trans-sodium-crocetinate and Dyslipidemias

The amelioration of insulin resistance by treatment with crocetin is closely related to the hypolipidaemic effect. The present study is designed to clarify the insulin-sensitizing mechanism of crocetin by elucidating the mechanism of regulation of lipid metabolism by crocetin.. Rats given a high-fat diet were treated with crocetin for 6 weeks before hyperinsulinaemic-euglycaemic clamp. 14C-palmitate was used as tracer to track the fate of non-esterified fatty acids or as substrate to measure beta-oxidation rate. Triglyceride clearance in plasma and lipoprotein lipase activity in tissues were tested. Content of lipids in plasma and tissues was determined. Real-time PCR was used to assay the level of mRNA from genes involved in non-esterified fatty acid and triglyceride uptake and oxidation.. Crocetin prevented high-fat-diet induced insulin resistance (increased clamp glucose infusion rate), raised hepatic non-esterified fatty acid uptake and oxidation, accelerated triglyceride clearance in plasma, enhanced lipoprotein lipase activity in liver, and reduced the accumulation of detrimental lipids (DAG and long-chain acyl CoA) in liver and muscle. Genes involved in hepatic lipid metabolism which are regulated by peroxisome proliferator-activated receptor-alpha, were modulated to accelerate lipid uptake and oxidation.. Through regulating genes involved in lipid metabolism, crocetin accelerated hepatic uptake and oxidation of non-esterified fatty acid and triglyceride, and reduced lipid availability to muscle, thus decreasing lipid accumulation in muscle and liver, and consequently improving sensitivity to insulin.

Topics: Adipose Tissue; Animals; Blood Glucose; Carnitine O-Palmitoyltransferase; Carotenoids; Dietary Fats; Disease Models, Animal; Dyslipidemias; Fatty Acids, Nonesterified; Glucose Clamp Technique; Hypolipidemic Agents; Insulin; Insulin Resistance; Lipase; Lipoprotein Lipase; Lipoproteins; Liver; Male; Muscle, Skeletal; Oxidation-Reduction; Polymerase Chain Reaction; Rats; Rats, Wistar; RNA, Messenger; Time Factors; Triglycerides; Vitamin A