Serotonin Regulates De Novo Lipogenesis in Adipose Tissues through Serotonin Receptor 2A.
Adipose tissue, white
Lipogenesis
Obesity
Serotonin
Journal
Endocrinology and metabolism (Seoul, Korea)
ISSN: 2093-5978
Titre abrégé: Endocrinol Metab (Seoul)
Pays: Korea (South)
ID NLM: 101554139
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
27
11
2019
accepted:
07
04
2020
entrez:
4
7
2020
pubmed:
4
7
2020
medline:
12
6
2021
Statut:
ppublish
Résumé
Obesity is defined as excessive fat mass and is a major cause of many chronic diseases such as diabetes, cardiovascular disease, and cancer. Increasing energy expenditure and regulating adipose tissue metabolism are important targets for the treatment of obesity. Serotonin (5-hydroxytryptophan [5-HT]) is a monoamine metabolite of the essential amino acid tryptophan. Here, we demonstrated that 5-HT in mature adipocytes regulated energy expenditure and lipid metabolism. Tryptophan hydroxylase 1 (TPH1) is the rate-limiting enzyme during 5-HT synthesis in non-neural peripheral tissues. We generated adipose tissue-specific Tph1 knockout (Tph1 FKO) mice and adipose tissue-specific serotonin receptor 2A KO (Htr2a FKO) mice and analyzed their phenotypes during high-fat diet (HFD) induced obesity. Tph1 FKO mice fed HFD exhibited reduced lipid accumulation, increased thermogenesis, and resistance to obesity. In addition, Htr2a FKO mice fed HFD showed reduced lipid accumulation in white adipose tissue and resistance to obesity. These data suggest that the inhibition of serotonin signaling might be an effective strategy in obesity.
Sections du résumé
BACKGROUND
Obesity is defined as excessive fat mass and is a major cause of many chronic diseases such as diabetes, cardiovascular disease, and cancer. Increasing energy expenditure and regulating adipose tissue metabolism are important targets for the treatment of obesity. Serotonin (5-hydroxytryptophan [5-HT]) is a monoamine metabolite of the essential amino acid tryptophan. Here, we demonstrated that 5-HT in mature adipocytes regulated energy expenditure and lipid metabolism.
METHODS
Tryptophan hydroxylase 1 (TPH1) is the rate-limiting enzyme during 5-HT synthesis in non-neural peripheral tissues. We generated adipose tissue-specific Tph1 knockout (Tph1 FKO) mice and adipose tissue-specific serotonin receptor 2A KO (Htr2a FKO) mice and analyzed their phenotypes during high-fat diet (HFD) induced obesity.
RESULTS
Tph1 FKO mice fed HFD exhibited reduced lipid accumulation, increased thermogenesis, and resistance to obesity. In addition, Htr2a FKO mice fed HFD showed reduced lipid accumulation in white adipose tissue and resistance to obesity.
CONCLUSION
These data suggest that the inhibition of serotonin signaling might be an effective strategy in obesity.
Identifiants
pubmed: 32615731
pii: EnM.2020.35.2.470
doi: 10.3803/EnM.2020.35.2.470
pmc: PMC7386107
doi:
Substances chimiques
Htr2a protein, mouse
0
Receptor, Serotonin, 5-HT2A
0
Serotonin Receptor Agonists
0
Serotonin
333DO1RDJY
Tph1 protein, mouse
EC 1.14.16.4
Tryptophan Hydroxylase
EC 1.14.16.4
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
470-479Commentaires et corrections
Type : ErratumIn
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