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?? T cells promote inflammation and insulin resistance during high fat diet-induced obesity in mice.

ABSTRACT: ?? T cells are resident in AT and increase during diet-induced obesity. Their possible contribution to the inflammatory response that accompanies diet-induced obesity was investigated in mice after a 5 to 10 week milk HFD. The HFD resulted in significant increases in CD44(hi), CD62L(lo), and TNF-?(+) ?? T cells in eAT of WT mice. Mice deficient in all ?? T cells (TCR?(-/-)) or only V?4 and V?6 subsets (V?4/6(-/-)) were compared with WT mice with regard to proinflammatory cytokine production and macrophage accumulation in eAT. Obesity among these mouse strains did not differ, but obese TCR?(-/-) and V?4/6(-/-) mice had significantly reduced eAT expression of F4/80, a macrophage marker, and inflammatory mediators CCL2 and IL-6 compared with WT mice. Obese TCR?(-/-) mice had significantly reduced CD11c(+) and TNF-?(+) macrophage accumulation in eAT after 5 and 10 weeks on the HFD, and obese V?4/6(-/-) mice had significantly increased CD206(+) macrophages in eAT after 5 weeks on the diet and significantly reduced macrophages after 10 weeks. Obese TCR?(-/-) mice had significant reductions in systemic insulin resistance and inflammation in liver and skeletal muscle after longer-term HFD feeding (10 and 24 weeks). In vitro studies revealed that isolated ?? T cells directly stimulated RAW264.7 macrophage TNF-? expression but did not stimulate inflammatory mediator expression in 3T3-L1 adipocytes. These findings are consistent with a role for ?? T cells in the proinflammatory response that accompanies diet-induced obesity.

SUBMITTER: Mehta P

PROVIDER: S-EPMC4377824 | biostudies-other | 2015 Jan

REPOSITORIES: biostudies-other

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γδ T cells promote inflammation and insulin resistance during high fat diet-induced obesity in mice.

Mehta Pooja P Nuotio-Antar Alli Martina AM Smith C Wayne CW

Journal of leukocyte biology 20141113 1

γδ T cells are resident in AT and increase during diet-induced obesity. Their possible contribution to the inflammatory response that accompanies diet-induced obesity was investigated in mice after a 5 to 10 week milk HFD. The HFD resulted in significant increases in CD44(hi), CD62L(lo), and TNF-α(+) γδ T cells in eAT of WT mice. Mice deficient in all γδ T cells (TCRδ(-/-)) or only Vγ4 and Vγ6 subsets (Vγ4/6(-/-)) were compared with WT mice with regard to proinflammatory cytokine production and ...[more]

PMID: 25395302

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Project description:Changes in the gut microbiota have been linked to metabolic endotoxemia as a contributing mechanism in the development of obesity and type 2 diabetes. Although identifying specific microbial taxa associated with obesity and type 2 diabetes remains difficult, certain bacteria may play an important role in initiating metabolic inflammation during disease development. The enrichment of the family Enterobacteriaceae, largely represented by Escherichia coli, induced by a high-fat diet (HFD) has been correlated with impaired glucose homeostasis; however, whether the enrichment of Enterobacteriaceae in a complex gut microbial community in response to an HFD contributes to metabolic disease has not been established. To investigate whether the expansion of Enterobacteriaceae amplifies HFD-induced metabolic disease, a tractable mouse model with the presence or absence of a commensal E. coli strain was established. With an HFD treatment, but not a standard-chow diet, the presence of E. coli significantly increased body weight and adiposity and induced impaired glucose tolerance. In addition, E. coli colonization led to increased inflammation in liver and adipose and intestinal tissue under an HFD regimen. With a modest effect on gut microbial composition, E. coli colonization resulted in significant changes in the predicted functional potential of microbial communities. The results demonstrated the role of commensal E. coli in glucose homeostasis and energy metabolism in response to an HFD, indicating contributions of commensal bacteria to the pathogenesis of obesity and type 2 diabetes. The findings of this research identified a targetable subset of the microbiota in the treatment of people with metabolic inflammation. IMPORTANCE Although identifying specific microbial taxa associated with obesity and type 2 diabetes remains difficult, certain bacteria may play an important role in initiating metabolic inflammation during disease development. Here, we used a mouse model distinguishable by the presence or absence of a commensal Escherichia coli strain in combination with a high-fat diet challenge to investigate the impact of E. coli on host metabolic outcomes. This is the first study to show that the addition of a single bacterial species to an animal already colonized with a complex microbial community can increase severity of metabolic outcomes. This study is of interest to a wide group of researchers because it provides compelling evidence to target the gut microbiota for therapeutic purposes by which personalized medicines can be made for treating metabolic inflammation. The study also provides an explanation for variability in studies investigating host metabolic outcomes and immune response to diet interventions.

Dataset Information

?? T cells promote inflammation and insulin resistance during high fat diet-induced obesity in mice.

Publications

γδ T cells promote inflammation and insulin resistance during high fat diet-induced obesity in mice.

Similar Datasets

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