An examination of resveratrol's mechanisms of action in human tissue: Impact of a single dose in vivo and dose responses in skeletal muscle ex vivo

PLoS ONE

Volumn 9, Issue 7, 2014, Pages

  Williams, Cameron B ^a   Hughes, Meghan C ^b   Edgett, Brittany A ^a   Scribbans, Trisha D ^a   Simpson, Craig A ^a   Perry, Christopher G R ^b   Gurd, Brendon J ^a  

^a QUEEN S UNIVERSITY   (Canada)

^b YORK UNIVERSITY   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE TRIPHOSPHATE; FATTY ACID; INSULIN; MITOGEN ACTIVATED PROTEIN KINASE P38; PLACEBO; PROTEIN P53; RESVERATROL; SIRTUIN 1; GLUCOSE BLOOD LEVEL; GLYCEROL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; SIRT1 PROTEIN, HUMAN; STILBENE DERIVATIVE;

ACETYLATION; ADIPOSE TISSUE; ADULT; ARTICLE; BLOOD SAMPLING; BODY MASS; DRUG EFFICACY; DRUG MECHANISM; DRUG RESPONSE; ENERGY TRANSFER; EX VIVO STUDY; FATTY ACID OXIDATION; HUMAN; HUMAN TISSUE; IN VIVO STUDY; INSULIN BLOOD LEVEL; MITOCHONDRIAL RESPIRATION; MUSCLE BIOPSY; PROTEIN PHOSPHORYLATION; SINGLE DRUG DOSE; SKELETAL MUSCLE; BLOOD; CONTROLLED STUDY; CROSSOVER PROCEDURE; DOUBLE BLIND PROCEDURE; DRUG EFFECTS; GLUCOSE BLOOD LEVEL; MALE; METABOLISM; MITOCHONDRION; RANDOMIZED CONTROLLED TRIAL; SIGNAL TRANSDUCTION;

ACETYLATION; ADIPOSE TISSUE; ADULT; AMP-ACTIVATED PROTEIN KINASES; BLOOD GLUCOSE; CROSS-OVER STUDIES; DOUBLE-BLIND METHOD; GLYCEROL; HUMANS; INSULIN; MALE; MITOCHONDRIA; MUSCLE, SKELETAL; SIGNAL TRANSDUCTION; SIRTUIN 1; STILBENES;

EID: 84904256315     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0102406     Document Type: Article

References (56)

1. Chung JH, Manganiello V, Dyck JR (2012) Resveratrol as a calorie restriction mimetic: therapeutic implications. Trends Cell Biol 22: 546-554. S0962-8924(12)00114-6 [pii];10.1016/j.tcb.2012.07.004 [doi].
2. Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, et al. (2006) Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell 127: 1109-1122. S0092-8674(06)01428-0 [pii];10.1016/j.cell.2006.11.013 [doi].
3. Dal-Pan A, Blanc S, Aujard F (2010) Resveratrol suppresses body mass gain in a seasonal non-human primate model of obesity. BMC Physiol 10: 11. 1472-6793-10-11 [pii];10.1186/1472-6793-10-11 [doi].
4. Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, et al. (2006) Resveratrol improves health and survival of mice on a high-calorie diet. Nature 444: 337-342. nature05354 [pii];10.1038/nature05354 [doi].
5. Pearson KJ, Baur JA, Lewis KN, Peshkin L, Price NL, et al. (2008) Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. Cell Metab 8: 157-168. S1550-4131(08)00182-4 [pii];10.1016/j.cmet.2008.06.011 [doi].
6. Su HC, Hung LM, Chen JK (2006) Resveratrol, a red wine antioxidant, possesses an insulin-like effect in streptozotocin-induced diabetic rats. Am J Physiol Endocrinol Metab 290: E1339-E1346. 00487.2005 [pii];10.1152/ajpendo. 00487.2005 [doi].
7. Kang W, Hong HJ, Guan J, Kim DG, Yang EJ, et al. (2012) Resveratrol improves insulin signaling in a tissue-specific manner under insulin-resistant conditions only: in vitro and in vivo experiments in rodents. Metabolism 61: 424-433. S0026-0495(11)00269-1 [pii];10.1016/j.metabol.2011.08.003 [doi].
8. Andersen G, Burkon A, Sulzmaier FJ, Walker JM, Leckband G, et al. (2011) High dose of dietary resveratrol enhances insulin sensitivity in healthy rats but does not lead to metabolite concentrations effective for SIRT1 expression. Mol Nutr Food Res 55: 1197-1206. 10.1002/mnfr.201100292 [doi].
9. Marchal J, Blanc S, Epelbaum J, Aujard F, Pifferi F (2012) Effects of chronic calorie restriction or dietary resveratrol supplementation on insulin sensitivity markers in a primate, Microcebus murinus. PLoS ONE 7: e34289. 10.1371/journal.pone.0034289 [doi];PONE-D-11-25547 [pii].
10. Canto C, Gerhart-Hines Z, Feige JN, Lagouge M, Noriega L, et al. (2009) AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. Nature 458: 1056-1060. nature07813 [pii];10.1038/nature07813 [doi].
11. Canto C, Auwerx J (2009) PGC-1alpha, SIRT1 and AMPK, an energy sensing network that controls energy expenditure. Curr Opin Lipidol 20: 98-105. 10.1097/MOL.0b013e328328d0a4 [doi];00041433-200904000-00004 [pii].
12. Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, et al. (2003) Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 425: 191-196. 10.1038/nature01960 [doi];nature01960 [pii].
13. Hubbard BP, Gomes AP, Dai H, Li J, Case AW, et al. (2013) Evidence for a common mechanism of SIRT1 regulation by allosteric activators. Science 339: 1216-1219. 339/6124/1216 [pii];10.1126/science.1231097 [doi].
14. Kaeberlein M, McDonagh T, Heltweg B, Hixon J, Westman EA, et al. (2005) Substrate-specific activation of sirtuins by resveratrol. J Biol Chem 280: 17038-17045. M500655200 [pii];10.1074/jbc.M500655200 [doi].
15. Pacholec M, Bleasdale JE, Chrunyk B, Cunningham D, Flynn D, et al. (2010) SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1. J Biol Chem 285: 8340-8351. M109.088682 [pii];10.1074/jbc.M109.088682 [doi].
16. Park CE, Kim MJ, Lee JH, Min BI, Bae H, et al. (2007) Resveratrol stimulates glucose transport in C2C12 myotubes by activating AMP-activated protein kinase. Exp Mol Med 39: 222-229. 2007043011 [pii];10.1038/emm.2007.25 [doi].
17. Um JH, Park SJ, Kang H, Yang S, Foretz M, et al. (2010) AMP-activated protein kinase-deficient mice are resistant to the metabolic effects of resveratrol. Diabetes 59: 554-563. db09-0482 [pii];10.2337/db09-0482 [doi].
18. Price NL, Gomes AP, Ling AJ, Duarte FV, Martin-Montalvo A, et al. (2012) SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function. Cell Metab 15: 675-690. S1550-4131(12)00143-X [pii];10.1016/j.cmet.2012.04.003 [doi].
19. Park SJ, Ahmad F, Philp A, Baar K, Williams T, et al. (2012) Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. Cell 148: 421-433. S0092-8674(12)00030-X [pii];10.1016/j.cell.2012.01.017 [doi].
20. Zheng J, Ramirez VD (2000) Inhibition of mitochondrial proton F0F1-ATPase/ATP synthase by polyphenolic phytochemicals. Br J Pharmacol 130: 1115-1123. 10.1038/sj.bjp.0703397 [doi]. (Pubitemid 30453547)
21. Higashida K, Kim SH, Jung SR, Asaka M, Holloszy JO, et al. (2013) Effects of Resveratrol and SIRT1 on PGC-1alpha Activity and Mitochondrial Biogenesis: A Reevaluation. PLoS Biol 11: e1001603. 10.1371/journal.pbio.1001603 [doi];PBIOLOGY-D-13-00038 [pii].
22. Zang M, Xu S, Maitland-Toolan KA, Zuccollo A, Hou X, et al. (2006) Polyphenols stimulate AMP-activated protein kinase, lower lipids, and inhibit accelerated atherosclerosis in diabetic LDL receptor-deficient mice. Diabetes 55: 2180-2191. 55/8/2180 [pii];10.2337/db05-1188 [doi].
23. Hawley SA, Ross FA, Chevtzoff C, Green KA, Evans A, et al. (2010) Use of cells expressing gamma subunit variants to identify diverse mechanisms of AMPK activation. Cell Metab 11: 554-565. S1550-4131(10)00112-9 [pii];10.1016/j.cmet. 2010.04.001 [doi].
24. Timmers S, Konings E, Bilet L, Houtkooper RH, van de Weijer T, et al. (2011) Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. Cell Metab 14: 612-622. S1550-4131(11)00386-X [pii];10.1016/j.cmet.2011.10.002 [doi].
25. Brasnyo P, Molnar GA, Mohas M, Marko L, Laczy B, et al. (2011) Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients. Br J Nutr 106: 383-389. S0007114511000316 [pii];10.1017/S0007114511000316 [doi].
26. Crandall JP, Oram V, Trandafirescu G, Reid M, Kishore P, et al. (2012) Pilot study of resveratrol in older adults with impaired glucose tolerance. J Gerontol A Biol Sci Med Sci 67: 1307-1312. glr235 [pii];10.1093/gerona/glr235 [doi].
27. Yoshino J, Conte C, Fontana L, Mittendorfer B, Imai S, et al. (2012) Resveratrol supplementation does not improve metabolic function in nonobese women with normal glucose tolerance. Cell Metab 16: 658-664. S1550-4131(12)00399-3 [pii];10.1016/j.cmet.2012.09.015 [doi].
28. Poulsen MM, Vestergaard PF, Clasen BF, Radko Y, Christensen LP, et al. (2013) High-dose resveratrol supplementation in obese men: an investigator-initiated, randomized, placebo-controlled clinical trial of substrate metabolism, insulin sensitivity, and body composition. Diabetes 62: 1186-1195. db12-0975 [pii];10.2337/db12-0975 [doi].
29. Lean ME, Han TS, Morrison CE (1995) Waist circumference as a measure for indicating need for weight management. BMJ 311: 158-161.
30. Bergstrom J (1975) Percutaneous needle biopsy of skeletal muscle in physiological and clinical research. Scand J Clin Lab Invest 35: 609-616.
31. Vissing K, Andersen JL, Schjerling P (2005) Are exercise-induced genes induced by exercise? FASEB J 19: 94-96. 04-2084fje [pii];10.1096/fj.04-2084fje [doi].
32. Guerra B, Gomez-Cabrera MC, Ponce-Gonzalez JG, Martinez-Bello VE, Guadalupe-Grau A, et al. (2011) Repeated muscle biopsies through a single skin incision do not elicit muscle signaling, but IL-6 mRNA and STAT3 phosphorylation increase in injured muscle. J Appl Physiol (1985) 110: 1708-1715. japplphysiol.00091.2011 [pii];10.1152/japplphysiol.00091.2011 [doi].
33. Holloway GP, Bezaire V, Heigenhauser GJ, Tandon NN, Glatz JF, et al. (2006) Mitochondrial long chain fatty acid oxidation, fatty acid translocase/CD36 content and carnitine palmitoyltransferase I activity in human skeletal muscle during aerobic exercise. J Physiol 571: 201-210. jphysiol.2005.102178 [pii];10.1113/jphysiol.2005.102178 [doi].
34. Gurd BJ, Yoshida Y, McFarlan JT, Holloway GP, Moyes CD, et al. (2011) Nuclear SIRT1 activity, but not protein content, regulates mitochondrial biogenesis in rat and human skeletal muscle. Am J Physiol Regul Integr Comp Physiol 301: R67-R75. ajpregu.00417.2010 [pii];10.1152/ajpregu.00417.2010 [doi].
35. Holloway GP, Gurd BJ, Snook LA, Lally J, Bonen A (2010) Compensatory increases in nuclear PGC1{alpha} protein are primarily associated with subsarcolemmal mitochondrial adaptations in ZDF rats. Diabetes. db09-1519 [pii];10.2337/db09-1519 [doi].
36. Little JP, Safdar A, Bishop D, Tarnopolsky MA, Gibala MJ (2011) An acute bout of high-intensity interval training increases the nuclear abundance of PGC-1alpha and activates mitochondrial biogenesis in human skeletal muscle. Am J Physiol Regul Integr Comp Physiol 300: R1303-R1310. ajpregu.00538.2010 [pii];10.1152/ajpregu.00538.2010 [doi].
37. Little JP, Safdar A, Cermak N, Tarnopolsky MA, Gibala MJ (2010) Acute endurance exercise increases the nuclear abundance of PGC-1alpha in trained human skeletal muscle. Am J Physiol Regul Integr Comp Physiol 298: R912-R917. 00409.2009 [pii];10.1152/ajpregu.00409.2009 [doi].
38. Kuznetsov AV, Tiivel T, Sikk P, Kaambre T, Kay L, et al. (1996) Striking differences between the kinetics of regulation of respiration by ADP in slowtwitch and fast-twitch muscles in vivo. Eur J Biochem 241: 909-915. (Pubitemid 26379396)
39. Tonkonogi M, Fernstrom M, Walsh B, Ji LL, Rooyackers O, et al. (2003) Reduced oxidative power but unchanged antioxidative capacity in skeletal muscle from aged humans. Pflugers Arch 446: 261-269. 10.1007/s00424-003-1044-9 [doi]. (Pubitemid 36683591)
40. Perry CG, Kane DA, Lin CT, Kozy R, Cathey BL, et al. (2011) Inhibiting myosin-ATPase reveals a dynamic range of mitochondrial respiratory control in skeletal muscle. Biochem J 437: 215-222. BJ20110366 [pii];10.1042/BJ20110366 [doi].
41. Perry CG, Kane DA, Lanza IR, Neufer PD (2013) Methods for assessing mitochondrial function in diabetes. Diabetes 62: 1041-1053. 62/4/1041 [pii];10.2337/db12-1219 [doi].
42. Kane DA, Lin CT, Anderson EJ, Kwak HB, Cox JH, et al. (2011) Progesterone increases skeletal muscle mitochondrial H2O2 emission in nonmenopausal women. Am J Physiol Endocrinol Metab 300: E528-E535. ajpendo.00389.2010 [pii];10.1152/ajpendo.00389.2010 [doi].
43. Pesta Gnaiger (2012) Mitochondrial Bioenergetics. Methods in Molecular Biology 810: 25-58.
44. Boocock DJ, Faust GE, Patel KR, Schinas AM, Brown VA, et al. (2007) Phase I dose escalation pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer chemopreventive agent. Cancer Epidemiol Biomarkers Prev 16: 1246-1252. 16/6/1246 [pii];10.1158/1055-9965.EPI-07-0022 [doi].
45. Patel KR, Scott E, Brown VA, Gescher AJ, Steward WP, et al. (2011) Clinical trials of resveratrol. Ann N Y Acad Sci 1215: 161-169. 10.1111/j.1749-6632.2010.05853.x [doi].
46. Brown VA, Patel KR, Viskaduraki M, Crowell JA, Perloff M, et al. (2010) Repeat dose study of the cancer chemopreventive agent resveratrol in healthy volunteers: safety, pharmacokinetics, and effect on the insulin-like growth factor axis. Cancer Res 70: 9003-9011. 0008-5472.CAN-10-2364 [pii];10.1158/0008-5472.CAN-10-2364 [doi].
47. Lasa A, Churruca I, Eseberri I, Andres-Lacueva C, Portillo MP (2012) Delipidating effect of resveratrol metabolites in 3T3-L1 adipocytes. Mol Nutr Food Res 56: 1559-1568. 10.1002/mnfr.201100772 [doi].
48. Horowitz JF (2003) Fatty acid mobilization from adipose tissue during exercise. Trends Endocrinol Metab 14: 386-392. S1043276003001437 [pii].
49. Gertz M, Nguyen GT, Fischer F, Suenkel B, Schlicker C, et al. (2012) A molecular mechanism for direct sirtuin activation by resveratrol. PLoS ONE 7: e49761. 10.1371/journal.pone.0049761 [doi];PONE-D-12-24873 [pii].
50. White AT, Schenk S (2012) NAD(+) /NADH and skeletal muscle mitochondrial adaptations to exercise. Am J Physiol Endocrinol Metab 303: E308-E321. ajpendo.00054.2012 [pii];10.1152/ajpendo.00054.2012 [doi].
51. Calabrese EJ, Mattson MP, Calabrese V (2010) Resveratrol commonly displays hormesis: occurrence and biomedical significance. Hum Exp Toxicol 29: 980-1015. 29/12/980 [pii];10.1177/0960327110383625 [doi].
52. Walle T, Hsieh F, DeLegge MH, Oatis JE, Jr., Walle UK (2004) High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab Dispos 32: 1377-1382. 10.1124/dmd.104.000885 [doi];dmd.104.000885 [pii].
53. Somwar R, Perreault M, Kapur S, Taha C, Sweeney G, et al. (2000) Activation of p38 mitogen-activated protein kinase alpha and beta by insulin and contraction in rat skeletal muscle: potential role in the stimulation of glucose transport. Diabetes 49: 1794-1800.
54. Thong FS, Derave W, Urso B, Kiens B, Richter EA (2003) Prior exercise increases basal and insulin-induced p38 mitogen-activated protein kinase phosphorylation in human skeletal muscle. J Appl Physiol 94: 2337-2341. 10.1152/japplphysiol.00036.2003 [doi];00036.2003 [pii].
55. Furtado LM, Somwar R, Sweeney G, Niu W, Klip A (2002) Activation of the glucose transporter GLUT4 by insulin. Biochem Cell Biol 80: 569-578. (Pubitemid 36124818)
56. Szkudelski T (2007) Resveratrol-induced inhibition of insulin secretion from rat pancreatic islets: evidence for pivotal role of metabolic disturbances. Am J Physiol EndocrinolMetab 293: E901-E907. 00564.2006 [pii];10.1152/ajpendo. 00564.2006 [doi].