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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Obesity and type 2 diabetes mellitus (T2DM) are multifactorial disorders characterized by insulin resistance, chronic low-grade inflammation, adipose tissue dysfunction, and multi-organ metabolic impairment. MicroRNAs (miRNAs) act as post-transcriptional gene regulators and play critical roles in metabolic homeostasis, the modulation of insulin signaling, adipogenesis, inflammatory pathways, and energy balance in key insulin-target tissues, including liver, skeletal muscle, and adipose tissue. This review summarizes mechanistic and translational insights into miRNA regulation in obesity, insulin resistance, and T2DM, integrating data from human studies and experimental models on miRNA sequence codes and extracellular vesicle sorting pathways. We focus on the tissue-specific and systemic roles of miRNAs, highlighting their contribution to inter-organ communication and metabolic network regulation. In addition, we emphasize their emerging roles as predictive biomarkers, modulators of treatment response, and promising targets for RNA-based interventions. Advances in sequence-specific miRNA sorting and extracellular vesicle-mediated delivery may provide avenues for therapeutic intervention. However, challenges related to delivery efficiency, tissue specificity, off-target effects, and variability in miRNA quantification remain important barriers to clinical translation. Addressing these limitations may help define the clinical utility of miRNAs as biomarkers and therapeutic targets in metabolic disorders.<\/jats:p>","DOI":"10.3390\/ijms27146501","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T10:48:28Z","timestamp":1784717308000},"page":"6501","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["MicroRNAs in Obesity, Insulin Resistance, and Type 2 Diabetes: Mechanistic Insights and Translational Perspectives"],"prefix":"10.3390","volume":"27","author":[{"given":"Tamires M.","family":"Zanotto","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, State University of Campinas (UNICAMP), Campinas 13083-887, SP, Brazil"},{"name":"Department of Medical Clinics, Obesity and Comorbidities Research Center (O.C.R.C.), State University of Campinas (UNICAMP), Campinas 13083-864, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario J. A.","family":"Saad","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, State University of Campinas (UNICAMP), Campinas 13083-887, SP, Brazil"},{"name":"Department of Medical Clinics, Obesity and Comorbidities Research Center (O.C.R.C.), State University of Campinas (UNICAMP), Campinas 13083-864, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2026, May 29). Obesity and Overweight. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/obesity-and-overweight."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1161\/ATVBAHA.107.151092","article-title":"Metabolic syndrome pandemic","volume":"28","author":"Grundy","year":"2008","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/S0140-6736(14)60460-8","article-title":"Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: A systematic analysis for the Global Burden of Disease Study 2013","volume":"384","author":"Ng","year":"2014","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/nature05485","article-title":"Inflammation and metabolic disorders","volume":"444","author":"Hotamisligil","year":"2006","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1038\/nature05482","article-title":"Mechanisms linking obesity to insulin resistance and type 2 diabetes","volume":"444","author":"Kahn","year":"2006","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1172\/JCI29069","article-title":"Inflammation and insulin resistance","volume":"116","author":"Shoelson","year":"2006","journal-title":"J. Clin. Investig."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.cell.2018.03.006","article-title":"Metazoan MicroRNAs","volume":"173","author":"Bartel","year":"2018","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/nrm3313","article-title":"MicroRNAs in metabolism and metabolic disorders","volume":"13","author":"Rottiers","year":"2012","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2785","DOI":"10.1210\/me.2007-0167","article-title":"Overexpression of micro ribonucleic acid 29, highly up-regulated in diabetic rats, leads to insulin resistance in 3T3-L1 adipocytes","volume":"21","author":"He","year":"2007","journal-title":"Mol. Endocrinol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1161\/ATVBAHA.112.300144","article-title":"MicroRNAs in metabolic disease","volume":"33","author":"Goedeke","year":"2013","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1373\/clinchem.2012.195776","article-title":"Targeting the circulating microRNA signature of obesity","volume":"59","author":"Ortega","year":"2013","journal-title":"Clin. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/ijo.2015.170","article-title":"MicroRNAs as regulators of metabolic disease: Pathophysiologic significance and emerging role as biomarkers and therapeutics","volume":"40","author":"Deiuliis","year":"2016","journal-title":"Int. J. Obes."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1161\/CIRCRESAHA.110.226357","article-title":"Plasma microRNA profiling reveals loss of endothelial miR-126 and other microRNAs in type 2 diabetes","volume":"107","author":"Zampetaki","year":"2010","journal-title":"Circ. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1038\/nrg2843","article-title":"The widespread regulation of microRNA biogenesis, function and decay","volume":"11","author":"Krol","year":"2010","journal-title":"Nat. Rev. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.cell.2009.01.002","article-title":"MicroRNAs: Target recognition and regulatory functions","volume":"136","author":"Bartel","year":"2009","journal-title":"Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"D127","DOI":"10.1093\/nar\/gkz757","article-title":"miRDB: An online database for prediction of functional microRNA targets","volume":"48","author":"Chen","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.tem.2013.05.002","article-title":"MicroRNA networks regulate development of brown adipocytes","volume":"24","author":"Trajkovski","year":"2013","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1038\/nrendo.2015.25","article-title":"MicroRNA regulatory networks in human adipose tissue and obesity","volume":"11","author":"Arner","year":"2015","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2056","DOI":"10.2337\/db14-1117","article-title":"miR-30 promotes thermogenesis and the development of beige fat by targeting RIP140","volume":"64","author":"Hu","year":"2015","journal-title":"Diabetes"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1038\/ncb2612","article-title":"MyomiR-133 regulates brown fat differentiation through Prdm16","volume":"14","author":"Trajkovski","year":"2012","journal-title":"Nat. Cell Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.bbrc.2009.09.098","article-title":"microRNA miR-27b impairs human adipocyte differentiation and targets PPARgamma","volume":"390","author":"Karbiener","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1021\/prechem.5c00007","article-title":"Adipose Tissue-Derived Extracellular Vesicle MicroRNAs: Diagnostic Biomarkers for the Pathophysiology Associated with Obesity","volume":"3","author":"Yang","year":"2025","journal-title":"Precis. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/s42255-024-01214-5","article-title":"Metabolic Messengers: Small extracellular vesicles","volume":"7","author":"Rohm","year":"2025","journal-title":"Nat. Metab."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"111837","DOI":"10.1016\/j.diabres.2024.111837","article-title":"The interplay of extracellular vesicles in the pathogenesis of metabolic impairment and type 2 diabetes","volume":"216","author":"Carciero","year":"2024","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"115732","DOI":"10.1016\/j.celrep.2025.115732","article-title":"Exploring adipose tissue-derived extracellular vesicles in inter-organ crosstalk: Implications for metabolic regulation and adipose tissue function","volume":"44","author":"Scherer","year":"2025","journal-title":"Cell Rep."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Diez-Roda, P., Perez-Navarro, E., and Garcia-Martin, R. (2024). Adipose Tissue as a Major Launch Spot for Circulating Extracellular Vesicle-Carried MicroRNAs Coordinating Tissue and Systemic Metabolism. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252413488"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1038\/nature21365","article-title":"Adipose-derived circulating miRNAs regulate gene expression in other tissues","volume":"542","author":"Thomou","year":"2017","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1038\/s41586-021-04234-3","article-title":"MicroRNA sequence codes for small extracellular vesicle release and cellular retention","volume":"601","author":"Wang","year":"2022","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.cmet.2006.01.005","article-title":"miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting","volume":"3","author":"Esau","year":"2006","journal-title":"Cell Metab."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"527","DOI":"10.18632\/aging.100184","article-title":"Controlling SIRT1 expression by microRNAs in health and metabolic disease","volume":"2","author":"Lee","year":"2010","journal-title":"Aging"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1882","DOI":"10.1136\/gutjnl-2014-308883","article-title":"Liver microRNA-21 is overexpressed in non-alcoholic steatohepatitis and contributes to the disease in experimental models by inhibiting PPAR\u03b1 expression","volume":"65","author":"Loyer","year":"2016","journal-title":"Gut"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/ncb2211","article-title":"Obesity-induced overexpression of miRNA-143 inhibits insulin-stimulated AKT activation and impairs glucose metabolism","volume":"13","author":"Jordan","year":"2011","journal-title":"Nat. Cell Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"943659","DOI":"10.1155\/2015\/943659","article-title":"MicroRNA-223 Expression is Upregulated in Insulin Resistant Human Adipose Tissue","volume":"2015","author":"Chuang","year":"2015","journal-title":"J. Diabetes Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"13729","DOI":"10.1038\/srep13729","article-title":"Effect of miR-34a in regulating steatosis by targeting PPAR\u03b1 expression in nonalcoholic fatty liver disease","volume":"5","author":"Ding","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1016\/j.bbagrm.2008.03.001","article-title":"MicroRNA-206: The skeletal muscle-specific myomiR","volume":"1779","author":"McCarthy","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1038\/ng1725","article-title":"The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation","volume":"38","author":"Chen","year":"2006","journal-title":"Nat. Genet."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1083\/jcb.200603008","article-title":"Muscle-specific microRNA miR-206 promotes muscle differentiation","volume":"174","author":"Kim","year":"2006","journal-title":"J. Cell Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4637","DOI":"10.1113\/jphysiol.2013.255695","article-title":"Regulation of miRNAs in human skeletal muscle following acute endurance exercise and short-term endurance training","volume":"591","author":"Russell","year":"2013","journal-title":"J. Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1073\/pnas.0610731104","article-title":"MicroRNA-155 is induced during the macrophage inflammatory response","volume":"104","author":"Taganov","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2735","DOI":"10.1073\/pnas.0811073106","article-title":"MicroRNA-155 modulates the interleukin-1 signaling pathway in activated human monocyte-derived dendritic cells","volume":"106","author":"Ceppi","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"12481","DOI":"10.1073\/pnas.0605298103","article-title":"NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses","volume":"103","author":"Taganov","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.ncrna.2023.02.005","article-title":"Regulation and mechanism of action of miRNAs on insulin resistance in skeletal muscles","volume":"8","author":"Beilerli","year":"2023","journal-title":"Noncoding RNA Res."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Karolina, D.S., Armugam, A., Tavintharan, S., Wong, M.T., Lim, S.C., Sum, C.F., and Jeyaseelan, K. (2011). MicroRNA 144 impairs insulin signaling by inhibiting the expression of insulin receptor substrate 1 in type 2 diabetes mellitus. PLoS ONE, 6.","DOI":"10.1371\/annotation\/698b7123-174f-4a09-95c9-fd6f5017d622"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1016\/j.bbadis.2013.03.021","article-title":"miR-135a targets IRS2 and regulates insulin signaling and glucose uptake in the diabetic gastrocnemius skeletal muscle","volume":"1832","author":"Agarwal","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/labinvest.2010.166","article-title":"Mirnome analysis reveals novel molecular determinants in the pathogenesis of diet-induced nonalcoholic fatty liver disease","volume":"91","author":"Alisi","year":"2011","journal-title":"Lab. Investig."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.2337\/dc13-1847","article-title":"Profiling of circulating microRNAs reveals common microRNAs linked to type 2 diabetes that change with insulin sensitization","volume":"37","author":"Ortega","year":"2014","journal-title":"Diabetes Care"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Milagro, F.I., Miranda, J., Portillo, M.P., Fernandez-Quintela, A., Campi\u00f3n, J., and Mart\u00ednez, J.A. (2013). High-throughput sequencing of microRNAs in peripheral blood mononuclear cells: Identification of potential weight loss biomarkers. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0054319"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.2337\/db08-1299","article-title":"MicroRNAs induced during adipogenesis that accelerate fat cell development are downregulated in obesity","volume":"58","author":"Xie","year":"2009","journal-title":"Diabetes"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1038\/nature10112","article-title":"MicroRNAs 103 and 107 regulate insulin sensitivity","volume":"474","author":"Trajkovski","year":"2011","journal-title":"Nature"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2348","DOI":"10.1111\/j.1742-4658.2009.06967.x","article-title":"A role of miR-27 in the regulation of adipogenesis","volume":"276","author":"Lin","year":"2009","journal-title":"FEBS J."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.bbrc.2010.01.012","article-title":"miR-27a is a negative regulator of adipocyte differentiation via suppressing PPARgamma expression","volume":"392","author":"Kim","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1210\/me.2008-0298","article-title":"MicroRNA let-7 regulates 3T3-L1 adipogenesis","volume":"23","author":"Sun","year":"2009","journal-title":"Mol. Endocrinol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3093","DOI":"10.1002\/stem.235","article-title":"MiR-21 regulates adipogenic differentiation through the modulation of TGF-beta signaling in mesenchymal stem cells derived from human adipose tissue","volume":"27","author":"Kim","year":"2009","journal-title":"Stem Cells"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4130","DOI":"10.1128\/MCB.00596-14","article-title":"MicroRNA 34a inhibits beige and brown fat formation in obesity in part by suppressing adipocyte fibroblast growth factor 21 signaling and SIRT1 function","volume":"34","author":"Fu","year":"2014","journal-title":"Mol. Cell Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/nature11793","article-title":"Obesity-induced overexpression of miR-802 impairs glucose metabolism through silencing of Hnf1b","volume":"494","author":"Kornfeld","year":"2013","journal-title":"Nature"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.2337\/db17-0141","article-title":"Altered miR-29 Expression in Type 2 Diabetes Influences Glucose and Lipid Metabolism in Skeletal Muscle","volume":"66","author":"Massart","year":"2017","journal-title":"Diabetes"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1038\/nature03076","article-title":"A pancreatic islet-specific microRNA regulates insulin secretion","volume":"432","author":"Poy","year":"2004","journal-title":"Nature"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2026","DOI":"10.1161\/CIRCULATIONAHA.113.001720","article-title":"Endothelial microparticle-mediated transfer of MicroRNA-126 promotes vascular endothelial cell repair via SPRED1 and is abrogated in glucose-damaged endothelial microparticles","volume":"128","author":"Jansen","year":"2013","journal-title":"Circulation"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"BSR20160589","DOI":"10.1042\/BSR20160589","article-title":"Plasma miR-21 expression: An indicator for the severity of Type 2 diabetes with diabetic retinopathy","volume":"37","author":"Jiang","year":"2017","journal-title":"Biosci. Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1007\/s00109-015-1296-9","article-title":"miR-375 gene dosage in pancreatic \u03b2-cells: Implications for regulation of \u03b2-cell mass and biomarker development","volume":"93","author":"Latreille","year":"2015","journal-title":"J. Mol. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/s00592-010-0226-0","article-title":"Significance of serum microRNAs in pre-diabetes and newly diagnosed type 2 diabetes: A clinical study","volume":"48","author":"Kong","year":"2011","journal-title":"Acta Diabetol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.cmet.2013.06.004","article-title":"MicroRNAs and metabolism crosstalk in energy homeostasis","volume":"18","author":"Dumortier","year":"2013","journal-title":"Cell Metab."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"E2271","DOI":"10.1210\/jc.2012-1996","article-title":"Circulating miRNA profiles in patients with metabolic syndrome","volume":"97","author":"Karolina","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.2147\/DMSO.S298735","article-title":"Assessing MicroRNA-375 Levels in Type 2 Diabetes Mellitus (T2DM) Patients and Their First-Degree Relatives with T2DM","volume":"14","author":"Wu","year":"2021","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1111\/1440-1681.13147","article-title":"Circulating miR-146a, miR-34a and miR-375 in type 2 diabetes patients, pre-diabetic and normal-glycaemic individuals in relation to \u03b2-cell function, insulin resistance and metabolic parameters","volume":"46","year":"2019","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/bs.vh.2016.02.002","article-title":"MicroRNA-34a and Impaired FGF19\/21 Signaling in Obesity","volume":"101","author":"Fu","year":"2016","journal-title":"Vitam. Horm."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"347","DOI":"10.2337\/db16-0731","article-title":"Circulating MicroRNA-122 Is Associated With the Risk of New-Onset Metabolic Syndrome and Type 2 Diabetes","volume":"66","author":"Willeit","year":"2017","journal-title":"Diabetes"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1038\/nm.3200","article-title":"MicroRNA-30c reduces hyperlipidemia and atherosclerosis in mice by decreasing lipid synthesis and lipoprotein secretion","volume":"19","author":"Soh","year":"2013","journal-title":"Nat. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2892","DOI":"10.1161\/CIRCULATIONAHA.111.087817","article-title":"A novel regulator of macrophage activation: miR-223 in obesity-associated adipose tissue inflammation","volume":"125","author":"Zhuang","year":"2012","journal-title":"Circulation"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1089\/hum.2024.113","article-title":"Advances in MicroRNA Therapeutics: From Preclinical to Clinical Studies","volume":"35","author":"Brillante","year":"2024","journal-title":"Hum. Gene Ther."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1056\/NEJMoa1912387","article-title":"Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol","volume":"382","author":"Ray","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Seyhan, A.A. (2024). Trials and Tribulations of MicroRNA Therapeutics. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25031469"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"104488","DOI":"10.1016\/j.drudis.2025.104488","article-title":"Artificial intelligence in the development of small nucleic acid therapeutics: Toward smarter and safer medicines","volume":"30","author":"Delre","year":"2025","journal-title":"Drug Discov. Today"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1055\/s-0033-1358523","article-title":"Transcriptional control of hepatic lipid metabolism by SREBP and ChREBP","volume":"33","author":"Xu","year":"2013","journal-title":"Semin. Liver Dis."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1007\/s11892-015-0670-x","article-title":"Adipose tissue inflammation in the pathogenesis of type 2 diabetes","volume":"15","author":"Kohlgruber","year":"2015","journal-title":"Curr. Diabetes Rep."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1186\/s12951-025-03763-7","article-title":"Extracellular vesicles in metabolic perspective: Mechanism and targeted therapy","volume":"23","author":"Sheng","year":"2025","journal-title":"J. Nanobiotechnol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1186\/s40001-025-03288-7","article-title":"Molecular mechanisms linking adipose tissue-derived small extracellular vesicles\/exosomes to the development or amelioration of obesity, insulin resistance, and diabetes-related complications","volume":"30","author":"Chen","year":"2025","journal-title":"Eur. J. Med. Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"115291","DOI":"10.1016\/j.addr.2024.115291","article-title":"Lipid nanoparticles for RNA delivery: Self-assembling vs driven-assembling strategies","volume":"208","author":"Nele","year":"2024","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"7617","DOI":"10.1039\/D4NR04778H","article-title":"Recent advances in functional lipid-based nanomedicines as drug carriers for organ-specific delivery","volume":"17","author":"Yun","year":"2025","journal-title":"Nanoscale"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2980","DOI":"10.1038\/ncomms3980","article-title":"Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs","volume":"4","author":"Vazquez","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2177","DOI":"10.1016\/j.jacc.2014.01.050","article-title":"microRNAs in cardiovascular diseases: Current knowledge and the road ahead","volume":"63","author":"Condorelli","year":"2014","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.2215\/CJN.01170212","article-title":"Circulating and urinary microRNAs in kidney disease","volume":"7","author":"Lorenzen","year":"2012","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1007\/s00125-022-05809-z","article-title":"MicroRNA biomarkers of type 2 diabetes: Evidence synthesis from meta-analyses and pathway modelling","volume":"66","author":"Zhu","year":"2023","journal-title":"Diabetologia"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1161\/CIRCULATIONAHA.109.889048","article-title":"MicroRNAs add a new dimension to cardiovascular disease","volume":"121","author":"Small","year":"2010","journal-title":"Circulation"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1936","DOI":"10.1161\/CIRCULATIONAHA.111.037572","article-title":"Transcoronary concentration gradients of circulating microRNAs","volume":"124","author":"Fichtlscherer","year":"2011","journal-title":"Circulation"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Formichi, C., Fignani, D., Nigi, L., Grieco, G.E., Brusco, N., Licata, G., Sabato, C., Ferretti, E., Sebastiani, G., and Dotta, F. (2021). Circulating microRNAs Signature for Predicting Response to GLP1-RA Therapy in Type 2 Diabetic Patients: A Pilot Study. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22179454"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Giglio, R.V., Nikolic, D., Volti, G.L., Stoian, A.P., Banerjee, Y., Magan-Fernandez, A., Castellino, G., Patti, A.M., Chianetta, R., and Castracani, C.C. (2020). Liraglutide Increases Serum Levels of MicroRNA-27b, -130a and -210 in Patients with Type 2 Diabetes Mellitus: A Novel Epigenetic Effect. Metabolites, 10.","DOI":"10.3390\/metabo10100391"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"879","DOI":"10.4093\/dmj.2023.0328","article-title":"Glimepiride Compared to Liraglutide Increases Plasma Levels of miR-206, miR-182-5p, and miR-766-3p in Type 2 Diabetes Mellitus: A Randomized Controlled Trial (Diabetes Metab J 2023;47:668-81)","volume":"47","author":"Lee","year":"2023","journal-title":"Diabetes Metab. J."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1186\/s12967-025-06461-y","article-title":"Impact of monotherapy and combination therapy with glucagon-like peptide-1 receptor agonists on exosomal and non-exosomal MicroRNA signatures in type 2 diabetes mellitus: A systematic review","volume":"23","author":"Yu","year":"2025","journal-title":"J. Transl. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s13098-025-01581-3","article-title":"Managing cardiovascular events, hyperglycemia, and obesity in type 2 diabetes through microRNA regulation linked to glucagon-like peptide-1 receptor agonists","volume":"17","author":"Miao","year":"2025","journal-title":"Diabetol. Metab. Syndr."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Santos, A.S., Bando, S.Y., Correa Giannella, M.L.C., and da Silva, M.E.R. (2025). MicroRNAs modulated by DPP-4 inhibitor and bedtime NPH insulin therapy in individuals with type 2 diabetes. Front. Endocrinol., 16.","DOI":"10.3389\/fendo.2025.1706951"},{"key":"ref_92","unstructured":"ClinicalTrials.gov (2026, May 29). Effect of AT-derived miRNA on the Biology and Insulin Sensitivity of Skeletal Muscle in Humans. (NCT02459106), Available online: https:\/\/clinicaltrials.gov\/study\/NCT02459106."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Ghai, V., Kim, T.K., Etheridge, A., Nielsen, T., Hansen, T., Pedersen, O., Galas, D., and Wang, K. (2019). Extracellular Vesicle Encapsulated MicroRNAs in Patients with Type 2 Diabetes Are Affected by Metformin Treatment. J. Clin. Med., 8.","DOI":"10.3390\/jcm8050617"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"6872635","DOI":"10.1155\/2018\/6872635","article-title":"Circulating MicroRNAs in Elderly Type 2 Diabetic Patients","volume":"2018","author":"Catanzaro","year":"2018","journal-title":"Int. J. Endocrinol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"9892","DOI":"10.1038\/s41598-019-46260-2","article-title":"Integrin \u03b17 expression is increased in asthmatic patients and its inhibition reduces Kras protein abundance in airway smooth muscle cells","volume":"9","author":"Teoh","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1007\/s10529-010-0380-z","article-title":"Normalization strategies for microRNA profiling experiments: A \u2018normal\u2019 way to a hidden layer of complexity?","volume":"32","author":"Meyer","year":"2010","journal-title":"Biotechnol. Lett."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/14\/6501\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T10:53:08Z","timestamp":1784717588000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/14\/6501"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,22]]},"references-count":96,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ijms27146501"],"URL":"https:\/\/doi.org\/10.3390\/ijms27146501","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,22]]}}}