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Melatonin Alleviates Liver Mitochondrial Dysfunction in Leptin-Deficient Mice
Beatriz de Luxán-Delgado1, Yaiza Potes1,2,3, Adrian Rubio-González1,2,3
1Department of Morphology and Cell Biology, University of Oviedo, Julián Clavería s/n, 33006 Oviedo, Spain.
Abstract:
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.
Insights
Melatonin treatment improved liver mitochondrial function and lipid metabolism in leptin-deficient mice. This suggests melatonin may be a therapeutic agent for obesity-related fatty liver disease.
Area of Science:
- Mitochondrial biology
- Obesity research
- Endocrinology
Background:
- Cellular bioenergetics is a key target for understanding obesity's harmful effects.
- Obesity leads to hazardous cellular adaptations requiring new therapeutic strategies.
Purpose of the Study:
- To investigate the effects of melatonin on liver mitochondrial function and lipid metabolism.
- To evaluate melatonin as a potential therapeutic agent for obesity-induced liver conditions.
Main Methods:
- Treatment of leptin-deficient (ob/ob) mice with melatonin for 4 weeks.
- Assessment of liver mitochondrial function, including ATP production, reactive oxygen species (ROS) levels, and electron transport chain (ETC) activity.
- Analysis of lipid metabolism and mitochondrial dynamics (biogenesis, fusion).
Main Results:
- Leptin deficiency caused increased liver lipid storage, mitochondrial dysfunction (impaired ATP production, ROS overproduction), and altered mitochondrial dynamics.
- Melatonin treatment ameliorated these defects, reducing the bioenergetic deficit and improving mitochondrial homeostasis.
- Melatonin alleviated alterations in ETC machinery, biogenesis, dynamics, respiration, and outer membrane permeabilization.
Conclusions:
- Melatonin effectively counteracted obesity-induced mitochondrial dysfunction and lipid accumulation in the liver.
- Melatonin demonstrates potential as a therapeutic agent for treating adipogenic steatosis and related metabolic disorders.
