Comparative effect of Fenofibrate on the Biosynthesis of Unsaturated Fatty Acids in Diabetic and Non-Diabetic Rats

BRENNER, RR; GONZALEZ, MS; BERNASCONI, AM; MONTANARO MA

Ioannina, Grecia

Congreso; 45th International Conference on the Bioscience of Lipids (ICBL); 2004

ICBL

Comparative effect of Fenofobrate on the Biosynthesis of Unsaturated Fatty Acids in Diabetic and Non-Diabetic Rats. Brenner, RR, Gonzalez, MS, Bernasconi, AM and Montanaro MA INIBIOLP (CONICET), La Plata, Argentina. Insulin dependent Diabetes Mellitus down regulates enzimatic actuvities and mRNAs of liver desaturases. Moreover, the increased supply of fattu acids to liver in diabetic state stimulates the expression of PPAR-a and its target genes. IN addition PPAR-a induces activation of fatty acid desaturases. Curently, we are investigating the effect of fenofibrate, a peroxisome-proliferator ligand of PPAR-a and activator of fatty acis desaturases on estreptozotocin diabetic and non-diabetic rats. Fenofibrate (100mg/kg/day) was force fed for nine days. The results show that fenofibrate does not modify the glycemia of controls, but over increases it in diabetic animals. IN liver, the mRNAs and enzymatic activities of SCD-1, isoform of D9 desaturase, and D6 and D5 desaturases, were significantly activated in control, but not in diabetic animals. Moreover, fenofibrate increases significantly the 20:4n-6/18:2n-6 ratio and decreases 22:6n-3 in total liver homogenate and microsomal lipids. However, no significat change was detected in the same lipids of diabetic rats treated with fenofibrate. No effect was observed in kidney lipid composition. These results that show that fenofibrate modifies unsaturated fatty acid biosyinthesis in control, but not in streptozotocin animals, suggest that the already activated PPAR-a in diabetic rats, evoked by the increase of free fatty acids, blocks a further activation by fenofibrate.