Pinch Loss Ameliorates Obesity, Glucose Intolerance and Fatty Liver by Modulating Adipocyte Apoptosis in Mice

• DOI: 10.2337/figshare.15125067.v1
• Publication Date: 2021-08-11T14:07:42Z
• Authors: Huanqing Gao; Yiming Zhong; Zhen Ding; Sixiong Lin; Xiaoting Hou; Wanze Tang; Xiaoqian Zhou; Xuenong Zou; Jie Shao; Fan Yang; Xiaochun Bai; Chuanju Liu; Huiling Cao; Guozhi Xiao
• Keywords: Diet-induced obese

The mammalian focal adhesion proteins Pinch1/2 activate integrins and promote cell-ECM migration; however, their roles in adipose tissue metabolism are unclear. Here we find that high fat diet (HFD) feeding dramatically increases expression of white tissues (WAT) mice. Furthermore, Pinch1 is largely up-regulated WAT the Leptin-deficient ob/ob type 2 diabetic mice obese humans. While with loss adipocytes or global Pinch2 do not display any notable phenotypes, deleting globally significantly decreases body weight WAT, but brown (BAT), mass HFD-, normal chow (NCD)-, fed Pinch ameliorates HFD-induced glucose intolerance fatty liver. After HFD challenge, slightly, significantly, accelerates energy expenditure. adipocyte size alters distribution, it greatly cell apoptosis primarily epididymal to a less extent subcutaneous WAT. In vitro studies demonstrate by activating Bim/Caspase-8 pathway. vivo, genetic ablation Caspase-8 essentially abolishes ameliorating effects deficiency on obesity, liver Thus, previously unknown function control mass, via modulation apoptosis. We may define novel target for prevention treatment metabolic diseases, such as obesity diabetics.