Regulatory effects of curcumin on lipid accumulation in monocytes/macrophages.
Recent evidence suggests potential benefits from phytochemicals and micronutrients in protecting against atherosclerosis and inflammation, but the molecular mechanisms of these actions are still unclear. Here, we investigated whether the dietary polyphenol curcumin can modulate the accumulation of lipids in monocytes/macrophages. Curcumin increased the expression of two lipid transport genes, the fatty acids transporter CD36/FAT and the fatty acids binding protein 4 (FABP4/aP2; P < 0.05), leading to increased lipid levels in THP-1 and RAW264.7 monocytes and macrophages (P < 0.05). To investigate the molecular mechanisms involved, we assessed the activity of Forkhead box O3a (FOXO3a), a transcription factor centrally involved in regulating several stress resistance and lipid transport genes. Curcumin increased FOXO3a-mediated gene expression by twofold (P < 0.05), possibly as a result of influencing FOXO3a phosphorylation and nuclear translocation. The curcumin derivative, tetrahydrocurcumin (THC), with similar chemical antioxidant activity as curcumin, did not show any measurable effects. In contrast to the in vitro results, curcumin showed a trend for reduction of lipid levels in peritoneal macrophages in LDL receptor knockout mice fed a high fat diet for 4 months, suggesting additional regulatory mechanisms in vivo. Thus, the up-regulation of FOXO3a activity by curcumin could be a mechanism to protect against oxidant- and lipid-induced damage in the inflammatory cells of the vascular system.
Vascular Biology Laboratory, Jean Mayer USDA-Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts 0111, USA. jean-marc.zingg@tufts.edu
Jean-Marc
JM
Zingg
Syeda T
ST
Hasan
Danica
D
Cowan
Roberta
R
Ricciarelli
Angelo
A
Azzi
Mohsen
M
Meydani
D000818:Animals; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D003474:Curcumin / Q000494:pharmacology*; D059305:Diet, High-Fat; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic; D011973:Receptors, LDL / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation
D018955:CD36 Antigens; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D051858:Forkhead Transcription Factors; D011973:Receptors, LDL; D003474:Curcumin