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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)

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Open Access Gold as soon as Publ. Version/Full Text is submitted to ZB.

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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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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Ester Amr101 Therapy; Eicosapentaenoic Acid; Arachidonic-acid; Cholesterol Transport; Quantitative-analysis; High-throughput; Fads2 Gene; Membrane; Obesity; Disruption

ISSN (print) / ISBN 2375-2548

e-ISSN 2375-2548

Journal Science Advances

Quellenangaben Volume: 9, Issue: 29, Article Number: eadf6710

Publisher American Association for the Advancement of Science (AAAS)

Publishing Place Washington, DC [u.a.]

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute for Pancreatic Beta Cell Research (IPI)

Grants Deutsche Forschungsgemeinschaft