Antidiabetic effects of cis-9, trans-11-conjugated linoleic acid may be mediated via anti-inflammatory effects in white adipose tissue.
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.
Moloney
Fiona
F
Nutrigenomics Research Group, Department of Clinical Medicine, Institute of Molecular Medicine, Trinity College Dublin, St. James's Hospital, Dublin 8, Ireland.
Toomey
Sinead
S
Noone
Enda
E
Nugent
Anne
A
Allan
Bernard
B
Loscher
Christine E
CE
Roche
Helen M
HM
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
D015415:Biomarkers; D007004:Hypoglycemic Agents; D044243:Linoleic Acids, Conjugated; C503589:cis-9, trans-11-conjugated linoleic acid