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Genetic deletion of mast cell serotonin synthesis prevents the development of obesity and insulin resistance
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 adip...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978527/ https://www.ncbi.nlm.nih.gov/pubmed/31974364 http://dx.doi.org/10.1038/s41467-019-14080-7 |
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author | 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. |
author_facet | 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. |
author_sort | Yabut, Julian M. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6978527 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-69785272020-01-27 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. Nat Commun Article 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. Nature Publishing Group UK 2020-01-23 /pmc/articles/PMC6978527/ /pubmed/31974364 http://dx.doi.org/10.1038/s41467-019-14080-7 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article 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. Genetic deletion of mast cell serotonin synthesis prevents the development of obesity and insulin resistance |
title | Genetic deletion of mast cell serotonin synthesis prevents the development of obesity and insulin resistance |
title_full | Genetic deletion of mast cell serotonin synthesis prevents the development of obesity and insulin resistance |
title_fullStr | Genetic deletion of mast cell serotonin synthesis prevents the development of obesity and insulin resistance |
title_full_unstemmed | Genetic deletion of mast cell serotonin synthesis prevents the development of obesity and insulin resistance |
title_short | Genetic deletion of mast cell serotonin synthesis prevents the development of obesity and insulin resistance |
title_sort | genetic deletion of mast cell serotonin synthesis prevents the development of obesity and insulin resistance |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978527/ https://www.ncbi.nlm.nih.gov/pubmed/31974364 http://dx.doi.org/10.1038/s41467-019-14080-7 |
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