Reduced triglyceride accumulation due to overactivation of farnesoid X receptor signaling contributes to impaired liver regeneration following 50% hepatectomy in extra‑cholestatic liver tissue
| Autor: | Liang Mao, Yudong Qiu, Qiao‑Li Tang, Shi‑Quan Sun, Wen‑Jun Jia, Luo‑Shun Huang |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Cancer Research medicine.medical_specialty Receptors Cytoplasmic and Nuclear Biochemistry Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound Cholestasis Internal medicine Genetics medicine Animals Hepatectomy Humans Carnitine Molecular Biology Fatty acid synthesis Triglycerides Cell Proliferation chemistry.chemical_classification biology Triglyceride Fatty acid medicine.disease Liver regeneration Liver Regeneration Fatty acid synthase 030104 developmental biology Endocrinology Oncology chemistry Liver biology.protein Hepatocytes Molecular Medicine Farnesoid X receptor medicine.drug Signal Transduction |
| Zdroj: | Molecular medicine reports. 17(1) |
| ISSN: | 1791-3004 |
| Popis: | The aim of the present study was to investigate the role of triglyceride metabolism in the effect of obstructive cholestasis on liver regeneration following 50% partial hepatectomy (PH). Obstructive cholestatic rat models were achieved via ligation of the common bile duct (BDL). Following comparisons between hepatic pathological alterations with patients with perihilar cholangiocarcinoma, rats in the 7 day post‑BDL group were selected as the BDL model for subsequent experiments. Liver weight restoration, proliferating cell nuclear antigen labeling index, cytokine and growth factor expression levels, and hepatic triglyceride content were evaluated to analyze liver regeneration post‑PH within BDL and control group rats. The results of the present study revealed that obstructive cholestasis impaired liver mass restoration, which occurred via inhibition of early stage hepatocyte proliferation. In addition, reduced triglyceride content and inhibited expression of fatty acid β‑oxidation‑associated genes, peroxisome proliferator activated receptor α and carnitine palmitoyltransferase, were associated with an insufficient energy supply within the BDL group post‑PH. Notably, the expression levels of fatty acid synthesis‑associated genes, including sterol‑regulatory element‑binding protein‑1c, acetyl‑coA carboxylase 1 and fatty acid synthase were also reduced within the BDL group, which accounted for the reduced triglyceride content and fatty acid utilization. Further investigation revealed that overactivated farnesoid X receptor (FXR) signaling may inhibit fatty acid synthesis within BDL group rats. Collectively, the role of triglycerides in liver regeneration following PH in extra‑cholestatic livers was identified in the present study. Additionally, the results indicated that overactivated FXR signaling‑induced triglyceride reduction is associated with insufficient energy supply and therefore contributes to the extent of impairment of liver regeneration following PH within extra‑cholestatic livers. |
| Databáze: | OpenAIRE |
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