Elevation of circulating <scp>microRNA</scp> levels in obese children compared to healthy controls

Thompson, Michael D.; Cismowski, Mary J.; Serpico, Mark; Pusateri, Antoinette; Brigstock, David R.

doi:10.1111/cob.12192

Cited by 45 publications

(44 citation statements)

References 25 publications

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“…The most abundant miRNA in the liver is miR‐122, which accounts for more than half of the total hepatic miRNA content . Multiple studies have reported increased circulatory levels of miR‐122 in pediatric CLDs such as biliary atresia, CFLD, nonalcoholic fatty liver disease (NAFLD), and hepatitis B . Our study shows increased circulatory miR‐122 levels in children with CFLD when compared to both CFnoLD and healthy controls.…”

Section: Discussionmentioning

confidence: 54%

“…(31) Multiple studies have reported increased circulatory levels of miR-122 in pediatric CLDs such as biliary atresia, CFLD, nonalcoholic fatty liver disease (NAFLD), and hepatitis B. (17,(32)(33)(34) Our study shows increased circulatory miR-122 levels in children with CFLD when compared to both CFnoLD and healthy controls. We also found overexpression of miR-122 in CFnoLD compared to healthy controls.…”

Section: Discussionmentioning

confidence: 55%

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MicroRNA Sequencing Identifies a Serum MicroRNA Panel, Which Combined With Aspartate Aminotransferase to Platelet Ratio Index Can Detect and Monitor Liver Disease in Pediatric Cystic Fibrosis

et al. 2018

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Cystic fibrosis (CF)-associated liver disease (CFLD) is a hepatobiliary complication of CF. Current diagnostic modalities rely on nonspecific assessments, whereas liver biopsy is the gold standard to assess severity of fibrosis. MicroRNAs (miRNAs) regulate liver disease pathogenesis and are proposed as diagnostic biomarkers. We investigated the combined use of serum miRNAs and aspartate aminotransferase (AST) to platelet ratio (APRI) to diagnose and assess CFLD severity. This was a cross-sectional cohort study of the circulatory miRNA signature of 124 children grouped by clinical, biochemical, and imaging assessments as follows: CFLD (n = 44), CF patients with no evidence of liver disease (CFnoLD; n = 40), and healthy controls (n = 40). Serum miRNAs were analyzed using miRNA sequencing (miRNA-Seq). Selected differentially expressed serum miRNA candidates were further validated by qRT-PCR and statistical analysis performed to evaluate utility to predict CFLD and fibrosis severity validated by liver biopsy, alone or in combination with APRI. Serum miR-122-5p, miR-365a-3p, and miR-34a-5p levels were elevated in CFLD compared to CFnoLD, whereas miR-142-3p and let-7g-5p were down-regulated in CFLD compared to CFnoLD. Logistic regression analysis combining miR-365a-3p, miR-142-3p, and let-7g-5p with APRI showed 21 times greater odds of accurately predicting liver disease in CF with an area under the receiver operating characteristics curve (AUROC) = 0.91 (sensitivity = 83%, specificity = 92%; P < 0.0001). Expression levels of serum miR-18a-5p were correlated with increasing hepatic fibrosis (HF) stage in CFLD (r = 0.56; P < 0.0001), showing good diagnostic accuracy for distinguishing severe (F3-F4) from mild/moderate fibrosis (F0-F2). A unit increase of miR-18a-5p showed a 7-fold increased odds of having severe fibrosis with an AUROC = 0.82 (sensitivity = 93%, specificity = 73%; P = 0.004), indicating its potential to predict fibrosis severity. Conclusion: We identified a distinct circulatory miRNA profile in pediatric CFLD with potential to accurately discriminate liver disease and fibrosis severity in children with CF.

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Section: Discussionmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 55%

MicroRNA Sequencing Identifies a Serum MicroRNA Panel, Which Combined With Aspartate Aminotransferase to Platelet Ratio Index Can Detect and Monitor Liver Disease in Pediatric Cystic Fibrosis

et al. 2018

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“…The NAFLD‐associated changes in the spectrum of extracellular miRNA species present in human blood have been the subject of more than one intensive investigation . Each of these reports showed that circulating miRNAs reflect liver damage more precisely than do serum transaminases.…”

Section: Mirnas Are Proposed Both As Biomarkers and As Regulators Of mentioning

confidence: 99%

“…According to a very thorough RNA-Seq-based study by Hou et al, miR-122 is expressed almost exclusively in the liver, comprising more than 52% of the total pool of liver miRNAs (66). Overwhelming majority of published reports agree that the levels of miR-122 in sera of NAFLD individuals are elevated (53)(54)(55)(56)(57)(59)(60)(61)(62). If a majority of miRNAs present in circulation of individuals with NAFLD originate from the liver, it would be reasonable to expect an increase in the expression of miR-122 in hepatic parenchyma, along with a progression of NAFLD across its stages.…”

Section: Mir-122: Intracellular-extracellular Seesaw Expression Paradoxmentioning

confidence: 99%

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Adipose may actively delay progression of NAFLD by releasing tumor‐suppressing, anti‐fibrotic miR‐122 into circulation

2018

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Summary Nonalcoholic fatty liver disease (NAFLD) is the most common liver pathology. Here we propose tissue‐cooperative, homeostatic model of NAFLD. During early stages of NAFLD the intrahepatic production of miR‐122 falls, while the secretion of miRNA‐containing exosomes by adipose increases. Bloodstream carries exosome to the liver, where their miRNA cargo is released to regulate their intrahepatic targets. When the deterioration of adipose catches up with the failing hepatic parenchyma, the external supply of liver‐supporting miRNAs gradually tapers off, leading to the fibrotic decompensation of the liver and an increase in hepatic carcinogenesis. This model may explain paradoxical observations of the disease‐associated decrease in intrahepatic production of certain miRNAs with an increase in their levels in serum. Infusions of miR‐122 and, possibly, some other miRNAs may be efficient for preventing NAFLD‐associated hepatocellular carcinoma. The best candidates for exosome‐wrapped miRNA producer are adipose tissue‐derived mesenchymal stem cells (MSCs), known for their capacity to shed large amounts of exosomes into the media. Notably, MSC‐derived exosomes with no specific loading are already tested in patients with liver fibrosis. Carrier exosomes may be co‐manufactured along with their cargo. Exosome‐delivered miRNA cocktails may augment functioning of human organs suffering from a variety of chronic diseases.

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High expression levels of circulating microRNA‐122 and microRNA‐222 are associated with obesity in children with Mayan ethnicity

González-Arce

Lara-Riegos

Pérez-Mendoza

et al. 2020

American J Hum Biol

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High expression levels (HELs) of microRNA-122 (miR-122) or microRNA-222 (miR-222) have been associated with insulin resistance (IR), which leads to the development of obesity. The association between HELs of circulating miR-122 and miR-222 and the risk of obesity was evaluated in Mexican school-aged children, where childhood obesity is the primary cause of morbidity.Methods: Anthropometric data, biochemical parameters, and caloric intake were obtained in 50 children with obesity and 49 children with normal weight.The expression of circulating miR-122 and miR-222 was measured by quantitative real-time polymerase chain reaction amplification. Data were analyzed using Student t test, Pearson correlation coefficient, associations with chisquare, and multiple linear and logistic regressions with SPSS software v.23. Results: The mean relative expression for miR-122 and miR-222 was 0.33 and 5.65, respectively, for children with obesity and 0.22 and 3.16, respectively, for children with normal weight. The expression of miR-122 and miR-222 was 1.47 and 1.78-fold higher, respectively, in children with obesity (P = 0.001 and P = 0.025). HELs of both miR-122 and miR-222 were associated with body mass index (BMI), waist to height ratio (WHR), fat percentage, serum highdensity lipid levels, triglycerides (TGs), and metabolic index (MI) (P < .001). Conclusions: The HELs of circulating miR-122 conferred a 3.85-fold increase in the risk for obesity, whereas the HELs of both miR-122 and miR-222 conferred a 3.11-fold increase in the risk for obesity, which were also associated with higher anthropometric or biochemical parameters, such as BMI, WHR, fat percentage, serum high-density lipid levels, TGs, and MI, in Mayan children.

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Elevation of circulating microRNA levels in obese children compared to healthy controls

Cited by 45 publications

References 25 publications

MicroRNA Sequencing Identifies a Serum MicroRNA Panel, Which Combined With Aspartate Aminotransferase to Platelet Ratio Index Can Detect and Monitor Liver Disease in Pediatric Cystic Fibrosis

MicroRNA Sequencing Identifies a Serum MicroRNA Panel, Which Combined With Aspartate Aminotransferase to Platelet Ratio Index Can Detect and Monitor Liver Disease in Pediatric Cystic Fibrosis

Adipose may actively delay progression of NAFLD by releasing tumor‐suppressing, anti‐fibrotic miR‐122 into circulation

High expression levels of circulating microRNA‐122 and microRNA‐222 are associated with obesity in children with Mayan ethnicity

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