Publication Date:
2012-06-23
Description:
Obesity and type-2 diabetes have increased markedly over the past few decades, in parallel. One of the major links between these two disorders is chronic, low-grade inflammation. Prolonged nutrient excess promotes the accumulation and activation of leukocytes in visceral adipose tissue (VAT) and ultimately other tissues, leading to metabolic abnormalities such as insulin resistance, type-2 diabetes and fatty-liver disease. Although invasion of VAT by pro-inflammatory macrophages is considered to be a key event driving adipose-tissue inflammation and insulin resistance, little is known about the roles of other immune system cell types in these processes. A unique population of VAT-resident regulatory T (Treg) cells was recently implicated in control of the inflammatory state of adipose tissue and, thereby, insulin sensitivity. Here we identify peroxisome proliferator-activated receptor (PPAR)-gamma, the 'master regulator' of adipocyte differentiation, as a crucial molecular orchestrator of VAT Treg cell accumulation, phenotype and function. Unexpectedly, PPAR-gamma expression by VAT Treg cells was necessary for complete restoration of insulin sensitivity in obese mice by the thiazolidinedione drug pioglitazone. These findings suggest a previously unknown cellular mechanism for this important class of thiazolidinedione drugs, and provide proof-of-principle that discrete populations of Treg cells with unique functions can be precisely targeted to therapeutic ends.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3387339/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3387339/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cipolletta, Daniela -- Feuerer, Markus -- Li, Amy -- Kamei, Nozomu -- Lee, Jongsoon -- Shoelson, Steven E -- Benoist, Christophe -- Mathis, Diane -- DK092541/DK/NIDDK NIH HHS/ -- DK51729/DK/NIDDK NIH HHS/ -- P30DK36836/DK/NIDDK NIH HHS/ -- R01 DK051729/DK/NIDDK NIH HHS/ -- R01 DK092541/DK/NIDDK NIH HHS/ -- R01 DK092541-02/DK/NIDDK NIH HHS/ -- R37 DK051729/DK/NIDDK NIH HHS/ -- T32 GM007753/GM/NIGMS NIH HHS/ -- England -- Nature. 2012 Jun 28;486(7404):549-53. doi: 10.1038/nature11132.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22722857" target="_blank"〉PubMed〈/a〉
Keywords:
Adipose Tissue/*cytology/immunology/pathology
;
Animals
;
Cell Differentiation
;
Diabetes Mellitus, Type 2/drug therapy/metabolism/pathology
;
Epididymis/cytology/immunology
;
Forkhead Transcription Factors/metabolism
;
Gene Expression
;
Hypoglycemic Agents/pharmacology
;
Inflammation/immunology/metabolism/pathology
;
Insulin Resistance/physiology
;
Lymphocyte Count
;
Male
;
Mice
;
Mice, Inbred C57BL
;
Mice, Obese
;
Obesity/metabolism/pathology
;
PPAR gamma/*metabolism
;
Phenotype
;
RNA, Messenger/genetics/metabolism
;
T-Lymphocytes, Regulatory/*cytology/drug effects/*metabolism
;
Thiazolidinediones/pharmacology
;
Transcription, Genetic
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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