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标题：Genetic Deletion of Syndecan-4 Alters Body Composition, Metabolic Phenotypes, and the Function of Metabolic Tissues in Female Mice Fed A High-Fat Diet
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作者：Maria De Luca , , Denise Vecchie’ , , Baskaran Athmanathan , Sreejit Gopalkrishna , Jennifer A. Valcin , Telisha M. Swain , Rogerio Sertie , Kennedy Wekesa , Glenn C. Rowe , Shannon M. Bailey ; Prabhakara R. Nagareddy
期刊名称：Nutrients
电子版ISSN：2072-6643
出版年度：2019
卷号：11
期号：11
页码：1-11
DOI：10.3390/nu11112810
出版社：MDPI Publishing
摘要：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.
关键词：heparan sulfate proteoglycans; extracellular matrix; obesity; lipid profile; steatosis; insulin resistance heparan sulfate proteoglycans ; extracellular matrix ; obesity ; lipid profile ; steatosis ; insulin resistance