Programmed Cell Death-4 Deficiency Prevents Diet-Induced Obesity, Adipose Tissue Inflammation, and Insulin Resistance

• DOI: 10.2337/db13-0097
• Publication Date: 2013-08-30T02:11:30Z
• Authors: Qun Wang; Zhaojing Dong; Xianglan Liu; Xingguo Song; Qiang Song; Qianwen Shang; Yang Jiang; Chun Guo; Lining Zhang
• Keywords: Steatosis; Proinflammatory cytokine; Adipose tissue macrophages

Programmed cell death-4 (PDCD4), a selective protein translation inhibitor, has shown proinflammatory effect in some inflammatory diseases, but its roles obesity remain unestablished. This study aims to investigate the effects of PDCD4 on obesity, inflammation, and insulin resistance. Surprisingly, high-fat diet (HFD)-fed PDCD4-deficient (PDCD4−/−) mice exhibited an absolutely lean phenotype together with improved sensitivity. Compared wild-type obese mice, HFD-fed PDCD4−/− showed higher energy expenditure, lower epididymal fat weight, reduced macrophage infiltration cytokine secretion white adipose tissue (WAT). Alleviated hepatic steatosis along decreased plasma levels triglyceride cholesterol was also observed these mice. Importantly, appeared disturb lipid metabolism via inhibiting expression liver X receptor (LXR)-α, master modulator homeostasis, which elevated accompanied by upregulation target genes relieved endoplasmic reticulum stress WAT. These data demonstrate that deficiency protects against diet-induced WAT resistance through restoring LXR-α, thereby proposing as potential for treating obesity-associated diseases.