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Cited by 25Circadian rhythm and melatoninMitochondrial Function and PathologyCardiac Ischemia and Reperfusion

Melatonin Efficacy in Obese Leptin-Deficient Mice Heart

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Stacchiotti, Alessandra, Favero, Gaia, Giugno, Lorena, Golic, Igor, Korac, Aleksandra, Rezzani, Rita·2017·Nutrients
DOI 10.3390/nu9121323PMC PMC5748773
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Abstract

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.

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Sorted by citations

Authors
Stacchiotti, A., Favero, G., Giugno, L., Golic, I., Korac, A., & Rezzani, R.
Affiliations
  • University of Brescia (IT)
  • Center for Electron Microscopy, Faculty of Biology, University of Belgrade, Studentski trg 16, 11000 Belgrade, Serbia
Corresponding author
Rezzani, Rita
ORCID
Venue
Nutrients
Publisher
MDPI AG
Published
2017-12-05
Volume
9
Issue
12
Pages
1323
ISSN
2072-6643 (ISSN-L)
DOI
10.3390/nu9121323
PMC
PMC5748773
OpenAlex
W2773474661
Cited by
25
References
7
Citations by year
2025: 1 · 2024: 4 · 2023: 3 · 2022: 2 · 2021: 7 · 2020: 2 · 2019: 2 · 2018: 4
FWCI
1.34
Type
journal article
Language
en
Open access
Licence
Locations
  • Nutrients (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
Funders
  • New Petfood Italia Srl
  • ex-60% University of Brescia (Italy)
  • Serbian Ministry of Education, Science and Technological Development (#173055)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
Keywords
melatonin, obesity, leptin deficiency, ob/ob mice, cardiomyocytes, mitochondrial dysfunction, mitochondrial cristae, 4-hydroxynonenal, lipid peroxidation, mitofusin 2, p62, autophagy, adipose tissue, adiponectin, cardioprotection, oxidative stress
MeSH terms
Sequestosome-1 Protein, Aldehydes, Animals, Disease Models, Animal, Gene Expression Regulation, Heart, Melatonin, Mice, Obese, Mitochondria, Heart, Obesity, Lipid Peroxidation, Gene Deletion, GTP Phosphohydrolases, Leptin, Myocytes, Cardiac, Mice, Adiponectin

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