Leptin suppresses microRNA-122 promoter activity by phosphorylation of foxO1 in hepatic stellate cell contributing to leptin promotion of mouse liver fibrosis

Cao, Qin; Zhu, Xiaofei; Zhai, Xuguang; Li, Ji; Cheng, Fangyun; Zhu, Yiqi; Yu, Pengfei; Zhou, Yajun

doi:10.1016/j.taap.2017.12.007

Cited by 17 publications

(5 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 114 Besides, leptin-induced multiple signalling pathways mediate HSC activation. 115 MAT2B-KO completely blocks leptin-mediated induction of STAT3 phosphorylation. 116 A recent study showed that leptin-induced β-catenin signalling attenuats E2F-4 binding to the MAT2A promoter, thus increasing its activity.…”

Section: Methionine Metabolism and Cldsmentioning

confidence: 86%

Methionine metabolism in chronic liver diseases: an update on molecular mechanism and therapeutic implication

Wang

Liang

et al. 2020

Sig Transduct Target Ther

View full text Add to dashboard Cite

As one of the bicyclic metabolic pathways of one-carbon metabolism, methionine metabolism is the pivot linking the folate cycle to the transsulfuration pathway. In addition to being a precursor for glutathione synthesis, and the principal methyl donor for nucleic acid, phospholipid, histone, biogenic amine, and protein methylation, methionine metabolites can participate in polyamine synthesis. Methionine metabolism disorder can aggravate the damage in the pathological state of a disease. In the occurrence and development of chronic liver diseases (CLDs), changes in various components involved in methionine metabolism can affect the pathological state through various mechanisms. A methionine-deficient diet is commonly used for building CLD models. The conversion of key enzymes of methionine metabolism methionine adenosyltransferase (MAT) 1 A and MAT2A/MAT2B is closely related to fibrosis and hepatocellular carcinoma. In vivo and in vitro experiments have shown that by intervening related enzymes or downstream metabolites to interfere with methionine metabolism, the liver injuries could be reduced. Recently, methionine supplementation has gradually attracted the attention of many clinical researchers. Most researchers agree that adequate methionine supplementation can help reduce liver damage. Retrospective analysis of recently conducted relevant studies is of profound significance. This paper reviews the latest achievements related to methionine metabolism and CLD, from molecular mechanisms to clinical research, and provides some insights into the future direction of basic and clinical research.

show abstract

Section: Methionine Metabolism and Cldsmentioning

confidence: 86%

Methionine metabolism in chronic liver diseases: an update on molecular mechanism and therapeutic implication

Wang

Liang

et al. 2020

Sig Transduct Target Ther

View full text Add to dashboard Cite

show abstract

“…Moreover, leptin was proven to downregulate miR-122 in HSCs also via the Hedgehog pathway, while miR-122 abolished leptin-mediated liver fibrosis in ob/ob mice [71]. Further studies revealed that leptin indirectly decreased promoter activity of miR-122 via inducing Forkhead box protein O1 (FoxO1) phosphorylation at serine 256 via the PI3K/Akt pathway [72]. When FoxO1 was unphosphorylated, it increased levels of miR-122 and suppressed leptin-dependent HSC activation as well as liver fibrosis in ob/ob mice [72].…”

Section: Leptin-induced Epigenetic Modifications In Metabolic Disomentioning

confidence: 99%

“…Further studies revealed that leptin indirectly decreased promoter activity of miR-122 via inducing Forkhead box protein O1 (FoxO1) phosphorylation at serine 256 via the PI3K/Akt pathway [72]. When FoxO1 was unphosphorylated, it increased levels of miR-122 and suppressed leptin-dependent HSC activation as well as liver fibrosis in ob/ob mice [72]. There have also been some studies suggesting the impact of leptin on miRNAs via the ob/ob model.…”

Section: Leptin-induced Epigenetic Modifications In Metabolic Disomentioning

confidence: 99%

Molecular Insight into the Interaction between Epigenetics and Leptin in Metabolic Disorders

et al. 2019

View full text Add to dashboard Cite

Nowadays, it is well-known that the deregulation of epigenetic machinery is a common biological event leading to the development and progression of metabolic disorders. Moreover, the expression level and actions of leptin, a vast adipocytokine regulating energy metabolism, appear to be strongly associated with epigenetics. Therefore, the aim of this review was to summarize the current knowledge of the epigenetic regulation of leptin as well as the leptin-induced epigenetic modifications in metabolic disorders and associated phenomena. The collected data indicated that the deregulation of leptin expression and secretion that occurs during the course of metabolic diseases is underlain by a variation in the level of promoter methylation, the occurrence of histone modifications, along with miRNA interference. Furthermore, leptin was proven to epigenetically regulate several miRNAs and affect the activity of the histone deacetylases. These epigenetic modifications were observed in obesity, gestational diabetes, metabolic syndrome and concerned various molecular processes like glucose metabolism, insulin sensitivity, liver fibrosis, obesity-related carcinogenesis, adipogenesis or fetal/early postnatal programming. Moreover, the circulating miRNA profiles were associated with the plasma leptin level in metabolic syndrome, and miRNAs were found to be involved in hypothalamic leptin sensitivity. In summary, the evidence suggests that leptin is both a target and a mediator of epigenetic changes that develop in numerous tissues during metabolic disorders.

show abstract

“…Chronic liver diseases remain a major problem throughout the world and lead to considerable morbidity and mortality (1). The most common pathological outcome and the most severe complication of chronic liver diseases are liver fibrosis which are global health and economic burdens (2). Liver fibrosis characteristically show over-accumulation of extracellular matrix (ECM), mainly type I fibrillar collagen (Collagen I) in response to chronic liver damage (3).…”

Section: Introductionmentioning

confidence: 99%

let-7a suppresses liver fibrosis via TGFβ/SMAD signaling transduction pathway

Zhang

Guo

et al. 2019

Exp Ther Med

View full text Add to dashboard Cite

Liver fibrosis is the most common pathological outcome and the most severe complication of chronic liver diseases. Accumulating evidence suggests that miRNAs are involved in cell proliferation, differentiation, apoptosis, as well as the occurrence and development of various diseases. In this study, we found that the expression of let-7a was markedly decreased in the liver tissue samples and blood samples from patients with liver fibrosis compared with healthy volunteers. Furthermore, let-7a was downregulated in the liver tissues and blood samples in mouse models of liver fibrosis. Further analysis indicated that let-7a suppresses the activation level of hepatic stellate cells (HSCs). In addition, overexpression of let-7a reduced cell viability and promoted apoptosis of HSCs. Western blot analysis showed that let-7a might inhibit HSCs through TGFβ/SMAD signaling pathway. The present study provides a potential accurate target and vital evidence to better understand the underlying pathogenesis for early diagnosis and treatment of liver fibrosis.

show abstract

Leptin suppresses microRNA-122 promoter activity by phosphorylation of foxO1 in hepatic stellate cell contributing to leptin promotion of mouse liver fibrosis

Cited by 17 publications

References 43 publications

Methionine metabolism in chronic liver diseases: an update on molecular mechanism and therapeutic implication

Methionine metabolism in chronic liver diseases: an update on molecular mechanism and therapeutic implication

Molecular Insight into the Interaction between Epigenetics and Leptin in Metabolic Disorders

let-7a suppresses liver fibrosis via TGFβ/SMAD signaling transduction pathway

Contact Info

Product

Resources

About