Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Department of Biology, Ecology and Earth Sciences, University of Calabria, 87036 Rende, Italy.
Nutrients. 2019 Nov 18;11(11):2810. doi: 10.3390/nu11112810.
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.
黏附素是一种跨膜蛋白聚糖，与整合素一样，可与细胞外基质的成分结合。此前，我们发现基因中的遗传变异与儿童的腹腔内脂肪、空腹血浆葡萄糖水平和胰岛素敏感指数以及健康老年人的空腹血清甘油三酯水平有显著相关性。一项独立研究还报告称，与中年患者的冠心病风险之间存在相关性。在这里，我们通过喂养纯合雄性和雌性缺失 () 基因的 () 小鼠及其同龄野生型 (WT) 小鼠高脂肪饮食 (HFD)，研究了缺失是否会促进与饮食诱导肥胖相关的代谢紊乱。我们发现 WT 和 小鼠体重增加相似。然而，在雄性中没有观察到差异，而 HFD 喂养的雌性 小鼠的体脂肪百分比高于对照组，并表现出血浆总胆固醇、甘油三酯和葡萄糖水平升高，以及全身胰岛素敏感性降低。此外，它们的内脏脂肪组织中脂肪细胞增大和巨噬细胞浸润增加，肝脏中的甘油三酯和脂肪酸合酶水平升高。结合我们之前的人类遗传发现，这些结果提供了证据，证明 在肥胖及其并发症中的作用是进化保守的。
