Keywords
anti-adipogenic activity
luteolin
quercetin
3T3-L1 cell
How to Cite
Abstract
Purpose: Quercetin has been reported as a more potent inhibitor of fat accumulation than other flavonoids. However, little information is available regarding the strength and mechanism of the repressive action of luteolin on fat accumulation. Therefore, the aim of the present study was to evaluate the comparative effects of luteolin and quercetin on the differentiation of 3T3-L1 preadipocytes into mature adipocytes.
Methods: 3T3-L1 preadipocytes were differentiated by treatment with insulin, dexamethasone, and 3-isobutyl-1-methylxanthine in the presence of luteolin or quercetin. Alterations in triacylglycerol (TG) levels, lipid-filled adipocyte quantity, and the mRNA and protein expression levels of CCAAT-enhancer-binding protein α (C/EBPα) and peroxisome proliferator–activated receptor γ (PPARγ) were measured.
Results: Both luteolin and quercetin reduced TG levels, the number of lipid-filled adipocytes, and the mRNA expression levels of C/EBPα and PPARγ; however, these effects occurred with lower concentrations of luteolin than quercetin.
Conclusions: These results suggest that luteolin may be more potent than quercetin in inhibiting adipocyte differentiation. These effects may be explained by differences in the inhibitory effects of the two compounds on C/EBPα and PPARγ expression. This study suggests that luteolin might be a beneficial dietary supplement for obesity and lifestyle-related diseases.
References
Hossain P, Kawar B, El Nahas M. Obesity and diabetes in the developing world–a growing challenge. New Engl J Med 2007; 356(3): 213-215. https://doi.org/10.1056/NEJMp068177
Mello MM, Studdert DM, Brennan TA. Obesity–the new frontier of public health law. New Engl J Med 2006; 354(24): 2601-2610. https://doi.org/10.1056/NEJMhpr060227
de Ferranti S, Mozaffarian D. The perfect storm, obesity, adipocyte dysfunction: and metabolic consequences. Clin Chem 2008; 54(6): 945-955. https://doi.org/10.1373/clinchem.2007.100156
Kopelman PG. Obesity as a medical problem. Nature 2000; 404(6778): 635-643. https://doi.org/10.1038/35007508
Gregoire FM, Smas CM, Sul HS. Understanding adipocyte differentiation. Physiol Rev 1998; 78(3): 783-809. https://doi.org/10.1152/physrev.1998.78.3.783
Ali AT, Hochfeld WE, Myburgh R, Pepper MS. Adipocyte and adipogenesis. Eur J Cell Biol 2013; 92(6-7): 229-236. https://doi.org/10.1016/j.ejcb.2013.06.001
Agullo G, Gamet-Payrastre L, Manenti S, Viala C, Remesy C, Chap H, et al. Relationship between flavonoid structure and inhibition of phosphatidylinositol 3-kinase: a comparison with tyrosine kinase and protein kinase C inhibition. Biochem Pharmacol 1997; 53(11): 1649-1657. https://doi.org/10.1016/S0006-2952(97)82453-7
Herrmann K. Flavonols and flavones in food plants: a review. Int J Food Sci Technol 1976; 11(5): 433-438. https://doi.org/10.1111/j.1365-2621.1976.tb00743.x
Iwashita K, Yamaki K, Tsushida T. Effect of flavonoids on the differentiation of 3T3-L1 adipocytes. Food SciTechnol Res 2001; 7(2): 154-160. https://doi.org/10.3136/fstr.7.154
Mosqueda-Solis A, Lasa A, Comez-Zorita S, Eseberri I, Pico C, Portillo MP. Screening of potential anti-adipogenic effects of phenolic compounds showing different chemical structure in 3T3-L1 preadipocytes. Food Funct 2017; 8(10): 3576- 3586. https://doi.org/10.1039/C7FO00679A
Kim SH, Shin KJ, Kim D, Kim YH, Han MS, Lee TG, et al. Luteolin inhibits the nuclear factor-k B transcriptional activity in Rat-1 fibroblasts. Biochem Pharmacol 2003; 66(6): 955- 963. https://doi.org/10.1016/S0006-2952(03)00465-9
Lim Y, Jeong Y, Tyner A, Park JHY. Induction of cell cycle arrest and apoptosis in HT-29 human colon cancer cells by the dietary compound luteolin. Am J Physiol Gastrointest Liver Physiol 2007; 292(1): G66-G75. https://doi.org/10.1152/ajpgi.00248.2006
Lopez-Lazaro M. Distribution and biological activities of the flavonoid luteolin. Mini Rev Med Chem 2009; 9(1): 31-59. https://doi.org/10.2174/138955709787001712
Sakuma S, Nishioka Y, Imanishi R, Nishikawa K, Sakamoto H, Fujisawa J, et al. cis9, trans11-Conjugated linoleic acid differentiates mouse 3T3-L1 preadipocytes into mature small adipocytes through induction of peroxisome proliferator- activated receptor γ. J Clin Biochem Nutr 2010; 47(2): 167- 173. https://doi.org/10.3164/jcbn.10-44
Sakuma S, Fujisawa J, Sumida M, Tanigawa M, Inoda R, Sujihera T, et al. The involvement of mitogen-activated protein kinases in the 1α,25-dihydroxy-cholecalciferol- induced inhibition of adipocyte differentiation in vitro. J Nutr Sci Vitaminol 2012; 58(1): 1-8. https://doi.org/10.3177/jnsv.58.1
Sakuma S, Sumida M, Endoh Y, Kurita A, Yamaguchi A, Watanabe T, et al. Curcumin inhibits adipogenesis induced by benzyl butyl phthalate in 3T3-L1 cells. Toxicol Appl Pharmacol 2017; 329: 158-164. https://doi.org/10.1016/j.taap.2017.05.036
Sottile V, Seuwen K. Bone morphogenetic protein-2 stimulates adipogenic differentiation of mesenchymal precursor cells in synergy with BRL 49653 (rosiglitazone). FEBS Lett 2000; 475(3): 201-204. https://doi.org/10.1016/S0014-5793(00)01655-0
Schubert M, Becher S, Wallert M, Maeβ MB, Abhari M, Rennert K, et al. The Peroxisome Proliferator–Activated Receptor (PPAR)-γ Antagonist 2-Chloro-5-Nitro-N- Phenylbenzamide (GW9662) Triggers Perilipin 2 Expression via PPARδ and Induces Lipogenesis and Triglyceride Accumulation in Human THP-1 Macrophages. Mol Pharmacol 2020; 97(3): 212-225. https://doi.org/10.1124/mol.119.117887
Jia Y, Wu C, Kim J, Kim B, Lee SJ. Astaxanthin reduces hepatic lipid accumulations in high-fat-fed C57BL/6J mice via activation of peroxisome proliferator-activated receptor (PPAR) alpha and inhibition of PPAR gamma and Akt. J Nutr Biochem 2016; 28: 9-18. https://doi.org/10.1016/j.jnutbio.2015.09.015
Shehzad A, Khan S, Lee YS. Curcumin molecular targets in obesity and obesity-related cancers. Future Oncol 2012; 8(2): 179-190. https://doi.org/10.2217/fon.11.145
Gebhardt R. Inhibition of cholesterol biosynthesis in primary cultured rat hepatocytes by artichoke (Cynara scolymus L.) extract. J Pharmacol Exp Ther 1998; 286(3): 1122-1128. URL: https://jpet.aspetjournals.org/content/jpet/286/3/ 1122.full.pdf
Baker RG, Hayden MS, Ghosh S. NF-κB, Inflammation, and Metabolic Disease. Cell Metab 2011; 13(1): 11-22. https://doi.org/10.1016/j.cmet.2010.12.008
Liu Y, Fu X, Lan N, Li S, Zhang J, Wang S, et al. Luteolin protects against high fat diet-induced cognitive deficits in obesity mice. Behav Brain Res 2014; 267: 178-88. https://doi.org/10.1016/j.bbr.2014.02.040
Xu N, Zhang L, Zhang X, Chen YG, Bao B, Liu J. Low-dose diet supplement of a natural flavonoid, luteolin, ameliorates diet-induced obesity and insulin resistance in mice. Mol Nutr Food. Res 2014; 58(6): 1258-1268. https://doi.org/10.1002/mnfr.201300830
Kwon EY, Jung UJ, Park T, Yun JW, Choi MS. Luteolin attenuates hepatic steatosis and insulin resistance through the interplay between the liver and adipose tissue in mice with diet-induced obesity. Diabetes 2015; 64(5): 1658-1669. https://doi.org/10.2337/db14-0631
Abu Bakar FI, Abu Bakar MF, Rahmat A, Abdullah N, Sabran SF, Endrini S. Anti-gout potential of Malaysian medicinal plants. Front Pharmacol 2018; 23(9): 261. https://doi.org/10.3389/fphar.2018.00261
Liu P, Xu H, Shi Y, Deng L, Chen X. Potential molecular mechanisms of plantain in the treatment of gout and hyperuricemia based on Network Pharmacology. Evid Based Complement Alternat Med 2020; 2020: 3023127. https://doi.org/10.1155/2020/3023127
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