Unfolded protein response on renal lipogenesis in C57BL/6 mice (1029.2)

It has been postulated that endoplasmic reticulum stress, which is associated with protein misfolding, may generate renal lipid accumulation. Thus the aim of this study was to demonstrate that endoplasmic reticulum stress induced by tunicamycin (T) administration up-regulate the expression of lipogenic enzymes in mice kidney. Male C57BL/6 mice were injected with tunicamycin and studied at several time points: 1) control, 2) T8 (8h), 3) T24 (24h). Serum glucose levels showed a significant decrease in the T24 group of mice compared to the control group or T8 group. Serum triglycerides, in T8 and T24 groups significantly decreased compared to control. Gene expression of proteins involved in the unfolded protein response (UPR) such as ATF6, CHOP and GRP78 in T8 and T24 groups were significantly higher than the control group. Assessment of the PERK pathway as part of the UPR, showed that eIF2alpha-total significantly decreased compared to the control and this effect was more evident after 24 hours of exposure to T with respect of T8 group. Finally, the state of phosphorylation of eIF- 2alpha protein, was significantly higher in the T8 and T24 than the control group. Changes in UPR were associated with an increase in the group T8 of renal mRNA and protein abundance of SREBP -1, ACC and FAS involved in fatty acid synthesis compared with the control and the T24 group.