Aberrant hepatic lipid storage and metabolism in canine portosystemic shunts.
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...
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2017-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5648188?pdf=render |
| _version_ | 1818999215233171456 |
|---|---|
| author | Lindsay Van den Bossche Vivien A C Schoonenberg Iwan A Burgener Louis C Penning Ingrid M Schrall Hedwig S Kruitwagen Monique E van Wolferen Guy C M Grinwis Anne Kummeling Jan Rothuizen Jeroen F van Velzen Nikolas Stathonikos Martijn R Molenaar Bernd J Helms Jos F H M Brouwers Bart Spee Frank G van Steenbeek |
| author_facet | Lindsay Van den Bossche Vivien A C Schoonenberg Iwan A Burgener Louis C Penning Ingrid M Schrall Hedwig S Kruitwagen Monique E van Wolferen Guy C M Grinwis Anne Kummeling Jan Rothuizen Jeroen F van Velzen Nikolas Stathonikos Martijn R Molenaar Bernd J Helms Jos F H M Brouwers Bart Spee Frank G van Steenbeek |
| author_sort | Lindsay Van den Bossche |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T22:13:53Z |
| format | Article |
| id | doaj.art-d24b3c0da950484b9acfde4701c548bc |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T22:13:53Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-d24b3c0da950484b9acfde4701c548bc2022-12-21T19:25:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-011210e018649110.1371/journal.pone.0186491Aberrant hepatic lipid storage and metabolism in canine portosystemic shunts.Lindsay Van den BosscheVivien A C SchoonenbergIwan A BurgenerLouis C PenningIngrid M SchrallHedwig S KruitwagenMonique E van WolferenGuy C M GrinwisAnne KummelingJan RothuizenJeroen F van VelzenNikolas StathonikosMartijn R MolenaarBernd J HelmsJos F H M BrouwersBart SpeeFrank G van SteenbeekNon-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.http://europepmc.org/articles/PMC5648188?pdf=render |
| spellingShingle | Lindsay Van den Bossche Vivien A C Schoonenberg Iwan A Burgener Louis C Penning Ingrid M Schrall Hedwig S Kruitwagen Monique E van Wolferen Guy C M Grinwis Anne Kummeling Jan Rothuizen Jeroen F van Velzen Nikolas Stathonikos Martijn R Molenaar Bernd J Helms Jos F H M Brouwers Bart Spee Frank G van Steenbeek Aberrant hepatic lipid storage and metabolism in canine portosystemic shunts. PLoS ONE |
| title | Aberrant hepatic lipid storage and metabolism in canine portosystemic shunts. |
| title_full | Aberrant hepatic lipid storage and metabolism in canine portosystemic shunts. |
| title_fullStr | Aberrant hepatic lipid storage and metabolism in canine portosystemic shunts. |
| title_full_unstemmed | Aberrant hepatic lipid storage and metabolism in canine portosystemic shunts. |
| title_short | Aberrant hepatic lipid storage and metabolism in canine portosystemic shunts. |
| title_sort | aberrant hepatic lipid storage and metabolism in canine portosystemic shunts |
| url | http://europepmc.org/articles/PMC5648188?pdf=render |
| work_keys_str_mv | AT lindsayvandenbossche aberranthepaticlipidstorageandmetabolismincanineportosystemicshunts AT vivienacschoonenberg aberranthepaticlipidstorageandmetabolismincanineportosystemicshunts AT iwanaburgener aberranthepaticlipidstorageandmetabolismincanineportosystemicshunts AT louiscpenning aberranthepaticlipidstorageandmetabolismincanineportosystemicshunts AT ingridmschrall aberranthepaticlipidstorageandmetabolismincanineportosystemicshunts AT hedwigskruitwagen aberranthepaticlipidstorageandmetabolismincanineportosystemicshunts AT moniqueevanwolferen aberranthepaticlipidstorageandmetabolismincanineportosystemicshunts AT guycmgrinwis aberranthepaticlipidstorageandmetabolismincanineportosystemicshunts AT annekummeling aberranthepaticlipidstorageandmetabolismincanineportosystemicshunts AT janrothuizen aberranthepaticlipidstorageandmetabolismincanineportosystemicshunts AT jeroenfvanvelzen aberranthepaticlipidstorageandmetabolismincanineportosystemicshunts AT nikolasstathonikos aberranthepaticlipidstorageandmetabolismincanineportosystemicshunts AT martijnrmolenaar aberranthepaticlipidstorageandmetabolismincanineportosystemicshunts AT berndjhelms aberranthepaticlipidstorageandmetabolismincanineportosystemicshunts AT josfhmbrouwers aberranthepaticlipidstorageandmetabolismincanineportosystemicshunts AT bartspee aberranthepaticlipidstorageandmetabolismincanineportosystemicshunts AT frankgvansteenbeek aberranthepaticlipidstorageandmetabolismincanineportosystemicshunts |