MiR-34a regulates mitochondrial content and fat ectopic deposition induced by resistin through the AMPK/PPARα pathway in HepG2 cells

Wen, Fengyun; An, Chaoqing; Wu, Xiaotian; Yang, Yi; Xu, Jingjing; Liu, Yasong; Wang, Chunming; Nie, Leitong; Fang, Hubin; Zhou, Yang

doi:10.1016/j.biocel.2017.11.008

Cited by 48 publications

(23 citation statements)

References 56 publications

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“…5e, f). Our results are consistent with one previous study [53], but are inconsistent with a recent report that overexpression of miR-34a increases lipid deposition in mouse liver and HepG2 cells [54]. The discrepancy may be due to differences between species or cell type.…”

Section: Discussioncontrasting

confidence: 63%

miR-34a regulates adipogenesis in porcine intramuscular adipocytes by targeting ACSL4

Wang

Ding

et al. 2020

BMC Genet

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Background: Intramuscular fat (IMF) content is an important factor in porcine meat quality. Previously, we showed that miR-34a was less abundant in liver tissue from pigs with higher backfat thickness, compared to pigs with lower backfat thickness. The purpose of this present study was to explore the role of miR-34a in adipogenesis. Result: Bioinformatics analysis identified Acyl-CoA synthetase long chain family member 4 (ACSL4) as a putative target of miR-34a. Using a luciferase reporter assay, we verified that miR-34a binds the ACSL4 mRNA at the 3'UTR. To examine the role of the miR-34a-ACSL4 interaction in IMF deposition in the pig, mRNA and protein expression of the ACSL4 gene was measured in primary intramuscular preadipocytes transfected with miR-34a mimic and inhibitor. Our results showed that ACSL4 is expressed throughout the entire differentiation process in pig preadipocytes, similar to the lipogenesis-associated genes PPARγ and aP2. Transfection with miR-34a mimic reduced lipid droplet formation during adipogenesis, while miR-34a inhibitor increased lipid droplet accumulation. Transfection with miR-34a mimic also reduced the mRNA and protein expression of ACSL4 and lipogenesis genes, including PPARγ, aP2, and SREBP-1C, but increased the expression of steatolysis genes such as ATGL and Sirt1. In contrast, the miR-34a inhibitor had the opposite effect on gene expression. Further, knockdown of ACSL4 decreased lipid droplet accumulation. Conclusions: Our results support the hypothesis that miR-34a regulates intramuscular fat deposition in porcine adipocytes by targeting ACSL4.

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Section: Discussioncontrasting

confidence: 63%

miR-34a regulates adipogenesis in porcine intramuscular adipocytes by targeting ACSL4

Wang

Ding

et al. 2020

BMC Genet

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“…Thus, miRNAs is very likely to be the link between gut microbiota and NAFLD. The miRNAs we scanned were stably expressed in the liver and involved in the course of NAFLD such as hepatic steatosis (miR10b [ 60 ], miR-24 [ 61 ], miR-29a [ 62 ], miR-155 [ 63 ], miR-34a [ 64 ], miR-125b [ 65 ], miR-486 [ 66 ], miR-199a [ 67 ], miR-30b [ 68 ], miR-30c [ 69 ], miR467b [ 70 ], miR-148a [ 71 ]), insulin resistance (miR-125b [ 72 ], miR-206 [ 73 ], miR-130a [ 74 ], miR-291b [ 75 ]), inflammatory and hepatic fibrosis (miR-21a [ 76 , 77 ], miR-199a [ 78 ], miR-370 [ 79 ], miR-130a [ 80 ], miR-34a [ 81 ], miR-24 [ 82 ]), as well as cirrhosis and HCC (miR-210 [ 83 ], miR-10b [ 84 ]). We further analyzed the correlation between the alteration of gut microbiota and miRNAs.…”

Section: Discussionmentioning

confidence: 99%

Amelioration of hepatic steatosis is associated with modulation of gut microbiota and suppression of hepatic miR-34a in Gynostemma pentaphylla (Thunb.) Makino treated mice

Jia

Lin

et al. 2018

Nutr Metab (Lond)

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BackgroundNon-alcoholic fatty liver disease (NAFLD) is a chronic and progressive liver disease with an increased risk of morbidity and mortality. However, so far no specific pharmacotherapy has been approved. Gynostemma pentaphylla (Thunb.) Makino (GP) is a traditional Chinese medicine that is widely used against hyperlipemia as well as hyperglycemia. This study aims to evaluate the effect of GP on NAFLD and explore the possible mechanism.MethodsHigh-fat-diet induced NAFLD mice model were orally administrated with GP at dose of 11.7 g/kg or equivalent volume of distilled water once a day for 16 weeks. Body weight, food intake and energy expenditure were assessed to evaluate the general condition of mice. The triglycerides, total cholesterol content in the liver and liver histopathology, serum lipid profile and serum insulin level, fecal microbiome, hepatic microRNAs and relative target genes were analyzed.ResultsMice in GP treatment group displayed improved hepatic triglycerides content with lower lipid droplet in hepatocyte and NAFLD activity score. Besides, GP treatment altered the composition of gut microbiota and the relative abundance of some of the key components that are implicated in metabolic disorders, especially phylum Firmicutes (Eubacterium, Blautia, Clostridium and Lactobacillus). Several hepatic microRNAs were downregulated by GP treatment such as miR-130a, miR-34a, miR-29a, miR-199a, among which the expression miR-34a was altered by more than four-fold compared to that of HFD group (3:14). The correlation analysis showed that miR-34a was strongly related to the change of gut microbiota especially phylum Firmicutes (R = 0.796). Additionally, the target genes of miR-34a (HNF4α, PPARα and PPARα) were restored by GP both in mRNA and protein levels.ConclusionOur results suggested that GP modulated the gut microbiota and suppressed hepatic miR-34a, which was associated with the amelioration of hepatic steatosis.

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“…Notably, by inhibiting SIRT1, miR-34a can affect the functioning of a multitude of pathways. Indeed, increased miR-34a levels have been detected in liver of NAFLD animals and morbid patients [91,92,93,94], while miR-34a inhibition resulted in active SIRT1 and increased PPARα level, with concomitant restoration of triacylglycerol content and mitochondrial transmembrane potential in mice liver [94,95]. Moreover, the downregulation of miR-34a resulted in a lower expression of fibrotic genes upon alcohol-feeding in mice [96].…”

Section: Resultsmentioning

confidence: 99%

Hepatic MicroRNA Expression by PGC-1α and PGC-1β in the Mouse

Piccinin

Arconzo

Graziano

et al. 2019

IJMS

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The fine-tuning of liver metabolism is essential to maintain the whole-body homeostasis and to prevent the onset of diseases. The peroxisome proliferator-activated receptor-γ coactivators (PGC-1s) are transcriptional key players of liver metabolism, able to regulate mitochondrial function, gluconeogenesis and lipid metabolism. Their activity is accurately modulated by post-translational modifications. Here, we showed that specific PGC-1s expression can lead to the upregulation of different microRNAs widely implicated in liver physiology and diseases development and progression, thus offering a new layer of complexity in the control of hepatic metabolism.

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MiR-34a regulates mitochondrial content and fat ectopic deposition induced by resistin through the AMPK/PPARα pathway in HepG2 cells

Cited by 48 publications

References 56 publications

miR-34a regulates adipogenesis in porcine intramuscular adipocytes by targeting ACSL4

miR-34a regulates adipogenesis in porcine intramuscular adipocytes by targeting ACSL4

Amelioration of hepatic steatosis is associated with modulation of gut microbiota and suppression of hepatic miR-34a in Gynostemma pentaphylla (Thunb.) Makino treated mice

Hepatic MicroRNA Expression by PGC-1α and PGC-1β in the Mouse

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