Calorie restriction combined with resveratrol induces autophagy and protects 26-month-old rat hearts from doxorubicin-induced toxicity

Free Radical Biology and Medicine

Volumn 74, Issue , 2014, Pages 252-262

  Dutta, Debariya ^a,b   Xu, Jinze ^a   Dirain, Marvin L S ^a   Leeuwenburgh, Christiaan ^a,b  

^a UNIVERSITY OF FLORIDA COLLEGE OF MEDICINE   (United States)

^b UNIVERSITY OF FLORIDA   (United States)

Author keywords

Autophagy; Calorie restriction; Doxorubicin; Free radicals; Heart; Oxidative stress; Resveratrol

Indexed keywords

AUTOPHAGY PROTEIN 12; AUTOPHAGY PROTEIN 5; BECLIN 1; CREATINE KINASE; DOXORUBICIN; LACTATE DEHYDROGENASE; MICROTUBULE ASSOCIATED LIGHT CHAIN 3; PROTEIN; PROTEIN P62; RESVERATROL; UNCLASSIFIED DRUG; ANTINEOPLASTIC AGENT; APOPTOSIS REGULATORY PROTEIN; ATG5 PROTEIN, RAT; BECN1 PROTEIN, RAT; HEAT SHOCK PROTEIN; SQSTM1 PROTEIN, RAT; STILBENE DERIVATIVE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; APOPTOSIS; ARTICLE; AUTOPHAGY; BODY COMPOSITION; BODY WEIGHT; CALORIC RESTRICTION; CARDIOTOXICITY; CONTROLLED STUDY; CREATINE KINASE BLOOD LEVEL; DOSE RESPONSE; DRUG BLOOD LEVEL; ENZYME ACTIVITY; FAT MASS; HEART LEFT VENTRICLE; HEART PROTECTION; HEART WEIGHT; LACTATE DEHYDROGENASE BLOOD LEVEL; LEAN BODY WEIGHT; MALE; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTEIN EXPRESSION; RAT; RATTUS NORVEGICUS; SHORT COURSE THERAPY; TREATMENT DURATION; ANIMAL; BLOOD; DRUG EFFECTS; HEART; INBRED RAT STRAIN; METABOLISM; PHYSIOLOGY;

ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; APOPTOSIS REGULATORY PROTEINS; AUTOPHAGY; CALORIC RESTRICTION; CREATINE KINASE; DOXORUBICIN; HEART; HEAT-SHOCK PROTEINS; L-LACTATE DEHYDROGENASE; MALE; PROTEINS; RATS; RATS, INBRED STRAINS; STILBENES;

EID: 84905389709     PISSN: 08915849     EISSN: 18734596     Source Type: Journal    
DOI: 10.1016/j.freeradbiomed.2014.06.011     Document Type: Article

References (84)

1. A.M. Choi, S.W. Ryter, and B. Levine Autophagy in human health and disease N. Engl. J. Med. 368 2013 651 662
2. A. Nakai, O. Yamaguchi, T. Takeda, Y. Higuchi, S. Hikoso, M. Taniike, S. Omiya, I. Mizote, Y. Matsumura, M. Asahi, K. Nishida, M. Hori, N. Mizushima, and K. Otsu The role of autophagy in cardiomyocytes in the basal state and in response to hemodynamic stress Nat. Med. 13 2007 619 624 (Pubitemid 46828485)
3. M. Taneike, O. Yamaguchi, A. Nakai, S. Hikoso, T. Takeda, I. Mizote, T. Oka, T. Tamai, J. Oyabu, T. Murakawa, K. Nishida, T. Shimizu, M. Hori, I. Komuro, T. Shirasawa, N. Mizushima, and K. Otsu Inhibition of autophagy in the heart induces age-related cardiomyopathy Autophagy 6 2010
4. A. Terman, and U.T. Brunk The aging myocardium: roles of mitochondrial damage and lysosomal degradation Heart Lung Circ. 14 2005 107 114 (Pubitemid 40895299)
5. H. Kanamori, G. Takemura, R. Maruyama, K. Goto, A. Tsujimoto, A. Ogino, L. Li, I. Kawamura, T. Takeyama, T. Kawaguchi, K. Nagashima, T. Fujiwara, H. Fujiwara, M. Seishima, and S. Minatoguchi Functional significance and morphological characterization of starvation-induced autophagy in the adult heart Am. J. Pathol. 174 2009 1705 1714
6. S.E. Wohlgemuth, D. Julian, D.E. Akin, J. Fried, K. Toscano, C. Leeuwenburgh, and W.A. Dunn Jr. Autophagy in the heart and liver during normal aging and calorie restriction Rejuvenation Res. 10 2007 281 292 (Pubitemid 47378708)
7. S.E. Wohlgemuth, A.Y. Seo, E. Marzetti, H.A. Lees, and C. Leeuwenburgh Skeletal muscle autophagy and apoptosis during aging: effects of calorie restriction and life-long exercise Exp. Gerontol. 45 2010 138 148
8. G.E. Mullin Red wine, grapes, and better health - resveratrol Nutr. Clin. Pract. 26 2011 722 723
9. S. Bradamante, L. Barenghi, and A. Villa Cardiovascular protective effects of resveratrol Cardiovasc. Drug Rev. 22 2004 169 188 (Pubitemid 39391187)
10. P.S. Ray, G. Maulik, G.A. Cordis, A.A. Bertelli, A. Bertelli, and D.K. Das The red wine antioxidant resveratrol protects isolated rat hearts from ischemia reperfusion injury Free Radic. Biol. Med. 27 1999 160 169 (Pubitemid 29353096)
11. H. Li, and U. Forstermann Resveratrol: a multifunctional compound improving endothelial function. Editorial to: Resveratrol supplementation gender independently improves endothelial reactivity and suppresses superoxide production in healthy rats by S. Soylemez et al Cardiovasc. Drugs Ther. 23 2009 425 429
12. V.R. Ramprasath, and P.J. Jones Anti-atherogenic effects of resveratrol Eur. J. Clin. Nutr. 64 2010 660 668
13. X.C. Lv, and H.Y. Zhou Resveratrol protects H9c2 embryonic rat heart derived cells from oxidative stress by inducing autophagy: role of p38 mitogen-activated protein kinase Can. J. Physiol. Pharmacol. 90 2012 655 662
14. F. Scarlatti, R. Maffei, I. Beau, R. Ghidoni, and P. Codogno Non-canonical autophagy: an exception or an underestimated form of autophagy? Autophagy 4 2008 1083 1085
15. J.K. Jeong, M.H. Moon, B.C. Bae, Y.J. Lee, J.W. Seol, H.S. Kang, J.S. Kim, S.J. Kang, and S.Y. Park Autophagy induced by resveratrol prevents human prion protein-mediated neurotoxicity Neurosci. Res. 73 2012 99 105
16. Y. Wu, X. Li, J.X. Zhu, W. Xie, W. Le, Z. Fan, J. Jankovic, and T. Pan Resveratrol-activated AMPK/SIRT1/autophagy in cellular models of Parkinson's disease Neurosignals 19 2011 163 174
17. Y. Octavia, C.G. Tocchetti, K.L. Gabrielson, S. Janssens, H.J. Crijns, and A.L. Moens Doxorubicin-induced cardiomyopathy: from molecular mechanisms to therapeutic strategies J. Mol. Cell. Cardiol. 52 2012 1213 1225
18. A.C. Childs, S.L. Phaneuf, A.J. Dirks, T. Phillips, and C. Leeuwenburgh Doxorubicin treatment in vivo causes cytochrome C release and cardiomyocyte apoptosis, as well as increased mitochondrial efficiency, superoxide dismutase activity, and Bcl-2 Bax ratio. Cancer Res. 62 2002 4592 4598
19. A. Mordente, E. Meucci, A. Silvestrini, G.E. Martorana, and B. Giardina Anthracyclines and mitochondria Adv. Exp. Med. Biol. 942 2012 385 419
20. G. Takemura, and H. Fujiwara Doxorubicin-induced cardiomyopathy from the cardiotoxic mechanisms to management Prog. Cardiovasc. Dis. 49 2007 330 352 (Pubitemid 46295436)
21. S. Kotamraju, E.A. Konorev, J. Joseph, and B. Kalyanaraman Doxorubicin-induced apoptosis in endothelial cells and cardiomyocytes is ameliorated by nitrone spin traps and ebselen: role of reactive oxygen and nitrogen species J. Biol. Chem. 275 2000 33585 33592
22. P.G. Reeves, F.H. Nielsen, and G.C. Fahey Jr. AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet J. Nutr. 123 1993 1939 1951 (Pubitemid 23342492)
23. Y.M. Jang, S. Kendaiah, B. Drew, T. Phillips, C. Selman, D. Julian, and C. Leeuwenburgh Doxorubicin treatment in vivo activates caspase-12 mediated cardiac apoptosis in both male and female rats FEBS Lett. 577 2004 483 490 (Pubitemid 39539206)
24. J.P. Nixon, M. Zhang, C. Wang, M.A. Kuskowski, C.M. Novak, J.A. Levine, C.J. Billington, and C.M. Kotz Evaluation of a quantitative magnetic resonance imaging system for whole body composition analysis in rodents Obesity (Silver Spring) 18 2010 1652 1659
25. M.M. Bradford A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding Anal. Biochem. 72 1976 248 254
26. T.M. Manini, K.R. Vincent, C.L. Leeuwenburgh, H.A. Lees, A.N. Kavazis, S.E. Borst, and B.C. Clark Myogenic and proteolytic mRNA expression following blood flow restricted exercise Acta Physiol. (Oxford) 201 2011 255 263
27. G. Bjorkoy, T. Lamark, S. Pankiv, A. Overvatn, A. Brech, and T. Johansen Monitoring autophagic degradation of p62/SQSTM1 Methods Enzymol. 452 2009 181 197
28. K.B. Larsen, T. Lamark, A. Overvatn, I. Harneshaug, T. Johansen, and G. Bjorkoy A reporter cell system to monitor autophagy based on p62/SQSTM1 Autophagy 6 2010 784 793
29. X.H. Liang, S. Jackson, M. Seaman, K. Brown, B. Kempkes, H. Hibshoosh, and B. Levine Induction of autophagy and inhibition of tumorigenesis by beclin 1 Nature 402 1999 672 676 (Pubitemid 129516338)
30. R. Kang, H.J. Zeh, M.T. Lotze, and D. Tang The Beclin 1 network regulates autophagy and apoptosis Cell Death Differ. 18 2011 571 580
31. A. Kihara, Y. Kabeya, Y. Ohsumi, and T. Yoshimori Beclin- phosphatidylinositol 3-kinase complex functions at the trans-Golgi network EMBO Rep. 2 2001 330 335 (Pubitemid 32401529)
32. J. Wang Beclin 1 bridges autophagy, apoptosis and differentiation Autophagy 4 2008 947 948
33. N. Mizushima, T. Noda, T. Yoshimori, Y. Tanaka, T. Ishii, M.D. George, D.J. Klionsky, M. Ohsumi, and Y. Ohsumi A protein conjugation system essential for autophagy Nature 395 1998 395 398 (Pubitemid 28450691)
34. N. Mizushima Autophagy: process and function Genes Dev. 21 2007 2861 2873 (Pubitemid 350133435)
35. R. Scherz-Shouval, E. Shvets, E. Fass, H. Shorer, L. Gil, and Z. Elazar Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4 EMBO J. 26 2007 1749 1760 (Pubitemid 46624042)
36. Y. Chen, M.B. Azad, and S.B. Gibson Superoxide is the major reactive oxygen species regulating autophagy Cell Death Differ. 16 2009 1040 1052
37. P. Brancaccio, G. Lippi, and N. Maffulli Biochemical markers of muscular damage Clin. Chem. Lab. Med. 48 2010 757 767
38. J.H. Glick Jr. Serum lactate dehydrogenase isoenzyme and total lactate dehydrogenase values in health and disease, and clinical evaluation of these tests by means of discriminant analysis Am. J. Clin. Pathol. 52 1969 320 328
39. V.I. Korolchuk, A. Mansilla, F.M. Menzies, and D.C. Rubinsztein Autophagy inhibition compromises degradation of ubiquitin-proteasome pathway substrates Mol. Cell 33 2009 517 527
40. V.W. Dolinsky, and J.R. Dyck Calorie restriction and resveratrol in cardiovascular health and disease Biochim. Biophys. Acta 1812 2011 1477 1489
41. P. Kapahi, B.M. Zid, T. Harper, D. Koslover, V. Sapin, and S. Benzer Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway Curr. Biol. 14 2004 885 890 (Pubitemid 38800910)
42. M. Hansen, S. Taubert, D. Crawford, N. Libina, S.J. Lee, and C. Kenyon Lifespan extension by conditions that inhibit translation in Caenorhabditis elegans Aging Cell 6 2007 95 110 (Pubitemid 46140143)
43. Liu, M.; Wilk, S. A.; Wang, A.; Zhou, L.; Wang, R. H.; Ogawa, W.; Deng, C.; Dong, L. Q.; Liu, F. Resveratrol inhibits mTOR signaling by promoting the interaction between mTOR and DEPTOR. J. Biol. Chem. 285:36387-36394.
44. B. Dasgupta, and J. Milbrandt Resveratrol stimulates AMP kinase activity in neurons Proc. Natl. Acad. Sci. USA 104 2007 7217 7222 (Pubitemid 47186035)
45. J. Kim, M. Kundu, B. Viollet, and K.L. Guan AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1 Nat. Cell Biol. 13 2011 132 141
46. I.H. Lee, L. Cao, R. Mostoslavsky, D.B. Lombard, J. Liu, N.E. Bruns, M. Tsokos, F.W. Alt, and T. Finkel A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy Proc. Natl. Acad. Sci. USA 105 2008 3374 3379 (Pubitemid 351723560)
47. K.T. Howitz, K.J. Bitterman, H.Y. Cohen, D.W. Lamming, S. Lavu, J.G. Wood, R.E. Zipkin, P. Chung, A. Kisielewski, L.L. Zhang, B. Scherer, and D.A. Sinclair Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan Nature 425 2003 191 196 (Pubitemid 37150899)
48. L. Guarente, and F. Picard Calorie restriction - the SIR2 connection Cell 120 2005 473 482 (Pubitemid 40269762)
49. D. Chen, A.D. Steele, S. Lindquist, and L. Guarente Increase in activity during calorie restriction requires Sirt1 Science 310 2005 1641 (Pubitemid 41780779)
50. M. Lagouge, C. Argmann, Z. Gerhart-Hines, H. Meziane, C. Lerin, F. Daussin, N. Messadeq, J. Milne, P. Lambert, P. Elliott, B. Geny, M. Laakso, P. Puigserver, and J. Auwerx Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha Cell 127 2006 1109 1122 (Pubitemid 44894520)
51. B. Magnuson, B. Ekim, and D.C. Fingar Regulation and function of ribosomal protein S6 kinase (S6K) within mTOR signalling networks Biochem. J. 441 2012 1 21
52. E. Marzetti, S.E. Wohlgemuth, S.D. Anton, R. Bernabei, C.S. Carter, and C. Leeuwenburgh Cellular mechanisms of cardioprotection by calorie restriction: state of the science and future perspectives Clin. Geriatr. Med. 25 ix 2009 715 732
53. J.G. Wood, B. Rogina, S. Lavu, K. Howitz, S.L. Helfand, M. Tatar, and D. Sinclair Sirtuin activators mimic caloric restriction and delay ageing in metazoans Nature 430 2004 686 689 (Pubitemid 39061685)
54. R. Weindruch, and E.J. Masoro Concerns about rodent models for aging research J. Gerontol. 46 1991 B87 88
55. R.D. Lipman, C.E. Chrisp, D.G. Hazzard, and R.T. Bronson Pathologic characterization of brown Norway, brown Norway × Fischer 344, and Fischer 344 × brown Norway rats with relation to age J. Gerontol. A Biol. Sci. Med. Sci. 51 1996 B54 59
56. T.A. Hacker, S.H. McKiernan, P.S. Douglas, J. Wanagat, and J.M. Aiken Age-related changes in cardiac structure and function in Fischer 344 × Brown Norway hybrid rats Am. J. Physiol. Heart Circ. Physiol. 290 2006 H304 311
57. E.M. Walker Jr, M.S. Nillas, E.I. Mangiarua, S. Cansino, R.G. Morrison, R.R. Perdue, W.E. Triest, G.L. Wright, M. Studeny, P. Wehner, K.M. Rice, and E.R. Blough Age-associated changes in hearts of male Fischer 344/Brown Norway F1 rats Ann. Clin. Lab. Sci. 36 2006 427 438 (Pubitemid 44786689)
58. R. Quinn Comparing rat's to human's age: how old is my rat in people years? Nutrition 21 2005 775 777 (Pubitemid 40733575)
59. J.A. Baur, K.J. Pearson, N.L. Price, H.A. Jamieson, C. Lerin, A. Kalra, V.V. Prabhu, J.S. Allard, G. Lopez-Lluch, K. Lewis, P.J. Pistell, S. Poosala, K.G. Becker, O. Boss, D. Gwinn, M. Wang, S. Ramaswamy, K.W. Fishbein, R.G. Spencer, E.G. Lakatta, C.D. Le, R.J. Shaw, P. Navas, P. Puigserver, D.K. Ingram, C.R. de, and D.A. Sinclair Resveratrol improves health and survival of mice on a high-calorie diet Nature 444 2006 337 342 (Pubitemid 44764104)
60. J.L. Barger, T. Kayo, T.D. Pugh, T.A. Prolla, and R. Weindruch Short-term consumption of a resveratrol-containing nutraceutical mixture mimics gene expression of long-term caloric restriction in mouse heart Exp. Gerontol. 43 2008 859 866
61. I.M. Kapetanovic, M. Muzzio, Z. Huang, T.N. Thompson, and D.L. McCormick Pharmacokinetics, oral bioavailability, and metabolic profile of resveratrol and its dimethylether analog, pterostilbene, in rats Cancer Chemother. Pharmacol. 68 2010 593 601
62. K.R. Patel, C. Andreadi, R.G. Britton, E. Horner-Glister, A. Karmokar, S. Sale, V.A. Brown, D.E. Brenner, R. Singh, W.P. Steward, A.J. Gescher, and K. Brown Sulfate metabolites provide an intracellular pool for resveratrol generation and induce autophagy with senescence Sci. Transl. Med. 5 2013 205ra133
63. G. Bjorkoy, T. Lamark, A. Brech, H. Outzen, M. Perander, A. Overvatn, H. Stenmark, and T. Johansen p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death J. Cell Biol. 171 2005 603 614 (Pubitemid 41668720)
64. N. Mizushima, T. Yoshimori, and B. Levine Methods in mammalian autophagy research Cell 140 2010 313 326
65. X. Guo, M. Kesimer, G. Tolun, X. Zheng, Q. Xu, J. Lu, J.K. Sheehan, J.D. Griffith, and X. Li The NAD(+)-dependent protein deacetylase activity of SIRT1 is regulated by its oligomeric status Sci. Rep. 2 2012 640
66. J. Milner Cellular regulation of SIRT1 Curr. Pharm. Des. 15 2009 39 44
67. A.J. Smuder, A.N. Kavazis, K. Min, and S.K. Powers Exercise protects against doxorubicin-induced markers of autophagy signaling in skeletal muscle J. Appl. Physiol. 111 2011 1190 1198
68. I. Manov, Y. Pollak, R. Broneshter, and T.C. Iancu Inhibition of doxorubicin-induced autophagy in hepatocellular carcinoma Hep3B cells by sorafenib - the role of extracellular signal-regulated kinase counteraction FEBS J. 278 2011 3494 3507
69. Y. Pan, Y. Gao, L. Chen, G. Gao, H. Dong, Y. Yang, B. Dong, and X. Chen Targeting autophagy augments in vitro and in vivo antimyeloma activity of DNA-damaging chemotherapy Clin. Cancer Res. 17 2011 3248 3258
70. N. Gebbia, G. Leto, M. Gagliano, F.M. Tumminello, and L. Rausa Lysosomal alterations in heart and liver of mice treated with doxorubicin Cancer Chemother. Pharmacol. 15 1985 26 30 (Pubitemid 15055612)
71. M. Tokarska-Schlattner, M. Zaugg, C. Zuppinger, T. Wallimann, and U. Schlattner New insights into doxorubicin-induced cardiotoxicity: the critical role of cellular energetics J. Mol. Cell. Cardiol. 41 2006 389 405 (Pubitemid 44362995)
72. K. Chatterjee, J. Zhang, N. Honbo, and J.S. Karliner Doxorubicin cardiomyopathy Cardiology 115 2009 155 162
73. M.S. Mitra, S. Donthamsetty, B. White, J.R. Latendresse, and H.M. Mehendale Mechanism of protection of moderately diet restricted rats against doxorubicin-induced acute cardiotoxicity Toxicol. Appl. Pharmacol. 225 2007 90 101 (Pubitemid 350017834)
74. D. Dutta, R. Calvani, R. Bernabei, C. Leeuwenburgh, and E. Marzetti Contribution of impaired mitochondrial autophagy to cardiac aging: mechanisms and therapeutic opportunities Circ. Res. 110 2012 1125 1138
75. B.J. Willcox, K. Yano, R. Chen, D.C. Willcox, B.L. Rodriguez, K.H. Masaki, T. Donlon, B. Tanaka, and J.D. Curb How much should we eat? The association between energy intake and mortality in a 36-year follow-up study of Japanese-American men J. Gerontol. A Biol. Sci. Med. Sci. 59 2004 789 795 (Pubitemid 39167420)
76. S.B. Racette, E.P. Weiss, D.T. Villareal, H. Arif, K. Steger-May, K.B. Schechtman, L. Fontana, S. Klein, and J.O. Holloszy One year of caloric restriction in humans: feasibility and effects on body composition and abdominal adipose tissue J. Gerontol. A Biol. Sci. Med. Sci. 61 2006 943 950 (Pubitemid 44413933)
77. E.P. Weiss, S.B. Racette, D.T. Villareal, L. Fontana, K. Steger-May, K.B. Schechtman, S. Klein, and J.O. Holloszy Improvements in glucose tolerance and insulin action induced by increasing energy expenditure or decreasing energy intake: a randomized controlled trial Am. J. Clin. Nutr. 84 2006 1033 1042 (Pubitemid 44730373)
78. T. Hofer, L. Fontana, S.D. Anton, E.P. Weiss, D. Villareal, B. Malayappan, and C. Leeuwenburgh Long-term effects of caloric restriction or exercise on DNA and RNA oxidation levels in white blood cells and urine in humans Rejuvenation Res. 11 2008 793 799
79. R.R. Wing, and R.W. Jeffery Effect of modest weight loss on changes in cardiovascular risk factors: are there differences between men and women or between weight loss and maintenance? Int. J. Obes. Relat. Metab. Disord. 19 1995 67 73
80. M.M. Sung, C.L. Soltys, G. Masson, J.J. Boisvenue, and J.R. Dyck Improved cardiac metabolism and activation of the RISK pathway contributes to improved post-ischemic recovery in calorie restricted mice J. Mol. Med. (Berlin) 89 2010 291 302
81. T.E. Meyer, S.J. Kovacs, A.A. Ehsani, S. Klein, J.O. Holloszy, and L. Fontana Long-term caloric restriction ameliorates the decline in diastolic function in humans J. Am. Coll. Cardiol. 47 2006 398 402 (Pubitemid 43063261)
82. L. Fontana, E.P. Weiss, D.T. Villareal, S. Klein, and J.O. Holloszy Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans Aging Cell 7 2008 681 687
83. J.M. Smoliga, J.A. Baur, and H.A. Hausenblas Resveratrol and health - a comprehensive review of human clinical trials Mol. Nutr. Food Res. 55 2011 1129 1141
84. S. Timmers, E. Konings, L. Bilet, R.H. Houtkooper, T. van de Weijer, G.H. Goossens, J. Hoeks, S. van der Krieken, D. Ryu, S. Kersten, E. Moonen-Kornips, M.K. Hesselink, I. Kunz, V.B. Schrauwen-Hinderling, E.E. Blaak, J. Auwerx, and P. Schrauwen Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans Cell Metab. 14 2011 612 622