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New strategies to delay the onset of the hazardous adaptations induced by obesity are needed. Therefore, we evaluated the effects of 4 weeks of melatonin treatment on mitochondrial function and lipid metabolism in the livers of leptin-deficient mice. Our results revealed that the absence of leptin increased lipid storage in the liver and induced significant mitochondrial alterations, which were ultimately responsible for defective ATP production and reactive oxygen species overproduction. Moreover, leptin deficiency promoted mitochondrial biogenesis, fusion, and outer membrane permeabilization. Melatonin treatment reduced the bioenergetic deficit found in ob\/ob mice, alleviating some mitochondrial alterations in the electron transport chain machinery, biogenesis, dynamics, respiration, ATP production, and mitochondrial outer membrane permeabilization. Given the role of melatonin in maintaining mitochondrial homeostasis, it could be used as a therapeutic agent against adipogenic steatosis.<\/jats:p>","DOI":"10.3390\/ijms25168677","type":"journal-article","created":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T07:59:07Z","timestamp":1723190347000},"page":"8677","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Melatonin Alleviates Liver Mitochondrial Dysfunction in Leptin-Deficient Mice"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4507-716X","authenticated-orcid":false,"given":"Beatriz","family":"de Lux\u00e1n-Delgado","sequence":"first","affiliation":[{"name":"Department of Morphology and Cell Biology, University of Oviedo, Juli\u00e1n Claver\u00eda s\/n, 33006 Oviedo, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4687-6230","authenticated-orcid":false,"given":"Yaiza","family":"Potes","sequence":"additional","affiliation":[{"name":"Department of Morphology and Cell Biology, University of Oviedo, Juli\u00e1n Claver\u00eda s\/n, 33006 Oviedo, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), Av. Del Hospital Universitario, 33011 Oviedo, Spain"},{"name":"Instituto de Neurociencias del Principado de Asturias (INEUROPA), University of Oviedo, Juli\u00e1n Claver\u00eda s\/n, 33006 Oviedo, Spain"}]},{"given":"Adrian","family":"Rubio-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Department of Morphology and Cell Biology, University of Oviedo, Juli\u00e1n Claver\u00eda s\/n, 33006 Oviedo, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), Av. Del Hospital Universitario, 33011 Oviedo, Spain"},{"name":"Instituto de Neurociencias del Principado de Asturias (INEUROPA), University of Oviedo, Juli\u00e1n Claver\u00eda s\/n, 33006 Oviedo, Spain"}]},{"given":"Juan Jos\u00e9","family":"Solano","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), Av. Del Hospital Universitario, 33011 Oviedo, Spain"},{"name":"Geriatrics Service, Monte Naranco Hospital, 33012 Oviedo, Spain"}]},{"given":"Jos\u00e9 Antonio","family":"Boga","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), Av. Del Hospital Universitario, 33011 Oviedo, Spain"},{"name":"Microbiology Department, Hospital Universitario Central de Asturias, Avenida de Roma s\/n, 33011 Oviedo, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1016-6306","authenticated-orcid":false,"given":"Eduardo","family":"Antu\u00f1a","sequence":"additional","affiliation":[{"name":"Department of Morphology and Cell Biology, University of Oviedo, Juli\u00e1n Claver\u00eda s\/n, 33006 Oviedo, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), Av. Del Hospital Universitario, 33011 Oviedo, Spain"},{"name":"Instituto de Neurociencias del Principado de Asturias (INEUROPA), University of Oviedo, Juli\u00e1n Claver\u00eda s\/n, 33006 Oviedo, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7244-7862","authenticated-orcid":false,"given":"Cristina","family":"Cach\u00e1n-Vega","sequence":"additional","affiliation":[{"name":"Department of Morphology and Cell Biology, University of Oviedo, Juli\u00e1n Claver\u00eda s\/n, 33006 Oviedo, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), Av. Del Hospital Universitario, 33011 Oviedo, Spain"},{"name":"Instituto de Neurociencias del Principado de Asturias (INEUROPA), University of Oviedo, Juli\u00e1n Claver\u00eda s\/n, 33006 Oviedo, Spain"}]},{"given":"Juan Carlos","family":"Bermejo-Millo","sequence":"additional","affiliation":[{"name":"Department of Morphology and Cell Biology, University of Oviedo, Juli\u00e1n Claver\u00eda s\/n, 33006 Oviedo, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), Av. Del Hospital Universitario, 33011 Oviedo, Spain"},{"name":"Instituto de Neurociencias del Principado de Asturias (INEUROPA), University of Oviedo, Juli\u00e1n Claver\u00eda s\/n, 33006 Oviedo, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4796-4965","authenticated-orcid":false,"given":"Nerea","family":"Men\u00e9ndez-Coto","sequence":"additional","affiliation":[{"name":"Department of Morphology and Cell Biology, University of Oviedo, Juli\u00e1n Claver\u00eda s\/n, 33006 Oviedo, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8422-230X","authenticated-orcid":false,"given":"Claudia","family":"Garc\u00eda-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), Av. Del Hospital Universitario, 33011 Oviedo, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9638-0615","authenticated-orcid":false,"given":"Gon\u00e7alo C.","family":"Pereira","sequence":"additional","affiliation":[{"name":"School of Biochemistry, Medical Sciences Building, University of Bristol, Bristol BS8 1TD, UK"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0242-9620","authenticated-orcid":false,"given":"Beatriz","family":"Caballero","sequence":"additional","affiliation":[{"name":"Department of Morphology and Cell Biology, University of Oviedo, Juli\u00e1n Claver\u00eda s\/n, 33006 Oviedo, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), Av. Del Hospital Universitario, 33011 Oviedo, Spain"},{"name":"Instituto de Neurociencias del Principado de Asturias (INEUROPA), University of Oviedo, Juli\u00e1n Claver\u00eda s\/n, 33006 Oviedo, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6609-6258","authenticated-orcid":false,"given":"Ana","family":"Coto-Montes","sequence":"additional","affiliation":[{"name":"Department of Morphology and Cell Biology, University of Oviedo, Juli\u00e1n Claver\u00eda s\/n, 33006 Oviedo, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), Av. 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Del Hospital Universitario, 33011 Oviedo, Spain"},{"name":"Instituto de Neurociencias del Principado de Asturias (INEUROPA), University of Oviedo, Juli\u00e1n Claver\u00eda s\/n, 33006 Oviedo, Spain"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1007\/s11684-021-0862-5","article-title":"Mechanism of insulin resistance in obesity: A role of ATP","volume":"15","author":"Ye","year":"2021","journal-title":"Front. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"326320","DOI":"10.4061\/2011\/326320","article-title":"Melatonin in mitochondrial dysfunction and related disorders","volume":"2011","author":"Srinivasan","year":"2011","journal-title":"Int. J. 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