Regulation of systemic energy homeostasis by serotonin in adipose tissues

Abstract

Central serotonin (5-HT) is an anorexigenic neurotransmitter in the brain. However, accumulating evidence suggests peripheral 5-HT may affect organismal energy homeostasis. Here we show 5-HT regulates white and brown adipose tissue function. Pharmacological inhibition of 5-HT synthesis leads to inhibition of lipogenesis in epididymal white adipose tissue (WAT), induction of browning in inguinal WAT and activation of adaptive thermogenesis in brown adipose tissue (BAT). Mice with inducible Tph1 KO in adipose tissues exhibit a similar phenotype as mice in which 5-HT synthesis is inhibited pharmacologically, suggesting 5-HT has localized effects on adipose tissues. In addition, Htr3a KO mice exhibit increased energy expenditure and reduced weight gain when fed a high-fat diet. Treatment with an Htr2a antagonist reduces lipid accumulation in 3T3-L1 adipocytes. These data suggest important roles for adipocyte-derived 5-HT in controlling energy homeostasis.

A Tryptophan Hydroxylase Inhibitor Decreases Hepatic FGF21 Expression and Circulating FGF21 in Mice Fed A High-Fat Diet

“…Our results support a previous report that treatment with PCPA prevents obesity in mice fed a high fat diet [7]. Treatment with PCPA inhibits lipogenesis in epididymal white adipose tissue and promotes thermogenesis via uncoupling prietin-1 (UCP1) in brown adipose tissue, leading to weight loss in mice fed a high-fat diet [7].…”

“…Treatment with PCPA inhibits lipogenesis in epididymal white adipose tissue and promotes thermogenesis via uncoupling prietin-1 (UCP1) in brown adipose tissue, leading to weight loss in mice fed a high-fat diet [7]. Although treatment with PCPA (300 mg/kg) for 12 weeks did not suppress daily food intake in the previous report [7], our results demonstrated that treatment with the PCPA (500 mg/kg) for 3 days significantly suppressed daily food intake in mice fed a highfat diet. The differences in the effect of PCPA on food intake might be due to the differences in the doses of PCPA.…”

“…On the other hand, Tph2-deficient mice fed a normal diet exhibit decreased food intake and increased energy expenditure, leading to decreases in body weight and fat pad weight [2,3]. Systemic administration of p-chlorophenylalanine (PCPA), a Tph inhibitor, remarkably decreases brain and serum 5-HT levels in mice [4][5][6] and prevents obesity and impaired glucose tolerance in mice fed a high-fat diet [7].…”

Energy Homeostasis by the Peripheral Serotonergic System

“…There is a report that adipocyte-derived serotonin has the important role in energy homeostasis in the whole body [34]. Tph1 expression and serotonin concentrations were increased in epididymal and subcutaneous WAT in a diet-induced obesity mouse model.…”

PKA regulatory subunit 1A inactivating mutation induces serotonin signaling in primary pigmented nodular adrenal disease

“…In peripheral organs, 5-HT is involved in the regulation of gastrointestinal mobility, cardiovascular functions, and bladder emptying (3)(4)(5). 5-HT is also able to act as an autocrine/paracrine factor to influence several physiological processes, including osteoclastogenesis (6), regulation of the pancreatic β cell mass during pregnancy (7), metabolism in adipose tissue (8,9), and mammary gland development (10).…”