Pharmacological and gene modification-based models for studying the impact of perinatal metabolic disturbances in adult life.

Abstract

Genetic modification approaches or pharmacological interventions may be useful for understanding the molecular mechanisms by which nutrient derivatives and metabolites exert their effects in the perinatal period and how they may influence longterm metabolism in adults. Examples for such experimental settings in rodents are targeted disruption of the gene for peroxisome proliferator-activated receptor (PPAR)-a, a lipid sensor and master regulator of lipid catabolism, or maternal treatment with agonists of PPARgamma, a master regulator of adipogenesis and target of insulin sensitizing drugs in adults. All these interventions show differential effects in the perinatal period compared to adults and indicate that altered activity of master regulators of metabolism results in profound metabolic alterations in the perinatal period that may influence adult metabolism.