title: Toll-like receptor agonists promote prolonged triglyceride storage in macrophages.
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.
authors: From the Antibacterial Host Defense Section, Laboratory of Clinical Infectious Diseases.
authors: Ying-ling
authors: YL
authors: Huang
authors: Joel
authors: J
authors: Morales-Rosado
authors: Jessica
authors: J
authors: Ray
authors: Timothy G
authors: TG
authors: Myers
authors: Terry
authors: T
authors: Kho
authors: Mingfang
authors: M
authors: Lu
authors: Robert S
authors: RS
authors: Munford
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003066:Coenzyme A Ligases / Q000378:metabolism; D051048:Diacylglycerol O-Acyltransferase / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005487:Foam Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008066:Lipolysis / Q000187:drug effects / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051194:Toll-Like Receptor 1 / Q000819:agonists*; D051195:Toll-Like Receptor 2 / Q000819:agonists; D051196:Toll-Like Receptor 3 / Q000819:agonists; D051197:Toll-Like Receptor 4 / Q000819:agonists; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D005227:Fatty Acids; D008070:Lipopolysaccharides; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D014280:Triglycerides; C494885:DGAT2 protein, human; C516957:DGAT2 protein, mouse; D051048:Diacylglycerol O-Acyltransferase; C544400:ACSL1 protein, mouse; D003066:Coenzyme A Ligases; C583414:ACSL1 protein, human
keywords: ACSL; Acyl-CoA Synthetase; Adipose Triglyceride Lipase; DGAT2; Lipid Droplet; Lipolysis; Lipopolysaccharide (LPS); Macrophages; Toll-like Receptors (TLR); Triglyceride