International Journal of Obesity https://doi.org/10.1038/s41366-019-0434-9 ARTICLE Animal Models The Iberian pig fed with high-fat diet: a model of renal disease in obesity and metabolic syndrome Rosa Rodríguez Rodríguez 1,2 ● Antonio González-Bulnes 3,4 ● Consolacion Garcia-Contreras 3 ● Ana Elena Rodriguez-Rodriguez 2 ● Susana Astiz 3 ● Marta Vazquez-Gomez 3 ● Jose Luis Pesantez 3 ● Beatriz Isabel 3 ● Eduardo Salido-Ruiz 1,2,5 ● Jorge González 6 ● Javier Donate Correa 7 ● Sergio Luis-Lima 5,7 ● Esteban Porrini 5,7,2 Received: 14 December 2018 / Revised: 7 May 2019 / Accepted: 28 May 2019 © The Author(s), under exclusive licence to Springer Nature Limited 2019 Abstract Background The pathogenesis of renal disease in the context of overweight/obesity, metabolic syndrome, and insulin resistance is not completely understood. This may be due to the lack of a definitive animal model of disease, which limits our understanding of obesity-induced renal damage. We evaluated the changes in renal histology and lipid deposits induced by obesity in a model of insulin resistance: the Iberian swine fed with fat-enriched food. Methods Twenty-eight female sows were randomized to standard (SD) or high-fat diet (HFD: 6.8% of saturated fat) for 100 days. Weight, adiposity, analytics, oral glucose tolerance tests, and measured renal function were determined. Renal histology and lipid deposits in renal tissue were analyzed. Results Animals on HFD developed obesity, hypertension, high levels of LDL cholesterol, triglycerides, insulin resistance, and glomerular hyperfiltration. No animal developed overt diabetes. Animals on HFD showed “diabetoid changes”, including mesangial expansion [21.40% ± 4 vs.13.20% ± 4.0, p < 0.0001], nodular glomerulosclerosis [7.40% ± 7, 0.75 vs. 2.40% ± 4.7, p = 0.02], and glomerulomegaly (18% vs. 10%, p = 0.010) than those on SD. Tubular atrophy, interstitial fibrosis, inflammation, arteriolar hyalinosis, or fibrointimal thickening were mild and similar between groups. Triglyceride content in renal tissue was higher in animals on HFD than in SD (15.4% ± 0.5 vs. 12.7% ± 0.7; p < 0.01). Conclusions Iberian pigs fed with fat-enriched food showed diabetoid changes and glomerulomegaly as observed in obese humans making this model suitable to study obesity-induced renal disease. Introduction Worldwide, about 2 billion people are overweight or obese [1]. This pandemic is associated with an increase in meta- bolic syndrome (MS), which varies from 20 to 40% in diverse countries [2]. MS reflects the coexistence of over- weight/obesity, hypertension, prediabetes, dyslipidemia, subclinical inflammation, among others factors [3] with a common link: insulin resistance. The burden of overweight, obesity, and MS may have important consequences in renal disease. In fact, several studies showed MS [4], its com- ponents [5–7] or insulin resistance as risk factors for chronic kidney disease [8]. However, the pathogenesis of renal disease in over- weight/obesity and MS is not completely understood. There is limited evidence in human studies and specific animal models of renal disease in these conditions. Renal biopsy is rarely performed in patients with MS and so, morphological changes induced by hypertension, obesity, dyslipidemia, These authors contributed equally: Rosa Rodríguez Rodríguez, Antonio González-Bulnes * Esteban Porrini esteban.l.porrini@gmail.com 1 Pathology Department, Hospital Universitario de Canarias, Tenerife, Spain 2 University of La Laguna, Santa Cruz de Tenerife, Spain 3 Comparative Physiology Group, SGIT-INIA, Madrid, Spain 4 Faculty of Veterinary, Universidad Complutense de Madrid, Madrid, Spain 5 Instituto Tecnologías Biomédicas (ITB), Tenerife, Spain 6 Microsvet, Micros Veterinaria, León, Spain 7 Nephrology Department, Research Unit Hospital Universitario de Canarias, Tenerife, Spain Supplementary information The online version of this article (https:// doi.org/10.1038/s41366-019-0434-9) contains supplementary material, which is available to authorized users. 1234567890();,: 1234567890();,: