Nuclear receptors and hepatic lipidogenic enzyme response to a dyslipidemic sucrose-rich diet and its reversal by fish oil n-3 polyunsaturated fatty acids.

Hein GJ, Bernasconi AM, Montanaro MA, Pellon-Maison M, Finarelli G, Chicco A, Lombardo YB, Brenner RR. Nuclear receptors and hepatic lipidogenic enzyme response to a dyslipidemic sucrose-rich diet and its reversal by fish oil n-3 polyunsaturated fatty acids. Am J Physiol Endocrinol Metab 298: E429-E439, 2010. First published December 8, 2009; doi:10.1152/ajpendo.00513.2009.-A sucrose-rich diet (SRD), compared with a starch diet, induces time-dependent metabolic disorders and insulin resistance with hypertriglyceridemia, similar to type 2 diabetes. In this study, we examined the effect of SRD, after 8 mo, on nuclear receptors peroxisome proliferator-activated receptor-alpha (PPAR alpha), and liver X receptor-alpha (LXR alpha), stearoyl-CoA desaturase-1 (SCD-1), and Delta 6 and Delta 5 desaturases mRNA and activity, hepatic enzymes involved in lipid metabolism, and fatty acid (FA) composition as well as the reversal produced by cod liver oil. SRD induced triglyceride increase in plasma and liver, increasing the anabolic FA synthase, malic enzyme, and glucose-6-phosphate dehydrogenase, but not the prooxidative enzymes FA oxidase and carnitine palmitoyltransferase I, and correspondingly decreased PPAR alpha and increased LXR alpha expressions. Results suggest a contribution of both nuclear receptors' interaction on these enzymatic activities. SRD depressed SCD-1 without altering oleic acid proportion and increased Delta 6 and Delta 5 desaturases and the proportion of n-6 arachidonic acid. Therefore, the data do not support that SRD hypertriglyceridemia is produced by increased SCD-1-dependent oleic acid biosynthesis. The administration of 7% cod liver oil for 2 mo depressed LXR alpha, enhancing PPAR alpha in control and SRD-fed rats, reversing the activity of the hepatic enzymes involved in lipid metabolism and therefore the hyperlipidemia produced by the SRD. Fish oil increased n-3 PUFA and depressed n-6 PUFA of liver lipids without altering the 18:1/18: 0 ratio, suggesting that its effects were produced mainly by competition of dietary n-6 and n-3 FA and not through desaturase activity modification.