Publication Date:
2015-11-19
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4670283/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4670283/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bapat, Sagar P -- Myoung Suh, Jae -- Fang, Sungsoon -- Liu, Sihao -- Zhang, Yang -- Cheng, Albert -- Zhou, Carmen -- Liang, Yuqiong -- LeBlanc, Mathias -- Liddle, Christopher -- Atkins, Annette R -- Yu, Ruth T -- Downes, Michael -- Evans, Ronald M -- Zheng, Ye -- AI099295/AI/NIAID NIH HHS/ -- AI107027/AI/NIAID NIH HHS/ -- CA014195/CA/NCI NIH HHS/ -- DK057978/DK/NIDDK NIH HHS/ -- DK090962/DK/NIDDK NIH HHS/ -- ES010337/ES/NIEHS NIH HHS/ -- F30 DK096828/DK/NIDDK NIH HHS/ -- HL088093/HL/NHLBI NIH HHS/ -- HL105278/HL/NHLBI NIH HHS/ -- P01 HL088093/HL/NHLBI NIH HHS/ -- P42 ES010337/ES/NIEHS NIH HHS/ -- R01 AI107027/AI/NIAID NIH HHS/ -- R01 HL105278/HL/NHLBI NIH HHS/ -- R24 DK090962/DK/NIDDK NIH HHS/ -- R37 DK057978/DK/NIDDK NIH HHS/ -- R56 AI099295/AI/NIAID NIH HHS/ -- T32 GM007198/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2015 Dec 3;528(7580):137-41. doi: 10.1038/nature16151. Epub 2015 Nov 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Immunobiology and Microbial Pathogenesis Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA. ; Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA. ; Graduate School of Medical Science and Engineering, KAIST 34141, South Korea. ; Department of Biotechnology, College of Life Sciences, Sejong University, Seoul 143-747, South Korea. ; Storr Liver Centre, Westmead Millennium Institute, Sydney Medical School, University of Sydney, Sydney 2145, Australia. ; Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26580014" target="_blank"〉PubMed〈/a〉
Keywords:
Adipose Tissue/*cytology/*immunology
;
Aging/*immunology
;
Animals
;
Diabetes Mellitus, Type 2/metabolism
;
Glucose/metabolism
;
Inflammation/immunology/metabolism
;
Insulin Resistance/*immunology
;
Macrophages/immunology
;
Male
;
Metabolic Syndrome X/immunology/metabolism
;
Mice
;
Obesity/metabolism
;
T-Lymphocytes, Regulatory/*cytology/*immunology
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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