Lab Anim Res.  2020 Dec;36(4):318-327. 10.1186/s42826-020-00076-8.

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

• Mishra AP
• Siva AB
• Gurunathan C
• Komala Y
• Lakshmi BJ

• KMID: 2510410
• DOI: http://doi.org/10.1186/s42826-020-00076-8

Abstract

WDR13 - 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 diabetic Lepr^db/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. In 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. The slower hepatic regeneration observed in CCl₄ administered Wdr13 ^−/0 mice, may be linked to liver hypertriglyceridemia because of activation of PPAR pathway.

Keyword

Fatty liver; PPARg; Hepatosteatosis; Hypertriglyceridemia; Hepatotoxin