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Publication : Phospholipid transfer protein (PLTP) deficiency attenuates high fat diet induced obesity and insulin resistance.

First Author  Song G Year  2019
Journal  Biochim Biophys Acta Mol Cell Biol Lipids Volume  1864
Issue  10 Pages  1305-1313
PubMed ID  31220615 Mgi Jnum  J:279668
Mgi Id  MGI:6343141 Doi  10.1016/j.bbalip.2019.06.012
Citation  Song G, et al. (2019) Phospholipid transfer protein (PLTP) deficiency attenuates high fat diet induced obesity and insulin resistance. Biochim Biophys Acta Mol Cell Biol Lipids 1864(10):1305-1313
abstractText  Increased phospholipid transfer protein (PLTP) activity has been found to be associated with 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 PLTP deficiency induced significantly more GLUT4 protein in the plasma membranes of adipocytes and muscle cells after insulin stimulation. Finally, we found that PLTP-deficient hepatocytes had less sphingomyelins and free cholesterols in the lipid rafts and plasma membranes than that of controls and this may provide a molecular basis for PLTP deficiency-mediated increase in insulin sensitivity. We have concluded that PLTP deficiency leads to an improvement in tissue and whole-body insulin sensitivity through modulating lipid levels in the plasma membrane, especially in the lipid rafts.
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