Coagonist of GLP-1 and glucagon decreases liver inflammation and atherosclerosis in dyslipidemic condition

Publication date: Available online 8 January 2018 Source:Chemico-Biological Interactions Author(s): Vishal Patel, Amit Joharapurkar, Samadhan Kshirsagar, Brijesh Sutariya, Maulik Patel, Dhreerendra Pandey, Hiren Patel, Ramchandra Ranvir, Shekhar Kadam, Dipam Patel, Rajesh Bahekar, Mukul Jain Dyslipidemia enhances progression of atherosclerosis. Coagonist of GLP-1 and glucagon are under clinical investigation for the treatment of obesity and diabetes. Earlier, we have observed that coagonist reduced circulating and hepatic lipids, independent of its anorexic effects. Here, we investigated the role of coagonist of GLP-1 and glucagon receptors in complications of diet-induced dyslipidemia in hamsters and humanized double transgenic mice. Hamsters fed on high fat high cholesterol diet were treated for 8 weeks with coagonist of GLP-1 and glucagon receptors (75 and 150 μg/kg). Pair-fed control was maintained. Cholesterol fed transgenic mice overexpressing hApoB100 and hCETP with coagonist (300 μg/kg) for 4 weeks. After the completion of treatment, biochemical estimations were done. Coagonist treatment reduced triglycerides in plasma, liver and aorta, plasma cholesterol and hepatic triglyceride secretion rate. Expressions of HMG-CoA reductase and SBREBP-1C were reduced and expressions of LDLR, CYP7A1, ABCA1 and ABCB11 were increased in liver, due to coagonist treatment. Coagonist treatment increased bile flow rate and biliary cholesterol excretion. IL-6 and TNF-Î...
Source: Chemico Biological Interactions - Category: Biochemistry Source Type: research