Dataset Information

Genetic Deletion of Syndecan-4 Alters Body Composition, Metabolic Phenotypes, and the Function of Metabolic Tissues in Female Mice Fed A High-Fat Diet.

ABSTRACT: Syndecans are transmembrane proteoglycans that, like integrins, bind to components of the extracellular matrix. Previously, we showed significant associations of genetic variants in the Syndecan-4 (SDC4) gene with intra-abdominal fat, fasting plasma glucose levels, and insulin sensitivity index in children, and with fasting serum triglyceride levels in healthy elderly subjects. An independent study also reported a correlation between SDC4 and the risk of coronary artery disease in middle-aged patients. Here, we investigated whether deletion of Sdc4 promotes metabolic derangements associated with diet-induced obesity by feeding homozygous male and female Sdc4-deficient (Sdc4-/-) mice and their age-matched wild-type (WT) mice a high-fat diet (HFD). We found that WT and Sdc4-/- mice gained similar weight. However, while no differences were observed in males, HFD-fed female Sdc4-/- mice exhibited a higher percentage of body fat mass than controls and displayed increased levels of plasma total cholesterol, triglyceride, and glucose, as well as reduced whole-body insulin sensitivity. Additionally, they had an increased adipocyte size and macrophage infiltration in the visceral adipose tissue, and higher triglyceride and fatty acid synthase levels in the liver. Together with our previous human genetic findings, these results provide evidence of an evolutionarily conserved role of SDC4 in adiposity and its complications.

SUBMITTER: De Luca M

PROVIDER: S-EPMC6893658 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genetic Deletion of Syndecan-4 Alters Body Composition, Metabolic Phenotypes, and the Function of Metabolic Tissues in Female Mice Fed A High-Fat Diet.

De Luca Maria M Vecchie' Denise D Athmanathan Baskaran B Gopalkrishna Sreejit S Valcin Jennifer A JA Swain Telisha M TM Sertie Rogerio R Wekesa Kennedy K Rowe Glenn C GC Bailey Shannon M SM Nagareddy Prabhakara R PR

Nutrients 20191118 11

Syndecans are transmembrane proteoglycans that, like integrins, bind to components of the extracellular matrix. Previously, we showed significant associations of genetic variants in the Syndecan-4 (SDC4) gene with intra-abdominal fat, fasting plasma glucose levels, and insulin sensitivity index in children, and with fasting serum triglyceride levels in healthy elderly subjects. An independent study also reported a correlation between SDC4 and the risk of coronary artery dise ...[more]

PMID: 31752080

Similar Datasets

Project description:BACKGROUND:Insulin resistance underlies metabolic syndrome and is associated with excess adiposity and visceral fat accumulation, which is more frequently observed in males than females. However, in young females, the prevalence of metabolic syndrome is rising, mainly driven by accumulation of abdominal visceral fat. The degree to which sex-related differences could influence the development of insulin resistance remains unclear, and studies of potential therapeutic strategies to combat metabolic syndrome using rodent models have focused predominantly on males. We therefore evaluated the effects of two nutritional supplements derived from botanical sources, an extract of Artemisia dracunculus L. (termed PMI5011) and Momordica charantia (commonly known as bitter melon), on female mice challenged with a high-fat diet in order to determine if dietary intake of these supplements could ameliorate obesity-induced insulin resistance and metabolic inflexibility in skeletal muscle. METHODS:Body composition, physical activity and energy expenditure, fatty acid oxidation, insulin signaling, and gene and protein expression of factors controlling lipid metabolism and ectopic lipid accumulation were evaluated in female mice fed a high-fat diet supplemented with either PMI5011 or bitter melon. Statistical significance was assessed by unpaired two-tailed t test and repeated measures ANOVA. RESULTS:PMI5011 supplementation resulted in increased body weight and adiposity, while bitter melon did not induce changes in these parameters. Pyruvate tolerance testing indicated that both supplements increased hepatic glucose production. Both supplements induced a significant suppression in fatty acid oxidation in skeletal muscle homogenates treated with pyruvate, indicating enhanced metabolic flexibility. PMI5011 reduced lipid accumulation in skeletal muscle, while bitter melon induced a downward trend in lipid accumulation in the skeletal muscle and liver. This was accompanied by transcriptional regulation of autophagic genes by bitter melon in the liver. CONCLUSIONS:Data from the current study indicates that dietary supplementation with PMI5011 and bitter melon evokes a divergent, and generally less favorable, set of metabolic responses in female mice compared to effects previously observed in males. Our findings underscore the importance of considering sex-related variations in responses to dietary supplementation aimed at combating metabolic syndrome.

Dataset Information

Genetic Deletion of Syndecan-4 Alters Body Composition, Metabolic Phenotypes, and the Function of Metabolic Tissues in Female Mice Fed A High-Fat Diet.

Publications

Genetic Deletion of <i>Syndecan-4</i> Alters Body Composition, Metabolic Phenotypes, and the Function of Metabolic Tissues in Female Mice Fed A High-Fat Diet.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets