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Stürzebecher, P.E.* ; Kralisch, S.* ; Schubert, M.R.* ; Filipova, V.* ; Hoffmann, A.* ; Oliveira, F. ; Sheikh, B. ; Blüher, M. ; Kogel, A.* ; Scholz, M.* ; Kokot, K.E.* ; Erbe, S.* ; Kneuer, J.M.* ; Ebert, T.* ; Fasshauer, M.* ; Miehle, K.* ; Laufs, U.* ; Tönjes, A.* ; Boeckel, J.N.*

Leptin treatment has vasculo-protective effects in lipodystrophic mice.

Proc. Natl. Acad. Sci. U.S.A. 119:e2110374119 (2022)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Lipodystrophy syndromes (LDs) are characterized by loss of adipose tissue, metabolic complications such as dyslipidemia, insulin resistance, and fatty liver disease, as well as accelerated atherosclerosis. As a result of adipose tissue deficiency, the systemic concentration of the adipokine leptin is reduced. A current promising therapeutic option for patients with LD is treatment with recombinant leptin (metreleptin), resulting in reduced risk of mortality. Here, we investigate the effects of leptin on endothelial to mesenchymal transition (EndMT), which impair the functional properties of endothelial cells and promotes atherogenesis in LD. Leptin treatment reduced inflammation and TGF-β2-induced expression of mesenchymal genes and prevented impairment of endothelial barrier function. Treatment of lipodystrophic- and atherosclerosis-prone animals (Ldlr-/-; aP2-nSrebp1c-Tg) with leptin reduced macrophage accumulation in atherosclerotic lesions, vascular plaque protrusion, and the number of endothelial cells with mesenchymal gene expression, confirming a reduction in EndMT in LD after leptin treatment. Treatment with leptin inhibited LD-mediated induction of the proatherosclerotic cytokine growth/differentiation factor 15 (GDF15). Inhibition of GDF15 reduced EndMT induction triggered by plasma from patients with LD. Our study reveals that in addition to the effects on adipose tissue function, leptin treatment exerts beneficial effects protecting endothelial function and identity in LD by reducing GDF15.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Atherosclerosis ; Endmt ; Gdf15 ; Leptin ; Lipodystrophy; To-mesenchymal Transition; Insulin-resistance; Adipose-tissue; Aortic-arch; Atherosclerotic Plaque; Diabetes-mellitus; Obesity; Atheromas; Risk; Endothelin-1
ISSN (print) / ISBN 0027-8424
e-ISSN 1091-6490
Zeitschrift Proceedings of the National Academy of Sciences of the United States of America
Quellenangaben Band: 119, Heft: 40, Seiten: , Artikelnummer: e2110374119 Supplement: ,
Verlag National Academy of Sciences
Verlagsort 2101 Constitution Ave Nw, Washington, Dc 20418 Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
Förderungen German Research Foundation (Deutsche Forschungsgemeinschaft, DFG)