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Role of endoplasmic reticulum stress response in regulation of adipose tissue metabolism

HU Yu-Rong, CHEN Yong, LIU Yong^*

Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan 430072, China

Abstract

In eukaryotic cells, the endoplasmic reticulum (ER) is the key quality control organelle for cellular protein synthesis and processing. It also serves as an important site for Ca2+ storage and lipid biosynthesis. In response to a variety of external stimuli, a cellular unfolded protein response (UPR) is activated to handle ER stress caused by increased accumulation of unfolded or misfolded proteins at the ER. The UPR plays a crucial role in maintaining ER homeostasis and cell functions. Three ER-localized transmembrane proteins, inositol-requiring enzyme 1α (IRE1α), PKR-like ER kinase (PERK), and activating transcription factor 6 (ATF6), act to sense ER stress and mediate three canonical UPR signaling pathways. Besides restoring the protein folding capability to relieve ER stress, the UPR pathways have also been implicated in the regulation of cell metabolism and energy balance. In the state of overnutrition, ER stress has been documented to occur in adipose tissue that has a key role in energy storage and consumption. As an endocrine organ, adipose tissue regulates glucose and lipid metabolism through secreting adipocyte cytokines, and it undergoes metabolic inflammation during pathogenic development of obesity, insulin resistance and type 2 diabetes. In this review, we attempt to summarize the recent progress with regard to the UPR regulation of adipose tissue physiology. We wish to focus upon the mechanism by which ER stress response is linked to adipose tissue dysfunction, hoping to promote our current understanding of UPR signaling in the pathophysiology of obesity and related metabolic diseases.

Key words: endoplasmic reticulum stress; unfolded protein response; adipose tissue; metabolic inflammation; obesity

Received: 2020-04-06　　Accepted: 2020-05-13

Corresponding author: 刘勇　　E-mail: liuyong31279@whu.edu.cn

DOI: 10.13294/j.aps.2021.0005

Citing This Article：

HU Yu-Rong, CHEN Yong, LIU Yong. Role of endoplasmic reticulum stress response in regulation of adipose tissue metabolism. Acta Physiol Sin 2021; 73 (1): 115-125 (in Chinese with English abstract).