Effect of highly purified eicosapentaenoic acid ethyl ester on insulin resistance and hypertension in Dahl salt-sensitive rats.
We investigated the effect of long-term administration of highly purified eicosapentaenoic acid ethyl ester (EPA-E), an n-3 polyunsaturated fatty acid derived from fish oil, in comparison to lard on the development of hypertension and insulin resistance in Dahl salt-sensitive (Dahl-S) rats fed a high-sucrose diet (HSD), a model of salt-sensitive hypertension. After 16 weeks of treatment, the glucose infusion rate (GIR) during the euglycemic insulin-glucose clamp test significantly increased in the HSD-EPA-E group compared with the HSD-water or -lard control group. The GIR was approximately three times higher in the HSD-EPA-E group versus the HSD-water or -lard control group, and it was about 70% of the rate in the calorically deprived control group fed a low-fat-high-fiber diet (LF-HFD). In addition, EPA-E significantly suppressed the elevation of plasma glucose and insulin levels after oral glucose loading. These results indicate that EPA-E prevents the development of insulin resistance in Dahl-S rats fed a HSD. Fatty acid analysis of phospholipids in skeletal muscle showed a significant increase in C18:2, C20:5, and C22:5 components in the HSD-EPA-E group and, conversely, a significant decrease in C16:0, C20:4, and C22:6. The present results indicate that the beneficial effect of EPA-E on insulin resistance in Dahl-S rats fed a HSD is likely dependent on the modification of phospholipid components in the skeletal muscle membrane. These findings suggest that EPA-E might prevent the development of insulin resistance in dietary obesity. In addition, the HSD-EPA-E group showed a significant increase in the level of uncoupling protein (UCP) in brown adipose tissue as compared with the HSD-water or -lard control group. However, EPA-E had no effect on the development of hypertension and obesity in Dahl-S rats fed the HSD.
Mori
Y
Y
Department of Internal Medicine, National East-Utsunomiya Hospital, Tochigi, Japan.
Murakawa
Y
Y
Yokoyama
J
J
Tajima
N
N
Ikeda
Y
Y
Nobukata
H
H
Ishikawa
T
T
Shibutani
Y
Y
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure; D001835:Body Weight; D002352:Carrier Proteins / Q000378:metabolism; D002395:Catecholamines / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D018752:Diet, Fat-Restricted; D004041:Dietary Fats / Q000378:metabolism; D004435:Eating; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D005227:Fatty Acids / Q000032:analysis; D006973:Hypertension / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007473:Ion Channels; D008055:Lipids / Q000032:analysis; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D024101:Mitochondrial Proteins; D051381:Rats; D020303:Rats, Inbred Dahl; D013395:Sucrose / Q000494:pharmacology; D000071256:Uncoupling Protein 1
D001786:Blood Glucose; D002352:Carrier Proteins; D002395:Catecholamines; D004041:Dietary Fats; D005227:Fatty Acids; D007328:Insulin; D007473:Ion Channels; D008055:Lipids; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D000071256:Uncoupling Protein 1; D013395:Sucrose; C035276:eicosapentaenoic acid ethyl ester; D015118:Eicosapentaenoic Acid; C029310:lard