We previously studied
fatty acid metabolism in the liver of
nonalcoholic fatty liver disease (
NAFLD) and reported the activation of the LXRalpha-SREBP-1c pathway in hepatocytes. LXRalpha regulates
cholesterol metabolism as well as
fatty acid metabolism, and its agonistic
ligands are
oxysterols. Moreover, there is some evidence that excess
cholesterol intake is involved in the onset of
NAFLD. Therefore, in this study, we examined the expression of
cholesterol metabolism-associated genes in the
NAFLD liver by real-time PCR. Expression of LXRalpha and ACAT1 was up-regulated in
NAFLD and this was more noticeable in non-obese rather than in obese patients. Although the expression of the
LDL receptor, which acts on
cholesterol uptake, and of SREBP-2, a positive key regulator of
cholesterol, was suppressed, the expression of
enzymes that promote
cholesterol synthesis was uniformly increased in
NAFLD. Gene expression of apoB100 and
microsomal triglyceride transfer protein, which are associated with VLDL secretion, and ABCG5, which is involved in
cholesterol excretion, was significantly elevated in
NAFLD. Because
cholesterol accumulates in hepatocytes in
NAFLD liver,
cholesterol uptake and synthesis should be physiologically down-regulated. However,
cholesterol synthesis was activated in
NAFLD liver, meaning that
cholesterol metabolism is dysregulated in
NAFLD. Overproduction of
cholesterol may lead to an increased level of
oxysterols, activation of LXRalpha and
SREBP-1c, and enhanced
fatty acid synthesis.