Abstract
Non-alcoholic fatty liver disease (NAFLD) is a poorly understood multifactorial pandemic disorder. One of the hallmarks of NAFLD, hepatic steatosis, is a common feature in canine congenital portosystemic shunts. The aim of this study was to gain detailed insight into the pathogenesis of steatosis in this large animal model. Hepatic lipid accumulation, gene-expression analysis and HPLC-MS of neutral lipids and phospholipids in extrahepatic (EHPSS) and intrahepatic portosystemic shunts (IHPSS) was compared to healthy control dogs. Liver organoids of diseased dogs and healthy control dogs were incubated with palmitic- and oleic-acid, and lipid accumulation was quantified using LD540. In histological slides of shunt livers, a 12-fold increase of lipid content was detected compared to the control dogs (EHPSS P<0.01; IHPSS P = 0.042). Involvement of lipid-related genes to steatosis in portosystemic shunting was corroborated using gene-expression profiling. Lipid analysis demonstrated different triglyceride composition and a shift towards short chain and omega-3 fatty acids in shunt versus healthy dogs, with no difference in lipid species composition between shunt types. All organoids showed a similar increase in triacylglycerols after free fatty acids enrichment. This study demonstrates that steatosis is probably secondary to canine portosystemic shunts. Unravelling the pathogenesis of this hepatic steatosis might contribute to a better understanding of steatosis in NAFLD.
Highlights
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in men with an estimated prevalence ranging 25% up to 45% worldwide [1]
This study provides detailed insight into the pathogenesis of hepatic steatosis in Congenital portosystemic shunts (CPSS) dogs by examination of the quantity of accumulating lipids, mRNA expression of genes involved in lipid metabolism, and lipid profiles in both extrahepatic portosystemic shunts (EHPSS) and intrahepatic portosystemic shunts (IHPSS) compared to control dogs
To further support our hypothesis, canine organoids of EHPSS, IHPSS and healthy controls demonstrated a similar increase in TAGs after free fatty acids enrichment
Summary
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in men with an estimated prevalence ranging 25% up to 45% worldwide [1]. There was no additional external funding received for this study
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
