Melatonin Enhances the Mitochondrial Functionality of Brown Adipose Tissue in Obese—Diabetic Rats
Developing novel drugs/targets remains a major effort toward controlling obesity-related type 2 diabetes (diabesity). Melatonin controls obesity and improves glucose homeostasis in rodents, mainly via the thermogenic effects of increasing the amount of brown adipose tissue (BAT) and increases in mit...
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MDPI AG
2021-09-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/9/1482 |
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| author | Ahmad Agil Miguel Navarro-Alarcon Fatma Abo Zakaib Ali Ashraf Albrakati Diego Salagre Cristina Campoy Ehab Kotb Elmahallawy |
| author_facet | Ahmad Agil Miguel Navarro-Alarcon Fatma Abo Zakaib Ali Ashraf Albrakati Diego Salagre Cristina Campoy Ehab Kotb Elmahallawy |
| author_sort | Ahmad Agil |
| collection | DOAJ |
| description | Developing novel drugs/targets remains a major effort toward controlling obesity-related type 2 diabetes (diabesity). Melatonin controls obesity and improves glucose homeostasis in rodents, mainly via the thermogenic effects of increasing the amount of brown adipose tissue (BAT) and increases in mitochondrial mass, amount of UCP1 protein, and thermogenic capacity. Importantly, mitochondria are widely known as a therapeutic target of melatonin; however, direct evidence of melatonin on the function of mitochondria from BAT and the mechanistic pathways underlying these effects remains lacking. This study investigated the effects of melatonin on mitochondrial functions in BAT of Zücker diabetic fatty (ZDF) rats, which are considered a model of obesity-related type 2 diabetes mellitus (T2DM). At five weeks of age, Zücker lean (ZL) and ZDF rats were subdivided into two groups, consisting of control and treated with oral melatonin for six weeks. Mitochondria were isolated from BAT of animals from both groups, using subcellular fractionation techniques, followed by measurement of several mitochondrial parameters, including respiratory control ratio (RCR), phosphorylation coefficient (ADP/O ratio), ATP production, level of mitochondrial nitrites, superoxide dismutase activity, and alteration in the mitochondrial permeability transition pore (mPTP). Interestingly, melatonin increased RCR in mitochondria from brown fat of both ZL and ZDF rats through the reduction of the proton leak component of respiration (state 4). In addition, melatonin improved the ADP/O ratio in obese rats and augmented ATP production in lean rats. Further, melatonin reduced mitochondrial nitrosative and oxidative status by decreasing nitrite levels and increasing superoxide dismutase activity in both groups, as well as inhibited mPTP in mitochondria isolated from brown fat. Taken together, the present data revealed that chronic oral administration of melatonin improved mitochondrial respiration in brown adipocytes, while decreasing oxidative and nitrosative stress and susceptibility of adipocytes to apoptosis in ZDF rats, suggesting a beneficial use in the treatment of diabesity. Further research regarding the molecular mechanisms underlying the effects of melatonin on diabesity is warranted. |
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| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T07:56:23Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-b8cb444f19e444e8ad070ab67d6c0f092023-11-22T11:49:29ZengMDPI AGAntioxidants2076-39212021-09-01109148210.3390/antiox10091482Melatonin Enhances the Mitochondrial Functionality of Brown Adipose Tissue in Obese—Diabetic RatsAhmad Agil0Miguel Navarro-Alarcon1Fatma Abo Zakaib Ali2Ashraf Albrakati3Diego Salagre4Cristina Campoy5Ehab Kotb Elmahallawy6Department of Pharmacology and Neurosciences Institute, School of Medicine, University of Granada, 18016 Granada, SpainDepartment of Nutrition and Bromatology, School of Pharmacy, University of Granada, 18071 Granada, SpainDepartment of Pathology and Clinical Pathology, Faculty of Veterinary Medicine, Sohag University, Sohag 82524, EgyptDepartment of Human Anatomy, College of Medicine, Taif University, P.O. Box 11099, Taif 21944, Saudi ArabiaDepartment of Pharmacology and Neurosciences Institute, School of Medicine, University of Granada, 18016 Granada, SpainBiosanitary Research Institute of Granada (ibs.GRANADA), University Hospital of Granada, 18016 Granada, SpainDepartment of Zoonoses, Faculty of Veterinary Medicine, Sohag University, Sohag 82524, EgyptDeveloping novel drugs/targets remains a major effort toward controlling obesity-related type 2 diabetes (diabesity). Melatonin controls obesity and improves glucose homeostasis in rodents, mainly via the thermogenic effects of increasing the amount of brown adipose tissue (BAT) and increases in mitochondrial mass, amount of UCP1 protein, and thermogenic capacity. Importantly, mitochondria are widely known as a therapeutic target of melatonin; however, direct evidence of melatonin on the function of mitochondria from BAT and the mechanistic pathways underlying these effects remains lacking. This study investigated the effects of melatonin on mitochondrial functions in BAT of Zücker diabetic fatty (ZDF) rats, which are considered a model of obesity-related type 2 diabetes mellitus (T2DM). At five weeks of age, Zücker lean (ZL) and ZDF rats were subdivided into two groups, consisting of control and treated with oral melatonin for six weeks. Mitochondria were isolated from BAT of animals from both groups, using subcellular fractionation techniques, followed by measurement of several mitochondrial parameters, including respiratory control ratio (RCR), phosphorylation coefficient (ADP/O ratio), ATP production, level of mitochondrial nitrites, superoxide dismutase activity, and alteration in the mitochondrial permeability transition pore (mPTP). Interestingly, melatonin increased RCR in mitochondria from brown fat of both ZL and ZDF rats through the reduction of the proton leak component of respiration (state 4). In addition, melatonin improved the ADP/O ratio in obese rats and augmented ATP production in lean rats. Further, melatonin reduced mitochondrial nitrosative and oxidative status by decreasing nitrite levels and increasing superoxide dismutase activity in both groups, as well as inhibited mPTP in mitochondria isolated from brown fat. Taken together, the present data revealed that chronic oral administration of melatonin improved mitochondrial respiration in brown adipocytes, while decreasing oxidative and nitrosative stress and susceptibility of adipocytes to apoptosis in ZDF rats, suggesting a beneficial use in the treatment of diabesity. Further research regarding the molecular mechanisms underlying the effects of melatonin on diabesity is warranted.https://www.mdpi.com/2076-3921/10/9/1482melatoninbrown adipose tissuemitochondrial functionZücker diabetic fatty rat |
| spellingShingle | Ahmad Agil Miguel Navarro-Alarcon Fatma Abo Zakaib Ali Ashraf Albrakati Diego Salagre Cristina Campoy Ehab Kotb Elmahallawy Melatonin Enhances the Mitochondrial Functionality of Brown Adipose Tissue in Obese—Diabetic Rats Antioxidants melatonin brown adipose tissue mitochondrial function Zücker diabetic fatty rat |
| title | Melatonin Enhances the Mitochondrial Functionality of Brown Adipose Tissue in Obese—Diabetic Rats |
| title_full | Melatonin Enhances the Mitochondrial Functionality of Brown Adipose Tissue in Obese—Diabetic Rats |
| title_fullStr | Melatonin Enhances the Mitochondrial Functionality of Brown Adipose Tissue in Obese—Diabetic Rats |
| title_full_unstemmed | Melatonin Enhances the Mitochondrial Functionality of Brown Adipose Tissue in Obese—Diabetic Rats |
| title_short | Melatonin Enhances the Mitochondrial Functionality of Brown Adipose Tissue in Obese—Diabetic Rats |
| title_sort | melatonin enhances the mitochondrial functionality of brown adipose tissue in obese diabetic rats |
| topic | melatonin brown adipose tissue mitochondrial function Zücker diabetic fatty rat |
| url | https://www.mdpi.com/2076-3921/10/9/1482 |
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