Effect of HFD/STZ on expression of genes involved in lipid, cholesterol and glucose metabolism in rats

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• 作者：Luisa Pozzo^a ; Andrea Vornoli^a ; ¹ ; Ilaria Coppola^a ; Clara Maria Della Croce^a ; Lucia Giorgetti^a ; Pier Giovanni Gervasi^a ; Vincenzo Longo^a ; ^{v.longo@ibba.cnr.it" class="auth_mail" title="E-mail the corresponding author}
• 关键词：HFD/STZ rat model ; Lipid ; Cholesterol and glucose metabolism ; Bile acid transporters ; Inflammation ; Mitochondrial and endoplasmic reticulum oxidative stress
• 刊名：Life Sciences
• 出版年：2016
• 出版时间：1 December 2016
• 年：2016
• 卷：166
• 期：Complete
• 页码：149-156
• 全文大小：1109 K

文摘

Aims: The aim of the study was to evaluate lipid, cholesterol and glucose metabolism in a novel rat model of non-alcoholic fatty liver disease (NAFLD).

Main methods: Rats (Wistar) were fed high fat/cholesterol diet (HFD) and a single low dose (35 mg/kg) of streptozotocin (STZ). Collagen and glycogen content, oxidative stress and glucokinase activity were measured using biochemical assays. Other metabolic pathways were assessed by qRT-PCR.

Key findings: HFD/STZ treated rats, compared to control ones, showed an increase in expression of biomarkers of inflammation (TNFα, IL6), fibrosis (TGFβ), mitochondrial stress (UCP2) and oxidative stress (GSH and carbonylated proteins) but not of ER stress (CHOP, XBP1). Additionally, HFD/STZ treatment caused a reduction in glycogen content, glucokinase activity (a limiting step in glycolysis) and expression of ChREBP gene (a de novo lipogenesis regulator), suggesting a modified glycolytic pathway.

The cholesterol biosynthesis in HFD/STZ treated rats was inhibited (reduced expression of SREBP-2-regulated HMGCoA red and LDLr), instead the cholesterol catabolism was increased, as shown by the mRNA induction of the CYP7A1 and CYP8B1 (key genes for BA acid).

A reduced gene expression of FXR-dependent SHP (a key gene for feedback inhibition of CYP7A1 and CYP8B1) and of bile acids (NTCP, OATP1A1, BSEP) and cholesterol (ABCA1) transporters was found.

Significance: These results widely extend the characterization of HFD/STZ rat model, which might mimic the NAFLD/NASH in diabetic humans.