PMID- 34573114
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211001
IS  - 2076-3921 (Print)
IS  - 2076-3921 (Electronic)
IS  - 2076-3921 (Linking)
VI  - 10
IP  - 9
DP  - 2021 Sep 17
TI  - Melatonin Enhances the Mitochondrial Functionality of Brown Adipose Tissue in 
      Obese-Diabetic Rats.
LID - 10.3390/antiox10091482 [doi]
LID - 1482
AB  - 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 Zucker 
      diabetic fatty (ZDF) rats, which are considered a model of obesity-related type 2 
      diabetes mellitus (T2DM). At five weeks of age, Zucker 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.
FAU - Agil, Ahmad
AU  - Agil A
AUID- ORCID: 0000-0003-0164-9648
AD  - Department of Pharmacology and Neurosciences Institute, School of Medicine, 
      University of Granada, 18016 Granada, Spain.
AD  - Biosanitary Research Institute of Granada (ibs.GRANADA), University Hospital of 
      Granada, 18016 Granada, Spain.
FAU - Navarro-Alarcon, Miguel
AU  - Navarro-Alarcon M
AUID- ORCID: 0000-0002-3189-3310
AD  - Department of Nutrition and Bromatology, School of Pharmacy, University of 
      Granada, 18071 Granada, Spain.
FAU - Ali, Fatma Abo Zakaib
AU  - Ali FAZ
AUID- ORCID: 0000-0001-6415-0647
AD  - Department of Pathology and Clinical Pathology, Faculty of Veterinary Medicine, 
      Sohag University, Sohag 82524, Egypt.
FAU - Albrakati, Ashraf
AU  - Albrakati A
AUID- ORCID: 0000-0002-4116-7865
AD  - Department of Human Anatomy, College of Medicine, Taif University, P.O. Box 
      11099, Taif 21944, Saudi Arabia.
FAU - Salagre, Diego
AU  - Salagre D
AUID- ORCID: 0000-0003-2888-6272
AD  - Department of Pharmacology and Neurosciences Institute, School of Medicine, 
      University of Granada, 18016 Granada, Spain.
AD  - Biosanitary Research Institute of Granada (ibs.GRANADA), University Hospital of 
      Granada, 18016 Granada, Spain.
FAU - Campoy, Cristina
AU  - Campoy C
AUID- ORCID: 0000-0002-9860-6785
AD  - Biosanitary Research Institute of Granada (ibs.GRANADA), University Hospital of 
      Granada, 18016 Granada, Spain.
AD  - Department of Pediatric, School of Medicine, University of Granada, 18071 
      Granada, Spain.
FAU - Elmahallawy, Ehab Kotb
AU  - Elmahallawy EK
AUID- ORCID: 0000-0003-4484-3678
AD  - Department of Zoonoses, Faculty of Veterinary Medicine, Sohag University, Sohag 
      82524, Egypt.
LA  - eng
PT  - Journal Article
DEP - 20210917
PL  - Switzerland
TA  - Antioxidants (Basel)
JT  - Antioxidants (Basel, Switzerland)
JID - 101668981
PMC - PMC8466890
OTO - NOTNLM
OT  - Zucker diabetic fatty rat
OT  - brown adipose tissue
OT  - melatonin
OT  - mitochondrial function
COIS- The authors declare no conflict of interest.
EDAT- 2021/09/29 06:00
MHDA- 2021/09/29 06:01
PMCR- 2021/09/17
CRDT- 2021/09/28 01:08
PHST- 2021/07/29 00:00 [received]
PHST- 2021/09/07 00:00 [revised]
PHST- 2021/09/13 00:00 [accepted]
PHST- 2021/09/28 01:08 [entrez]
PHST- 2021/09/29 06:00 [pubmed]
PHST- 2021/09/29 06:01 [medline]
PHST- 2021/09/17 00:00 [pmc-release]
AID - antiox10091482 [pii]
AID - antioxidants-10-01482 [pii]
AID - 10.3390/antiox10091482 [doi]
PST - epublish
SO  - Antioxidants (Basel). 2021 Sep 17;10(9):1482. doi: 10.3390/antiox10091482.