Silymarin ameliorates fructose induced insulin resistance syndrome by reducing de novo hepatic lipogenesis in the rat

详细信息    查看全文

• 作者：Prem Prakash ; Vishal Singh ; Manish Jain ; Minakshi Rana ; Vivek Khanna ; Manoj Kumar Barthwal ; Madhu Dikshit ; ^{madhu_dikshit@cdri.res.in" class="auth_mail} ; ^{madhudikshit@yahoo.com" class="auth_mail}
• 关键词：Fructose diet ; Hepatic de novo lipogenesis ; Fatty liver diseases ; Insulin resistance syndrome ; Myocardial ischemia reperfusion injury ; Silymarin
• 刊名：European Journal of Pharmacology
• 出版年：15 March, 2014
• 年：2014
• 卷：727
• 期：Complete
• 页码：15-28
• 全文大小：4152 K

文摘

High dietary fructose causes insulin resistance syndrome (IRS), primarily due to simultaneous induction of genes involved in glucose, lipid and mitochondrial oxidative metabolism. The present study evaluates effect of a hepatoprotective agent, silymarin (SYM) on fructose-induced metabolic abnormalities in the rat and also assessed the associated thrombotic complications. Wistar rats were kept on high fructose (HFr) diet throughout the 12-week study duration (9 weeks of HFr feeding and subsequently 3 weeks of HFr plus SYM oral administration [once daily]). SYM treatment significantly reduced the HFr diet-induced increase expression of peroxisome proliferator-activated receptor gamma coactivator (PGC)-1伪/尾, peroxisome proliferator-activated receptor (PPAR)-伪, forkhead box protein O1 (FOXO1), sterol regulatory element binding protein (SREBP)-1c, liver X receptor (LXR)-尾, fatty acid synthase (FAS) and PPAR纬 genes in rat liver. SYM also reduced HFr diet mediated increase in plasma triglycerides (TG), non-esterified fatty acids (NEFA), uric acid, malondialdehyde (MDA), total nitrite and pro-inflammatory cytokines (C-reactive protein [CRP], interleukin-6 [IL-6], interferon-gamma [IFN-纬] and tumor necrosis factor [TNF]) levels. Moreover, SYM ameliorated HFr diet induced reduction in glucose utilization and endothelial dysfunction. Additionally, SYM significantly reduced platelet activation (adhesion and aggregation), prolonged ferric chloride-induced blood vessel occlusion time and protected against exacerbated myocardial ischemia reperfusion (MI-RP) injury. SYM treatment prevented HFr induced mRNA expression of hepatic PGC-1伪/尾 and also its target transcription factors which was accompanied with recovery in insulin sensitivity and reduced propensity towards thrombotic complications and aggravated MI-RP injury.