Melatonin Alleviates Liver Mitochondrial Dysfunction in Leptin-Deficient Mice

• Published in: International journal of molecular sciences Vol. 25; no. 16; p. 8677
• Main Authors: de Luxán-Delgado, Beatriz, Potes, Yaiza, Rubio-González, Adrian, Solano, Juan José, Boga, José Antonio, Antuña, Eduardo, Cachán-Vega, Cristina, Bermejo-Millo, Juan Carlos, Menéndez-Coto, Nerea, García-González, Claudia, Pereira, Gonçalo C, Caballero, Beatriz, Coto-Montes, Ana, Vega-Naredo, Ignacio
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 08-08-2024; MDPI
• Subjects: Adenosine Triphosphate - metabolism; adipogenesis; Animals; Biosynthesis; Body fat; Circadian rhythm; Cytochrome; Dehydrogenases; Diabetes; Energy Metabolism - drug effects; Glucose; Homeostasis; Insulin resistance; Leptin - deficiency; Leptin - metabolism; Lipid Metabolism - drug effects; Lipids; Liver; Liver - drug effects; Liver - metabolism; Male; Melatonin; Melatonin - pharmacology; Metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Mitochondria; Mitochondria, Liver - drug effects; Mitochondria, Liver - metabolism; Mitochondrial DNA; mitochondrial dysfunction; Obesity; Obesity - drug therapy; Obesity - metabolism; Oxidation; Proteins; Reactive Oxygen Species - metabolism; Respiration; Weight control; mitochondrial dysfunction; adipogenesis; melatonin; liver; leptin deficiency; obesity
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25168677

Despite efforts to elucidate the cellular adaptations induced by obesity, cellular bioenergetics is currently considered a crucial target. 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.