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PMID: 19633656 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Nature medicine ·Vol. 15 ·No. 8 ·2009-08-00 ·Pages 930-9

Feuerer M, Herrero L, Cipolletta D, Naaz A, Wong J, Nayer A, Lee J, Goldfine AB, Benoist C, Shoelson S, Mathis D

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.

MeSH Terms
Adipose Tissue/immunology,metabolism,pathology Animals Cell Proliferation Cell Separation Gene Expression Profiling Lymphocyte Count Male Metabolic Networks and Pathways/genetics,immunology Mice Mice, Inbred C57BL Mice, Obese Obesity/genetics,immunology,metabolism T-Lymphocytes, Regulatory/pathology,physiology Thinness/genetics,immunology,metabolism Up-Regulation/immunology
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Feuerer Markus
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Joslin Diabetes Center, Boston, Massachusetts, USA.
Herrero Laura
Cipolletta Daniela
Naaz Afia
Wong Jamie
Nayer Ali
Lee Jongsoon
Goldfine Allison B
Benoist Christophe
Shoelson Steven
Mathis Diane
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Article Info
Journal
Nature medicine
Abbr.
Nat Med
ISSN
1546-170X
DOI
10.1038/nm.2002
Published
2009-08-00
Epub
2009-00-26
Pages
930-9
Language
English
Region
United States
NLM ID
9502015
PMCID
PMC3115752
Subset
IM
Grants
NIDDK NIH HHS · R01 DK051729 · United States
NIDDK NIH HHS · R01 DK073547-05 · United States
NIDDK NIH HHS · T32 DK007260 · United States
NIDDK NIH HHS · T32 DK7260 · United States
NIDDK NIH HHS · DK73547 · United States
NIDDK NIH HHS · R37 DK051729-14 · United States
NIDDK NIH HHS · DK51729 · United States
NIDDK NIH HHS · R01 DK073547 · United States
NIDDK NIH HHS · R37 DK051729 · United States
Databases
GEO
GSE7852
Corrections
CommentIn
PMID: 19661987
External Links
PubMed source DOI: 10.1038/nm.2002 PMC Full Text View journal details
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