ER stress in obesity pathogenesis and management

Amir Ajoolabady; Simin Liu; Daniel J Klionsky; Gregory Y H Lip; Jaakko Tuomilehto; Sina Kavalakatt; David M Pereira; Afshin Samali; Jun Ren

doi:10.1016/j.tips.2021.11.011

ER stress in obesity pathogenesis and management

Trends Pharmacol Sci. 2022 Feb;43(2):97-109. doi: 10.1016/j.tips.2021.11.011. Epub 2021 Dec 8.

Authors

Amir Ajoolabady¹, Simin Liu², Daniel J Klionsky³, Gregory Y H Lip⁴, Jaakko Tuomilehto⁵, Sina Kavalakatt⁶, David M Pereira⁷, Afshin Samali⁸, Jun Ren⁹

Affiliations

¹ University of Wyoming College of Health Sciences, Laramie, WY 82071, USA; Shanghai Institute of Cardiovascular Diseases, Department of Cardiology, Zhongshan Hospital Fudan University, Shanghai 200032, China.
² Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Departments of Epidemiology, Medicine, and Surgery and Center for Global Cardiometabolic Health, Brown University, Providence, RI, USA.
³ Life Sciences Institute and Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
⁴ University of Liverpool Institute of Ageing and Chronic Disease, Liverpool Centre for Cardiovascular Science, Liverpool, UK.
⁵ Public Health Promotion Unit, Finnish Institute for Health and Welfare, Helsinki, Finland; Department of Public Health, University of Helsinki, Helsinki, Finland; Diabetes Research Group, King Abdulaziz University, Jeddah, Saudi Arabia.
⁶ Biochemistry and Molecular Biology Department, Research Division, Dasman Diabetes Institute, Dasman, Kuwait.
⁷ REQUIMTE/LAQV, Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal. Electronic address: dpereira@ff.up.pt.
⁸ Apoptosis Research Centre, School of Natural Sciences, National University of Ireland, Galway, Ireland. Electronic address: afshin.samali@nuigalway.ie.
⁹ Shanghai Institute of Cardiovascular Diseases, Department of Cardiology, Zhongshan Hospital Fudan University, Shanghai 200032, China; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98195, USA. Electronic address: jren_aldh2@outlook.com.

Abstract

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

Grants and funding

R35 GM131919/GM/NIGMS NIH HHS/United States