PLoS ONE (Jan 2016)

Serotonin Improves High Fat Diet Induced Obesity in Mice.

  • Hitoshi Watanabe,
  • Tatsuya Nakano,
  • Ryo Saito,
  • Daisuke Akasaka,
  • Kazuki Saito,
  • Hideki Ogasawara,
  • Takeshi Minashima,
  • Kohtaro Miyazawa,
  • Takashi Kanaya,
  • Ikuro Takakura,
  • Nao Inoue,
  • Ikuo Ikeda,
  • Xiangning Chen,
  • Masato Miyake,
  • Haruki Kitazawa,
  • Hitoshi Shirakawa,
  • Kan Sato,
  • Kohji Tahara,
  • Yuya Nagasawa,
  • Michael T Rose,
  • Shyuichi Ohwada,
  • Kouichi Watanabe,
  • Hisashi Aso

DOI
https://doi.org/10.1371/journal.pone.0147143
Journal volume & issue
Vol. 11, no. 1
p. e0147143

Abstract

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There are two independent serotonin (5-HT) systems of organization: one in the central nervous system and the other in the periphery. 5-HT affects feeding behavior and obesity in the central nervous system. On the other hand, peripheral 5-HT also may play an important role in obesity, as it has been reported that 5-HT regulates glucose and lipid metabolism. Here we show that the intraperitoneal injection of 5-HT to mice inhibits weight gain, hyperglycemia and insulin resistance and completely prevented the enlargement of intra-abdominal adipocytes without having any effect on food intake when on a high fat diet, but not on a chow diet. 5-HT increased energy expenditure, O2 consumption and CO2 production. This novel metabolic effect of peripheral 5-HT is critically related to a shift in the profile of muscle fiber type from fast/glycolytic to slow/oxidative in soleus muscle. Additionally, 5-HT dramatically induced an increase in the mRNA expression of peroxisome proliferator-activated receptor coactivator 1α (PGC-1α)-b and PGC-1α-c in soleus muscle. The elevation of these gene mRNA expressions by 5-HT injection was inhibited by treatment with 5-HT receptor (5HTR) 2A or 7 antagonists. Our results demonstrate that peripheral 5-HT may play an important role in the relief of obesity and other metabolic disorders by accelerating energy consumption in skeletal muscle.