Genetic deletion of mast cell serotonin synthesis prevents the development of obesity and insulin resistance.
Julian M YabutEric M DesjardinsEric J ChanEmily A DayJulie M LerouxBo WangElizabeth D CraneWesley WongKatherine Mary MorrisonJustin D CraneWaliul I KhanGregory R SteinbergPublished in: Nature communications (2020)
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.
Keyphrases
- insulin resistance
- adipose tissue
- high fat diet induced
- high fat diet
- type diabetes
- metabolic syndrome
- polycystic ovary syndrome
- skeletal muscle
- glycemic control
- weight gain
- cardiovascular disease
- signaling pathway
- small molecule
- electronic health record
- deep learning
- genome wide
- dna methylation
- gene expression
- protein protein