Publications by authors named "José Cipolla-Neto"

96 Publications

Exogenous melatonin decreases circadian misalignment and body weight among early types.

J Pineal Res 2021 Jun 6:e12750. Epub 2021 Jun 6.

Department of Health, Life Cycles and Society, School of Public Health, University of São Paulo, São Paulo, Brazil.

Shift workers experience chronic circadian misalignment, which can manifest itself in reduced melatonin production, and has been associated with metabolic disorders. In addition, chronotype modulates the effect of night shift work, with early types presenting greater circadian misalignment when working night shift as compared to late types. Melatonin supplementation has shown positive results reducing weight gain in animal models, but the effect of exogenous melatonin in humans on body weight in the context of shift work remains inconsistent. The aim of this study was thus to evaluate the effects of exogenous melatonin on circadian misalignment and body weight among overweight night shift workers, according to chronotype, under real-life conditions. We conducted a double-blind, randomized, placebo-controlled, crossover trial where melatonin (3 mg) or placebo was administered on non-night shift nights for 12 weeks in 27 female nurses (37.1 yo, ±5.9 yo; BMI 29.9 kg/m , ±3.3 kg/m ). Melatonin (or placebo) was only taken on nights when the participants did not work night shifts, that is, on nights when they slept (between night shifts and on days off). Composite Phase Deviations (CPD) of actigraphy-based mid-sleep timing were calculated to measure circadian misalignment. The analyses were performed for the whole group and by chronotype. We found approximately 20% reduction in circadian misalignment after exogenous melatonin administration considering all chronotypes. Moreover, melatonin supplementation in those who presented high circadian misalignment, as observed in early chronotypes, reduced body weight, BMI, waist circumference, and hip circumference, without any change in the participants' calorie intake or physical activity levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jpi.12750DOI Listing
June 2021

The crosstalk between melatonin and sex steroid hormones.

Neuroendocrinology 2021 Mar 26. Epub 2021 Mar 26.

Melatonin, an indolamine mainly released from the pineal gland, is associated with many biological functions namely the modulation of circadian and seasonal rhythms, sleep inducer, regulator of energy metabolism, antioxidant and anticarcinogenic. Although several evidences also recognize the influence of melatonin in the reproductive physiology, the crosstalk between melatonin and sex hormones is not clear. Here, we review the effects of sex differences in the circulating levels of melatonin and update the current knowledge on the link between sex hormones and melatonin. Furthermore, we explore the effects of melatonin on gonadal steroidogenesis and hormonal control in females. The literature review shows that despite the strong evidence that sex differences impact on the circadian profiles of melatonin, reports are still considerably ambiguous and these differences may arise from several factors, like the use of contraceptive pills, hormonal status and sleep deprivation. Furthermore, there has been an inconclusive debate about the characteristics of the reciprocal relationship between melatonin and reproductive hormones. In this regard, there is evidence for the role of melatonin in gonadal steroidogenesis brought about by research that shows that melatonin affects multiple transduction pathways that modulate Sertoli cell physiology and consequently spermatogenesis, and also estrogen and progesterone production. From the outcome of our research, it is possible to conclude that understanding the correlation between melatonin and reproductive hormones is crucial for the correction of several complications occurring during pregnancy, like pre-eclampsia and for the control of climacteric symptoms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000516148DOI Listing
March 2021

Pretreatment with melatonin improves ovarian tissue cryopreservation for transplantation.

Reprod Biol Endocrinol 2021 Feb 3;19(1):17. Epub 2021 Feb 3.

Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Av. Dr. Arnaldo, 455 - Cerqueira César, São Paulo, SP, CEP 01246-903, Brazil.

Backgroud: Melatonin has anti-inflammatory and antioxidative actions at the mitochondrial level. This indole-containing molecule may protect ovarian grafts during the process of cryopreservation. Therefore, we aimed to determine whether melatonin pretreatment improves rat ovarian graft quality.

Methods: Twenty-six female rats were allocated to two study groups of thirteen animals each: 1) control group: ovaries cryopreserved using the standard protocol; and 2) melatonin group: ovaries cryopreserved in a medium with melatonin. Ten rats of each group were submitted to 24-h freezing, and whole ovaries autologous and avascular transplantation with retroperitoneal placement. After postoperative (PO) day 15, daily vaginal smears were obtained for estrous cycle characterization. Between PO days 30 and 35, the animals were euthanized and ovarian grafts were recovered for histological and immunohistochemical (Ki-67, cleaved caspase-3, TUNEL, von Willebrand factor, estrogen, and progesterone receptors) analyses. The ovaries of the three remaining rats from each group were studied immediately after thawing to assess the effects of cryopreservation. ANOVA and Tukey's tests were used and the rejection level of the null hypothesis was set at 0.05 or 5% (p < 0.05).

Results: Melatonin promoted faster restart of the estrous cycle and increased the expression of mature follicles, collagen type I, von Willebrand factor, Ki-67, and cleaved caspase-3 on corpora lutea and estrogen receptors in the ovaries as compared to control. There was a reduction in apoptosis by TUNEL on follicles, corpora lutea, and collagen type III.

Conclusion: Based on the evaluated parameters, melatonin may promote the quality of ovarian grafts. Reproductive function enhancement should be further studied.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12958-021-00705-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856714PMC
February 2021

Melatonin regulates maternal pancreatic remodeling and B-cell function during pregnancy and lactation.

J Pineal Res 2021 Aug 1;71(1):e12717. Epub 2021 Feb 1.

Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, São Paulo, Brazil.

The endocrine pancreas of pregnant rats shows evident plasticity, which allows the morphological structures to return to the nonpregnant state right after delivery. Furthermore, it is well-known the role of melatonin in the maintenance of the endocrine pancreas and its tropism. Studies indicate increasing nocturnal serum concentrations of maternal melatonin during pregnancy in both humans and rodents. The present study investigated the role of melatonin on energy metabolism and in pancreatic function and remodeling during pregnancy and early lactation in rats. The results confirm that the absence of melatonin during pregnancy impairs glucose metabolism. In addition, there is a dysregulation in insulin secretion at various stages of the development of pregnancy and an apparent failure in the glucose-stimulated insulin secretion during the lactation period, evidencing the role of melatonin on the regulation of insulin secretion. This mechanism seems not to be dependent on the antioxidant effect of melatonin and probably dependent on MT2 receptors. We also observed changes in the mechanisms of death and cell proliferation at the end of pregnancy and beginning of lactation, crucial periods for pancreatic remodeling. The present observations strongly suggest that both functionality and remodeling of the endocrine pancreas are impaired in the absence of melatonin and its adequate replacement, mimicking the physiological increase seen during pregnancy, is able to reverse some of the damage observed. Thus, we conclude that pineal melatonin is important to metabolic adaptation to pregnancy and both the functionality of the beta cells and the remodeling of the pancreas during pregnancy and early lactation, ensuring the return to nonpregnancy conditions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jpi.12717DOI Listing
August 2021

Eating habits, sleep, and a proxy for circadian disruption are correlated with dyslipidemia in overweight night workers.

Nutrition 2021 03 22;83:111084. Epub 2020 Nov 22.

Department of Epidemiology, Public Health Graduate Program, Catholic University of Santos, Sao Paulo, Brazil; Department of Health, Life Cycles and Society, School of Public Health, University of São Paulo, Sao Paulo, Brazil. Electronic address:

Objective: The aim of this study was to evaluate the relationship between proxy for circadian disruption, eating habits, sleep characteristics, and dyslipidemic parameters.

Methods: This was a randomized, double-blind, crossover controlled clinical trial, and for this study, only baseline data were used. The sample was composed of 36 overweight female nurses who worked on a fixed night shift (12 × 36 h). Linear regression models were used to assess the relationship between the mentioned variables.

Results: The participants' average age was 39.4 y (Standard error (SE) 1 y) and the average nighttime sleep duration was 5.76 h (SE 0.16 h). The average chronotype indicated a moderate early type (03:03 h; SE 20 min) and the average social jetlag was 03:42 h (SE 10 min). It was found that 1 h less of nighttime sleep increased very-low-density lipoprotein cholesterol levels by 2.75 mg/dL and triacylglyceride levels by 3.62 mg/dL. Additionally, higher social jetlag was associated with higher low-density lipoprotein cholesterol levels. On the other hand, each additional hour in the chronotype increased high-density lipoprotein cholesterol levels by 3.06 mg/dL and a time interval >2 h between the last meal and sleep onset was associated with higher high-density lipoprotein cholesterol levels.

Conclusion: Short duration of nighttime sleep and high social jetlag are risk factors for dyslipidemia, whereas the late type and the longer time interval between the last meal and sleep onset appear to be protective factors for dyslipidemia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nut.2020.111084DOI Listing
March 2021

The effects of melatonin daily supplementation to aged rats on the ability to withstand cold, thermoregulation and body weight.

Life Sci 2021 Jan 9;265:118769. Epub 2020 Dec 9.

Neurobiology Lab, Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil. Electronic address:

Aims: Investigate the role of melatonin on the regulation of body temperature in aged animals that have impaired melatonin production.

Material And Methods: Aged Male Wistar rats were randomly assigned to the following groups: 1) control (vehicle added to the water bottles during the dark phase) and 2) melatonin-treated (10 mg/kg melatonin added to the water bottles during the dark phase). Before and after 16 weeks of vehicle or melatonin treatment, control group and melatonin-treated animals were acutely exposed to 18 °C for 2 h for an acute cold challenge and thermal images were obtained using an infrared camera. After 16 weeks, animals were euthanized and brown and beige adipocytes were collected for analysis of genes involved in the thermogenesis process by real-time PCR, and the uncoupling protein expression was evaluated by immunoblotting. Browning intensity of beige adipocytes were quantified by staining with hematoxylin-eosin.

Key Findings: Chronic melatonin supplementation induced a minor increase in body mass and increased the animal's thermogenic potential in the cold acute challenge. Brown and beige adipocytes acted in a coordinated and complementary way to ensure adequate heat production.

Significance: Melatonin plays an important role in the thermoregulatory mechanisms, ensuring greater capacity to withstand cold and, also, participating in the regulation of energy balance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lfs.2020.118769DOI Listing
January 2021

Melatonin supplementation in the management of obesity and obesity-associated disorders: A review of physiological mechanisms and clinical applications.

Pharmacol Res 2021 01 17;163:105254. Epub 2020 Oct 17.

School of Medicine, Federal University of Uberlandia (UFU), Uberlandia, Minas Gerais, Brazil. Electronic address:

Despite the evolving advances in clinical approaches to obesity and its inherent comorbidities, the therapeutic challenge persists. Among several pharmacological tools already investigated, recent studies suggest that melatonin supplementation could be an efficient therapeutic approach in the context of obesity. In the present review, we have amalgamated the evidence so far available on physiological effects of melatonin supplementation in obesity therapies, addressing its effects upon neuroendocrine systems, cardiometabolic biomarkers and body composition. Most studies herein appraised employed melatonin supplementation at dosages ranging from 1 to 20 mg/day, and most studies followed up participants for periods from 3 weeks to 12 months. Overall, it was observed that melatonin plays an important role in glycaemic homeostasis, in addition to modulation of white adipose tissue activity and lipid metabolism, and mitochondrial activity. Additionally, melatonin increases brown adipose tissue volume and activity, and its antioxidant and anti-inflammatory properties have also been demonstrated. There appears to be a role for melatonin in adiposity reduction; however, several questions remain unanswered, for example melatonin baseline levels in obesity, and whether any seeming hypomelatonaemia or melatonin irresponsiveness could be clarifying factors. Supplementation dosage studies and more thorough clinical trials are needed to ascertain not only the relevance of such findings but also the efficacy of melatonin supplementation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phrs.2020.105254DOI Listing
January 2021

Maternal pineal melatonin in gestation and lactation physiology, and in fetal development and programming.

Gen Comp Endocrinol 2021 01 5;300:113633. Epub 2020 Oct 5.

Neurobiology Lab, Department of Physiology and Biophysics, 1524 Prof. Lineu Prestes Ave., Institute of Biomedical Sciences, Bldg 1, Lab 118, University of São Paulo, São Paulo 05508-000, Brazil. Electronic address:

Pregnancy and lactation are reproductive processes that rely on physiological adaptations that should be timely and adequately triggered to guarantee both maternal and fetal health. Pineal melatonin is a hormone that presents daily and seasonal variations that synchronizes the organism's physiology to the different demands across time through its specific mechanisms and ways of action. The reproductive system is a notable target for melatonin as it actively participates on reproductive physiology and regulates the hypothalamus-pituitary-gonads axis, influencing gonadotropins and sexual hormones synthesis and release. For its antioxidant properties, melatonin is also vital for the oocytes and spermatozoa quality and viability, and for blastocyst development. Maternal pineal melatonin blood levels increase during pregnancy and triggers the maternal physiological alterations in energy metabolism both during pregnancy and lactation to cope with the energy demands of both periods and to promote adequate mammary gland development. Moreover, maternal melatonin freely crosses the placenta and is the only source of this hormone to the fetus. It importantly times the conceptus physiology and influences its development and programing of several functions that depend on neural and brain development, ultimately priming adult behavior and energy and glucose metabolism. The present review aims to explain the above listed melatonin functions, including the potential alterations observed in the progeny gestated under maternal chronodisruption and/or hypomelatoninemia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ygcen.2020.113633DOI Listing
January 2021

Melatonin deficiency decreases brown adipose tissue acute thermogenic capacity of in rats measured by F-FDG PET.

Diabetol Metab Syndr 2020 21;12:82. Epub 2020 Sep 21.

Department of Physiology and Biophysics, Institute of Biomedical Sciences, Universidade de São Paulo, São Paulo, Brazil.

Objective: Melatonin has been shown to increase brown adipose tissue (BAT) mass, which can lead to important metabolic effects, such as bodyweight reduction and glycemic improvement. However, BAT mass can only be measured invasively and. The gold standard for non-invasive measurement of BAT activity is positron emission tomography with 2-deoxy-2-[fluorine-18] fluoro-d-glucose (F-FDG PET). There is no study, to our knowledge, that has evaluated if melatonin influences BAT activity, measured by this imaging technique in animals.

Methods: Three experimental groups of Wistar rats (control, pinealectomy, and pinealectomy replaced with melatonin) had an F-FDG PET performed at room temperature and after acute cold exposure. The ratio of increased BAT activity after cold exposure/room temperature was called "acute thermogenic capacity" (ATC) We also measured UCP-1 mRNA expression to correlate with the F-FDG PET results.

Results: Pinealectomy led to reduced acute thermogenic capacity, compared with the other groups, as well as reduced UCP1 mRNA expression.

Conclusion: Melatonin deficiency impairs BAT response when exposed to acute cold exposure. These results can lead to future studies of the influence of melatonin on BAT, in animals and humans, without needing an invasive evaluation of BAT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13098-020-00589-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504678PMC
September 2020

Sweet dreams: therapeutic insights, targeting imaging and physiologic evidence linking sleep, melatonin and diabetic nephropathy.

Clin Kidney J 2020 Aug 6;13(4):522-530. Epub 2020 Feb 6.

Division of Nephrology, Department of Medicine, Koç University School of Medicine, Istanbul, Turkey.

Melatonin is the main biochronologic molecular mediator of circadian rhythm and sleep. It is also a powerful antioxidant and has roles in other physiologic pathways. Melatonin deficiency is associated with metabolic derangements including glucose and cholesterol dysregulation, hypertension, disordered sleep and even cancer, likely due to altered immunity. Diabetic nephropathy (DN) is a key microvascular complication of both type 1 and 2 diabetes. DN is the end result of a complex combination of metabolic, haemodynamic, oxidative and inflammatory factors. Interestingly, these same factors have been linked to melatonin deficiency. This report will collate in a clinician-oriented fashion the mechanistic link between melatonin deficiency and factors contributing to DN.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ckj/sfz198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7467577PMC
August 2020

The Rat Mammary Gland as a Novel Site of Expression of Melanin-Concentrating Hormone Receptor 1 mRNA and Its Protein Immunoreactivity.

Front Endocrinol (Lausanne) 2020 31;11:463. Epub 2020 Jul 31.

Instituto de Psicologia, Nucleo de Neurociencias e Comportamento, Universidade de São Paulo, São Paulo, Brazil.

Lactation is a complex physiological process, depending on orchestrated central and peripheral events, including substantial brain plasticity. Among these events is a novel expression of pro-melanin-concentrating hormone () mRNA in the rodent hypothalamus, such as the ventral part of the medial preoptic area (vmMPOA). This expression reaches its highest levels around postpartum day 19 (PPD19), when dams transition from lactation to the weaning period. The appearance of this lactation-related expression occurs simultaneously with the presence of one of the products, melanin-concentrating hormone (MCH), in the serum. Given the relevance of the MPOA to maternal physiology and the contemporaneity between expression in this structure and the weaning period, we hypothesized that MCH has a role in the termination of lactation, acting as a mediator between central and peripheral changes. To test this, we investigated the presence of the MCH receptor 1 (MCHR1) and its gene expression in the mammary gland of female rats in different stages of the reproductive cycle. To that end, hybridization, RT-PCR, RT-qPCR, nucleotide sequencing, immunohistochemistry, and Western blotting were employed. Although expression was detected in the epidermis and dermis of both diestrus and lactating rats, parenchymal expression was exclusively found in the functional mammary gland of lactating rats. The expression of mRNA oscillated through the lactation period and reached its maximum in PPD19 dams. Presence of MCHR1 was confirmed with immunohistochemistry with preferential location of MCHR1 immunoreactive cells in the alveolar secretory cells. As was the case for gene expression, the MCHR1 protein levels were significantly higher in PPD19 than in other groups. Our data demonstrate the presence of an anatomical basis for the participation of MCH peptidergic system on the control of lactation through the mammary gland, suggesting that MCH could modulate a prolactation action in early postpartum days and the opposite role at the end of the lactation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2020.00463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411258PMC
May 2021

Editorial: Decoding the Fetal Circadian System and Its Role in Adult Sickness and Health: Melatonin, a Dark History.

Front Endocrinol (Lausanne) 2020 16;11:380. Epub 2020 Jul 16.

Department of Biology, Washington University, St. Louis, MO, United States.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2020.00380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378382PMC
May 2021

The Rhythmicity of Clock Genes is Disrupted in the Choroid Plexus of the APP/PS1 Mouse Model of Alzheimer's Disease.

J Alzheimers Dis 2020 ;77(2):795-806

CICS-UBI - Health Sciences Research Center, University of Beira Interior, Covilhã, Portugal.

Background: The choroid plexus (CP), which constitutes the blood-cerebrospinal fluid barrier, was recently identified as an important component of the circadian clock system.

Objective: The fact that circadian rhythm disruption is closely associated to Alzheimer's disease (AD) led us to investigate whether AD pathology can contribute to disturbances of the circadian clock in the CP.

Methods: For this purpose, we evaluated the expression of core-clock genes at different time points, in 6- and 12-month-old female and male APP/PS1 mouse models of AD. In addition, we also assessed the effect of melatonin pre-treatment in vitro before amyloid-β stimulus in the daily pattern of brain and muscle Arnt-like protein 1 (Bmal1) expression.

Results: Our results showed a dysregulation of circadian rhythmicity of Bmal1 expression in female and male APP/PS1 transgenic 12-month-old mice and of Period 2 (Per2) expression in male mice. In addition, a significant circadian pattern of Bmal1 was measured the intermittent melatonin pre-treatment group, showing that melatonin can reset the CP circadian clock.

Conclusion: These results demonstrated a connection between AD and the disruption of circadian rhythm in the CP, representing an attractive target for disease prevention and/or treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/JAD-200331DOI Listing
September 2021

Poor sleep quality is associated with cardiac autonomic dysfunction in treated hypertensive men.

J Clin Hypertens (Greenwich) 2020 08 2;22(8):1484-1490. Epub 2020 Aug 2.

Exercise Hemodynamic Laboratory, School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil.

Hypertensives present cardiac autonomic dysfunction. Reduction in sleep quality increases blood pressure (BP) and favors hypertension development. Previous studies suggested a relationship between cardiovascular autonomic dysfunction and sleep quality, but it is unclear whether this association is present in hypertensives. Thus, this study evaluated the relationship between sleep quality and cardiac autonomic modulation in hypertensives. Forty-seven middle-aged hypertensive men under consistent anti-hypertensive treatment were assessed for sleep quality by the Pittsburgh Sleep Quality Index (PSQI-higher score means worse sleep quality). Additionally, their beat-by-beat BP and heart rate (HR) were recorded, and cardiac autonomic modulation was assessed by their variabilities. Mann-Whitney and t tests were used to compare different sleep quality groups: poor (PSQI > 5, n = 24) vs good (PSQI ≤ 5, n = 23), and Spearman's correlations to investigate associations between sleep quality and autonomic markers. Patients with poor sleep quality presented lower cardiac parasympathetic modulation (HR high-frequency band = 26 ± 13 vs 36 ± 15 nu, P = .03; HR total variance = 951 ± 1373 vs 1608 ± 2272 ms , P = .05) and cardiac baroreflex sensitivity (4.5 ± 2.3 vs 7.1 ± 3.7 ms/mm Hg, P = .01). Additionally, sleep quality score presented significant positive correlation with HR (r = +0.34, P = .02) and negative correlations with HR high-frequency band (r = -0.34, P = .03), HR total variance (r = -0.35, P = .02), and cardiac baroreflex sensitivity (r = -0.42, P = .01), showing that poor sleep quality is associated with higher HR and lower cardiac parasympathetic modulation and baroreflex sensitivity. In conclusion, in treated hypertensive men, poor sleep quality is associated with cardiac autonomic dysfunction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jch.13949DOI Listing
August 2020

Melatonin Therapy Improves Cardiac Autonomic Modulation in Pinealectomized Patients.

Front Endocrinol (Lausanne) 2020 30;11:239. Epub 2020 Apr 30.

Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.

The purpose of this investigational study was to assess the effects of melatonin replacement therapy on cardiac autonomic modulation in pinealectomized patients. This was an open-label, single-arm, single-center, proof-of-concept study consisting of a screening period, a 3-month treatment period with melatonin (3 mg/day), and a 6-month washout period. The cardiac autonomic function was determined through heart rate variability (HRV) measures during polysomnography. Pinealectomized patients ( = 5) with confirmed absence of melatonin were included in this study. Melatonin treatment increased vagal-dominated HRV indices including root mean square of the successive R-R interval differences (RMSSD) (39.7 ms, 95% CI 2.0-77.4, = 0.04), percentage of successive R-R intervals that differ by more than 50 ms (pNN50) (17.1%, 95% CI 9.1-25.1, = 0.003), absolute power of the high-frequency band (HF power) (1,390 ms, 95% CI 511.9-2,267, = 0.01), and sympathetic HRV indices like standard deviation of normal R-R wave interval (SDNN) (57.6 ms, 95% CI 15.2-100.0, = 0.02), and absolute power of the low-frequency band (LF power) (4,592 ms, 95% CI 895.6-8,288, = 0.03). These HRV indices returned to pretreatment values when melatonin treatment was discontinued. The HRV entropy-based regularity parameters were not altered in this study, suggesting that there were no significant alterations of the REM-NREM ratios between the time stages of the study. These data show that 3 months of melatonin treatment may induce an improvement in cardiac autonomic modulation in melatonin-non-proficient patients. NCT03885258.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2020.00239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7213221PMC
May 2021

Evidence that Melatonin Increases Inhibin Beta-A and Follistatin Gene Expression in Ovaries of Pinealectomized Rats.

Reprod Sci 2020 07 10;27(7):1455-1464. Epub 2020 Feb 10.

Laboratório de Investigação Médica (LIM 58) - Disciplina de Ginecologia, Departamento de Obstetrícia e Ginecologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.

Melatonin plays an important role in the regulation of ovarian function including oocyte maturation in different mammalian species. Many studies indicate that melatonin has an impact on the ovarian function of a variety of ovarian cells. However, the information on the exact mechanism and involved hormones is low. To evaluate inhibin beta-A (INHBA) and follistatin (FST) expression in the ovaries of pinealectomized rats treated with melatonin, thirty adult female Wistar rats were randomized into three groups of ten animals each: group 1 (GSh), sham-operated controls receiving vehicle; group 2 (GPx), pinealectomized animals receiving vehicle; and group 3 (GPxMe), pinealectomized animals receiving replacement melatonin (1.0 mg/kg body weight. It was assumed that each animal drank 6.5 ± 1.2 ml per night and weighs approximately 300 g.) for 60 consecutive days. The ovaries were collected for mRNA abundance and protein of INHBA and FST by qRT-PCR and immunohistochemical analyses, respectively. Treatment with melatonin resulted in the upregulation of INHBA and FST genes in the ovarian tissue of the melatonin-treated animals (GPxMe), when compared with GPx. These findings were then confirmed by analyzing the expression of protein by immunohistochemical analyses, which revealed higher immunoreactivity of INHBA and FST in GPxMe animals in the follicular cells compared with GSh and GPx rats. Melatonin increases the expression of INHBA and FST in the ovaries of pinealectomized female rats.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s43032-020-00162-1DOI Listing
July 2020

Eating Behavior (Duration, Content, and Timing) Among Workers Living under Different Levels of Urbanization.

Nutrients 2020 Jan 31;12(2). Epub 2020 Jan 31.

School of Public Health, University of São Paulo, 715 Av. Dr. Arnaldo, São Paulo SP 01246-904, Brazil.

Urbanization has contributed to extended wakefulness, which may in turn be associated with eating over a longer period. Here, we present a field study conducted in four groups with different work hours and places of living in order to investigate eating behavior (duration, content, and timing). Anthropometric measures were taken from the participants (rural ( = 22); town ( = 19); city-day workers ( = 11); city-night workers ( = 14)). In addition, a sociodemographic questionnaire was self-answered and 24-h food recalls were applied for three days. The 24-h food recalls revealed that fat intake varied according to the groups, with the highest consumption by the city-day workers. By contrast, city-day workers had the lowest intake of carbohydrate, whereas the rural group had the highest. In general, all groups had some degree of inadequacy in food consumption. Eating duration was negatively correlated with total energy intake, fat, and protein consumption in the rural and town groups. There was a positive correlation between body mass index and eating duration in both city groups. The rural group had the earliest start time of eating, and this was associated with a lower body mass index. This study suggested that food content and timing, as well as eating duration, differed according to place of living, which in turn may be linked to lifestyle.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu12020375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7071231PMC
January 2020

Evaluation of Hepatic Steatosis in Rodents by Time-Domain Nuclear Magnetic Resonance.

Diagnostics (Basel) 2019 Nov 20;9(4). Epub 2019 Nov 20.

Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo 05508-000, Brazil.

Devices that analyze body composition of rodents by time-domain nuclear magnetic resonance (TD-NMR) are becoming popular in research centers that study metabolism. Theoretically, TD-NMR devices can also evaluate lipid content in isolated tissues. However, the accuracy of TD-NMR to determine hepatic steatosis in the liver of small laboratory animals has not been evaluated in detail. We observed that TD-NMR was able to detect increased lipid content in the liver of rats consuming high-fat diet (HFD) for 12 weeks and in genetically obese ( and ) mice. The lipid content determined by TD-NMR showed a positive correlation with triglyceride content measured by colorimetric assays. In contrast, TD-NMR did not detect hepatic steatosis in C57BL/6 mice consuming HFD for 4 or 12 weeks, despite their obesity and increased liver triglyceride content. These findings indicate that tissue mass and the severity of hepatic steatosis affect the sensitivity of TD-NMR to detect liver lipid content.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/diagnostics9040198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6963644PMC
November 2019

Neutrophil activation causes tumor regression in Walker 256 tumor-bearing rats.

Sci Rep 2019 11 11;9(1):16524. Epub 2019 Nov 11.

Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.

The role of neutrophils in cancer is still very contradictory. Several studies have demonstrated the cytotoxic capacity of neutrophils against different types of tumors, by releasing inflammatory cytokines, ROS and activating other immune cells. On the other hand, recent papers have claimed the protumorigenic action of neutrophils, mainly by changing their phenotype and producing cytokines that promote tumor growth. In this context, this study aimed to evaluate neutrophil action and function during tumor development. To do so, we used male Wistar rats inoculated with Walker 256 breast carcinoma. Tumor, circulating neutrophils and bone marrow were studied in the following time points after tumor inoculation: 12 h, 24 h, 48 h, 3 d, 5 d, 7 d, 10 d, and 14 d, in order to analyze neutrophil migration kinetics, circulating neutrophil phenotype and bone marrow response to the tumor growth. Herein, our results demonstrated that W256T was unable to trigger an intratumoral inflammatory response after 5 days of tumor development and consequently, from that point on, prevented neutrophil migration to its microenvironment. Also, the tumor changed circulating neutrophil phenotype by up-regulating inflammation-related genes. Even though circulating neutrophils were entirely able to respond to an inflammatory stimulus, they did not recognize and attack the tumor, allowing the tumor to grow without any immune interference. To promote the entry of neutrophils into the tumor microenvironment, LPS was injected intratumorally. Neutrophil migration and activation due to LPS injection resulted in complete tumor regression in all subjects. In conclusion, activating neutrophils, within the tumor, turned the carcinoma into a recognizable immune target and eliminated it.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-019-52956-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6848483PMC
November 2019

Melatonin effects on ovarian follicular cells: a systematic review.

Rev Assoc Med Bras (1992) 2019 Sep 12;65(8):1122-1127. Epub 2019 Sep 12.

Disciplina de Ginecologia do Departamento de Obstetrícia e Ginecologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brasil.

Melatonin is known for its effects on both the sleep and reproductive system of mammals. The latter has melatonin receptors type 1 and 2, which act to regulate, among other things, cyclic AMP. Notwithstanding all the literature data, there is still no sound knowledge or a clear understanding of the hormone's action on the physiology of ovarian follicular cells. OBJECTIVE To review and evaluate studies about melatonin action on the ovarian granulosa/theca interna cells from the literature. METHODS The systematic review was carried out according to the PRISMA recommendations. The MEDLINE and Cochrane primary databases were consulted with the use of specific terms. There was no limitation on language or publication year. RESULTS Seven papers about melatonin action on granulosa cells were selected. The following can be attributed to the hormone's effects: a) progesterone increase in culture medium; b) increased estrogen production; c) antagonistic action on estrogen; d) improvement in cell quality resulting in improved embryo and higher pregnancy rates; e) improved cell proliferation via MAPK; f) reduction of free radicals. Nevertheless, there are contrarian papers reporting a reduction in progesterone production. Melatonin interferes in sex steroid production, boosting progesterone output. Such action may help improve oocyte quality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1590/1806-9282.65.8.1122DOI Listing
September 2019

Cardioprotective Melatonin: Translating from Proof-of-Concept Studies to Therapeutic Use.

Int J Mol Sci 2019 Sep 5;20(18). Epub 2019 Sep 5.

Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-900, Brazil.

In this review we summarized the actual clinical data for a cardioprotective therapeutic role of melatonin, listed melatonin and its agonists in different stages of development, and evaluated the melatonin cardiovascular target tractability and prediction using machine learning on ChEMBL. To date, most clinical trials investigating a cardioprotective therapeutic role of melatonin are in phase 2a. Selective melatonin receptor agonists Tasimelteon, Ramelteon, and combined melatonergic-serotonin Agomelatine, and other agonists with registered structures in CHEMBL were not yet investigated as cardioprotective or cardiovascular drugs. As drug-able for these therapeutic targets, melatonin receptor agonists have the benefit over melatonin of well-characterized pharmacologic profiles and extensive safety data. Recent reports of the X-ray crystal structures of MT1 and MT2 receptors shall lead to the development of highly selective melatonin receptor agonists. Predictive models using machine learning could help to identify cardiovascular targets for melatonin. Selecting ChEMBL scores > 4.5 in cardiovascular assays, and melatonin scores > 4, we obtained 284 records from 162 cardiovascular assays carried out with 80 molecules with predicted or measured melatonin activity. Melatonin activities (agonistic or antagonistic) found in these experimental cardiovascular assays and models include arrhythmias, coronary and large vessel contractility, and hypertension. Preclinical proof-of-concept and early clinical studies (phase 2a) suggest a cardioprotective benefit from melatonin in various heart diseases. However, larger phase 3 randomized interventional studies are necessary to establish melatonin and its agonists' actions as cardioprotective therapeutic agents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms20184342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770816PMC
September 2019

Current understanding of pineal gland structure and function in headache.

Cephalalgia 2019 Nov 1;39(13):1700-1709. Epub 2019 Aug 1.

Instituto de Ciencias Biomédicas, Universidade de São Paulo, São Paulo, Brazil.

Purpose: The pineal gland plays an important role in biological rhythms, circadian and circannual variations, which are key aspects in several headache disorders.

Overview: Melatonin, the main pineal secreting hormone, has been extensively studied in primary and secondary headache disorders. Altered melatonin secretion occurs in many headache syndromes. Experimental data show pineal gland and melatonin both interfere in headache animal models, decreasing trigeminal activation. Melatonin has been shown to regulate CGRP and control its release.

Discussion: Melatonin has been used successfully as a treatment for migraine, cluster headaches and other headaches. There is a rationale for including the pineal gland as a relevant brain structure in the mechanisms of headache pathophysiology, and melatonin as a treatment option in primary headache.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0333102419868187DOI Listing
November 2019

New insights into the function of melatonin and its role in metabolic disturbances.

Expert Rev Endocrinol Metab 2019 07 13;14(4):293-300. Epub 2019 Jun 13.

b Department of Physiology and Biophysics , Institute of Biomedical Sciences, University of São Paulo , São Paulo , Brazil.

Introduction: Melatonin is a pineal hormone that has acquired several unique modes of regulating the physiological effects in mammals due to its characteristic phylogenetic history. While melatonin exhibits immediate nocturnal effects, it also has next-day prospective effects that take place in the absence of this hormone. Besides that, the daily repetition and the annual variation in the duration of its synthesis determine its circadian and seasonal effects that characterize melatonin as a chronobiotic, a molecule that encodes time to the internal environment. Additionally, it presents transgenerational effects that are important for fetal programming, leading to a balanced energy metabolism in the adult life.

Areas Covered: Physiology, pathophysiology and therapeutic value of melatonin in metabolism and metabolic disorders.

Expert Opinion: The typical mechanisms of action of melatonin (immediate, prospective, chronobiotic and transgenerational) should be considered to adequately understand its physiological effects on the regulation of metabolism in humans and, as a result, to understand the metabolic pathophysiological consequences caused by its synthesis and/or signaling disturbances. That points to the importance of a broader understanding of melatonin actions, besides the classical endocrinological point of view, that would allow the clinician/research to proper interpret its role in health maintenance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/17446651.2019.1631158DOI Listing
July 2019

Repercussions of melatonin on the risk of breast cancer: a systematic review and meta-analysis.

Rev Assoc Med Bras (1992) 2019 Jun 3;65(5):699-705. Epub 2019 Jun 3.

Discipline of Gynecology, Department of Obstetrics and Gynecology, Hospital das Clínicas, USP Medical School; São Paulo, Brasil.

Breast Cancer is common in women, but its etiology is not yet fully understood. Several factors may contribute to its genesis, such as genetics, lifestyle, and the environment. Melatonin may be involved in the process of breast cancer. Therefore, the aim of this study is to evaluate the influence of the levels of melatonin on breast cancer through a systematic review and meta-analysis. We performed a systematic review according to PRISMA recommendations. The primary databases MEDLINE, Embase, and Cochrane were consulted. There was no restriction on the year of publication and language. Data of systematic reviews from April 2017 to September to 2017 were analyzed. The meta-analysis was conducted using RevMan 5.3 software provided by the Cochrane Collaboration. From a total of 570 articles, 9 manuscripts were included in this review. They analy onzed women with breast cancer and control patients, of which 10% and 90% were in the reproductive period and after menopause, respectively. The lowest level of melatonin was found in approximately 55% of studies with breast cancer in post-menopause. The metanalyses of the studies demonstrated low levels of melatonin in breast cancer patients (n=963) compared with control patients (n= 1332), with a mean difference between the studies of -3.54 (CI -6.01, -1.06). Another difference found was in the comparison between smoking patients, with an average difference between 1.80 [0.97-2.63]. Our data suggest that low levels of melatonin might be a risk factor for breast cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1590/1806-9282.65.5.699DOI Listing
June 2019

Melatonin Reduces Excitability in Dorsal Root Ganglia Neurons with Inflection on the Repolarization Phase of the Action Potential.

Int J Mol Sci 2019 May 28;20(11). Epub 2019 May 28.

Laboratório de Eletrofisiologia, Instituto Superior de Ciências Biomédicas, Universidade Estadual do Ceará, Fortaleza 60714-903, CE, Brazil.

Melatonin is a neurohormone produced and secreted at night by pineal gland. Many effects of melatonin have already been described, for example: Activation of potassium channels in the suprachiasmatic nucleus and inhibition of excitability of a sub-population of neurons of the dorsal root ganglia (DRG). The DRG is described as a structure with several neuronal populations. One classification, based on the repolarizing phase of the action potential (AP), divides DRG neurons into two types: Without (N) and with (N) inflection on the repolarization phase of the action potential. We have previously demonstrated that melatonin inhibits excitability in N neurons, and in the present work, we aimed to investigate the melatonin effects on the other neurons (N) of the DRG neuronal population. This investigation was done using sharp microelectrode technique in the current clamp mode. Melatonin (0.01-1000.0 nM) showed inhibitory activity on neuronal excitability, which can be observed by the blockade of the AP and by the increase in rheobase. However, we observed that, while some neurons were sensitive to melatonin effect on excitability (excitability melatonin sensitive-EMS), other neurons were not sensitive to melatonin effect on excitability (excitability melatonin not sensitive-EMNS). Concerning the passive electrophysiological properties of the neurons, melatonin caused a hyperpolarization of the resting membrane potential in both cell types. Regarding the input resistance (R), melatonin did not change this parameter in the EMS cells, but increased its values in the EMNS cells. Melatonin also altered several AP parameters in EMS cells, the most conspicuously changed was the (dV/dt) of AP depolarization, which is in coherence with melatonin effects on excitability. Otherwise, in EMNS cells, melatonin (0.1-1000.0 nM) induced no alteration of (dV/dt) of AP depolarization. Thus, taking these data together, and the data of previous publication on melatonin effect on N neurons shows that this substance has a greater pharmacological potency on N neurons. We suggest that melatonin has important physiological function related to N neurons and this is likely to bear a potential relevant therapeutic use, since N neurons are related to nociception.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms20112611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6600424PMC
May 2019

Removing melatonin receptor type 1 signaling leads to selective leptin resistance in the arcuate nucleus.

J Pineal Res 2019 Sep 29;67(2):e12580. Epub 2019 Apr 29.

Department of Pharmacology and Toxicology and Neuroscience Institute, Morehouse School of Medicine, Atlanta, Georgia.

Recent studies have highlighted the involvement of melatonin in the regulation of energy homeostasis. In this study, we report that mice lacking melatonin receptor 1 (MT KO) gained more weight, had a higher cumulative food intake, and were more hyperphagic after fasting compared to controls (WT). In response to a leptin injection, MT KO mice showed a diminished reduction in body weight and food intake. To evaluate hypothalamic leptin signaling, we tested leptin-induced phosphorylation of the signal transducer and activator of transcription 3 (STAT3). Leptin failed to induce STAT3 phosphorylation in MT KO mice beyond levels observed in mice injected with phosphate-buffered saline (PBS). Furthermore, STAT3 phosphorylation within the arcuate nucleus (ARH) was decreased in MT KO mice. Leptin receptor mRNA levels in the hypothalamus of MT KO were significantly reduced (about 50%) compared to WT. This study shows that: (a) MT deficiency causes weight gain and increased food intake; (b) a lack of MT signaling induces leptin resistance; (c) leptin resistance is ARH region-specific; and (d) leptin resistance is likely due to down-regulation of the leptin receptor. Our data demonstrate that MT signaling is an important modulator of leptin signaling.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jpi.12580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6687516PMC
September 2019

Melatonin Increases Brown Adipose Tissue Volume and Activity in Patients With Melatonin Deficiency: A Proof-of-Concept Study.

Diabetes 2019 05 14;68(5):947-952. Epub 2019 Feb 14.

Department of Physiology and Biophysics, Institute of Biomedical Sciences, Universidade de São Paulo, São Paulo, Brazil.

Melatonin, a pineal hormone synthesized at night, is critical for the synchronization of circadian and seasonal rhythms, being a key regulator of energy metabolism in many animal species. Although studies in humans are lacking, several reports, mainly on hibernating animals, demonstrated that melatonin supplementation and a short photoperiod increase brown adipose tissue (BAT) mass. The present proof-of-concept study is the first, to our knowledge, to evaluate BAT in patients with melatonin deficiency (radiotherapy or surgical removal of pineal gland) before and after daily melatonin (3 mg) replacement for 3 months. All four studied patients presented increased BAT volume and activity measured by positron emission tomography-MRI. We also found an improvement in total cholesterol and triglyceride blood levels without significant effects on body weight, liver fat, and HDL and LDL levels. Albeit not statistically significant, fasting insulin levels and HOMA of insulin resistance decreased in all four patients. The present results show that oral melatonin replacement increases BAT volume and activity and improves blood lipid levels in patients with melatonin deficiency, suggesting that melatonin is a possible BAT activator. Future studies are warranted because hypomelatoninemia is usually present in aging and appears as a result of light-at-night exposure and/or the use of β-blocker drugs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2337/db18-0956DOI Listing
May 2019

Rhythmic changes in Fabry disease: Inversion and non-oscillatory pattern in 6-sulfatoxymelatonin daily profile.

Chronobiol Int 2019 04 7;36(4):470-480. Epub 2019 Jan 7.

a Department of Psychobiology , Universidade Federal de Sao Paulo , Sao Paulo , Brazil.

Fabry disease is a progressive disease characterized by an enzymatic deficiency of acid alpha-galactosidase and glycosphingolipids storage within the lysosomes. The disease has two phenotypes: classic and nonclassic. Excessive daytime sleepiness is a common sign reported by patients and can be caused by a circadian rhythm sleep disorder. Activity and rest cycle, variation of body temperature and melatonin biosynthesis are known rhythmicity markers. In the face of these evidences, our goal was to evaluate the rhythmic profile in Fabry's disease patients using rhythmicity markers. For this purpose, we recruited 17 patients diagnosed with Fabry disease (11 classic and 6 nonclassic variant) that answered the Epworth Sleepiness Scale and the Morningness-Eveningness questionnaire adapted from Horne and Ostberg; recorded activity and body temperature rhythms by an actigraphy during at least 10 days and collected urine to assess 6-sulfatoxymelatonin excretion load during the day (from the second urine in the morning until 7 p.m.) and night (starting from 7 p.m. until the first urine in the morning of the following day). We observed that control subjects presented higher excretion load of 6-sulfatoxymelatonin during the night (p < 0.05, d = 7.8), as expected. Patients with the nonclassic variant presented an inversion on 6-sulfatoxymelatonin daily profile (p < 0.05, d = 3.8) and there was no difference between the day and night profile of classic variant patients when compared to the other two groups. Patients with the classic variant also presented temperature period greater than 24 hours (p < 0.05, d = 2.0). Therefore, we came to the conclusion that there is an alteration in the circadian rhythms in Fabry disease patients, evidenced by modifications in the 6-sulfatoxymelatonin daily profile and in the body temperature rhythm period.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/07420528.2018.1560308DOI Listing
April 2019

Melatonin multiple effects on brown adipose tissue molecular machinery.

J Pineal Res 2019 Mar 31;66(2):e12549. Epub 2019 Jan 31.

Pineal Neurobiology Lab, Department of Physiology, Federal University of São Paulo, São Paulo, Brazil.

Brown adipose tissue (BAT) influences energy balance through nonshivering thermogenesis, and its metabolism daily and seasonal variations are regulated by melatonin through partially known mechanisms. We evaluated the role of melatonin in BAT molecular machinery of male Control, pinealectomized (PINX), and melatonin-treated pinealectomized (PINX/Mel) adult rats. BAT was collected either every 3 hours over 24 hours or after cold or high-fat diet (HFD) acute exposure. HFD PINX animals presented decreased Dio2 expression, while HFD PINX/Mel animals showed increased Dio2, Ucp1, and Cidea expression. Cold-exposed PINX rats showed decreased Dio2 and Lhs expression, and melatonin treatment augmented Adrβ3, Dio2, Ucp1, and Cidea expression. Daily profiles analyses showed altered Dio2, Lhs, Ucp1, Pgc1α, and Cidea gene and UCP1 protein expression in PINX animals, leading to altered rhythmicity under sub-thermoneutral conditions, which was partially restored by melatonin treatment. The same was observed for mitochondrial complexes I, II, and IV protein expression and enzyme activity. Melatonin absence seems to impair BAT responses to metabolic challenges, and melatonin replacement reverses this effect, with additional increase in the expression of crucial genes, suggesting that melatonin plays an important role in several key points of the thermogenic activation pathway, influencing both the rhythmic profile of the tissue and its ability to respond to metabolic challenges, which is crucial for the organism homeostasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jpi.12549DOI Listing
March 2019

A brief review about melatonin, a pineal hormone.

Arch Endocrinol Metab 2018 Aug;62(4):472-479

Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo (USP), São Paulo, SP, Brasil.

Melatonin is a ubiquitous molecule in nature, being locally synthesized in several cells and tissues, besides being a hormone that is centrally produced in the pineal gland of vertebrates, particularly in mammals. Its pineal synthesis is timed by the suprachiasmatic nucleus, that is synchronized to the light-dark cycle via the retinohypothalamic tract, placing melatonin synthesis at night, provided its dark. This unique trait turns melatonin into an internal synchronizer that adequately times the organism's physiology to the daily and seasonal demands. Besides being amphiphilic, melatonin presents specific mechanisms and ways of action devoted to its role as a time-giving agent, being widely spread in the organism. The present review aims to focus on melatonin as a pineal hormone with specific mechanisms and ways of action, besides presenting the clinical syndromes related to its synthesis and/or function disruptions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.20945/2359-3997000000066DOI Listing
August 2018
-->