Abstract
Excessive intake of fat causes accumulation of fat in liver, leading to non-alcoholic fatty liver disease (NAFLD). High-fat diet (HFD) upregulates the expression of Factor D, a complement pathway component, in the liver of mice. However, the functions of Factor D in liver are not well known. Therefore, the current study investigated the relationship between Factor D and hepatic lipid accumulation using CRISPR/Cas9-mediated Factor D knockout (FD-KO) mice. Factor D deficiency downregulated expression of genes related to fatty acid uptake and de novo lipogenesis in the liver. Furthermore, Factor D deficiency reduced the expression of inflammatory factors (Tnf and Ccl2) and fibrosis markers and decreased accumulation of F4/80-positive macrophages. These data suggest that the Factor D deficiency improved hepatic lipid accumulation and hepatic inflammation in HFD-fed mice.
Highlights
Excessive intake of fat causes accumulation of fat in liver, leading to non-alcoholic fatty liver disease (NAFLD)
Mice, 17 weeks of High-fat diet (HFD) resulted in significantly higher liver fat accumulation compared with mice fed normal chow (NC)
Lipid droplets (Fig. 1a) with elevated hepatic triglyceride (TG) and total cholesterol (TC) levels compared with NC (TG; NC 10.1 ± 2.9 mg/g liver, HFD 340.5 ± 3.6, p < 0.0001, TC; NC 2.8 ± 0.2 mg/g liver, HFD 26.6 ± 0.8, p < 0.0001, Fig. 1b)
Summary
Excessive intake of fat causes accumulation of fat in liver, leading to non-alcoholic fatty liver disease (NAFLD). Factor D deficiency reduced the expression of inflammatory factors (Tnf and Ccl2) and fibrosis markers and decreased accumulation of F4/80-positive macrophages. These data suggest that the Factor D deficiency improved hepatic lipid accumulation and hepatic inflammation in HFD-fed mice. Recent studies demonstrated that mRNA levels of Factor D, a complement system component, increased dramatically in livers of mice fed high-fat diet (HFD)[11,12]. Ethanol-induced liver injury has been reported to be more severe in the absence of Factor D 17 Based on these previous studies, we investigated the role of Factor D in the development of NAFLD and hepatic lipid accumulation in mice
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