Serotonin Improves High Fat Diet Induced Obesity in Mice

• Published in: PloS one Vol. 11; no. 1; p. e0147143
• Main Authors: Watanabe, Hitoshi, Nakano, Tatsuya, Saito, Ryo, Akasaka, Daisuke, Saito, Kazuki, Ogasawara, Hideki, Minashima, Takeshi, Miyazawa, Kohtaro, Kanaya, Takashi, Takakura, Ikuro, Inoue, Nao, Ikeda, Ikuo, Chen, Xiangning, Miyake, Masato, Kitazawa, Haruki, Shirakawa, Hitoshi, Sato, Kan, Tahara, Kohji, Nagasawa, Yuya, Rose, Michael T., Ohwada, Shyuichi, Watanabe, Kouichi, Aso, Hisashi
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 14.01.2016; Public Library of Science (PLoS)
• Subjects: Adipocytes; Adipose Tissue - metabolism; Adiposity; Animals; Biology; Biosynthesis; Body Weight; Body weight gain; Carbon dioxide; Central nervous system; Diet; Diet, High-Fat - adverse effects; Disease Models, Animal; Energy consumption; Energy expenditure; Energy Metabolism; Enlargement; Enzymes; Feeding behavior; Food intake; Gene Expression; Glucose; Glucose metabolism; Glycolysis; High fat diet; Hyperglycemia; Injection; Insulin; Laboratories; Lipid metabolism; Lipids; Male; Metabolic disorders; Metabolism; Mice; Muscle, Skeletal - metabolism; Muscles; Musculoskeletal system; Nervous system; Obesity; Obesity - etiology; Obesity - metabolism; Oxygen consumption; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Physiological aspects; Risk factors; RNA, Messenger - genetics; Rodents; Science; Serotonin; Serotonin - metabolism; Skeletal muscle; Soleus muscle; Transcription Factors - genetics; Transcription Factors - metabolism; United Kingdom; United States > US; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0147143

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.