Toll-like Receptor Agonists Promote Prolonged Triglyceride Storage in Macrophages |
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Authors: | Ying-ling Huang Joel Morales-Rosado Jessica Ray Timothy G Myers Terry Kho Mingfang Lu Robert S Munford |
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Institution: | From the ‡Antibacterial Host Defense Section, Laboratory of Clinical Infectious Diseases.;§Genomic Technologies Section, Research Technologies Branch, NIAID, National Institutes of Health, Bethesda, Maryland 20892-3206 |
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Abstract: | Macrophages in infected tissues may sense microbial molecules that significantly alter their metabolism. In a seeming paradox, these critical host defense cells often respond by increasing glucose catabolism while simultaneously storing fatty acids (FA) as triglycerides (TAG) in lipid droplets. We used a load-chase strategy to study the mechanisms that promote long term retention of TAG in murine and human macrophages. Toll-like receptor (TLR)1/2, TLR3, and TLR4 agonists all induced the cells to retain TAG for ≥3 days. Prolonged TAG retention was accompanied by the following: (a) enhanced FA uptake and FA incorporation into TAG, with long lasting increases in acyl-CoA synthetase long 1 (ACSL1) and diacylglycerol acyltransferase-2 (DGAT2), and (b) decreases in lipolysis and FA β-oxidation that paralleled a prolonged drop in adipose triglyceride lipase (ATGL). TLR agonist-induced TAG storage is a multifaceted process that persists long after most early pro-inflammatory responses have subsided and may contribute to the formation of “lipid-laden” macrophages in infected tissues. |
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Keywords: | Adipose Triglyceride Lipase Lipid Droplet Lipolysis Lipopolysaccharide (LPS) Macrophages Toll-like Receptors (TLR) Triglyceride ACSL DGAT2 Acyl-CoA Synthetase |
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