Leptin prevents insulin resistance induced by conjugated linoleic acid in obese mice

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2006-04-17T14:08:32Z

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Conjugated linoleic acid (CLA) reduces adipose mass and enhances insulin sensitivity in several animal models. Conversely, in some rodent models, CLA induces lipodystrophy, insulin resistance, and reduces adipokines. Leptin is an insulin sensitizing adipokine that may work by suppressing steatosis in liver and muscle, a condition that may contribute to insulin resistance. Therefore, we hypothesize that leptin prevents CLA-induced insulin resistance in obese mice by attenuating steatosis. In a 2x2 factorial design, 6-week old, male ob/ob mice were fed either a control diet or a diet supplemented with 1.5% mixed isomer CLA and received daily intraperitoneal injections of either PBS or 1.0 mg/kg leptin for 4 weeks. CLA and leptin alone or in combination decreased weight gain, which was reflected by a reduction of epididymal fat mass. At 2 and 4 weeks of feeding, leptin significantly attenuated CLA-induced increased fasting glucose, and at 4 weeks, leptin prevented CLA-induced insulin resistance. Although CLA alone significantly increased fasting insulin, leptin reduced fasting insulin levels in both diet groups. CLA significantly reduced serum adiponectin, regardless of leptin treatment. Liver and muscle triglycerides (TG) were not altered by CLA alone; however, leptin reduced liver and muscle TG in both diet groups. Fatty acid synthase mRNA, a marker of lipid synthesis was decreased by leptin, regardless of diet, but CPT-1, a marker of lipid oxidation, was not changed. These data suggest that restoration of insulin sensitivity by leptin may partially be attributed to the reduction of hepatic steatosis and by compensating for the reduction of adiponectin.

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conjugated linoleic acid, leptin, ob/ob mice, hepatic steatosis

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