title: Antidiabetic effects of cis-9, trans-11-conjugated linoleic acid may be mediated via anti-inflammatory effects in white adipose tissue.
abstract: Adipose tissue may be the source of insulin desensitizing proinflammatory molecules that predispose to insulin resistance. This study investigated whether dietary fatty acids could attenuate the proinflammatory insulin-resistant state in obese adipose tissue. The potential antidiabetic effect of cis-9, trans-11-conjugated linoleic acid (c9,t11-CLA) was determined, focusing on the molecular markers of insulin sensitivity and inflammation in adipose tissue of ob/ob C57BL-6 mice. Feeding a c9,t11-CLA-enriched diet reduced fasting glucose (P < 0.05), insulin (P < 0.05), and triacylglycerol concentrations (P < 0.01) and increased adipose tissue plasma membrane GLUT4 (P < 0.05) and insulin receptor (P < 0.05) expression compared with the control linoleic acid-enriched diet. Interestingly, after the c9,t11-CLA diet, adipose tissue macrophage infiltration was less, with marked downregulation of several inflammatory markers in adipose tissue, including reduced tumor necrosis factor-alpha and CD68 mRNA (P < 0.05), nuclear factor-kappaB (NF-kappaB) p65 expression (P < 0.01), NF-kappaB DNA binding (P < 0.01), and NF-kappaB p65, p50, c-Rel, p52, and RelB transcriptional activity (P < 0.01). To define whether these observations were direct effects of the nutrient intervention, complimentary cell culture studies showed that c9,t11-CLA inhibited tumor necrosis factor-alpha-induced downregulation of insulin receptor substrate 1 and GLUT4 mRNA expression and promoted insulin-stimulated glucose transport in 3T3-L1 adipocytes compared with linoleic acid. This study suggests that altering fatty acid composition may attenuate the proinflammatory state in adipose tissue that predisposes to obesity-induced insulin resistance.
authors.affiliation: Nutrigenomics Research Group, Department of Clinical Medicine, Institute of Molecular Medicine, Trinity College Dublin, St. James's Hospital, Dublin 8, Ireland.
authors.forename: Fiona
authors.initials: F
authors.lastname: Moloney
authors.forename: Sinead
authors.initials: S
authors.lastname: Toomey
authors.forename: Enda
authors.initials: E
authors.lastname: Noone
authors.forename: Anne
authors.initials: A
authors.lastname: Nugent
authors.forename: Bernard
authors.initials: B
authors.lastname: Allan
authors.forename: Christine E
authors.initials: CE
authors.lastname: Loscher
authors.forename: Helen M
authors.initials: HM
authors.lastname: Roche
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism; D052436:Adipose Tissue, White / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D015415:Biomarkers; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000517:prevention & control; D005786:Gene Expression Regulation; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy*; D007333:Insulin Resistance / Q000502:physiology; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology* / Q000627:therapeutic use; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008820:Mice, Obese
chemical_list: D015415:Biomarkers; D007004:Hypoglycemic Agents; D044243:Linoleic Acids, Conjugated; C503589:cis-9, trans-11-conjugated linoleic acid