Interactions of LXR, Insulin and PPAR-¨¢ in unsaturated fatty acid biosynthesis

RR BRENNER; MA MONTANARO; MS GONZ¨¢LEZ; AM BERNASCONI

Cairns, Australia

Congreso; 7th Congress of ISSFAL (International Society for the Study of Fatty Acids and Lipids) and 6th International Congress on Essential Fatty Acids and Eicosanoids and PUFA in Maternal and Infant Health; 2006

ISSFAL

INTERACTIONS OF LXR, INSULIN AND PPAR-¦Á IN UNSATURATED FATTY ACID BIOSYNTHESIS RR Brenner, MA Montanaro, MS Gonz¨¢lez, AM Bernasconi Instituto de Investigaciones Bioqu¨ªmicas de La Plata (UMLP-CONICET), Facultad de Ciencias M¨¦dicas, La Plata, Argentina   Background ¨C Unsaturated fatty acids (FA) biosynthesis may be modulated in vivo by, insulin, sterol responsive element binding protein (SREBP-1c), peroxisome proliferator activating receptors (PPARs), liver X receptor (LXR), hormones and dietary components. Objective ¨C To recognize mutual interaction in the modulation of desaturases and FA biosynthesis. Design ¨C Normal and streptozotocin diabetic rats were treated with insulin, T091317 (10 mg/kg weight for 6 days) agonist of LXR (provided by AMGEN) and fenofibrate (100 mg/kg weight for 6 days) agonist of PPAR-¦Á. Blood parameters, liver FA composition, ¦¤6, ¦¤5 and ¦¤9 desaturases mRNAs and enzymatic activity, palmitoil-CoA chain elongase and extramitochondrial acyl-CoA oxidase, were measured. Outcome - In control rats LXR activation did not modify the glycemia, trigliceridemia, insulinemia, NEFA and cholesterolemia, but PPAR-¦Á increased the insulinemia and the simultaneous activation of LXR maintained this hyperinsulinemia, but decreased the cholesterolemia. The typical values of diabetic rat parameters were not modified by T09, but T09 combined with insulin enhanced 8 fold the triglyceridemia. T09 increased liver SCD-1 and ¦¤6 and ¦¤5 desaturases mRNA in control and diabetic rats, but in diabetic rats insulina administration together with T09 shot up a ¡À 5 fold increase in the desaturasas mRNA expression, even higher than that evoked by insulin or T09 alone. These changes modified specifically the lipid FA composition in liver. Conclusion - LXR, insulin, SREBP-1c and PPAR-¦Á interact strongly in FA desaturasas mRNA and enzymatic activity modulation that regulates the unsaturated fatty acid biosynthesis.