Serotonin Improves High Fat Diet Induced Obesity in Mice

PLoS One. 2016 Jan 14;11(1):e0147143. doi: 10.1371/journal.pone.0147143. eCollection 2016.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism
  • Adiposity
  • Animals
  • Body Weight
  • Diet, High-Fat* / adverse effects
  • Disease Models, Animal
  • Energy Metabolism
  • Gene Expression
  • Male
  • Mice
  • Muscle, Skeletal / metabolism
  • Obesity / etiology*
  • Obesity / metabolism*
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • RNA, Messenger / genetics
  • Serotonin / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, mouse
  • RNA, Messenger
  • Transcription Factors
  • Serotonin

Grants and funding

This work was supported by a grant for Research Project on Development of Agricultural Products and Foods with Health-promoting benefits (NARO) from the Ministry of Agriculture, Forestry and Fisheries and by Research Fellowship (23.7413) for Young Scientists Program from Japan Society for the Promotion of Science (JSPS). Co-author Kohji Tahara is employed by BML Inc. BML Inc. provided support in the form of salary for author KT but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific role of this author is articulated in the ‘author contributions’ section.