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Updated: Oct 9, 2025

Quantitative Determination of De Novo Fatty Acid Synthesis in Brown Adipose Tissue Using Deuterium Oxide
Published on: May 12, 2023
New understandings of the pathway of long-chain polyunsaturated fatty acid biosynthesis
J Thomas Brenna1,2, Kumar S D Kothapalli1
1Dell Pediatric Research Institute, Departments of Pediatrics, of Chemistry, and of Nutrition, Dell Medical School and College of Natural Sciences, University of Texas at Austin, Austin, Texas.
Purpose Of Review:
Molecular studies have clarified the roles of the fatty acid desaturase (FADSx) and elongation of very long chain fatty acid (ELOVLx) genes, as well as acyl-coenzyme A synthase long-chain isoforms (ACSLx) required for entry to long-chain polyunsaturated fatty acid (LCPUFA) biosynthetic pathways.
Recent Findings:
FADS1 and FADS2 but not FADS3 are active toward PUFA. FADS1 is a Δ5-desaturase operating on five C20 PUFA, and is strongly regulated by human genetic polymorphisms, modulating circulating arachidonic acid (20:4n-6) levels. In contrast, FADS2 operates on at least 16 substrates, including five saturates, and catalyzes Δ6, Δ4, and Δ8 desaturation. FADS2 silencing in cancer cells leads to FADS1 synthesis of unusual fatty acids. ACSL6 and ACSL4 are required to maintain tissue 22:6n-3 and 20:4n-6, respectively. FADS2AT2, is the first transcript to differentially inhibit desaturation, attenuating 18:3n-3 but not 18:2n-6 desaturation. The PUFA elongases ELOVL5, 2, and 4 are implicated in cancer, age-related methylation, and retinal degeneration, respectively.
Summary:
The mixture of fatty acids available to FADS2 in any tissue defines the product mixture available for further synthesis of membrane lipids and signaling molecules and may be relevant in many clinical conditions including cancer. Functional genetic variants define the levels of circulating arachidonic acid via FADS1 regulation; genotypes that drive high arachidonic acid may predispose to disease.
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