Novel insights and mechanisms of diet-induced obesity: Mid-term versus long-term effects on hepatic transcriptome and antioxidant capacity in Sprague-Dawley rats García Beltrán, Alejandro Martínez Martínez, Rosario Porres Foulquie, Jesús María Arrebola Vargas, Francisco Jesús Ruiz Artero, Inmaculada Galisteo Moya, Milagros Aranda Ramírez, Pilar Kapravelou, Garyfallia López-Jurado Romero De La Cruz, María Obesity Aging Liver Glucose & lipid metabolism Antioxidant capacity Rats Supplementary data to this article can be found online at https://doi.org/10.1016/j.lfs.2023.121746 Aims The study of molecular mechanisms related to obesity and associated pathologies like type 2-diabetes and non-alcoholic fatty liver disease requires animal experimental models in which the type of obesogenic diet and length of the experimental period to induce obesity deeply affect the metabolic alterations. Therefore, this study aimed to test the influence of aging along a rat model of diet-induced obesity in gene expression of the hepatic transcriptome. Main methods A high-fat/high-fructose diet to induce obesity was used. Mid- (13 weeks) and long-term (21 weeks) periods were established. Caloric intake, bodyweight, hepatic fat, fatty acid profile, histological changes, antioxidant activity, and complete transcriptome were analyzed. Key findings Excess bodyweight, hepatic steatosis and altered lipid histology, modifications in liver antioxidant activity, and dysregulated expression of transcripts related to cell structure, glucose & lipid metabolism, antioxidant & detoxifying capacity were found. Modifications in obese and control rats were accounted for by the different lengths of the experimental period studied. Significance Main mechanisms of hepatic fat accumulation were de novo lipogenesis or altered fatty acid catabolism for mid- or long-term study, respectively. Therefore, the choice of obesity-induction length is a key factor in the model of obesity used as a control for each specific experimental design. 2023-06-23T07:48:24Z 2023-06-23T07:48:24Z 2023-04-29 journal article A. García-Beltrán et al. Novel insights and mechanisms of diet-induced obesity: Mid-term versus long-term effects on hepatic transcriptome and antioxidant capacity in Sprague-Dawley rats. Life Sciences 324 (2023) 121746 [https://doi.org/10.1016/j.lfs.2023.121746] https://hdl.handle.net/10481/82754 10.1016/j.lfs.2023.121746 eng http://creativecommons.org/licenses/by-nc-nd/4.0/ open access Attribution-NonCommercial-NoDerivatives 4.0 Internacional Elsevier