{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T11:29:06Z","timestamp":1789644546128,"version":"4.0.0"},"reference-count":56,"publisher":"National Academy of Sciences","issue":"40","license":[{"start":{"date-parts":[[2022,9,26]],"date-time":"2022-09-26T00:00:00Z","timestamp":1664150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,10,4]]},"abstract":"<jats:p>\n                    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-\u03b22\u2013induced expression of mesenchymal genes and prevented impairment of endothelial barrier function. Treatment of lipodystrophic- and atherosclerosis-prone animals (Ldlr\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ; 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 (\n                    <jats:italic>GDF15<\/jats:italic>\n                    ). Inhibition of\n                    <jats:italic>GDF15<\/jats:italic>\n                    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\n                    <jats:italic>GDF15<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1073\/pnas.2110374119","type":"journal-article","created":{"date-parts":[[2022,9,26]],"date-time":"2022-09-26T15:21:09Z","timestamp":1664205669000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":23,"title":["Leptin treatment has vasculo-protective effects in lipodystrophic mice"],"prefix":"10.1073","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5297-7137","authenticated-orcid":false,"given":"Paulina Elena","family":"St\u00fcrzebecher","sequence":"first","affiliation":[{"name":"Klinik und Poliklinik f\u00fcr Kardiologie, Universit\u00e4tsklinikum Leipzig, Leipzig, 04103, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Kralisch","sequence":"additional","affiliation":[{"name":"Medical Department III \u2013 Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, 04103, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie Ruth","family":"Schubert","sequence":"additional","affiliation":[{"name":"Klinik und Poliklinik f\u00fcr Kardiologie, Universit\u00e4tsklinikum Leipzig, Leipzig, 04103, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0854-4750","authenticated-orcid":false,"given":"Vanina","family":"Filipova","sequence":"additional","affiliation":[{"name":"Klinik und Poliklinik f\u00fcr Kardiologie, Universit\u00e4tsklinikum Leipzig, Leipzig, 04103, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annett","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Medical Department III \u2013 Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, 04103, Germany"},{"name":"Department of General, Visceral, Vascular and Pediatric Surgery, University Hospital of W\u00fcrzburg, W\u00fcrzburg, 97080, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiana","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum M\u00fcnchen at the University of Leipzig and University Hospital Leipzig, Leipzig, 04103, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1970-6236","authenticated-orcid":false,"given":"Bilal N.","family":"Sheikh","sequence":"additional","affiliation":[{"name":"Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum M\u00fcnchen at the University of Leipzig and University Hospital Leipzig, Leipzig, 04103, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0208-2065","authenticated-orcid":false,"given":"Matthias","family":"Bl\u00fcher","sequence":"additional","affiliation":[{"name":"Medical Department III \u2013 Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, 04103, Germany"},{"name":"Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum M\u00fcnchen at the University of Leipzig and University Hospital Leipzig, Leipzig, 04103, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1842-4480","authenticated-orcid":false,"given":"Alexander","family":"Kogel","sequence":"additional","affiliation":[{"name":"Klinik und Poliklinik f\u00fcr Kardiologie, Universit\u00e4tsklinikum Leipzig, Leipzig, 04103, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Scholz","sequence":"additional","affiliation":[{"name":"Institute for Medical Informatics, Statistics and Epidemiology, Medical Faculty, University of Leipzig, Leipzig, 04107, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8130-4289","authenticated-orcid":false,"given":"Karoline Elizabeth","family":"Kokot","sequence":"additional","affiliation":[{"name":"Klinik und Poliklinik f\u00fcr Kardiologie, Universit\u00e4tsklinikum Leipzig, Leipzig, 04103, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0139-8981","authenticated-orcid":false,"given":"Stephan","family":"Erbe","sequence":"additional","affiliation":[{"name":"Klinik und Poliklinik f\u00fcr Kardiologie, Universit\u00e4tsklinikum Leipzig, Leipzig, 04103, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0273-3614","authenticated-orcid":false,"given":"Jasmin Marga","family":"Kneuer","sequence":"additional","affiliation":[{"name":"Klinik und Poliklinik f\u00fcr Kardiologie, Universit\u00e4tsklinikum Leipzig, Leipzig, 04103, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1683-9276","authenticated-orcid":false,"given":"Thomas","family":"Ebert","sequence":"additional","affiliation":[{"name":"Medical Department III \u2013 Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, 04103, Germany"},{"name":"Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institute, Stockholm, SE-141 86, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Fasshauer","sequence":"additional","affiliation":[{"name":"Institute of 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Carter, A. Caron, D. Richard, F. Picard, Role of leptin resistance in the development of obesity in older patients. Clin. Interv. Aging 8, 829\u2013844 (2013).","journal-title":"Clin. Interv. Aging"},{"key":"e_1_3_5_53_2","doi-asserted-by":"publisher","DOI":"10.2147\/DMSO.S182406"},{"key":"e_1_3_5_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.04.018"},{"key":"e_1_3_5_55_2","doi-asserted-by":"publisher","DOI":"10.1089\/dna.2017.3779"},{"key":"e_1_3_5_56_2","doi-asserted-by":"crossref","unstructured":"P. E. St\u00fcrzebecher S. Kralisch S. Erbe J. Boeckel Leptin treatment has vasculo-protective effects in lipodystrophic mice. NCBI Gene Expression Omnibus. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE213438. 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