Melatonin in the Regulation of Liver Steatosis following Prenatal Glucocorticoid Exposure

Tiao, Mao‐Meng; Huang, Laura; Chen, Chih‐Jen; Sheen, Jiunn‐Ming; Tain, You‐Lin; Chen, Chih‐Cheng; Kuo, H.P.; Huang, Ying‐Hsien; Tang, Kuo-Shu; Chu, En-Wei; Yu, Hong‐Ren

doi:10.1155/2014/942172

Cited by 28 publications

(73 citation statements)

References 34 publications

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“…The bottles were covered with aluminum foil to protect them from light. This melatonin regimen has been used in our laboratory, and rats have shown good compliance with beneficial results [3,4,25]. In order to eliminate litter effects on the epigenetic modifications, the offspring in each cohort's treatment group were derived from at least 3 different dams.…”

Section: Methodsmentioning

confidence: 99%

“…Fetal exposure to maternal glucocorticoids represents one potential mechanism whereby prenatal stress may program the adult phenotype in utero [3,4]. In a cross-sectional study, Woods et al [5] reported that 6% of pregnant women had high levels of psychological stress, including depression, panic disorder, and/or domestic violence, during pregnancy.…”

Section: Introductionmentioning

confidence: 99%

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Effects of Melatonin on Prenatal Dexamethasone-Induced Epigenetic Alterations in Hippocampal Morphology and Reelin and Glutamic Acid Decarboxylase 67 Levels

et al. 2015

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Prenatal glucocorticoid exposure causes brain damage in adult offspring; however, the underlying mechanisms remain unclear. Melatonin has been shown to have beneficial effects in compromised pregnancies. Pregnant Sprague-Dawley rats were administered vehicle (VEH) or dexamethasone between gestation days 14 and 21. The programming effects of prenatal dexamethasone exposure on the brain were assessed at postnatal days (PND) 7, 42, and ∼120. Melatonin was administered from PND21 to the rats exposed to dexamethasone, and the outcome was assessed at ∼PND120. In total, there were four groups: VEH, vehicle plus melatonin (VEHM), prenatal dexamethasone-exposure (DEX), and prenatal dexamethasone exposure plus melatonin (DEXM). Spatial memory, gross hippocampal morphology, and hippocampal biochemistry were examined. Spatial memory assessed by the Morris water maze showed no significant differences among the four groups. Brain magnetic resonance imaging showed that all rats with prenatal dexamethasone exposure (DEX + DEXM) exhibited increased T2-weighted signals in the hippocampus. There were no significant differences in the levels of mRNA expression of hippocampal reln, which encodes reelin, and GAD1, which encodes glutamic acid decarboxylase 67, at PND7. At both PND42 and ∼PND120, reln and GAD1 mRNA expression levels were decreased. At ∼PND120, melatonin restored the reduced levels of hippocampal reln and GAD1 mRNA expression in the DEXM group. In addition, melatonin restored the reln mRNA expression levels by (1) reducing DNA methyltransferase 1 (DNMT1) mRNA expression and (2) reducing the binding of DNMT1 and the methyl-CpG binding protein 2 (MeCP2) to the reln promoter. The present study showed that prenatal dexamethasone exposure induced gross alterations in hippocampal morphology and reduced the levels of hippocampal mRNA expression of reln and GAD1. Spatial memory was unimpaired. Thus, melatonin had a beneficial effect in restoring hippocampal reln mRNA expression by reducing DNMT1 and MeCP2 binding to the reln promoter.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of Melatonin on Prenatal Dexamethasone-Induced Epigenetic Alterations in Hippocampal Morphology and Reelin and Glutamic Acid Decarboxylase 67 Levels

et al. 2015

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“…HNF4α is implicated in the regulation of the cytokine‐induced inflammatory response in the liver, 64 which indicates that the hepatic immune response is regulated by pregnancy in mice. Prenatal glucocorticoid overexposure induces liver steatosis by altering leptin expression, and melatonin can reverse the methylation of leptin and decrease liver steatosis at postnatal day 7 65 . Melatonin treatment can reduce lipid peroxidation induced by obstructive cholestasis during the last third of pregnancy in rats by stimulating the expression of components of the endogenous cellular antioxidant defence in the maternal liver 66 .…”

Section: Discussionmentioning

confidence: 99%

Expression of melatonin receptors and CD4 in the ovine thymus, lymph node, spleen and liver during early pregnancy

et al. 2020

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As a pineal gland hormone, melatonin acts through its receptors to modulate the immune system. The immune system is composed of primary and secondary organs, and immune organs are adapted to the presence of the fetal alloantigen during pregnancy. However, it is unclear whether melatonin affects maternal immune organs during early pregnancy in sheep. In this study, the ovine thymus, lymph node, spleen and liver were sampled at day 16 of the oestrous cycle, and at days 13, 16 and 25 of pregnancy. The expression of melatonin receptor 1A (MT1), melatonin receptor 1B (MT2) and cluster of differentiation 4 (CD4) was detected by quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry experiments. Our results showed that during early pregnancy there was an upregulation of MT1 mRNA and protein in the thymus, lymph node and liver, and there was a downregulation in the spleen. The expression of MT2 mRNA and protein was increased in the thymus but decreased in the spleen and liver, and there was no significant change in the lymph node during early pregnancy. CD4 protein was upregulated in the thymus, lymph node and liver, but there were no significant changes in the spleen during early pregnancy. In conclusion, early pregnancy induces tissue-specific expression of MT1, MT2 and CD4, which may be due to the different functions of the thymus, lymph node, spleen and liver. Further, melatonin is involved in immune regulation of the maternal thymus, lymph node, spleen and liver during early pregnancy in sheep.

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“…The present study aimed to expand upon the results of a previous study by our group, which also investigated the effect of melatonin (9). In addition, our previous study identified that postnatal high-fat diet increased liver steatosis and apoptosis exacerbated by prenatal dexamethasone exposure via an oxidative effect (6). High-fat diet is an environmental risk factor for disease progression in patients with NAFLD subsequent to prenatal stress.…”

Section: Introductionmentioning

confidence: 91%

“…It has become increasingly clear that early environmental influences also have a long-lasting impact on the development and physiology of the fetus. For instance, prenatal glucocorticoid overexposure may result in liver steatosis (6). Previous studies have observed that prenatal exposure to dexamethasone increased lipid accumulation in Melatonin alleviates liver steatosis induced by prenatal dexamethasone exposure and postnatal high-fat diet the liver in rats on a high-fat diet, while the deleterious effects of the high-fat diet in the perinatal and post-weaning periods persisted into adulthood (7,8).…”

Section: Introductionmentioning

confidence: 99%

Melatonin alleviates liver steatosis induced by prenatal dexamethasone exposure and postnatal high‑fat diet

Tsai

Lin

et al. 2018

Exp Ther Med

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Prenatal exposure to glucocorticoids is associated with negative health consequences for the offspring that persist into adulthood, including liver steatosis. Melatonin has previously been demonstrated to suppress liver steatosis and oxidative stress in humans with non-alcoholic fatty liver disease and in animal models of obesity. The present study aimed to determine whether melatonin protects against liver steatosis induced by prenatal dexamethasone exposure followed by postnatal high-fat diet. Pregnant Sprague-Dawley rats at gestational days 14-21 were administered dexamethasone (0.1 mg/kg/day) or saline via intraperitoneal injection. The offspring were then divided into five groups, as follows: Vehicle, postnatal high-fat diet (VHF), prenatal dexamethasone exposure (DEX), prenatal dexamethasone exposure + postnatal high-fat diet (DHF), and prenatal dexamethasone exposure + postnatal high-fat diet + melatonin (DHFM) group. Following vehicle or dexamethasone exposure of the maternal rats, the offspring rats in the VHF, DHF and DHFM groups received a high-fat diet (58% fat) between weaning and 6 months of age. In the DHFM group, melatonin was administered to the mothers from gestational days 14-21 until weaning. The offspring continued to receive melatonin until they were sacrificed at 6 months old. Oil Red O staining demonstrated stronger intensity in the DHF group compared with that in the other four groups. Western blot analysis also revealed higher levels of cleaved caspase-3, tumor necrosis factor-α (TNF-α), suppressor of cytokine signaling 3 (SOCS3) and malondialdehyde (MDA), as well as reduced expression of manganese superoxide dismutase (MnSOD) and phosphoinositide 3-kinase (PI3K) in the DHF group compared with the vehicle and DHFM groups. In addition, melatonin reduced the Oil Red O staining intensity and the levels of cleaved caspase-3, TNF-α, SOCS3 and MDA, while it increased the MnSOD and PI3K levels, in the DHFM group compared with the DHF group. In conclusion, postnatal high-fat diet aggravated the prenatal dexamethasone-induced liver steatosis in adult rat offspring via inflammation, oxidative stress and cellular apoptosis, which may be ameliorated by prenatal melatonin therapy.

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Melatonin in the Regulation of Liver Steatosis following Prenatal Glucocorticoid Exposure

Cited by 28 publications

References 34 publications

Effects of Melatonin on Prenatal Dexamethasone-Induced Epigenetic Alterations in Hippocampal Morphology and Reelin and Glutamic Acid Decarboxylase 67 Levels

Effects of Melatonin on Prenatal Dexamethasone-Induced Epigenetic Alterations in Hippocampal Morphology and Reelin and Glutamic Acid Decarboxylase 67 Levels

Expression of melatonin receptors and CD4 in the ovine thymus, lymph node, spleen and liver during early pregnancy

Melatonin alleviates liver steatosis induced by prenatal dexamethasone exposure and postnatal high‑fat diet

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