Regulation of stearoyl-CoA desaturase activity by the trans-10,cis-12 isomer of conjugated linoleic acid in HepG2 cells

Stearoyl-CoA desaturase (SCD) catalyzes the rate-limiting step in the cellu lar synthesis of monounsaturated fatty acids mainly oleate (C18:1) and palm itoleate (C16:1) which are the major monounsaturated fatty acids of membran e phospholipids, cholesterol esters, waxes, and triglycerides. Several SCD isoforms exist in the mouse whereas the human has one well-characterized SC D gene. The trans-10,cis-12 isomer of conjugated linoleic acid has been pre viously shown to repress the expression of the mouse SCD1 gene isomer by de creasing SCD gene expression as well as by direct inhibition of SCD enzyme activity. We studied the regulation of human stearoyl-Coa desaturase (SCD) expression by conjugated linoleic acid (CLA) in cultured human hepatoblasto ma cell line, HepG2. Treatment of the cells with the trans-10,cis-12 CLA is omer did not cause changes in the SCD gene transcription, mRNA and protein levels. However, this isomer decreased both the SCD activity as well as the levels of monounsaturated fatty acids. The other major CLA isomer, cis-9,t rans-11 CLA, had no effect on SCD gene expression and activity. These resul ts suggest that in HepG2 cells the trans-10,cis-12 CLA isomer regulates hum an SCD activity mainly by a posttranslational mechanism. (C) 2001 Academic Press.