In:
Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 36, No. suppl_1 ( 2016-05)
Abstract:
Background: Accumulation of inflammatory leukocytes is a prerequisite of adipose tissue inflammation during cardio-metabolic disease. We recently reported that a genetic deficiency of the intracellular signalling adaptor TRAF-1 attenuates inflammatory cell recruitment and vascular inflammation in atherosclerosis. Here, we tested the contribution of TRAF-1 to diet-induced obesity (DIO) in mice. Methods and Results: To test the association of TRAFs and obesity we screened for expression of different TRAFs in adipose tissue. We found an up-regulation of TRAF-1 mRNA in obese mouse and human adipose tissue, resulting from higher gene expression in adipocytes, but not in adipose tissue macrophages. To test a functional relevance of TRAF-1 signalling in obesity, WT or TRAF-1 -/- mice consumed a high fat diet HFD for 20 weeks. Surprisingly, genetic deficiency of TRAF-1 abolished diet-induced weight gain by supressing peripheral fat depositions. Consequently, TRAF-1 -/- mice demonstrated ameliorated glucose levels after glucose and insulin tolerance tests and dampened insulin signalling. Consistently, we also found reduced accumulation of adipose tissue macrophages. Mechanistically, TRAF-1 -/- mice demonstrated no differences in basic energy metabolism, such as in energy expenditure. However, TRAF-1 -/- adipocytes had higher expression of Adipose Triglyceride Lipase (ATGL) and Hormone-sensitive Lipase (HSL), suggesting increased lipid breakdown in adipocytes. In accord, plasma levels of free fatty acids were higher, while leptin levels were reduced in TRAF-1 -/- mice. Finally, in a collective of patients with a high prevalence of the metabolic syndrome, TRAF-1 expression correlated with the metabolic syndrome, suggesting clinical relevance of our findings. Conclusion: We present the novel finding that the signalling adapter TRAF-1 correlates with obesity in mice and humans. Genetic deficiency of TRAF-1 attenuates diet-induced obesity by increasing lipolysis in adipocytes. These findings identify TRAF-1 as a novel therapeutic target in obesity and adipose-tissue inflammation.
Type of Medium:
Online Resource
ISSN:
1079-5642
,
1524-4636
DOI:
10.1161/atvb.36.suppl_1.597
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2016
detail.hit.zdb_id:
1494427-3
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