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

Background and AimWDR13 - 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 {beta}-cell proliferation, hyperinsulinemia and age dependent mild obesity. Previously, we have reported that the absence of WDR13 in diabetic Leprdb/db mice helps in amelioration of fatty liver phenotype along with diabetes and systemic inflammation. This intrigued us to study direct liver injury and hepatic regeneration in Wdr13-/0 mice using hepatotoxin CCl4.\n\nMethodsMice were injected with CCl4 twice a week for 8 consecutive weeks. Controls were injected with vehicle (olive oil) similarly. After the last injection, mice were given a 10-days of recovery period and then sacrificed for physiological and molecular analyses.\n\nResultsIn the present study we report slower hepatic regeneration in Wdr13-/0 mice as compared to their wild type littermates after CCl4 administration. Interestingly, during the regeneration phase, hepatic hypertriglyceridemia was observed in Wdr13-/0 mice. Further analyses revealed an upregulation of PPAR pathway in the liver of CCl4-administered Wdr13-/0 mice, causing de novo lipogenesis.\n\nConclusionsThe slower hepatic regeneration observed in CCl4 administered Wdr13-/0 mice, may be linked to liver hypertriglyceridemia because of activation of PPAR pathway.