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Obes Rev. 2018 Jun;19(6):770-785. doi: 10.1111/obr.12673. Epub 2018 Mar 7.

Hypothalamic endoplasmic reticulum stress as a key mediator of obesity-induced leptin resistance.

Ye Z1,2, Liu G3, Guo J1, Su Z1,2.

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Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Key Unit of Modulating Liver to Treat Hyperlipemia SATCM (State Administration of Traditional Chinese Medicine), Guangdong Pharmaceutical University, Guangzhou, China.
Guangdong Engineering Research Center of Natural Products and New Drugs, Guangdong Pharmaceutical University, Guangzhou, China.
Shenzhen Center for Disease Control and Prevention, Shenzhen, China.


Obesity is an epidemic disease that is increasing worldwide and is a major risk factor for many metabolic diseases. However, effective agents for the prevention or treatment of obesity remain limited. Therefore, it is urgent to clarify the pathophysiological mechanisms underlying the development and progression of obesity and exploit potential agents to cure and prevent this disease. According to a recent study series, obesity is associated with the development of endoplasmic reticulum stress and the activation of its stress responses (unfolded protein response) in metabolically active tissues, which contribute to the development of obesity-related insulin and leptin resistance, inflammation and energy imbalance. Hypothalamic endoplasmic reticulum stress is the central mechanism underlying the development of obesity-associated leptin resistance and disruption of energy homeostasis; thus, targeting endoplasmic reticulum stress offers a promising therapeutic strategy for improving leptin sensitivity, increasing energy expenditure and ultimately combating obesity. In this review, we highlight the relationship between and mechanism underlying hypothalamic endoplasmic reticulum stress and obesity-associated leptin resistance and energy imbalance and provide new insight regarding strategies for the treatment of obesity.


Obesity; endoplasmic reticulum stress; energy balance; leptin resistance

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