Oleoyl-CoA is the major de novo product of stearoyl-CoA desaturase 1 gene isoform and substrate for the biosynthesis of the Harderian gland 1-alkyl-2,3-diacylglycerol

1-Alkyl-2,3-diacylglycerol (ADG) is a unique neutral lipid found in the eye ball-associated Harderian gland (HG) of the mouse and acts as a lubricant t o facilitate eyelid movement. We found that the HG of the mice with a disru ption in the gene for stearoyl-CoA desaturase 1 (SCD1) (SCD1-/-) is deficie nt 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 propose d to elongate it from C18:1n-9. HG from SCD1-/- mice exhibited high desatur ase activity toward C16:0-CoA as substrate but had very low desaturase acti vity toward C18:0-CoA. Feeding diets containing high levels of oleate to th e SCD1-/- mice did not increase the levels of C18:1n-9 or C20:1n-9 in the H G and failed to restore the ADG to the levels found in the HG of the wild-t ype mouse. De novo ADG synthesis as measured by the incorporation of [H-3]g lycerol and [C-14]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 demonstra te that SCD1-synthesized oleoyl-CoA is a major substrate required for the b iosynthesis of normal levels of ADG and that the SCD isoforms present in th e HG have different substrate specificity.