Hepatic miR‐33a/miR‐144 and their target gene <i>ABCA1</i> are associated with steatohepatitis in morbidly obese subjects

Vega-Badillo, Joel; Gutiérrez-Vidal, Roxana; Hernández-Pérez, Hugo A.; Villamil‐Ramírez, Hugo; León-Mimila, Paola; Sánchez‐Muñoz, Fausto; Morán-Ramos, Sofía; Larrieta‐Carrasco, Elena; Fernández-Silva, Itzel; Méndez-Sánchez, Nahúm; Tovar, Armando R.; Campos-Pérez, Francisco; Villarreal-Molina, Teresa; Hernández-Pando, Rogelio; Aguilar-Salinas, Carlos A.; Canizales‐Quinteros, Samuel

doi:10.1111/liv.13109

Cited by 68 publications

(51 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, some authors have reported that liver miR122 expression is decreased in NASH [20,26] and miR33a was increased in NASH individuals [38]. These discrepancies might be partially explained by differences in the cohort of patients studied.…”

Section: Discussionmentioning

confidence: 99%

“…They also showed that miR33 and miR33* represses key enzymes involved in cholesterol efflux (ABCA1 and NPC1) and fatty acid metabolism (CROT and CPT1α) in human hepatocyte cell lines [16], in agreement with our findings. Accordingly, Vega-Vadillo et al [38], in a MO cohort, have described that the relative expression of miR33a correlated inversely with ABCA1 protein levels. Moreover, miR33 target gene, CROT , correlated inversely with miR33a .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

miR33a/miR33b* and miR122 as Possible Contributors to Hepatic Lipid Metabolism in Obese Women with Nonalcoholic Fatty Liver Disease

Auguet

Aragonès

Berlanga

et al. 2016

IJMS

View full text Add to dashboard Cite

Specific miRNA expression profiles have been shown to be associated with nonalcoholic fatty liver disease (NAFLD). We examined the correlation between the circulating levels and hepatic expression of miR122 and miR33a/b*, the key lipid metabolism-related gene expression and the clinicopathological factors of obese women with NAFLD. We measured miR122 and miR33a/b* expression in liver samples from 62 morbidly obese (MO), 30 moderately obese (ModO), and eight normal-weight controls. MiR122 and miR33a/b* expression was analyzed by qRT-PCR. Additionally, miR122 and miR33b* circulating levels were analyzed in 122 women. Hepatic miR33b* expression was increased in MO compared to ModO and controls, whereas miR122 expression was decreased in the MO group compared to ModO. In obese cohorts, miR33b* expression was increased in nonalcoholic steatohepatitis (NASH). Regarding circulating levels, MO patients with NASH showed higher miR122 levels than MO with simple steatosis (SS). These circulating levels are good predictors of histological features associated with disease severity. MO is associated with altered hepatic miRNA expression. In obese women, higher miR33b* liver expression is associated with NASH. Moreover, multiple correlations between miRNAs and the expression of genes related to lipid metabolism were found, that would suggest a miRNA-host gene circuit. Finally, miR122 circulating levels could be included in a panel of different biomarkers to improve accuracy in the non-invasive diagnosis of NASH.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

miR33a/miR33b* and miR122 as Possible Contributors to Hepatic Lipid Metabolism in Obese Women with Nonalcoholic Fatty Liver Disease

Auguet

Aragonès

Berlanga

et al. 2016

IJMS

View full text Add to dashboard Cite

show abstract

“…Overall, the sequencing-based analysis in the present study identified seven miRNAs that are consistently elevated across multiple IR/T2D models. Several of these seven miRNAs are in families that have been strongly connected previously to the control of insulin signaling (e.g., miR-107, miR-802, miR-34a, and miR-29a/b/c) (9, 21, 23, 26, 37, 44), obesity-related phenotypes (e.g., miR-28) (21), gluconeogenesis (e.g., miR-29a/b/c) (13,51), and/or lipid homeostasis (e.g., miR-148, miR-222 and miR-29a/b/c) (7,17,29,30,45). Liver miRNA profiles in the rodent models with metabolic dysfunction included in the present study are provided here: https://github.com/Sethupathy-Lab/metabomir.…”

Section: Seven Dysregulated Hepatic Mirnas Are Shared Across Multiplementioning

confidence: 99%

Acute suppression of insulin resistance-associated hepatic miR-29 in vivo improves glycemic control in adult mice

Hung

Kanke

Kurtz

et al. 2019

Physiological Genomics

View full text Add to dashboard Cite

MicroRNAs (miRNAs) are important posttranscriptional regulators of metabolism and energy homeostasis. Dysregulation of certain miRNAs in the liver has been shown to contribute to the pathogenesis of Type 2 diabetes (T2D), in part by impairing hepatic insulin sensitivity. By small RNA-sequencing analysis, we identified seven hepatic miRNAs (including miR-29b) that are consistently aberrantly expressed across five different rodent models of metabolic dysfunction that share the feature of insulin resistance (IR). We also showed that hepatic miR-29b exhibits persistent dysregulation during disease progression in a rat model of diabetes, UCD-T2DM. Furthermore, we observed that hepatic levels of miR-29 family members are attenuated by interventions known to improve IR in rodent and rhesus macaque models. To examine the function of the miR-29 family in modulating insulin sensitivity, we used locked nucleic acid (LNA) technology and demonstrated that acute in vivo suppression of the miR-29 family in adult mice leads to significant reduction of fasting blood glucose (in both chow-fed lean and high-fat diet-fed obese mice) and improvement in insulin sensitivity (in chow-fed lean mice). We carried out whole transcriptome studies and uncovered candidate mechanisms, including regulation of DNA methyltransferase 3a ( Dnmt3a) and the hormone-encoding gene Energy homeostasis associated ( Enho). In sum, we showed that IR/T2D is linked to dysregulation of hepatic miR-29b across numerous models and that acute suppression of the miR-29 family in adult mice leads to improved glycemic control. Future studies should investigate the therapeutic utility of miR-29 suppression in different metabolic disease states. Enho; insulin resistance; liver; microRNA-29 (miR-29); UCD-T2DM

show abstract

“…Zhang et al (2015) reported that upregulation of miR-125b by estrogen protected against NAFLD in female mice. Hepatic miR-33a/miR-144 and their target gene ABCA1 were associated with steatohepatitis in morbidly obese subjects (Vega-Badillo et al, 2016), and down-regulation of miR-144 elicited proinflammatory cytokine production by targeting toll-like receptor 2 in nonalcoholic steatohepatitis of high-fat-diet-induced metabolic syndrome E3 rats (Li et al, 2015). Based on our findings of increased BMI and VI with obesity resulting from DKA exposure, we posit that miR-144 and miR-125b possibly regulate lipid metabolism, and further induce lipid-metabolism-disorder syndrome.…”

Section: Introductionmentioning

confidence: 97%

Lipid metabolism disorder induced by up-regulation of miR-125b and miR-144 following β-diketone antibiotic exposure to F0-zebrafish (Danio rerio)

Wang

Zheng

et al. 2018

Ecotoxicology and Environmental Safety

View full text Add to dashboard Cite

β-Diketone antibiotics (DKAs) are widely used in human and veterinary medicine to prevent and treat a large variety of infectious diseases. Long-term DKA exposure to zebrafish can result in lipid metabolism disorders and liver function abnormalities. Based on our previous miRNA-seq analyses, miR-144 and miR-125b were identified as target genes regulating lipid metabolism. DKA-exposure at 12.5 and 25 mg/L significantly increased the expressions of miR-144 and miR-125b. The expression levels for the two miRNAs exhibited an inverse relationship with their lipid-metabolism-related target genes (ppardb, bcl2a, pparaa and pparda). Over-expression and inhibition of miR-144 and miR-125b were observed by micro-injection of agomir-144, agomir-125b, antagomir-144 and antagomir-125b. The over-expression of miR-144 and miR-125b enhanced lipid accumulation and further induced lipid-metabolism-disorder syndrome in F1-zebrafish. The expression of ppardb and bcl2a in whole-mount in situ hybridization was in general agreement with results from qRT-PCR and was concentration-dependent. Oil red O and H&E staining, as well as related physiological and biochemical indexes, showed that chronic DKA exposure resulted in lipid-metabolism-disorder in F0-adults, and in F1-larvae fat accumulation, increased lipid content, abnormal liver function and obesity. The abnormal levels of triglyceride (TG) and total cholesterol (TCH) in DKA-exposed zebrafish increased the risk of hyperlipidemia, atherosclerosis and coronary heart disease. These observations improve our understanding of mechanisms leading to liver disease from exposure to environmental pollution, thereby having relevant practical significance in health prevention, early intervention, and gene therapy for drug-induced diseases.

show abstract

Hepatic miR‐33a/miR‐144 and their target gene ABCA1 are associated with steatohepatitis in morbidly obese subjects

Abstract: miR-33a/144 and their target gene ABCA1 may contribute to the pathogenesis of NASH in morbidly obese subjects.

Cited by 68 publications

References 38 publications

miR33a/miR33b* and miR122 as Possible Contributors to Hepatic Lipid Metabolism in Obese Women with Nonalcoholic Fatty Liver Disease

miR33a/miR33b* and miR122 as Possible Contributors to Hepatic Lipid Metabolism in Obese Women with Nonalcoholic Fatty Liver Disease

Acute suppression of insulin resistance-associated hepatic miR-29 in vivo improves glycemic control in adult mice

Lipid metabolism disorder induced by up-regulation of miR-125b and miR-144 following β-diketone antibiotic exposure to F0-zebrafish (Danio rerio)

Contact Info

Product

Resources

About