Depletion of fat-resident Treg cells prevents age-associated insulin resistance
Autor: | Mathias Leblanc, Christopher Liddle, Ronald M. Evans, Annette R. Atkins, Ruth T. Yu, Jae Myoung Suh, Yuqiong Liang, Ye Zheng, Michael Downes, Sihao Liu, Carmen Zhou, Sungsoon Fang, Yang Zhang, Albert Cheng, Sagar P. Bapat |
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Rok vydání: | 2015 |
Předmět: |
Male
Aging Cell Peroxisome proliferator-activated receptor Adipose tissue Inflammation Biology Carbohydrate metabolism T-Lymphocytes Regulatory Mice 03 medical and health sciences 0302 clinical medicine Immune system Insulin resistance medicine Animals Obesity 030304 developmental biology Metabolic Syndrome chemistry.chemical_classification 0303 health sciences Multidisciplinary Macrophages medicine.disease Cell biology Glucose medicine.anatomical_structure Adipose Tissue Diabetes Mellitus Type 2 chemistry Ageing 030220 oncology & carcinogenesis Immunology Insulin Resistance medicine.symptom |
Zdroj: | Nature. 528:137-141 |
ISSN: | 1476-4687 0028-0836 |
Popis: | Age-associated insulin resistance (IR) and obesity-associated IR are two physiologically distinct forms of adult-onset diabetes. While macrophage-driven inflammation is a core driver of obesity-associated IR, the underlying mechanisms of the obesity-independent yet highly prevalent age-associated IR are largely unexplored. Here we show, using comparative adipo-immune profiling in mice, that fat-resident regulatory T cells, termed fTreg cells, accumulate in adipose tissue as a function of age, but not obesity. Supporting the existence of two distinct mechanisms underlying IR, mice deficient in fTreg cells are protected against age-associated IR, yet remain susceptible to obesity-associated IR and metabolic disease. By contrast, selective depletion of fTreg cells via anti-ST2 antibody treatment increases adipose tissue insulin sensitivity. These findings establish that distinct immune cell populations within adipose tissue underlie ageing- and obesity-associated IR, and implicate fTreg cells as adipo-immune drivers and potential therapeutic targets in the treatment of age-associated IR. |
Databáze: | OpenAIRE |
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