NUCLEAR RECEPTORS AND HEPATIC LIPIDOGENIC ENZYMES RESPONSE TO A DYSLIPIDEMIC SUCROSE RICH DIET AND ITS REVERTION BY FISH OIL N-3 POLYUNSATURATED FATTY ACIDS

HEIN, GJ; BERNASCONI, AM; MONTANARO, MA; PELLON-MAISON M; FINARELLI, GS; CHICCO, A; LOMBARDO, YB; BRENNER, RR

AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM

AMER PHYSIOLOGICAL SOC

Año: 2010 vol. 298 p. 429 - 439

0193-1849

A sucrose- rich diet (SRD) compared to a starch diet, induces time-dependent metabolic disorders and insulin resistance with hypertriglyceridemia, similar to diabetes type 2. In this study we examined the effect of SRD, after 8 months, on nuclear receptors, peroxisome-proliferator activated receptor-á (PPAR-á), and liver X receptor-á (LXR-á), stearoyl-CoA desaturase-1 (SCD-1), Ä6, and Ä5 desaturases mRNA and activity, hepatic enzymes involved in lipid metabolism, and fatty acid (FA) composition as well as the revertion produced by cod liver oil. SRD induced triglycerides increase in plasma and liver, increasing the anabolic FA synthase, malic enzyme and glucose 6-phosphate dehydrogenase, but not the pro-oxidative enzymes FA oxydase and carnitine palmitoyl transferase I, and correspondingly decreased PPAR-á and increased LXR-á expressions. Results suggest a contribution of both nuclear receptors interaction on these enzymatic activities. SRD depressed stearoyl-CoA desaturase -1 (SCD-1) without altering oleic acid proportion and increased Ä6 and Ä5 desaturases, and the proportion of n-6 arachidonic acid. Therefore, 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 two months depressed LXR-á, enhancing PPAR-á in control and SRD fed rats, reverting 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 18:1/18:0 ratio suggesting that its effects were mainly produced by competition of dietary n-6 and n-3 FA and not through desaturase activity modification.