ER stress in obesity pathogenesis and management

Trends Pharmacol Sci. 2022 Feb;43(2):97-109. doi: 10.1016/ Epub 2021 Dec 8.


Given the unprecedented global pandemic of obesity, a better understanding of the etiology of adiposity will be necessary to ensure effective management of obesity and related complications. Among the various potential factors contributing to obesity, endoplasmic reticulum (ER) stress refers to a state of excessive protein unfolding or misfolding that is commonly found in metabolic diseases including diabetes mellitus, insulin resistance (IR), and non-alcoholic fatty liver disease, although its role in obesogenesis remains controversial. ER stress is thought to drive adiposity by dampening energy expenditure, making ER stress a likely therapeutic target for the management of obesity. We summarize the role of ER stress and the ER stress response in the onset and development of obesity, and discuss the underlying mechanisms involved with a view to identifying novel therapeutic strategies for obesity prevention and management.

Keywords: ER stress; adaptive UPR; maladaptive UPR; obesity; unfolded protein response.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Endoplasmic Reticulum Stress
  • Humans
  • Insulin Resistance*
  • Metabolic Diseases*
  • Non-alcoholic Fatty Liver Disease* / etiology
  • Non-alcoholic Fatty Liver Disease* / therapy
  • Obesity / metabolism
  • Obesity / therapy