It is indefinite whether
nonalcoholic steatohepatitis (NASH) results as by-product from general metabolic perturbations and
adipokine dysregulations or whether defined dietary factors also play a pathogenetic role. Here, we examine the effects of a modification of dietary
lipids in a NASH inducing diet on metabolic changes as well as hepatic steatosis,
inflammation, and
fibrosis in rats. Male Wistar rats were fed with variations of the atherogenic diet (AD), which induces pathophysiological changes resembling human NASH. Dietary variants (AD without
cholesterol,
cholate, or
choline; change of neutral fat to
olive oil or
coconut oil) were fed for 8 weeks.
Insulin resistance,
adipokine profile, liver histology, and
lipid content as well as expression of proinflammatory and profibrogenic genes were examined. AD led to clear signs of hepatic steatosis and
inflammation together with an increase in TNF and
collagen type 1 expression. AD without
cholesterol showed markedly less liver damage without changes of
insulin action and
adipokine profile. AD with
olive oil and AD without
cholate clearly attenuated hepatic
inflammation, whereas fat deposition and features of the
metabolic syndrome were increased in these animals.
Insulin resistance and hepatic fat deposition per se do not cause significant hepatic
inflammation in this rodent model. However,
dietary cholesterol is an important causal agent for the development of NASH.
Olive oil plays a protective role in this respect, which might be due to the high content of
monounsaturated fatty acids.