Mechanisms of triglyceride accumulation in activated macrophages

• DOI: 10.1189/jlb.1111537
• Publication Date: 2012-06-30T04:14:37Z
• Authors: Kenneth R Feingold; Judy K Shigenaga; Mahmood R Kazemi; Carol M McDonald; Sophie M Patzek; Andrew S Cross; Arthur Moser; Carl Grunfeld
• Keywords: Lipopolysaccharides; 0301 basic medicine; 0303 health sciences; Lipolysis; Macrophages; Fatty Acids; Toll-Like Receptors; Gene Expression; Macrophage Activation; Cell Line; 3. Good health; Mice; 03 medical and health sciences; Glucose; Myeloid Differentiation Factor 88; Animals; Triglycerides

LPS treatment of macrophages induces TG accumulation, which is accentuated by TG-rich lipoproteins or FFA. We defined pathways altered during macrophage activation that contribute to accumulation. Glucose uptake increased with activation, accompanied GLUT1. Oxidation glucose markedly decreased, whereas incorporation glucose-derived carbon into FA and sterols increased. Macrophage also FFA, associated an increase in CD36. was reduced, the TGs increased, GPAT3 DGAT2. Additionally, decreased lipolysis; however, expression ATGL HSL not altered. gene similarly when incubated exogenous AcLDL. Whereas ligands TLR2 (zymosan), TLR3 (poly I:C), TLR4 (LPS) induced alterations expression, leading cytokines had minimal effects. Thus, TLRs leads accumulation multiple may have beneficial effects host defense but could accelerated atherosclerosis chronic infections inflammatory diseases.