title: Suppression of fatty acid synthase, differentiation and lipid accumulation in adipocytes by curcumin.
abstract: Curcumin is a well-known component of the cook seasoning and traditional herb turmeric (Curcuma longa), which has been reported to prevent obesity. However, the mechanism still remains to be determined. In this study, curcumin is found to be an effective inhibitor of fatty acid synthase (FAS), and its effects on adipocytes are further evaluated. Curcumin shows both fast-binding and slow-binding inhibitions to FAS. Curcumin inhibits FAS with an IC₅₀ value of 26.8 μM, noncompetitively with respect to NADPH, and partially competitively against both substrates acetyl-CoA and malonyl-CoA. This suggests that the malonyl/acetyl transferase domain of FAS possibly is the main target of curcumin. The time-dependent inactivation shows that curcumin inactivates FAS with two-step irreversible inhibition, a specific reversible binding followed by an irreversible modification by curcumin. Like other classic FAS inhibitors, curcumin prevents the differentiation of 3T3-L1 cells, and thus represses lipid accumulation. In the meantime, curcumin decreases the expression of FAS, down-regulates the mRNA level of PPARγ and CD36 during adipocyte differentiation. Curcumin is reported here as a novel FAS inhibitor, and it suppresses adipocyte differentiation and lipid accumulation, which is associated with its inhibition of FAS. Hence, curcumin is considered to be having potential application in the prevention of obesity.
authors.affiliation: College of Life Science, Graduate University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Jiong
authors.initials: J
authors.lastname: Zhao
authors.forename: Xue-Bing
authors.initials: XB
authors.lastname: Sun
authors.forename: Fei
authors.initials: F
authors.lastname: Ye
authors.forename: Wei-Xi
authors.initials: WX
authors.lastname: Tian
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D018955:CD36 Antigens / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects*; D003474:Curcumin / Q000494:pharmacology*; D017931:DNA Primers; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors*; D007700:Kinetics; D050356:Lipid Metabolism; D051379:Mice; D047495:PPAR gamma / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018955:CD36 Antigens; D017931:DNA Primers; D047495:PPAR gamma; D012333:RNA, Messenger; D064429:Fatty Acid Synthases; D003474:Curcumin