Diet-induced Lipid Accumulation in Liver Enhances ATP-binding Cassette Transporter g5/g8 Expression in Bile Canaliculi

Yamazaki, Yoji; Hashizume, Takumi; Morioka, Hiroko; Sadamitsu, Satoshi; Ikari, Akira; Miwa, Masao; Sugatani, Junko

doi:10.2133/dmpk.dmpk-11-rg-025

Cited by 10 publications

(9 citation statements)

References 44 publications

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“…On the other hand, liver ABCG5 mRNA was increased by the HF diet. High-fat and high-sucrose diets, known to cause an accumulation of lipids in liver have been reported to increase the protein levels of ABCG5 and ABCG8 [ 36 ] . The impact of the present increase in ABCG5 with the HF diet is, however, limited by the fact that ABCG8 gene expression was not changed and based on results obtained in vitro and in vivo, ABCG5 and ABCG8 are half-transporters proposed to function as obligate heterodimers [ 37 ] .…”

Section: Figmentioning

confidence: 99%

Ovariectomy Stimulates Hepatic Fat and Cholesterol Accumulation in High-fat Diet-fed Rats

et al. 2012

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This study was designed to determine how estrogens withdrawal during a high-fat (HF) diet regimen affects liver triacylglycerol (TAG) and cholesterol accumulation. Female Sprague-Dawley rats were submitted to a HF (42% energy as fat) or a standard (SD) diet for 6 weeks before being either ovariectomized (Ovx) or sham operated (Sham). Thereafter, Ovx and Sham rats were kept on the same diet for another 6 weeks leading to euthanasia. Liver TAG content was increased (p<0.01) in Ovx rats but not by the HF diet alone. However, the combination of HF diet and Ovx resulted in a greater liver TAG accumulation (p<0.06) than that observed in Ovx-SD/SD. Measurement of molecular markers of liver lipid metabolism revealed an increase in transcripts of markers of lipid oxidation (CPT-1 and PGC1; p<0.05) in rats fed the HF diet. This increase was, however, substantially less if HF fed rats were Ovx. Liver total cholesterol levels were increased (p<0.01) only in the Ovx-HF/HF rats while plasma cholesterol levels were increased in Ovx-SD/SD and in SHAM-HF/HF and Ovx-HF/HF rats. Transcripts of molecular markers of cholesterol metabolism suggest that biliary acids synthesis (CYP7a-1) was reduced in Ovx-SD/SD and Sham-HF/HF rats and even more so in Ovx-HF/HF rats. It is concluded that the effects of a HF diet on liver TAG accumulation are especially observed in Ovx rats possibly through a reduction in hepatic lipid oxidation. The combination of Ovx and HF diet also acts synergistically to favor liver cholesterol accumulation.

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Section: Figmentioning

confidence: 99%

Ovariectomy Stimulates Hepatic Fat and Cholesterol Accumulation in High-fat Diet-fed Rats

et al. 2012

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“…On the basis of results obtained from genetically modified mice, they are essential for biliary cholesterol secretion . We previously reported that diet‐induced lipid loading of the liver caused a significant increase in the expression of Abcg5/Abcg8 in bile canaliculi and that this increase was much higher than that due to administration of a liver X receptor agonist . These observations imply that cholesterol accumulation induced Abcg5/Abcg8 transport to the bile canaliculi by posttranslational regulation.…”

mentioning

confidence: 94%

Involvement of a cyclic adenosine monophosphate–dependent signal in the diet‐induced canalicular trafficking of adenosine triphosphate–binding cassette transporter g5/g8

et al. 2015

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The adenosine triphosphate-binding cassette (ABC) half-transporters Abcg5 and Abcg8 promote the secretion of neutral sterol into bile. Studies have demonstrated the dietinduced gene expression of these transporters, but the regulation of their trafficking when the nutritional status changes in the liver remains to be elucidated. Here, we generated a novel in vivo kinetic analysis that can monitor the intracellular trafficking of Abcg5/ Abcg8 in living mouse liver by in vivo transfection of the genes of fluorescent proteintagged transporters and investigated how hypernutrition affects the canalicular trafficking of these transporters. The kinetic analysis showed that lithogenic diet consumption accelerated the translocation of newly synthesized fluorescent-tagged transporters to intracellular pools in an endosomal compartment and enhanced the recruitment of these pooled gene products into the bile canalicular membrane in mouse liver. Because some ABC transporters are reported to be recruited from intracellular pools to the bile canaliculi by cyclic adenosine monophosphate (cAMP) signaling, we next evaluated the involvement of this machinery in a diet-induced event. Administration of a protein kinase A inhibitor, N-(2-{[3-(4-bromophenyl)22-propenyl]amino}ethyl)25-isoquinolinesulfonamide, decreased the canalicular expression of native Abcg5/Abcg8 in lithogenic diet-fed mice, and injection of a cAMP analog, dibutyryl cAMP, transiently increased their levels in standard diet-fed mice, indicating the involvement of cAMP signaling. Indeed, canalicular trafficking of the fluorescent-tagged Abcg5/Abcg8 was enhanced by dibutyryl cAMP administration. Conclusion: These observations suggest that diet-induced lipid loading into liver accelerates the trafficking of Abcg5/Abcg8 to the bile canalicular membrane through cAMP signaling machinery. (HEPATOLOGY 2015;62:1215-1226 T he bile canalicular membrane of mammalian hepatocytes contains several adenosine triphosphate-binding cassette (ABC) transporters that couple adenosine triphosphate hydrolysis to the transport of specific substrates into the bile canaliculus.

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“…In this study, the COS treatment increased the expression of ABCG5/8 in the small intestine, which may have been due to: 1) similar to chitosan, COS promotes cholesterol excretion from enterocytes via the ABCG5/8 pathway or 2) a high calorie diet induced hyperlipidemia, leading to a concentration gradient of cholesterol, which subsequently drove the plasma cholesterol transportation from the bloodstream to the lumen via the induction of ABCG5/8, but not ABCA1. Conversely, increased ABCG5/8 expression without ABCA1 alteration was reported previously, suggesting that the regulation of the LXR target genes is complicated and some posttranslational mechanisms, such as transporter trafficking, may be involved 23,24) . Further investigation utilizing enterocytes under COS treatment, particularly via promoter assays, will therefore be necessary.…”

Section: Effects Of the Cos Treatment On Cultured Hepg2 Cells And Rawmentioning

confidence: 88%

Chitosan Oligosaccharides Attenuate Atherosclerosis and Decrease Non-HDL in ApoE-/- Mice

Luo

Liu

et al. 2015

JAT

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Diet-induced Lipid Accumulation in Liver Enhances ATP-binding Cassette Transporter g5/g8 Expression in Bile Canaliculi

Cited by 10 publications

References 44 publications

Ovariectomy Stimulates Hepatic Fat and Cholesterol Accumulation in High-fat Diet-fed Rats

Ovariectomy Stimulates Hepatic Fat and Cholesterol Accumulation in High-fat Diet-fed Rats

Involvement of a cyclic adenosine monophosphate–dependent signal in the diet‐induced canalicular trafficking of adenosine triphosphate–binding cassette transporter g5/g8

Chitosan Oligosaccharides Attenuate Atherosclerosis and Decrease Non-HDL in ApoE-/- Mice

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