Melatonin prevents mitochondrial dysfunction and insulin resistance in rat skeletal muscle

Teodoro, Bruno Gonzaga; Baraldi, Flávia G.; Sampaio, Igor H.; Bomfim, Lucas Henrique Montes; Queiroz, André Lima; Passos, Madla A.; Carneiro, Everardo M.; Alberici, Luciane C.; Gomis, Ramón; Amaral, Fernanda Gaspar do; Cipolla‐Neto, José; Araújo, Michel Barbosa de; Lima, Tanes I.; Uyemura, Sérgio Akira; Silveira, Leonardo R.; Vieira, Elaine

doi:10.1111/jpi.12157

Cited by 92 publications

(80 citation statements)

References 45 publications

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“…The above hypothesis is supported by the observation that the exposure to saturated fatty acids of isolated mitochondria (Abdul-Ghani et al 2008) or cells (Hirabara et al 2010, Jheng et al 2012, Yang et al 2012, Teodoro et al 2014 clearly elicits mitochondrial dysfunction, which in the cells is accompanied by IR. However, in more complex systems, such as in men and experimental animal models, the link between plasma NEFA delivery to skeletal muscle, mitochondrial impairment and insulin resistance is less strong.…”

Section: Mitochondrial Dysfunction In Insulin Resistancesupporting

confidence: 61%

Skeletal muscle insulin resistance: role of mitochondria and other ROS sources

Meo

Iossa

Venditti

2017

Journal of Endocrinology

228

103

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At present, obesity is one of the most important public health problems in the world because it causes several diseases and reduces life expectancy. Although it is well known that insulin resistance plays a pivotal role in the development of type 2 diabetes mellitus (the more frequent disease in obese people) the link between obesity and insulin resistance is yet a matter of debate. One of the most deleterious effects of obesity is the deposition of lipids in non-adipose tissues when the capacity of adipose tissue is overwhelmed. During the last decade, reduced mitochondrial function has been considered as an important contributor to 'toxic' lipid metabolite accumulation and consequent insulin resistance. More recent reports suggest that mitochondrial dysfunction is not an early event in the development of insulin resistance, but rather a complication of the hyperlipidemia-induced reactive oxygen species (ROS) production in skeletal muscle, which might promote mitochondrial alterations, lipid accumulation and inhibition of insulin action. Here, we review the literature dealing with the mitochondria-centered mechanisms proposed to explain the onset of obesity-linked IR in skeletal muscle. We conclude that the different pathways leading to insulin resistance may act synergistically because ROS production by mitochondria and other sources can result in mitochondrial dysfunction, which in turn can further increase ROS production leading to the establishment of a harmful positive feedback loop.

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Section: Mitochondrial Dysfunction In Insulin Resistancesupporting

confidence: 61%

Skeletal muscle insulin resistance: role of mitochondria and other ROS sources

Meo

Iossa

Venditti

2017

Journal of Endocrinology

228

103

View full text Add to dashboard Cite

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“…(F) Insulin sensitivity index (ISI; L 4 /mmol 2 *mU 2 ); statistical comparisons were made by Mann-Whitney U test; *p < 0.05; mean ± SEM. See also Figure S4. tolerance has been reported after melatonin therapy (RubioSastre et al, 2014;Teodoro et al, 2014). The use of different species and experimental models may be a reason for these discrepancies.…”

Section: Discussionmentioning

confidence: 93%

Increased Melatonin Signaling Is a Risk Factor for Type 2 Diabetes

et al. 2016

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Type 2 diabetes (T2D) is a global pandemic. Genome-wide association studies (GWASs) have identified >100 genetic variants associated with the disease, including a common variant in the melatonin receptor 1 b gene (MTNR1B). Here, we demonstrate increased MTNR1B expression in human islets from risk G-allele carriers, which likely leads to a reduction in insulin release, increasing T2D risk. Accordingly, in insulin-secreting cells, melatonin reduced cAMP levels, and MTNR1B overexpression exaggerated the inhibition of insulin release exerted by melatonin. Conversely, mice with a disruption of the receptor secreted more insulin. Melatonin treatment in a human recall-by-genotype study reduced insulin secretion and raised glucose levels more extensively in risk G-allele carriers. Thus, our data support a model where enhanced melatonin signaling in islets reduces insulin secretion, leading to hyperglycemia and greater future risk of T2D. The findings also imply that melatonin physiologically serves to inhibit nocturnal insulin release.

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“…Secondly, our study is the first to show the arsenite-induced reduction in PGC-1α levels, a transcriptional co-activator which controls mitochondrial biosynthesis [48][49][50]. Previous studies have reported that melatonin improved mitochondrial function by promoting PGC-1α-dependent mitochondrial biogenesis in hepatocytes [51] and skeletal muscle cells [52]. Accordingly, melatonin may maintain mitochondrial mass by increasing PGC-1 levels in arsenite-treated primary cultured cortical neurons.…”

Section: Melatonin Attenuates Arsenite-induced Mitochondrial Lossmentioning

confidence: 85%

Melatonin Ameliorates Arsenite-Induced Neurotoxicity: Involvement of Autophagy and Mitochondria

Teng¹,

Tai²,

Huang

et al. 2015

Mol Neurobiol

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In the present study, the neuroprotective effect of melatonin on arsenite-induced neurotoxicity was investigated in rat primary cultured cortical neurons. Incubation of melatonin prevented arsenite-induced neuronal cell loss in a concentration-dependent manner. Furthermore, melatonin significantly attenuated arsenite-induced elevation in microtubule-associated protein light chain 3 (LC3)-II levels, a biomarker of autophagy. Our fluorescent staining assay showed that melatonin decreased arsenite-induced elevation of co-localized fluorescent puncta of monodansylcadaverine (a specific marker of autophagic vacuoles) and lysotracker red (a specific marker of lysosomes), indicating that melatonin is capable of inhibiting arsenite-induced autophagy and autolysosome formation. Because 3-methyladenine (an autophagic inhibitor) attenuated the arsenite-reduced α-synuclein levels (a protein essential for the neurite outgrowth and synaptic plasticity), melatonin via inhibiting autophagy attenuated the arsenite-reduced α-synuclein levels. At the same time, melatonin ameliorated the arsenite-induced reduction in growth associated protein 43 (a hallmark protein of neurite outgrowth) and discontinuous neurites of rat primary cultured cortical neurons. In addition, melatonin was found to prevent arsenite-induced decreases in cytochrome c oxidase levels (a biomarker of mitochondrial mass) and elevation in co-localized fluorescent puncta of autolysosomes and cytochrome c oxidase. Moreover, melatonin prevented arsenite-induced reduction in peroxisome proliferator-activated receptor gamma co-activator 1 α, a transcriptional co-activator of mitochondrial biosynthesis. Taken together, melatonin may exert its neuroprotective action via inhibiting arsenite-induced autophagy and enhancing mitochondrial biogenesis and thus restoring α-synuclein levels, neuronal integrity, and mitochondrial mass in rat primary cultured cortical neurons.

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Melatonin prevents mitochondrial dysfunction and insulin resistance in rat skeletal muscle

Cited by 92 publications

References 45 publications

Skeletal muscle insulin resistance: role of mitochondria and other ROS sources

Skeletal muscle insulin resistance: role of mitochondria and other ROS sources

Increased Melatonin Signaling Is a Risk Factor for Type 2 Diabetes

Melatonin Ameliorates Arsenite-Induced Neurotoxicity: Involvement of Autophagy and Mitochondria

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