Z Gastroenterol 2020; 58(01): e31
DOI: 10.1055/s-0039-3402182
Poster Visit Session III Metabolism (incl. NAFLD): Friday, February 14, 2020, 4:40 pm – 5:25 pm, Lecture Hall P1
Georg Thieme Verlag KG Stuttgart · New York

Abcb4-knockout reduces hepatic lipid steatosis in HBs transgenic mice

K Irungbam
1   Justus Liebig University, Gastroenterology, Gießen, Germany
,
M Roderfeld
1   Justus Liebig University, Gastroenterology, Gießen, Germany
,
Y Churin
1   Justus Liebig University, Gastroenterology, Gießen, Germany
,
H Glimm
1   Justus Liebig University, Gastroenterology, Gießen, Germany
,
I Yüce
2   Justus Liebig University, Institute of Nutritional Science, Chair of Food Science, and Interdisciplinary Research Center, Gießen, Germany
,
G Morlock
2   Justus Liebig University, Institute of Nutritional Science, Chair of Food Science, and Interdisciplinary Research Center, Gießen, Germany
,
E Roeb
1   Justus Liebig University, Gastroenterology, Gießen, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
03 January 2020 (online)

Also available at
 

Introduction:

ATP-binding cassette subfamily B member 4 (ABCB4) is a phospholipid translocator present at the canalicular membrane of hepatocytes, which "flops" phosphatidylcholine into bile. Abcb4-/- mice represent the most reproducible in vivo model to study chronic cholestatic liver diseases. Abcb4-/- mice exhibit a dysregulated lipid metabolism which is associated with disease pathogenesis. Hepatitis B transgenic mice (HBs) spontaneously develop hepatic steatosis. We previously reported that Hepatitis B virus surface proteins accelerate cholestatic injury and tumor progression in HBs/Abcb4-/- double-transgenic mice. With the current study, we aimed to investigate the effect of Abcb4-/- induced cholestasis on the hepatic lipid metabolism in HBs transgenic mice.

Methods:

Hybrids of HBs transgenic mice and Abcb4-/- mice were bred on BALB/c background. qPCR, Western blot, Oil Red O staining, High-performance thin-layer chromatography (HPTLC) and immunohistochemistry (IHC) methods were used to characterize alterations in lipid metabolism.

Results:

Hepatic neutral lipid depots were found in HBs transgenic mice. In comparison, intracellular lipid storage was remarkably reduced in the hepatocytes of both, Abcb4-/- and HBs/Abcb4-/-. Similarly, HPTLC based lipid quantification of the liver tissues revealed a significant reduction in the amount of triacylglycerol (TAGs) while the amount of free fatty acids was significantly increased in Abcb4-/- and HBs/Abcb4-/- in comparison to wild type and HBs mice, respectively. Serum analysis also showed a reduction in TAGs and cholesterol levels. The expression level of perilipin2 (PLIN2), a lipid droplet associated protein, was reduced in Abcb4-/- and HBs/Abcb4-/-. Reduction of PLIN2 was associated with suppression of TAGs synthesis and de novo lipogenesis associated gene expression (MGAT1, DGAT1, FASN, HMG-CoA, ACC1, and SREBP1-c, PPARγ). We further analysed regulatory pathways that can regulate intracellular lipid metabolism and PLIN2, found that PLIN2 can be regulated through the activation of AMPK and CREB signaling pathways.

Conclusion:

Cholestatic conditions mediated by the Abcb4 knockout reduced lipogenesis in the hepatocytes of HBs transgenic mice, thus ameliorating intrahepatic steatosis.