{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T20:36:13Z","timestamp":1772310973593,"version":"3.50.1"},"reference-count":65,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2017,12,5]],"date-time":"2017-12-05T00:00:00Z","timestamp":1512432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"New Petfood Italia Srl"},{"name":"ex-60% University of Brescia (Italy)"},{"name":"Serbian Ministry of Education, Science and Technological Development","award":["#173055"],"award-info":[{"award-number":["#173055"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Cardiomyocytes are particularly sensitive to oxidative damage due to the link between mitochondria and sarcoplasmic reticulum necessary for calcium flux and contraction. Melatonin, important indoleamine secreted by the pineal gland during darkness, also has important cardioprotective properties. We designed the present study to define morphological and ultrastructural changes in cardiomyocytes and mainly in mitochondria of an animal model of obesity (ob\/ob mice), when treated orally or not with melatonin at 100 mg\/kg\/day for 8 weeks (from 5 up to 13 week of life). We observed that ob\/ob mice mitochondria in sub-sarcolemmal and inter-myofibrillar compartments are often devoid of cristae with an abnormally large size, which are called mega-mitochondria. Moreover, in ob\/ob mice the hypertrophic cardiomyocytes expressed high level of 4hydroxy-2-nonenal (4HNE), a marker of lipid peroxidation but scarce degree of mitofusin2, indicative of mitochondrial sufferance. Melatonin oral supplementation in ob\/ob mice restores mitochondrial cristae, enhances mitofusin2 expression and minimizes 4HNE and p62\/SQSTM1, an index of aberrant autophagic flux. At pericardial fat level, adipose tissue depot strictly associated with myocardium infarction, melatonin reduces adipocyte hypertrophy and inversely regulates 4HNE and adiponectin expressions. In summary, melatonin might represent a safe dietary adjuvant to hamper cardiac mitochondria remodeling and the hypoxic status that occur in pre-diabetic obese mice at 13 weeks of life.<\/jats:p>","DOI":"10.3390\/nu9121323","type":"journal-article","created":{"date-parts":[[2017,12,5]],"date-time":"2017-12-05T11:50:28Z","timestamp":1512474628000},"page":"1323","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Melatonin Efficacy in Obese Leptin-Deficient Mice Heart"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6767-6617","authenticated-orcid":false,"given":"Alessandra","family":"Stacchiotti","sequence":"first","affiliation":[{"name":"Anatomy and Physiopathology Division, Department of Clinical and Experimental Sciences, University of Brescia, Viale Europa 11, 25123 Brescia, Italy"},{"name":"Interdipartimental University Center of Research \u201cAdaptation and Regeneration of Tissues and Organs (ARTO)\u201d, University of Brescia, 25123 Brescia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6895-7106","authenticated-orcid":false,"given":"Gaia","family":"Favero","sequence":"additional","affiliation":[{"name":"Anatomy and Physiopathology Division, Department of Clinical and Experimental Sciences, University of Brescia, Viale Europa 11, 25123 Brescia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorena","family":"Giugno","sequence":"additional","affiliation":[{"name":"Anatomy and Physiopathology Division, Department of Clinical and Experimental Sciences, University of Brescia, Viale Europa 11, 25123 Brescia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5944-5053","authenticated-orcid":false,"given":"Igor","family":"Golic","sequence":"additional","affiliation":[{"name":"Center for Electron Microscopy, Faculty of Biology, University of Belgrade, Studentski trg 16, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksandra","family":"Korac","sequence":"additional","affiliation":[{"name":"Center for Electron Microscopy, Faculty of Biology, University of Belgrade, Studentski trg 16, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7515-5846","authenticated-orcid":false,"given":"Rita","family":"Rezzani","sequence":"additional","affiliation":[{"name":"Anatomy and Physiopathology Division, Department of Clinical and Experimental Sciences, University of Brescia, Viale Europa 11, 25123 Brescia, Italy"},{"name":"Interdipartimental University Center of Research \u201cAdaptation and Regeneration of Tissues and Organs (ARTO)\u201d, University of Brescia, 25123 Brescia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2017,12,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/nrendo.2012.199","article-title":"Global obesity: Trends, risk factors and policy implications","volume":"9","author":"Malik","year":"2013","journal-title":"Nat. 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