HFD-induced hepatic lipid accumulation and inflammation are decreased in Factor D deficient mouse

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.

One Week Feeding of CDAHFD Induces Steatohepatitis and Mitochondrial Dysfunction with Oxidative Stress in Liver

“…If researchers select this model, they can save a lot of time on NAFLD research. Many studies using NAFLD models have reported requiring long-term feeding periods of 8 to 12 or more weeks [6][7][8][9][10][11][12] to establish the model, which means severe time loss. On the other hand, this model progresses in pathology faster than normal HFD even though it is able to be established faster, so if researchers want to develop a drug with this model, they may need a stronger efficacy.…”

“…There are many studies using animal models of NAFLD to develop new treatments and to investigate its molecular mechanisms. In general, the NAFLD model is created by feeding an unbalanced diet, such as a high-fat diet (HFD) [6][7][8], a high-fat high-sucrose diet (HS-HFD) [9,10], or a high-fat, high-cholesterol diet [11,12]. Moreover, NASH models including fibrosis and steatohepatitis have made using a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) [13][14][15][16].…”

“…Moreover, NASH models including fibrosis and steatohepatitis have made using a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) [13][14][15][16]. The duration of the animal experiments using the various models mentioned above was the long term, from 8 to 12 weeks or longer [6][7][8][9][10][11][12][13][14][15][16]. Such long-term experiments can sometimes be a major impediment to the progress of research, as it takes a very long time to obtain results.…”

Alzheimer’s Disease and Diabetes: Role of Diet, Microbiota and Inflammation in Preclinical Models

“…In addition, He et al found out that the phenotypic switch in adipose tissue from anti-inflammatory to pro-inflammatory macrophages is detected after 5 weeks on HFD, while metabolic inflammation is noted after 9 weeks [ 201 ]. An overall increase of pro-inflammatory cytokines such as TNF-α, IL-6, leptin and TGFβ1 is detected in the liver of HFD-fed mice for 17 weeks [ 202 ] and up to 40 weeks [ 200 ]. Moreover, other markers, such as MCP-1, PAI-1 and CCL2 are increased in adipose tissue of mice on HFD for 9 weeks [ 176 ] or up to 17 weeks [ 202 ].…”

“…An overall increase of pro-inflammatory cytokines such as TNF-α, IL-6, leptin and TGFβ1 is detected in the liver of HFD-fed mice for 17 weeks [ 202 ] and up to 40 weeks [ 200 ]. Moreover, other markers, such as MCP-1, PAI-1 and CCL2 are increased in adipose tissue of mice on HFD for 9 weeks [ 176 ] or up to 17 weeks [ 202 ].…”