{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T12:23:58Z","timestamp":1789907038633,"version":"4.0.1"},"reference-count":72,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,11,29]],"date-time":"2022-11-29T00:00:00Z","timestamp":1669680000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"EFSD\/Boehringer Ingelheim"},{"name":"asic Research in Diabetes"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Most cells release extracellular vesicles (EVs) that can be detected circulating in blood. We and others have shown that the microRNA contents of these vesicles induce transcriptomic changes in acceptor cells, contributing to the adjustment of metabolic homeostasis in response to environmental demands. Here, we explore the potential for modulating obesity- and exercise-derived EV-microRNAs to treat the metabolic dysfunction associated with obesity in mice. Treatment with EV-miRNAs alleviated glucose intolerance and insulin resistance in obese mice to an extent similar to that of high-intensity interval training, although only exercise improved cardiorespiratory fitness and decreased body weight. Mechanistically, EV-miRNAs decreased fatty acid and cholesterol biosynthesis pathways in the liver, reducing hepatic steatosis and increasing insulin sensitivity, resulting in decreased glycemia and triglyceridemia. Our data suggest that manipulation of EV-miRNAs may be a viable strategy to alleviate metabolic dysfunction in obese and diabetic patients who are unable to exercise, although actual physical activity is needed to improve cardiorespiratory fitness.<\/jats:p>","DOI":"10.3390\/ijms232314920","type":"journal-article","created":{"date-parts":[[2022,11,29]],"date-time":"2022-11-29T02:53:29Z","timestamp":1669690409000},"page":"14920","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Treatment with EV-miRNAs Alleviates Obesity-Associated Metabolic Dysfunction in Mice"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1671-7826","authenticated-orcid":false,"given":"Carlos","family":"Casta\u00f1o","sequence":"first","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Diabetes y Enfermedades Metab\u00f3licas (CIBERDEM), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1393-9258","authenticated-orcid":false,"given":"Aline","family":"Meza-Ramos","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Montserrat","family":"Batlle","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBERCV), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4238-5319","authenticated-orcid":false,"given":"Eduard","family":"Guasch","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBERCV), 08036 Barcelona, Spain"},{"name":"Cardiovascular Institute, Hospital Clinic, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0465-2949","authenticated-orcid":false,"given":"Anna","family":"Novials","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Diabetes y Enfermedades Metab\u00f3licas (CIBERDEM), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1296-8302","authenticated-orcid":false,"given":"Marcelina","family":"P\u00e1rrizas","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Diabetes y Enfermedades Metab\u00f3licas (CIBERDEM), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17034","DOI":"10.1038\/nrdp.2017.34","article-title":"Obesity","volume":"3","author":"Hu","year":"2017","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"154820","DOI":"10.1016\/j.metabol.2021.154820","article-title":"An updated meta-analysis on the relationship between obesity and COVID-19 mortality","volume":"122","author":"Wang","year":"2021","journal-title":"Metab. Clin. Exp."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1146\/annurev-pathol-012615-044359","article-title":"Obesity, Inflammation, and Cancer","volume":"11","author":"Deng","year":"2016","journal-title":"Annu. Rev. Pathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1172\/JCI92035","article-title":"Inflammatory mechanisms linking obesity and metabolic disease","volume":"127","author":"Saltiel","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/j.cmet.2017.04.015","article-title":"Metabolic Flexibility in Health and Disease","volume":"25","author":"Goodpaster","year":"2017","journal-title":"Cell Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"520","DOI":"10.2337\/db15-0950","article-title":"Lifestyle and Metformin Ameliorate Insulin Sensitivity Independently of the Genetic Burden of Established Insulin Resistance Variants in Diabetes Prevention Program Participants","volume":"65","author":"Hivert","year":"2016","journal-title":"Diabetes"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.atherosclerosis.2015.09.016","article-title":"Cardiorespiratory fitness and risk of type 2 diabetes: A 23-year cohort study and a meta-analysis of prospective studies","volume":"243","author":"Zaccardi","year":"2015","journal-title":"Atherosclerosis"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Brugnara, L., Murillo, S., Novials, A., Rojo-Mart\u00ednez, G., Soriguer, F., Goday, A., Calle-Pascual, A., Casta\u00f1o, L., Gaztambide, S., and Vald\u00e9s, S. (2016). Low physical activity and its association with diabetes and other cardiovascular risk factors. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0160959"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5551","DOI":"10.1113\/jphysiol.2009.179432","article-title":"Exercise protects the cardiovascular system: Effects beyond traditional risk factors","volume":"587","author":"Joyner","year":"2009","journal-title":"J. Physiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s00421-017-3756-0","article-title":"Changes in fat oxidation in response to various regimes of high intensity interval training (HIIT)","volume":"118","author":"Astorino","year":"2018","journal-title":"Eur. J. Appl. Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1097\/MCO.0000000000000283","article-title":"Skeletal muscle as a gene regulatory endocrine organ","volume":"19","author":"Karstoft","year":"2016","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"522","DOI":"10.3389\/fphys.2019.00522","article-title":"Extracellular Vesicles: Delivery Vehicles of Myokines","volume":"10","author":"Trovato","year":"2019","journal-title":"Front. Physiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.cmet.2017.12.001","article-title":"Extracellular Vesicles Provide a Means for Tissue Crosstalk during Exercise","volume":"27","author":"Whitham","year":"2018","journal-title":"Cell Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"658218","DOI":"10.3389\/fphys.2021.658218","article-title":"Physical Activity as a Preventive Lifestyle Intervention Acts Through Specific Exosomal miRNA Species-Evidence From Human Short- and Long-Term Pilot Studies","volume":"12","author":"Garai","year":"2021","journal-title":"Front. Physiol."},{"key":"ref_15","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_16","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.cell.2012.04.005","article-title":"Roles for microRNAs in conferring robustness to biological processes","volume":"149","author":"Ebert","year":"2012","journal-title":"Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1038\/cr.2008.282","article-title":"Characterization of microRNAs in serum: A novel class of biomarkers for diagnosis of cancer and other diseases","volume":"18","author":"Chen","year":"2008","journal-title":"Cell Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e3107","DOI":"10.1002\/dmrr.3107","article-title":"Exosomes and diabetes","volume":"35","author":"Novials","year":"2019","journal-title":"Diabetes\/Metab. Res. Rev."},{"key":"ref_19","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_20","doi-asserted-by":"crossref","first-page":"12158","DOI":"10.1073\/pnas.1808855115","article-title":"Obesity-associated exosomal miRNAs modulate glucose and lipid metabolism in mice","volume":"115","author":"Kalko","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"30335","DOI":"10.1073\/pnas.2016112117","article-title":"Delivery of muscle-derived exosomal miRNAs induced by HIIT improves insulin sensitivity through down-regulation of hepatic FoxO1 in mice","volume":"117","author":"Mirasierra","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1016\/j.cmet.2020.12.019","article-title":"MiR-690, an exosomal-derived miRNA from M2-polarized macrophages, improves insulin sensitivity in obese mice","volume":"33","author":"Ying","year":"2021","journal-title":"Cell Metab."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.cell.2017.08.035","article-title":"Adipose Tissue Macrophage-Derived Exosomal miRNAs Can Modulate In Vivo and In Vitro Insulin Sensitivity","volume":"171","author":"Ying","year":"2017","journal-title":"Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1186\/s13063-018-2541-7","article-title":"Efficacy of high-intensity, low-volume interval training compared to continuous aerobic training on insulin resistance, skeletal muscle structure and function in adults with metabolic syndrome: Study protocol for a randomized controlled clinical trial","volume":"19","author":"Aristizabal","year":"2018","journal-title":"Trials"},{"key":"ref_25","first-page":"195","article-title":"The Molecular Signature of High-intensity Training in the Human Body","volume":"43","author":"Wahl","year":"2021","journal-title":"Int. J. Sport. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.resp.2019.05.009","article-title":"High- or moderate-intensity training promotes change in cardiorespiratory fitness, but not visceral fat, in obese men: A randomised trial of equal energy expenditure exercise","volume":"266","author":"Panissa","year":"2019","journal-title":"Respir. Physiol. Neurobiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2551","DOI":"10.1007\/s00421-018-3980-2","article-title":"Extremely short duration interval exercise improves 24-h glycaemia in men with type 2 diabetes","volume":"118","author":"Metcalfe","year":"2018","journal-title":"Eur. J. Appl. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e13245","DOI":"10.1111\/apha.13245","article-title":"Effects of one-legged high-intensity interval training on insulin-mediated skeletal muscle glucose homeostasis in patients with type 2 diabetes","volume":"226","author":"Dela","year":"2019","journal-title":"Acta Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1111\/obr.12317","article-title":"The effects of high-intensity interval training on glucose regulation and insulin resistance: A meta-analysis","volume":"16","author":"Jelleyman","year":"2015","journal-title":"Obes. Rev. Off. J. Int. Assoc. Study Obes."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Paramanantham, A., Asfiya, R., Das, S., McCully, G., and Srivastava, S. (2022). Extracellular Vesicle (EVs) Associated Non-Coding RNAs in Lung Cancer and Therapeutics. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232113637"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Rajput, A., Varshney, A., Bajaj, R., and Pokharkar, V. (2022). Exosomes as New Generation Vehicles for Drug Delivery: Biomedical Applications and Future Perspectives. Molecules, 27.","DOI":"10.3390\/molecules27217289"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1007\/s13577-021-00593-1","article-title":"Human Umbilical Cord-Derived Mesenchymal Stem Cell-Exosomal MiR-627-5p Ameliorates Non-Alcoholic Fatty Liver Disease by Repressing FTO Expression","volume":"34","author":"Cheng","year":"2021","journal-title":"Hum. Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1080\/21623945.2022.2098583","article-title":"Adipose-Derived Mesenchymal Stem Cell-Secreted Extracellular Vesicles Alleviate Non-Alcoholic Fatty Liver Disease via Delivering MiR-223-3p","volume":"11","author":"Niu","year":"2022","journal-title":"Adipocyte"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"12868","DOI":"10.1074\/jbc.RA120.012522","article-title":"Adipose Mesenchymal Stem Cell-Derived Extracellular Vesicles Containing MicroRNA-26a-5p Target TLR4 and Protect against Diabetic Nephropathy","volume":"295","author":"Duan","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1186\/s12951-021-00942-0","article-title":"Hypoxia Adipose Stem Cell-Derived Exosomes Promote High-Quality Healing of Diabetic Wound Involves Activation of PI3K\/Akt Pathways","volume":"19","author":"Wang","year":"2021","journal-title":"J. Nanobiotechnol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"17543","DOI":"10.1038\/srep17543","article-title":"Targeted Exosome-Mediated Delivery of Opioid Receptor Mu SiRNA for the Treatment of Morphine Relapse","volume":"5","author":"Liu","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"H459","DOI":"10.1152\/ajpheart.00763.2016","article-title":"Severity of structural and functional right ventricular remodeling depends on training load in an experimental model of endurance exercise","volume":"313","author":"Rubies","year":"2017","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1038\/s41467-018-08239-x","article-title":"Regulation of substrate utilization and adiposity by Agrp neurons","volume":"10","author":"Bober","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_39","first-page":"628","article-title":"Calculation of substrate oxidation rates in vivo from gaseous exchange","volume":"55","author":"Frayn","year":"1983","journal-title":"J. Appl. Physiol. Respir. Environ. Exerc. Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"102353","DOI":"10.1016\/j.redox.2022.102353","article-title":"Remission of obesity and insulin resistance is not sufficient to restore mitochondrial homeostasis in visceral adipose tissue","volume":"54","author":"Kulis","year":"2022","journal-title":"Redox Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"101550","DOI":"10.1016\/j.molmet.2022.101550","article-title":"Tirzepatide induces a thermogenic-like amino acid signature in brown adipose tissue","volume":"64","author":"Samms","year":"2022","journal-title":"Mol. Metab."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1097\/MCG.0b013e31825692ce","article-title":"Obesity and the elderly","volume":"46","year":"2012","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"R49","DOI":"10.1530\/JME-16-0073","article-title":"Nuclear receptors and AMPK: Can exercise mimetics cure diabetes?","volume":"57","author":"Wall","year":"2016","journal-title":"J. Mol. Endocrinol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.7150\/thno.51605","article-title":"Extracellular vesicle-shuttled miRNAs: A critical appraisal of their potential as nano-diagnostics and nano-therapeutics in type 2 diabetes mellitus and its cardiovascular complications","volume":"11","author":"Prattichizzo","year":"2021","journal-title":"Theranostics"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/s41569-020-0389-5","article-title":"Native and bioengineered extracellular vesicles for cardiovascular therapeutics","volume":"17","author":"Fernandes","year":"2020","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1038\/s42255-021-00467-8","article-title":"Small extracellular vesicle-mediated targeting of hypothalamic AMPK\u03b11 corrects obesity through BAT activation","volume":"3","author":"Milbank","year":"2021","journal-title":"Nat. Metab."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1038\/nature22341","article-title":"Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer","volume":"546","author":"Kamerkar","year":"2017","journal-title":"Nature"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/ncb2210","article-title":"MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins","volume":"13","author":"Vickers","year":"2011","journal-title":"Nat. Cell Biol."},{"key":"ref_49","first-page":"114","article-title":"How close are miRNAs from clinical practice? A perspective on the diagnostic and therapeutic market","volume":"30","author":"Bonneau","year":"2019","journal-title":"EJIFCC"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"26316","DOI":"10.3402\/jev.v4.26316","article-title":"Extracellular vesicle in vivo biodistribution is determined by cell source, route of administration and targeting","volume":"4","author":"Wiklander","year":"2015","journal-title":"J. Extracell. Vesicles"},{"key":"ref_51","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_52","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/nature04303","article-title":"Silencing of microRNAs in vivo with \u201cantagomirs\u201d","volume":"438","author":"Krutzfeldt","year":"2005","journal-title":"Nature"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"E407","DOI":"10.1210\/jc.2014-2574","article-title":"Circulating miR-192 and miR-193b are markers of prediabetes and are modulated by an exercise intervention","volume":"100","author":"Brugnara","year":"2015","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"546","DOI":"10.2337\/dc16-1354","article-title":"Extracellular RNAs are associated with insulin resistance and metabolic phenotypes","volume":"40","author":"Shah","year":"2017","journal-title":"Diabetes Care"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1136\/gutjnl-2014-306996","article-title":"Circulating microRNA signature in non-alcoholic fatty liver disease: From serum non-coding RNAs to liver histology and disease pathogenesis","volume":"64","author":"Pirola","year":"2015","journal-title":"Gut"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s10020-019-0085-2","article-title":"miR-122 promotes hepatic lipogenesis via inhibiting the LKB1\/AMPK pathway by targeting Sirt1 in non-alcoholic fatty liver disease","volume":"25","author":"Long","year":"2019","journal-title":"Mol. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1002\/oby.23365","article-title":"Exosomal miR-122 promotes adipogenesis and aggravates obesity through the VDR\/SREBF1 axis","volume":"30","author":"Huang","year":"2022","journal-title":"Obesity"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"852","DOI":"10.7150\/ijbs.19370","article-title":"Emerging roles of SIRT1 in fatty liver diseases","volume":"13","author":"Ding","year":"2017","journal-title":"Int. J. Biol. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Kolb, H., Stumvoll, M., Kramer, W., Kempf, K., and Martin, S. (2018). Insulin translates unfavourable lifestyle into obesity. BMC Med., 16.","DOI":"10.1186\/s12916-018-1225-1"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1934","DOI":"10.1002\/stem.2365","article-title":"Vav1 Regulates Mesenchymal Stem Cell Differentiation Decision Between Adipocyte and Chondrocyte via Sirt1","volume":"34","author":"Qu","year":"2016","journal-title":"Stem Cells"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"630097","DOI":"10.3389\/fendo.2021.630097","article-title":"NT3\/TrkC Pathway Modulates the Expression of UCP-1 and Adipocyte Size in Human and Rodent Adipose Tissue","volume":"12","author":"Monto","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1158\/1055-9965.EPI-16-0969","article-title":"A review of physical activity and circulating miRNA expression: Implications in cancer risk and progression","volume":"27","author":"Dufresne","year":"2018","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"903","DOI":"10.3389\/fphar.2018.00903","article-title":"miR-133: A Suppressor of Cardiac Remodeling?","volume":"9","author":"Li","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_64","first-page":"79","article-title":"Exercise training attenuates diabetes-induced cardiac injury through increasing miR-133a and improving pro-apoptosis\/anti-apoptosis balance in ovariectomized rats","volume":"23","author":"Habibi","year":"2020","journal-title":"Iran. J. Basic Med. Sci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"101544","DOI":"10.1016\/j.jbc.2021.101544","article-title":"The protease SENP2 controls hepatic gluconeogenesis by regulating the SUMOylation of the fuel sensor AMPK\u03b1","volume":"298","author":"Dou","year":"2022","journal-title":"J. Biol. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.cmet.2017.07.009","article-title":"Acetyl CoA Carboxylase Inhibition Reduces Hepatic Steatosis but Elevates Plasma Triglycerides in Mice and Humans: A Bedside to Bench Investigation","volume":"26","author":"Kim","year":"2017","journal-title":"Cell Metab."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1002\/hep.32148","article-title":"Therapeutic targeting of hepatic ACSL4 ameliorates NASH in mice","volume":"75","author":"Duan","year":"2022","journal-title":"Hepatology"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.lfs.2017.08.023","article-title":"High-intensity interval versus moderate-intensity continuous training: Superior metabolic benefits in diet-induced obesity mice","volume":"191","author":"Wang","year":"2017","journal-title":"Life Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1016\/j.molmet.2015.09.006","article-title":"High intensity interval training improves liver and adipose tissue insulin sensitivity","volume":"4","author":"Marcinko","year":"2015","journal-title":"Mol. Metab."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"459","DOI":"10.3389\/fphys.2019.00459","article-title":"Constant-Moderate and High-Intensity Interval Training Have Differential Benefits on Insulin Sensitive Tissues in High-Fat Fed Mice","volume":"10","author":"Ban","year":"2019","journal-title":"Front. Physiol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"5527","DOI":"10.1113\/jphysiol.2009.179507","article-title":"Lack of adequate appreciation of physical exercise\u2019s complexities can pre-empt appropriate design and interpretation in scientific discovery","volume":"587","author":"Booth","year":"2009","journal-title":"J. Physiol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/0160-5402(89)90015-6","article-title":"An improved method to correct the QT interval of the electrocardiogram for changes in heart rate","volume":"22","author":"Verheyen","year":"1989","journal-title":"J. Pharmacol. Methods"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/23\/14920\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:29:00Z","timestamp":1760146140000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/23\/14920"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,29]]},"references-count":72,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["ijms232314920"],"URL":"https:\/\/doi.org\/10.3390\/ijms232314920","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,29]]}}}