Abstract 213: Phospholipid Transfer Protein Deficiency Attenuates High-Fat Diet--Induced Obesity and Insulin Resistance

Increased phospholipid transfer protein (PLTP) activity has been found to be associated with diabetes, obesity, and metabolic syndrome in humans. However, whether or not PLTP has a direct effect on insulin sensitivity and obesity is largely unknown. Here we analyzed the effect by using PLTP knockout (PLTP-/-) mouse model. Although, PLTP-/- mice have normal body-weight-gain under chow diet, these mice were protected from high-fat-diet-induced obesity and insulin resistance, compared with wild type mice. In order to understand the mechanism, we evaluated insulin receptor and Akt activation and found that PLTP deficiency significantly enhanced phosphorylated insulin receptor and Akt levels in high-fat-diet fed mouse livers, adipose tissues, and muscles after insulin stimulation, while total Akt and insulin receptor levels were unchanged. Moreover we found that the deficiency induced significantly more GLUT4 immunostaining in the plasma membranes of adipocytes and muscle cells after insulin stimulation. Finally, we found that PLTP deficient hepatocytes had less sphingomyelin and free cholesterol in the plasma membrane and lipid raft than that of controls and this may provide a molecular basis for PLTP deficiency-mediated increasing in insulin sensitivity. We have concluded that PLTP deficiency leads to an improvement in tissue and whole-body insulin sensitivity in high-fat-diet induced insulin resistance mice model. Foundation:National Natural Science Foundation of China (# 81070247, 81170785) and Taishan Scholar Foundation of Shandong Province.