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SMA is a multi-system disease involving patients with alterations in multiple organs and metabolic pathways. Approved therapies focus on increasing SMN protein level either in the central nervous system or systemically. However, none of these therapies result in a cure. Patients show perturbations in several organs, including altered lipid metabolism such as leptin proteohormone levels, dicarboxylic aciduria and altered \u03b2-oxidation. In this study, we describe alterations along the neuroendocrine axis of leptin homeostasis in white adipose tissue (WAT) and hypothalamus of the severe Taiwanese SMA mouse model. Body weight was significantly decreased in SMA mice accompanied by significantly changed leptin protein levels in WAT of pre-symptomatic (P3) mice. Additionally, transcriptome and proteome analyses of WAT and hypothalamus revealed alterations in lipid and glucose metabolic pathways. We also identified several altered targets associated with appetite regulation. Our findings emphasize dysregulations in lipid and glucose metabolism and reinforce the need for research on metabolism in a disease with a predominant neuromuscular phenotype.<\/jats:p>","DOI":"10.1093\/hmg\/ddaf172","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T15:38:29Z","timestamp":1763393909000},"source":"Crossref","is-referenced-by-count":1,"title":["Alterations along the neuroendocrine axis of leptin homeostasis: white adipose tissue and hypothalamus in a severe SMA mouse model"],"prefix":"10.1093","volume":"35","author":[{"given":"Ines","family":"B\u00fcnermann","sequence":"first","affiliation":[{"name":"Hannover Medical School, Department of Conservative Dentistry, Periodontology and Preventive Dentistry , Carl-Neuberg-Str. 1, 30625 Hannover ,","place":["Germany"]},{"name":"Hannover Medical School, Laboratory of Molecular Neurosciences, Dept. of Psychiatry, Social Psychiatry and Psychotherapy , Carl-Neuberg-Str. 1, 30625 Hannover ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nora","family":"Detering","sequence":"additional","affiliation":[{"name":"Center for Systems Neuroscience (ZSN) , B\u00fcnteweg 2, 30559 Hannover ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ines","family":"Tapken","sequence":"additional","affiliation":[{"name":"Center for Systems Neuroscience (ZSN) , B\u00fcnteweg 2, 30559 Hannover ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Kuhn","sequence":"additional","affiliation":[{"name":"Hannover Medical School, Department of Conservative Dentistry, Periodontology and Preventive Dentistry , Carl-Neuberg-Str. 1, 30625 Hannover ,","place":["Germany"]},{"name":"Department of Oral and Maxillofacial Surgery, Henrietten Foundation Hospital , Marienstra\u00dfe 72 - 90, 30171 Hannover 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,","place":["Germany"]},{"name":"Center for Systems Neuroscience (ZSN) , B\u00fcnteweg 2, 30559 Hannover ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1611-8906","authenticated-orcid":false,"given":"Niko","family":"Hensel","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, Martin Luther University Halle-Wittenberg, Faculty of Medicine , Grosse Steinstrasse 52, 06108 Halle (Saale) ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tobias","family":"Sch\u00fcning","sequence":"additional","affiliation":[{"name":"Center for Systems Neuroscience (ZSN) , B\u00fcnteweg 2, 30559 Hannover ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oliver","family":"Dittrich-Breiholz","sequence":"additional","affiliation":[{"name":"Hannover Medical School, Research Core Unit Genomics , Carl-Neuberg-Str. 1, 30625 Hannover ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Pich","sequence":"additional","affiliation":[{"name":"Hannover Medical School, Research Core Unit Proteomics , Carl-Neuberg-Str. 1, 30625 Hannover ,","place":["Germany"]},{"name":"Hannover Medical School, Institute of Toxicology , Carl-Neuberg-Str. 1, 30625 Hannover ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3824-9445","authenticated-orcid":false,"given":"Peter","family":"Claus","sequence":"additional","affiliation":[{"name":"Hannover Medical School, Laboratory of Molecular Neurosciences, Dept. of Psychiatry, Social Psychiatry and Psychotherapy , Carl-Neuberg-Str. 1, 30625 Hannover ,","place":["Germany"]},{"name":"Center for Systems Neuroscience (ZSN) , B\u00fcnteweg 2, 30559 Hannover 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