Crocetin improves the insulin resistance induced by high-fat diet in rats.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Sheng
L
L
Department of Pharmacology, China Pharmaceutical University, Nanjing, PR China.
Qian
Z
Z
Shi
Y
Y
Yang
L
L
Xi
L
L
Zhao
B
B
Xu
X
X
Ji
H
H
D000273:Adipose Tissue / Q000187:drug effects / Q000201:enzymology; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D002338:Carotenoids / Q000494:pharmacology*; D004041:Dietary Fats; D004195:Disease Models, Animal; D050171:Dyslipidemias / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D015309:Glucose Clamp Technique; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008049:Lipase / Q000378:metabolism; D008071:Lipoprotein Lipase / Q000378:metabolism; D008074:Lipoproteins / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D010084:Oxidation-Reduction; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014280:Triglycerides / Q000097:blood; D014801:Vitamin A / Q000031:analogs & derivatives
D001786:Blood Glucose; D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D000960:Hypolipidemic Agents; D007328:Insulin; D008074:Lipoproteins; D012333:RNA, Messenger; D014280:Triglycerides; C487773:trans-sodium crocetinate; D014801:Vitamin A; D002338:Carotenoids; D002334:Carnitine O-Palmitoyltransferase; D008049:Lipase; C502353:hepatic lipase, rat; D008071:Lipoprotein Lipase