miRNA Signatures of Insulin Resistance in Obesity

Jones, Angela L.; Danielson, Kirsty; Benton, Miles C.; Ziegler, Olivia; Shah, Ravi; Stubbs, Richard S.; Das, Saumya; Macartney-Coxson, Donia

doi:10.1002/oby.21950

Cited by 122 publications

(127 citation statements)

References 40 publications

(53 reference statements)

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“…Recently, this miRNA was associated with the prediction of liver dysfunction after liver resection [48]. Furthermore, previous publications suggested a role for hsa-miR-122 as a biomarker for obesity [49]. Here we were able to demonstrate that patients showed reduced levels of hsa-miR122 1 year after RYGB surgery regardless of diabetic status.…”

Section: Discussionsupporting

confidence: 65%

Roux-en-Y-Bariatric Surgery Reduces Markers of Metabolic Syndrome in Morbidly Obese Patients

et al. 2019

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Background Obesity is closely linked to increased markers of metabolic syndrome and development of diabetes. Roux-en-Y bariatric surgery reduces hyperinsulinemia and improves insulin sensitivity and hence benefits morbidly obese patients. Aim To determine changes in markers of metabolic syndrome, pancreatic function, and hepatic insulin sensitivity in patients before and 1 year after undergoing Roux-en-Y gastric bypass surgery. Methods We enrolled 43 consecutive patients in a single center. Markers for metabolic syndrome included proinsulin, insulin, Cpeptide, liver enzymes, and serum levels of selected microRNAs hsa-miR-122, hsa-miR-130, hsa-miR-132, and hsa-miR-375. Results After surgery, all patients showed a significant 37% drop of body mass index (p < 0.001). Furthermore, proinsulin (59% reduction, p < 0.001), insulin (76% reduction, p < 0.001), and C-peptide (56% reduction, p < 0.001) were all reduced 1 year after surgery. Using the hepatic insulin clearance score, we determined a significant increase in hepatic insulin clearance after surgery (76% increase, p < 0.001). Especially diabetic patients showed a marked 2.1-fold increase after surgery. Hepatic enzymes ALT (35% reduction, p = 0.002) and γGT (48% reduction, p < 0.001) were significantly reduced in all patients with similar improvement in diabetic and non-diabetic patients. miRNAs hsa-miR-122, hsa-miR-130, and hsa-miR-132 were all significantly reduced whereas hsa-miR-375 was increased after gastric bypass surgery (p < 0.001 for all miRNAs). Conclusion Both liver and pancreatic stress parameters were reduced significantly 1 year after Roux-en-Y gastric bypass surgery suggesting an overall amelioration of the metabolic syndrome in all patients regardless of previous health status.

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Section: Discussionsupporting

confidence: 65%

Roux-en-Y-Bariatric Surgery Reduces Markers of Metabolic Syndrome in Morbidly Obese Patients

et al. 2019

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“…miR‐144‐5p, first discovered to be a potential biomarker of follicular thyroid cancer, may also be a regulatory factor in various disease, including metabolic disease (metabolic syndrome and diabetes), malignant tumour (non‐small‐cell lung cancer, breast cancer, bladder cancer, oesophageal carcinoma and gastric cancer), inflammatory diseases (tuberculosis, obesity and amyotrophic lateral sclerosis), Alzheimer's disease, depressive disorders and coronary syndrome . miR‐144‐5p inhibited antibacterial autophagy and the immune response to Mycobacterium tuberculosis via repressing DNA damage‐regulated autophagy modulator 2, which is a coordinator of antimicrobial autophagy …”

Section: Discussionmentioning

confidence: 99%

Assessment of microRNA‐144‐5p and its putative targets in inflamed gingiva from chronic periodontitis patients

Wang

Chen

et al. 2018

J of Periodontal Research

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Background and Objective This study aimed to discover the distinctive MicroRNAs (miRNA) functioning in the pathogenesis of periodontal inflammation, which might be potential therapy targets of chronic periodontitis. Material and Methods miRNA profiles of human inflamed gingival tissue from three previous microarrays were re‐analysed. Gingival tissues were collected for the validation of overlapping miRNAs, and a network was constructed to show regulatory connection between overlapping miRNAs and periodontitis‐associated target genes. Potential miRNAs were screened based on their expression levels and predicted target genes. Correlation analysis and binding site prediction were conducted to reveal the relationship between the potential miRNAs and their target genes. Results miR‐144‐5p, found to be upregulated in all three studies, showed the greatest upregulation (P < 0.0001). Another 16 miRNAs (10 upregulated and six downregulated) overlapped between any two of the three studies. All overlapping miRNAs had expected expression levels except for miR‐203 during validation. Ten miRNAs (six upregulated and four downregulated) were found to have periodontal inflammation‐associated targets. Cyclooxygenase 2 (COX2) and interleukin‐17F (IL17F), predicted target genes of upregulated miR‐144‐5p, showed significant decreases and were negatively correlated with miR‐144‐5p in the periodontitis group (r = −0.742 for COX2, r = −0.615 for IL17F). Conclusion This re‐analysis of miRNA signatures has implied the potential regulatory mechanism of miR‐144‐5p and its potential for exploring alternative therapeutic approaches, especially those that use miRNA delivery systems to treat chronic periodontitis. Nevertheless, further study based on larger sample size and homogenous cells is needed to reveal the exact roles of miRNAs in chronic periodontitis.

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“…Regarding miR-532-5p as a candidate marker for training performance outcome after carbohydrate uptake, an independent study by Cui et al found that miR-532-5p was de-regulated in participants conducting muscular strength endurance training, and it showed a negative correlation with the insulin-like growth factor-1 [26]. Moreover, several earlier publications investigated the prominent role of miR-532-5p in the context of adult obesity and diabetes type 2, in particular insulin resistance [27,28,29,30]. Interestingly, most of these studies have in common that miR-532-5p is down-regulated in patients suffering from obesity or diabetes.…”

Section: Discussionmentioning

confidence: 99%

Systematic assessment of blood-borne microRNAs highlights molecular profiles of endurance sport and carbohydrate uptake

Kern

Ludwig

Backes

et al. 2019

Preprint

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Multiple studies endorsed the positive effect of regular exercising on mental and physical health. However, the molecular mechanisms underlying training-induced fitness in combination with personal life-style remain largely unexplored. Circulating biomarkers such as microRNAs (miRNAs) offer themselves for studying systemic and cellular changes since they can be collected from the bloodstream in a low-invasive manner. In Homo sapiens miRNAs are known to regulate a substantial number of protein-coding genes in a post-transcriptional manner and hence are of great interest to understand differential gene expression profiles, offering a cost-effective mechanism to study molecular training adaption, and connecting the dots from genomics to observed phenotypes. Here, we investigated molecular expression patterns of 2, 549 miRNAs in whole-blood samples from 23 healthy and untrained adult participants of a cross-over study, consisting of 8 weeks of endurance training, with several sessions per week, followed by 8 weeks of washout and another 8 weeks of running, using microarrays. Participants were randomly assigned to one of the two study groups, one of which administered carbohydrates before each session in the first training period, switching the treatment group for the second training period. During running sessions clinical parameters as heartbeat frequencyw ere recorded. This information was extended with four measurements of maximum oxygen uptake (VO2 max) for each participant. We observed that multiple circulating miRNAs show expression changes after endurance training, leveraging the capability to separate the blood samples by training status. To this end, we demonstrate that most of the variance in miRNA expression can be explained by both common and known biological and technical factors. Our findings highlight six distinct clusters of miRNAs, each exhibiting an oscillating expression profile across the four study timepoints, that can effectively be utilized to predict phenotypic VO2 max levels. In addition, we identified miR-532-5p as a candidate marker to determine personal alterations in physical training performance on a case-by-case analysis taking the influence of a carbohydrate-rich nutrition into account. In literature, miR-532-5p is known as a common down-regulated miRNA in diabetes and obesity, possibly providing a molecular link between cellular homeostasis, personal fitness levels, and health in aging. We conclude that circulating miRNAs expression can be altered due to regular endurance training, independent of the carbohydrate availability in the timeframe around training. Further validation studies are required to confirm the role of exercise-affected miRNAs and the extraordinary function of miR-532-5p in modulating the metabolic response to a high availability of glucose.

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miRNA Signatures of Insulin Resistance in Obesity

Cited by 122 publications

References 40 publications

Roux-en-Y-Bariatric Surgery Reduces Markers of Metabolic Syndrome in Morbidly Obese Patients

Roux-en-Y-Bariatric Surgery Reduces Markers of Metabolic Syndrome in Morbidly Obese Patients

Assessment of microRNA‐144‐5p and its putative targets in inflamed gingiva from chronic periodontitis patients

Systematic assessment of blood-borne microRNAs highlights molecular profiles of endurance sport and carbohydrate uptake

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