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Characterization of Hepatic Triglyceride Metabolism in the ApcMin/＋ Mouse
25 Pages Posted: 25 Oct 2018More...
The ApcMin/＋ mouse exhibits an intestinal cachexia accompanied by hypertriglyceridemia (HTG). Because the liver governs systemic energy demands through lipid metabolism regulation, the liver is a likely pathological target of HTG in the ApcMin/＋ mouse.
Methods: On the basal diet, at 8, 14 and 20 weeks of age, the mice were fasted for 4 h prior to undergoing a hepatic triglyceride production test. Several rate-limiting enzymes and transcription factors participate in hepatic lipid metabolism were determined by RT-qPCR and western blot analysis.
Findings: Hepatic de novo lipogenesis (DNL) and β-oxidation were found to be regulated by the AMPK pathway in the ApcMin/＋ mouse at 20 weeks of age. Although hepatic triglyceride production was significantly decreased at 20 weeks of age (p<0.001), hepatic steatosis remained in the ApcMin/＋ mouse. Glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1) is governed by the transcription factor octamer-binding transcription factor-1 (Oct-1), which is involved in the nuclear factor-κB (NF-κB) signaling pathway in the liver of the ApcMin/＋ mouse. Additionally, in HepG2 cells, sn50 (an inhibitor of the NF-κB signaling pathway) reversed the tumor necrosis factor α (TNFα)-induced Oct-1 and GPIHBP1 reduction.
Interpretation: Our findings indicate that the liver might be responsible for the metabolic complications of HTG in individuals with APC defects and in the ApcMin/＋ mouse.
Funding Statement: This work was financially supported by the National Natural Science Foundation of China (Grant No. 31472053 and 31572345) and Graduate Innovation Fund of Jilin University (Grant No. 2017094). The Program for JLU Science and Technology Innovative Research Team (JLUSTIRT, No. 2017TD497 28), the Fundamental Research Funds for the Central Universities.
Declaration of Interests: The authors declare that they have no competing interests.
Ethics Approval Statement: All animal welfare and experimental procedures were performed strictly according to the guidelines from the National Institutes of Health Guide for the Care and Use of Laboratory animals (NIH Publications No. 8023, revised 1978). Additionally, the procedures were approved by the Institutional Animal Care and Use Committee of Jilin University under the approved protocol number 201707025.
Keywords: Adenomatous Polyposis Coli; GPIHBP1; Hypertriglyceridemia; Oct1; NF-κB
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