| 61. |
- Larsson, Susanna C., et al.
(författare)
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Genome-wide association and Mendelian randomization study of fibroblast growth factor 21 reveals causal associations with hyperlipidemia and possibly NASH
- 2022
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Ingår i: Metabolism. - : Elsevier. - 0026-0495 .- 1532-8600. ; 137
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Tidskriftsartikel (refereegranskat)abstract
- Background: Fibroblast growth factor 21 (FGF21) is a hepatokine that produces metabolic benefits, such as improvements of lipid profile. We performed a genome-wide association study (GWAS) to identify genetic variants associated with circulating FGF21 and investigated the causal effects of FGF21 on pertinent outcomes using Mendelian randomization (MR).Methods: We conducted a GWAS testing similar to 7.8 million DNA sequence variants with circulating FGF21 in a discovery cohort of 6259 Swedish adults with replication in 4483 Swedish women. We then performed two-sample MR analyses of genetically predicted circulating FGF21 in relation to alcohol and nutrient intake, cardiovascular and metabolic biomarkers and diseases, and liver function biomarkers using publicly available GWAS summary statistics data.Results: Our GWAS identified multiple single-nucleotide polymorphisms with genome-wide significant associations (P < 5 x 10(-8)) with circulating FGF21 on chromosomes 2 and 19 in or near the GCKR and FGF21 genes, respectively. The strongest signal at the FGF21 locus (rs2548957, beta = 0.181, P < 2.18 x 10(-42)) displayed in twosample MR analyses robust associations with lower alcohol intake, lower circulating low-density lipoprotein cholesterol, apolipoprotein B, C-reactive protein, gamma-glutamyl transferase, and galectin-3 concentrations, and higher circulating insulin-like growth factor-I and alkaline phosphatase concentrations after correcting for multiple testing (P < 0.0018) whereas associations with fat mass, type 2 diabetes, and cardiovascular disease were largely null.Conclusions: We identified robust associations of certain genetic variants in or near the GCKR and FGF21 genes with circulating FGF21 concentrations. Furthermore, our results support a strong causal effect of FGF21 on improved lipid profile, reduced alcohol consumption and C-reactive protein concentrations, and liver function biomarkers including fibrosis. We found largely null or weak positive associations with fat mass, diabetes, and cardiovascular disease as well as higher insulin-like growth factor-I concentrations, which could indicate a compensatory increase to regulate the above FGF21 resistant states in humans.
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| 62. |
- Lidfeldt, Jonas, et al.
(författare)
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The influence of hormonal status and features of the metabolic syndrome on bone density: A population-based study of Swedish women aged 50 to 59 years. The women's health in the Lund area study
- 2002
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Ingår i: Metabolism, Clinical and Experimental. - : Elsevier BV. - 1532-8600. ; 51:2, s. 267-270
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Tidskriftsartikel (refereegranskat)abstract
- This study investigated whether there is an association between bone density and features of the metabolic syndrome in relation to hormonal status. All women aged 50 to 59 years living in a defined geographic area in Sweden were offered a health assessment program including blood glucose, lipid profile, blood pressure, and bone densitometry. Women were divided into 3 groups according to their hormonal status: premenopausal (PM), postmenopausal with hormone replacement therapy (PMT), and postmenopausal without hormone replacement therapy (PMO). Of the 6,886 women investigated, 7% were PM, 41% PMT, and 52% PMO. The overall prevalence of osteopenia and osteoporosis, according to the World Health Organization (WHO) definition, was 42.6% and 6.6%, respectively. T-score in the PM group was higher than in the PMT (P <.05) and PMO groups (P <.001) and higher in the PMT group compared with the PMO group (P <.001). Also, in the total cohort, the bone density was positively associated with body weight, body mass index (BMI), waist-to-hip ratio (WHR), systolic blood pressure (SBP), diastolic blood pressure (DBP), serum triglycerides, and blood glucose (P <.001 for all) and negatively associated with serum levels of cholesterol (P <.05) and high-density lipoprotein (HDL) (P <.001). This was most evident among the PMO women, suggesting that the influence of metabolic factors on bone density increases when the levels of hormones decrease. This indicates that hormone replacement therapy maintains treated women in a premenopausal status concerning the metabolic factors.
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| 63. |
- Lindgärde, F, et al.
(författare)
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Overweight is associated with lower serum leptin in Peruvian Indian than in Caucasian women : A dissociation contributing to low blood pressure?
- 2001
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Ingår i: Metabolism. - : Elsevier BV. - 0026-0495 .- 1532-8600. ; 50:3, s. 325-329
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Tidskriftsartikel (refereegranskat)abstract
- We tested whether plasma levels of leptin and insulin are associated with the lower blood pressure in women of Peruvian Indian heritage compared with Caucasian women. A total of 181 women from Peru and 85 from Sweden, aged 20 to 60 years, with normal plasma glucose levels participated in the study. Measurements of anthropometry, blood pressure, and blood tests were performed after overnight fasting. Compared with women from Umeå in Sweden, women from Lima, Peru had higher body mass index (BMI) (26.2 +/- 4.9 v 24.4 +/- 3.8 kg/m(2)), waist circumference (85 +/- 11 v 79 +/- 10 cm), lower systolic blood pressure (99 +/- 15 v 114 +/- 14 mm; P <.001) and diastolic blood pressure (67 +/- 7 v 74 +/- 10 mm; P <.001). In addition, they had a reduction of the ratio of plasma leptin to BMI (0.52 +/- 0.22 v 0.61 +/- 0.36; P <.001), greater plasma insulin (80 +/- 42 v 41 +/- 21 pmol/L), but lower plasma glucose (4.2 +/- 0.5 v 5.1 +/- 0.5 mmol/L; P <.001). Furthermore, the 181 women from Lima had higher plasma triglyceride levels (1.5 +/- 0.8 v 1.3 +/- 0.7; P =.039), but lower plasma high-density lipoprotein (HDL)-cholesterol (1.0 +/- 0.2 v 1.5 +/- 0.4 mmol/L; P <.001) and total plasma cholesterol (5.0 +/- 1.1 v 5.9 +/- 1.3 mmol/L; P <.001) levels. Plasma leptin correlated with blood pressure and BMI in both populations (P <.001). In multiple regression analysis, BMI, but not log leptin, emerged as the determinant for systolic blood pressure. We concluded that women living in Lima have significant lower blood pressure levels in association with elevated plasma insulin concentrations, but lower plasma leptin values adjusted for BMI in comparison with women from northern Sweden. This may suggest that the concept of metabolic syndrome is different among women with Peruvian Indian heritage in comparison to a Caucasian population.
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| 64. |
- Lindgärde, Folke, et al.
(författare)
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Traditional versus agricultural lifestyle among Shuar women of the Ecuadorian Amazon: Effects on leptin levels
- 2004
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Ingår i: Metabolism, Clinical and Experimental. - : Elsevier BV. - 1532-8600. ; 53:10, s. 1355-1358
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Tidskriftsartikel (refereegranskat)abstract
- Leptin is a key biological marker related to energy balance and development of diabetes and cardiovascular diseases. Its levels are increased in populations with a high degree of the metabolic syndrome. Life history of evolution has, however, largely taken place under the ecological context of hunting and gathering. In this study, we explored whether the first steps of transition to sedentary agriculture involve a change of body composition, plasma leptin concentration, and markers of the metabolic syndrome. A total of 59 healthy Shuar Amerindian women living in 5 isolated communities in the Ecuadorian Amazonian rain forest were examined. Women (n = 33) from the largest and oldest community, Yuwientsa, who are more dependent on agriculture had higher fat mass (11.7 +/- 3.3 v 14.5 +/- 4.0 kg; P = .023) but the same body mass index (24.1 +/- 2.7 v 23.1 +/- 2.8 kg/m(2); not significant [NS]) and lean body mass (41.0 +/- 5.0 v 40.2 +/- 6.2 kg; NS) than women (n = 26) from the 4 traditional hunter/gather settlements. Furthermore, women from Yuwientsia had higher leptin (5.5 +/- 3.1 v 4.1 +/- 2.7 ng/mL; P = .021), and plasma insulin levels (49.8 +/- 37.4 v 35.5 +/- 12.7 pmol/L; P = .013). Homeostasis model assessment (HOMA) values (8.8 +/- 4.8 v 6.1 +/- 2.2; P = .004) and plasma triglyceride levels (2.3 +/- 1.0 v 1.7 +/- 0.6 mmol/L; P = .025) as markers of the metabolic syndrome were also increased in the Yuwientsa population. Mean plasma glucagon concentrations were not different between the groups. We conclude that body fat and levels of insulin and leptin are higher in the population more dependent on agriculture for living. In fact, the leptin concentrations from the 4 hunter/gather communities are the lowest mean value ever reported from a population of healthy females. As there are no genetic or biologic differences between the Shuar Indians from the 5 communities, we hypothesize that behavioral responses to a changing environment may be the key to the development of the metabolic syndrome and elevated plasma leptin concentrations. (C) 2004 Elsevier Inc. All rights reserved.
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| 65. |
- Lopes, Patricia C., et al.
(författare)
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Short and long term in vivo effects of Cyclosporine A and Sirolimus on genes and proteins involved in lipid metabolism in Wistar rats
- 2014
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Ingår i: Metabolism. - : Elsevier BV. - 0026-0495 .- 1532-8600. ; 63:5, s. 702-715
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Cyclosporine A (CsA) and sirolimus (SRL) are immunosuppressive agents (IA) associated with new onset diabetes after transplantation and dyslipidemia. We aim to evaluate the molecular effects of CsA (5 mg/kg/day) and SRL (1 mg/kg/day) treatment for 3 and 9 weeks on lipid metabolism, in Wistar rats. Materials/Methods. Lipolysis was evaluated in isolated adipocytes, while triglycerides (TG) and non-esterified fatty acid (NEFA) were measured in serum. Gene and protein expression involved in lipid metabolism was assessed in adipose tissue and liver. Results. CsA and SRL treatments of rats for 3 and 9 weeks increased isoproterenol-stimulated lipolysis by 5-9 fold and 4-6 fold in isolated adipocytes, respectively. While CsA increased adipocyte weight and diameter, as well as NEFA and TG levels in circulation after 9 weeks, SRL treatment caused ectopic deposition of TG in the liver after 3 weeks. Moreover, ACC1 and FAS protein expression was increased after 3 weeks (>100%, p < 0.01), while HSL was increased after 9 weeks of CsA treatment. On the other hand, SRL decreased the expression of lipogenic genes, including ACC1 (50%, p < 0.05), lipin1 (25%, p < 0.05), PPAR-gamma (42%, p < 0.05) and SCD1 (80%, p < 0.001) in adipose tissue, after 3 weeks of treatment. Conclusion. The effects of both IAs on expression of lipolytic and lipogenic genes suggest that these agents influence lipid metabolism, thus contributing to the dyslipidemia observed during immunosuppressive therapy.
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| 66. |
- Magnusson, Björn, 1976, et al.
(författare)
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Cell death-inducing DFF45-like effector C is reduced by caloric restriction and regulates adipocyte lipid metabolism.
- 2008
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Ingår i: Metabolism: clinical and experimental. - : Elsevier BV. - 1532-8600. ; 57:9, s. 1307-13
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Tidskriftsartikel (refereegranskat)abstract
- Members of the cell death-inducing DFF45-like effector (CIDE) gene family have been shown to regulate lipid metabolism. In this article, we report that the third member of the human CIDE family, CIDEC, is down-regulated in response to a reduced caloric intake. The down-regulation was demonstrated by microarray and real-time polymerase chain reaction analysis of subcutaneous adipose tissue in 2 independent studies on obese patients undergoing treatment with a very low calorie diet. By analysis of CIDEC expression in 65 human tissues, we conclude that human CIDEC is predominantly expressed in subcutaneous adipocytes. Together, these observations led us to investigate the effect of decreased CIDEC expression in cultured 3T3-L1 adipocytes. Small interfering RNA-mediated knockdown of CIDEC resulted in an increased basal release of nonesterified fatty acids, decreased responsiveness to adrenergic stimulation of lipolysis, and increased oxidation of endogenous fatty acids. Thus, we suggest that CIDEC is a regulator of adipocyte lipid metabolism and may be important for the adipocyte to adapt to changes in energy availability.
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| 67. |
- Mostad, Ingrid L, et al.
(författare)
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Addition of n-3 fatty acids to a 4-hour lipid infusion does not affect insulin sensitivity, insulin secretion, or markers of oxidative stress in subjects with type 2 diabetes mellitus
- 2009
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Ingår i: Metabolism. - : Elsevier BV. - 0026-0495 .- 1532-8600. ; 58:12, s. 1753-1761
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Tidskriftsartikel (refereegranskat)abstract
- Fatty acids (FA) can impair glucose metabolism to a varying degree depending on time of exposure and also of type of FA. Here we tested for acute effects of marine n-3 FA on insulin sensitivity, insulin secretion, energy metabolism, and oxidative stress. This was a randomized, double-blind, crossover study in 11 subjects with type 2 diabetes mellitus. A 4-hour lipid infusion (Intralipid [Fresenius Kabi, Halden, Norway], total of 384 mL) was compared with a similar lipid infusion partly replaced by Omegaven (Fresenius Kabi) that contributed a median of 0.1 g fish oil per kilogram body weight, amounting to 0.04 g/kg of marine n-3 FA. Insulin sensitivity was assessed by isoglycemic hyperinsulinemic clamps; insulin secretion (measured after the clamps), by C-peptide glucagon tests; and energy metabolism, by indirect calorimetry. Infusion of Omegaven increased the proportion of n-3 FA in plasma nonesterified fatty acids (NEFA) compared with Intralipid alone (20:5n-3: median, 1.5% [interquartile range, 0.6%] vs -0.2% [0.2%], P = .001; 22:6n-3: 0.8% [0.4%] vs -0.7% [0.2%], P = .001). However, glucose utilization was not affected; neither was insulin secretion or total energy production (P = .966, .210, and .423, respectively, for the differences between the lipid clamps). Omegaven tended to lower oxidation of fat (P = .062) compared with Intralipid only, correlating with the rise in individual n-3 NEFA (r = 0.627, P = .039). The effects of clamping on phospholipid FA composition, leptin, adiponectin, or F(2)-isoprostane concentrations were not affected by Omegaven. Enrichment of NEFA with n-3 FA during a 4-hour infusion of Intralipid failed to affect insulin sensitivity, insulin secretion, or markers of oxidative stress in subjects with type 2 diabetes mellitus.
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| 68. |
- Müllner, Elisabeth, et al.
(författare)
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Serum metabolomics analysis reveals increased lipid catabolism in mildly hyperbilirubinemic Gilbert's syndrome individuals
- 2021
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Ingår i: Metabolism. - : Elsevier BV. - 0026-0495 .- 1532-8600. ; 125
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Tidskriftsartikel (refereegranskat)abstract
- Background: The protective role of mildly elevated bilirubin against CVD and diabetes mellitus type 2 (DMT2) is associated with a favorable lipid phenotype. As the mechanistic understanding of this protection in humans remains elusive, we aimed to assess the metabolomics profile of mildly hyperbilirubinemic (Gilbert's syndrome; GS) individuals especially targeting lipid catabolism. Methods and results: Using NMR serum metabolomics of 56 GS individuals and 56 age and gender-matched healthy controls, GS individuals demonstrated significantly greater concentrations of acetylcarnitine (+20%, p < 0.001) and the ketone bodies, 3-hydroxybutyric acid (+132%, p < 0.001), acetoacetic acid (+95%, p < 0.001) and acetone (+46%, p < 0.001). Metabolites associated with an increased mitochondrial lipid metabolism such as citrate (+15%, p < 0.001), anaplerotic amino acid intermediates and creatinine were significantly greater and creatine significantly reduced in GS individuals. Stimulators of lipid catabolism including AMPK (+59%, p < 0.001), pPPAR alpha (+24%, p < 0.001) and T3 (+9%, p = 0.009) supported the metabolomics data while concomitantly blood glucose and insulin (-33%, p = 0.002) levels were significantly reduced. We further showed that the increased lipid catabolism partially mediates the favorable lipid phenotype (lower triglycerides) of GS individuals. Increased trimethylamine (+35%, p < 0.001) indicated changes in trimethylamine metabolism, an emerging predictor of metabolic health. Conclusion: We showed an enhanced lipid catabolism in mildly hyperbilirubinemic individuals, novel evidence as to why these individuals are leaner and protected against chronic metabolic diseases emphasizing bilirubin to be a promising future target in obese and dyslipidemia patients. (c) 2021 Published by Elsevier Inc.
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| 69. |
- Nayak, RC, et al.
(författare)
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Albuminuria and hypertension are independently associated with circulating antipericyte autoantibodies in type 2 diabetic patients
- 2005
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Ingår i: Metabolism, Clinical and Experimental. - : Elsevier BV. - 1532-8600. ; 54:2, s. 188-193
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To determine whether albuminuria, hypertension, or HbA(1c) are independently associated with antipericyte autoantibodies (APAAs) in type 2 diabetes mellitus. Methods: Two hundred ninety-nine subjects with different degrees of retinopathy according to the Early Treatment Diabetic Retinopathy Study Scale participated in this study. Albuminuria was defined as an albumin/creatinine ratio above the normal cutoff limit, that is, 2.0 g/mol for men and 2.8 g/mol for women. Hypertension was defined as a diastolic blood pressure more than 90 mm Hg, a systolic blood pressure more than 140 mm Hg, or pharmacological antihypertensive treatment. Serum APAAs were detected by immunofluorescence on tissue-cultured bovine retinal pericytes. Association analysis was performed using univariate and multivariate statistical tools. Results: In type 2 diabetes, APAAs were independently associated with albuminuria (OR = 0.56; P < .04), hypertension (OR = 2.21; P < .01), as well as with proliferative retinopathy (OR = 0.39; P < .01). Conclusions: The increased prevalence of APAA in patients with hypertension may suggest that these antibodies are related to tissue damage and repair and that the decline in frequency with albuminuria may serve as a marker for more advanced angiopathy. Future longitudinal studies are needed to determine whether the frequency of APAA is associated with the progression of angiopathy, and to determine the biological activity and antigens recognized by the antibody.
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| 70. |
- Nedelcut, Sebastian, et al.
(författare)
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The risk and benefit of revisional vs. primary metabolic- bariatric surgery and drug therapy - A narrative review
- 2024
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Ingår i: Metabolism. - : Elsevier. - 0026-0495 .- 1532-8600. ; 154
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Tidskriftsartikel (refereegranskat)abstract
- Metabolic and bariatric surgery (MBS) leads to long-term weight loss, reduced risk of cardiovascular events and cancer, and reduced mortality. Sleeve gastrectomy and Roux-en-Y gastric bypass are currently the most common surgical techniques. Weight loss after MBS was previously believed to work through restriction and malabsorption, however, mechanistic studies show that MBS techniques with long term efficacy instead alter physiological signaling between the gut and the brain. In revisional MBS, the initial surgical technique is corrected, modified, or converted to a new one. The indication for revisional MBS can be to achieve further weight loss or improvement in obesity comorbidity, but it may be necessary due to complications (e.g., gastroesophageal reflux or obstruction). Revisional MBS is associated with an increased risk of surgical complications and often less weight loss compared to the results following primary surgery. This narrative review summarizes data from revisional MBS where information is often presented with inconsistent definitions for indications and outcomes, making comparison between strategies difficult. In summary, we suggest careful weighing of potential benefits and risks with revisional MBS, bearing in mind the option of add-on therapy with new anti-obesity drugs.
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