{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:45:55Z","timestamp":1790790355266,"version":"4.1.0"},"reference-count":21,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T00:00:00Z","timestamp":1724889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Secretar\u00eda de Educaci\u00f3n, Ciencia, Tecnolog\u00eda e Innovaci\u00f3n de la Ciudad de M\u00e9xico","award":["SECTEI-158-2023"],"award-info":[{"award-number":["SECTEI-158-2023"]}]},{"name":"Secretar\u00eda de Educaci\u00f3n, Ciencia, Tecnolog\u00eda e Innovaci\u00f3n de la Ciudad de M\u00e9xico","award":["UACM-CCYT-CON-05"],"award-info":[{"award-number":["UACM-CCYT-CON-05"]}]},{"name":"Colegio de Ciencia y Tecnolog\u00eda de la Universidad Aut\u00f3noma de la Ciudad de M\u00e9xico","award":["SECTEI-158-2023"],"award-info":[{"award-number":["SECTEI-158-2023"]}]},{"name":"Colegio de Ciencia y Tecnolog\u00eda de la Universidad Aut\u00f3noma de la Ciudad de M\u00e9xico","award":["UACM-CCYT-CON-05"],"award-info":[{"award-number":["UACM-CCYT-CON-05"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Non-alcoholic fatty liver disease (NAFLD), now referred to as metabolic dysfunction-associated steatotic liver disease (MASLD), is alarmingly increasing alongside the cases of obesity worldwide. MASLD is an underestimated metabolic abnormality closely linked with a higher risk of developing systemic arterial hypertension (SAH). However, the underlying mechanism of association between MASLD and SAH remains unknown. Inflammation may link these two entities by regulating the renin-angiotensin system (RAS). For this reason, in this study, we evaluated the hepatic expression of a cytokine profile and critical molecules in the RAS pathway in patients with morbid obesity and MASLD, both with SAH. We found a statistically significant correlation between ACE levels and the cytokines IL-4, IL-10, and IL-13 of Th2 response. Furthermore, according to a multiple linear regression analysis, the cytokines IL-4 and IL-13 were the best predictors of ACE levels. Moreover, we observed increased hepatic IL-13 expression in patients with morbid obesity, MASLD, and SAH compared to those without SAH. These results allow us to propose, for the first time, that the Th2 response, through regulating the RAS, could play a critical role in developing SAH in individuals with MASLD and obesity.<\/jats:p>","DOI":"10.3390\/life14091080","type":"journal-article","created":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T03:40:39Z","timestamp":1724902839000},"page":"1080","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Exploring the Th2 Response in Obesity and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A Potential Modulator of the Renin-Angiotensin System (RAS) Pathway in Hypertension Development"],"prefix":"10.3390","volume":"14","author":[{"given":"Luc\u00eda Ang\u00e9lica","family":"M\u00e9ndez-Garc\u00eda","sequence":"first","affiliation":[{"name":"Immunometabolism Laboratory, General Hospital of Mexico \u201cEduardo Liceaga\u201d, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9224-7400","authenticated-orcid":false,"given":"Galileo","family":"Escobedo","sequence":"additional","affiliation":[{"name":"Immunometabolism Laboratory, General Hospital of Mexico \u201cEduardo Liceaga\u201d, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itzel","family":"Baltazar-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Immunometabolism Laboratory, General Hospital of Mexico \u201cEduardo Liceaga\u201d, Mexico City 06720, Mexico"},{"name":"Genomics Sciences Program, Oncogenomics and Cancer Proteomics Laboratory, Autonomous University of Mexico City, Avenue San Lorenzo 290, Mexico City 03100, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3680-3793","authenticated-orcid":false,"given":"Nydia Ang\u00e9lica","family":"Ocampo-Aguilera","sequence":"additional","affiliation":[{"name":"Immunometabolism Laboratory, General Hospital of Mexico \u201cEduardo Liceaga\u201d, Mexico City 06720, Mexico"},{"name":"Genomics Sciences Program, Oncogenomics and Cancer Proteomics Laboratory, Autonomous University of Mexico City, Avenue San Lorenzo 290, Mexico City 03100, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Alfonso","family":"Arreola-Miranda","sequence":"additional","affiliation":[{"name":"Immunometabolism Laboratory, General Hospital of Mexico \u201cEduardo Liceaga\u201d, Mexico City 06720, Mexico"},{"name":"Genomics Sciences Program, Oncogenomics and Cancer Proteomics Laboratory, Autonomous University of Mexico City, Avenue San Lorenzo 290, Mexico City 03100, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel Angel","family":"Cid-Soto","sequence":"additional","affiliation":[{"name":"Sequencing Laboratory, Division of Research Development, National Medical Center \u201cSiglo XXI\u201d, Mexican Social Security Institute, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Alfaro-Cruz","sequence":"additional","affiliation":[{"name":"Pathological Anatomy Department, General Hospital of Mexico \u201cDr. Eduardo Liceaga\u201d, Mexico City 06726, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Gonz\u00e1lez-Ch\u00e1vez","sequence":"additional","affiliation":[{"name":"Comprehensive Care Clinic for Patients with Diabetes and Obesity (CAIDO), General Hospital of Mexico \u201cDr. Eduardo Liceaga\u201d, Mexico City 06726, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9884-7386","authenticated-orcid":false,"given":"Aquiles Ranferi","family":"Oca\u00f1a-Guzm\u00e1n","sequence":"additional","affiliation":[{"name":"Integrative Immunology Laboratory, National Institute of Respiratory Diseases, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Solleiro-Villavicencio","sequence":"additional","affiliation":[{"name":"Genomics Sciences Program, Oncogenomics and Cancer Proteomics Laboratory, Autonomous University of Mexico City, Avenue San Lorenzo 290, Mexico City 03100, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1161\/HYPERTENSIONAHA.119.13419","article-title":"Nonalcoholic Fatty Liver Disease: An Emerging Driver of Hypertension","volume":"75","author":"Zhao","year":"2020","journal-title":"Hypertension"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2809","DOI":"10.1016\/j.cgh.2021.12.002","article-title":"2019 Global NAFLD Prevalence: A Systematic Review and Meta-analysis","volume":"20","author":"Le","year":"2022","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1038\/s41440-022-01117-6","article-title":"Mechanisms underlying the bidirectional association between nonalcoholic fatty liver disease and hypertension","volume":"46","author":"Nakagami","year":"2022","journal-title":"Hypertens. Res."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"M\u00e9ndez-Garc\u00eda, L.A., Escobedo, G., Minguer-Uribe, A.G., Viurcos-Sanabria, R., Aguayo-Guerrero, J.A., Carrillo-Ruiz, J.D., and Solleiro-Villavicencio, H. (2022). Role of the renin-angiotensin system in the development of COVID-19-associated neurological manifestations. Front. Cell. Neurosci., 16.","DOI":"10.3389\/fncel.2022.977039"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Cao, X., Yang, F., Shi, T., Yuan, M., Xin, Z., Xie, R., Li, S., Li, H., and Yang, J.-K. (2016). Angiotensin-converting enzyme 2\/angiotensin-(1-7)\/Mas axis activates Akt signaling to ameliorate hepatic steatosis. Sci. Rep., 6.","DOI":"10.1038\/srep21592"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3396","DOI":"10.3748\/wjg.v23.i19.3396","article-title":"Renin angiotensin system in liver diseases: Friend or foe?","volume":"23","author":"Silva","year":"2017","journal-title":"World J. Gastroenterol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"16291","DOI":"10.1096\/fj.202001639R","article-title":"Angiotensin-(1-7), the product of ACE2 ameliorates NAFLD by acting through its receptor Mas to regulate hepatic mitochondrial function and glycolipid metabolism","volume":"34","author":"Song","year":"2020","journal-title":"FASEB J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"42","DOI":"10.5049\/EBP.2008.6.1.42","article-title":"Renin-Angiotensin System\u2014Considerations for Hypertension and Kidney","volume":"6","author":"Yim","year":"2008","journal-title":"Electrolytes Blood Press."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1111\/j.1523-1755.2004.00462.x","article-title":"An ACE inhibitor reduces Th2 cytokines and TGF-\u03b21 and TGF-\u03b22 isoforms in murine lupus nephritis","volume":"65","author":"Saxena","year":"2004","journal-title":"Kidney Int."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"G\u0142uszy\u0144ska, P., Lemancewicz, D., Dzi\u0119cio\u0142, J.B., and Hady, H.R. (2021). Non-Alcoholic Fatty Liver Disease (NAFLD) and Bariatric\/Metabolic Surgery as Its Treatment Option: A Review. J. Clin. Med., 10.","DOI":"10.3390\/jcm10245721"},{"key":"ref_11","first-page":"45","article-title":"A multisociety Delphi consensus statement on new fatty liver disease nomenclature","volume":"44","author":"Rinella","year":"2023","journal-title":"Hepatology"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Cheng, W., Du, Y., Zhang, Q., Wang, X., He, C., He, J., Jing, F., Ren, H., Guo, M., and Tian, J. (2022). Age-related changes in the risk of high blood pressure. Front. Cardiovasc. Med., 9.","DOI":"10.3389\/fcvm.2022.939103"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1038\/hr.2017.75","article-title":"The relationship between obesity and hypertension: An updated comprehensive overview on vicious twins","volume":"40","author":"Leggio","year":"2017","journal-title":"Hypertens. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1161\/HYPERTENSIONAHA.117.10546","article-title":"Hypertension and Diabetes Mellitus Coprediction and Time Trajectories","volume":"71","author":"Tsimihodimos","year":"2018","journal-title":"Hypertension"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.jhep.2017.09.021","article-title":"Hypertension, diabetes, atherosclerosis and NASH: Cause or consequence?","volume":"68","author":"Lonardo","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"9028969","DOI":"10.1155\/2022\/9028969","article-title":"Exploring the Impact of ACE Inhibition in Immunity and Disease","volume":"2022","author":"Oosthuizen","year":"2022","journal-title":"J. Renin-Angiotensin-Aldosterone Syst."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Barhoumi, T., and Todryk, S. (2023). Role of monocytes\/macrophages in renin-angiotensin system-induced hypertension and end organ damage. Front. Physiol., 14.","DOI":"10.3389\/fphys.2023.1199934"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Nasiri-Ansari, N., Androutsakos, T., Flessa, C.M., Kyrou, I., Siasos, G., Randeva, H.S., Kassi, E., and Papavassiliou, A.G. (2022). Endothelial Cell Dysfunction and Nonalcoholic Fatty Liver Disease (NAFLD): A Concise Review. Cells, 11.","DOI":"10.3390\/cells11162511"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1007\/s11892-024-01542-6","article-title":"Metabolic dysfunction-associated steatotic liver disease and atherosclerosis","volume":"24","year":"2024","journal-title":"Curr. Diab. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1161\/CIRCULATIONAHA.113.004146","article-title":"Endothelial cell-specific liver kinase B1 deletion causes endothelial dysfunction and hypertension in mice in vivo","volume":"129","author":"Zhang","year":"2014","journal-title":"Circulation"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Kokubo, K., Onodera, A., Kiuchi, M., Tsuji, K., Hirahara, K., and Nakayama, T. (2022). Conventional and pathogenic Th2 cells in inflammation, tissue repair, and fibrosis. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.945063"}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/14\/9\/1080\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:44:38Z","timestamp":1760111078000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/14\/9\/1080"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,29]]},"references-count":21,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["life14091080"],"URL":"https:\/\/doi.org\/10.3390\/life14091080","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,29]]}}}