Fatty acid desaturase 2 determines the lipidomic landscape and steroidogenic function of the adrenal gland

Research output: Contribution to journalResearch articleContributedpeer-review



Corticosteroids regulate vital processes, including stress responses, systemic metabolism, and blood pressure. Here, we show that corticosteroid synthesis is related to the polyunsaturated fatty acid (PUFA) content of mitochondrial phospholipids in adrenocortical cells. Inhibition of the rate-limiting enzyme of PUFA synthesis, fatty acid desaturase 2 (FADS2), leads to perturbations in the mitochondrial lipidome and diminishes steroidogenesis. Consistently, the adrenocortical mitochondria of Fads2-/- mice fed a diet with low PUFA concentration are structurally impaired and corticoid levels are decreased. On the contrary, FADS2 expression is elevated in the adrenal cortex of obese mice, and plasma corticosterone is increased, which can be counteracted by dietary supplementation with the FADS2 inhibitor SC-26192 or icosapent ethyl, an eicosapentaenoic acid ethyl ester. In humans, FADS2 expression is elevated in aldosterone-producing adenomas compared to non-active adenomas or nontumorous adrenocortical tissue and correlates with expression of steroidogenic genes. Our data demonstrate that FADS2-mediated PUFA synthesis determines adrenocortical steroidogenesis in health and disease.


Original languageEnglish
Article numberadf6710
Pages (from-to)eadf6710
Number of pages19
JournalScience advances
Issue number29
Publication statusPublished - 21 Jul 2023

External IDs

PubMedCentral PMC10361602
WOS 001037141300003
unpaywall 10.1126/sciadv.adf6710
ORCID /0000-0002-6932-333X/work/142239673
Scopus 85171422783
ORCID /0000-0002-4692-3885/work/148143332
ORCID /0000-0003-2083-0506/work/148607266


Subject groups, research areas, subject areas according to Destatis

ASJC Scopus subject areas


  • Arachidonic-acid, Cholesterol transport, Disruption, Eicosapentaenoic acid, Ester amr101 therapy, Fads2 gene, High-throughput, Membrane, Obesity, Quantitative-analysis, Fatty Acid Desaturases/genetics, Humans, Lipidomics, Adenoma, Animals, Fatty Acids, Unsaturated/metabolism, Adrenal Glands/metabolism, Mice