Fasting up‐regulates ferroportin 1 expression via a Ghrelin/GHSR/MAPK signaling pathway

Luo, Qianqian; Zhou, Yu‐Fu; Chen, Mesona Yung-Jin; Liu, Li; Ma, Juan; Zhang, Meng-Wan; Zhang, Fa‐Li; Ke, Ya; Qian, Zhong Ming

doi:10.1002/jcp.25931

Cited by 18 publications

(15 citation statements)

References 49 publications

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“…It has been confirmed that the proliferative role of ghrelin is related to the activation of its downstream MAPK signaling cascade in multiple types of cells [43,44]. Our previous investigation also suggested that Fpn1 expression increased after ERK phosphorylation in the spleen/macrophages [25]. To determine whether ghrelin also increases the expression of Fpn1 through the GHSR1a/MAPK signaling pathway in cultured hepatocytes, we explored the role of ghrelin in ERK phosphorylation in the presence or absence of a MAPK signaling pathway inhibitor (U0126).…”

Section: Discussionsupporting

confidence: 53%

“…An investigation by Dogan et al suggested that while children suffering from IDA showed lower levels of serum hepcidin and ghrelin than healthy children, iron treatment significantly elevated the hepcidin and ghrelin levels in the serum of IDA children [24]. In our previous study, a statistically significant negative correlation was also found between iron levels and ghrelin in the serum [25]. Based on these findings, we hypothesized that ghrelin may modulate the balance of iron homeostasis under physiological conditions.…”

Section: Introductionmentioning

confidence: 53%

“…q-PCR was performed using the FastStart Universal SYBR Green Master Mix (Vazyme Biotech Co., Ltd., China) in an LC96 instrument (Roche, Switzerland). The primer sequences (Sangon Biological Engineering Technology & Services Co., Ltd.,Shanghai, China) [25] used in this study are listed below (Table 1). The CT values of each target gene were normalized to those of β-actin in each group.…”

Section: Total Rna Extraction and Semiquantitative And Quantitative Rmentioning

confidence: 99%

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Fasting Increases Iron Export by Modulating Ferroportin 1 Expression Through the Ghrelin/GHSR1α/MAPK Pathway in the Liver

Luo

Yang

et al. 2020

Biol Trace Elem Res

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Background: The liver is the metabolic organ considered to contribute the most to maintaining body iron homeostasis and is a regulator of body adaptation to fasting. Our previous studies implied a negative relationship between iron and ghrelin in both mice and humans and indicated that ghrelin was able to increase ferroportin 1 (Fpn1) expression in the spleen and macrophages through the GHSR/MAPK pathway. However, it remains to be explored whether fasting or ghrelin has a functional effect on iron homeostasis in the liver. Methods: In this study, we examined the roles of fasting and ghrelin in modulating the protein expression of Fpn1, transferrin receptor 1 (TfR1), and ferritin light chain (Ft-L), as well as the mRNA expression of ghrelin, hepcidin, ghrelin O-acyltransferase (GOAT) and growth hormone secretagogue receptor 1 alpha (GHSR1α) in mouse liver and cultured hepatocytes. Results: Our in vivo results suggested that fasting significantly upregulated the mRNA expression of ghrelin, GOAT and GHSR1α as well as the protein levels of ghrelin, Fpn1 and Ft-L, but not TfR1, in mouse liver. Meanwhile, in cultured hepatocytes, ghrelin significantly increased the protein expression of Fpn1 but not Ft-L and TfR1 and significantly enhanced ERK phosphorylation. Furthermore, the pretreatment of cultured hepatocytes with either a pERK inhibitor or a GHSR1α antagonist abolished the effects of ghrelin on Fpn1 expression and ERK phosphorylation. Conclusions: Our findings confirmed that fasting increases iron export in the liver by upregulating Fpn1 expression through the ghrelin/GHSR1α/MAPK signaling pathway.

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Section: Discussionsupporting

confidence: 53%

Section: Introductionmentioning

confidence: 53%

Section: Total Rna Extraction and Semiquantitative And Quantitative Rmentioning

confidence: 99%

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Fasting Increases Iron Export by Modulating Ferroportin 1 Expression Through the Ghrelin/GHSR1α/MAPK Pathway in the Liver

Luo

Yang

et al. 2020

Biol Trace Elem Res

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“…Ghrelin concentrations are primarily regulated by food intake. Hence, ghrelin levels increase during fasting (in line with increased hunger) and are generally lower in individuals with higher body weights compared with lean individuals, suggesting a role for ghrelin in the regulation of body weight [49].…”

Section: Discussionmentioning

confidence: 99%

Effects of Ramadan Intermittent Fasting on Gut Hormones and Body Composition in Males with Obesity

Bagheri

Triki

Saeidi

et al. 2020

IJERPH

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We studied the effects of Ramadan intermittent fasting (RIF) on gut hormones (leptin, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), cholecystokinin (CCK), and ghrelin) in males with obesity. Thirty sedentary males were randomly allocated to either an experimental group (EG, n = 15) or a control group (CG, n = 15). The EG group completed their Ramadan fasting rituals (30 days), whereas the CG continued with their normal daily habits. Blood samples were collected at four time points: 24 h before the start of Ramadan (T0), on the 15th day of Ramadan (T1), the day after the end of Ramadan (T2) and 21 days after Ramadan (T3). There were significant pre-to-post improvements for leptin (p = 0.01, d = 1.52), GLP-1 (p = 0.022, d = 0.75), PYY (p = 0.031, d = 0.69) and CCK (p = 0.027, d = 0.81) in the EG, with no interaction effect for ghrelin (p = 0.74; d = 0.008). No significant changes (p > 0.05) occurred in plasma volume variations (ΔPV) after RIF in both EG (−0.03 ± 0.01%) and CG (0.06 ± 0.07%). RIF represents an effective strategy to modify appetite-regulating hormones, leading to improved body composition indices and reduced obesity.

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“…Immunofluorescence staining was performed as described in our previous work (Luo et al, 2018 ). Cells were fixed in 4% paraformaldehyde for 30 min followed by three washes in 0.01 M PBS.…”

Section: Methodsmentioning

confidence: 99%

Hepcidin Decreases Rotenone-Induced α-Synuclein Accumulation via Autophagy in SH-SY5Y Cells

Yuan

et al. 2020

Front. Mol. Neurosci.

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Parkinson's disease (PD) is a neurodegenerative disorder, and the hallmarks of this disease include iron deposition and α-synuclein (α-syn) aggregation. Hepcidin could reduce iron in the central and peripheral nervous systems. Here, we hypothesized that hepcidin could further decrease α-syn accumulation via reducing iron. Therefore, rotenone or α-syn was introduced into human neuroblastoma SH-SY5Y cells to imitate the pathological progress of PD in vitro. This study investigated the clearance effects of hepcidin on α-syn induced by a relatively low concentration of rotenone exposure or α-syn overexpression to elucidate the potential clearance pathway involved in this process. We demonstrated that SH-SY5Y cell viability was impaired after rotenone treatment in a dose-dependent manner. α-syn expression and iron content increased under a low concentration rotenone (25 nM for 3 days) treatment in SH-SY5Y cells. Pre-treatment with hepcidin peptide suppressed the abovementioned effects of rotenone. However, hepcidin did not affect treatment with rotenone under high iron conditions. Hepcidin also played a role in reducing α-syn accumulation in rotenone and α-syn overexpression conditions. We identified that the probable clearance effect of hepcidin on α-syn was mediated by the autophagy pathway using pretreatment with autophagy inhibitors (3-MA and CQ) and detection of autophagy protein markers (LC3II/I and p62). In conclusion, hepcidin eliminated α-syn expression via the autophagy pathway in rotenone-treated and α-syn overexpression SH-SY5Y cells. This study highlights that hepcidin may offer a potential therapeutic perspective in α-syn accumulation diseases.

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Fasting up‐regulates ferroportin 1 expression via a Ghrelin/GHSR/MAPK signaling pathway

Cited by 18 publications

References 49 publications

Fasting Increases Iron Export by Modulating Ferroportin 1 Expression Through the Ghrelin/GHSR1α/MAPK Pathway in the Liver

Fasting Increases Iron Export by Modulating Ferroportin 1 Expression Through the Ghrelin/GHSR1α/MAPK Pathway in the Liver

Effects of Ramadan Intermittent Fasting on Gut Hormones and Body Composition in Males with Obesity

Hepcidin Decreases Rotenone-Induced α-Synuclein Accumulation via Autophagy in SH-SY5Y Cells

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