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Multiomics reveals persistence of obesity-associated immune cell phenotypes in adipose tissue during weight loss and weight regain in mice

Within adipose tissue (AT), immune cells and parenchymal cells closely interact creating a complex microenvironment. In obesity, immune cell derived inflammation contributes to insulin resistance and glucose intolerance. Diet-induced weight loss improves glucose tolerance; however, weight regain fur...

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Autores principales: Cottam, Matthew A., Caslin, Heather L., Winn, Nathan C., Hasty, Alyssa H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9135744/
https://www.ncbi.nlm.nih.gov/pubmed/35618862
http://dx.doi.org/10.1038/s41467-022-30646-4
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author Cottam, Matthew A.
Caslin, Heather L.
Winn, Nathan C.
Hasty, Alyssa H.
author_facet Cottam, Matthew A.
Caslin, Heather L.
Winn, Nathan C.
Hasty, Alyssa H.
author_sort Cottam, Matthew A.
collection PubMed
description Within adipose tissue (AT), immune cells and parenchymal cells closely interact creating a complex microenvironment. In obesity, immune cell derived inflammation contributes to insulin resistance and glucose intolerance. Diet-induced weight loss improves glucose tolerance; however, weight regain further exacerbates the impairment in glucose homeostasis observed with obesity. To interrogate the immunometabolic adaptations that occur in AT during murine weight loss and weight regain, we utilized cellular indexing of transcriptomes and epitopes by sequencing (CITEseq) in male mice. Obesity-induced imprinting of AT immune cells persisted through weight-loss and progressively worsened with weight regain, ultimately leading to impaired recovery of type 2 regulatory cells, activation of antigen presenting cells, T cell exhaustion, and enhanced lipid handling in macrophages in weight cycled mice. This work provides critical groundwork for understanding the immunological causes of weight cycling-accelerated metabolic disease. For further discovery, we provide an open-access web portal of diet-induced AT immune cell imprinting: https://hastylab.shinyapps.io/MAIseq.
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spelling pubmed-91357442022-05-28 Multiomics reveals persistence of obesity-associated immune cell phenotypes in adipose tissue during weight loss and weight regain in mice Cottam, Matthew A. Caslin, Heather L. Winn, Nathan C. Hasty, Alyssa H. Nat Commun Article Within adipose tissue (AT), immune cells and parenchymal cells closely interact creating a complex microenvironment. In obesity, immune cell derived inflammation contributes to insulin resistance and glucose intolerance. Diet-induced weight loss improves glucose tolerance; however, weight regain further exacerbates the impairment in glucose homeostasis observed with obesity. To interrogate the immunometabolic adaptations that occur in AT during murine weight loss and weight regain, we utilized cellular indexing of transcriptomes and epitopes by sequencing (CITEseq) in male mice. Obesity-induced imprinting of AT immune cells persisted through weight-loss and progressively worsened with weight regain, ultimately leading to impaired recovery of type 2 regulatory cells, activation of antigen presenting cells, T cell exhaustion, and enhanced lipid handling in macrophages in weight cycled mice. This work provides critical groundwork for understanding the immunological causes of weight cycling-accelerated metabolic disease. For further discovery, we provide an open-access web portal of diet-induced AT immune cell imprinting: https://hastylab.shinyapps.io/MAIseq. Nature Publishing Group UK 2022-05-26 /pmc/articles/PMC9135744/ /pubmed/35618862 http://dx.doi.org/10.1038/s41467-022-30646-4 Text en © This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2022 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Cottam, Matthew A.
Caslin, Heather L.
Winn, Nathan C.
Hasty, Alyssa H.
Multiomics reveals persistence of obesity-associated immune cell phenotypes in adipose tissue during weight loss and weight regain in mice
title Multiomics reveals persistence of obesity-associated immune cell phenotypes in adipose tissue during weight loss and weight regain in mice
title_full Multiomics reveals persistence of obesity-associated immune cell phenotypes in adipose tissue during weight loss and weight regain in mice
title_fullStr Multiomics reveals persistence of obesity-associated immune cell phenotypes in adipose tissue during weight loss and weight regain in mice
title_full_unstemmed Multiomics reveals persistence of obesity-associated immune cell phenotypes in adipose tissue during weight loss and weight regain in mice
title_short Multiomics reveals persistence of obesity-associated immune cell phenotypes in adipose tissue during weight loss and weight regain in mice
title_sort multiomics reveals persistence of obesity-associated immune cell phenotypes in adipose tissue during weight loss and weight regain in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9135744/
https://www.ncbi.nlm.nih.gov/pubmed/35618862
http://dx.doi.org/10.1038/s41467-022-30646-4
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