How different factors modify the fatty acid composition of the microsomal membrane, its physical properties, structure, and membrane bound enzymes

BRENNER, R.R.; BERNASCONI, A.M.; MONTANARO, M.A.

Turku, Finlandia

Congreso; 48th International Conference on Biociences of Lipids (ICBL); 2007

ICBL

The FA composition of the hepatic microsomal membrane may be altered by  food composition  or factors that modify the activity of enzymes like  desaturases that modulate the unsaturated FA biosynthesis. Currently, the effects of EFA deficiency, cholesterol administration, diabetes (insulin) and several nuclear receptors were compared, determining the hepatic microsomal lipidic composition, phospholipid molecular species, mRNA and activity of the microsomal SCD-1, ∆6 and ∆5 desaturases as well as the dynamic properties of the membrane measured at different depths. The mentioned factors modify the unsaturated fatty acid composition and molecular species distribution, but  in different ways and with different effects. Dietary EFA deficiency and 1% cholesterol administration similarly depress 20:4n-6 and 18:0/20:4n-6 and 16:0/20:4n-6 molecular species due in the first case to deficiency of 18:2n-6 and in the second to depression of ∆6 and ∆5 desaturases whereas 16:1 and 18:1n-9 increased in both cases due to increased SCD-1 activity and 20:3n-9 by compensatory desaturation and elongation of 18:1n-9. However, cholesterol administration  did not modify the free cholesterol percentage, but increased the cholesterol esters of microsomes, suggesting that free cholesterol was not the cause of a general membrane packing change. This would be validated if we accept it is not randomly distributed and different lipid domains exist in membranes. Diabetes  1 due to insulin absence, differently decreased both monoenoic FA and 20:4n-6/18:2 ratio due to a depression  of both SCD-1 and ∆6 and ∆5 desaturases mRNAs and activity evoking different molecular species changes. Insulin corrected these effects in a similar way to LXR, PPAR-¦Á and SREBP-1c by activation of  desaturases, modifying double bonds densities and dynamics  at different depths of the membrane, changing  properties of microsomal bound proteins.