Abstract
AbstractWithin 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.
Funder
U.S. Department of Health & Human Services | National Institutes of Health
American Heart Association
Department of Veterans Affairs | Office of Academic Affiliations, Department of Veterans Affairs
U.S. Department of Health & Human Services | NIH | National Cancer Institute
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Reference92 articles.
1. Hruby, A. & Hu, F. B. The epidemiology of obesity: a big picture. Pharmacoeconomics 33, 673–689 (2015).
2. World Health Organization. Obesity And Overweight. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight (2021).
3. Ferrante, A. W. Jr. Macrophages, fat, and the emergence of immunometabolism. J. Clin. Invest. 123, 4992–4993 (2013).
4. Russo, L. & Lumeng, C. N. Properties and functions of adipose tissue macrophages in obesity. Immunology 155, 407–417 (2018).
5. Zatterale, F. et al. Chronic adipose tissue inflammation linking obesity to insulin resistance and type 2 diabetes. Front. Physiol. 10, 1607 (2019).
Cited by
88 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献