Fatty Acid Desaturase 2 (FADS2) Actions on Branched Chain and Normal Odd Chain Saturated Fatty Acids

Abstract

Abstract Objectives Branched chain fatty acids (BCFA), linear chain/normal odd chain fatty acids (n-OCFA) and sapienic acid (16:1n-10), are the most abundant lipids on human skin, especially sebaceous gland (SG) wax esters. Sapienic acid synthesis is mediated by fatty acid desaturase 2 (FADS2) in the sebaceous glands. FADS2 is an abundant mRNA in human skin, producing a classical transcript that introduces a double bond at the Δ6, Δ4 and Δ8 positions acting on at least eleven substrates, including one saturate (n-16:0). Our main objective was to test the hypothesis that FADS2 catalyze desaturation reaction(s) operating on specific BCFA and n-OCFA. Methods We created MCF-7 cells stably expressing FADS1 and FADS2 by using pcDNA3.1 expression vector system along with empty vector cells as control. Cells were cultured in standard MEM-α media and incubated at concentration of 50 μM of bovine serum albumin (BSA)-bound fatty acid substrates individually (anteiso-15:0, iso-16:0, iso-17:0, anteiso-17:0, iso-18:0 or n-17:0). FAME were structurally identified by gas chromatography (GC) - covalent adduct chemical ionization mass spectrometry (CACI-MS/MS) and quantified by GC-flame ionization detector (GC-FID). Results FADS2 desaturated BCFA as follows: iso-16:0 → iso-6Z-16:1, iso-17:0 → iso-6Z-17:1, anteiso-17:0 → anteiso-6Z-17:1 and iso-18:0 → iso-6Z-18:1. FADS2 had no action on anteiso-15:0. FADS2 converted n-17:0 → n-6Z-17:1. FADS1 had no activity towards any of these substrates. Conclusions We provide the first molecular evidence demonstrating novel FADS2-coded enzymatic activity towards BCFA and n-OCFA producing predominant human sebaceous monounsaturated fatty acids (MUFA). Our results extends FADS2 activity to BCFA and n-OCFA and expands FADS2 actions on saturated fatty acid substrates from one to six. Changes in the levels or the activity of FADS2 can influence the fatty acid composition of the sebum, which may play a role in certain skin abnormalities. Funding Sources NIH R01 AT007003.