title: Palmitic acid (16:0) competes with omega-6 linoleic and omega-3 ɑ-linolenic acids for FADS2 mediated Δ6-desaturation.
abstract: Sapienic acid, 16:1n-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 16:0, 18:2n-6, and 18:3n-3. Our aim was to characterize the competition for accessing FADS2 mediated Δ6 desaturation between 16:0 and the most abundant polyunsaturated fatty acids (PUFA) in the human diet, 18:2n-6 and 18:3n-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 16:1n-10 from exogenous 16:0 in preference to 16:1n-7, the immediate product of SCD highly expressed in cancer cell lines, and 16:1n-9 via partial β-oxidation of 18:1n-9. Increasing availability of 18:2n-6 or 18:3n-3 resulted in decreased bioconversion of 16:0 to 16:1n-10, simultaneously increasing the levels of highly unsaturated products. FADS2 cells accumulate the desaturation-elongation products 20:3n-6 and 20:4n-3 in preference to the immediate desaturation products 18:3n-6 and 18:4n-3 implying prompt/coupled elongation of the nascent desaturation products. MCF7 cells incorporate newly synthesized 16:1n-10 into phospholipids. These data suggest that excess 16:0 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.
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Hui Gyu
authors.initials: HG
authors.lastname: Park
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA. Electronic address: ksk25@cornell.edu.
authors.forename: Kumar S D
authors.initials: KSD
authors.lastname: Kothapalli
authors.affiliation: Department of Marine Food Science and Technology, Gangneung-Wonju National University, Gangneung, Gangwon, 210-702, Korea.
authors.forename: Woo Jung
authors.initials: WJ
authors.lastname: Park
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: DeAllie
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Allison
authors.initials: A
authors.lastname: Liang
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Lawrence
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA. Electronic address: jtb4@cornell.edu.
authors.forename: J Thomas
authors.initials: JT
authors.lastname: Brenna
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001692:Biological Transport; D044943:Fatty Acid Desaturases / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D006801:Humans; D019787:Linoleic Acid / Q000494:pharmacology*; D050155:Lipogenesis / Q000502:physiology; D008099:Liver / Q000737:chemistry; D061986:MCF-7 Cells; D010084:Oxidation-Reduction; D019308:Palmitic Acid / Q000378:metabolism / Q000494:pharmacology*; D010169:Palmitic Acids / Q000494:pharmacology*; D010215:Papio; D017962:alpha-Linolenic Acid / Q000494:pharmacology*
chemical_list: D005231:Fatty Acids, Unsaturated; D010169:Palmitic Acids; C090151:delta(6)-hexadecenoic acid; D017962:alpha-Linolenic Acid; D019308:Palmitic Acid; D019787:Linoleic Acid; D044943:Fatty Acid Desaturases; C533241:FADS2 protein, human
keywords: Fatty acid desaturases; Monounsaturated fatty acids; Palmitic acid; Polyunsaturated fatty acids; Sapienic acid; Δ6 desaturase