Guava Leaf Extracts Inhibit 3T3-L1 Adipocyte Differentiation Via Activating AMPK
DOI:
https://doi.org/10.6000/1929-5634.2012.01.02.2Keywords:
AMP-activated protein kinase, 3T3-L1 differentiation, guava leaf extract, Mitotic clonal expansion, obesityAbstract
The guava tree (psidium guajava linn.) is commonly used not only as food but also as folk medicine. In our previous studies, we showed that oral administration of guava leaf extracts (GLE) had beneficial anti-obesity effects using metabolic syndrome model rats. However, we did not clarify molecular mechanism by which GLE administration leads to anti-obesity effect. This study was designed to evaluate the mechanism of anti-obesity by GLE using 3T3-L1 pre-adipocyte cell lines. We found that GLE significantly inhibited 3T3-L1 differentiation via down-regulation of adipogenic transcription factors and markers. Mitotic clonal expansion, which is essential for adipose differentiation, was also depressed in the early phase. Interestingly, GLE increased the phosphorylation of AMPK on 3T3-L1 cells and, by pretreatment with AMPK siRNA, the GLE treatment group showed restored adipocyte differentiation. In conclusion, these results showed that GLE is capable of inhibiting adipocyte differentiation via AMPK activation and therefore it may prevent obesity in vivo.
References
Gutierrez RM, Mitchell S, Solis RV. Psidium guajava: a review of its traditional uses, phytochemistry and pharmacology. J Ethnopharmacol 2008; 117: 1-27. http://dx.doi.org/10.1016/j.jep.2008.01.025
Keji C. Understanding and treatment of diabetes mellitus by traditional Chinese medicine. Am J Chin Med 1981; 9: 93-94. http://dx.doi.org/10.1142/S0192415X81000123
Begum S, Hassan SI, Ali SN, Siddiqui BS. Chemical constituents from the leaves of Psidium guajava. Nat Prod Res 2004; 18: 135-40. http://dx.doi.org/10.1080/14786410310001608019
Begum S, Hassan SI, Siddiqui BS. Two new triterpenoids from the fresh leaves of Psidium guajava. Planta Med 2002; 68: 1149-52. http://dx.doi.org/10.1055/s-2002-36353
Lozoya X, Meckes M, Abou-Zaid M. Quercetin glycosides in Psidium guajava L. leaves and determination of a spasmolytic principle. Arch Med Res 1994; 25: 11-5.
de Rezende FM, Furlan CM. Anthocyanins and tannins in ozone-fumigated guava trees. Chemosphere 2009; 76: 1445-50. http://dx.doi.org/10.1016/j.chemosphere.2009.05.028
Yoshitomi H, Guo X, Liu T,Gao M. Guava leaf extracts alleviate fatty liver via expression of adiponectin receptors in SHRSP.Z-Leprfa/Izm rats. Nutr Metab 9: 13. http://dx.doi.org/10.1186/1743-7075-9-13
Farmer SR. Transcriptional control of adipocyte formation. Cell Metab 2006; 4: 263-73. http://dx.doi.org/10.1016/j.cmet.2006.07.001
Rosen ED, Spiegelman BM. Molecular regulation of adipogenesis. Annu Rev Cell Dev Biol 2000; 16: 145-71. http://dx.doi.org/10.1146/annurev.cellbio.16.1.145
Tang QQ, Otto TC, Lane MD. Mitotic clonal expansion: a synchronous process required for adipogenesis. Proc Natl Acad Sci USA 2003; 100: 44-9. http://dx.doi.org/10.1073/pnas.0137044100
Towler MC, Hardie DG. AMP-activated protein kinase in metabolic control and insulin signaling. Circ Res 2007; 100: 328-41. http://dx.doi.org/10.1161/01.RES.0000256090.42690.05
Hardie DG. AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy. Nat Rev Mol Cell Biol 2007; 8: 774-85. http://dx.doi.org/10.1038/nrm2249
Sim AT, Hardie DG. The low activity of acetyl-CoA carboxylase in basal and glucagon-stimulated hepatocytes is due to phosphorylation by the AMP-activated protein kinase and not cyclic AMP-dependent protein kinase. FEBS Lett 1988; 233: 294-8. http://dx.doi.org/10.1016/0014-5793(88)80445-9
Ruderman N, Prentki M. AMP kinase and malonyl-CoA: targets for therapy of the metabolic syndrome. Nat Rev Drug Discov 2004; 3: 340-51. http://dx.doi.org/10.1038/nrd1344
MacDougald OA, Lane MD. Transcriptional regulation of gene expression during adipocyte differentiation. Annu Rev Biochem 1995; 64: 345-73. http://dx.doi.org/10.1146/annurev.bi.64.070195.002021
Kudo M, Sugawara A, Uruno A, Takeuchi K, Ito S. Transcription suppression of peroxisome proliferator-activated receptor gamma2 gene expression by tumor necrosis factor alpha via an inhibition of CCAAT/ enhancer-binding protein delta during the early stage of adipocyte differentiation. Endocrinology 2004; 145: 4948-56. http://dx.doi.org/10.1210/en.2004-0180
Picard F, Kurtev M, Chung N, Topark-Ngarm A, Senawong T, Machado De Oliveira R, et al. Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma. Nature 2004; 429: 771-76. http://dx.doi.org/10.1038/nature02583
Zhou Y, Wang D, Zhu Q, Gao X, Yang S, Xu A, et al. Inhibitory effects of A-769662, a novel activator of AMP-activated protein kinase, on 3T3-L1 adipogenesis. Biol Pharm Bull 2009; 32: 993-98. http://dx.doi.org/10.1248/bpb.32.993
Habinowski SA, Witters LA. The effects of AICAR on adipocyte differentiation of 3T3-L1 cells. Biochem Biophys Res Commun 2001; 286: 852-6. http://dx.doi.org/10.1006/bbrc.2001.5484
Moon HS, Chung CS, Lee HG, Kim TG, Choi YJ, Cho CS. Inhibitory effect of (-)-epigallocatechin-3-gallate on lipid accumulation of 3T3-L1 cells. Obesity (Silver Spring) 2007; 15: 2571-82. http://dx.doi.org/10.1038/oby.2007.309
Chen S, Li Z, Li W, Shan Z, Zhu W. Resveratrol inhibits cell differentiation in 3T3-L1 adipocytes via activation of AMPK. Can J Physiol Pharmacol 89: 793-99.
Hwang JT, Park IJ, Shin JI, Lee YK, Lee SK, Baik HW, et al. Genistein, EGCG, and capsaicin inhibit adipocyte differentiation process via activating AMP-activated protein kinase. Biochem Biophys Res Commun 2005; 338: 694-99. http://dx.doi.org/10.1016/j.bbrc.2005.09.195
Downloads
Published
How to Cite
Issue
Section
License
Policy for Journals/Articles with Open Access
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are permitted and encouraged to post links to their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work
Policy for Journals / Manuscript with Paid Access
Authors who publish with this journal agree to the following terms:
- Publisher retain copyright .
- Authors are permitted and encouraged to post links to their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work .
