Modulation of the hypolipidemic effect of fish oil by inhibition of adipose tissue lipolysis with acipimox, a nicotinic acid analog.
To assess the possible benefits of combined hypolipidemic therapy (acipimox+marine fish oil) on lipid and lipoprotein metabolism, male Wistar rats were fed for 14 days a high sucrose diet (70 cal% sucrose) alone or a high sucrose diet supplemented with acipimox (0.2 g/100 g diet) and/or fish oil (1 ml orally daily; 30 wt% of n-3 PUFA). Feeding a high sucrose diet increased (control: 61 +/- 6 vs HS: 110 +/- 8 nmol.min-1.mg-1, p < 0.001) the activity of acetyl CoA carboxylase in the liver, this was normalized by fish oil but not acipimox alone (HS+FO: 68 +/- 4; HS+ACI: 95 +/- 4; HS+ACI+FO: 71 +/- 2 nmol.min-1.mg-1). Increased triglyceride concentration in serum and muscle tissue (m. soleus and heart) of high sucrose-fed animals was suppressed equally by fish oil, acipimox, and/or both. The cholesterol-lowering effect of fish oil was also present in the liver (p < 0.005). The cholesterol-lowering action of acipimox was accompanied by the accumulation of cholesterol in the liver (p < 0.005), whereas the combination of acipimox+fish oil did not change the liver cholesterol content. After fish oil the LDL binding capacity of liver plasma membranes was increased 1.6-fold (p < 0.001). LDL receptor activity was significantly decreased in HS+ACI group (p < 0.05), but remained unchanged in HS+FO+ACI-fed animals. In summary, (a) the hypotriglyceridemic effect of fish oil in high sucrose-induced HTG is due to its inhibitory effects at the level of fatty acid synthesis; (b) decreased triglyceride production and output from the liver prevent triglyceride accumulation in muscle tissue; (c) the cholesterol-lowering action of acipimox but not fish oil was accompanied by an accumulation of cholesterol in the liver; (d) the latter phenomenon may be due to the opposite effects of both drugs on cholesterol catabolism via hepatic LDL receptors.
Seböková
E
E
Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava.
Klimes
I
I
Hermann
M
M
Minchenko
A
A
Mitková
A
A
Hromadová
M
M
D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage / Q000494:pharmacology*; D004435:Eating; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005395:Fish Oils / Q000008:administration & dosage / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood*; D008066:Lipolysis / Q000187:drug effects*; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008297:Male; D011719:Pyrazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011973:Receptors, LDL / Q000378:metabolism; D013395:Sucrose / Q000008:administration & dosage; D014280:Triglycerides / Q000097:blood / Q000378:metabolism
D001786:Blood Glucose; D004042:Dietary Fats, Unsaturated; D005230:Fatty Acids, Nonesterified; D005395:Fish Oils; D007328:Insulin; D008055:Lipids; D011719:Pyrazines; D011973:Receptors, LDL; D014280:Triglycerides; D013395:Sucrose; D002784:Cholesterol; D000103:Acetyl-CoA Carboxylase; C027696:acipimox