Endoplasmic reticulum stress: bridging inflammation and obesity-associated adipose tissue

Abstract

Obesity presents a significant global health challenge, increasing the susceptibility to chronic conditions such as diabetes, cardiovascular disease, and hypertension. Within the context of obesity, lipid metabolism, adipose tissue formation, and inflammation are intricately linked to endoplasmic reticulum stress (ERS). ERS modulates metabolism, insulin signaling, inflammation, as well as cell proliferation and death through the unfolded protein response (UPR) pathway. Serving as a crucial nexus, ERS bridges the functionality of adipose tissue and the inflammatory response. In this review, we comprehensively elucidate the mechanisms by which ERS impacts adipose tissue function and inflammation in obesity, aiming to offer insights into targeting ERS for ameliorating metabolic dysregulation in obesity-associated chronic diseases such as hyperlipidemia, hypertension, fatty liver, and type 2 diabetes.

The cellular and molecular targets of natural products against metabolic disorders: a translational approach to reach the bedside

“… 140 Excess metabolites in the ER compartment can disrupt the interactions of 78 kDa GRP78 with inositol‐requiring enzyme 1, protein kinase R‐like ER kinase, and activating transcription factor 6 (ATF6), leading to ER stress and metabolic inflammation. 141 Previously, celastrol was shown to reduce ER stress; however, the exact molecular mechanisms and target proteins involved have not been determined. 142 In 2022, Rong's group 143 showed that GRP78 was the major celastrol‐bound protein in RAW264.7 murine macrophages.…”