Cannabinoid receptor type 1 (CB1) antagonist, SR141716 suppresses hepatic CPT1 gene expression in rat

Abstract

SRI 41716 is the antagonist of Cannabinoid Receptor type 1 (CB1). The study was conducted to investigate the effects of SR141716 on body weight gain, body fat, hepatic fat deposit and Carnitine Palmitoyltransferase 1 (CPT1) expression in obese Sprague-Dawley (SD) rats induced by High Fat Diet (HFD). Twenty four SD rats were randomly allocated to three groups: the Normal Diet (ND) as control group, the High Fat Diet (HFD) and SR141716 treated HFD-diet (SFD) animals as experimental groups. Plasma was collected immediately for following plasma indexes determination. Liver samples were flash frozen in lipid nitrogen and stored at -80°C until use for following experiments. Compared with the ND group, HFD significantly increased the body weight gain (p<0.05), total viscera fat pad (p<0.05) and hepatic Triglyceride (TG) (p<0.05) in rats while SR141716 significantly suppressed these effects (p<0.05). Furthermore, hepatic CPT1 mRNA level was significant decreased by HFD (p<0.05). Hepatic CPT1 and PPARy mRNA level were significantly suppressed by SRI 41716 accompany with CB1 mRNA expression decrease (p<0.05). The results indicated that SR141716 can significantly suppress the excess hepatic adipose deposit induced by HFD in rats. During this process, the pivotal role of CB1 in hepatic fat deposit may considerably to a large extent be due to modulation of CPT1 expression through PPARy. However, the accurate mechanism remains to be elucidated in the future. © Medwell Journals, 2012.