Stearoyl-CoA desaturase (SCD) is a regulatory
enzyme in lipogenesis, catalyzing the rate-limiting step in the overall de novo synthesis of monounsaturated FA, mainly
oleate and
palmitoleate from stearoyl- and
palmitoyl-CoA, respectively.
Oleate and
palmitoleate are the major monounsaturated FA of membrane
phospholipids, TG, wax
esters, cholesterol esters, and alkyldiacylglycerol. Several SCD gene
isoforms (SCD1, SCD2, SCD3, and SCD4) exist in mice, and two have been characterized in humans. SCD1 gene expression in liver cells is regulated by numerous stimuli including diet and
hormones. We are interested in why SCD is such a highly regulated
enzyme even though
oleate, the major product of this
enzyme, is one of the most abundant FA in the diet and is therefore readily available. Dietary
oleate is also well known for its TG-lowering effects and, as a major component of
olive oil, is expected to have beneficial effects. However, high SCD activity has been implicated in diabetes,
obesity,
atherosclerosis, and
cancer in several animal models; therefore, the role that de novo
oleate plays in these disease states has to be carefully evaluated. By using SCD1-/- mice, which are deficient in tissue
oleate, we begin to learn more about the physiological role of SCD gene expression and
oleate in normal and disease states.