Programmed Cell Death-4 Deficiency Prevents Diet-Induced Obesity, Adipose Tissue Inflammation, and Insulin Resistance
- Qun Wang1⇑,
- Zhaojing Dong1,
- Xianglan Liu1,
- Xingguo Song1,
- Qiang Song2,
- Qianwen Shang1,
- Yang Jiang1,
- Chun Guo1 and
- Lining Zhang1⇑
- 1Department of Immunology, Shandong University School of Medicine, Jinan, Shangdong, China
- 2Department of Radiology, Shandong Chest Hospital, Jinan, Shangdong, China
- Corresponding authors: Qun Wang, , and Lining Zhang, .
Programmed cell death-4 (PDCD4), a selective protein translation inhibitor, has shown proinflammatory effect in some inflammatory diseases, but its roles in 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 insulin sensitivity. Compared with wild-type obese mice, HFD-fed PDCD4−/− mice showed higher energy expenditure, lower epididymal fat weight, and reduced macrophage infiltration inflammatory cytokine secretion in white adipose tissue (WAT). Alleviated hepatic steatosis along with decreased plasma levels of triglyceride and cholesterol was also observed in these mice. Importantly, PDCD4 appeared to disturb lipid metabolism via inhibiting the expression of liver X receptor (LXR)-α, a master modulator of lipid homeostasis, which was elevated in HFD-fed PDCD4−/− mice accompanied by upregulation of its target genes and relieved endoplasmic reticulum stress in WAT. These data demonstrate that PDCD4 deficiency protects mice against diet-induced obesity, WAT inflammation, and insulin resistance through restoring the expression of LXR-α, thereby proposing PDCD4 as a potential target for treating obesity-associated diseases.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db13-0097/-/DC1.
- Received January 25, 2013.
- Accepted August 26, 2013.
- © 2013 by the American Diabetes Association.
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