Abnormality of hepatic triglyceride metabolism in Apc/+ mice with colon cancer cachexia
| Autor: | Jiahuan Chen, Dazhong Zhao, He Wang, Xinwei Zhang, Xiaohuan Peng, Biao Yu, Anbei Wang, Hongsheng Ouyang, Daxin Pang, Lingyu Wang, Mingjun Zhang, Xiaochun Tang |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Lipoprotein lipase Triglyceride business.industry Hypertriglyceridemia GPIHBP1 General Medicine medicine.disease 030226 pharmacology & pharmacy General Biochemistry Genetics and Molecular Biology Cachexia 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine Endocrinology chemistry Internal medicine Lipogenesis Hyperlipidemia medicine General Pharmacology Toxicology and Pharmaceutics Steatosis business |
| Zdroj: | Life Sciences. 227:201-211 |
| ISSN: | 0024-3205 |
| Popis: | Aims Colorectal cancer syndrome has been one of the greatest concerns in the world. Although several epidemiological studies have shown that hepatic low lipoprotein lipase (LPL) mRNA expression may be associated with dyslipidemia and tumor progression, it is still not known whether the liver plays an essential role in hyperlipidemia of ApcMin/+ mice. Main methods We measured the expression of metabolic enzymes that involved fatty acid uptake, de novo lipogenesis (DNL), β-oxidation and investigated hepatic triglyceride production in the liver of wild-type and ApcMin/+ mice. Key findings We found that hepatic fatty acid uptake and DNL decreased, but there was no significant difference in fatty acid β-oxidation. Interestingly, the production of hepatic very low-density lipoprotein-triglyceride (VLDL-TG) decreased at 20 weeks of age, but marked steatosis was observed in the livers of the ApcMin/+ mouse. To further explore hypertriglyceridemia, we assessed the function of hepatic glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1) for the first time. GPIHBP1 is governed by the transcription factor octamer-binding transcription factor-1 (Oct-1) which are involved in the nuclear factor-κB (NF-κB) signaling pathway in the liver of ApcMin/+ mice. Importantly, it was also confirmed that sn50 (100 μg/mL, an inhibitor of the NF-κB) reversed the tumor necrosis factor α (TNFα)-induced Oct-1 and GPIHBP1 reduction in HepG2 cells. Significance Altogether, these findings highlighted a novel role of GPIHBP1 that might be responsible for hypertriglyceridemia in ApcMin/+ mice. Hypertriglyceridemia in these mice may be associated with their hepatic lipid metabolism development. |
| Databáze: | OpenAIRE |
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