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Worldwide, obesity has doubled since 1980. WHO declares obesity as preventable and attributes the increase in prevalence to high consumption of energy-rich foods and decreased physical activity. Epidemiological and experimental studies suggest that parents' and grandparents' diet could also have a role. We established a model of grandparents' high-fat diet (HFD) to explore potential mechanisms.

Sprague-Dawley rats were fed a HFD (45% fat) or a matched control diet (10% fat) from weaning for 14 weeks. After metabolic testing, founders (F0) were bred with controls to establish an F1 generation. F1 rats were maintained on the control diet for 14 weeks after weaning and then underwent metabolic testing followed by mating with control rats to generate F2 offspring. We analysed F0 data with ANOVA and the F1 and F2 data using mixed models, with group and sex as a fixed factor and litter …