Knockout of inositol-requiring enzyme 1? in pro-opiomelanocortin neurons decreases fat mass via increasing energy expenditure.

ABSTRACT: Although numerous functions of inositol-requiring enzyme 1? (IRE1?) have been identified, a role of IRE1? in pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus is largely unknown. Here, we showed that mice lacking IRE1? specifically in POMC neurons (PIKO) are lean and resistant to high-fat diet-induced obesity and obesity-related insulin resistance, liver steatosis and leptin resistance. Furthermore, PIKO mice had higher energy expenditure, probably due to increased thermogenesis in brown adipose tissue. Additionally, ?-melanocyte-stimulating hormone production was increased in the hypothalamus of PIKO mice. These results demonstrate that IRE1? in POMC neurons plays a critical role in the regulation of obesity and obesity-related metabolic disorders. Our results also suggest that IRE1? is not only an endoplasmic reticulum stress sensor, but also a new potential therapeutic target for obesity and obesity-related metabolic diseases.

SUBMITTER: Xiao Y 

PROVIDER: S-EPMC5008012 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature