Effect of n-3 fatty acids on the key enzymes involved in cholesterol and triglyceride turnover in rat liver.
The effect of long-chain n-3 fatty acids on hepatic key enzymes of cholesterol metabolism and triglyceride biosynthesis was investigated in two rat models. In the first model, rats were intravenously infused for two weeks with a fat emulsion containing 20% of triglycerides in which either n-6 or n-3 fatty acids predominated. The treatment with n-3 fatty acids led to a reduction primarily of serum cholesterol (45%), but also of serum triglycerides (18%). HMG-CoA reductase activity and cholesterol 7 alpha-hydroxylase activity were reduced by 45% and 36%, respectively. There were no significant effects on diacylglycerol acyltransferase (DGAT) or phosphatidate phosphohydrolase (PAP) activities. In the second model, rats were fed a diet enriched with sucrose, coconut oil and either sunflower oil (n-6 fatty acids) or fish oil (long-chain n-3 fatty acid ethyl esters). The treatment with n-3 fatty acids decreased serum triglycerides (41%) and, to a lesser extent, serum cholesterol (17%). Neither glycerol 3-phosphate acyltransferase (GPAT) or DGAT were affected by n-3 fatty acids. In contrast, PAP activity was reduced by 26%. HMG-CoA reductase was not significantly affected, whereas cholesterol 7 alpha-hydroxylase activity was reduced by 36%. The results indicate that part of the TG-lowering effect of long-chain n-3 fatty acids may be mediated by inhibition of the soluble phosphatidate phosphohydrolase. The effect on serum cholesterol may be partly due to inhibition of HMG-CoA reductase.
al-Shurbaji
A
A
Department of Clinical Chemistry, Karolinska Institute Huddinge University Hospital, Sweden.
Larsson-Backström
C
C
Berglund
L
L
Eggertsen
G
G
Björkhem
I
I
D000217:Acyltransferases / Q000378:metabolism; D000818:Animals; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism*; D000074263:Coconut Oil; D051048:Diacylglycerol O-Acyltransferase; D004041:Dietary Fats / Q000494:pharmacology*; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005395:Fish Oils / Q000494:pharmacology*; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D010711:Phosphatidate Phosphatase / Q000378:metabolism; D010938:Plant Oils / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013024:Soybean Oil / Q000494:pharmacology*; D000074242:Sunflower Oil; D014280:Triglycerides / Q000097:blood / Q000378:metabolism*
D004041:Dietary Fats; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D010938:Plant Oils; D000074242:Sunflower Oil; D014280:Triglycerides; D013024:Soybean Oil; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D002790:Cholesterol 7-alpha-Hydroxylase; D000217:Acyltransferases; D051048:Diacylglycerol O-Acyltransferase; D010711:Phosphatidate Phosphatase; D000074263:Coconut Oil