Impaired liver regeneration and lipid homeostasis in CCl4 treated WDR13 deficient mice
Autor: | Chandrashekaran Gurunathan, Y. Komala, B. Jyothi Lakshmi, Archana B. Siva, Arun Prakash Mishra |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
medicine.medical_specialty 03 medical and health sciences 0302 clinical medicine Internal medicine Fatty liver medicine Hyperinsulinemia PPARg lcsh:QH301-705.5 Liver injury Hypertriglyceridemia lcsh:R5-920 business.industry Research Hepatotoxin Hepatosteatosis PPAR Pathway medicine.disease Liver regeneration 030104 developmental biology Endocrinology lcsh:Biology (General) Lipogenesis 030211 gastroenterology & hepatology business lcsh:Medicine (General) |
Zdroj: | Laboratory Animal Research, Vol 36, Iss 1, Pp 1-10 (2020) Laboratory Animal Research |
ISSN: | 2233-7660 |
Popis: | 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 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.MethodsMice 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.ResultsIn 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.ConclusionsThe slower hepatic regeneration observed in CCl4 administered Wdr13−/0 mice, may be linked to liver hypertriglyceridemia because of activation of PPAR pathway. |
Databáze: | OpenAIRE |
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