Genetic deletion of mast cell serotonin synthesis prevents the development of obesity and insulin resistance.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31974364.
- Also identified by DOI 10.1038/s41467-019-14080-7 and PMC identifier 6978527.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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<sup>-/-</sup> 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.
Medical subject headings
- Insulin Resistance
- Mast Cells
- Obesity
- Serotonin
- Tryptophan Hydroxylase