MicroRNAs in the Pathogenesis of Nonalcoholic Fatty Liver Disease

Fang, Zhiqiang; Dou, Guo‐Rui; Wang, Lin

doi:10.7150/ijbs.59588

Cited by 51 publications

(53 citation statements)

References 137 publications

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“…The mechanism of folic acid effects could be attributed to the modulation of the miR-21, -34a, and -122 expressions which in turn, induce alterations in the expression of their corresponding genes; HBP1, SIRT1, and SREBP-1c, respectively. These genes are involved in the NAFL development by inducing lipogenesis, insulin resistance, and imbalanced cytokine production [ 51 ]. Folic acid treatment may affect microRNAs expression in NAFL rats’ liver possibly through changing the methylation status of promoter regions of the gene.…”

Section: Discussionmentioning

confidence: 99%

The regulation of HBP1, SIRT1, and SREBP-1c genes and the related microRNAs in non-alcoholic fatty liver rats: The association with the folic acid anti-steatosis

et al. 2022

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Folic acid is one of the vital micronutrients that contribute to the genetic stability and other biological activities. In addition, microRNAs regulate gene expression through a multittude of pathways. Our current work aimd to explore the possible ameliorative potency of folic acid and its association with the hepatic miR-21, -34a, and -122 expression as well as their targeted genes, HBP1, SIRT1, and SREBP-1c in rats with non-alcoholic fatty liver disease (NAFL). A total of 50 Wistar rats were randomly divided into two groups, a control group (n = 10) and NAFL group (n = 40). Rats in NAFL group were fed a high-fat diet (HFD) containing 20% fats for 14 weeks. The NAFL group was further subdivided into four groups (n = 10/group), one untreated and three orally folic acid-treated groups (25, 50, and 75 μg/Kg b.wt). NAFL characteristics was evaluated in rats in addition to the miR-21, -34a, and -122 profile as well as the transcriptional levels of HBP1, SIRT1, and SREBP-1c genes. NAFL rats exhibited the classic traits of fatty liver disease profile and dysregulation in the pattern of miR-21, -34a, and -122 expression as well as their targeted genes (HBP1, SIRT1, and SREBP-1c, respectively) in the liver. Additionally, NAFL rats had altered levels of TNF-α and adiponectin. These alterations were significantly ameliorated in a dose-dependent pattern following the folic acid treatments. In conclusions, the anti-steatotic, insulin-sensitizing, glucose-lowering and lipotropic potencies of folic acid in NAFL rats may be linked to the epigenetic modulation of the hepatic microRNAs (miR-21, -34a, and -122) and the expression of their target genes (HBP1, SIRT1, and SREBP-1c).

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Section: Discussionmentioning

confidence: 99%

The regulation of HBP1, SIRT1, and SREBP-1c genes and the related microRNAs in non-alcoholic fatty liver rats: The association with the folic acid anti-steatosis

et al. 2022

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“…Other biomolecules and pathways most recently identified as potential therapeutic targets in NAFLD have been highlighted in many comprehensive review articles [ 246 , 247 , 248 , 249 ]. Of those, the sirtuins, a family of highly conserved histone and protein deacetylases, can be considered of special interest regarding future therapeutic concepts for NAFLD.…”

Section: Future Directionsmentioning

confidence: 99%

Pharmacotherapy for Non-Alcoholic Fatty Liver Disease: Emerging Targets and Drug Candidates

2022

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Non-alcoholic fatty liver disease (NAFLD), or metabolic (dysfunction)-associated fatty liver disease (MAFLD), is characterized by high global incidence and prevalence, a tight association with common metabolic comorbidities, and a substantial risk of progression and associated mortality. Despite the increasingly high medical and socioeconomic burden of NAFLD, the lack of approved pharmacotherapy regimens remains an unsolved issue. In this paper, we aimed to provide an update on the rapidly changing therapeutic landscape and highlight the major novel approaches to the treatment of this disease. In addition to describing the biomolecules and pathways identified as upcoming pharmacological targets for NAFLD, we reviewed the current status of drug discovery and development pipeline with a special focus on recent evidence from clinical trials.

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“…Next, we focus on discussing the currently available knowledge regarding the best characterized epigenetic changes, such as DNA methylation and histone modifications, and how these alterations contribute to the development and progression of NAFLD in response to nutritional intake. As for advancement in the understanding of the mechanistic roles of ncRNAs in NAFLD, we refer the readers to recent well-detailed reviews [ 18 , 53 , 54 , 55 ].…”

Section: Epigenetic Mechanisms Underlying the Link Between Nutrition And Aberrant Gene Expression In Nafldmentioning

confidence: 99%

Dietary Patterns Influence Target Gene Expression through Emerging Epigenetic Mechanisms in Nonalcoholic Fatty Liver Disease

et al. 2021

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Nonalcoholic fatty liver disease (NAFLD) refers to the pathologic buildup of extra fat in the form of triglycerides in liver cells without excessive alcohol intake. NAFLD became the most common cause of chronic liver disease that is tightly associated with key aspects of metabolic disorders, including insulin resistance, obesity, diabetes, and metabolic syndrome. It is generally accepted that multiple mechanisms and pathways are involved in the pathogenesis of NAFLD. Heredity, sedentary lifestyle, westernized high sugar saturated fat diet, metabolic derangements, and gut microbiota, all may interact on a on genetically susceptible individual to cause the disease initiation and progression. While there is an unquestionable role for gene-diet interaction in the etiopathogenesis of NAFLD, it is increasingly apparent that epigenetic processes can orchestrate many aspects of this interaction and provide additional mechanistic insight. Exciting research demonstrated that epigenetic alterations in chromatin can influence gene expression chiefly at the transcriptional level in response to unbalanced diet, and therefore predispose an individual to NAFLD. Thus, further discoveries into molecular epigenetic mechanisms underlying the link between nutrition and aberrant hepatic gene expression can yield new insights into the pathogenesis of NAFLD, and allow innovative epigenetic-based strategies for its early prevention and targeted therapies. Herein, we outline the current knowledge of the interactive role of a high-fat high-calories diet and gene expression through DNA methylation and histone modifications on the pathogenesis of NAFLD. We also provide perspectives on the advancement of the epigenomics in the field and possible shortcomings and limitations ahead.

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MicroRNAs in the Pathogenesis of Nonalcoholic Fatty Liver Disease

Cited by 51 publications

References 137 publications

The regulation of HBP1, SIRT1, and SREBP-1c genes and the related microRNAs in non-alcoholic fatty liver rats: The association with the folic acid anti-steatosis

The regulation of HBP1, SIRT1, and SREBP-1c genes and the related microRNAs in non-alcoholic fatty liver rats: The association with the folic acid anti-steatosis

Pharmacotherapy for Non-Alcoholic Fatty Liver Disease: Emerging Targets and Drug Candidates

Dietary Patterns Influence Target Gene Expression through Emerging Epigenetic Mechanisms in Nonalcoholic Fatty Liver Disease

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