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Myeloid cell TRAF3 promotes metabolic inflammation, insulin resistance, and hepatic steatosis in obesity

Abstract

Myeloid cell TRAF3 promotes metabolic inflammation,insulin resistance, and hepatic steatosis in obesity. Am J Physiol Endocrinol Metab 308: E460?E469, 2015. First published January 27, 2015; doi:10.1152/ajpendo.00470.2014.?Myeloid cells, particularly macrophages, mediate metabolic inflammation, thus promoting insulin resistance and metabolic disease progression in obesity. Numerous cytokines, toxic metabolites, damage-associated molecular patterns, and pathogen-associated molecular patterns are involved in activating macrophages via their cognate receptors in obesity. TRAF3 (TNF receptor-associated factor 3) is a common signaling molecule for these ligands/receptors and negatively regulates the pro inflammatory NF- B and MAPK pathways, but its metabolic activity is unknown. We here show that myeloid cell TRAF3 is required for metabolic inflammation and metabolic disease progression in obesity. Myeloid cell-specific deletion of TRAF3 significantly attenuated insulin resistance, hyperglycemia, hyperinsulinemia, glucose intolerance, and hepatic steatosis in mice with either genetic (ob/ob) or high-fat diet (HFD)-induced obesity. Myeloid cell-specific deletion of TRAF3 had the opposite effects on metabolic inflammation between obese and lean mice. It decreased the expression of pro inflammatory cytokines in the liver and adipose tissue of obese mice and largely prevented HFD-induced inflammation in these metabolic tissues; by contrast, in lean mice, it increased the expression of proinflammatory cytokines in the liver and adipose tissue. These data suggest that, in obesity progression, myeloid TRAF3 functionally switches its activity from anti-inflammatory to proinflammatorymodes, thereby coupling overnutrition metabolic inflammation, insulin resistance, and metabolic disease.

Type Journal
Authors Chen, Z.; Shen, H.; Sun, C.; Yin, L.; Tang, F.; Zheng, P.; Liu, Y.; Brink, R.; Rui, L.;
Publisher Name AM J PHYSIOL-ENDOC M
Published Date 2015-03-15 00:00:00
Published Volume 308
Published Issue 6
Published Pages E460-9
URL http://www.ncbi.nlm.nih.gov/pubmed/25628422
Status Published in-print