(The) role of adipose-derived serotonin in regulating of energy metabolism and adipocyte remodeling

Abstract

Obesity is defined as excessive fat mass and it is the major cause of many chronic disease such as diabetes, cardiovascular disease and cancer. Increased fat mass is the result of positive energy balance between energy intake and energy expenditure. Therefore, increasing energy expenditure and regulating adipose tissue metabolism are major targets for obesity treatment. The Serotonin (5-HT, 5-hyroxytryptamine) is a monoamine metabolite of the essential amino acid tryptophan and tryptophan hydroxylase 1 (TPH1) is the rate-limiting enzyme for 5-HT synthesis in non-neural peripheral tissues. Here, we show 5-HT in mature adipocytes regulates energy expenditure and lipid metabolism. Adipose tissue specific Tph1 knockout mice fed high fat diet (HFD) exhibit reduced lipid accumulation, increased thermogenesis and resistance to obesity. In addition, adipose tissue specific serotonin receptor 2A (Htr2a) KO mice fed HFD showed reduced lipid accumulation in eWAT and resistance to obesity. Serotonin receptor 1B (Htr1b) KO mice also showed reduced lipid accumulation in iWAT and BAT and increased energy expenditure. These data suggest that inhibition of serotonin signaling might be an effective strategy for obesity.