Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters

Markus Feuerer, Laura Herrero, Daniela Cipolletta, Afia Naaz, Jamie Wong, Ali Nayer, Jongsoon Lee, Allison B. Goldfine, Christophe Benoist, Steven Shoelson, Diane Mathis

Research output: Contribution to journalArticle

1170 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)930-939
Number of pages10
JournalNature medicine
Volume15
Issue number8
DOIs
StatePublished - Aug 1 2009

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Feuerer, M., Herrero, L., Cipolletta, D., Naaz, A., Wong, J., Nayer, A., Lee, J., Goldfine, A. B., Benoist, C., Shoelson, S., & Mathis, D. (2009). Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nature medicine, 15(8), 930-939. https://doi.org/10.1038/nm.2002