Grandmaternal high-fat diet primed anxiety-like behaviour in the second-generation female offspring

The health consequences of maternal obesity during pregnancy are disturbing as they may contribute to mental disorders in subsequent generations. We examine the influence of suboptimal grandmaternal diet on potential metabolic and mental health outcome of grand-progenies with a high-fat diet (HFD) manipulation in adulthood in a rat HFD model. Grandmaternal exposure to HFD exacerbated granddaughter's anxiety-like phenotype. Grandmaternal exposure to HFD led to upregulated corticotropin-releasing hormone receptor 2 mRNA expression involved in the stress axis in the male F₂ offspring. Thus, we demonstrate that suboptimal grandmaternal diet prior to and during pregnancy and lactation may persist across subsequent generations. These findings have important implications for understanding both individual rates of metabolic and mental health problems and the clinical impact of current global trends towards comorbidity of obesity and depression and anxiety. In conclusion, the effect of grandmaternal HFD consumption during pregnancy on stress axis function and mental disorders may be transmitted to future generations.