Latexin deficiency attenuates adipocyte differentiation and protects mice against obesity and metabolic disorders induced by high-fat diet

作者：Shuang Kan, Rong Li, Yanhui Tan, Fang Yang, Shaohua Xu, Lingzhu Wang, Lijun Zhang, Xuchen Sun, Xuanming Chen, Yuting Yang, Wei Shu, Huaibin Wan, Zhengfeng Chen, Hong Liang, Ming Chen · 发表于：Cell Death and Disease · 年份：2022 · DOI：10.1038/s41419-022-04636-9 · 被引用次数：25 · 研究领域：Adipokines, Inflammation, and Metabolic Diseases、Adipose Tissue and Metabolism、Retinoids in leukemia and cellular processes

Abstract Obesity is a risk factor for many chronic diseases, and is associated with increased incidence rate of type 2 diabetes, hypertension, dyslipidemia and cardiovascular diseases. Adipocyte differentiation play critical role during development of obesity. Latexin (LXN), a mammalian carboxypeptidase inhibitor, plays important role in the proliferation and differentiation of stem cells, and highlights as a differentiation-associated gene that was significantly downregulated in prostate stem cells and whose expression increases through differentiation. However, it is unclear whether LXN is involved in adipocyte differentiation. The aim of this study was to evaluate the role of LXN on adipocyte differentiation, as well as its effects on high fat-induced obesity and metabolic disorders. In this study, we determine the expression of LXN in adipose tissue of lean and fat mice by Western blot, qPCR and immunohistochemistry. We found that LXN in fat tissues was continuous increased during the development of diet-induced obesity. We fed wild-type (WT) and LXN −/− mice with high-fat diet (HFD) to study the effects of LXN on obesity and related metabolic functions. We found that mice deficient in LXN showed resistance against high-fat diet (HFD)-induced obesity, glucose tolerance, insulin tolerance and hepatic steatosis. In vitro studies indicated that LXN was highly induced during adipocyte differentiation, and positively regulated adipocyte differentiation and adipogenesis in 3T3-...