Novel Role of Peripheral Serotonin as an Obesity

  • Hit 58
  • Writer 최고관리자
  • 2017-09-29


[2017 Fall Life Sciences & IBB  Seminar]

▶Subject: Novel Role of Peripheral Serotonin as an Obesity

▶Speaker: Prof. Hail Kim (KAIST)
▶Date: 4:30PM/Oct. 13 (Fri.)/2017
▶Place: Auditorium(1F), POSTECH Biotech Center
▶Abctract: Serotonin (5-HT) has been thought as a target for anti-obesity treatment since central serotonin is an anorexigenic neurotransmitter in the brain. However, recent studies suggest the different actions of 5-HT on systemic energy homeostasis at the periphery. Body weight is reduced in Tph1 and Tph2 knockout (KO) mice. Mice with a SERT-null mutation (Slc6a4 KO) exhibit an obese phenotype despite they are expected to be slim due to the increased 5-HT activity. Pharmacological inhibition of 5-HT synthesis inhibits lipogenesis in epididymal white adipose tissue (WAT), induces browning in inguinal WAT, activates thermogenesis in brown adipose tissue (BAT) and reduces lipid accumulation in the liver.
Since whole body energy balance is achieved through the coordinated regulation of energy intake and energy expenditure in various tissues, we have been trying to identify how 5-HT regulates systemic energy homeostasis in peripheral tissues. In this regard, we have generated and analyzed several tissue specific knock-out (KO) mice of Tph1 and Htr genes to tease out the tissue specific role of peripheral 5-HT. Adipose tissue specific Tph1 KO exhibit similar phenotypes as mice in which 5-HT synthesis is inhibited systemically, suggesting the localized effects of 5-HT on adipose tissues. Htr3a KO mice exhibit increased energy expenditure suggesting its inhibitory role in BAT. Adipose tissue specific Htr2a KO mice showed the reduction of lipid accumulation without induction of beige adipocyte in WAT, indicating its specific role in lipogenesis. We have also identified a novel role of gut-derived 5-HT on hepatic energy metabolism using gut specific Tph1 KO mice. Our works can provide a novel insight on the role of peripheral 5-HT in the regulation of systemic energy homeostasis.