Fudan Researchers’ New Finding Offers a Breakthrough in Combating Obesity
Professor Wu Xiaohui and his team found out the significant role of GPR45 in obesity. The paper entitled “Disruption of Gpr45 causes reduced hypothalamic POMC expression and obesity” was published on Journal of Clinical Investigation as a research article.
Obesity increases the risks of diabetes, cardiovascular diseases and tumour. The rise in the occurrence of obesity has driven exploration of its underlying genetic basis and potential targets for intervention. In this study, Wu and his colleagues identified 5 additional obesity loci out of 408 in a forward genetic screen of mutant mice generated by piggyBac insertional mutagenesis.
Disruption of GPR45 led to increased adiposity at the time of weaning and increases in body mass, fat content, glucose intolerance, and hepatic steatosis with advancing age. Mice with disruptions in GPR45 also displayed a reduction in expression of the metabolic regulator POMC and less energy expenditure prior to the onset of obesity. Mechanistically, the team determined that GPR45 regulates POMC expression via the JAK/STAT pathway in a cell-autonomous manner. Consistent with this finding, intraventricular administration of melanotan-2, an analog of the POMC derivative α-MSH, suppressed adult obesity in GPR45 mutants.
These results revealed that GPR45 is a regulator of POMC signaling and energy expenditure, which suggests that it may be a potential intervention target to combat obesity.
The research has been sponsored by the National Committee of Natural Science Fund, Project 863 of the Department of Science and Technology as well as the Committee of Science and Technology of Shanghai.