4‐PBA inhibits hypoxia‐induced lipolysis in rat adipose tissue and lipid accumulation in the liver through regulating ER stress

Author:

Xiong Yanlei12ORCID,Wang Yueming3,Xiong Yanlian3ORCID,Teng Lianghong1ORCID

Affiliation:

1. Department of Pathology Xuanwu Hospital, Capital Medical University Beijing China

2. Department of Pathophysiology Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS); School of Basic Medicine, Peking Union Medical College (PUMC) Beijing China

3. Department of Anatomy School of Basic Medicine, Binzhou Medical University Yantai China

Abstract

AbstractHigh‐altitude hypoxia may disturb the metabolic modulation and function of both adipose tissue and liver. The endoplasmic reticulum (ER) is a crucial organelle in lipid metabolism and ER stress is closely correlated with lipid metabolism dysfunction. The aim of this study is to elucidate whether the inhibition of ER stress could alleviate hypoxia‐induced white adipose tissue (WAT) lipolysis and liver lipid accumulation‐mediated hepatic injury. A rat model of high‐altitude hypoxia (5500 m) was established using hypobaric chamber. The response of ER stress and lipolysis‐related pathways were analyzed in WAT under hypoxia exposure with or without 4‐phenylbutyric acid (PBA) treatment. Liver lipid accumulation, liver injury, and apoptosis were evaluated. Hypoxia evoked significant ER stress in WAT, evidenced by increased GRP78, CHOP, and phosphorylation of IRE1α, PERK. Moreover, Lipolysis in perirenal WAT significantly increased under hypoxia, accompanied with increased phosphorylation of hormone‐sensitive lipase (HSL) and perilipin. Treatment with 4‐PBA, inhibitor of ER stress, effectively attenuated hypoxia‐induced lipolysis via cAMP‐PKA‐HSL/perilipin pathway. In addition, 4‐PBA treatment significantly inhibited the increase in fatty acid transporters (CD36, FABP1, FABP4) and ameliorated liver FFA accumulation. 4‐PBA treatment significantly attenuated liver injury and apoptosis, which is likely resulting from decreased liver lipid accumulation. Our results highlight the importance of ER stress in hypoxia‐induced WAT lipolysis and liver lipid accumulation.

Funder

National Natural Science Foundation of China

Natural Science Foundation of Shandong Province

Publisher

Wiley

Subject

Food Science

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