PI3K/Akt pathway mediates high glucose-induced lipid accumulation in human renal proximal tubular cells via spliced XBP-1.

In the present study, we investigated the effect of X-box-binding protein-1 (XBP-1) splicing on lipogenesis in high glucose-stimulated human renal proximal tubular cell line (HKC). The results revealed that high glucose promoted the splicing of XBP-1, concomitant with up-regulation of lipogenic genes including fatty acid synthase, acetyl-CoA carboxylase, adipocyte differentiation-related protein, and cellular triglyceride. Again, silence of XBP-1 with shRNA vector inhibited high glucose-caused increased lipogenesis. Furthermore, we confirmed that the inhibition of phosphotidyl inositol 3-kinase (PI3K)/Akt pathway with LY294002 or Akt shRNA vector blocked the effect of high glucose on XBP-1 splicing and cellular triglyceride. These above data suggest that spliced XBP-1 mediates high glucose-induced lipid accumulation in HKC cells and PI3K/Akt pathway may be involved in high glucose-caused XBP-1 splicing.