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Nature. 2015 Dec 3;528(7580):137-41. doi: 10.1038/nature16151. Epub 2015 Nov 18.

Depletion of fat-resident Treg cells prevents age-associated insulin resistance.

Author information

1
Immunobiology and Microbial Pathogenesis Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
2
Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
3
Graduate School of Medical Science and Engineering, KAIST 34141, South Korea.
4
Department of Biotechnology, College of Life Sciences, Sejong University, Seoul 143-747, South Korea.
5
Storr Liver Centre, Westmead Millennium Institute, Sydney Medical School, University of Sydney, Sydney 2145, Australia.
6
Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.

Abstract

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.

PMID:
26580014
PMCID:
PMC4670283
DOI:
10.1038/nature16151
[Indexed for MEDLINE]
Free PMC Article

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