{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T13:35:16Z","timestamp":1772804116608,"version":"3.50.1"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T00:00:00Z","timestamp":1696464000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["720321"],"award-info":[{"award-number":["720321"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006087","name":"Direcci\u00f3n General de Asuntos del Personal Acad\u00e9mico, Universidad Nacional Aut\u00f3noma de M\u00e9xico","doi-asserted-by":"publisher","award":["IN214419"],"award-info":[{"award-number":["IN214419"]}],"id":[{"id":"10.13039\/501100006087","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Metabolic syndrome is a multifactorial disease with high prevalence worldwide. It is related to cardiovascular disease, diabetes, and obesity. Approximately 80% of patients with metabolic syndrome have some degree of fatty liver disease. An adenosine derivative (IFC-305) has been shown to exert protective effects in models of liver damage as well as on elements involved in central metabolism; therefore, here, we evaluated the effect of IFC-305 in an experimental model of metabolic syndrome in rats induced by a high-fat diet and 10% sucrose in drinking water for 18 weeks. We also determined changes in fatty acid uptake in the Huh-7 cell line. In the experimental model, increases in body mass, serum triglycerides and proinflammatory cytokines were induced in rats, and the adenosine derivative significantly prevented these changes. Interestingly, IFC-305 prevented alterations in glucose and insulin tolerance, enabling the regulation of glucose levels in the same way as in the control group. Histologically, the alterations, including mitochondrial morphological changes, observed in response to the high-fat diet were prevented by administration of the adenosine derivative. This compound exerted protective effects against metabolic syndrome, likely due to its action in metabolic regulation, such as in the regulation of glucose blood levels and hepatocyte fatty acid uptake.<\/jats:p>","DOI":"10.1371\/journal.pone.0292448","type":"journal-article","created":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T17:29:15Z","timestamp":1696526955000},"page":"e0292448","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["An adenosine derivative prevents the alterations observed in metabolic syndrome in a rat model induced by a rich high-fat diet and sucrose supplementation"],"prefix":"10.1371","volume":"18","author":[{"given":"Enrique","family":"Ch\u00e1vez","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alejandro Rusbel","family":"Aparicio-Cadena","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriela","family":"Velasco-Loyden","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Guadalupe","family":"Lozano-Rosas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariana","family":"Dom\u00ednguez-L\u00f3pez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amairani","family":"Cancino-Bello","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nimbe","family":"Torres","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Armando R.","family":"Tovar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alejandro","family":"Cabrera-Aguilar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8577-1186","authenticated-orcid":true,"given":"Victoria","family":"Chagoya-de S\u00e1nchez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,10,5]]},"reference":[{"issue":"9468","key":"pone.0292448.ref001","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1016\/S0140-6736(05)66378-7","article-title":"The metabolic syndrome","volume":"365","author":"RH Eckel","year":"2005","journal-title":"Lancet"},{"issue":"10","key":"pone.0292448.ref002","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1001\/archinte.159.10.1104","article-title":"Clustering of metabolic factors and coronary heart disease","volume":"159","author":"PW Wilson","year":"1999","journal-title":"Arch Intern Med"},{"key":"pone.0292448.ref003","unstructured":"World Obesity Atlas. No Title [Internet]. 2022. Available from: https:\/\/www.worldobesityday.org\/policy-makers"},{"key":"pone.0292448.ref004","first-page":"355","article-title":"Mexico and the USA: The world\u2019s leaders in the obesity epidemic","volume":"55","author":"JP Elder","year":"2013","journal-title":"Salud p\u00fablica M\u00e9x"},{"key":"pone.0292448.ref005","doi-asserted-by":"crossref","first-page":"17034","DOI":"10.1038\/nrdp.2017.34","article-title":"Obesity","volume":"3","author":"P Gonz\u00e1lez-Muniesa","year":"2017","journal-title":"Nat Rev Dis Primers"},{"issue":"4","key":"pone.0292448.ref006","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/s12291-011-0175-6","article-title":"Inflammation and the Metabolic Syndrome","volume":"26","author":"P Sharma","year":"2011","journal-title":"Indian Journal of Clinical Biochemistry"},{"issue":"11","key":"pone.0292448.ref007","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1038\/nrg2468","article-title":"Metabolic syndrome: from epidemiology to systems biology","volume":"9","author":"AJ Lusis","year":"2008","journal-title":"Nat Rev Genet"},{"issue":"7","key":"pone.0292448.ref008","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1172\/JCI29069","article-title":"Inflammation and insulin resistance","volume":"116","author":"SE Shoelson","year":"2006","journal-title":"J Clin Invest"},{"issue":"6","key":"pone.0292448.ref009","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1053\/j.gastro.2007.03.055","article-title":"Abnormal Lipid and Glucose Metabolism in Obesity: Implications for Nonalcoholic Fatty Liver Disease","volume":"132","author":"S Parekh","year":"2007","journal-title":"Gastroenterology"},{"issue":"1","key":"pone.0292448.ref010","doi-asserted-by":"crossref","first-page":"15080","DOI":"10.1038\/nrdp.2015.80","article-title":"Nonalcoholic fatty liver disease","volume":"1","author":"EM Brunt","year":"2015","journal-title":"Nat Rev Dis Primers"},{"issue":"2","key":"pone.0292448.ref011","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1021\/jm990499b","article-title":"2-Alkynyl-8-aryl-9-methyladenines as novel adenosine receptor antagonists: their synthesis and structure-activity relationships toward hepatic glucose production induced via agonism of the A(2B) receptor","volume":"44","author":"H Harada","year":"2001","journal-title":"J Med Chem"},{"issue":"2","key":"pone.0292448.ref012","doi-asserted-by":"crossref","first-page":"669","DOI":"10.2337\/db10-1070","article-title":"Links between insulin resistance, adenosine A2B receptors, and inflammatory markers in mice and humans","volume":"60","author":"RA Figler","year":"2011","journal-title":"Diabetes"},{"issue":"2","key":"pone.0292448.ref013","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1271\/bbb.64.237","article-title":"Serum Glucose and Insulin Response in Rats Administered with Sucrose or Starch Containing Adenosine, Inosine or Cytosine","volume":"64","author":"Y Fukumori","year":"2000","journal-title":"Biosci Biotechnol Biochem"},{"issue":"8","key":"pone.0292448.ref014","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.1093\/jn\/130.8.1946","article-title":"Blood Glucose and Insulin Concentrations Are Reduced in Humans Administered Sucrose with Inosine or Adenosine","volume":"130","author":"Y Fukumori","year":"2000","journal-title":"J Nutr"},{"issue":"1","key":"pone.0292448.ref015","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1017\/S0007114510000255","article-title":"Anti-metabolic syndrome effects of adenosine ingestion in stroke-prone spontaneously hypertensive rats fed a high-fat diet","volume":"104","author":"Ardiansyah","year":"2010","journal-title":"British Journal of Nutrition"},{"key":"pone.0292448.ref016","first-page":"31","volume-title":"Liver Cirrhosis Causes, Diagnosis and Treatment:","author":"V. Chagoya de S\u00e1nchez","year":"2011"},{"issue":"2","key":"pone.0292448.ref017","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1002\/hep.1840120210","article-title":"Adenosine partially prevents cirrhosis induced by carbon tetrachloride in rats","volume":"12","author":"R Hern\u00e1ndez-mu\u00f1oz","year":"1990","journal-title":"Hepatology"},{"issue":"8","key":"pone.0292448.ref018","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1016\/0006-2952(79)90444-1","article-title":"Mechanism of the fatty liver induced by cycloheximide and its reversibility by adenosine","volume":"28","author":"JA Garc\u00eda-S\u00e1inz","year":"1979","journal-title":"Biochem Pharmacol [Internet]"},{"key":"pone.0292448.ref019","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2012\/212530","article-title":"Recovery of the Cell Cycle Inhibition in CCl(4)-Induced Cirrhosis by the Adenosine Derivative IFC-305","volume":"2012","author":"V Chagoya de S\u00e1nchez","year":"2012","journal-title":"Int J Hepatol"},{"issue":"2","key":"pone.0292448.ref020","doi-asserted-by":"crossref","first-page":"101042831769119","DOI":"10.1177\/1010428317691190","article-title":"Cancer chemoprevention by an adenosine derivative in a model of cirrhosis-hepatocellular carcinoma induced by diethylnitrosamine in rats","volume":"39","author":"G Velasco-Loyden","year":"2017","journal-title":"Tumor Biology"},{"issue":"2","key":"pone.0292448.ref021","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1124\/jpet.116.239301","article-title":"Functional, metabolic, and dynamic mitochondrial changes in the rat cirrhosis-hepatocellular carcinoma model and the protective effect of IFC-305","volume":"361","author":"E Ch\u00e1vez","year":"2017","journal-title":"Journal of Pharmacology and Experimental Therapeutics"},{"issue":"6","key":"pone.0292448.ref022","first-page":"1844","article-title":"Role of autophagy in the chemopreventive effect of the IFC-305 compound in the sequential model of cirrhosis-hepatocellular carcinoma in the rat and in vitro","volume":"10","author":"E Ch\u00e1vez","year":"2020","journal-title":"Am J Cancer Res [Internet]."},{"key":"pone.0292448.ref023","unstructured":"Chagoya de S\u00e1nchez, V; Hern\u00e1ndez-Mu\u00f1\u00f3z Rolando. Aspartato de adenosina, su m\u00e9todo de preparaci\u00f3n a partir de la adenosina y su uso para la preparaci\u00f3n de medicamentos para el tratamiento de enfermedades hep\u00e1ticas fibrosantes y composici\u00f3n farmac\u00e9utica. M\u00e9xico; 207422, 1998."},{"issue":"11","key":"pone.0292448.ref024","first-page":"1939","article-title":"AIN-93 Purified Diets for Laboratory Rodents: Final Report of the American Institute of Nutrition Ad Hoc Writing Committee on the Reformulation of the AIN-76","volume":"123","author":"PG Reeves","year":"1993","journal-title":"A Rodent Diet. J Nutr"},{"issue":"1","key":"pone.0292448.ref025","doi-asserted-by":"crossref","first-page":"4716","DOI":"10.1038\/s41598-017-05096-4","article-title":"Nopal (Opuntia ficus indica) protects from metabolic endotoxemia by modifying gut microbiota in obese rats fed high fat\/sucrose diet","volume":"7","author":"M S\u00e1nchez-Tapia","year":"2017","journal-title":"Sci Rep [Internet]"},{"issue":"6","key":"pone.0292448.ref026","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1002\/hep.20701","article-title":"Design and validation of a histological scoring system for nonalcoholic fatty liver disease","volume":"41","author":"DE Kleiner","year":"2005","journal-title":"Hepatology"},{"issue":"3","key":"pone.0292448.ref027","first-page":"284","article-title":"Lipotoxicity in HepG2 cells triggered by free fatty acids","volume":"3","author":"HR Yao","year":"2011","journal-title":"Am J Transl Res"},{"issue":"6","key":"pone.0292448.ref028","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1007\/BF00316069","article-title":"Quantitation of adipose conversion and triglycerides by staining intracytoplasmic lipids with oil red O","volume":"97","author":"JL Ram\u00edrez-Zacar\u00edas","year":"1992","journal-title":"Histochemistry"},{"key":"pone.0292448.ref029","first-page":"221","article-title":"The Pathogenesis of Obesity-Associated Adipose Tissue Inflammation. In","author":"A. Engin","year":"2017"},{"issue":"1","key":"pone.0292448.ref030","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1002\/jcb.26192","article-title":"Epigenetic Effects of an Adenosine Derivative in a Wistar Rat Model of Liver Cirrhosis","volume":"119","author":"JR Rodr\u00edguez\u2010Aguilera","year":"2018","journal-title":"J Cell Biochem"},{"issue":"8","key":"pone.0292448.ref031","doi-asserted-by":"crossref","DOI":"10.1007\/s00125-004-1460-1","article-title":"Women and men have similar amounts of liver and intra-abdominal fat, despite more subcutaneous fat in women: implications for sex differences in markers of cardiovascular risk","volume":"47","author":"J Westerbacka","year":"2004","journal-title":"Diabetologia"},{"key":"pone.0292448.ref032","doi-asserted-by":"crossref","first-page":"g4596","DOI":"10.1136\/bmj.g4596","article-title":"Non-alcoholic fatty liver disease","volume":"349","author":"N Sattar","year":"2014","journal-title":"BMJ"},{"key":"pone.0292448.ref033","doi-asserted-by":"crossref","first-page":"S135","DOI":"10.1055\/s-2001-18576","article-title":"Insulin resistance: definition and consequences","volume":"109","author":"HE Lebovitz","year":"2001","journal-title":"Exp Clin Endocrinol Diabetes"},{"key":"pone.0292448.ref034","first-page":"77","author":"BB Fredholm","year":"2011","journal-title":"Adenosine and the Regulation of Metabolism and Body Temperature. In"},{"issue":"7\u20138","key":"pone.0292448.ref035","doi-asserted-by":"crossref","first-page":"580","DOI":"10.3109\/1061186X.2015.1058803","article-title":"Adenosine-associated delivery systems","volume":"23","author":"M Kazemzadeh-Narbat","year":"2015","journal-title":"J Drug Target"},{"issue":"8","key":"pone.0292448.ref036","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1016\/j.metabol.2016.05.003","article-title":"Non-alcoholic fatty liver disease and dyslipidemia: An update","volume":"65","author":"N Katsiki","year":"2016","journal-title":"Metabolism"},{"issue":"1","key":"pone.0292448.ref037","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/0003-9861(78)90263-1","article-title":"On the mechanism of ethanol-induced fatty liver and its reversibility by adenosine","volume":"190","author":"R Hern\u00e1ndez-Mu\u00f1oz","year":"1978","journal-title":"Arch Biochem Biophys [Internet]"},{"issue":"5","key":"pone.0292448.ref038","doi-asserted-by":"crossref","first-page":"2241","DOI":"10.1002\/hep.30333","article-title":"Mouse Models of Nonalcoholic Steatohepatitis: Toward Optimization of Their Relevance to Human Nonalcoholic Steatohepatitis","volume":"69","author":"G Farrell","year":"2019","journal-title":"Hepatology"},{"issue":"8","key":"pone.0292448.ref039","first-page":"686","article-title":"Lipophagy: Molecular Mechanisms and Implications in Metabolic Disorders","volume":"43","author":"DW Shin","year":"2020","journal-title":"Mol Cells"},{"issue":"3","key":"pone.0292448.ref040","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1016\/0006-291X(77)91572-8","article-title":"Regulation of fatty acid oxidation by adenosine at the level of its extramitochondrial activation","volume":"76","author":"VC de S\u00e1nchez","year":"1977","journal-title":"Biochem Biophys Res Commun"},{"issue":"10","key":"pone.0292448.ref041","doi-asserted-by":"crossref","first-page":"2198","DOI":"10.1161\/ATVBAHA.107.148429","article-title":"Transcriptional Activation of Hepatic ACSL3 and ACSL5 by Oncostatin M Reduces Hypertriglyceridemia Through Enhanced \u03b2-Oxidation","volume":"27","author":"Y Zhou","year":"2007","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"5","key":"pone.0292448.ref042","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1194\/jlr.M032599","article-title":"High-fructose diet downregulates long-chain acyl-CoA synthetase 3 expression in liver of hamsters via impairing LXR\/RXR signaling pathway","volume":"54","author":"B Dong","year":"2013","journal-title":"J Lipid Res"},{"key":"pone.0292448.ref043","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.biocel.2017.12.019","article-title":"Mitochondria in non-alcoholic fatty liver disease","volume":"95","author":"ICM Sim\u00f5es","year":"2018","journal-title":"Int J Biochem Cell Biol"},{"issue":"4","key":"pone.0292448.ref044","doi-asserted-by":"crossref","first-page":"389","DOI":"10.18388\/abp.2010_2422","article-title":"Liver mitochondria and insulin resistance","volume":"57","author":"G Vial","year":"2010","journal-title":"Acta Biochim Pol"},{"key":"pone.0292448.ref045","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.intimp.2017.10.019","article-title":"Inflammation is regulated by the adenosine derivative molecule, IFC-305, during reversion of cirrhosis in a CCl4 rat model","volume":"54","author":"R P\u00e9rez-Cabeza de Vaca","year":"2018","journal-title":"Int Immunopharmacol [Internet]"},{"issue":"1","key":"pone.0292448.ref046","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1111\/j.1600-065X.2012.01145.x","article-title":"Inflammation links excess fat to insulin resistance: the role of the interleukin-1 family","volume":"249","author":"CJ Tack","year":"2012","journal-title":"Immunol Rev"},{"issue":"2","key":"pone.0292448.ref047","doi-asserted-by":"crossref","DOI":"10.1042\/BSR20181202","article-title":"Serum profile of cytokines and their genetic variants in metabolic syndrome and healthy subjects: a comparative study","volume":"39","author":"U Zafar","year":"2019","journal-title":"Biosci Rep"},{"issue":"5","key":"pone.0292448.ref048","doi-asserted-by":"crossref","first-page":"E1056","DOI":"10.1152\/ajpendo.90345.2008","article-title":"Enhanced angiogenesis in obesity and in response to PPAR\u03b3 activators through adipocyte VEGF and ANGPTL4 production","volume":"295","author":"O Gealekman","year":"2008","journal-title":"American Journal of Physiology-Endocrinology and Metabolism"},{"issue":"9","key":"pone.0292448.ref049","doi-asserted-by":"crossref","first-page":"2362","DOI":"10.1172\/JCI32239","article-title":"Angiogenesis modulates adipogenesis and obesity","volume":"117","author":"Y. Cao","year":"2007","journal-title":"J Clin Invest"},{"issue":"11","key":"pone.0292448.ref050","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1038\/s41574-021-00538-6","article-title":"Hepatic sexual dimorphism\u2014implications for non-alcoholic fatty liver disease","volume":"17","author":"P Lefebvre","year":"2021","journal-title":"Nat Rev Endocrinol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0292448","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T17:29:52Z","timestamp":1696526992000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0292448"}},"subtitle":[],"editor":[{"given":"Nobuyuki","family":"Takahashi","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2023,10,5]]},"references-count":50,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,10,5]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0292448","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,5]]}}}