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 desaturase (SCD) activity by decreasing mRNA expression. This investigation was designed to determine whether structurally related compounds of CLA have a direct inhibitory effect on SCD activity. Trans-10,cis-12 CLA had strong inhibitory activity on SCD while cis-9,trans-11, and trans-9,trans-11 isomers 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 octadecadienoate was a more effective inhibitor than trans-10,cis-12 CLA, whereas 9-hydroxy-trans-10, cis-12 octadecadienoate was less effective. Interestingly, cis-11 octadecadienoate and cis-12 octadecen-10-ynoate were slightly inhibitory. However, trans-9 and trans-11 octadecenoates, and trans-9,cis-12 octadecadienoate were all inactive under test condition, as were linoleate, oleate, 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 structural feature for inhibiting SCD activity, especially when coupled with a trans-10 double, whereas a cis-11 double bond is less effective.
Park
Y
Y
Department of Food Microbiology and Toxicology, Food Research Institute, University of Wisconsin-Madison 53706, USA.
Storkson
J M
JM
Ntambi
J M
JM
Cook
M E
ME
Sih
C J
CJ
Pariza
M W
MW
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007536:Isomerism; D008041:Linoleic Acids / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008862:Microsomes, Liver / Q000201:enzymology*; D013230:Stearoyl-CoA Desaturase / Q000037:antagonists & inhibitors*
D008041:Linoleic Acids; D016718:Arachidonic Acid; D013230:Stearoyl-CoA Desaturase