期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 289, 期 5, 页码 3001-3012出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M113.524587
关键词
Adipose Triglyceride Lipase; Lipid Droplet; Lipolysis; Lipopolysaccharide (LPS); Macrophages; Toll-like Receptors (TLR); Triglyceride; ACSL; DGAT2; Acyl-CoA Synthetase
资金
- National Institutes of Health, Division of Intramural Research, NIAID
Background: How microbial agonists induce macrophages to store triglycerides (TAG) for prolonged periods was not known. Results: Toll-like receptor (TLR)1/2, TLR3, and TLR4 agonists increased fatty acid uptake, increased TAG synthesis, and decreased lipolysis, augmenting TAG storage for 72 h. Conclusion: TAG retention is an active, multifaceted, and long lasting response to sensing microbes. Significance: Prolonged TAG storage contributes to foam cell formation. 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 -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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