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Adenovirus Overexpression of human ApoF in C57BL6/J mice

ABSTRACT: Adenovirus Overexpression of human ApoF in C57BL6/J mice

PROVIDER: PRJNA839363 | ENA |

REPOSITORIES: ENA

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Adenovirus Overexpression of human ApoF in C57BL6/J mice

Project description:Background: Non-alcoholic fatty liver disease (NAFLD) affects nearly 25% of the global population. Cardiovascular disease (CVD) is the most common cause of death among patients with NAFLD, in line with highly prevalent dyslipidemia in this population. Increased plasma triglyceride (TG)-rich lipoprotein (TRL) concentrations, an important risk factor for CVD, are closely linked with hepatic TG content. Therefore, it is of great interest to identify regulatory mechanisms of hepatic TRL production and remnant uptake in the setting of hepatic steatosis. Approach and results: To identify liver-regulated pathways linking intra-hepatic and plasma TG metabolism, we performed transcriptomic analysis of liver biopsies from two independent cohorts of obese patients. Hepatic APOF (encoding apolipoprotein F) expression showed the 4th strongest negatively correlation with hepatic steatosis and the strongest negative correlation with plasma TG levels. The effects of adenoviral-mediated human ApoF (hApoF) overexpression on plasma and hepatic TG were assessed in C57BL6/J mice. Surprisingly, hApoF overexpression increased both hepatic VLDL-TG secretion and hepatic lipoprotein remnant clearance, associated a ~25% reduction in plasma TG levels. Conversely, reducing endogenous ApoF expression reduced VLDL secretion in vivo, and reduced hepatocyte VLDL uptake by ~15% in vitro. Transcriptomic analysis of APOF-overexpressing mouse livers revealed a gene signature related to enhanced ApoB-lipoprotein clearance, including increased expression of Ldlr and Lrp1, among others. Conclusion: These data reveal a previously undescribed role for ApoF in the control of plasma and hepatic lipoprotein metabolism by favoring VLDL-TG secretion and hepatic lipoprotein remnant particle clearance.

2022-06-29 | GSE203290 | GEO

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Project description:Proteomic dataset of 15 murine kidneys of 14-week-old male C57Bl6 mice. Mice were divided into 3 treatment groups four weeks prior to nephrectomy and 5 mice had ad libitum access to food and water, while another 10 mice received 30% food restriction. Calorically restricted mice either received intraperitoneal supplementation of 20-HETE or vehicle (EtOH in sodiumchloride 0.9%) for 8 days on a daily basis prior to nephrectomy. Ad libitum fed mice received vehicle injections for 8 days on a daily basis prior to nephrectomy.

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Liver tissue transcriptomic analysis of db/db mice expressing adenovirus-delivered GFP or NAMPT

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