Modulation of Unsaturated Fatty Acid Biosynthesis by Insulin and Nuclear Transcription Factors

MONTANARO MA; GONZÁLEZ MS; BERNASCONI AM; BRENNER RR

Rosario, Argentina

Congreso; 42 Reunión Anual de SAIB; 2006

Sociedad Argentina de Investigación Bioquímica y Biología Molecular

Monoenoic and polyenoic fatty acids play leading roles in human and animal physiology. Their biosynthesis is mainly regulated by D9, D6 and D5 desaturases. Currently, we are investigating the crucial roles played by the interaction of insulin, SREBP-1c, PPAR-a, LXR and RXR in the transcription and activity of the three desaturases in the rat liver. Normal and streptozotocin diabetic rats were investigated. The modification of blood parameters: insulinemia, glycemia, triglyceridemia and cholesterolemia was measured as well as hepatic mRNAs and enzymatic activity of the desaturases and liver fatty acid composition before and after treatment with LXR agonist T0901317 (for 6 days) and PPAR-a agonist fenofibrate (for 9 days). It was found that PPAR-a activated insulin secretion in the normal animal and LXR did not modify this effect. Besides, PPAR-a and LXR activated the three desaturases mRNAs and activity. In the diabetic rats insulin and LXR showed a strong interaction that led to a many fold increase of the desaturases mRNAs, apparently through a cooperative effect on nuclear SREBP-1c increase. However, little variation was shown in this short-time experiment on liver fatty acid composition except for 18:1/18:0 ratio.