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Witt, A.* ; Mateska, I.* ; Palladini, A. ; Sinha, A.* ; Wölk, M.* ; Harauma, A.* ; Bechmann, N.* ; Pamporaki, C.* ; Dahl, A.* ; Rothe, M.* ; Kopaliani, I.* ; Adolf, C.* ; Riester, A.* ; Wielockx, B.* ; Bornstein, S.R.* ; Kroiss, M.* ; Peitzsch, M.* ; Moriguchi, T.* ; Fedorova, M.* ; Grzybek, M. ; Chavakis, T.* ; Mirtschink, P.* ; Alexaki, V.I.*

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

Sci. Adv. 9:eadf6710 (2023)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Ester Amr101 Therapy; Eicosapentaenoic Acid; Arachidonic-acid; Cholesterol Transport; Quantitative-analysis; High-throughput; Fads2 Gene; Membrane; Obesity; Disruption
Sprache englisch
Veröffentlichungsjahr 2023
HGF-Berichtsjahr 2023
ISSN (print) / ISBN 2375-2548
e-ISSN 2375-2548
Zeitschrift Science Advances
Quellenangaben Band: 9, Heft: 29, Seiten: , Artikelnummer: eadf6710 Supplement: ,
Verlag American Association for the Advancement of Science (AAAS)
Verlagsort Washington, DC [u.a.]
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Pancreatic Islet Research (IPI)
POF Topic(s) 90000 - German Center for Diabetes Research
Forschungsfeld(er) Helmholtz Diabetes Center
PSP-Element(e) G-502600-002
Förderungen Deutsche Forschungsgemeinschaft
DOI 10.1126/sciadv.adf6710
WOS ID 001037141300003
Scopus ID 85171422783
PubMed ID 37478183
Erfassungsdatum 2023-10-06
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