title: Conjugated linoleic acid-mediated inflammation and insulin resistance in human adipocytes are attenuated by resveratrol.
abstract: Inflammation plays a role in trans-10, cis-12 (10,12)-conjugated linoleic acid (CLA)-mediated delipidation and insulin resistance in adipocytes. Given the anti-inflammatory role of resveratrol (RSV), we hypothesized that RSV would attenuate inflammation and insulin resistance caused by 10,12 CLA in human adipocytes. RSV blocked 10,12 CLA induction of the inflammatory response by preventing activation of extracellular signal-related kinase and induction of inflammatory gene expression (i.e., IL-6, IL-8, IL-1beta) within 12 h. Similarly, RSV suppressed 10,12 CLA-mediated activation of the inflammatory prostaglandin pathway involving phospholipase A(2), cyclooxygenase-2, and PGF(2alpha). In addition, RSV attenuated 10,12 CLA increase of intracellular calcium and reactive oxygen species associated with cellular stress, and activation of stress-related proteins (i.e., activating transcription factor 3, JNK) within 12 h. 10,12 CLA-mediated insulin resistance and suppression of fatty acid uptake and triglyceride content were attenuated by RSV. Finally, 10,12 CLA-mediated decrease of peroxisome proliferator-activated receptor gamma (PPARgamma) protein levels and activation of a peroxisome proliferator response element (PPRE) reporter were prevented by RSV. RSV increased the basal activity of PPRE, suggesting that RSV increases PPARgamma activity. Collectively, these data demonstrate for the first time that RSV prevents 10,12 CLA-mediated insulin resistance and delipidation in human adipocytes by attenuating inflammation and cellular stress and increasing PPARgamma activity.
authors.affiliation: Department of Nutrition, University of North Carolina at Greensboro, Greensboro, NC 27402-6170, USA.
authors.forename: Arion
authors.initials: A
authors.lastname: Kennedy
authors.forename: Angel
authors.initials: A
authors.lastname: Overman
authors.forename: Kathleen
authors.initials: K
authors.lastname: Lapoint
authors.forename: Robin
authors.initials: R
authors.lastname: Hopkins
authors.forename: Tiffany
authors.initials: T
authors.lastname: West
authors.forename: Chia-Chi
authors.initials: CC
authors.lastname: Chuang
authors.forename: Kristina
authors.initials: K
authors.lastname: Martinez
authors.forename: Doris
authors.initials: D
authors.lastname: Bell
authors.forename: Michael
authors.initials: M
authors.lastname: McIntosh
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002478:Cells, Cultured; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D044243:Linoleic Acids, Conjugated / Q000378:metabolism*; D008875:Middle Aged; D047495:PPAR gamma / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D014162:Transfection; D014280:Triglycerides / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D005227:Fatty Acids; D018836:Inflammation Mediators; D044243:Linoleic Acids, Conjugated; D047495:PPAR gamma; D013267:Stilbenes; D014280:Triglycerides; D000077185:Resveratrol
references.citation: J Nutr. 2008 Mar;138(3):455-61
references.pmid: 18287349
references.citation: Biochem Biophys Res Commun. 2008 Mar 7;367(2):406-12
references.pmid: 18167310
references.citation: Endocrinology. 2006 Nov;147(11):5340-51
references.pmid: 16873530
references.citation: Am J Physiol Endocrinol Metab. 2007 Jul;293(1):E219-27
references.pmid: 17389706
references.citation: Physiol Genomics. 2007 Nov 14;31(3):544-53
references.pmid: 17878318
references.citation: J Biol Chem. 2005 Nov 18;280(46):38445-56
references.pmid: 16155293
references.citation: Nature. 2004 Jun 17;429(6993):771-6
references.pmid: 15175761
references.citation: Am J Physiol Gastrointest Liver Physiol. 2007 Jun;292(6):G1671-82
references.pmid: 17322064
references.citation: J Lipid Res. 2003 Jul;44(7):1287-300
references.pmid: 12730300
references.citation: Cancer Res. 2006 Jul 15;66(14):7348-54
references.pmid: 16849586
references.citation: Am J Physiol Lung Cell Mol Physiol. 2008 Mar;294(3):L478-88
references.pmid: 18162601
references.citation: Exp Mol Med. 2007 Apr 30;39(2):222-9
references.pmid: 17464184
references.citation: Biochem Biophys Res Commun. 2007 Dec 28;364(4):972-7
references.pmid: 17967414
references.citation: J Biol Chem. 2006 Dec 29;281(52):39915-24
references.pmid: 17090532
references.citation: Nat Cell Biol. 2003 Mar;5(3):224-30
references.pmid: 12598905
references.citation: Circulation. 2002 Oct 8;106(15):1925-9
references.pmid: 12370214
references.citation: J Biol Chem. 1997 Feb 21;272(8):5128-32
references.pmid: 9030579
references.citation: Biomed Pharmacother. 2008 Jul-Aug;62(6):366-72
references.pmid: 17988825
references.citation: Nature. 2005 Sep 29;437(7059):759-63
references.pmid: 16127449
references.citation: Mol Cell. 2007 Jan 12;25(1):57-70
references.pmid: 17218271
references.citation: J Biol Chem. 2004 Jun 18;279(25):26735-47
references.pmid: 15067015
references.citation: Acta Pharmacol Sin. 2007 Nov;28(11):1724-30
references.pmid: 17959022
references.citation: Cell. 2006 Dec 15;127(6):1109-22
references.pmid: 17112576
references.citation: J Lipid Res. 2007 Feb;48(2):444-52
references.pmid: 17050906
references.citation: Diabetes Care. 2002 Sep;25(9):1516-21
references.pmid: 12196420
references.citation: Mutat Res. 2008 Jan-Feb;658(1-2):68-94
references.pmid: 17890139
references.citation: Cell Metab. 2007 Oct;6(4):307-19
references.pmid: 17908559
references.citation: Am J Physiol Cell Physiol. 2007 Jul;293(1):C411-8
references.pmid: 17475668
references.citation: Am J Physiol Heart Circ Physiol. 2006 Oct;291(4):H1694-9
references.pmid: 16973825
references.citation: J Biol Chem. 2003 Jul 25;278(30):28181-92
references.pmid: 12732648
references.citation: Vascul Pharmacol. 2007 Feb;46(2):114-21
references.pmid: 17055343
references.citation: Nature. 1992 Aug 27;358(6389):771-4
references.pmid: 1324435
references.citation: Biochim Biophys Acta. 2007 Aug;1771(8):926-35
references.pmid: 17433773
references.citation: J Nutr. 2001 Sep;131(9):2316-21
references.pmid: 11533273
references.citation: Trends Immunol. 2007 Dec;28(12):551-8
references.pmid: 17981503
references.citation: Nature. 2006 Nov 16;444(7117):337-42
references.pmid: 17086191
references.citation: Nature. 2006 Apr 13;440(7086):944-8
references.pmid: 16612386
references.citation: Lipids. 1999 Mar;34(3):235-41
references.pmid: 10230716
references.citation: Obes Rev. 2005 Aug;6(3):247-58
references.pmid: 16045640
references.citation: Diabetes. 2006 Jun;55(6):1634-41
references.pmid: 16731825
references.citation: Br J Pharmacol. 1999 Sep;128(1):149-57
references.pmid: 10498846
references.citation: J Lipid Res. 2007 Sep;48(9):1905-14
references.pmid: 17699733
references.citation: Am J Clin Nutr. 2007 May;85(5):1203-11
references.pmid: 17490954
references.citation: J Lipid Res. 2005 May;46(5):885-95
references.pmid: 15716587
references.citation: Eur J Pharmacol. 2008 Feb 2;580(1-2):271-6
references.pmid: 18031730
references.citation: J Biol Chem. 2005 Jan 28;280(4):2550-61
references.pmid: 15531761