Abstract
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.
Key words
nonalcoholic steatohepatitis - atherogenic diet - insulin resistance
