Novel insights and mechanisms of diet-induced obesity: Mid-term versus long-term effects on hepatic transcriptome and antioxidant capacity in Sprague-Dawley rats

• Published in: Life sciences (1973) 2023-07, Vol.324, p.121746-121746, Article 121746
• Main Authors: García-Beltrán, Alejandro, Martínez, Rosario, Porres, Jesus M., Arrebola, Francisco, Artero, Inmaculada Ruiz, Galisteo, Milagros, Aranda, Pilar, Kapravelou, Garyfallia, López-Jurado, María
• Format: Article
• Language: English
• Subjects: Aging; Animals; Antioxidant capacity; Antioxidants - pharmacology; Diet, High-Fat - adverse effects; Fatty Acids - metabolism; Glucose & lipid metabolism; Lipid Metabolism; Liver; Liver - metabolism; Non-alcoholic Fatty Liver Disease - metabolism; Obesity; Obesity - metabolism; Rats; Rats, Sprague-Dawley; Transcriptome
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2023.121746

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. 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. 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. 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. [Display omitted] •High-fat high-fructose diet increased body and liver weight and total liver fat.•High-fat high-fructose diet modified hepatic transcriptome.•Obesogenic diet enhanced hepatic fat accumulation by de novo lipogenesis.•Aging promoted hepatic fat accumulation related to β-oxidation of fatty acids.•Obesogenic diet and aging modified antioxidant status more than aging per se.