Leptin Modulates Norepinephrine-Mediated Melatonin Synthesis in Cultured Rat Pineal Gland

Peliciari-Garcia, Rodrigo A.; Andrade-Silva, Jéssica; Cipolla‐Neto, José; Carvalho, Carla Roberta de Oliveira

doi:10.1155/2013/546516

Cited by 15 publications

(11 citation statements)

References 40 publications

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“…In ewes, leptin treatment increased melatonin secretion from pineal cell cultures explanted during the short‐day season, but decreased its secretion from pinealocyte cultures explanted during the long‐day season . In the cultured rat pineal gland, administration of leptin inhibited the norepinephrine‐mediated synthesis of melatonin . These findings point out that leptin is part of a complex regulatory system, important for modulating pineal melatonin secretion.…”

Section: Human Studies On Leptin and Melatonin Interactionsmentioning

confidence: 79%

Inter‐relationships of the chronobiotic, melatonin, with leptin and adiponectin: implications for obesity

Szewczyk-Golec

Woźniak

Reíter

2015

Journal of Pineal Research

123

111

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Obesity and its medical complications represent a significant problem throughout the world. In recent decades, mechanisms underlying the progression of obesity have been intensively examined. The involvement of both the behavioral aspects, such as calorie-rich diet, low physical activity and sleep deprivation, and the intrinsic factors, including adipose tissue deregulation, chronic inflammation, oxidative stress, and chronodisruption, has been identified. The circadian disturbances of the adipose tissue endocrine function have been correlated with obesity. Leptin and adiponectin are adipokines strongly associated with glucose and lipid metabolism and with energy balance. Their synthesis and secretion display circadian rhythms that are disturbed in the obese state. Hyperleptinemia resulting in leptin resistance, and hypo-adiponectinemia have been linked to the pathophysiology of the obesity-related disorders. A deficiency of melatonin, one of the consequences of sleep deprivation, has also been demonstrated to correlate with obesity. Melatonin is a pineal secretory product involved in numerous actions, such as regulation of internal biological clocks and energy metabolism, and it functions as an antioxidant and as an anti-inflammatory agent. There exists a substantial amount of evidence supporting the beneficial effects of melatonin supplementation on obesity and its complications. In the current review, the results of studies related to the interactions between melatonin, and both leptin and adiponectin are discussed. Despite the existence of some inconsistencies, melatonin has been found to normalize the expression and secretion patterns of both adipokines. These results support the concept of melatonin as a potential therapeutic agent for obesity and related disorders.

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Section: Human Studies On Leptin and Melatonin Interactionsmentioning

confidence: 79%

Inter‐relationships of the chronobiotic, melatonin, with leptin and adiponectin: implications for obesity

Szewczyk-Golec

Woźniak

Reíter

2015

Journal of Pineal Research

123

111

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“…Leptin concentrations were significantly affected by melatonin treatment [2, 19]. A recent report has demonstrated that the maternal melatonin secretion plays an important role in programming energy metabolism in the offspring [18].…”

Section: Discussionmentioning

confidence: 99%

Melatonin in the Regulation of Liver Steatosis following Prenatal Glucocorticoid Exposure

Tiao

Huang

Chen

et al. 2014

BioMed Research International

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Nonalcoholic fatty liver disease patients are characterized by hepatic steatosis. Prenatal glucocorticoid overexposure can result in steatosis. In this study, we aimed to determine the mechanism and cellular apoptosis of prenatal glucocorticoid overexposure in rats and whether melatonin can rescue the prenatal glucocorticoid-induced steatosis and apoptosis in neonatal rats. Pregnant Sprague-Dawley rats at gestational days 14 to 21 were administered dexamethasone. Acute effects of prenatal programming liver were assessed at postnatal day 7. The expression of proteins involved in the apoptotic and methylation pathways was analyzed by RT-PCR and Western blotting. Apoptosis and steatosis were examined by histology staining. The liver steatosis and apoptosis were increased in prenatal glucocorticoid group more than in control group and decreased in melatonin group. The expression of leptin decreased in prenatal glucocorticoid and increased in melatonin group by liver RT-PCR and Western blot study. Caspase 3, TNF-α proteins expression, and TUNEL stains increased in prenatal glucocorticoid compared with control and decreased in melatonin group. The liver histone deacetylase, DNA methyltransferase activity, and DNA methylation were increased in prenatal glucocorticoid and decreased in melatonin group. The present study showed that the prenatal glucocorticoid induced programming liver steatosis at day 7 after delivery, possibly via altered leptin expression. Melatonin can reverse the methylation of leptin and decreased liver steatosis.

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“…The positive regulatory factors including norepinephrine (NE), neutral amino acids, angiotensin II, and angiotensin IV promote melatonin synthesis and secretion. The negative regulatory factors such as anhydroecgonine methyl ester, β‐ N ‐methylamino‐ l ‐alanine, adenosine triphosphate, dexamethasone, and leptin have inhibitory effects on melatonin synthesis. However, the interactions among these factors remain to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

“…Leptin signals are transduced by binding to their corresponding membrane receptor, thus activating the intracellular JAK/STAT3, PI3K/AKT, and MAPK signaling pathways. In addition, the inhibitory effect of leptin on NE‐induced pineal melatonin synthesis appears to be mediated by a reduction in AANAT activity and expression in rat pineal glands . This led the researchers to question whether and how the NE and leptin signaling pathways interact to regulate melatonin synthesis in the pineal gland.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‐7 inhibits melatonin synthesis by acting as a linking molecule between leptin and norepinephrine signaling pathways in pig pineal gland

Qiu

Zhang

Zhou

et al. 2019

Journal of Pineal Research

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MicroRNAs, including microRNA‐7 (miR‐7), are important modulators of numerous gene expressions and the related biological processes. Melatonin is a key hormone regulating daily and seasonal rhythms, in which a variety of positive and negative regulatory factors, such as norepinephrine (NE) and leptin, are involved. However, the interactions among these factors and the mechanisms remain to be elucidated. The aims of the present study were to identify the functions and the related mechanisms of miR‐7 in regulating melatonin synthesis and secretion through in vitro and in vivo experiments in pineal gland of pigs, which is an important animal model for agricultural and biomedical studies. Our results firstly show that miR‐7 is specifically expressed in porcine pinealocytes and negatively regulates melatonin synthesis. The further functional studies show that the dynamic expression levels of miR‐7 are contrary to the melatonin levels throughout the day, and the forced inhibition of endogenous miR‐7 in porcine pinealocytes sharply increases arylalkylamine N‐acetyltransferase (AANAT) expression by 80.0% (P = 0.0031) and melatonin levels by 81.0% (P = 0.0421), whereas miR‐7 over‐expression down‐regulates AANAT expression by 38.6% (P = 0.0004) and melatonin levels by 37.6% (P = 0.0212). In addition, the miR‐7 expression is up‐regulated by leptin through the JAK/STAT3 signaling pathway, and the in vivo intracerebroventricular injection of leptin increases miR‐7 expression by 80.0% (P = 0.0044) in porcine pineal glands and reduces melatonin levels by 57.1% (P = 0.0060) compared with the controls. This functional inhibition of melatonin synthesis by miR‐7 is accomplished by its binding to the 3′‐UTR of Raf1. Further, our results demonstrate that the RAF1/MEK/ERK signaling pathway mediates NE‐induced AANAT expression, whereas leptin attenuates NE's function through miR‐7. Taken together, the results demonstrated that leptin activates the JAK/STAT3 signaling pathway to increase the expression of miR‐7, which acts as a negative regulatory molecule inhibiting NE‐activated RAF1/MEK/ERK signaling pathway by targeting Raf1, resulting in decreased AANAT expression and melatonin synthesis. These findings suggest that miR‐7 is a novel negative regulator of melatonin synthesis and links leptin‐ and NE‐mediated signaling pathways in porcine pineal glands, which will contribute to our understanding in the establishment of the biological rhythms resulting from melatonin.

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Leptin Modulates Norepinephrine-Mediated Melatonin Synthesis in Cultured Rat Pineal Gland

Cited by 15 publications

References 40 publications

Inter‐relationships of the chronobiotic, melatonin, with leptin and adiponectin: implications for obesity

Inter‐relationships of the chronobiotic, melatonin, with leptin and adiponectin: implications for obesity

Melatonin in the Regulation of Liver Steatosis following Prenatal Glucocorticoid Exposure

MicroRNA‐7 inhibits melatonin synthesis by acting as a linking molecule between leptin and norepinephrine signaling pathways in pig pineal gland

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