Serotonin Improves High Fat Diet Induced Obesity in Mice

Hitoshi Watanabe, Tatsuya Nakano, Ryo Saito, D Aksaka, K Saito, Hideki Ogasawara, Takeshi Minashima, Kohtaro Miyazawa, Takashi Kanaya, Ikuro Takakura, N Inoue, Ikuo Ikeda, X Chen, M. Miyake, haruki kitazawa, H Shirakawa, Katsuyoshi Sato, Koji Tahara, Yuya Nagasawa, Kouichi WatanabeMichael Rose, Hisashi Aso

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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.
Original languageEnglish
Article numbere0147143
JournalPLoS One
Issue number1
Publication statusPublished - 14 Jan 2016


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