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

Syndecans are transmembrane proteoglycans that, like integrins, bind to components of the extracellular matrix. Previously, we showed significant associations of genetic variants in the () 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 and the risk of coronary artery disease in middle-aged patients. Here, we investigated whether deletion of promotes metabolic derangements associated with diet-induced obesity by feeding homozygous male and female -deficient () mice and their age-matched wild-type (WT) mice a high-fat diet (HFD). We found that WT and mice gained similar weight. However, while no differences were observed in males, HFD-fed female 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 in adiposity and its complications.