Oleoyl-CoA Is the Major de NovoProduct of Stearoyl-CoA Desaturase 1 Gene Isoform and Substrate for the Biosynthesis of the Harderian Gland 1-Alkyl-2,3-diacylglycerol

Abstract

1-Alkyl-2,3-diacylglycerol (ADG) is a unique neutral lipid found in the eyeball-associated Harderian gland (HG) of the mouse and acts as a lubricant to facilitate eyelid movement. We found that the HG of the mice with a disruption in the gene for stearoyl-CoA desaturase 1 (SCD1) (SCD1-/-) is deficient in ADG. The amount of C20:1n-9, which is a major fatty acid of ADG, was reduced by greater than 90% despite normal elongase enzyme activity proposed to elongate it from C18:1n-9. HG from SCD1-/- mice exhibited high desaturase activity toward C16:0-CoA as substrate but had very low desaturase activity toward C18:0-CoA. Feeding diets containing high levels of oleate to the SCD1-/- mice did not increase the levels of C18:1n-9 or C20:1n-9 in the HG and failed to restore the ADG to the levels found in the HG of the wild-type mouse. De novo ADG synthesis as measured by the incorporation of [(3)H]glycerol and [(14)C]glucose was high in the SCD1+/+ mouse but was reduced by greater than 90% in the HG of SCD1-/- mouse. The deficiencies in the levels of ADG and C20:1n-9 were not compensated for by the expression of SCD2 and SCD3 isoforms in the HG of the SCD1-/- mouse. These observations demonstrate that SCD1-synthesized oleoyl-CoA is a major substrate required for the biosynthesis of normal levels of ADG and that the SCD isoforms present in the HG have different substrate specificity.