Improved insulin sensitivity despite increased visceral adiposity in mice deficient for the immune cell transcription factor T-bet
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Published version
Author(s)
Type
Journal Article
Abstract
Low-grade inflammation in fat is associated with insulin resistance, although the mechanisms are unclear. We report that mice deficient in the immune cell transcription factor T-bet have lower energy expenditure and increased visceral fat compared with wild-type mice, yet paradoxically are more insulin sensitive. This striking phenotype, present in young T-bet(-/-) mice, persisted with high-fat diet and increasing host age and was associated with altered immune cell numbers and cytokine secretion specifically in visceral adipose tissue. However, the favorable metabolic phenotype observed in T-bet-deficient hosts was lost in T-bet(-/-) mice also lacking adaptive immunity (T-bet(-/-)xRag2(-/-)), demonstrating that T-bet expression in the adaptive rather than the innate immune system impacts host glucose homeostasis. Indeed, adoptive transfer of T-bet-deficient, but not wild-type, CD4(+) T cells to Rag2(-/-) mice improved insulin sensitivity. Our results reveal a role for T-bet in metabolic physiology and obesity-associated insulin resistance.
Date Issued
2013-04-02
Date Acceptance
2013-02-27
ISSN
1932-7420
Publisher
Elsevier
Start Page
520
End Page
533
Journal / Book Title
Cell Metabolism
Volume
17
Issue
4
Copyright Statement
Open access under CC BY license.
Subjects
Adipose Tissue
Animals
CD4-Positive T-Lymphocytes
Cytokines
DNA-Binding Proteins
Diet, High-Fat
Energy Metabolism
Immune System
In Vitro Techniques
Insulin Resistance
Interferon-gamma
Intra-Abdominal Fat
Male
Mice
Mice, Inbred BALB C
Mice, Knockout
Obesity
Phenotype
T-Box Domain Proteins
0601 Biochemistry And Cell Biology
1101 Medical Biochemistry And Metabolomics
Publication Status
Published