Non-alcoholic fatty liver disease (
NAFLD) is considered a hepatic manifestation of
metabolic syndrome, which is known to be associated with
insulin resistance (IR).
NAFLD occurs when the rate of hepatic
fatty acid uptake from plasma and de novo
fatty acid synthesis is greater than the rate of
fatty acid oxidation and excretion as
very low-density lipoprotein (VLDL). To estimate the effects of IR on hepatic
lipid excretion,
mRNA expression levels of genes involved in VLDL assembly were analyzed in
NAFLD liver. Twenty-two histologically proven
NAFLD patients and 10 healthy control subjects were enrolled in this study.
mRNA was extracted from liver biopsy samples and real-time PCR was performed to quantify the expression levels of
apolipoprotein B (
apoB),
microsomal triglyceride transfer protein (MTP) and
liver fatty-acid binding protein (L-FABP). Hepatic expression levels of the genes were compared between
NAFLD patients and control subjects. In
NAFLD patients, we also examined correlations between expression levels of the genes and metabolic factors, including IR, and the extent of
obesity and hepatic
lipid accumulation. Hepatic expression levels of
apoB, MTP and L-FABP were significantly up-regulated in
NAFLD patients compared to control subjects. The expression levels of MTP were correlated with those of
apoB, but not with those of L-FABP. In the
NAFLD liver, the expression levels of MTP were significantly reduced in patients with HOMA-IR >2.5. In addition, a significant reduction in MTP expression was observed in livers with advanced steatosis. Enhanced expression of genes involved in VLDL assembly may be promoted to release excess
lipid from
NAFLD livers. However, the progression of IR and hepatic steatosis may attenuate this compensatory process.