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

Suppression of fatty acid synthase, differentiation and lipid accumulation in adipocytes by curcumin 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Molecular and Cellular Biochemistry Springer Journals

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

Download PDF
10 pages
Read Article

Loading next page...
 
/lp/springer-journals/suppression-of-fatty-acid-synthase-differentiation-and-lipid-r5YbAXITP3
Publisher
Springer Journals
Copyright
Copyright © 2011 by Springer Science+Business Media, LLC.
Subject
Life Sciences; Cardiology; Oncology; Biochemistry, general; Medical Biochemistry
ISSN
0300-8177
eISSN
1573-4919
DOI
10.1007/s11010-010-0707-z
pmid
21221723
Publisher site
See Article on Publisher Site

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.

Journal

Molecular and Cellular Biochemistry – Springer Journals

Published: Jan 9, 2011

References

  • Obesity as a medical problem
    Kopelman, PG
  • The animal fatty acid synthase: one gene, one polypeptide, seven enzymes
    Smith, S
  • Expression of fas within hypothalamic neurons: a model for decreased food intake after c75 treatment
    Kim, EK; Miller, I; Landree, LE; Borisy-Rudin, FF; Brown, P; Tihan, T; Townsend, CA; Witters, LA; Moran, TH; Kuhajda, FP; Ronnett, GV
  • Reduced food intake and body weight in mice treated with fatty acid synthase inhibitors
    Loftus, TM; Jaworsky, DE; Frehywot, GL; Townsend, CA; Ronnett, GV; Lane, MD; Kuhajda, FP
  • Hypothalamic malonyl-coa as a mediator of feeding behavior
    Hu, Z; Cha, SH; Chohnan, S; Lane, MD
  • Inhibition of fatty acid synthase prevents preadipocyte differentiation
    Schmid, B; Rippmann, JF; Tadayyon, M; Hamilton, BS
  • Curcumin: the Indian solid gold
    Aggarwal, BB; Sundaram, C; Malani, N; Ichikawa, H
  • Dietary curcuminoids prevent high-fat diet-induced lipid accumulation in rat liver and epididymal adipose tissue
    Asai, A; Miyazawa, T
  • Curcumin inhibits adipogenesis in 3t3–l1 adipocytes and angiogenesis and obesity in c57/bl mice
    Ejaz, A; Wu, D; Kwan, P; Meydani, M
  • Curcumin exerts antidifferentiation effect through ampkalpha-ppar-gamma in 3t3–l1 adipocytes and antiproliferatory effect through ampkalpha-cox-2 in cancer cells
    Lee, YK; Lee, WS; Hwang, JT; Kwon, DY; Surh, YJ; Park, OJ
  • Beneficial effects of curcumin on hyperlipidemia and insulin resistance in high-fat-fed hamsters
    Jang, EM; Choi, MS; Jung, UJ; Kim, MJ; Kim, HJ; Jeon, SM; Shin, SK; Seong, CN; Lee, MK
  • 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
    Tian, WX; Hsu, RY; Wang, YS
  • Green tea epigallocatechin gallate: a natural inhibitor of fatty-acid synthase
    Wang, X; Tian, W
  • 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
    Menendez, JA; Mehmi, I; Atlas, E; Colomer, R; Lupu, R
  • Inhibitory effects of flavonoids on animal fatty acid synthase
    Li, BH; Tian, WX
  • Regulating adipogenesis
    Mandrup, S; Lane, MD
  • Regulation of fat/cd36 gene expression: further evidence in support of a role of the protein in fatty acid binding/transport
    Sfeir, Z; Ibrahimi, A; Amri, E; Grimaldi, P; Abumrad, N
  • Adipocyte-specific gene expression and adipogenic steatosis in the mouse liver due to peroxisome proliferator-activated receptor gamma1 (ppargamma1) overexpression
    Yu, S; Matsusue, K; Kashireddy, P; Cao, WQ; Yeldandi, V; Yeldandi, AV; Rao, MS; Gonzalez, FJ; Reddy, JK
  • The potential role of green tea catechins in the prevention of the metabolic syndrome—a review
    Thielecke, F; Boschmann, M
  • Chronic c75 treatment of diet-induced obese mice increases fat oxidation and reduces food intake to reduce adipose mass
    Thupari, JN; Kim, EK; Moran, TH; Ronnett, GV; Kuhajda, FP
  • Green tea polyphenol epigallocatechin gallate inhibits adipogenesis and induces apoptosis in 3t3–l1 adipocytes
    Lin, J; Della-Fera, MA; Baile, CA
  • Transcriptional regulation of fatty acid translocase/cd36 expression by ccaat/enhancer-binding protein alpha
    Qiao, L; Zou, C; Shao, P; Schaack, J; Johnson, PF; Shao, J
  • Fatty acids as signal transducing molecules: involvement in the differentiation of preadipose to adipose cells
    Amri, EZ; Ailhaud, G; Grimaldi, PA
  • Inducers of adipose conversion activate transcription promoted by a peroxisome proliferators response element in 3t3–l1 cells
    Brandes, R; Arad, R; Bar-Tana, J
  • Thiazolidinediones and fatty acids convert myogenic cells into adipose-like cells
    Teboul, L; Gaillard, D; Staccini, L; Inadera, H; Amri, EZ; Grimaldi, PA
  • Regulated production of a peroxisome proliferator-activated receptor-gamma ligand during an early phase of adipocyte differentiation in 3t3–l1 adipocytes
    Tzameli, I; Fang, H; Ollero, M; Shi, H; Hamm, JK; Kievit, P; Hollenberg, AN; Flier, JS

You’re reading a free preview. Subscribe to read the entire article.

Try 2 weeks free now

DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

or browse the journals available

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create folders to
organize your research

Export folders, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

Sign up
for free
Start 14 day
Free Trial