Leptin Reverses CLA-induccd Disorders Of Aktcose Metabolism

Disorders of glucose metabolism is harmful to animals and humans. Leptin deficiency isone of the factors that can cause it. Under this circumstance, the addition of leptin can ameliorate thedisorders of glucose metabolism. Yet the mechanism of leptin-mediated reversal of glucose metabolismdisorders has not been fully defined. To understand it, we used CLA to induce mice with glucosemetabolism successfully. The mice exhibited leptin deficiency(p＜0.05), hyperglycemia(p＜0.05), andhyperinsulinemia (p＜0.01), and the concentration of insulin in plasma was even60times higher than thecontrol. Subsequently, the mice underwent subcutaneous implantation of an micro-osmotic pumpcontaining either vehicle or leptin at a dose of1mg/ml for2weeks. Then we found that the circulatingleptin levels were increased, and hyperglycemia and hyperinsulinemia ameliorated greatly(p＜0.05). Wealso conducted glucose tolerance test and insulin tolerance test to measure insulin sensitivity and theresults showed that leptin can eliminate insulin resistance and increase insulin sensitivity. To make themechanism of leptin increasing insulin sensitivity clear, we used CLA mice to test the response to leptinin hypothalamus and the gene expression related to glucose metabolism and insulin signaling passway inliver by QPCR and Western. The data suggested that leptin can reverse CLA-induced gluconeogenesisintensification, glycolysis inhibition and insulin signaling suppression (p＜0.05). We conclude that CLAcan induce mice exhibit leptin deficiency, hyperglycemia, and hyperinsulinemia. The administration ofleptin increases circulating leptin levels, reverses hyperglycemia and hyperinsulinemia, and enhancesinsulin sensitivity, thus to regulate glucose metabolism. The mechanism that leptin influences insulinsensitivity is that the OBRb signaling is enhanced in hypothalamus and the insulin signaling passway isactivated in liver. Morever, leptin can regulate glucose homeostasis by suppressing the expression ofgluconeogenic genes and enhancing the expression of glycolysis genes in the liver.