Lean, but Not Obese, Fat Is Enriched for a Unique Population of Regulatory T Cells That Affect Metabolic Parameters

Nat Med. 2009 Aug;15(8):930-9. doi: 10.1038/nm.2002. Epub 2009 Jul 26.

Abstract

Obesity is accompanied by chronic, low-grade inflammation of adipose tissue, which promotes insulin resistance and type-2 diabetes. These findings raise the question of how fat inflammation can escape the powerful armamentarium of cells and molecules normally responsible for guarding against a runaway immune response. CD4(+) Foxp3(+) T regulatory (T(reg)) cells with a unique phenotype were highly enriched in the abdominal fat of normal mice, but their numbers were strikingly and specifically reduced at this site in insulin-resistant models of obesity. Loss-of-function and gain-of-function experiments revealed that these T(reg) cells influenced the inflammatory state of adipose tissue and, thus, insulin resistance. Cytokines differentially synthesized by fat-resident regulatory and conventional T cells directly affected the synthesis of inflammatory mediators and glucose uptake by cultured adipocytes. These observations suggest that harnessing the anti-inflammatory properties of T(reg) cells to inhibit elements of the metabolic syndrome may have therapeutic potential.

Publication types

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

MeSH terms

  • Adipose Tissue / immunology*
  • Adipose Tissue / metabolism
  • Adipose Tissue / pathology
  • Animals
  • Cell Proliferation
  • Cell Separation
  • Gene Expression Profiling
  • Lymphocyte Count
  • Male
  • Metabolic Networks and Pathways / genetics
  • Metabolic Networks and Pathways / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Obese
  • Obesity / genetics
  • Obesity / immunology*
  • Obesity / metabolism*
  • T-Lymphocytes, Regulatory / pathology
  • T-Lymphocytes, Regulatory / physiology*
  • Thinness / genetics
  • Thinness / immunology*
  • Thinness / metabolism*
  • Up-Regulation / immunology

Associated data

  • GEO/GSE7852