Impaired liver regeneration and lipid homeostasis in CCl4 treated WDR13 deficient mice

Abstract

AbstractWDR13 - a WD repeat protein, is abundant in pancreas, liver, ovary and testis. Absence of this protein in mice has been seen to be associated with pancreatic β-cell proliferation, hyperinsulinemia and age dependent mild obesity. Previously, we have reported that the absence of WDR13 in diabeticLeprdb/dbmice helps in amelioration of fatty liver phenotype along with diabetes and systemic inflammation. This intrigued us to study direct liver injury and hepatic regeneration inWdr13−/0mice using hepatotoxin CCl4. In the present study we report slower hepatic regeneration inWdr13−/0mice as compared to their wild type littermates after CCl4administration. Interestingly, during the regeneration phase, hepatic hypertriglyceridemia was observed inWdr13−/0mice. Further analyses revealed an upregulation of PPAR pathway in the liver of CCl4- administeredWdr13−/0mice, causing de novo lipogenesis. The slower hepatic regeneration observed in CCl4administeredWdr13−/0mice, may be linked to liver hypertriglyceridemia because of activation of PPAR pathway.