Resveratrol and inflammation: Challenges in translating pre-clinical findings to improved patient outcomes

Biochimica et Biophysica Acta - Molecular Basis of Disease

Volumn 1852, Issue 6, 2015, Pages 1124-1136

  Poulsen, Morten Møller ^a   Fjeldborg, Karen ^a   Ornstrup, Marie Juul ^a   Kjær, Thomas Nordstrøm ^a   Nøhr, Mark Klitgaard ^a   Pedersen, Steen Bønløkke ^a  

^a AARHUS UNIVERSITY HOSPITAL   (Denmark)

Author keywords

Clinical trial; In vitro; In vivo; Inflammation; Metabolism; Resveratrol

Indexed keywords

ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; RESVERATROL; STILBENES;

ADIPOSE TISSUE; ANIMALS; CLINICAL TRIALS AS TOPIC; DRUG EFFECTS; HUMANS; INFLAMMATION; METABOLISM; OBESITY; TRANSLATIONAL MEDICAL RESEARCH;

ADIPOSE TISSUE; ANIMALS; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; CLINICAL TRIALS AS TOPIC; HUMANS; INFLAMMATION; OBESITY; STILBENES; TRANSLATIONAL MEDICAL RESEARCH;

EID: 84939956599     PISSN: 09254439     EISSN: 1879260X     Source Type: Journal    
DOI: 10.1016/j.bbadis.2014.12.024     Document Type: Review

References (172)

1. World Health Organization Obesity and overweight (Www. Who. Int 2012). http://www.who.int/mediacentre/factsheets/fs311/en/index.html.
2. Agarwal B., Campen M.J., Channell M.M., Wherry S.J., Varamini B., Davis J.G., Baur J.A., Smoliga J.M. Resveratrol for primary prevention of atherosclerosis: clinical trial evidence for improved gene expression in vascular endothelium. Int. J. Cardiol. 2013, 166:246-248.
3. Ahima R.S. Metabolic actions of adipocyte hormones: focus on adiponectin. Obesity (Silver Spring) 2006, 14(Suppl. 1):9S-15S.
4. Ahmad R., Al-Mass A., Atizado V., Al-Hubail A., Al-Ghimlas F., Al-Arouj M., Bennakhi A., Dermime S., Behbehani K. Elevated expression of the toll like receptors 2 and 4 in obese individuals: its significance for obesity-induced inflammation. J. Inflamm. (Lond.) 2012, 9:48.
5. Amri A., Chaumeil J.C., Sfar S., Charrueau C. Administration of resveratrol: what formulation solutions to bioavailability limitations?. J. Control. Release 2012, 158:182-193.
6. Annabi B., Lord-Dufour S., Vezina A., Beliveau R. Resveratrol targeting of carcinogen-induced brain endothelial cell inflammation biomarkers MMP-9 and COX-2 is Sirt1-independent. Drug Target. Insights 2012, 6:1-11.
7. Aron-Wisnewsky J., Tordjman J., Poitou C., Darakhshan F., Hugol D., Basdevant A., Aissat A., Guerre-Millo M., Clement K. Human adipose tissue macrophages: m1 and m2 cell surface markers in subcutaneous and omental depots and after weight loss. J. Clin. Endocrinol. Metab. 2009, 94:4619-4623.
8. Bakker G.C., van Erk M.J., Pellis L., Wopereis S., Rubingh C.M., Cnubben N.H., Kooistra T., van O.B., Hendriks H.F. An antiinflammatory dietary mix modulates inflammation and oxidative and metabolic stress in overweight men: a nutrigenomics approach. Am. J. Clin. Nutr. 2010, 91:1044-1059.
9. Barbarroja N., Lopez-Pedrera R., Mayas M.D., Garcia-Fuentes E., Garrido-Sanchez L., Macias-Gonzalez M., El B.R., Vidal-Puig A., Tinahones F.J. The obese healthy paradox: is inflammation the answer?. Biochem. J. 2010, 430:141-149.
10. Bastard J.P., Jardel C., Bruckert E., Blondy P., Capeau J., Laville M., Vidal H., Hainque B. Elevated levels of interleukin 6 are reduced in serum and subcutaneous adipose tissue of obese women after weight loss. J. Clin. Endocrinol. Metab. 2000, 85:3338-3342.
11. 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., Pistell P.J., Poosala S., Becker K.G., Boss O., Gwinn D., Wang M., Ramaswamy S., Fishbein K.W., Spencer R.G., Lakatta E.G., Le C.D., Shaw R.J., Navas P., Puigserver P., Ingram D.K., de C.R., Sinclair D.A. Resveratrol improves health and survival of mice on a high-calorie diet. Nature 2006, 444:337-342.
12. Bereswill S., Munoz M., Fischer A., Plickert R., Haag L.M., Otto B., Kuhl A.A., Loddenkemper C., Gobel U.B., Heimesaat M.M. Anti-inflammatory effects of resveratrol, curcumin and simvastatin in acute small intestinal inflammation. PLoS ONE 2010, 5:e15099.
13. Bhatt J.K., Thomas S., Nanjan M.J. Resveratrol supplementation improves glycemic control in type 2 diabetes mellitus. Nutr. Res. 2012, 32:537-541.
14. Bo S., Ciccone G., Castiglione A., Gambino R., De M.F., Villois P., Durazzo M., Cavallo-Perin P., Cassader M. Anti-inflammatory and antioxidant effects of resveratrol in healthy smokers a randomized, double-blind, placebo-controlled, cross-over trial. Curr. Med. Chem. 2013, 20:1323-1331.
15. Bowers J.L., Tyulmenkov V.V., Jernigan S.C., Klinge C.M. Resveratrol acts as a mixed agonist/antagonist for estrogen receptors alpha and beta. Endocrinology 2000, 141:3657-3667.
16. Brasnyo P., Molnar G.A., Mohas M., Marko L., Laczy B., Cseh J., Mikolas E., Szijarto I.A., Merei A., Halmai R., Meszaros L.G., Sumegi B., Wittmann I. Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients. Br. J. Nutr. 2011, 1-7.
17. Bruun J.M., Helge J.W., Richelsen B., Stallknecht B. Diet and exercise reduce low-grade inflammation and macrophage infiltration in adipose tissue but not in skeletal muscle in severely obese subjects. Am. J. Physiol. Endocrinol. Metab. 2006, 290:E961-E967.
18. Bruun J.M., Lihn A.S., Madan A.K., Pedersen S.B., Schiott K.M., Fain J.N., Richelsen B. Higher production of IL-8 in visceral vs. subcutaneous adipose tissue. Implication of nonadipose cells in adipose tissue. Am. J. Physiol. Endocrinol. Metab. 2004, 286:E8-E13.
19. Bruun J.M., Lihn A.S., Pedersen S.B., Richelsen B. Monocyte chemoattractant protein-1 release is higher in visceral than subcutaneous human adipose tissue (AT): implication of macrophages resident in the AT. J. Clin. Endocrinol. Metab. 2005, 90:2282-2289.
20. Calamini B., Ratia K., Malkowski M.G., Cuendet M., Pezzuto J.M., Santarsiero B.D., Mesecar A.D. Pleiotropic mechanisms facilitated by resveratrol and its metabolites. Biochem. J. 2010, 429:273-282.
21. Cancello R., Henegar C., Viguerie N., Taleb S., Poitou C., Rouault C., Coupaye M., Pelloux V., Hugol D., Bouillot J.L., Bouloumie A., Barbatelli G., Cinti S., Svensson P.A., Barsh G.S., Zucker J.D., Basdevant A., Langin D., Clement K. Reduction of macrophage infiltration and chemoattractant gene expression changes in white adipose tissue of morbidly obese subjects after surgery-induced weight loss. Diabetes 2005, 54:2277-2286.
22. Cancello R., Tordjman J., Poitou C., Guilhem G., Bouillot J.L., Hugol D., Coussieu C., Basdevant A., Bar H.A., Bedossa P., Guerre-Millo M., Clement K. Increased infiltration of macrophages in omental adipose tissue is associated with marked hepatic lesions in morbid human obesity. Diabetes 2006, 55:1554-1561.
23. Candelario-Jalil E., de Oliveira A.C., Graf S., Bhatia H.S., Hull M., Munoz E., Fiebich B.L. Resveratrol potently reduces prostaglandin E2 production and free radical formation in lipopolysaccharide-activated primary rat microglia. J. Neuroinflammation 2007, 4:25.
24. Cani P.D., Amar J., Iglesias M.A., Poggi M., Knauf C., Bastelica D., Neyrinck A.M., Fava F., Tuohy K.M., Chabo C., Waget A., Delmee E., Cousin B., Sulpice T., Chamontin B., Ferrieres J., Tanti J.F., Gibson G.R., Casteilla L., Delzenne N.M., Alessi M.C., Burcelin R. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 2007, 56:1761-1772.
25. Cani P.D., Bibiloni R., Knauf C., Waget A., Neyrinck A.M., Delzenne N.M., Burcelin R. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes 2008, 57:1470-1481.
26. Cavelti-Weder C., Babians-Brunner A., Keller C., Stahel M.A., Kurz-Levin M., Zayed H., Solinger A.M., Mandrup-Poulsen T., Dinarello C.A., Donath M.Y. Effects of gevokizumab on glycemia and inflammatory markers in type 2 diabetes. Diabetes Care 2012, 35:1654-1662.
27. Cerda C., Sanchez C., Climent B., Vazquez A., Iradi A., El A.F., Bediaga A., Saez G.T. Oxidative stress and DNA damage in obesity-related tumorigenesis. Adv. Exp. Med. Biol. 2014, 824:5-17.
28. Chachay V.S., Macdonald G.A., Martin J.H., Whitehead J.P., O'Moore-Sullivan T.M., Lee P., Franklin M., Klein K., Taylor P.J., Ferguson M., Coombes J.S., Thomas G.P., Cowin G.J., Kirkpatrick C.M., Prins J.B., Hickman I.J. Resveratrol does not benefit patients with nonalcoholic fatty liver disease. Clin. Gastroenterol. Hepatol. 2014 Dec, 12(12):2092-2103.
29. Choe S.S., Shin K.C., Ka S., Lee Y.K., Chun J.S., Kim J.B. Macrophage HIF-2alpha ameliorates adipose tissue inflammation and insulin resistance in obesity. Diabetes 2014 Oct, 63(10):3359-3371.
30. Choi M.S., Kim Y., Jung J.Y., Yang S.H., Lee T.R., Shin D.W. Resveratrol induces autophagy through death-associated protein kinase 1 (DAPK1) in human dermal fibroblasts under normal culture conditions. Exp. Dermatol. 2013, 22:491-494.
31. Christiansen T., Paulsen S.K., Bruun J.M., Pedersen S.B., Richelsen B. Exercise training versus diet-induced weight-loss on metabolic risk factors and inflammatory markers in obese subjects: a 12-week randomized intervention study. Am. J. Physiol. Endocrinol. Metab. 2010, 298:E824-E831.
32. Christiansen T., Richelsen B., Bruun J.M. Monocyte chemoattractant protein-1 is produced in isolated adipocytes, associated with adiposity and reduced after weight loss in morbid obese subjects. Int. J. Obes. (Lond.) 2005, 29:146-150.
33. Cinti S., Mitchell G., Barbatelli G., Murano I., Ceresi E., Faloia E., Wang S., Fortier M., Greenberg A.S., Obin M.S. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J. Lipid Res. 2005, 46:2347-2355.
34. Cox A.J., West N.P., Cripps A.W. Obesity, inflammation, and the gut microbiota. Lancet Diabetes Endocrinol. 2014, (Jul 21, pii: S2213-8587(14)70134-2).
35. Crandall J.P., Oram V., Trandafirescu G., Reid M., Kishore P., Hawkins M., Cohen H.W., Barzilai N. Pilot study of resveratrol in older adults with impaired glucose tolerance. J. Gerontol. A Biol. Sci. Med. Sci. 2012 Dec, 67(12):1307-1312.
36. Criqui M.H., Ringel B.L. Does diet or alcohol explain the French paradox?. Lancet 1994, 344:1719-1723.
37. Csiszar A., Smith K., Labinskyy N., Orosz Z., Rivera A., Ungvari Z. Resveratrol attenuates TNF-alpha-induced activation of coronary arterial endothelial cells: role of NF-kappaB inhibition. Am. J. Physiol. Heart Circ. Physiol. 2006, 291:H1694-H1699.
38. Cullberg K.B., Olholm J., Paulsen S.K., Foldager C.B., Lind M., Richelsen B., Pedersen S.B. Resveratrol has inhibitory effects on the hypoxia-induced inflammation and angiogenesis in human adipose tissue in vitro. Eur. J. Pharm. Sci. 2013, 49:251-257.
39. Curat C.A., Miranville A., Sengenes C., Diehl M., Tonus C., Busse R., Bouloumie A. From blood monocytes to adipose tissue-resident macrophages: induction of diapedesis by human mature adipocytes. Diabetes 2004, 53:1285-1292.
40. Dalmas E., Clement K., Guerre-Millo M. Defining macrophage phenotype and function in adipose tissue. Trends Immunol. 2011, 32:307-314.
41. Dandona P., Aljada A., Bandyopadhyay A. Inflammation: the link between insulin resistance, obesity and diabetes. Trends Immunol. 2004, 25:4-7.
42. de Lemos J.A., Morrow D.A., Sabatine M.S., Murphy S.A., Gibson C.M., Antman E.M., McCabe C.H., Cannon C.P., Braunwald E. Association between plasma levels of monocyte chemoattractant protein-1 and long-term clinical outcomes in patients with acute coronary syndromes. Circulation 2003, 107:690-695.
43. Deo R., Khera A., McGuire D.K., Murphy S.A., Meo Neto J.P., Morrow D.A., de Lemos J.A. Association among plasma levels of monocyte chemoattractant protein-1, traditional cardiovascular risk factors, and subclinical atherosclerosis. J. Am. Coll. Cardiol. 2004, 44:1812-1818.
44. Dioum E.M., Chen R., Alexander M.S., Zhang Q., Hogg R.T., Gerard R.D., Garcia J.A. Regulation of hypoxia-inducible factor 2alpha signaling by the stress-responsive deacetylase sirtuin 1. Science 2009, 324:1289-1293.
45. Dixon J.B. The effect of obesity on health outcomes. Mol. Cell. Endocrinol. 2010, 316:104-108.
46. Dominguez H., Storgaard H., Rask-Madsen C., Steffen H.T., Ihlemann N., Baunbjerg N.D., Spohr C., Kober L., Vaag A., Torp-Pedersen C. Metabolic and vascular effects of tumor necrosis factor-alpha blockade with etanercept in obese patients with type 2 diabetes. J. Vasc. Res. 2005, 42:517-525.
47. Elmali N., Baysal O., Harma A., Esenkaya I., Mizrak B. Effects of resveratrol in inflammatory arthritis. Inflammation 2007, 30:1-6.
48. Elmali N., Esenkaya I., Harma A., Ertem K., Turkoz Y., Mizrak B. Effect of resveratrol in experimental osteoarthritis in rabbits. Inflamm. Res. 2005, 54:158-162.
49. Emilsson V., Thorleifsson G., Zhang B., Leonardson A.S., Zink F., Zhu J., Carlson S., Helgason A., Walters G.B., Gunnarsdottir S., Mouy M., Steinthorsdottir V., Eiriksdottir G.H., Bjornsdottir G., Reynisdottir I., Gudbjartsson D., Helgadottir A., Jonasdottir A., Jonasdottir A., Styrkarsdottir U., Gretarsdottir S., Magnusson K.P., Stefansson H., Fossdal R., Kristjansson K., Gislason H.G., Stefansson T., Leifsson B.G., Thorsteinsdottir U., Lamb J.R., Gulcher J.R., Reitman M.L., Kong A., Schadt E.E., Stefansson K. Genetics of gene expression and its effect on disease. Nature 2008, 452:423-428.
50. Esser N., Paquot N., Scheen A.J. Anti-inflammatory agents to treat or prevent type 2 diabetes, metabolic syndrome and cardiovascular disease. Expert. Opin. Investig. Drugs 2014, 1-25.
51. Fain J.N. Release of interleukins and other inflammatory cytokines by human adipose tissue is enhanced in obesity and primarily due to the nonfat cells. Vitam. Horm. 2006, 74:443-477.
52. Fain J.N., Madan A.K., Hiler M.L., Cheema P., Bahouth S.W. Comparison of the release of adipokines by adipose tissue, adipose tissue matrix, and adipocytes from visceral and subcutaneous abdominal adipose tissues of obese humans. Endocrinology 2004, 145:2273-2282.
53. Fjeldborg K., Christiansen T., Bennetzen M., Moller J., Pedersen S.B., Richelsen B. The macrophage-specific serum marker, soluble CD163, is increased in obesity and reduced after dietary-induced weight loss. Obesity (Silver Spring) 2013, 21:2437-2443.
54. Fjeldborg K., Pedersen S.B., Moller H.J., Christiansen T., Bennetzen M., Richelsen B. Human adipose tissue macrophages are enhanced but changed to an anti-inflammatory profile in obesity. J. Immunol. Res. 2014, 2014:309548.
55. Fleischman A., Shoelson S.E., Bernier R., Goldfine A.B. Salsalate improves glycemia and inflammatory parameters in obese young adults. Diabetes Care 2008, 31:289-294.
56. Floyd Z.E., Wang Z.Q., Kilroy G., Cefalu W.T. Modulation of peroxisome proliferator-activated receptor gamma stability and transcriptional activity in adipocytes by resveratrol. Metabolism 2008, 57:S32-S38.
57. Furukawa S., Fujita T., Shimabukuro M., Iwaki M., Yamada Y., Nakajima Y., Nakayama O., Makishima M., Matsuda M., Shimomura I. Increased oxidative stress in obesity and its impact on metabolic syndrome. J. Clin. Invest. 2004, 114:1752-1761.
58. Ghanim H., Abuaysheh S., Sia C.L., Korzeniewski K., Chaudhuri A., Fernandez-Real J.M., Dandona P. Increase in plasma endotoxin concentrations and the expression of Toll-like receptors and suppressor of cytokine signaling-3 in mononuclear cells after a high-fat, high-carbohydrate meal: implications for insulin resistance. Diabetes Care 2009, 32:2281-2287.
59. Ghanim H., Sia C.L., Abuaysheh S., Korzeniewski K., Patnaik P., Marumganti A., Chaudhuri A., Dandona P. An antiinflammatory and reactive oxygen species suppressive effects of an extract of Polygonum cuspidatum containing resveratrol. J. Clin. Endocrinol. Metab. 2010, 95:E1-E8.
60. Ghisletti S., Meda C., Maggi A., Vegeto E. 17beta-estradiol inhibits inflammatory gene expression by controlling NF-kappaB intracellular localization. Mol. Cell. Biol. 2005, 25:2957-2968.
61. Gliemann L., Schmidt J.F., Olesen J., Bienso R.S., Peronard S.L., Grandjean S.U., Mortensen S.P., Nyberg M., Bangsbo J., Pilegaard H., Hellsten Y. Resveratrol blunts the positive effects of exercise training on cardiovascular health in aged men. J. Physiol. 2013 Oct 15, 591(Pt 20):5047-5059.
62. Goldfine A.B., Fonseca V., Jablonski K.A., Pyle L., Staten M.A., Shoelson S.E. The effects of salsalate on glycemic control in patients with type 2 diabetes: a randomized trial. Ann. Intern. Med. 2010, 152:346-357.
63. Gomez-Zorita S., Fernandez-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.
64. Gonzalez F., Thusu K., Abdel-Rahman E., Prabhala A., Tomani M., Dandona P. Elevated serum levels of tumor necrosis factor alpha in normal-weight women with polycystic ovary syndrome. Metabolism 1999, 48:437-441.
65. Goossens G.H., Bizzarri A., Venteclef N., Essers Y., Cleutjens J.P., Konings E., Jocken J.W., Cajlakovic M., Ribitsch V., Clement K., Blaak E.E. Increased adipose tissue oxygen tension in obese compared with lean men is accompanied by insulin resistance, impaired adipose tissue capillarization, and inflammation. Circulation 2011, 124:67-76.
66. Gregor M.F., Hotamisligil G.S. Thematic review series: adipocyte biology. Adipocyte stress: the endoplasmic reticulum and metabolic disease. J. Lipid Res. 2007, 48:1905-1914.
67. Gregor M.F., Hotamisligil G.S. Inflammatory mechanisms in obesity. Annu. Rev. Immunol. 2011, 29:415-445.
68. Guven S., El-Bershawi A., Sonnenberg G.E., Wilson C.R., Hoffmann R.G., Krakower G.R., Kissebah A.H. Plasma leptin and insulin levels in weight-reduced obese women with normal body mass index: relationships with body composition and insulin. Diabetes 1999, 48:347-352.
69. Haffner S., Temprosa M., Crandall J., Fowler S., Goldberg R., Horton E., Marcovina S., Mather K., Orchard T., Ratner R., Barrett-Connor E. Intensive lifestyle intervention or metformin on inflammation and coagulation in participants with impaired glucose tolerance. Diabetes 2005, 54:1566-1572.
70. Hamdy O., Porramatikul S., Al-Ozairi E. Metabolic obesity: the paradox between visceral and subcutaneous fat. Curr. Diabetes Rev. 2006, 2:367-373.
71. Harman-Boehm I., Bluher M., Redel H., Sion-Vardy N., Ovadia S., Avinoach E., Shai I., Kloting N., Stumvoll M., Bashan N., Rudich A. Macrophage infiltration into omental versus subcutaneous fat across different populations: effect of regional adiposity and the comorbidities of obesity. J. Clin. Endocrinol. Metab. 2007, 92:2240-2247.
72. Hevener A.L., Olefsky J.M., Reichart D., Nguyen M.T., Bandyopadyhay G., Leung H.Y., Watt M.J., Benner C., Febbraio M.A., Nguyen A.K., Folian B., Subramaniam S., Gonzalez F.J., Glass C.K., Ricote M. Macrophage PPAR gamma is required for normal skeletal muscle and hepatic insulin sensitivity and full antidiabetic effects of thiazolidinediones. J. Clin. Invest. 2007, 117:1658-1669.
73. Hirosumi J., Tuncman G., Chang L., Gorgun C.Z., Uysal K.T., Maeda K., Karin M., Hotamisligil G.S. A central role for JNK in obesity and insulin resistance. Nature 2002, 420:333-336.
74. Hoshino J., Park E.J., Kondratyuk T.P., Marler L., Pezzuto J.M., van Breemen R.B., Mo S., Li Y., Cushman M. Selective synthesis and biological evaluation of sulfate-conjugated resveratrol metabolites. J. Med. Chem. 2010, 53:5033-5043.
75. Hotamisligil G.S. Inflammation and metabolic disorders. Nature 2006, 444:860-867.
76. Hotamisligil G.S., Arner P., Caro J.F., Atkinson R.L., Spiegelman B.M. Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J. Clin. Invest. 1995, 95:2409-2415.
77. Hotamisligil G.S., Shargill N.S., Spiegelman B.M. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 1993, 259:87-91.
78. Hung J., McQuillan B.M., Thompson P.L., Beilby J.P. Circulating adiponectin levels associate with inflammatory markers, insulin resistance and metabolic syndrome independent of obesity. Int. J. Obes. (Lond.) 2008, 32:772-779.
79. Ibrahim M.M. Subcutaneous and visceral adipose tissue: structural and functional differences. Obes. Rev. 2010, 11:11-18.
80. Jeon B.T., Jeong E.A., Shin H.J., Lee Y., Lee D.H., Kim H.J., Kang S.S., Cho G.J., Choi W.S., Roh G.S. Resveratrol attenuates obesity-associated peripheral and central inflammation and improves memory deficit in mice fed a high-fat diet. Diabetes 2012 Jun, 61(6):1444-1454.
81. Jimenez-Gomez Y., Mattison J.A., Pearson K.J., Martin-Montalvo A., Palacios H.H., Sossong A.M., Ward T.M., Younts C.M., Lewis K., Allard J.S., Longo D.L., Belman J.P., Malagon M.M., Navas P., Sanghvi M., Moaddel R., Tilmont E.M., Herbert R.L., Morrell C.H., Egan J.M., Baur J.A., Ferrucci L., Bogan J.S., Bernier M., de C.R. Resveratrol improves adipose insulin signaling and reduces the inflammatory response in adipose tissue of rhesus monkeys on high-fat, high-sugar diet. Cell Metab. 2013, 18:533-545.
82. Johnson J.J., Nihal M., Siddiqui I.A., Scarlett C.O., Bailey H.H., Mukhtar H., Ahmad N. Enhancing the bioavailability of resveratrol by combining it with piperine. Mol. Nutr. Food Res. 2011, 55:1169-1176.
83. Karelis A.D. Metabolically healthy but obese individuals. Lancet 2008, 372:1281-1283.
84. Karelis A.D., Faraj M., Bastard J.P., St-Pierre D.H., Brochu M., Prud'homme D., Rabasa-Lhoret R. The metabolically healthy but obese individual presents a favorable inflammation profile. J. Clin. Endocrinol. Metab. 2005, 90:4145-4150.
85. Karelis A.D., St-Pierre D.H., Conus F., Rabasa-Lhoret R., Poehlman E.T. Metabolic and body composition factors in subgroups of obesity: what do we know?. J. Clin. Endocrinol. Metab. 2004, 89:2569-2575.
86. Kern P.A., Saghizadeh M., Ong J.M., Bosch R.J., Deem R., Simsolo R.B. The expression of tumor necrosis factor in human adipose tissue. Regulation by obesity, weight loss, and relationship to lipoprotein lipase. J. Clin. Invest. 1995, 95:2111-2119.
87. Kim C.S., Park H.S., Kawada T., Kim J.H., Lim D., Hubbard N.E., Kwon B.S., Erickson K.L., Yu R. Circulating levels of MCP-1 and IL-8 are elevated in human obese subjects and associated with obesity-related parameters. Int. J. Obes. (Lond.) 2006, 30:1347-1355.
88. Kim H.J., Braun H.J., Dragoo J.L. The effect of resveratrol on normal and osteoarthritic chondrocyte metabolism. Bone Joint Res. 2014, 3:51-59.
89. Kim M.H., Yoo D.S., Lee S.Y., Byeon S.E., Lee Y.G., Min T., Rho H.S., Rhee M.H., Lee J., Cho J.Y. The TRIF/TBK1/IRF-3 activation pathway is the primary inhibitory target of resveratrol, contributing to its broad-spectrum anti-inflammatory effects. Pharmazie 2011, 66:293-300.
90. Kiortsis D.N., Mavridis A.K., Vasakos S., Nikas S.N., Drosos A.A. Effects of infliximab treatment on insulin resistance in patients with rheumatoid arthritis and ankylosing spondylitis. Ann. Rheum. Dis. 2005, 64:765-766.
91. Knobloch J., Wahl C., Feldmann M., Jungck D., Strauch J., Stoelben E., Koch A. Resveratrol attenuates the release of inflammatory cytokines from human bronchial smooth muscle cells exposed to lipoteichoic acid in chronic obstructive pulmonary disease. Basic Clin. Pharmacol. Toxicol. 2014, 114:202-209.
92. Koster A., Stenholm S., Alley D.E., Kim L.J., Simonsick E.M., Kanaya A.M., Visser M., Houston D.K., Nicklas B.J., Tylavsky F.A., Satterfield S., Goodpaster B.H., Ferrucci L., Harris T.B. Body fat distribution and inflammation among obese older adults with and without metabolic syndrome. Obesity (Silver Spring) 2010, 18:2354-2361.
93. Krogh-Madsen R., Plomgaard P., Moller K., Mittendorfer B., Pedersen B.K. Influence of TNF-alpha and IL-6 infusions on insulin sensitivity and expression of IL-18 in humans. Am. J. Physiol. Endocrinol. Metab. 2006, 291:E108-E114.
94. Lai M.Z., Chen R.H. Regulation of inflammation by DAPK. Apoptosis 2014, 19:357-363.
95. Larrosa M., Yanez-Gascon M.J., Selma M.V., Gonzalez-Sarrias A., Toti S., Ceron J.J., Tomas-Barberan F., Dolara P., Espin J.C. Effect of a low dose of dietary resveratrol on colon microbiota, inflammation and tissue damage in a DSS-induced colitis rat model. J. Agric. Food Chem. 2009, 57:2211-2220.
96. Larsen C.M., Faulenbach M., Vaag A., Ehses J.A., Donath M.Y., Mandrup-Poulsen T. Sustained effects of interleukin-1 receptor antagonist treatment in type 2 diabetes. Diabetes Care 2009, 32:1663-1668.
97. Larsen C.M., Faulenbach M., Vaag A., Volund A., Ehses J.A., Seifert B., Mandrup-Poulsen T., Donath M.Y. Interleukin-1-receptor antagonist in type 2 diabetes mellitus. N. Engl. J. Med. 2007, 356:1517-1526.
98. Lavoie M.E., Rabasa-Lhoret R., Doucet E., Mignault D., Messier L., Bastard J.P., Faraj M. Association between physical activity energy expenditure and inflammatory markers in sedentary overweight and obese women. Int. J. Obes. (Lond.) 2010, 34:1387-1395.
99. Lee D.E., Kehlenbrink S., Lee H., Hawkins M., Yudkin J.S. Getting the message across: mechanisms of physiological cross talk by adipose tissue. Am. J. Physiol. Endocrinol. Metab. 2009, 296:E1210-E1229.
100. Lee J.Y., Sohn K.H., Rhee S.H., Hwang D. Saturated fatty acids, but not unsaturated fatty acids, induce the expression of cyclooxygenase-2 mediated through Toll-like receptor 4. J. Biol. Chem. 2001, 276:16683-16689.
101. Lee M., Kim S., Kwon O.K., Oh S.R., Lee H.K., Ahn K. Anti-inflammatory and anti-asthmatic effects of resveratrol, a polyphenolic stilbene, in a mouse model of allergic asthma. Int. Immunopharmacol. 2009, 9:418-424.
102. Lee Y.H., Pratley R.E. The evolving role of inflammation in obesity and the metabolic syndrome. Curr. Diabetes Rep. 2005, 5:70-75.
103. Li C., Wang L., Huang K., Zheng L. Endoplasmic reticulum stress in retinal vascular degeneration: protective role of resveratrol. Invest. Ophthalmol. Vis. Sci. 2012, 53:3241-3249.
104. Lindsay R.S., Funahashi T., Hanson R.L., Matsuzawa Y., Tanaka S., Tataranni P.A., Knowler W.C., Krakoff J. Adiponectin and development of type 2 diabetes in the Pima Indian population. Lancet 2002, 360:57-58.
105. Little J.P., Safdar A., Wilkin G.P., Tarnopolsky M.A., Gibala M.J. A practical model of low-volume high-intensity interval training induces mitochondrial biogenesis in human skeletal muscle: potential mechanisms. J. Physiol. 2010, 588:1011-1022.
106. Liu F.C., Hung L.F., Wu W.L., Chang D.M., Huang C.Y., Lai J.H., Ho L.J. Chondroprotective effects and mechanisms of resveratrol in advanced glycation end products-stimulated chondrocytes. Arthritis Res. Ther. 2010, 12:R167.
107. Magyar K., Halmosi R., Palfi A., Feher G., Czopf L., Fulop A., Battyany I., Sumegi B., Toth K., Szabados E. Cardioprotection by resveratrol: a human clinical trial in patients with stable coronary artery disease. Clin. Hemorheol. Microcirc. 2012, 50:179-187.
108. Manna S.K., Mukhopadhyay A., Aggarwal B.B. Resveratrol suppresses TNF-induced activation of nuclear transcription factors NF-kappa B, activator protein-1, and apoptosis: potential role of reactive oxygen intermediates and lipid peroxidation. J. Immunol. 2000, 164:6509-6519.
109. Martin A.R., Villegas I., Sanchez-Hidalgo M., de la Lastra C.A. The effects of resveratrol, a phytoalexin derived from red wines, on chronic inflammation induced in an experimentally induced colitis model. Br. J. Pharmacol. 2006, 147:873-885.
110. McAnulty L.S., Miller L.E., Hosick P.A., Utter A.C., Quindry J.C., McAnulty S.R. Effect of resveratrol and quercetin supplementation on redox status and inflammation after exercise. Appl. Physiol. Nutr. Metab. 2013, 38:760-765.
111. Mukhopadhyay R., Ray P.S., Arif A., Brady A.K., Kinter M., Fox P.L. DAPK-ZIPK-L13a axis constitutes a negative-feedback module regulating inflammatory gene expression. Mol. Cell 2008, 32:371-382.
112. Nakav S., Cohen S., Feigelson S.W., Bialik S., Shoseyov D., Kimchi A., Alon R. Tumor suppressor death-associated protein kinase attenuates inflammatory responses in the lung. Am. J. Respir. Cell Mol. Biol. 2012, 46:313-322.
113. O'Neill L.A., Hardie D.G. Metabolism of inflammation limited by AMPK and pseudo-starvation. Nature 2013, 493:346-355.
114. Ofei F., Hurel S., Newkirk J., Sopwith M., Taylor R. Effects of an engineered human anti-TNF-alpha antibody (CDP571) on insulin sensitivity and glycemic control in patients with NIDDM. Diabetes 1996, 45:881-885.
115. Olholm J., Paulsen S.K., Cullberg K.B., Richelsen B., Pedersen S.B. Anti-inflammatory effect of resveratrol on adipokine expression and secretion in human adipose tissue explants. Int. J. Obes. (Lond.) 2010, 34:1546-1553.
116. Ouchi N., Kihara S., Funahashi T., Matsuzawa Y., Walsh K. Obesity, adiponectin and vascular inflammatory disease. Curr. Opin. Lipidol. 2003, 14:561-566.
117. Ozcan U., Cao Q., Yilmaz E., Lee A.H., Iwakoshi N.N., Ozdelen E., Tuncman G., Gorgun C., Glimcher L.H., Hotamisligil G.S. Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science 2004, 306:457-461.
118. Ozcan U., Yilmaz E., Ozcan L., Furuhashi M., Vaillancourt E., Smith R.O., Gorgun C.Z., Hotamisligil G.S. Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes. Science 2006, 313:1137-1140.
119. Paquot N., Castillo M.J., Lefebvre P.J., Scheen A.J. No increased insulin sensitivity after a single intravenous administration of a recombinant human tumor necrosis factor receptor: Fc fusion protein in obese insulin-resistant patients. J. Clin. Endocrinol. Metab. 2000, 85:1316-1319.
120. Pedersen S.B., Olholm 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.
121. Pischon T., Boeing H., Hoffmann K., Bergmann M., Schulze M.B., Overvad K., van der Schouw Y.T., Spencer E., Moons K.G., Tjonneland A., Halkjaer J., Jensen M.K., Stegger J., Clavel-Chapelon F., Boutron-Ruault M.C., Chajes V., Linseisen J., Kaaks R., Trichopoulou A., Trichopoulos D., Bamia C., Sieri S., Palli D., Tumino R., Vineis P., Panico S., Peeters P.H., May A.M., Bueno-de-Mesquita H.B., van Duijnhoven F.J., Hallmans G., Weinehall L., Manjer J., Hedblad B., Lund E., Agudo A., Arriola L., Barricarte A., Navarro C., Martinez C., Quiros J.R., Key T., Bingham S., Khaw K.T., Boffetta P., Jenab M., Ferrari P., Riboli E. General and abdominal adiposity and risk of death in Europe. N. Engl. J. Med. 2008, 359:2105-2120.
122. Poulsen M.M., Larsen J.O., Hamilton-Dutoit S., Clasen B.F., Jessen N., Paulsen S.K., Kjaer T.N., Richelsen B., Pedersen S.B. Resveratrol up-regulates hepatic uncoupling protein 2 and prevents development of nonalcoholic fatty liver disease in rats fed a high-fat diet. Nutr. Res. 2012, 32:701-708.
123. Poulsen M.M., Vestergaard P.F., Clasen B.F., Radko Y., Christensen L.P., Stodkilde-Jorgensen H., Moller N., Jessen N., Pedersen S.B., Jorgensen J.O. High-dose resveratrol supplementation in obese men: an investigator-initiated, randomized, placebo-controlled clinical trial of substrate metabolism, insulin sensitivity, and body composition. Diabetes 2013 Apr, 62(4):1186-1195.
124. Price N.L., Gomes A.P., Ling A.J., Duarte F.V., Martin-Montalvo A., North B.J., Agarwal B., Ye L., Ramadori G., Teodoro J.S., Hubbard B.P., Varela A.T., Davis J.G., Varamini B., Hafner A., Moaddel R., Rolo A.P., Coppari R., Palmeira C.M., de C.R., Baur J.A., Sinclair D.A. SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function. Cell Metab. 2012, 15:675-690.
125. Renaud S., de L.M. Wine, alcohol, platelets, and the French paradox for coronary heart disease. Lancet 1992, 339:1523-1526.
126. Renes J., Rosenow A., Roumans N., Noben J.P., Mariman E.C. Calorie restriction-induced changes in the secretome of human adipocytes, comparison with resveratrol-induced secretome effects. Biochim. Biophys. Acta 2014, 1844:1511-1522.
127. Ridker P.M., Howard C.P., Walter V., Everett B., Libby P., Hensen J., Thuren T. Effects of interleukin-1beta inhibition with canakinumab on hemoglobin A1c, lipids, C-reactive protein, interleukin-6, and fibrinogen: a phase IIb randomized, placebo-controlled trial. Circulation 2012, 126:2739-2748.
128. Rivera L., Moron 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.
129. Rosenbaum M., Leibel R.L., Hirsch J. Obesity. N. Engl. J. Med. 1997, 337:396-407.
130. Royce S.G., Dang W., Yuan G., Tran J., El O.A., Karagiannis T.C., Tang M.L. Resveratrol has protective effects against airway remodeling and airway hyperreactivity in a murine model of allergic airways disease. Pathobiol. Aging Age Relat Dis. 2011, 1.
131. Semba R.D., Ferrucci L., Bartali B., Urpi-Sarda M., Zamora-Ros R., Sun K., Cherubini A., Bandinelli S., Andres-Lacueva C. Resveratrol levels and all-cause mortality in older community-dwelling adults. JAMA Intern. Med. 2014, 174:1077-1084.
132. Shakibaei M., Csaki C., Nebrich S., Mobasheri A. Resveratrol suppresses interleukin-1beta-induced inflammatory signaling and apoptosis in human articular chondrocytes: potential for use as a novel nutraceutical for the treatment of osteoarthritis. Biochem. Pharmacol. 2008, 76:1426-1439.
133. Shi H., Kokoeva M.V., Inouye K., Tzameli I., Yin H., Flier J.S. TLR4 links innate immunity and fatty acid-induced insulin resistance. J. Clin. Invest. 2006, 116:3015-3025.
134. Simpson J.A., MacInnis R.J., Peeters A., Hopper J.L., Giles G.G., English D.R. A comparison of adiposity measures as predictors of all-cause mortality: the Melbourne Collaborative Cohort Study. Obesity (Silver Spring) 2007, 15:994-1003.
135. Skurk T., Alberti-Huber C., Herder C., Hauner H. Relationship between adipocyte size and adipokine expression and secretion. J. Clin. Endocrinol. Metab. 2007, 92:1023-1033.
136. Sloan-Lancaster J., Abu-Raddad E., Polzer J., Miller J.W., Scherer J.C., De G.A., Berg J.K., Landschulz W.H. Double-blind, randomized study evaluating the glycemic and anti-inflammatory effects of subcutaneous LY2189102, a neutralizing IL-1beta antibody, in patients with type 2 diabetes. Diabetes Care 2013, 36:2239-2246.
137. Spielman L.J., Little J.P., Klegeris A. Inflammation and insulin/IGF-1 resistance as the possible link between obesity and neurodegeneration. J. Neuroimmunol. 2014, 273:8-21.
138. Stanley T.L., Zanni M.V., Johnsen S., Rasheed S., Makimura H., Lee H., Khor V.K., Ahima R.S., Grinspoon S.K. TNF-alpha antagonism with etanercept decreases glucose and increases the proportion of high molecular weight adiponectin in obese subjects with features of the metabolic syndrome. J. Clin. Endocrinol. Metab. 2011, 96:E146-E150.
139. Stervbo U., Vang O., Bonnesen C. A review of the content of the putative chemopreventive phytoalexin resveratrol in red wine. Food Chem. 2007, 101:449-457.
140. Sun S., Ji Y., Kersten S., Qi L. Mechanisms of inflammatory responses in obese adipose tissue. Annu. Rev. Nutr. 2012, 32:261-286.
141. Tilg H., Moschen A.R. Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat. Rev. Immunol. 2006, 6:772-783.
142. 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., Moonen-Kornips E., Hesselink M.K., Kunz I., Schrauwen-Hinderling V.B., Blaak E.E., Auwerx J., Schrauwen P. Calorie restriction-like effects of 30days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. Cell Metab. 2011, 14:612-622.
143. Tome-Carneiro J., Gonzalvez M., Larrosa M., Yanez-Gascon M.J., Garcia-Almagro F.J., Ruiz-Ros J.A., Garcia-Conesa M.T., Tomas-Barberan F.A., Espin J.C. One-year consumption of a grape nutraceutical containing resveratrol improves the inflammatory and fibrinolytic status of patients in primary prevention of cardiovascular disease. Am. J. Cardiol. 2012, 110:356-363.
144. Tome-Carneiro J., Gonzalvez M., Larrosa M., Yanez-Gascon M.J., Garcia-Almagro F.J., Ruiz-Ros J.A., Tomas-Barberan F.A., Garcia-Conesa M.T., Espin J.C. Grape resveratrol increases serum adiponectin and downregulates inflammatory genes in peripheral blood mononuclear cells: a triple-blind, placebo-controlled, one-year clinical trial in patients with stable coronary artery disease. Cardiovasc. Drugs Ther. 2013, 27:37-48.
145. Tome-Carneiro J., Larrosa M., Yanez-Gascon M.J., Davalos A., Gil-Zamorano J., Gonzalvez M., Garcia-Almagro F.J., Ruiz Ros J.A., Tomas-Barberan F.A., Espin J.C., Garcia-Conesa M.T. One-year supplementation with a grape extract containing resveratrol modulates inflammatory-related microRNAs and cytokines expression in peripheral blood mononuclear cells of type 2 diabetes and hypertensive patients with coronary artery disease. Pharmacol. Res. 2013, 72:69-82.
146. Trayhurn P. Hypoxia and adipocyte physiology: implications for adipose tissue dysfunction in obesity. Annu. Rev. Nutr. 2014, 34:207-236.
147. Trayhurn P., Wang B., Wood I.S. Hypoxia in adipose tissue: a basis for the dysregulation of tissue function in obesity?. Br. J. Nutr. 2008, 100:227-235.
148. Tsai S.H., Lin-Shiau S.Y., Lin J.K. Suppression of nitric oxide synthase and the down-regulation of the activation of NFkappaB in macrophages by resveratrol. Br. J. Pharmacol. 1999, 126:673-680.
149. Turer A.T., Khera A., Ayers C.R., Turer C.B., Grundy S.M., Vega G.L., Scherer P.E. Adipose tissue mass and location affect circulating adiponectin levels. Diabetologia 2011, 54:2515-2524.
150. Uysal K.T., Wiesbrock S.M., Marino M.W., Hotamisligil G.S. Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function. Nature 1997, 389:610-614.
151. Ventre J., Doebber T., Wu M., MacNaul K., Stevens K., Pasparakis M., Kollias G., Moller D.E. Targeted disruption of the tumor necrosis factor-alpha gene: metabolic consequences in obese and nonobese mice. Diabetes 1997, 46:1526-1531.
152. Vgontzas A.N., Papanicolaou D.A., Bixler E.O., Kales A., Tyson K., Chrousos G.P. Elevation of plasma cytokines in disorders of excessive daytime sleepiness: role of sleep disturbance and obesity. J. Clin. Endocrinol. Metab. 1997, 82:1313-1316.
153. Virtue S., Vidal-Puig A. Adipose tissue expandability, lipotoxicity and the Metabolic Syndrome-an allostatic perspective. Biochim. Biophys. Acta 2010, 1801:338-349.
154. Visser M., Bouter L.M., McQuillan G.M., Wener M.H., Harris T.B. Elevated C-reactive protein levels in overweight and obese adults. JAMA 1999, 282:2131-2135.
155. Voduc N., la P.C., Tessier C., Mallick R., Cameron D.W. Effect of resveratrol on exercise capacity: a randomized placebo-controlled crossover pilot study. Appl. Physiol. Nutr. Metab. 2014, 1-5.
156. Voloshyna I., Hai O., Littlefield M.J., Carsons S., Reiss A.B. Resveratrol mediates anti-atherogenic effects on cholesterol flux in human macrophages and endothelium via PPARgamma and adenosine. Eur. J. Pharmacol. 2013, 698:299-309.
157. 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.
158. Wang B., Sun J., Li X., Zhou Q., Bai J., Shi Y., Le G. Resveratrol prevents suppression of regulatory T-cell production, oxidative stress, and inflammation of mice prone or resistant to high-fat diet-induced obesity. Nutr. Res. 2013, 33:971-981.
159. Weisberg S.P., McCann D., Desai M., Rosenbaum M., Leibel R.L., Ferrante A.W. Obesity is associated with macrophage accumulation in adipose tissue. J. Clin. Invest. 2003, 112:1796-1808.
160. Wentworth J.M., Naselli G., Brown W.A., Doyle L., Phipson B., Smyth G.K., Wabitsch M., O'Brien P.E., Harrison L.C. Pro-inflammatory CD11c+CD206+ adipose tissue macrophages are associated with insulin resistance in human obesity. Diabetes 2010, 59:1648-1656.
161. Wild S., Roglic G., Green A., Sicree R., King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 2004, 27:1047-1053.
162. Witte A.V., Kerti L., Margulies D.S., Floel A. Effects of resveratrol on memory performance, hippocampal functional connectivity, and glucose metabolism in healthy older adults. J. Neurosci. 2014, 34:7862-7870.
163. Yamauchi T., Kamon J., Waki H., Imai Y., Shimozawa N., Hioki K., Uchida S., Ito Y., Takakuwa K., Matsui J., Takata M., Eto K., Terauchi Y., Komeda K., Tsunoda M., Murakami K., Ohnishi Y., Naitoh T., Yamamura K., Ueyama Y., Froguel P., Kimura S., Nagai R., Kadowaki T. Globular adiponectin protected ob/ob mice from diabetes and ApoE-deficient mice from atherosclerosis. J. Biol. Chem. 2003, 278:2461-2468.
164. Yamauchi T., Kamon J., Waki H., Terauchi Y., Kubota N., Hara K., Mori Y., Ide T., Murakami K., Tsuboyama-Kasaoka N., Ezaki O., Akanuma Y., Gavrilova O., Vinson C., Reitman M.L., Kagechika H., Shudo K., Yoda M., Nakano Y., Tobe K., Nagai R., Kimura S., Tomita M., Froguel P., Kadowaki T. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat. Med. 2001, 7:941-946.
165. Ye J. Emerging role of adipose tissue hypoxia in obesity and insulin resistance. Int. J. Obes. (Lond.) 2009, 33:54-66.
166. Yoshino J., Conte C., Fontana L., Mittendorfer B., Imai S., Schechtman K.B., Gu C., Kunz I., Rossi F.F., Patterson B.W., Klein S. Resveratrol supplementation does not improve metabolic function in nonobese women with normal glucose tolerance. Cell Metab. 2012, 16:658-664.
167. Youssef-Elabd E.M., McGee K.C., Tripathi G., Aldaghri N., Abdalla M.S., Sharada H.M., Ashour E., Amin A.I., Ceriello A., O'Hare J.P., Kumar S., McTernan P.G., Harte A.L. Acute and chronic saturated fatty acid treatment as a key instigator of the TLR-mediated inflammatory response in human adipose tissue, in vitro. J. Nutr. Biochem. 2012, 23:39-50.
168. Yuan M., Konstantopoulos N., Lee J., Hansen L., Li Z.W., Karin M., Shoelson S.E. Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta. Science 2001, 293:1673-1677.
169. Yusuf S., Hawken S., Ounpuu S., Bautista L., Franzosi M.G., Commerford P., Lang C.C., Rumboldt Z., Onen C.L., Lisheng L., Tanomsup S., Wangai P., Razak F., Sharma A.M., Anand S.S. Obesity and the risk of myocardial infarction in 27,000 participants from 52 countries: a case-control study. Lancet 2005, 366:1640-1649.
170. Zahedi H.S., Jazayeri S., Ghiasvand R., Djalali M., Eshraghian M.R. Effects of Polygonum cuspidatum containing resveratrol on inflammation in male professional basketball players. Int J. Prev. Med. 2013, 4:S1-S4.
171. Zhang C., Rexrode K.M., van Dam R.M., Li T.Y., Hu F.B. Abdominal obesity and the risk of all-cause, cardiovascular, and cancer mortality: sixteen years of follow-up in US women. Circulation 2008, 117:1658-1667.
172. Zhu J., Yong W., Wu X., Yu Y., Lv J., Liu C., Mao X., Zhu Y., Xu K., Han X., Liu C. Anti-inflammatory effect of resveratrol on TNF-alpha-induced MCP-1 expression in adipocytes. Biochem. Biophys. Res. Commun. 2008, 369:471-477.