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However, cases of hepatotoxicity have been reported due to the consumption of this drug. On the other hand, piperine is an alkaloid found in black pepper that has demonstrated antiobesity, antihyperlipidemic, antioxidant, prebiotic, and hepatoprotective effects. The aim of this study was to evaluate the protective effect of piperine on the toxicity of orlistat in liver tissue. Obese male rats were administered piperine (30\u2009mg\/kg), orlistat (60\u2009mg\/kg), and the orlistat\u2010piperine combination (30\u2009mg\/kg\u2009+\u200960\u2009mg\/kg) daily for 6 weeks. It was observed that the orlistat\u2010piperine treatment resulted in greater weight loss, decreased biochemical markers (lipid profile, liver enzymes, pancreatic lipase activity), and histopathological analysis showed decreased hepatic steatosis and reduction of duodenal inflammation. Transcriptomic analysis revealed that the administration of piperine with orlistat increased the expression of genes related to the beta\u2010oxidation of fatty acids, carbohydrate metabolism, detoxification of xenobiotics, and response to oxidative stress. Therefore, the results suggest that the administration of orlistat\u2010piperine activates signaling pathways that confer a hepatoprotective effect, reducing the toxic impact of this drug.<\/jats:p>","DOI":"10.1002\/jbt.70040","type":"journal-article","created":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T10:49:25Z","timestamp":1730890165000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Transcriptomic Analysis of the Protective Effect of Piperine on Orlistat Hepatotoxicity in Obese Male Wistar Rats"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-2318-8224","authenticated-orcid":false,"given":"Jessica","family":"Ledesma\u2010Aparicio","sequence":"first","affiliation":[{"name":"Departamento de Farmacobiolog\u00eda Centro de Investigaci\u00f3n y de Estudios Avanzados del IPN Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Mailloux\u2010Salinas","sequence":"additional","affiliation":[{"name":"Departamento de Farmacobiolog\u00eda Centro de Investigaci\u00f3n y de Estudios Avanzados del IPN Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David Julian","family":"Arias\u2010Ch\u00e1vez","sequence":"additional","affiliation":[{"name":"Departamento de Farmacobiolog\u00eda Centro de Investigaci\u00f3n y de Estudios Avanzados del IPN Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elihu","family":"Campos\u2010P\u00e9rez","sequence":"additional","affiliation":[{"name":"Departamento de Patolog\u00eda Hospital General Dra Matilde Petra Montoya Lafragua, ISSSTE Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Calixto\u2010Tlacomulco","sequence":"additional","affiliation":[{"name":"Laboratorio de Estructura de Prote\u00ednas Instituto Nacional de Medicina Gen\u00f3mica (INMEGEN) Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armando","family":"Cruz\u2010Rangel","sequence":"additional","affiliation":[{"name":"Laboratorio de Estructura de Prote\u00ednas Instituto Nacional de Medicina Gen\u00f3mica (INMEGEN) Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Pablo","family":"Reyes\u2010Grajeda","sequence":"additional","affiliation":[{"name":"Laboratorio de Estructura de Prote\u00ednas Instituto Nacional de Medicina Gen\u00f3mica (INMEGEN) Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guadalupe","family":"Bravo","sequence":"additional","affiliation":[{"name":"Departamento de Farmacobiolog\u00eda Centro de Investigaci\u00f3n y de Estudios Avanzados del IPN Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,6]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(11)60813-1"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1503\/cmaj.191707"},{"key":"e_1_2_9_4_1","unstructured":"\"Obesity and Overweight \" World Health Organization accessed May 29 2023 https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/obesity-and-overweight."},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-142-7-200504050-00012"},{"key":"e_1_2_9_6_1","unstructured":"\"Prescription Medications to Treat Overweight & Obesity \" National Institute of Diabetes and Digestive and Kidney Diseases accessed June 21 2023 https:\/\/www.niddk.nih.gov\/health-information\/weight-management\/prescription-medications-treat-overweight-obesity."},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.281361"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.2165\/00002018-200831010-00005"},{"key":"e_1_2_9_9_1","volume-title":"LiverToX: Clinical and Research Information on Drug\u2010Induced Liver Injury","author":"National Institute of Diabetes and Digestive and Kidney Diseases","year":"2012"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2014.07.008"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodchem.2013.06.028"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12013-011-9306-1"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jff.2020.104011"},{"key":"e_1_2_9_14_1","doi-asserted-by":"crossref","unstructured":"S.Mitra U.Anand N. 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