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Genetic deletion of mast cell serotonin synthesis prevents the development of obesity and insulin resistance.
Yabut, Julian M; Desjardins, Eric M; Chan, Eric J; Day, Emily A; Leroux, Julie M; Wang, Bo; Crane, Elizabeth D; Wong, Wesley; Morrison, Katherine M; Crane, Justin D; Khan, Waliul I; Steinberg, Gregory R.
Affiliation
  • Yabut JM; Centre for Metabolism, Obesity and Diabetes Research, McMaster University, 1280 Main St. W., Hamilton, ON, Canada, L8N 3Z5.
  • Desjardins EM; Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, 1280 Main St. W., Hamilton, ON, Canada, L8N 3Z5.
  • Chan EJ; Centre for Metabolism, Obesity and Diabetes Research, McMaster University, 1280 Main St. W., Hamilton, ON, Canada, L8N 3Z5.
  • Day EA; Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, 1280 Main St. W., Hamilton, ON, Canada, L8N 3Z5.
  • Leroux JM; Centre for Metabolism, Obesity and Diabetes Research, McMaster University, 1280 Main St. W., Hamilton, ON, Canada, L8N 3Z5.
  • Wang B; Department of Biochemistry and Biomedical Sciences, McMaster University, 1280 Main St. W., Hamilton, ON, Canada, L8N 3Z5.
  • Crane ED; Centre for Metabolism, Obesity and Diabetes Research, McMaster University, 1280 Main St. W., Hamilton, ON, Canada, L8N 3Z5.
  • Wong W; Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, 1280 Main St. W., Hamilton, ON, Canada, L8N 3Z5.
  • Morrison KM; Centre for Metabolism, Obesity and Diabetes Research, McMaster University, 1280 Main St. W., Hamilton, ON, Canada, L8N 3Z5.
  • Crane JD; Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, 1280 Main St. W., Hamilton, ON, Canada, L8N 3Z5.
  • Khan WI; Centre for Metabolism, Obesity and Diabetes Research, McMaster University, 1280 Main St. W., Hamilton, ON, Canada, L8N 3Z5.
  • Steinberg GR; Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, 1280 Main St. W., Hamilton, ON, Canada, L8N 3Z5.
Nat Commun ; 11(1): 463, 2020 01 23.
Article in En | MEDLINE | ID: mdl-31974364
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-/- 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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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Tryptophan Hydroxylase / Insulin Resistance / Serotonin / Mast Cells / Obesity Limits: Animals Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2020 Type: Article
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Tryptophan Hydroxylase / Insulin Resistance / Serotonin / Mast Cells / Obesity Limits: Animals Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2020 Type: Article