotein lipase activity in human adipose tissue.
- 1995
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 80:3, s. 936-41
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Tidskriftsartikel (refereegranskat)abstract
- The in vitro effects of GH on human adipose tissue lipoprotein lipase (LPL) activity and messenger ribonucleic acid (mRNA) levels were studied using a tissue incubation technique. After preincubation for 3 days, abdominal sc adipose tissue pieces were exposed to cortisol (1000 nmol/L) for 3 days to induce LPL activity. Addition of GH (50 micrograms/L) to the cortisol-containing medium during the last 24 h (day 6) caused a decrease by 84 +/- 4% (P < 0.01) in heparin-releasable LPL activity and by 65 +/- 4% (P < 0.01) in total LPL activity. Moreover, the heparin-releasable fraction was reduced from 42% of the total LPL activity with cortisol alone to 17% when both GH and cortisol were present in the incubation medium during the last 24 h (P < 0.01). The reduction in LPL activity in response to GH was not accompanied by a decrease in the level of LPL mRNA measured by a solution hybridization ribonuclease protection assay. In adipose tissue incubated in the control medium for 6 days, the addition of GH alone during the last 24 h caused an insignificant decrease in heparin-releasable LPL activity. Low control activities limited the scope for further decrease. It is concluded that GH counteracts the potent stimulatory effect of glucocorticoids on LPL activity without affecting LPL mRNA levels. Therefore, the inhibition of LPL activity by GH probably occurs during translation and/or posttranslational processing of the enzyme, and the mechanism may involve a decreased channeling of the lipase to the cell surface.
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| 25. |
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| 26. |
- Svensson, Henrik, 1982, et al.
(författare)
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Adiponectin, chemerin, cytokines, and dipeptidyl peptidase 4 are released from human adipose tissue in a depot-dependent manner: an in vitro system including human serum albumin
- 2014
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Ingår i: BMC Endocrine Disorders. - : Springer Science and Business Media LLC. - 1472-6823. ; 1:7
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Background Adipose tissue (AT) contributes to metabolic dysfunction through imbalanced production of adipokines, including cytokines. Visceral AT in particular is associated with metabolic disorders, indicating a specific secretory status. The relative significance of different human AT depots in adipokine release is not fully known. Further, previous in vitro systems usually included medium containing bovine serum albumin (BSA), which may induce cytokine release. Our aim was to compare release of a number of adipokines/cytokines – all implicated in insulin resistance – from human subcutaneous and visceral AT in a short-term incubation system minimizing cytokine induction and including repeated measurements during 24 h. A prerequisite was to evaluate a potential alternative to BSA in the incubation medium. Methods Subcutaneous and/or visceral AT from 17 patients (age 20–68 years; BMI 22.6–56.7 kg/m2) undergoing elective surgery was incubated for 2, 4, 6, 8, and 24 h in medium with or without 1% BSA or human serum albumin (HSA). Medium concentrations of adiponectin, chemerin, nine cytokines, dipeptidyl peptidase 4 (DPP4), and omentin were analyzed by multiplex immunoassay or ELISA. Adipocyte size, AT macrophage density, and medium concentrations of endotoxin were determined. Results Cytokine release was induced by BSA but not by HSA. In evaluation of the final incubation protocol including 1% HSA, and as expected, adiponectin release was higher from subcutaneous biopsies of nonobese than of obese subjects and inversely associated with adipocyte size; omentin was released almost exclusively from visceral AT. Exploratory incubations revealed more abundant release of chemerin, cytokines (except IL-6), and DPP4 from the visceral depot, while adiponectin release was higher from subcutaneous than visceral AT. Release was linear for a maximum of 2–6 h. Macrophage density was higher in visceral than subcutaneous AT. Levels of endotoxin in the medium were negligible. Conclusions Adiponectin, chemerin, many cytokines, and DPP4 are released from human AT in a depot-dependent manner. These results highlight functional differences between visceral and subcutaneous AT, and a mechanistic link between regional fat accumulation and metabolic disorders. Supplementation of human AT incubation medium with HSA rather than BSA is recommended to minimize induction of cytokine release.
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| 27. |
- Svensson, Henrik, et al.
(författare)
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Inflammatory and metabolic markers in relation to outcome of in vitro fertilization in a cohort of predominantly overweight and obese women.
- 2022
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- For overweight and obese women undergoing in vitro fertilization (IVF) the pregnancy and live birth rates are compromised while the underlying mechanisms and predictors are unclear. The aim was to explore the association between adipose tissue-related inflammatory and metabolic markers and the pregnancy and live birth outcome of IVF in a cohort of predominantly overweight and obese women. Serum samples, fulfilling standardizing criteria, were identified from 195 women having participated in either the control (n=131) or intervention (n=64) group of a randomized controlled trial (RCT), seeking to evaluate the effect of a weight reduction intervention on IVF outcome in obese women. Serum high-sensitivity C-reactive protein (hsCRP) and the adipokines leptin and adipocyte fatty acid-binding protein (AFABP) were analyzed for the whole cohort (n=195) in samples collected shortly before IVF [at randomization (control group), after intervention (intervention group)]. Information on age, anthropometry [BMI, waist circumference, waist-to-height ratio (WHtR)], pregnancy and live birth rates after IVF, as well as the spontaneous pregnancy rate, was extracted or calculated from collected data. The women of the original intervention group were also characterized at randomization regarding all variables. Eight women [n=3 original control group (2.3%), n=5 original intervention group (7.8%)] conceived spontaneously before starting IVF. BMI category proportions in the cohort undergoing IVF (n=187) were 1.6/20.1/78.3% (normal weight/overweight/obese). The pregnancy and live birth rates after IVF for the cohort were 35.8% (n=67) and 24.6% (n=46), respectively. Multivariable logistic regression revealed that none of the variables (age, hsCRP, leptin, AFABP, BMI, waist circumference, WHtR) were predictive factors of pregnancy or live birth after IVF. Women of the original intervention group displayed reductions in hsCRP, leptin, and anthropometric variables after intervention while AFABP was unchanged. In this cohort of predominantly overweight and obese women undergoing IVF, neither low-grade inflammation, in terms of hsCRP, other circulating inflammatory and metabolic markers released from adipose tissue (leptin, AFABP), nor anthropometric measures of adiposity or adipose tissue distribution (BMI, waist, WHtR) were identified as predictive factors of pregnancy or live birth rate.Trial registration: ClinicalTrials.gov number, NCT01566929. Trial registration date 30-03-2012, retrospectively registered.
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| 28. |
- Xu, X, et al.
(författare)
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Postreceptor events involved in the up-regulation of beta-adrenergic receptor mediated lipolysis by testosterone in rat white adipocytes.
- 1993
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Ingår i: Endocrinology. - 0013-7227. ; 132:4, s. 1651-7
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Tidskriftsartikel (refereegranskat)abstract
- In the previous studies we have shown that testosterone increases lipolytic responsiveness to catecholamines in rat white adipocytes, and that is associated with an up-regulation of beta-adrenergic receptor density. However, the postreceptor events involved in the testosterone induced enhancement of beta-adrenergic receptor activated lipolysis in these cells have not been adequately studied, and were therefore investigated in the present study. Male Sprague Dawley rats were divided into three groups: control, castrated, and castrated treated with testosterone. The beta-adrenergic receptor-mediated cAMP accumulation, measured with RIA after isoproterenol (a beta-adrenergic agonist) stimulation was decreased in castrated rats, and reversed by testosterone treatment, suggesting a testosterone effect at or proximal to adenylate cyclase. However, no differences between the groups were found in abundance of G alpha protein messenger RNAs (G alpha s, G alpha i-1, and G alpha i-2) as analyzed by Northern blot and a solution hybridization RNase protection assay, or in G protein mass measured with a quantitative enzyme-linked immunosorbent assay in fat cell membrane preparation. Lipolysis stimulated by N6-monobutyryl-cAMP was reduced in castrated rats and recovered by testosterone treatment, suggesting that components distal to the adenylate cyclase, i.e. protein kinase A (PKA) and/or hormone sensitive lipase (HSL) also are involved in testosterone regulation of lipolysis. In conclusion, these and previous results suggest that the testosterone-induced increase in lipolytic response to catecholamines in rat white adipocytes is mediated through several events including an increased beta-adrenergic receptor density, probably an increased adenylate cyclase activity and an increased protein kinase A/hormone sensitive lipase activity at the postreceptor level with apparent absence of effect on the expression of G-proteins.
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| 29. |
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