Mechanisms of desaturases modulation in diabetes: interactions of nuclear receptors, hormones, and other factors

MONTANARO, MA; BERNASCONI, AM; FINARELLI, GS; HERNÁNDEZ, LE; PELLON-MAISON M,; BRENNER, RR

LIPIDS

AOCS Press

Lugar: Champaign; Año: 2008

0024-4201

TRABAJO EN REVISION D9, D6 y D5 desaturases catlyze reactions that modulate the biosynthesis of unsaturated fatty acids in the endoplasmic reticulum, being it regulated by diet composition, hormones and other factors. Currently, we investigated specially the function and interaction of liver X receptor (LXR), peroxisome proliferator activated receptor-a (PPAR-a) and insulin in the streptozotocin diabetic rat. LXR-a and PPAR-a were activated in vivo by administration of agonists T0901317 and fenofibrate, respectively. After nine days of xenobiotics administration, mRNA expression, and enzymatic activity of desaturases as well as the fatty acid composition of liver lipids were measured. It was shown that both receptors increased the desaturases mRNA level and activity through insulin-dependent and –independent machanisms. However, LXR and PPAR-a compete between them and this competition was recognized to happen in the presence or absence of insulin. It was apparently the consequence that both required their heterodimerization with RXR to become active messengers for the desaturases DNA expresssion. A high cooperation was found between LXR and insuli, even in the presence of PPAR-a. Stearoyl-CoA desaturase-1 response was higher than that of D6 and D5 desaturases. The high increase of the mRNAs was not equivalently evoked on the enzymes activity. The reasons of this effects are discussed considering the estructuration of the membrane bound desaturating systems and an overview of factors, interactions and events in desaturases regulation is also given. The changes of liver lipids composition mainly shown in this short period were on the oleic/stearic ratio.