Palmitic acid (16:0) competes with omega-6 linoleic and omega-3 ɑ-linolenic acids for FADS2 mediated Δ6-desaturation.

ABSTRACT

Sapienic acid, 161n-10 is the most abundant unsaturated fatty acid on human skin where its synthesis is mediated by FADS2 in the sebaceous glands. The FADS2 product introduces a double bond at the Δ6, Δ4 and Δ8 positions by acting on at least ten substrates, including 160, 182n-6, and 183n-3. Our aim was to characterize the competition for accessing FADS2 mediated Δ6 desaturation between 160 and the most abundant polyunsaturated fatty acids (PUFA) in the human diet, 182n-6 and 183n-3, to evaluate whether competition may be relevant in other tissues and thus linked to metabolic abnormalities associated with FADS2 or fatty acid levels. MCF7 cells stably transformed with FADS2 biosynthesize 161n-10 from exogenous 160 in preference to 161n-7, the immediate product of SCD highly expressed in cancer cell lines, and 161n-9 via partial ß-oxidation of 181n-9. Increasing availability of 182n-6 or 183n-3 resulted in decreased bioconversion of 160 to 161n-10, simultaneously increasing the levels of highly unsaturated products. FADS2 cells accumulate the desaturation-elongation products 203n-6 and 204n-3 in preference to the immediate desaturation products 183n-6 and 184n-3 implying prompt/coupled elongation of the nascent desaturation products. MCF7 cells incorporate newly synthesized 161n-10 into phospholipids. These data suggest that excess 160 due to, for instance, de novo lipogenesis from high carbohydrate or alcohol consumption, inhibits synthesis of highly unsaturated fatty acids, and may in part explain why supplemental preformed EPA and DHA in some studies improves insulin resistance and other factors related to diabetes and metabolic syndrome aggravated by excess calorie consumption.