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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology*
  • Adipose Tissue / immunology*
  • Aging / immunology*
  • Animals
  • Diabetes Mellitus, Type 2 / metabolism
  • Glucose / metabolism
  • Inflammation / immunology
  • Inflammation / metabolism
  • Insulin Resistance / immunology*
  • Macrophages / immunology
  • Male
  • Metabolic Syndrome / immunology
  • Metabolic Syndrome / metabolism
  • Mice
  • Obesity / metabolism
  • T-Lymphocytes, Regulatory / cytology*
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • Glucose

Associated data

  • SRA/SRP053799