Extracellular Vesicles and Circulating miRNAs—Exercise-Induced Mitigation of Obesity and Associated Metabolic Diseases

2020 ◽  
pp. 59-80
Author(s):  
Patience Oluchukwu Obi ◽  
Benjamin Bydak ◽  
Adeel Safdar ◽  
Ayesha Saleem
Keyword(s):  
Extracellular Vesicles ◽  
Metabolic Diseases ◽  
Circulating Mirnas ◽  
Exercise Induced

scholarly journals Extracellular Vesicles and Matrix Remodeling Enzymes: The Emerging Roles in Extracellular Matrix Remodeling, Progression of Diseases and Tissue Repair

Cells ◽  
2018 ◽  
Vol 7 (10) ◽  
pp. 167 ◽  
Author(s):  
Muhammad Nawaz ◽  
Neelam Shah ◽  
Bruna Zanetti ◽  
Marco Maugeri ◽  
Renata Silvestre ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Extracellular Vesicles ◽  
Tissue Repair ◽  
Metabolic Diseases ◽  
Bioactive Molecules ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Matrix Remodeling ◽  
Pathological Conditions ◽  
Potential Applications ◽  
Non Coding Rnas

Extracellular vesicles (EVs) are membrane enclosed micro- and nano-sized vesicles that are secreted from almost every species, ranging from prokaryotes to eukaryotes, and from almost every cell type studied so far. EVs contain repertoire of bioactive molecules such as proteins (including enzymes and transcriptional factors), lipids, carbohydrates and nucleic acids including DNA, coding and non-coding RNAs. The secreted EVs are taken up by neighboring cells where they release their content in recipient cells, or can sail through body fluids to reach distant organs. Since EVs transport bioactive cargo between cells, they have emerged as novel mediators of extra- and intercellular activities in local microenvironment and inter-organ communications distantly. Herein, we review the activities of EV-associated matrix-remodeling enzymes such as matrix metalloproteinases, heparanases, hyaluronidases, aggrecanases, and their regulators such as extracellular matrix metalloproteinase inducers and tissue inhibitors of metalloproteinases as novel means of matrix remodeling in physiological and pathological conditions. We discuss how such EVs act as novel mediators of extracellular matrix degradation to prepare a permissive environment for various pathological conditions such as cancer, cardiovascular diseases, arthritis and metabolic diseases. Additionally, the roles of EV-mediated matrix remodeling in tissue repair and their potential applications as organ therapies have been reviewed. Collectively, this knowledge could benefit the development of new approaches for tissue engineering.

scholarly journals Exercise-Induced Myokines can Explain the Importance of Physical Activity in the Elderly: An Overview

Healthcare ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 378
Author(s):  
Jenny Hyosun Kwon ◽  
Kyoung Min Moon ◽  
Kyueng-Whan Min
Keyword(s):  
Physical Activity ◽  
Skeletal Muscle ◽  
Growth Factor ◽  
Metabolic Diseases ◽  
The Elderly ◽  
Anaerobic Exercise ◽  
Small Proteins ◽  
Stromal Cell Derived Factor ◽  
Exercise Induced ◽  
Aerobic And Anaerobic

Physical activity has been found to aid the maintenance of health in the elderly. Exercise-induced skeletal muscle contractions lead to the production and secretion of many small proteins and proteoglycan peptides called myokines. Thus, studies on myokines are necessary for ensuring the maintenance of skeletal muscle health in the elderly. This review summarizes 13 myokines regulated by physical activity that are affected by aging and aims to understand their potential roles in metabolic diseases. We categorized myokines into two groups based on regulation by aerobic and anaerobic exercise. With aging, the secretion of apelin, β-aminoisobutyric acid (BAIBA), bone morphogenetic protein 7 (BMP-7), decorin, insulin-like growth factor 1 (IGF-1), interleukin-15 (IL-15), irisin, stromal cell-derived factor 1 (SDF-1), sestrin, secreted protein acidic rich in cysteine (SPARC), and vascular endothelial growth factor A (VEGF-A) decreased, while that of IL-6 and myostatin increased. Aerobic exercise upregulates apelin, BAIBA, IL-15, IL-6, irisin, SDF-1, sestrin, SPARC, and VEGF-A expression, while anaerobic exercise upregulates BMP-7, decorin, IGF-1, IL-15, IL-6, irisin, and VEGF-A expression. Myostatin is downregulated by both aerobic and anaerobic exercise. This review provides a rationale for developing exercise programs or interventions that maintain a balance between aerobic and anaerobic exercise in the elderly.

Signs of embryo-maternal communication: miRNAs in the maternal serum of pregnant pigs

Reproduction ◽  
2017 ◽  
Vol 154 (3) ◽  
pp. 217-228 ◽  
Author(s):  
Z P Reliszko ◽  
Z Gajewski ◽  
M M Kaczmarek
Keyword(s):  
Extracellular Vesicles ◽  
Dynamic Range ◽  
Target Prediction ◽  
Digital Pcr ◽  
Maternal Serum ◽  
Biological Processes ◽  
Circulating Mirnas ◽  
Maternal Communication ◽  
First Time ◽  
Reliable Methods

Circulating miRNAs were proposed to be indicators of normal or complicated pregnancies. Based on this knowledge and our recent transcriptomic approach showing expression of miRNAs in the porcine endometrium, conceptuses and uterine extracellular vesicles during pregnancy, we have hypothesized that signs of ongoing local embryo-maternal crosstalk involving miRNAs can be detected in the circulation of pregnant gilts as early as a few days after maternal recognition of pregnancy. By applying several molecular biology techniques that differ in dynamic range and precision in maternal serum of Day 16 pregnant pigs, we were able to show for the first time increased levels of several miRNAs, previously reported to be expressed in either conceptuses and extracellular vesicles (miR-26a and miR-125b) or pregnant endometrium (miR-23b). Our results clearly showed that real-time RT-PCR and digital PCR are the most reliable methods, being able to detect small-fold changes of low-abundant circulating miRNAs. Further validation in a separate group of gilts confirmed an increase in miR-23b and miR-125b levels.In silicoanalyses identified pregnancy-related biological processes and pathways affected by these miRNAs. Target prediction analysis revealed hundreds of porcine transcripts with conserved sites for these miRNAs, which were classified into signaling pathways relevant to pregnancy. We conclude that a unique set of miRNAs can already be observed in the circulation of pigs during the first weeks of pregnancy, as a result of the initiation of embryo-maternal communication.

scholarly journals Circulating extracellular vesicles are associated with lipid and insulin metabolism

2018 ◽  
Vol 315 (4) ◽  
pp. E574-E582 ◽  
Author(s):  
Yoshinao Kobayashi ◽  
Akiko Eguchi ◽  
Mina Tempaku ◽  
Tatsuro Honda ◽  
Kenji Togashi ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Extracellular Vesicles ◽  
Metabolic Diseases ◽  
Cell Function ◽  
Characteristic Curve ◽  
Elevated Serum ◽  
Oral Glucose ◽  
Model Assessment ◽  
Homeostasis Model Assessment ◽  
Insulin Metabolism

We have reported that hypertrophic adipocytes release extracellular vesicles (EVs) and the number of circulating adipocyte-derived EVs correlated with insulin and homeostasis model assessment-insulin resistance (HOMA-IR) in a pilot study using obese patients. Here, we explored the association between circulating EV level and various metabolic parameters, including obesity and lipid and glucose metabolisms, among 203 subjects (76 men and 127 women; median age, 54 yr) with or without risk factor for metabolic diseases, who received a 75-g oral glucose tolerance test (OGTT). Circulating EV number was significantly higher in men than in women ( P < 0.001). Circulating EV number in individuals with impaired OGTT pattern was significantly higher compared with those with normal OGTT patterns ( P < 0.05). Multiple regression analysis revealed that circulating EV number correlated most strongly and significantly with elevated triglyceride (TG; t = 8.55, P < 0.001). Additionally, circulating EV number correlated significantly with homeostasis model assessment-β-cell function (HOMA-β; t = 2.38, P < 0.05). Receiver operating characteristic curve revealed that the cutoff value of EV numbers in individuals with elevated serum TG levels (≧150 mg/dl) was identified (136,738 EVs/μl of plasma, P < 0.001, sensitivity 0.842, false-positive rate of 0.257). Perilipin and asialoglycoprotein receptor 1 were detected on a part of isolated circulating EVs, indicating EV release from adipocytes and hepatocytes, which were related to lipid and glucose metabolism. Circulating EVs represent a promising metabolic biomarker for lipid and glucose metabolism and have potential for monitoring metabolic status in humans, including individuals without metabolic risk factors.

scholarly journals Liver injury changed the biological characters of serum small extracellular vesicles and reprogramed hepatic macrophages in mice

2021 ◽  
Author(s):  
Xiufang Lv ◽  
Jing Li ◽  
Li He ◽  
Li Cheng ◽  
Min Zhao ◽  
...  
Keyword(s):  
Liver Injury ◽  
Extracellular Vesicles ◽  
Liver Diseases ◽  
Human Liver ◽  
Mouse Liver ◽  
Liver Steatosis ◽  
Biological Significance ◽  
Circulating Mirnas ◽  
Hepatic Macrophages ◽  
Liver Macrophage

Abstract Background Serum small extracellular vesicles (sEVs) and their small RNA (sRNA) cargoes could be promising biomarkers for the diagnosis of liver injury. However, the dynamic changes of serum sEVs and their sRNA components during liver injury and the biological functions of these liver-injury-serum sEVs have not been well characterized. Methods To identify serum sEV biomarkers for liver injury, we established a carbon tetrachloride-induced mouse liver injury model to simulate acute liver injury (ALI), chronic liver injury (CLI) and recovery. Serum sEVs were obtained and characterized. Serum sEV sRNAs were profiled. Differentially expressed microRNAs (miRNA) were compared to mouse liver enriched miRNAs and previously reported circulating miRNAs that related to human liver diseases. The biological significance was evaluated by Ingenuity Pathway Analysis of altered sEV miRNAs, and conditional culture of ALI serum sEVs with primary hepatic macrophages. Results We found that both ALI and CLI changed the concentration and morphology of serum sEVs. The proportion of serum sEV miRNA increased upon liver injury, with the liver as the primary contributor. The altered serum sEV miRNAs based on mice's study were consistent with those human liver diseases-related circulating miRNAs. Serum sEV miRNA signatures for ALI and CLI, and a panel of miRNAs as common marker for liver injury, were established. The differential serum sEV miRNAs in ALI mainly contributed to liver steatosis and inflammation, while those in CLI primarily contributed to hepatocellular carcinoma and hyperplasia. ALI serum sEVs decreased both CD86 and CD206 expression in monocyte-derived macrophages, but increased CD206 expression in resident macrophages. Conclusion Serum sEVs in the different stages of liver injury carried different sRNA messages and contributed to diverse pathological processes. ALI serum sEVs might alleviate liver damage by depolarizing monocyte-derived macrophages and educating resident liver macrophage to M2 like cells.

scholarly journals Adipose Extracellular Vesicles: Messengers From and to Macrophages in Regulating Immunometabolic Homeostasis or Disorders

2021 ◽  
Vol 12 ◽  
Author(s):  
Zixin Zhou ◽  
Yan Tao ◽  
Hui Zhao ◽  
Qun Wang
Keyword(s):  
Stem Cells ◽  
Adipose Tissue ◽  
Energy Metabolism ◽  
Extracellular Vesicles ◽  
Intercellular Communication ◽  
Metabolic Diseases ◽  
Cell Populations ◽  
Vicious Cycle ◽  
Immune Reactions ◽  
Inflammatory Macrophages

Adipose tissue is comprised of heterogenous cell populations that regulate both energy metabolism and immune reactions. Macrophages play critical roles in regulating immunometabolic homeostasis or disorders through cooperation with adipocytes, adipose tissue-derived stem cells (ADSCs) or other cells in adipose tissue. Extracellular vesicles (EVs) are recently recognized as efficient messengers for intercellular communication. Emerging evidences have demonstrated that adipose EVs are actively involved in the mutual interactions of macrophages, adipocytes and ADSCs, which produce considerable influences on immunometabolism under healthy or obese conditions. Here, we will elaborate the production and the characteristics of adipose EVs that are related to macrophages under different metabolic demands or stresses, whilst discuss the roles of these EVs in regulating local or systemic immunometabolic homeostasis or disorders in the context of adipocyte-macrophage dialogue and ADSC-macrophage interaction. Particularly, we provide a profile of dynamic adipose microenvironments based on macrophages. Adipose EVs act as the messengers between ADSCs and macrophages to maintain the balance of metabolism and immunity, while drive a vicious cycle between hypertrophic adipocytes and inflammatory macrophages to cause immunometabolic imbalance. This review may provide valuable information about the physio- or pathological roles of adipose EVs and the application of adipose EVs in the diagnosis and treatment of metabolic diseases.

Exercise-induced Modulation of Extracellular Vesicles’ Cargo: a Focus on Antioxidants, Stress Proteins and miRNAs

2020 ◽  
Vol 159 ◽  
pp. S26
Author(s):  
Veronica Lisi ◽  
Chantalle Moulton ◽  
Ambra Antonioni ◽  
Cristina Fantini ◽  
Elisa Grazioli ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Stress Proteins ◽  
Exercise Induced

Changes in Circulating MicroRNAs Are Associated With Childhood Obesity

2013 ◽  
Vol 98 (10) ◽  
pp. E1655-E1660 ◽  
Author(s):  
Anna Prats-Puig ◽  
Francisco J. Ortega ◽  
Josep M. Mercader ◽  
José M. Moreno-Navarrete ◽  
María Moreno ◽  
...  
Keyword(s):  
Childhood Obesity ◽  
Metabolic Diseases ◽  
Plasma Concentrations ◽  
Mirna Profile ◽  
Model Assessment ◽  
Circulating Mirnas ◽  
Obese Children ◽  
High Molecular Weight Adiponectin ◽  
Circulating Micrornas ◽  
Circulating Mirna

Abstract Context: Circulating microRNAs (miRNAs) are valuable biomarkers of metabolic diseases and potential therapeutic targets in this field. Objective: Our objective was to define the circulating pattern of miRNAs in childhood obesity. Design, Settings, and Main Outcome Measure: The genome-wide circulating miRNA profile was assessed by RT-PCR in 10 boys (5 lean and 5 obese children). The most relevant miRNAs were cross-sectionally validated in 85 lean versus 40 obese children (63 boys and 62 girls) and longitudinally evaluated in samples from the same children when they were ∼7 and ∼10 years old (23 boys and 22 girls). Results: The cross-sectional validation study disclosed that 15 specific circulating miRNAs were significantly deregulated in prepubertal obesity, including the decreased miR-221 and miR-28-3p and increased concentrations in plasma of miR-486-5p, miR-486-3p, miR-142-3p, miR-130b, and miR-423-5p (all P &lt; .0001). The circulating concentration of these miRNAs was significantly associated with body mass index and other measures of obesity such as percent fat mass, waist, regional fat distribution and with laboratory parameters such as homeostasis model assessment of insulin resistance, high-molecular-weight adiponectin, C-reactive protein, and circulating lipids in concordance with anthropometric associations. Plasma concentrations of 10 of these circulating miRNAs changed significantly and differently during the 3-year follow-up in children who increased or decreased their normalized weight. Conclusion: This study provides the first evidence that circulating miRNAs are deregulated in prepubertal obese children. Thus, the very early detection of an abnormal circulating miRNA profile may be a promising strategy to identify obese children who may suffer from metabolic abnormalities.

Novel Interactions Between Circulating microRNAs and Gut Microbiota Composition in Human Obesity.

2020 ◽  
Author(s):  
Taís Silveira Assmann ◽  
Amanda Cuevas-Sierra ◽  
José Ignacio Riezu-Boj ◽  
Fermin Milagro ◽  
J Alfredo Martínez
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Target Genes ◽  
Metabolic Diseases ◽  
Bacterial Species ◽  
Microbiota Composition ◽  
Circulating Mirnas ◽  
Clinical Trial Registration ◽  
Body Adiposity ◽  
Gut Microbiota Composition

Abstract Background: Unbalances in microRNAs (miRNA) and gut microbiota patterns have been proposed as putative factors concerning onset and development of obesity and other metabolic diseases. However, the determinants that mediate the interactions between miRNAs and the gut microbiome impacting on obesity are scarcely understood. Thus, the aim of this article was to investigate possible interactions between circulating miRNAs and gut microbiota composition in obesity. Method: The analyzed sample comprised 78 subjects with obesity [cases, body mass index (BMI): 30 – 40 kg/m2] and 25 eutrophic individuals (controls, BMI £ 25 kg/m2). The expression of 96 miRNAs was investigated in plasma of all individuals using miRCURY LNA miRNA Custom PCR Panels (Exiqon). Bacterial DNA sequencing was performed following the Illumina 16S protocol. The FDR (Benjamini-Hochberg test, q-value) correction was used for multiple comparison analyses.Results: A total of 26 circulating miRNAs and 12 bacterial species were found differentially expressed between cases and controls. Interestingly, an interaction among three miRNAs (miR-130b-3p, miR-185-5p, and miR-21-5p) with Bacteroides eggerthi, and BMI levels was evidenced (r2= 0.148, P= 0.004). Those miRNAs that correlated with obesity-associated gut bacteria abundance are known to regulate target genes that participate in metabolism-related pathways, such as fatty acid degradation, carbohydrate digestion and absorption, insulin signaling, and glycerolipid metabolism. Conclusion: This study characterized an interaction between the abundance of 4 bacterial species and 14 circulating miRNAs in relation to body adiposity. Moreover, the current study also suggests that miRNAs may serve as a communication mechanism between the gut microbiome and human hosts. Clinical trial registration: clinicaltrials.gov (reg. no. NCT02737267).

Sign in / Sign up

Export Citation Format

Share Document