Molecular and Cellular Biochemistry

, Volume 351, Issue 1–2, pp 19–28 | Cite as

Suppression of fatty acid synthase, differentiation and lipid accumulation in adipocytes by curcumin

  • Jiong Zhao
  • Xue-Bing Sun
  • Fei Ye
  • Wei-Xi Tian


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.


Curcumin Fatty acid synthase Inhibitor Lipid accumulation Adipocyte differentiation 



This study was supported by Grants from the National Natural Science Foundation of China No. 30670455 and No. 30572252.


  1. 1.
    Kopelman PG (2000) Obesity as a medical problem. Nature 404(6778):635–643PubMedGoogle Scholar
  2. 2.
    Smith S (1994) The animal fatty acid synthase: one gene, one polypeptide, seven enzymes. Faseb J 8(15):1248–1259PubMedGoogle Scholar
  3. 3.
    Kim EK, Miller I, Landree LE, Borisy-Rudin FF, Brown P, Tihan T, Townsend CA, Witters LA, Moran TH, Kuhajda FP, Ronnett GV (2002) Expression of fas within hypothalamic neurons: a model for decreased food intake after c75 treatment. Am J Physiol 283(5):E867–E879Google Scholar
  4. 4.
    Loftus TM, Jaworsky DE, Frehywot GL, Townsend CA, Ronnett GV, Lane MD, Kuhajda FP (2000) Reduced food intake and body weight in mice treated with fatty acid synthase inhibitors. Science 288(5475):2379–2381PubMedCrossRefGoogle Scholar
  5. 5.
    Hu Z, Cha SH, Chohnan S, Lane MD (2003) Hypothalamic malonyl-coa as a mediator of feeding behavior. Proceedings of the National Academy of Sciences of the United States of America 100(22):12624–12629Google Scholar
  6. 6.
    Schmid B, Rippmann JF, Tadayyon M, Hamilton BS (2005) Inhibition of fatty acid synthase prevents preadipocyte differentiation. Biochem Biophys Res Commun 328(4):1073–1082PubMedCrossRefGoogle Scholar
  7. 7.
    Aggarwal BB, Sundaram C, Malani N, Ichikawa H (2007) Curcumin: the Indian solid gold. Adv Exp Med Biol 595:1–75PubMedCrossRefGoogle Scholar
  8. 8.
    Asai A, Miyazawa T (2001) Dietary curcuminoids prevent high-fat diet-induced lipid accumulation in rat liver and epididymal adipose tissue. J Nutr 131(11):2932–2935PubMedGoogle Scholar
  9. 9.
    Ejaz A, Wu D, Kwan P, Meydani M (2009) Curcumin inhibits adipogenesis in 3t3–l1 adipocytes and angiogenesis and obesity in c57/bl mice. J Nutr 139(5):919–925PubMedCrossRefGoogle Scholar
  10. 10.
    Lee YK, Lee WS, Hwang JT, Kwon DY, Surh YJ, Park OJ (2009) Curcumin exerts antidifferentiation effect through ampkalpha-ppar-gamma in 3t3–l1 adipocytes and antiproliferatory effect through ampkalpha-cox-2 in cancer cells. J Agric Food Chem 57(1):305–310PubMedCrossRefGoogle Scholar
  11. 11.
    Jang EM, Choi MS, Jung UJ, Kim MJ, Kim HJ, Jeon SM, Shin SK, Seong CN, Lee MK (2008) Beneficial effects of curcumin on hyperlipidemia and insulin resistance in high-fat-fed hamsters. Metab Clin Exp 57(11):1576–1583PubMedGoogle Scholar
  12. 12.
    Tian WX, Hsu RY, Wang YS (1985) Studies on the reactivity of the essential sulfhydryl groups as a conformational probe for the fatty acid synthetase of chicken liver. Inactivation by 5, 5′-dithiobis-(2-nitrobenzoic acid) and intersubunit cross-linking of the inactivated enzyme. J Biol Chem 260(20):11375–11387PubMedGoogle Scholar
  13. 13.
    Wang X, Tian W (2001) Green tea epigallocatechin gallate: a natural inhibitor of fatty-acid synthase. Biochem Biophys Res Commun 288(5):1200–1206PubMedCrossRefGoogle Scholar
  14. 14.
    Menendez JA, Mehmi I, Atlas E, Colomer R, Lupu R (2004) Novel signaling molecules implicated in tumor-associated fatty acid synthase-dependent breast cancer cell proliferation and survival: role of exogenous dietary fatty acids, p53–p21waf1/cip1, erk1/2 mapk, p27kip1, brca1, and nf-kappab. Int J Oncol 24(3):591–608PubMedGoogle Scholar
  15. 15.
    Li BH, Tian WX (2004) Inhibitory effects of flavonoids on animal fatty acid synthase. J Biochem 135(1):85–91PubMedCrossRefGoogle Scholar
  16. 16.
    Mandrup S, Lane MD (1997) Regulating adipogenesis. J Biol Chem 272(9):5367–5370PubMedCrossRefGoogle Scholar
  17. 17.
    Sfeir Z, Ibrahimi A, Amri E, Grimaldi P, Abumrad N (1997) Regulation of fat/cd36 gene expression: further evidence in support of a role of the protein in fatty acid binding/transport. Prostaglandins Leukot Essent Fat acids 57(1):17–21CrossRefGoogle Scholar
  18. 18.
    Yu S, Matsusue K, Kashireddy P, Cao WQ, Yeldandi V, Yeldandi AV, Rao MS, Gonzalez FJ, Reddy JK (2003) Adipocyte-specific gene expression and adipogenic steatosis in the mouse liver due to peroxisome proliferator-activated receptor gamma1 (ppargamma1) overexpression. J Biol Chem 278(1):498–505PubMedCrossRefGoogle Scholar
  19. 19.
    Thielecke F, Boschmann M (2009) The potential role of green tea catechins in the prevention of the metabolic syndrome—a review. Phytochemistry 70(1):11–24PubMedCrossRefGoogle Scholar
  20. 20.
    Thupari JN, Kim EK, Moran TH, Ronnett GV, Kuhajda FP (2004) Chronic c75 treatment of diet-induced obese mice increases fat oxidation and reduces food intake to reduce adipose mass. Am J Physiol 287(1):E97–E104CrossRefGoogle Scholar
  21. 21.
    Lin J, Della-Fera MA, Baile CA (2005) Green tea polyphenol epigallocatechin gallate inhibits adipogenesis and induces apoptosis in 3t3–l1 adipocytes. Obes Res 13(6):982–990PubMedCrossRefGoogle Scholar
  22. 22.
    Qiao L, Zou C, Shao P, Schaack J, Johnson PF, Shao J (2008) Transcriptional regulation of fatty acid translocase/cd36 expression by ccaat/enhancer-binding protein alpha. J Biol Chem 283(14):8788–8795PubMedCrossRefGoogle Scholar
  23. 23.
    Amri EZ, Ailhaud G, Grimaldi PA (1994) Fatty acids as signal transducing molecules: involvement in the differentiation of preadipose to adipose cells. J Lipid Res 35(5):930–937PubMedGoogle Scholar
  24. 24.
    Brandes R, Arad R, Bar-Tana J (1995) Inducers of adipose conversion activate transcription promoted by a peroxisome proliferators response element in 3t3–l1 cells. Biochem Pharmacol 50(11):1949–1951PubMedCrossRefGoogle Scholar
  25. 25.
    Teboul L, Gaillard D, Staccini L, Inadera H, Amri EZ, Grimaldi PA (1995) Thiazolidinediones and fatty acids convert myogenic cells into adipose-like cells. J Biol Chem 270(47):28183–28187PubMedCrossRefGoogle Scholar
  26. 26.
    Tzameli I, Fang H, Ollero M, Shi H, Hamm JK, Kievit P, Hollenberg AN, Flier JS (2004) Regulated production of a peroxisome proliferator-activated receptor-gamma ligand during an early phase of adipocyte differentiation in 3t3–l1 adipocytes. J Biol Chem 279(34):36093–36102PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  1. 1.College of Life ScienceGraduate University of Chinese Academy of SciencesBeijingChina
  2. 2.Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Personalised recommendations