1985-P: Inhibition of Adipocyte-Derived Serotonin Protects from High-Fat Diet-Induced Obesity by Increasing Energy Expenditure

Serotonin (5-HT) is a monoamine that has various functions in both neuronal and non-neuronal systems. 5-HT has been known as an anorexigenic neurotransmitter in central nervous system. However, accumulating evidences suggest that peripheral 5-HT may also affect organismal energy homeostasis. Here we demonstrate the role of adipocyte-derived 5-HT in the regulation of systemic energy metabolism. The expression of tryptophan hydroxylase-1 (Tph1), the rate-limiting enzyme for 5-HT synthesis, and tissue 5-HT level were increased in white adipose tissue (WAT) when mice were fed with high fat diet. Pharmacological inhibition of 5-HT synthesis using Tph inhibitor suppressed the lipogenesis in epididymal WAT, induced beige adipogenesis in inguinal WAT and activated the adaptive thermogenesis in brown adipose tissue (BAT). Adipocyte-specific Tph1 KO (Tph1 FKO) mice exhibited similar phenotypes, suggesting the localized effects of 5-HT on adipose tissues. Tph1 FKO mice showed decreased body fat mass and increased energy expenditure, resulting in improved glucose tolerance. Ucp1 expression increased in the Tph1 FKO iWAT. These data suggest important roles of adipocyte-derived 5-HT in controlling energy homeostasis.