MiR-30c-5p ameliorates hepatic steatosis in leptin receptor-deficient (db/db) mice via down-regulating FASN

Fan, Jiahui; Li, Huaping; Nie, Xiang; Yin, Zongsheng; Zhang, Yanru; Chen, Chen; Wang, Dao Wen

doi:10.18632/oncotarget.14561

Cited by 28 publications

(26 citation statements)

References 32 publications

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“…Similar to our findings, Das et al, have found that miR-30c-5p targeting regulates fatty acid synthase, reduces triglyceride accumulation and lipid deposition, and improves NAFLD [23]. In fact, abnormal accumulation of TG in the liver is one of the characteristics of NAFLD [24,25].…”

Section: Discussionsupporting

confidence: 92%

Inhibition of miR-499-5p expression improves nonalcoholic fatty liver disease

Liu

Wang

Chen

et al. 2019

Preprint

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Background: Nonalcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver diseases. However, the pathogenesis of NAFLD is largely unknown. Here, we investigated the specific role of miR-499-5p in NAFLD. Method: Free fatty acid (FFA) was used to induce HL-7702 cell line to establish a NAFLD cell model, and animal models of NAFLD were constructed by feeding C57BL/6 mice with high fat diet (HFD). Expression levels of miR-499-5p in the HL-7702 cells and C57BL/6 mice were determined by RT-qPCR. In addition, functional experiments were carried out through transfecting miR-499-5p inhibitor into NAFLD cells, and injecting NAFLD mice with a lentiviral vector with knock down the miR-499-5p . Furthermore, the effects of miR-499-5p inhibition on lipidation and inflammation were investigated by oil red O staining, HE staining, and biochemical analysis. Results: Compared with normal controls, the expression of miR-499-5p was significantly up-regulated in NAFLD cells and tissues in mouse (P < 0.05). After NAFLD cells transfected by miR-499-5p inhibitor, the expression of miR-499-5p was inhibited, the lipid deposition and content of TG were reduced, and the lipidation was improved (P < 0.05). Simultaneously, after NAFLD mice were injected with knocked down the miR-499-5p lentiviral vector, the degree of lipid droplet deposition and content of TG were also reduced. Besides, it also decreased the levels of TC and AST in serum, and improved hepatic lipid metabolism (P < 0.05). Conclusion: Inhibition of miR-499-5p expression improved NAFLD in mice, which provided a new direction for the treatment of NAFLD.

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Section: Discussionsupporting

confidence: 92%

Inhibition of miR-499-5p expression improves nonalcoholic fatty liver disease

Liu

Wang

Chen

et al. 2019

Preprint

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“… 31 However, rAAV9-delivered miR-217 may also target other organs, such as the liver and kidney, and may also exert functions on these organs; thus, potential systemic effects of miR-217 should not be ruled out. 32 Organ-specific miR-217 transgenic or knockout mice can be used to regulate miR-217 expression in the heart to further explore the role of miR-217 in cardiac hypertrophy and heart failure.…”

Section: Discussionmentioning

confidence: 99%

“…rAAV9 vectors containing hsa-miR-217, hsa-miR-217-TUD, PTEN, or GFP were constructed by triple plasmid co-transfection, respectively, as described previously. 32 The vectors were purified and stored at −80°C before injection.…”

Section: Methodsmentioning

confidence: 99%

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miR-217 Promotes Cardiac Hypertrophy and Dysfunction by Targeting PTEN

Nie

Fan

et al. 2018

Molecular Therapy - Nucleic Acids

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Previously, we found that the miR-217 expression level was increased in hearts from chronic heart failure (CHF) patients by using miRNA profile analysis. This study aimed to explore the role of miR-217 in cardiac dysfunction. Heart tissue samples from CHF patients were used to detect miR-217 expression levels. A type 9 recombinant adeno-associated virus (rAAV9) was employed to manipulate miR-217 expression in mice with thoracic aortic constriction (TAC)-induced cardiac dysfunction. Cardiac structure and function were measured by echocardiography and invasive pressure-volume analysis. The expression levels of miR-217 were increased in hearts from both CHF patients and TAC mice. Overexpression of miR-217 in vivo aggravated pressure overload-induced cardiac hypertrophy, fibrosis, and cardiac dysfunction, whereas miR-217-TUD-mediated downregulation of miR-217 reversed these effects. PTEN was predicted and validated as a direct target of miR-217, and re-expression of PTEN attenuated miR-217-mediated cardiac hypertrophy and cardiac dysfunction. Importantly, cardiomyocyte-derived miR-217-containing exosomes enhanced proliferation of fibroblasts in vitro. All of these findings show that miR-217 participates in cardiac hypertrophy and cardiac fibrosis processes through regulating PTEN, which suggests a promising therapeutic target for CHF.

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“…miR-29 and miR-486 are reported to regulate cholesterol metabolism by targeting hydroxy-3-methyl-glutaryl-CoA reductase and histone acetyltransferase-1, respectively (17,28). Furthermore, miR-30b-5p and miR-30c-5p belong to the same family of miRNAs regulating fatty acid synthesis genes, targeting elongation of very long chain fatty acids protein 5 (ELOVL5) and fatty acid synthase (FAS), respectively (18,19). miR-34a has been reported to participate in proinflammatory NAFLD (24), while miR-130a-3p directly targets transforming growth factor-β receptors 1 and 2, which may contribute to hepatic fibrosis (21).…”

Section: Discussionmentioning

confidence: 99%

Integrated microRNA and proteome analysis reveal a regulatory module in hepatic lipid metabolism disorders in mice with subclinical hypothyroidism

et al. 2019

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Subclinical hypothyroidism (SCH) is becoming a global health problem due to its increasing prevalence and potential adverse effects, including cardiovascular diseases and nonalcoholic fatty liver disease (NAFLD). However, the association between SCH and NAFLD remains controversial. MicroRNAs (miRNAs/miRs) have been reported to be implicated in lipid metabolism disorders; however, how miRNAs regulate hepatic lipid metabolism in SCH mice remains unknown. The present study investigated miRNA alterations and proteome profiles in an SCH mouse model, which was generated by methimazole administration in mice for 16 weeks. Next, the profiles of 17 miRNAs that are critical to hepatic lipid metabolism and the proteome were investigated using reverse transcription-quantitative polymerase chain reaction and iTRAQ labeling in the liver specimens of SCH (n=9) and control (n=7) mice. Putative target prediction of miRNAs was also conducted using TargetScan and miRanda. Compared with the control mice, SCH mice had 8 miRNAs and 36 proteins with significantly different expression in the liver tissues. Furthermore, a regulatory module containing 3 miRNAs (miR-34a-5p, miR-24-3p and miR-130a-3p) and 4 proteins (thioredoxin, selenium-binding protein 2, elongation factor 1β and prosaposin) was identified. Overall, integrated analysis of miRNAs and the proteome highlighted a regulatory module between miRNAs and proteins, which, to a certain extent, may contribute to a better understanding of hepatic lipid metabolism disorders in SCH mice.

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MiR-30c-5p ameliorates hepatic steatosis in leptin receptor-deficient (db/db) mice via down-regulating FASN

Cited by 28 publications

References 32 publications

Inhibition of miR-499-5p expression improves nonalcoholic fatty liver disease

Inhibition of miR-499-5p expression improves nonalcoholic fatty liver disease

miR-217 Promotes Cardiac Hypertrophy and Dysfunction by Targeting PTEN

Integrated microRNA and proteome analysis reveal a regulatory module in hepatic lipid metabolism disorders in mice with subclinical hypothyroidism

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