Melatonin, energy metabolism, and obesity: a review (original) (raw)
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Melatonin: A Silent Regulator of the Glucose Homeostasis
Carbohydrate, 2017
In the human organism, the circadian regulation of carbohydrates metabolism is essential for the glucose homeostasis and energy balance. Unbalances in glucose and insulin tissue and blood levels have been linked to a variety of metabolic disorders such as obesity, metabolic syndrome, cardiovascular diseases and type 2 diabetes. Melatonin, the pineal hormone, is the key mediator molecule for the integration between the cyclic environment and the circadian distribution of physiological and behavioral processes and for the optimization of energy balance and body weight regulation, events that are crucial for a healthy organism. This chapter reviews the interplay between melatonin modulatory physiological effects, glucose homeostasis and metabolic balance, from the endocrinology perspective. The tremendous effect of melatonin in the regulation of metabolic processes is observed from the chronobiology perspective, considering melatonin as a major synchronizer of the circadian internal order of the physiological processes involved in energy metabolism.
Acta Physiologica, 2012
The metabolic syndrome is a cluster of metabolic abnormalities associated with increased risk for cardiovascular diseases. Apart from its powerful antioxidant properties, the pineal gland hormone melatonin has recently attracted the interest of various investigators as a multifunctional molecule. Melatonin has been shown to have beneficial effects in cardiovascular disorders including ischaemic heart disease and hypertension. However its role in cardiovascular risk factors including obesity and other related metabolic abnormalities is not yet established, particularly in humans. New emerging data show that melatonin may play an important role in body weight regulation and energy metabolism. This review will address the role of melatonin in the metabolic syndrome focusing on its effects in obesity, insulin resistance and leptin resistance. The overall findings suggest that melatonin should be exploited as a therapeutic tool to prevent or reverse the harmful effects of obesity and its related metabolic disorders.
Endocrinology, 2000
Pineal melatonin secretion declines with aging, whereas visceral fat, plasma insulin, and plasma leptin tend to increase. We have previously demonstrated that daily melatonin administration at middle age suppressed male rat intraabdominal visceral fat, plasma leptin, and plasma insulin to youthful levels; the current study was designed to begin investigating mechanisms that mediate these responses. Melatonin (0.4 g/ml) or vehicle was administered in the drinking water of 10-month-old male Sprague Dawley rats (18/treatment) for 12 weeks. Half (9/treatment) were then killed, and the other half were submitted to cross-over treatment for an additional 12 weeks. Twelve weeks of melatonin treatment decreased (P Ͻ 0.05) body weight (BW; by 7% relative to controls), relative intraabdominal adiposity (by 16%), plasma leptin (by 33%), and plasma insulin (by 25%) while increasing (P Ͻ 0.05) locomotor activity (by 19%), core body temperature (by 0.5 C), and morning plasma corticosterone (by 154%), restoring each of these parameters toward more youthful levels. Food intake and total body fat were not changed by melatonin treatment. Melatonin-treated rats that were then crossed over to control treatment for a further 12 weeks gained BW, whereas control rats that were crossed to melatonin treatment lost BW, but food intake did not change in either group. Feed efficiency (grams of BW change per g cumulative food intake), a measure of metabolic function, was negative in melatonin-treated rats and positive in control rats before cross-over (P Ͻ 0.001); this relationship was reversed after cross-over (P Ͻ 0.001). Thus, melatonin treatment in middle age decreased BW, intraabdominal adiposity, plasma insulin, and plasma leptin, without altering food intake or total adiposity. These results suggest that the decrease in endogenous melatonin with aging may alter metabolism and physical activity, resulting in increased BW, visceral adiposity, and associated detrimental metabolic conse-
International journal …, 2007
Obesity and its associated metabolic pathologies are the most common and detrimental diseases, affecting over 50% of the adult population. Our knowledge about the protective effects of melatonin against high-fat diet (HFD)-induced obesity is still marginal. In this investigation, we hypothesized that melatonin can minimize the metabolic pathologies and morphological changes associated with obesity in animals receiving an HFD. To examine these effects, and to test our hypothesis, an animal model formed of male Boscat white rabbits was established. The animals were divided into three groups: (i) a control group fed regular diet; (ii) an obesity group fed an HFD for 12 weeks; and (iii) a treated group fed HFD for 12 weeks and then treated with melatonin for 4 weeks. The animals were killed and their serum and tissues were evaluated for: (i) lipid profile (cholesterol, triglycerides and low-density lipoprotein) and glucose; (ii) antioxidant enzyme (serum glutathione peroxidase, GSH-PX); and (iii) fatty changes (liver, kidney and blood vessels). Compared with the control group, intake of HFD (obesity group) was associated with: (i) a statistically significant increase in blood pressure, heart rate, sympathetic nerve activity, body weight, food consumption, serum lipids, blood glucose levels and atherogenic index; (ii) decreased level of GSH-PX and high-density lipoprotein (HDL); and (iii) fatty changes in the liver and kidney as well as atheromatous changes in the blood vessels. Compared with the obesity group, intake of melatonin (treated group) was associated with: (i) a statistically significant decrease in blood pressure, heart rate, sympathetic nerve activity, body weight, food consumption, serum lipids, blood glucose levels and atherogenic index; (ii) increased level of GSH-PX and HDL; and (iii) disappearance of fatty changes in the liver and kidney as well as atheromatous changes in the blood vessels. The administration of melatonin reduced the metabolic pathologies associated with the intake of HFD, suggesting a protective role. Although the underlying mechanisms are unclear, they may include its antioxidant and receptormediated effects. The clinical ramifications of these effects await further investigations.
Melatonin improves insulin sensitivity independently of weight loss in old obese rats
Journal of Pineal Research, 2013
In aged rats, insulin signaling pathway (ISP) is impaired in tissues that play a pivotal role in glucose 2 homeostasis, such as liver, skeletal muscle and adipose tissue. Moreover, the aging process is also 3 associated with obesity and reduction of melatonin synthesis from the pineal gland and other organs.
Melatonin Signaling a Key Regulator of Glucose Homeostasis and Energy Metabolism
Frontiers in Endocrinology, 2019
Melatonin, a hormone synthesized by both the pineal gland and retina, functions as an important modulator of a number of physiological functions. In addition to its rather well-established roles in the regulation of circadian rhythms, sleep, and reproduction, melatonin has also been identified as an important regulator of glucose metabolism. Recent genomic studies have also shown that disruption of melatonin receptors signaling may contribute to the pathogenesis of type 2 diabetes, although the exact mechanisms underlying its action remain unclear. Additionally, a large number of animal studies have highlighted a role for melatonin in the regulation of both glucose metabolism and energy balance. This review summarizes the current knowledge on the role that melatonin and its associated receptors play in the regulation of metabolism.
Melatonin Absence Leads to Long-Term Leptin Resistance and Overweight in Rats
Frontiers in endocrinology, 2018
Melatonin (Mel), a molecule that conveys photoperiodic information to the organisms, is also involved in the regulation of energy homeostasis. Mechanisms of action of Mel in the energy balance remain unclear; herein we investigated how Mel regulates energy intake and expenditure to promote a proper energy balance. Male Wistar rats were assigned to control, control + Mel, pinealectomized (PINX) and PINX + Mel groups. To restore a 24-h rhythm, Mel (1 mg/kg) was added to the drinking water exclusively during the dark phase for 13 weeks. After this treatment period, rats were subjected to a 24-h fasting test, an acute leptin responsiveness test and cold challenge. Mel treatment reduced food intake, body weight, and adiposity. When challenged to 24-h fasting, Mel-treated rats also showed reduced hyperphagia when the food was replaced. Remarkably, PINX rats exhibited leptin resistance; this was likely related to the capacity of leptin to affect body weight, food intake, and hypothalamic s...
2011
From a physiological perspective the sleep-wake cycle can be envisioned as a sequence of three physiological states (wakefulness, non-rapid eye movement, NREM, sleep and REM sleep) which are defined by a particular neuroendocrine-immune profile regulating the metabolic balance, body weight and inflammatory responses. Sleep deprivation and circadian disruption in contemporary "24/7 Society" lead to the predominance of pro-orexic and proinflammatory mechanisms that contribute to a pandemic metabolic syndrome (MS) including obesity, diabetes and atherosclerotic disease. Thus, a successful management of MS may require a drug that besides antagonizing the trigger factors of MS could also correct a disturbed sleep-wake rhythm. This review deals with the analysis of the therapeutic validity of melatonin in MS. Melatonin is an effective chronobiotic agent changing the phase and amplitude of the sleep/wake rhythm and having cytoprotective and immunomodulatory properties useful to prevent a number of MS sequels. Several studies support that melatonin can prevent hyperadiposity in animal models of obesity. Melatonin at a low dose (2-5 mg/day) has been used for improving sleep in patients with insomnia and circadian rhythm sleep disorders. More recently, attention has been focused on the development of potent melatonin analogs with prolonged effects (ramelteon, agomelatine, tasimelteon, TK 301). In clinical trials these analogs were employed in doses considerably higher than those usually employed for melatonin. In view that the relative potencies of the analogs are higher than that of the natural compound, clinical trials employing melatonin doses in the range of 50-100 mg/day are needed to assess its therapeutic value in MS.