PT  - JOURNAL ARTICLE
AU  - Arun Prakash Mishra
AU  - Archana B Siva
AU  - Chandrashekaran Gurunathan
AU  - Y Komala
AU  - B Jyothi Lakshmi
TI  - Impaired liver regeneration and lipid homeostasis in CCl<sub>4</sub> treated WDR13 deficient mice
AID  - 10.1101/763433
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 763433
4099  - http://biorxiv.org/content/early/2019/09/09/763433.short
4100  - http://biorxiv.org/content/early/2019/09/09/763433.full
AB  - Background and Aim 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 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.Methods Mice 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.Results 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.Conclusions The slower hepatic regeneration observed in CCl4 administered Wdr13−/0 mice, may be linked to liver hypertriglyceridemia because of activation of PPAR pathway.