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.