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

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The dietary fatty acid 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 10 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 treatment significantly attenuated CLA-induced increased fasting glucose, and at 4 weeks, leptin prevented CLA-induced impairment of insulin tolerance. Although CLA alone significantly increased fasting insulin, leptin reduced fasting insulin levels in both control- and CLA-fed mice. Concentrations of liver and muscle triglycerides (TG) were not altered by CLA alone; however, when adjusted for tissue mass and body weight, CLA alone increased hepatic, but not muscle, TG levels. Leptin reduced liver and muscle TG concentrations in both diet groups, and when adjusted for liver mass and body weight. These data suggest that the restoration of insulin sensitivity by leptin may partially be attributed to the reduction of total hepatic TG in obese mice fed CLA.