Mechanisms of triglyceride accumulation in activated macrophages

Abstract

TLR activation by multiple pathways leads to triglyceride accumulation in macrophages that could contribute to the accelerated atherosclerosis seen in chronic infections and inflammatory diseases.

Inflammation stimulates niacin receptor (GPR109A/HCA2) expression in adipose tissue and macrophages

“…Moreover, previous studies have shown that LPS stimulates the incorporation of fatty acids into TGs, which is associated with the increased expression of GPAT3 and DGAT2, two key enzymes in the synthesis of TGs ( 29 ). As seen in prior studies, this increase in LPS-induced TG accumulation is associated with an increase in GPAT3 and DGAT2 expression ( Fig.…”

“…Previous studies by our and other laboratories have shown that the activation of macrophages with LPS and other TLR activators increases macrophage TG accumulation ( 29,30 ). We therefore next examined the effect of have failed to demonstrate that niacin therapy when added to statins reduces cardiovascular disease events (34)(35)(36).…”

UCP2-induced fatty acid synthase promotes NLRP3 inflammasome activation during sepsis

“…The accumulation of lipid metabolites has been associated with systemic inflammation in mice and humans (37,38). Moreover, alterations in glucose metabolism, including glucose consumption and glycolysis, have been linked to cytokine production in immune cells (7,9,39).…”

HIV, Inflammation, and Calcium in Atherosclerosis

“…21,43,[47][48][49][50][51] First, TLRs induce foam cell formation by increasing the uptake of lipoproteins and the storage of lipid (via increases in CD36, AP2, fatty acid-binding proteins, MyD88-adaptor-like, adipose differentiation-related protein, lipin 1, glycerol-3-phosphate acyltransferase 3, and diacylglycerol O-acyltransferase 2). 52,53 Second, TLRs decrease the delivery of cholesterol macrophages to high-density lipoprotein (HDL), the first step in reverse cholesterol transport (via decreases in macrophages ATP-binding cassette transporter subfamily A (ABCA)-1, ATP-binding cassette transporter subfamily G, scavenger receptor class B, member 1/CD36 antigen-like 1, and apolipoprotein E). [54][55][56] The HIV Nef gene is also known to activate macrophages, in part, by increasing CD36, and to facilitate the transformation of macrophages to foam cells.…”