A novel FADS1 isoform potentiates FADS2-mediated production of eicosanoid precursor fatty acids
JOURNAL OF LIPID RESEARCH
Authors: Park, Woo Jung; Kothapalli, Kumar S. D.; Reardon, Holly T.; Lawrence, Peter; Qian, Shu-Bing; Brenna, J. Thomas
Abstract
The fatty acid desaturase (FADS) genes code for the rate-limiting enzymes required for the biosynthesis of long-chain polyunsaturated fatty acids (LCPUFA). Here we report discovery and function of a novel FADS1 splice variant. FADS1 alternative transcript 1 (FADS1AT1) enhances desaturation of FADS2, leading to increased production of eicosanoid precursors, the first case of an isoform modulating the enzymatic activity encoded by another gene. Multiple protein isoforms were detected in primate liver, thymus, and brain. In human neuronal cells, their expression patterns are modulated by differentiation and result in alteration of cellular fatty acids. FADS1, but not FADS1AT1, localizes to endoplasmic reticulum and mitochondria. Ribosomal footprinting demonstrates that all three FADS genes are translated at similar levels.(jlr) The noncatalytic regulation of FADS2 desaturation by FADS1AT1 is a novel, plausible mechanism by which several phylogenetically conserved FADS isoforms may regulate LCPUFA biosynthesis in a manner specific to tissue, organelle, and developmental stage.-Park, W. J., K. S. D. Kothapalli, H. T. Reardon, P. Lawrence, S-B. Qian, and J. T. Brenna. A novel FADS1 isoform potentiates FADS2-mediated production of eicosanoid precursor fatty acids. J. Lipid Res. 2012. 53: 1502-1512.
Dietary and ontogenic regulation of fatty acid desaturase and elongase expression in broiler chickens
PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS
Authors: Jing, M.; Gakhar, N.; Gibson, R. A.; House, J. D.
Abstract
Effects of diet and ontogeny on the expression of fatty acid desaturases and elongases were examined in broiler chickens. In Study 1, 120 day-old male chicks received one of six diets with LA:ALA ranging from 46:4 to 16:34, for 33 days. Total n-6 PUFA decreased, and n-3 PUFA increased in response to a decrease in the dietary LA:ALA. FADS1, FADS2, ELOVL2 and ELOVL5 mRNAs were highest (P < 0.05) in birds fed lower LA:ALA diets. In Study 2, 60 day-old male chicks were fed a basal diet, and liver samples were collected on day of hatch, and on days 2, 7, 14, 21 and 35 post-hatch. Total n-6 and n-3 PUFA increased (P < 0.01) from days 7 to days 21. FADS1, FADS2 and ELOVL2 mRNAs generally increased (P < 0.01) with age. These findings provide evidence for the dietary and developmental regulation of PUFA metabolism in broiler chickens. (C) 2013 Elsevier Ltd. All rights reserved.