Effect of peripheral serotonin on energy metabolic capacities of skeletal muscle in mice fed a high fat diet

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 702-709-Obesity: Response to Interventions
Basic
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-703
Tatsuya Nakano1, Hitoshi Watanabe*1, Ryo Saito2, Yuya Nagasawa1, Keisuke Sumiyoshi2, Naoki Shirasu2, Kouichi Watanabe1 and Hisashi Aso1
1Tohoku University, Sendai, Japan, 2Tohoku University
[Objective]  Serotonin (5-HT) is synthesized by two distinct tryptophan hydroxylase (TPH) rate-limiting enzyme in brain (TPH2) and in periphery (TPH1). As 5-HT is inability to cross the blood-brain barrier, there are two independent serotonin systems: one in the central nervous system and the other in the periphery. 5-HT is a monoaminergic neurotransmitter with activities that modulate central and peripheral functions. 5-HT affects food intake, sleep, anxiety, sexual behavior and mood in the central nervous system. In periphery, it has been shown 5-HT is involved in glucose and lipid metabolism. However, the functions of 5-HT in peripheral tissue have not yet been fully elucidated. In this study, we have examined that the effect of the intraperitoneal injection of 5-HT on energy metabolism in skeletal muscle using obesity mouse model induced by high fat diet (HF).

[Results] Mice (C57BL/6, male) were fed a chow diet (Ch) or HF from 5 to 14 weeks of age. Mice were intraperitoneal injected with 1 mg 5-HT or PBS twice a week in both diet. Soleus muscle and gastrocnemius muscle were obtained from fasted mice in 14 weeks old. 5-HT shifted the profile of muscle fiber type from fast/glycolytic to slow/oxidative in the soleus muscle of HF fed mice. 5-HT increased the oxidative muscle fibers and the NAD+/NADH ratio in gastrocnemius muscle in HF fed mice. Additionally, the intraperitoneal injection of 5-HT elevated the expression of key genes related to energy homeostasis, such as type 2 iodothyronine deiodinase and uncoupling protein 3 in soleus muscle. 5-HT dramatically induced the elevation of mRNA expressions of peroxisome proliferator-activated receptor (PPAR)-γ coactivator 1α (PGC-1α)-b and -c, which were known as novel isoforms of PGC-1α and involved in mitochondrial biogenesis and fatty acid oxidation. Moreover, the pretreatment of several kinds of 5-HT receptor (5HTR) antagonist revealed that 5-HT induced the elevation of expression of PGC-1α-b and -c through the 5HTR2A or 7 in the soleus muscle and 5-HTR7 in the gastrocnemius muscle in mice at 8 weeks of age. Our findings suggest that peripheral 5-HT may contribute to increase the profile of slow/oxidative muscle fiber type and the energy expenditure of skeletal muscle by inducing the gene expressions of PGC-1α-b and -c.

Nothing to Disclose: TN, HW, RS, YN, KS, NS, KW, HA

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