Melatonin Signaling a Key Regulator of Glucose Homeostasis and Energy Metabolism

Owino, Sharon; Buonfiglio, Daniella do Carmo; Tchio, Cynthia; Tosini, Gianluca

doi:10.3389/fendo.2019.00488

Cited by 86 publications

(57 citation statements)

References 67 publications

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“…For example, mouse removal of MT 1 leads to systemic insulin resistance by modulating of PI3K transcription and activity. [55][56][57] In turn, circadian time also affects melatonin-mediated responses via MT receptors. 58 Indeed, mice lacking MT 1 show a tendency to accumulate more fat mass and weight gain and induce leptin resistance in an arcuate nucleus region-specific manner.…”

Section: Melatoninmentioning

confidence: 99%

Circadian rhythms and obesity: Timekeeping governs lipid metabolism

Yao

et al. 2020

Journal of Pineal Research

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115

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Almost all living organisms have evolved autoregulatory transcriptional‐translational feedback loops that produce oscillations with a period of approximately 24‐h. These endogenous time keeping mechanisms are called circadian clocks. The main function of these circadian clocks is to drive overt circadian rhythms in the physiology of the organisms to ensure that main physiological functions are in synchrony with the external environment. Disruption of circadian rhythms caused by genetic or environmental factors has long‐term consequences for metabolic health. Of relevance, host circadian rhythmicity and lipid metabolism are increasingly recognized to cross‐regulate and the circadian clock‐lipid metabolism interplay may involve in the development of obesity. Multiple systemic and molecular mechanisms, such as hormones (ie, melatonin, leptin, and glucocorticoid), the gut microbiome, and energy metabolism, link the circadian clock and lipid metabolism, and predictably, the deregulation of circadian clock‐lipid metabolism interplay can increase the risk of obesity, which in turn may exacerbate circadian disorganization. Feeding time and dietary nutrients are two of key environmental Zeitgebers affecting the circadian rhythm‐lipid metabolism interplay, and the influencing mechanisms in obesity development are highlighted in this review. Together, the characterization of the clock machinery in lipid metabolism aimed at producing a healthy circadian lifestyle may improve obesity care.

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Section: Melatoninmentioning

confidence: 99%

Circadian rhythms and obesity: Timekeeping governs lipid metabolism

Yao

et al. 2020

Journal of Pineal Research

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115

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“…Moreover, MT 1 KO mice subjected to a high‐fat diet also showed a significant increase in cumulative weight gain and basal glucose levels (>200 mg/dL) after 10 weeks 11 . Interestingly in our previous study, we did not observe any phenotype in mice lacking MT 2 11,13 …”

Section: Introductionmentioning

confidence: 57%

Removal of melatonin receptor type 1 signalling induces dyslipidaemia and hormonal changes in mice subjected to environmental circadian disruption

Tchio

Baba

Piccione

et al. 2020

Endocrino Diabet & Metabol

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Background Melatonin is a hormone secreted by the pineal gland in a circadian rhythmic manner with peak synthesis at night. Melatonin signalling was suggested to play a critical role in metabolism during the circadian disruption. Methods Melatonin‐proficient (C3H‐f+/+ or WT) and melatonin receptor type 1 knockout (MT1 KO) male and female mice were phase‐advanced (6 hours) once a week for 6 weeks. Every week, we measured weight, food intake and basal glucose levels. At the end of the experiment, we sacrificed the animals and measured the blood's plasma for lipids profile (total lipids, phospholipids, triglycerides and total cholesterol), metabolic hormones profiles (ghrelin, leptin, insulin, glucagon, glucagon‐like‐peptide and resistin) and the body composition. Results Environmental circadian disruption (ECD) did not produce any significant effects in C3H‐f+/+, while it increased lipids profile in MT1 KO with the significant increase observed in total lipids and triglycerides. For metabolic hormones profile, ECD decreased plasma ghrelin and increased plasma insulin in MT1 KO females. Under control condition, MT1 KO females have significantly different body weight, fat mass, total lipids and total cholesterol than the control C3H‐f+/+ females. Conclusion Our data show that melatonin‐proficient mice are not affected by ECD. When the MT1 receptors are removed, ECD induced dyslipidaemia in males and females with females experiencing the most adverse effect. Overall, our data demonstrate that MT1 signalling is an essential modulator of lipid and metabolic homeostasis during ECD.

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“…The neurohormone melatonin (5-methoxy-N-acetyltryptamine), mainly produced by the pineal gland, has multiple actions including the modulation of circadian and seasonal rhythms, sleep, and glucose regulation in mammals ( Dubocovich et al, 2010 ; Gobbi and Comai, 2019 ; Karamitri and Jockers, 2019 ; Owino et al, 2019 ). Circadian melatonin production is controlled by endogenous oscillators within the hypothalamic suprachiasmatic nucleus (SCN), the biological master clock, and entrained by the environmental light-dark cycle with nocturnal peak levels ( Zhao et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

“…Previous evidence from animal and human studies indicate that melatonin also modulates glucose metabolism ( Van Cauter et al, 1997 ; Owino et al, 2019 ). The underlying mechanisms are not well understood, but current data indicates that melatonin can act through central and peripheral receptors to directly and indirectly modulate glucose uptake, pancreatic insulin secretion, and β-cell survival ( Wehrens et al, 2017 ; Karamitri and Jockers, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Circadian, Sleep and Caloric Intake Phenotyping in Type 2 Diabetes Patients With Rare Melatonin Receptor 2 Mutations and Controls: A Pilot Study

et al. 2020

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Background Melatonin modulates circadian rhythms in physiology and sleep initiation. Genetic variants of the MTNR1B locus, encoding the melatonin MT 2 receptor, have been associated with increased type 2 diabetes (T2D) risk. Carriers of the common intronic MTNR1B rs10830963 T2D risk variant have modified sleep and circadian traits such as changes of the melatonin profile. However, it is currently unknown whether rare variants in the MT 2 coding region are also associated with altered sleep and circadian phenotypes, including meal timing. Materials and Methods In this pilot study, 28 individuals [50% male; 46–82 years old; 50% with rare MT 2 mutations (T2D MT 2 )] wore actigraphy devices and filled out daily food logs for 4 weeks. We computed circadian, sleep, and caloric intake phenotypes, including sleep duration, timing, and regularity [assessed by the Sleep Regularity Index (SRI)]; composite phase deviations (CPD) as well a sleep timing-based proxy for circadian misalignment; and caloric intake patterns throughout the day. Using regression analyses, we estimated age- and sex-adjusted mean differences (MD) and 95% confidence intervals (95%CI) between the two patient groups. Secondary analyses also compare T2D MT 2 to 15 healthy controls. Results Patients with rare MT 2 mutations had a later sleep onset (MD = 1.23, 95%CI = 0.42;2.04), and midsleep time (MD = 0.91, 95%CI = 0.12;1.70), slept more irregularly (MD in SRI = −8.98, 95%CI = −16.36;−1.60), had higher levels of behavioral circadian misalignment (MD in CPD = 1.21, 95%CI = 0.51;1.92), were more variable in regard to duration between first caloric intake and average sleep offset (MD = 1.08, 95%CI = 0.07;2.08), and had more caloric episodes in a 24 h day (MD = 1.08, 95%CI = 0.26;1.90), in comparison to T2D controls. Secondary analyses showed similar patterns between T2D MT 2 and non-diabetic controls. Conclusion This pilot study suggests that compared to diabetic controls, T2D MT 2 patients display a number of adverse sleep, circadian, and caloric intake phenotypes, including more irregular behavioral timing. A prospective study is needed to determine the role of these behavioral phenotypes in T2D onset and severity, especially in view of rare MT 2 mutations.

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Melatonin Signaling a Key Regulator of Glucose Homeostasis and Energy Metabolism

Cited by 86 publications

References 67 publications

Circadian rhythms and obesity: Timekeeping governs lipid metabolism

Circadian rhythms and obesity: Timekeeping governs lipid metabolism

Removal of melatonin receptor type 1 signalling induces dyslipidaemia and hormonal changes in mice subjected to environmental circadian disruption

Circadian, Sleep and Caloric Intake Phenotyping in Type 2 Diabetes Patients With Rare Melatonin Receptor 2 Mutations and Controls: A Pilot Study

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