M. Miyazaki, Hyoun-ju Kim, W. C. Man
Oct 19, 2001
Citations
5
Influential Citations
112
Citations
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Journal
The Journal of Biological Chemistry
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 [3H]glycerol and [14C]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.