Peripheral blood mononuclear cells‐expressed miRNA profiles derived from children with metabolic‐associated fatty liver disease and insulin resistance

Osés, Maddi; Medrano, María; Sanchez, Javier Margareto; Portillo, Marı́a P.; Aguilera, Concepción M.; Altmäe, Signe; Labayen, Idoia

doi:10.1111/ijpo.12966

Cited by 6 publications

(3 citation statements)

References 55 publications

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“…Clinical studies have also found reduced miR-142-3p expression in peripheral blood mononuclear cells (PBMCs) of children with metabolic-associated fatty liver disease (MAFLD) that was potentially correlated with serum triglyceride levels 59 , suggesting that miR-142-3p may be closely associated with the occurrence of MAFLD. Although a growing number of studies con rm that NAFLD/NASH has a paternal origin, the programming mechanisms remain unelucidated, leading to di culties in early prevention and treatment.…”

Section: Discussionmentioning

confidence: 99%

Sperm miR-142-3p reprogramming mediates paternal stress-induced non-alcoholic steatohepatitis in offspring rats

Wang,

Zhang,

Guo

et al. 2024

Preprint

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Although epidemiological data suggest a strong association between paternal adverse environmental exposure and susceptibility to multiple diseases in offspring, the sperm-to-liver pathway involved in offspring disease is complicated and worthy of further exploration. Caffeine contained in many beverages is regarded as a chronic stressor, and exerts reproductive and developmental toxicity. Effects of paternal pre-pregnant caffeine exposure (PPCE) on the long-term health of offspring and the underlying mechanisms remain unclear. This study innovatively reported the occurrence and transgenerational inheritance of PPCE-induced non-alcoholic steatohepatitis (NASH) in offspring, and aimed to elucidate its sperm reprogramming mechanism and the potential intervention targets. Male rats were administrated with caffeine (15 ~ 60 mg/kg/d) by gavage for 8 weeks before mating. Symptoms of NASH were found in two successive generations of male rats (F1 and F2) whose fathers or grandfathers (F0) were exposed to caffeine. RNA-seq was employed to screen out a novel miRNA mediating equilibrant of liver fatty metabolism: miR-142-3p. Role of sperm miR-142-3p in PPCE-induced offspring NAFLD was validated by in vitro fertilization of the sperm of PPCE or miR-142-3pKO sperm with normal oocytes. Overexpression of miR-142-3p in offspring liver reversed NASH manifestation in PPCE male offspring. We further proved that caffeine-induced paternal chronic stress (high glucocorticoid level) but not caffeine itself is the main cause of methylation changes in sperm and offspring NAFLD, via experiments in vitro and glucocorticoid receptor blockade. Moreover, the linkage between serum high glucocorticoids and sperm miR-142-3p low programming was also verified in clinical samples. Overall, we demonstrated for the first time that PPCE induced NASH in offspring with transgenerational inheritance, confirmed the reprogramming mechanism of sperm miR-142-3p, and identified miR-142-3p as a potential intervention target for paternal-derived NASH.

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Section: Discussionmentioning

confidence: 99%

Sperm miR-142-3p reprogramming mediates paternal stress-induced non-alcoholic steatohepatitis in offspring rats

Wang,

Zhang,

Guo

et al. 2024

Preprint

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“… 66 However, hsa‐miR‐139‐3p has only been proved to participate in various cancers, 67 , 68 and there has been no research about its relationship with psoriasis, NASH, or other metabolic diseases, which suggests more further studies. As for hsa‐miR‐142‐3p and hsa‐miR‐142‐5p, some researchers identified their participation in metabolic diseases, including insulin resistance and obesity in preadolescent children 69 , 70 as well as metabolic syndrome‐associated cardiovascular disease by regulating metabolic and inflammatory signals. 71 So, we suppose hsa‐miR‐142‐3p and hsa‐miR‐142‐5p may take part in psoriasis and NASH as well, and even be possible therapies for them, which need more experiments.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis to reveal the potential comorbidity mechanism in psoriasis and nonalcoholic steatohepatitis

Xian,

Bai,

Guo

et al. 2023

Skin Research and Technology

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PurposeAn increasing amount of evidence suggests that psoriasis and nonalcoholic steatohepatitis (NASH) may occur simultaneously, whereas the underlying mechanisms remain unclear. Our research aims to explore the potential comorbidity mechanism in psoriasis and nonalcoholic steatohepatitis.Materials and MethodsThe expression profiles of psoriasis (GSE30999, GSE13355) and NASH (GSE24807, GSE17470) were downloaded from GEO datasets. Next, common differently expressed genes (DEGs) of psoriasis and NASH were investigated. Then, GO and KEGG enrichment, protein interaction network (PPI) construction, and hub gene identification for DEGs were performed. Finally, immune cells expression, target genes predicted by common miRNAs, and transcription factors interaction analysis for hub genes were carried out.ResultsTwenty DEGs were identified in totally. GO analysis revealed response to the virus was the most enriched term, and hepatitis C and coronavirus disease‐COVID‐19 infection‐associated pathways were mainly enriched in KEGG. A total of eight hub genes were collected, including IFIT1, IFIT3, OAS1, HPGDS, IFI27, IFI44, CXCL10, IRF9, and 11 TFs were predicted. Then, neutrophils and monocytes were identified as immune cells that express the most hub genes. Moreover, five common miRNAs for psoriasis and NASH and one common miRNAs (hsa‐miR‐1305)‐mRNAs (CHL1, MBNL2) network were presented.ConclusionCHL1 and MBNL2 may participate in the process of psoriasis and NASH via regulating hsa‐miR‐1305, and together with eight hub genes may be potential therapeutic targets for future treatment for the co‐occurrence of these two diseases. This comprehensive bioinformatic analysis provides new insights on molecular pathogenesis and identification of potential therapeutic targets for the co‐occurrence of them.

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“…A previous study [ 12 ] reported that AT macrophages modulate obesity-related β-cell adaptations through the secretion of miRNA-containing (miR-155) extracellular vesicles. Recently, several miRNAs, such as miR-320a, miR-142-3p, and the let-7 family, were identified as potential circulating biomarkers of IR in pre-adolescent children [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Visceral Adipose Tissue Molecular Networks and Regulatory microRNA in Pediatric Obesity: An In Silico Approach

Roy

Modi

Ghosh

et al. 2022

IJMS

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Childhood obesity carries an increased risk of metabolic complications, sleep disturbances, and cancer. Visceral adiposity is independently associated with inflammation and insulin resistance in obese children. However, the underlying pathogenic mechanisms are still unclear. We aimed to detect the gene expression pattern and its regulatory network in the visceral adipose tissue of obese pediatric individuals. Using differentially-expressed genes (DEGs) identified from two publicly available datasets, GSE9624 and GSE88837, we performed functional enrichment, protein–protein interaction, and network analyses to identify pathways, targeting transcription factors (TFs), microRNA (miRNA), and regulatory networks. There were 184 overlapping DEGs with six significant clusters and 19 candidate hub genes. Furthermore, 24 TFs targeted these hub genes. The genes were regulated by miR-16-5p, miR-124-3p, miR-103a-3p, and miR-107, the top miRNA, according to a maximum number of miRNA–mRNA interaction pairs. The miRNA were significantly enriched in several pathways, including lipid metabolism, immune response, vascular inflammation, and brain development, and were associated with prediabetes, diabetic nephropathy, depression, solid tumors, and multiple sclerosis. The genes and miRNA detected in this study involve pathways and diseases related to obesity and obesity-associated complications. The results emphasize the importance of the TGF-β signaling pathway and its regulatory molecules, the immune system, and the adipocytic apoptotic pathway in pediatric obesity. The networks associated with this condition and the molecular mechanisms through which the potential regulators contribute to pathogenesis are open to investigation.

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Peripheral blood mononuclear cells‐expressed miRNA profiles derived from children with metabolic‐associated fatty liver disease and insulin resistance

Cited by 6 publications

References 55 publications

Sperm miR-142-3p reprogramming mediates paternal stress-induced non-alcoholic steatohepatitis in offspring rats

Sperm miR-142-3p reprogramming mediates paternal stress-induced non-alcoholic steatohepatitis in offspring rats

Bioinformatics analysis to reveal the potential comorbidity mechanism in psoriasis and nonalcoholic steatohepatitis

Visceral Adipose Tissue Molecular Networks and Regulatory microRNA in Pediatric Obesity: An In Silico Approach

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