Ethyl all-cis-5,8,11,14,17-icosapentaenoate modifies the biochemical properties of rat very low-density lipoprotein.
The biochemical properties of serum very low-density lipoprotein (VLDL) were investigated in rats given highly purified all-cis-5,8,11,14,17-icosapentaenoate (EPA), an ethyl-ester derivative (EPA-E). The elution time (gel filtration) of VLDL from EPA-E-treated serum was increased significantly compared with that of the control. EPA-E-treated VLDL isolated by ultracentrifugation exhibited a marked decrease in triglyceride content with a relative increase in cholesterol. In treated VLDL, a significant increase in the ratio of apo E/apo C was observed. There was a remarkable increase in the content of EPA in all the fractions of phospholipids, cholesteryl esters and triglycerides after EPA-E treatment, resulting in n-3 polyunsaturated fatty acid-rich VLDL. EPA-E also reduced the incorporation of [14C]oleate into triglycerides in hepatic microsomes and the rate of hepatic triglyceride secretion. Moreover, lipoprotein lipase activity in heparin-injected plasma was increased in rats given EPA-E without there being an effect on hepatic triglyceride lipase activity. These findings indicate that EPA-E exerts an inhibitory effect on hepatic triglyceride synthesis/secretion and a stimulatory effect on triglyceride degradation, resulting in a reduction in particle size and an increase in the ratio of apo E/apo C. Triglyceride-poor and EPA-rich VLDL may rapidly be converted into the density of intermediate low-density lipoprotein and low-density lipoprotein and/or may be absorbed into the liver rapidly.
Fuji Central Research Laboratory, Mochida Pharmaceutical Co., Ltd., Gotemba, Japan.
K
K
Mizuguchi
T
T
Yano
M
M
Ishibashi
A
A
Masada
M
M
Mizota
Y
Y
Saito
D000818:Animals; D001053:Apolipoproteins / Q000032:analysis; D002851:Chromatography, High Pressure Liquid; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism; D008049:Lipase / Q000187:drug effects / Q000378:metabolism; D008071:Lipoprotein Lipase / Q000097:blood / Q000187:drug effects; D008079:Lipoproteins, VLDL / Q000097:blood / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000096:biosynthesis / Q000378:metabolism
D001053:Apolipoproteins; D005227:Fatty Acids; D008079:Lipoproteins, VLDL; D014280:Triglycerides; C035276:eicosapentaenoic acid ethyl ester; D015118:Eicosapentaenoic Acid; D008049:Lipase; D008071:Lipoprotein Lipase