Maternal exercise attenuates the lower skeletal muscle glucose uptake and insulin secretion caused by paternal obesity in female adult rat offspring

Abstract

Key points: Paternal obesity negatively influences metabolic outcomes in adult rat offspring. Maternal voluntary physical activity has previously been reported to improve glucose metabolism in adult rat offspring sired by healthy fathers. Here, we investigated whether a structured programme of maternal exercise training before and during gestation can attenuate the negative impacts that paternal obesity has on insulin sensitivity and secretion in female adult offspring. Exercise before and during pregnancy normalised the lower insulin sensitivity in skeletal muscle and the lower insulin secretion observed in female offspring sired by obese fathers. This paper presents a feasible, low-cost and translatable intervention strategy that can be applied perinatally to support multifactor interventions to break the cycle of metabolic dysfunction caused by paternal obesity.

Abstract: We investigated whether maternal exercise before and during gestation could attenuate the negative metabolic effects of paternal high-fat diet-induced obesity in female adult rat offspring. Fathers consumed a normal chow or high-fat diet before mating. Mothers exercised on a treadmill before and during gestation or remained sedentary. In adulthood, female offspring were assessed using intraperitoneal insulin and glucose tolerance tests (IPITT and IPGTT, respectively), pancreatic morphology, ex vivo skeletal muscle insulin-stimulated glucose uptake and mitochondrial respiratory function. Paternal obesity impaired whole-body and skeletal muscle insulin sensitivity and insulin secretion in adult offspring. Maternal exercise attenuated the lower insulin-stimulated glucose uptake in offspring sired by obese fathers but distal insulin signalling components (p-AKT Thr308 and Ser473, p-TBC1D4 Thr642 and GLUT4) remained unchanged (P > 0.05). Maternal exercise increased citrate synthase activity only in offspring sired by obese fathers. Maternal exercise also reversed the lower insulin secretion in vivo observed in offspring of obese fathers, probably due to an attenuation of the decrease in pancreatic beta cell mass. In summary, maternal exercise before and during pregnancy in rats attenuated skeletal muscle insulin resistance and attenuated the decrease in pancreatic beta cell mass and insulin secretion observed in the female offspring of obese fathers.

Keywords: developmental origins of health and disease (DOHaD); gestation; high-fat diet; mitochondria; pancreas; physical activity; pregnancy; signalling; skeletal muscle.