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Publication : Genetic deletion of mast cell serotonin synthesis prevents the development of obesity and insulin resistance.

First Author  Yabut JM Year  2020
Journal  Nat Commun Volume  11
Issue  1 Pages  463
PubMed ID  31974364 Mgi Jnum  J:288178
Mgi Id  MGI:6387469 Doi  10.1038/s41467-019-14080-7
Citation  Yabut JM, et al. (2020) Genetic deletion of mast cell serotonin synthesis prevents the development of obesity and insulin resistance. Nat Commun 11(1):463
abstractText  Obesity is linked with insulin resistance and is characterized by excessive accumulation of adipose tissue due to chronic energy imbalance. Increasing thermogenic brown and beige adipose tissue futile cycling may be an important strategy to increase energy expenditure in obesity, however, brown adipose tissue metabolic activity is lower with obesity. Herein, we report that the exposure of mice to thermoneutrality promotes the infiltration of white adipose tissue with mast cells that are highly enriched with tryptophan hydroxylase 1 (Tph1), the rate limiting enzyme regulating peripheral serotonin synthesis. Engraftment of mast cell-deficient mice with Tph1(-/-) mast cells or selective mast cell deletion of Tph1 enhances uncoupling protein 1 (Ucp1) expression in white adipose tissue and protects mice from developing obesity and insulin resistance. These data suggest that therapies aimed at inhibiting mast cell Tph1 may represent a therapeutic approach for the treatment of obesity and type 2 diabetes.
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