What is the influence of complement factor C3 and lipid metabolism of adipose tissue on hepatic steatosis in mice?

Abstract

NALFD (non-alcoholic fatty liver disease) represents a fatty liver whereby lipid accumulation (steatosis) occurs. In recent decades, the prevalence of NAFLD has dramatically increased. Activation of the complement system, which is an important subset of the immune system, and especially complement factor C3, may have a significant role in the progression of NAFLD. In this study is examined if there are, next to alterations in hepatic lipid metabolism, also alterations present in the lipid metabolism of adipose tissue. It appears that acylation stimulating protein (ASP) has an important role in linking the activation of complement and lipid metabolism of adipose tissue in NAFLD. In this study the following research question is stated: What is the influence of complement factor C3 and the lipid metabolism of adipose tissue on hepatic steatosis in mice? It is expected that wild type mice on a HFD diet will show the highest hepatic lipid accumulation. Furthermore the expression of some enzymes involved in lipid metabolism will be altered. Liver and adipose tissue from C3+/+ (n=17) and C3-/- (n=17) mice is used. The control group (n=12) received a chow diet and the experimental group (n=22) a high fat diet (HFD). The hepatic lipid accumulation and the expression of some enzymes, involved in the lipid metabolism of adipose tissue, are determined in these mice. The results, showed no significant differences in lipid accumulation between both mouse groups. The expression levels of the enzymes FASN, SCD1, PPARγ and DGAT1 were significantly different between the diets in one or both mouse groups. The expression of the enzymes HSL and DGAT1 were significantly higher in the C3+/+ mice compared to the C3-/- mice. It can be concluded from histological stainings and preliminary scoring results that hepatic lipid accumulation occurs the most in C3+/+ mice on a HFD. However it seems that lipids do not only accumulate by C3 activation, but also other mechanisms seems to play a role. It is assumed that in C3-/- mice the ASP pathway is disturbed, which will lead to an increased flux of fatty acids to the liver. In C3+/+ mice there is a higher adipose tissue lipolysis and lipogenesis present since the expression of HSL and DGAT were increased.