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

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, anti-oxidant & 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.

Automated summary

In this study, a rat model of diet-induced obesity was used to investigate the effects of aging on the gene expression of the liver transcriptome. The results showed that different lengths of diet-induced obesity resulted in significant differences in metabolic changes, including increased body weight, hepatic fat deposition, and abnormal fatty acid metabolism. The study suggests that the choice of obesity-induction length is crucial for controlling the obesity model in specific experimental designs.