Resveratrol: Anti-obesity mechanisms of action

Molecules

Volumn 19, Issue 11, 2014, Pages 18632-18655

  Aguirre, Leixuri ^a,b   Fernández Quintela, Alfredo ^a,b   Arias, Noemí ^a,b   Portillo, Maria P ^a,b  

^a UNIVERSITY OF THE BASQUE COUNTRY UPV EHU   (Spain)

^b INSTITUTO DE SALUD CARLOS III   (Spain)

Author keywords

Adipogenesis; Apoptosis; Fatty acid oxidation; Lipogenesis; Lipolysis; Resveratrol; Thermogenesis

Indexed keywords

CCAAT ENHANCER BINDING PROTEIN; CEBPA PROTEIN, HUMAN; FATTY ACID; NONSTEROID ANTIINFLAMMATORY AGENT; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; RESVERATROL; STILBENE DERIVATIVE;

ADIPOCYTE; APOPTOSIS; BIOSYNTHESIS; DOWN REGULATION; DRUG EFFECTS; HUMAN; LIPOGENESIS; LIVER; METABOLISM; OBESITY; PATHOLOGY; SKELETAL MUSCLE;

ADIPOCYTES; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; APOPTOSIS; CCAAT-ENHANCER-BINDING PROTEINS; DOWN-REGULATION; FATTY ACIDS; HUMANS; LIPOGENESIS; LIVER; MUSCLE, SKELETAL; OBESITY; PPAR GAMMA; STILBENES;

EID: 84914689065     PISSN: None     EISSN: 14203049     Source Type: Journal    
DOI: 10.3390/molecules191118632     Document Type: Review

References (80)

1. Leiherer, A.; Mündlein, A.; Drexel, H. Phytochemicals and their impact on adipose tissue inflammation and diabetes. Vascul. Pharmacol. 2013, 58, 3-20.
2. Burns, J.; Yokota, T.; Ashihara, H.; Lean, M.E.; Crozier, A. Plant foods and herbal sources of resveratrol. J. Agric. Food Chem. 2002, 50, 3337-3340.
3. Borriello, A.; Cucciolla, V.; Della Ragione, F.; Galletti, P. Dietary polyphenols: Focus on resveratrol, a promising agent in the prevention of cardiovascular diseases and control of glucose homeostasis. Nutr. Metab. Cardiovasc. Dis. 2010, 20, 618-625.
4. Wenzel, E.; Somoza, V. Metabolism and bioavailability of trans-resveratrol. Mol. Nutr. Food Res. 2005, 49, 472-481.
5. Walle, T.; Hsieh, F.; DeLegge, M.H.; Oatis, J.E.; Walle, U.K. High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab. Dispos. 2004, 32, 1377-1382.
6. Baur, J.A.; Pearson, K.J.; Price, N.L.; Jamieson, H.A.; Lerin, C.; Kalra, A.; Prabhu, V.V.; Allard, J.S.; Lopez-Lluch, G.; Lewis, K.; et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature 2006, 444, 337-342.
7. Espín, J.C.; García-Conesa, M.T.; Tomás-Barberán, F.A. Nutraceuticals: Facts and fiction. Phytochemistry 2007, 68, 2986-3008.
8. Szkudelska, K.; Szkudelski, T. Resveratrol, obesity and diabetes. Eur. J. Pharmacol. 2010, 635, 1-8.
9. Szkudelski, T.; Szkudelska, K. Anti-diabetic effects of resveratrol. Ann. N. Y. Acad. Sci. 2011, 1215, 34-39.
10. Timmers, S.; Konings, E.; Bilet, L.; Houtkooper, R.H.; van de Weijer, T.; Goossens, G.H.; Hoeks, J.; van der Krieken, S.; Ryu, D.; Kersten, S.; et al. Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. Cell Metab. 2011, 14, 612-622.
11. Meydani, M.; Hasan, S.T. Dietary polyphenols and obesity. Nutrients 2010, 2, 737-751.
12. Catalán, V.; Gómez-Ambrosi, J.; Rodríguez, A.; Frühbeck, G. Role of extracellular matrix remodelling in adipose tissue pathophysiology: Relevance in the development of obesity. Histol. Histopathol. 2012, 27, 1515-1522.
13. Rosen, E.D.; MacDougald, O.A. Adipocyte differentiation from the inside out. Nat. Rev. Mol. Cell Biol. 2006, 7, 885-896.
14. Gregoire, F.M.; Smas, C.M.; Sul, H.S. Understanding adipocyte differentiation. Physiol. Rev. 1998, 78, 783-809.
15. Farmer, S.R. Transcriptional control of adipocyte formation. Cell Metab. 2006, 4, 263-273.
16. Kwon, J.Y.; Seo, S.G.; Yue, S; Cheng, J.X.; Lee, K.W.; Kim, K.H. An inhibitory effect of resveratrol in the mitotic clonal expansion and insulin signaling pathway in the early phase of adipogenesis. Nutr. Res. 2012, 32, 607-616.
17. 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. 2011, 89, 793-799.
18. Rayalam, S.; Yang, J.Y.; Ambati, S.; Della-Fera, M.A.; Baile, C.A. Resveratrol induces apoptosis and inhibits adipogenesis in 3T3-L1 adipocytes. Phytother. Res. 2008, 22, 1367-1371.
19. Kang, N.E.; Ha, A.W.; Kim, J.Y.; Kim, W.K. Resveratrol inhibits the protein expression of transcription factors related adipocyte differentiation and the activity of matrix metalloproteinase in mouse fibroblast 3T3-L1 preadipocytes. Nutr. Res. Pract. 2012, 6, 499-504.
20. Lasa, A.; Churruca, I.; Eseberri, I.; Andrés-Lacueva, C.; Portillo, M.P. Delipidating effect of resveratrol metabolites in 3T3-L1 adipocytes. Mol. Nutr. Food Res. 2012, 56, 1559-1568.
21. Hu, P.; Zhao, L.; Chen, J. Physiologically achievable doses of resveratrol enhance 3T3-L1 adipocyte differentiation. Eur. J. Nutr. 2014, doi:10.1007/s00394-014-0738-4.
22. Carpéné, C.; Gómez-Zorita, S.; Deleruyelle, S.; Carpéné, M.A. Novel strategies for preventing diabetes and obesity complications with natural polyphenols. Curr. Med. Chem. 2014, in press.
23. Bai, L.; Pang, W.J.; Yang, Y.J.; Yang, G.S. Modulation of Sirt1 by resveratrol and nicotinamide alters proliferation and differentiation of pig preadipocytes. Mol. Cell. Biochem. 2008, 307, 129-140.
24. Fisher-Posovszky, P.; Kukulus, V.; Tews, D.; Unterkircher, T.; Debatin, K.M.; Fulda, S.; Wabitsch, M. Resveratrol regulates human adipocyte number and function in a Sirt1-dependent manner. Am. J. Clin. Nutr. 2010, 92, 5-15.
25. Howitz, K.T.; Bitterman, K.J.; Cohen, H.Y.; Lamming, D.W.; Lavu, S.; Wood, J.G.; Zipkin, R.E.; Chung, P.; Kisielewski, A.; Zhang, L.L.; et al. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 2003, 425, 191-196.
26. Barger, J.L.; Kayo, T.; Vann, J.M.; Arias, E.B.; Wang, J.; Hacker, T.A.; Wang, Y.; Raederstorff, D.; Morrow, J.D.; Leeuwenburgh, C.; et al . A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice. PLoS One 2008, 3, doi:10.1371/journal.pone.0002264.
27. Ajmo, J.M.; Liang, X.; Rogers, C.Q.; Pennock, B.; You, M. Resveratrol alleviates alcoholic fatty liver in mice. Am. J. Physiol. Gastrointest. Liver Physiol. 2008, 295, G833-G842.
28. Tauriainen, E.; Luostarinen, M.; Martonen, E.; Finckenberg, P.; Kovalainen, M.; Huotari, A.; Herzig, K.H.; Lecklin, A.; Mervaala, E. Distinct effects of calorie restriction and resveratrol on diet-induced obesity and fatty liver formation. J. Nutr. Metab. 2011, 2011, doi:10.1155/2011/525094.
29. Andres-Lacueva, C.; Macarulla, M.T.; Rotches-Ribalta, M.; Boto-Ordóñez, M.; Urpi-Sarda, M.; Rodríguez, V.M.; Portillo, M.P. Distribution of resveratrol metabolites in liver, adipose tissue, and skeletal muscle in rats fed different doses of this polyphenol. J. Agric. Food Chem. 2012, 60, 4833-4840.
30. Frémont, L. Biological effects of resveratrol. Life Sci. 2000, 66, 663-673.
31. Thornberry, N.A.; Lazebnik, Y. Caspases: Enemies within. Science 1998, 281, 1312-1316.
32. Ashkenazi, A.; Salvesen, G. Regulated Cell Death: Signaling and Mechanisms. Ann. Rev. Cell Dev. Biol. 2014, 30, 337-356.
33. Salvesen, G.S.; Ashkenazi, A. Snapshot: Caspases. Cell 2011, 147, 476-476.e1, doi:10.1016/j.cell.2011.09.030.
34. Adams, J.M.; Cory, S. The Bcl-2 protein family: Arbiters of cell survival. Science 1998, 281, 1322-1326.
35. Yang, J.Y.; Della-Fera, M.A.; Rayalam, S.; Ambati, S.; Hartzell, D.L.; Park, H.J.; Baile, C.A. Enhanced inhibition of adipogenesis and induction of apoptosis in 3T3-L1 adipocytes with combinations of resveratrol and quercetin. Life Sci. 2008, 82, 1032-1039.
36. Rayalam, S.; Della-Fera, M.A.; Yang, J.Y.; Park, H.J.; Ambati, S.; Baile, C.A. Resveratrol potentiates genistein's antiadipogenic and proapoptotic effects in 3T3-L1 adipocytes. J. Nutr. 2007, 137, 2668-2673.
37. Park, H.J.; Yang, J.Y.; Ambati, S.; Della-Fera, M.A.; Hausman, D.B.; Rayalam, S.; Baile, C.A. Combined effects of genistein, quercetin, and resveratrol in human and 3T3-L1 adipocytes. J. Med. Food 2008, 11, 773-783.
38. Chen, S.; Xiao, X.; Feng, X.; Li, W.; Zhou, N.; Zheng, L.; Sun, Y.; Zhang, Z.; Zhu, W. Resveratrol induces Sirt1-dependent apoptosis in 3T3-L1 preadipocytes by activating AMPK and suppressing AKT activity and survivin expression. J. Nutr. Biochem. 2012, 23, 1100-1112.
39. Pang, W.J.; Xiong, Y.; Zhang, Z.; Wei, N.; Chen, N.; Yang, G.S. Lentivirus-mediated Sirt1 shRNA and resveratrol independently induce porcine preadipocyte apoptosis by canonical apoptotic pathway. Mol. Biol. Rep. 2013, 40, 129-139.
40. Vázquez-Vela, M.E.; Torres, N.; Tovar, A.R. White adipose tissue as endocrine organ and its role in obesity. Arch. Med. Res. 2008, 39, 715-728.
41. Wang, C.; Hartsuck, J.; McConathy, W. Structure and functional properties of lipoprotein lipase. Biochim. Biophys. Acta 1992, 1123, 1-17.
42. Auwerx, J.; Schoonjans, K.; Fruchart, J.C.; Staels, B. Transcriptional control of triglyceride metabolism: Fibrates and fatty acids change the expression of the LPL and apo C-III genes by activating the nuclear receptor PPAR. Atherosclerosis 1996, 124, S29-S37.
43. 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.
44. 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.
45. Gómez-Zorita, S.; Fernández-Quintela, A.; Lasa, A.; Hijona, E.; Bujanda, L.; Portillo, M.P. Effects of resveratrol on obesity-related inflammation markers in adipose tissue of genetically obese rats. Nutrition 2013, 29, 1374-1380.
46. Nagao, K.; Jinnouchi, T.; Kai, S.; Yanagita, T. Effect of dietary resveratrol on the metabolic profile of nutrients in obese OLETF rats. Lipids Health Dis. 2013, 12, doi:10.1186/1476-511X-12-8.
47. Alberdi, G.; Rodríguez, V.M.; Miranda, J.; Macarulla, M.T.; Arias, N.; Andrés-Lacueva, C.; Portillo, M.P. Changes in white adipose tissue metabolism induced by resveratrol in rats. Nutr. Metab. (Lond.) 2011, 8, 29, doi:10.1186/1743-7075-8-29.
48. Arias, N.; Miranda, J.; Macarulla, M.T.; Aguirre, L.; Fernández-Quintela, A.; Andres-Lacueva, C.; Urpi-Sarda, M.; Portillo, M.P. The combination of resveratrol and conjugated linoleic acid attenuates the individual effects of these molecules on triacylglycerol metabolism in adipose tissue. Eur. J. Nutr. 2014, 53, 575-582.
49. Kim, S.; Jin, Y.; Choi, Y.; Park, T. Resveratrol exerts anti-obesity effects via mechanisms involving down-regulation of adipogenic and inflammatory processes in mice. Biochem. Pharmacol. 2011, 81, 1343-1351.
50. Cho, S.J.; Jung, U.J.; Choi, M.S. Differential effects of low-dose resveratrol on adiposity and hepatic steatosis in diet-induced obese mice. Br. J. Nutr. 2012, 108, 2166-2175.
51. Qiao, Y.; Sun, J.; Xia, S.; Tang, X.; Shi, Y.; Le, G. Effects of resveratrol on gut microbiota and fat storage in a mouse model with high-fat-induced obesity. Food Funct. 2014, 5, 1241-1249.
52. Azorín-Ortuño, M.; Yáñez-Gascón, M.J.; González-Sarrías, A.; Larrosa, M.; Vallejo, F.; Pallarés, F.J.; Lucas, R.; Morales, J.C.; Tomás-Barberán, F.A.; García-Conesa, M.T.; et al . Effects of long-term consumption of low doses of resveratrol on diet-induced mild hypercholesterolemia in pigs: A transcriptomic approach to disease prevention. J. Nutr. Biochem. 2012, 23, 829-837.
53. Zang, M.; Xu, S.; Maitland-Toolan, K.; Zuccollo, A.; Hou, X.; Jiang, B.; Wierzbicki, M.; Verbeuren, T.; Cohen, R. Polyphenols stimulate AMP-activated protein kinase, lower lipids, and inhibit accelerated atherosclerosis in diabetic LDL receptor-deficient mice. Diabetes 2006, 55, 2180-2191.
54. Hwang, J.T.; Kwon, D.Y.; Park, O.J.; Kim, M.S. Resveratrol protects ROS-induced cell death by activating AMPK in H9c2 cardiac muscle cells. Genes Nutr. 2008, 2, 323-326.
55. Shang, J.; Chen, L.L.; Xiao, F.X.; Sun, H.; Ding, H.C.; Xiao, H. Resveratrol improves non-alcoholic fatty liver disease by activating AMP-activated protein kinase. Acta Pharmacol. Sin. 2008, 29, 698-706.
56. Gómez-Zorita, S.; Fernández-Quintela, A.; Macarulla, M.T.; Aguirre, L.; Hijona, E.; Bujanda, L.; Milagro, F.; Martínez, J.A.; Portillo, M.P. Resveratrol attenuates steatosis in obese Zucker rats by decreasing fatty acid availability and reducing oxidative stress. Br. J. Nutr. 2012, 107, 202-210.
57. Vaughan, M.; Berger, J.E.; Steinberg, D. Hormone-sensitive lipase and monoglyceride lipase activities in adipose tissue. J. Biol. Chem. 1964, 239, 401-409.
58. Zimmermann, R.; Strauss, J.G.; Haemmerle, G.; Schoiswohl, G.; Birner-Gruenberger, R.; Riederer, M.; Lass, A.; Neuberger, G.; Eisenhaber, F.; Hermetter, A.; et al. Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase. Science 2004, 306, 1383-1386.
59. Lafontan, M.; Langin, D. Lipolysis and lipid mobilization in human adipose tissue. Prog. Lipid Res. 2009, 48, 275-297.
60. Picard, F.; Kurtev, M.; Chung, N.; Topark-Ngarm, A.; Senawong, T.; Machado de Oliveira, R.; Leid, M.; McBurney, M.W.; Guarente, L. Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma. Nature 2004, 429, 771-776.
61. Picard, F.; Guarente, L. Molecular links between aging and adipose tissue. Int. J. Obes. (Lond.) 2005, 29, S36-S39.
62. Shan, T.; Ren, Y.; Wang, Y. Sirtuin 1 affects the transcriptional expression of adipose triglyceride lipase in porcine adipocytes. J. Anim. Sci. 2013, 91, 1247-1254.
63. Lasa, A.; Schweiger, M.; Kotzbeck, P.; Churruca, I.; Simón, E.; Zechner, R.; Portillo, M.P. Resveratrol regulates lipolysis via adipose triglyceride lipase. J. Nutr. Biochem. 2012, 23, 379-384.
64. Rosenow, A.; Noben, J.P.; Jocken, J.; Kallendrusch, S.; Fischer-Posovszky, P.; Mariman, E.C.; Renes, J. Resveratrol-induced changes of the human adipocyte secretion profile. J. Proteome Res. 2012, 11, 4733-4743.
65. Pedersen, S.B.; Ølholm, J.; Paulsen, S.K.; Bennetzen, M.F.; Richelsen, B. Low Sirt1 expression, which is upregulated by fasting, in human adipose tissue from obese women. Int. J. Obes. (Lond.) 2008, 32, 1250-1255.
66. Gomez-Zorita, S.; Tréguer, K.; Mercader, J.; Carpéné, C. Resveratrol directly affects in vitro lipolysis and glucose transport in human fat cells. J. Physiol Biochem 2013, 69, 585-593.
67. Lowell, B.B.; Spiegelman, B.M. Towards a molecular understanding of adaptive thermogenesis. Nature 2000, 404, 652-660.
68. Ricquier, D.; Casteilla, L.; Bouillaud, F. Molecular studies of the uncoupling protein. FASEB J. 1991, 5, 2237-2242.
69. Alberdi, G.; Rodríguez, V.M.; Miranda, J.; Macarulla, M.T.; Churruca, I.; Portillo, M.P. Thermogenesis is involved in the body-fat lowering effects of resveratrol in rats. Food Chem. 2013, 141, 1530-1535.
70. Cioffi, F.; Senese, R.; de Lange, P.; Goglia, F.; Lanni, A.; Lombardi, A. Uncoupling proteins: A complex journey to function discovery. Biofactors 2009, 35, 417-428.
71. Azzu, V.; Brand, M.D. The on-off switches of the mitochondrial uncoupling proteins. Trends Biochem. Sci. 2010, 35, 298-307.
72. Lagouge, M.; Argmann, C.; Gerhart-Hines, Z.; Meziane, H.; Lerin, C.; Daussin, F.; Messadeq, N.; Milne, J.; Lambert, P.; Elliott, P.; et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell 2006, 127, 1109-1122.
73. Oliveira, J.M.; Montes, A.C.; Bohnen, J.; Freitas, K.M.; Paz, M.T.; Sena, A.L.; Batista de Paula, A.M.; Coimbra, C.C.; Sousa, S.H. Resveratrol increases brown adipose tissue thermogenesis markers by increasing SIRT1 and energy expenditure and decreasing fat accumulation in adipose tissue of mice fed a standard diet. Eur. J. Nutr. 2014, 53, 1503-1510.
74. Galgani, J.; Ravussin, E. Energy metabolism, fuel selection and body weight regulation. Int. J. Obes. (Lond.) 2008, 32, S109-S119.
75. Isken, F.; Klaus, S.; Petzke, K.J.; Loddenkemper, C.; Pfeiffer, A.F.; Weickert, M.O. Impairment of fat oxidation under high- vs. low-glycemic index diet occurs before the development of an obese phenotype. Am. J. Physiol. Endocrinol. Metab. 2010, 298, E287-E295.
76. Eaton, S.; Bartlett, K.; Pourfarzam, M. Mammalian mitochondrial beta-oxidation. Biochem. J. 1996, 320, 345-357.
77. Kerner, J.; Hoppel, C. Fatty acid import into mitochondria. Biochim. Biophys. Acta 2000, 1486, 1-17.
78. Duplus, E.; Forest, C. Is there a single mechanism for fatty acid regulation of gene transcription? Biochem. Pharmacol. 2002, 64, 893-901.
79. Alberdi, G.; Rodríguez, V.M.; Macarulla, M.T.; Miranda, J.; Churruca, I.; Portillo, M.P. Hepatic lipid metabolic pathways modified by resveratrol in rats fed an obesogenic diet. Nutrition 2013, 29, 562-567.
80. 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.