Changes in white adipose tissue metabolism induced by resveratrol in rats

Goiuri Alberdi, Víctor M Rodríguez, Jonatan Miranda, María T Macarulla, Noemí Arias, Cristina Andrés-Lacueva, María P Portillo, Goiuri Alberdi, Víctor M Rodríguez, Jonatan Miranda, María T Macarulla, Noemí Arias, Cristina Andrés-Lacueva, María P Portillo

Abstract

Background: A remarkable range of biological functions have been ascribed to resveratrol. Recently, this polyphenol has been shown to have body fat lowering effects. The aim of the present study was to assess some of the potential underlying mechanisms of action which take place in adipose tissue.

Methods: Sixteen male Sprague-Dawley rats were randomly divided into two groups: control and treated with 30 mg resveratrol/kg body weight/d. All rats were fed an obesogenic diet and after six weeks of treatment white adipose tissues were dissected. Lipoprotein lipase activity was assessed by fluorimetry, acetyl-CoA carboxylase by radiometry, and malic enzyme, glucose-6P-dehydrogenase and fatty acid synthase by spectrophotometry. Gene expression levels of acetyl-CoA carboxylase, fatty acid synthase, lipoprotein lipase, hormone-sensitive lipase, adipose triglyceride lipase, PPAR-gamma, SREBP-1c and perilipin were assessed by Real time RT-PCR. The amount of resveratrol metabolites in adipose tissue was measured by chromatography.

Results: There was no difference in the final body weight of the rats; however, adipose tissues were significantly decreased in the resveratrol-treated group. Resveratrol reduced the activity of lipogenic enzymes, as well as that of heparin-releasable lipoprotein lipase. Moreover, a significant reduction was induced by this polyphenol in hormone-sensitive lipase mRNA levels. No significant changes were observed in other genes. Total amount of resveratrol metabolites in adipose tissue was 2.66 ± 0.55 nmol/g tissue.

Conclusions: It can be proposed that the body fat-lowering effect of resveratrol is mediated, at least in part, by a reduction in fatty acid uptake from circulating triacylglycerols and also in de novo lipogenesis.

Figures

Figure 1
Figure 1
Food intake, final body weight and body weigt gain. Values are means for eight animals per group with the standard errors of the means, shown by vertical bars.
Figure 2
Figure 2
White adipose tissue weights in experimental groups. Values are means for eight animals per group with the standard errors of the means, shown by vertical bars. *P < 0.05; **P < 0.01. PR: perirenal; EP: epididymal; MS: mesenteric; SC: subcutaneous.
Figure 3
Figure 3
Total and heparin-releasable (HR) lipopoprotein lipase activities in adipose tissue. Values are means for eight animals per group with the standard errors of the means, shown by vertical bars. *P < 0.05.
Figure 4
Figure 4
Lipogenic enzyme activities in adipose tissue. Values are means for eight animals per group with the standard errors of the means, shown by vertical bars. *P < 0.05; **P < 0.01. G6PDH: Glucose-6P-dehydrogenase; ME: malic enzyme; FAS: fatty acid synthase; ACC: acetyl-CoA-Carboxylase.

References

    1. James P, Rigby N, Leach R, Force IOT. The obesity epidemic, metabolic syndrome and future prevention strategies. Eur J Cardiovasc Prev Rehabil. 2004;11:3–8. doi: 10.1097/01.hjr.0000114707.27531.48.
    1. Langcake P, Pryce RJ. The production of resveratrol by Vitis vinifera and other members of the Vitaceae as a response to infection or injury. Physiological Plant Pathology. 1976;9:77–86. doi: 10.1016/0048-4059(76)90077-1.
    1. Frémont L. Biological effects of resveratrol. Life Sci. 2000;66:663–673. doi: 10.1016/S0024-3205(99)00410-5.
    1. Goswami S, Das D. Resveratrol and chemoprevention. Cancer Lett. 2009;284:1–6. doi: 10.1016/j.canlet.2009.01.041.
    1. Cucciolla V, Borriello A, Oliva A, Galletti P. et al.Resveratrol: from basic science to the clinic. Cell Cycle. 2007;6:2495–2510. doi: 10.4161/cc.6.20.4815.
    1. Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H. et al.Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell. 2006;27:1109–1122.
    1. Baur J, Pearson K, Price N, Jamieson H. et al.Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 2006;444:337–342. doi: 10.1038/nature05354.
    1. Ahn J, Cho I, Kim S, Kwon D, Ha T. Dietary resveratrol alters lipid metabolism-related gene expression of mice on an atherogenic diet. J Hepatol. 2008;49:1019–1028. doi: 10.1016/j.jhep.2008.08.012.
    1. Rivera L, Morón R, Zarzuelo A, Galisteo M. Long-term resveratrol administration reduces metabolic disturbances and lowers blood pressure in obese Zucker rats. Biochem Pharmacol. 2009;77:1053–1063. doi: 10.1016/j.bcp.2008.11.027.
    1. Shang J, Chen L, Xiao F, Sun H. et al.Resveratrol improves non-alcoholic fatty liver disease nyactivatingAMP-activated protein kinase. Acta Pharmacol Sin. 2008;29:698–706. doi: 10.1111/j.1745-7254.2008.00807.x.
    1. Wong YT, Gruber J, Jenner AM, Pei-Ern NgM. et al.Elevation of oxidative-damage biomarkers during aging in F2 hybrid mice: Protection by chronic oral intake of resveratrol. Free Radic Biol Med. 2009;46:799–809. doi: 10.1016/j.freeradbiomed.2008.12.016.
    1. Dal-Pan A, Blanc S, Aujard F. Resveratrol suppresses body mass gain in a seasonal non-human primate model of obesity. BMC Physiology. 2010;10:11. doi: 10.1186/1472-6793-10-11.
    1. Baile CA, Yang JY, Rayalam S, Hartzell DL. et al.Effect of resveratrol on fat mobilization. Ann N Y Acad Sci. 2011;1215:40–47. doi: 10.1111/j.1749-6632.2010.05845.x.
    1. Rayalam S, Della-Fera M, Yang J, Park H. et al.Resveratrol potentiates genistein's antiadipogenic and proapoptotic effects in 3T3-L1 adipocytes. J Nutr. 2007;137:2668–2673.
    1. Mader I, Wabitsch M, Fischer-Posovsky P, Fulda S. Identification of a novel proapoptotic function of resveratrol in fat cells:SIRT1-independent sensitization to TRAIL-induced apoptosis. FASEB J. 2010;14:1997–2009.
    1. Picard F, Kurtev M, Chung N, Topark-Ngarm A. et al.Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma. Nature. 2004;429:771–776. doi: 10.1038/nature02583.
    1. Bai L, Pang W, Yang Y, Yang G. Modulation of Sirt1 by resveratrol and nicotinamide alters proliferation and differentiation of pig preadipocytes. Mol Cell Biochem. 2008;307:129–140.
    1. Fischer-Posovsky P, Kukulus V, Tews D, Unterkircher T. et al.Resveratrol regulates human adipocyte number and function in a Sirt1-dependent manner. Am J Clin Nutr. 2010;92:5–15. doi: 10.3945/ajcn.2009.28435.
    1. Szkudelska K, Szkudelski T. Resveratrol, obesity and diabetes. Eur J Pharmacol. 2010;635:1–8. doi: 10.1016/j.ejphar.2010.02.054.
    1. Macarulla M, Alberdi G, Gómez S, Tueros I. et al.Effects of different doses of resveratrol on body fat and serum parameters in rats fed a hypercaloric diet. J Physiol Biochem. 2009;65:369–376. doi: 10.1007/BF03185932.
    1. Gonzales A, Orlando R. Curcumin and resveratrol inhibit nuclear factor-kappaB-mediated cytokine expression in adipocytes. Nutr Metab (Lond) 2008;5:17. doi: 10.1186/1743-7075-5-17.
    1. Del Prado M, Hernandez-Montes H, Villalpando S. Characterization of a fluorometric method for lipoprotein lipase. Arch Med Res. 1994;25:331–335.
    1. Miranda J, Churruca I, Fernández-Quintela A, Rodríguez V. et al.Weak effect of trans-10, cis-12-conjugated linoleic acid on body fat accumulation in adult hamsters. Br J Nutr. 2009;102:1583–1589. doi: 10.1017/S0007114509990912.
    1. Zabala A, Churruca I, Macarulla MT, Rodriguez VM. et al.The trans-10,cis-12 isomer of conjugated linoleic acid reduces hepatic triacylglycerol content without affecting lipogenic enzymes in hamsters. Br J Nutr. 2004;92:383–389. doi: 10.1079/BJN20041220.
    1. Urpi-Sarda M, Zamora-Ros R, Lamuela-Raventos R, Cherubini A. et al.HPLC-tandem mass spectrometric method to characterize resveratrol metabolism in humans. Clin Chem. 2007;53:292–299.
    1. Urpí-Sardà M, Jáuregui O, Lamuela-Raventós R, Jaeger W. et al.Uptake of diet resveratrol into the human low-density lipoprotein. Identification and quantification of resveratrol metabolites by liquid chromatography coupled with tandem mass spectrometry. Anal Chem. 2005;77:3149–3155. doi: 10.1021/ac0484272.
    1. Andres-Lacueva C, Shukitt-Hale B, Galli R, Jauregui O. et al.Anthocyanins in aged blueberry-fed rats are found centrally and may enhance memory. Nutr Neurosci. 2005;8:111–120. doi: 10.1080/10284150500078117.
    1. Goldberg DM, Ng E, Yan J, Karumanchiri A. et al.Regional differences in resveratrol isomer concentrations of wines from various cultivars. Journal of Wine Research. 1996;7:13–24. doi: 10.1080/09571269608718057.
    1. Zamora-Ros R, Andres-Lacueva C, Lamuela-Raventós R, Berenguer T. et al.Concentrations of resveratrol and derivatives in foods and estimation of dietary intake in a Spanish population: European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain cohort. Br J Nutr. 2008;100:188–196.
    1. Munday MR. Regulation of mammalian acetyl.CoA carboxylase. Biochem Soc Trans. 2002;30:1059–1064.
    1. Katsurada A, Iritani N, Fukuda H, Matsumura Y. et al.Effects of nutrients and hormones on transcriptional and post-transcriptional regulation of fatty acid synthase in rat liver. Eur J Biochem. 1990;190:427–433. doi: 10.1111/j.1432-1033.1990.tb15592.x.
    1. Kim K, Park S, Kim Y. Regulation of fatty acid synthase at transcriptional and post-transcriptional levels in rat liver. Yonsei Med J. 1992;33:199–208.
    1. Szkudelska K, Nogowski L, Szkudelski T. Resveratrol, a naturally occurring diphenolic compound, affects lipogenesis, lipolysis and the antilipolytic action of insulin in isolated rat adipocytes. J Steroid Biochem Mol Biol. 2009;113:17–24. doi: 10.1016/j.jsbmb.2008.11.001.
    1. Floyd Z, Wang Z, Kilroy G, Cefalu W. Modulation of peroxisome proliferator-activated receptor gamma stability and transcriptional activity in adipocytes by resveratrol. Metabolism. 2008;57:S32–S38.
    1. Asensi M, Medina I, Ortega A, Carretero J. et al.Inhibition of cancer growth by resveratrol is related to its low bioavailability. Free Radic Biol Med. 2002;33:387–398. doi: 10.1016/S0891-5849(02)00911-5.
    1. Meng X, Maliakal P, Lu H, Lee M, Yang C. Urinary and plasma levels of resveratrol and quercetin in humans, mice, and rats after ingestion of pure compounds and grape juice. J Agric Food Chem. 2004;52:935–942. doi: 10.1021/jf030582e.

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