Melatonin Enhances the Mitochondrial Functionality of Brown Adipose Tissue in Obese—Diabetic Rats
Metadatos
Mostrar el registro completo del ítemAutor
Agil Abdalla, Mhmad Ahmad; Navarro Alarcón, Miguel; Zakaib Ali, Fatma Abo; Albrakati, Ashraf; Salagre Simón, Diego; Campoy Folgoso, Cristina; Kotb Elmahallawy, EhabEditorial
MDPI
Materia
Melatonin Brown adipose tissue Mitochondrial function/dynamic Zücker diabetic fatty rat
Fecha
2021Referencia bibliográfica
Agil, A.; Navarro-Alarcon, M.; Ali, F.A.Z.; Albrakati, A.; Salagre, D.; Campoy, C.; Elmahallawy, E.K. Melatonin Enhances the Mitochondrial Functionality of Brown Adipose Tissue in Obese—Diabetic Rats. Antioxidants 2021, 10, 1482. https://doi.org/ 10.3390/antiox10091482
Patrocinador
SAF2016-79794-R from the Ministerio de Ciencia e Innovación (Spain); European Regional Development Fund (ERDF)Resumen
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.