{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:17:54Z","timestamp":1783487874146,"version":"3.55.0"},"reference-count":309,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"crossref","award":["155029\/2025-8"],"award-info":[{"award-number":["155029\/2025-8"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The Developmental Origins of Health and Disease framework proposes that environmental exposures during critical periods of development can shape physiological systems and influence the risk of chronic diseases later in life, including diabetes and metabolic syndrome. Most research on metabolic programming has focused on classical metabolic organs such as the liver, pancreas, and adipose tissue. However, skeletal muscle plays a central role in systemic glucose homeostasis and metabolic flexibility, accounting for the majority of insulin-stimulated glucose uptake in the body. Because muscle metabolism is closely regulated by neural activity through the organisation of motor units, the development of the motor neuromuscular axis may represent an underexplored dimension of metabolic programming. This review examines evidence linking early-life metabolic environments to neuromuscular development and discusses how alterations in the maturation of motor neurons, neuromuscular junctions, and muscle fibre phenotype may influence long-term metabolic outcomes. Evidence from epidemiological studies, experimental models, and mechanistic research suggests that maternal metabolic disturbances, including hyperglycaemia, obesity, and systemic inflammation, can influence foetal development through metabolic and inflammatory pathways affecting both neural and muscular components of the motor system. These findings support the hypothesis that the motor neuromuscular axis may represent a structural interface linking early developmental exposures to long-term metabolic regulation and risk of metabolic syndrome.<\/jats:p>","DOI":"10.3390\/ijms27136049","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T13:43:14Z","timestamp":1783345394000},"page":"6049","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Motor Neuromuscular Axis: The Overlooked Element of Developmental Programming in Diabetes and Metabolic Syndrome"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4760-5977","authenticated-orcid":false,"given":"Matheus Felipe","family":"Zazula","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Plasticidade Morfofuncional, Departamento de Biologia Celular, Setor de Ci\u00eancias Biol\u00f3gicas, Centro Polit\u00e9cnico, Universidade Federal do Paran\u00e1, Curitiba 81531-908, Paran\u00e1, Brazil"},{"name":"Laborat\u00f3rio de Fisiologia Celular, Departamento de Fisiologia, Instituto de Ci\u00eancias B\u00e1sicas da Sa\u00fade, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-003, Rio Grande do Sul, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie Rubianne Silva","family":"Carvalhal","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Metabolismo Celular, Departamento de Fisiologia, Setor de Ci\u00eancias Biol\u00f3gicas, Centro Polit\u00e9cnico, Universidade Federal do Paran\u00e1, Curitiba 81531-908, Paran\u00e1, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Djennifer T.","family":"Maciel","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Plasticidade Morfofuncional, Departamento de Biologia Celular, Setor de Ci\u00eancias Biol\u00f3gicas, Centro Polit\u00e9cnico, Universidade Federal do Paran\u00e1, Curitiba 81531-908, Paran\u00e1, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas","family":"Moritz","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Plasticidade Morfofuncional, Departamento de Biologia Celular, Setor de Ci\u00eancias Biol\u00f3gicas, Centro Polit\u00e9cnico, Universidade Federal do Paran\u00e1, Curitiba 81531-908, Paran\u00e1, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hellen Yukari Ito","family":"Beirauti","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Plasticidade Morfofuncional, Departamento de Biologia Celular, Setor de Ci\u00eancias Biol\u00f3gicas, Centro Polit\u00e9cnico, Universidade Federal do Paran\u00e1, Curitiba 81531-908, Paran\u00e1, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiza","family":"Amorim","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Plasticidade Morfofuncional, Departamento de Biologia Celular, Setor de Ci\u00eancias Biol\u00f3gicas, Centro Polit\u00e9cnico, Universidade Federal do Paran\u00e1, Curitiba 81531-908, Paran\u00e1, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2177-8275","authenticated-orcid":false,"given":"Mateus Teixeira da","family":"Rocha","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Plasticidade Morfofuncional, Departamento de Biologia Celular, Setor de Ci\u00eancias Biol\u00f3gicas, Centro Polit\u00e9cnico, Universidade Federal do Paran\u00e1, Curitiba 81531-908, Paran\u00e1, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2103-7315","authenticated-orcid":false,"given":"M\u00f4nica","family":"Maciel","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Plasticidade Morfofuncional, Departamento de Biologia Celular, Setor de Ci\u00eancias Biol\u00f3gicas, Centro Polit\u00e9cnico, Universidade 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Biologia Celular, Setor de Ci\u00eancias Biol\u00f3gicas, Centro Polit\u00e9cnico, Universidade Federal do Paran\u00e1, Curitiba 81531-908, Paran\u00e1, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tayn\u00e1 Nery","family":"Banckes","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Plasticidade Morfofuncional, Departamento de Biologia Celular, Setor de Ci\u00eancias Biol\u00f3gicas, Centro Polit\u00e9cnico, Universidade Federal do Paran\u00e1, Curitiba 81531-908, Paran\u00e1, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6506-0605","authenticated-orcid":false,"given":"Thomas","family":"Horlem","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Metabolismo Celular, Departamento de Fisiologia, Setor de Ci\u00eancias Biol\u00f3gicas, Centro Polit\u00e9cnico, Universidade Federal do Paran\u00e1, Curitiba 81531-908, Paran\u00e1, 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