Global prevalence of obesity has increased to epidemic proportions over the past 40 years, with childhood obesity reaching alarming rates. In this study, we determined changes in liver and adipose tissue transcriptomes of a porcine model for prepubertal early obesity induced by a high-calorie diet and supplemented with bioactive ingredients. A total of 43 nine-weeks-old animals distributed in four pens were fed with four different dietary treatments for 10 weeks: a conventional diet; a western-type diet; and a western-type diet with Bifidobacterium breve and rice hydrolysate, either adding or not omega-3 fatty acids. Animals fed a western-type diet increased body weight and total fat content and exhibited elevated serum concentrations of cholesterol, whereas animals supplemented with bioactive ingredients showed lower body weight gain and tended to accumulate less fat. An RNA-seq experiment was performed with a total of 20 animals (five per group). Differential expression analyses revealed an increase in lipogenesis, cholesterogenesis and inflammatory processes in animals on the western-type diet while the supplementation with bioactive ingredients induced fatty acid oxidation and cholesterol catabolism, and decreased adipogenesis and inflammation. These results reveal molecular mechanisms underlying the beneficial effects of bioactive ingredient supplementation in an obese pig model. administration of Bifidobacterium breve B-3 modified the hepatic expression of genes related to lipid metabolism and response to stress 4 . A reduction in body fat has been also observed in healthy pre-obese individuals receiving Bifidobacterium breve B-3, but no significant improvement of blood parameters was found 5 . In partial agreement, studies with rodent models of obesity have demonstrated the anti-obesity effect of n-3 polyunsaturated fatty acids (PUFA). Reduction of fat mass was predominantly observed in mice fed a HFD and supplemented with n-3 PUFA (reviewed in 6 ). However, the effects of n-3 PUFA in human obesity remain inconclusive. On the other hand, rice proteins and their hydrolysates added to high fat and/or high cholesterol diets have shown to have anti-obesity and hypocholesterolemic effects through the effective modulation of cholesterol and triglyceride metabolism, and the activity of hepatic genes related to lipid metabolism 7,8 .Overall, these experimental evidences reinforce the relevance of using bioactive dietetic supplements to prevent and treat obesity. However, as most of these studies were performed in rodent models, the underlying biological mechanisms determining anti-obesity effects are difficult to translate into humans, due to the vast differences between these species at the physiological and metabolic level 9 . In contrast, pigs are excellent models for human obesity and its comorbidities, given their similarity in terms of anatomy, physiology, metabolism, and genetics 9-11 .To date, a limited number of pig models for childhood obesity have been developed by short term (≤ 12 wk.) dietary interven...