Inhibition of hepatic stearoyl-CoA desaturase activity by trans-10,cis-12 conjugated linoleic acid and its derivatives

Conjugated linoleic acid (CLA) has been reported to decrease stearoyl-CoA d esaturase (SCD) activity by decreasing mRNA expression. This investigation was designed to determine whether structurally related compounds of CLA hav e a direct inhibitory effect on SCD activity. Trans-10,cis-12 CLA had stron g inhibitory activity on SCD while cis-9,trans-11, and trans-9,trans-11 iso mers had no effect. Trans-10 octadecenoate was not inhibitory, whereas cis- 12 octadecenate was inhibitory, but not as effective as trans-10,cis-12 CLA . Of the oxygenated derivatives, 9-peroxy-cis/trans-10, trans-12 octadecadi enoate was a more effective inhibitor than trans-10,cis-12 CLA, whereas 9-h ydroxy-trans-10, cis-12. octadecadienoate was less effective. Interestingly , cis-11 octadecadienoate and cis-12 octadecen-10-ynoate were slightly inhi bitory. However, trans-9 and trans-11 octadecenoates, and trans-9,cis-12 oc tadecadienoate were all inactive under test condition, as were linoleate, o leate, and arachidonate. Derivatives of CLA acid modified to alcohol, amide or chloride were all inactive. A cis-12 double bond appears to be a key st ructural feature for inhibiting SCD activity, especially when coupled with a trans-10 double, whereas a cis-11 double bond is less effective. (C) 2000 Elsevier Science B.V. All rights reserved.