Successive Generations in a Rat Model Respond Differently to a Constant Obesogenic Environment

Research has shown that if a mother experiences a transitory perturbation to her environment during pregnancy or lactation, there are transgenerational consequences often involving a disordered metabolic phenotype in first generation offspring with recovery across subsequent generations. In contrast, little is known about the nature of the transgenerational response of offspring when a mother experiences a perturbation that is not transitory but instead persists across generations. Our study, using a rat model, subjected the parental generation to a change in environment and concomitant shift from a grain-based to obesogenic diets to generate an adipose phenotype in first generation offspring emulating a common scenario in human urbanisation and migration. We then investigated whether the obese phenotype was stable across generations when maintained in the transitioned environment, and whether dietary macronutrient balance affected the response. We found that second and third generation offspring had a reduced body fat to lean mass ratio and a reduced appetite relative to first generation offspring, irrespective of dietary macronutrient balance. The trajectory of this response is suggestive of a reduction in chronic disease risk across generations. This is one of the first studies, to our knowledge, to investigate the transgenerational response following parental transition to a persistent obesogenic environment, and to demonstrate that successive generations respond differently to this constant environment.