title: Effects of insulin resistance and hepatic lipid accumulation on hepatic mRNA expression levels of apoB, MTP and L-FABP in non-alcoholic fatty liver disease.
abstract: 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.
authors.affiliation: Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582;
authors.forename: Nobito
authors.initials: N
authors.lastname: Higuchi
authors.forename: Masaki
authors.initials: M
authors.lastname: Kato
authors.forename: Masatake
authors.initials: M
authors.lastname: Tanaka
authors.forename: Masayuki
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Takao
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Kohjima
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kotoh
authors.forename: Munechika
authors.initials: M
authors.lastname: Enjoji
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakamuta
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Takayanagi