PTPRT Regulates High-Fat Diet-Induced Obesity and Insulin Resistance

Obesity is a risk factor for many human diseases. However, the underlying molecular causes of obesity are not well understood. Here, we report that protein tyrosine phosphatase receptor T (PTPRT) knockout mice are resistant to high-fat diet-induced obesity. Those mice avoid many deleterious side effects of high-fat diet-induced obesity, displaying improved peripheral insulin sensitivity, lower blood glucose and insulin levels. Compared to wild type littermates, PTPRT knockout mice show reduced food intake. Consistently, STAT3 phosphorylation is up-regulated in the hypothalamus of PTPRT knockout mice. These studies implicate PTPRT-modulated STAT3 signaling in the regulation of high-fat diet-induced obesity.肥胖是多种人类疾病的危险因素。然而，肥胖发生的潜在分子机制尚未完全明确。本研究发现，蛋白酪氨酸磷酸酶受体T（Protein Tyrosine Phosphatase Receptor T, PTPRT）敲除小鼠可抵抗高脂饮食诱导的肥胖。该类小鼠可规避高脂饮食诱导肥胖所引发的多种有害不良反应，表现为外周胰岛素敏感性提升、血糖与胰岛素水平降低。与野生型同窝仔鼠相比，PTPRT敲除小鼠的进食量显著减少。与之相一致的是，PTPRT敲除小鼠下丘脑组织中信号转导与转录激活因子3（STAT3）的磷酸化水平上调。本研究结果表明，PTPRT调控的STAT3信号通路参与了高脂饮食诱导肥胖的调控过程。