Abnormality of hepatic triglyceride metabolism in Apc mice with colon cancer cachexia.

Life Sci 2019 Jun 17;227:201-211. Epub 2019 Apr 17.

Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, No.5333 Xi'an Road, Lvyuan District, Changchun 130062, Jilin Province, China. Electronic address:

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 Apc 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 Apc 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 Apc 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 Apc 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 Apc mice. Hypertriglyceridemia in these mice may be associated with their hepatic lipid metabolism development.

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http://dx.doi.org/10.1016/j.lfs.2019.04.041DOI Listing

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June 2019
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