Aberrant miR199a-5p/caveolin1/PPARα axis in hepatic steatosis

Li, Bo; Zhang, Zhiguo; Zhang, Huizhi; Quan, Kai; Lu, Yan; Cai, Dongsheng; Ning, Guang

doi:10.1530/jme-14-0127

Cited by 43 publications

(31 citation statements)

References 37 publications

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“…Similar results have been observed in a previous study that demonstrated that the downregulated expression of OA/PA induced steatosis in hepatocytes and livers from HFD mice, db/db mice and ob/ob mice, and NAFLD patients [18]. One study reported a major decrease in CAV1 expression in the visceral adipose tissue of obese patients [9].…”

Section: Discussionsupporting

confidence: 89%

Caveolin1 protects against diet induced hepatic lipid accumulation in mice

Chen

Huang

et al. 2017

PLoS ONE

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Background and aimCaveolin1 (CAV1) is involved in lipid homeostasis and endocytosis, but little is known about the significance of CAV1 in the pathogenesis and development of nonalcoholic fatty liver disease (NAFLD). This study aimed to determine the role of CAV1 in NAFLD.MethodsExpression of CAV1 in the in vitro and in vivo models of NAFLD was analyzed. The effects of CAV1 knockdown or overexpression on free fatty acid (FFA)-induced lipid accumulation in L02 cells and AML12 cells were determined. CAV1 knockout (CAV1-KO) mice and their wild-type (WT) littermates were subjected to a high fat diet (HFD) for 4 weeks, and the functional consequences of losing the CAV1 gene and its subsequent molecular mechanisms were also examined.ResultsNoticeably, CAV1 expression was markedly reduced in NAFLD. CAV1 knockdown led to the aggravation of steatosis that was induced by FFA in both L02 cells and AML12 cells, while CAV1 overexpression markedly attenuated lipid accumulation in the cells. Consistent with CAV1 repression in the livers of HFD-induced mice, the CAV1-KO mice exhibited more severe hepatic steatosis upon HFD intake. In addition, increased cholesterol levels and elevated transaminases were detected in the plasma of CAV1-KO mice. The protein expression of SREBP1, a key gene involved in lipogenesis, was augmented following CAV1 suppression in FFA-treated hepatocytes and in the livers of HFD-fed CAV1-KO mice.ConclusionsCAV1 serves as an important protective factor in the development of NAFLD by modulating lipid metabolism gene expression.

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Section: Discussionsupporting

confidence: 89%

Caveolin1 protects against diet induced hepatic lipid accumulation in mice

Chen

Huang

et al. 2017

PLoS ONE

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“…miR-1 is associated with fatty acid uptake in cardiomyocytes by negatively regulating the expression of heart-type fatty acid binding protein 3 (FABP3) [67]. miR-199a participated in mitochondrial activity by inhibiting the expression of mitochondrial fatty acid β-oxidation related genes through CAV1 suppression [68]. In cultured myocytes, overexpression of miR-696 resulted in decreased fatty acid oxidation compared with normal control myocytes, through direct targeting PGC-1α [69].…”

Section: The Role Of Mirnas In Cardiac Metabolic Homeostasismentioning

confidence: 99%

MicroRNAs in heart failure: Non-coding regulators of metabolic function

Schulze

2016

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Heart failure (HF) is the inability of the heart to provide sufficient cardiac output for the energy demands of the body. Over the last decades, our understanding of the role of microRNAs (miRNAs), a class of small non-coding RNA regulators of gene expression at the post-transcriptional level, in cardiovascular diseases has expanded at a rapid rate. Importantly, multiple miRNAs have been specifically implicated in the progression of HF. Growing evidence suggests that miRNAs regulate central metabolic pathways and thus are highly implicated in the maintenance of energy homeostasis. In this review, we highlight recent discoveries of the mechanistic role of miRNAs in regulating metabolic functions in HF, with specific focus on the implication of miRNAs in metabolic rearrangements, discuss the potential value of miRNA profiles as novel HF biomarkers, and summarize the recent investigations on therapeutic approaches using miRNAs in heart disease. This article is part of a Special Issue entitled: The role of post-translational protein modifications on heart and vascular metabolism edited by Jason R.B. Dyck & Jan F.C. Glatz.

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“…It has been shown that miR-27a regulates lipid metabolism by targeting the lipid synthetic RXRα and the lipid transporter ATP-binding cassette subfamily A1 in addition in regulating several lipid metabolismrelated genes which play a crucial role in the production of infectious viral particles 47. Upregulation of miR-199a-5p impaired fibrillar Aβ-oxidation via inhibition of caveolin 1 (CAV1) and the PPARα pathway which refers to its vial role in the development of NAFLD 48. The positive correlation between declining of miR-27a/miR-93 and elevation of miR-199 with the severity of hepatic steatosis in CHC patient in the current study suggest their attractive therapeutic targets for NAFLD.5 | CONCLUSIONOur data indicated that serum miRNAs might be useful biomarkers for prediction of CHC (miR-21, miR-23b, miR-27a, miR-106, and miR-122) and liver disease progression (miR-27a, miR-93, and miR-199) in addition to their attractive therapeutic targets.…”

mentioning

confidence: 99%

Circulating microRNAs as predictive biomarkers for liver disease progression of chronic hepatitis C (genotype‐4) Egyptian patients

Elhefny

Fouad

Hussein

et al. 2018

Journal of Medical Virology

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Egypt is one of the highest prevalence rates of hepatitis C virus (HCV) infection worldwide. HCV is among major reasons for chronic liver diseases. MicroRNA (miRNAs), small noncoding regulatory molecules play a key role in the pathogenesis of liver. Circulating miRNAs represent potential noninvasive biomarkers for diagnosis and monitoring patients with liver diseases progression. To investigate the potential role of circulating miRNAs for surveillance of liver disease progression, we assessed the expression of 20 liver-related miRNAs in sera of 47 chronic hepatitis C Egyptian patients compared with 25 controls using quantitative reverse-transcription polymerase chain reaction assay. The sensitivity and specificity were evaluated using receiver operating characteristic (ROC) curve. The correlations between their levels and the clinicopathological features were assessed. Fourteen miRNAs showed upregulation and six miRNAs showed downregulation. ROC curve analyses revealed that the explored miRNAs could serve as valuable biomarkers for chronic hepatitis with an area under the curve ranged from 0.708 (95% confidence interval [95% CI], 0.587 to 0.829; P = 0.004) for miR-199 up to 0.974 (95% CI, 0.943 to 1.00; P < 0.001) for miR-23b. The expression level of miR-21 demonstrated significant correlation with age, liver enzymes, ALT/AST, and α-fetoprotein level. AST level was directly correlated with miR-122, while an inversely correlated with miR-23b. Fibrosis and steatosis stages possessed positive correlation with miR-199 expression and negative correlation with miR-27a and miR-93. In conclusion, miR-23b and miR-106 might be a useful biomarker for chronic hepatitis C (CHC). MiR-27a, miR-93, and miR-199 might have a potential role in the progression of liver diseases. Unravel the role of these miRNAs in CHC patients might lead to precise prognosis and management.

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Aberrant miR199a-5p/caveolin1/PPARα axis in hepatic steatosis

Cited by 43 publications

References 37 publications

Caveolin1 protects against diet induced hepatic lipid accumulation in mice

Caveolin1 protects against diet induced hepatic lipid accumulation in mice

MicroRNAs in heart failure: Non-coding regulators of metabolic function

Circulating microRNAs as predictive biomarkers for liver disease progression of chronic hepatitis C (genotype‐4) Egyptian patients

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