Oral Presentation Annual Meetings of the Endocrine Society of Australia and Society for Reproductive Biology and Australia and New Zealand Bone and Mineral Society 2016

Sex-dependent impairment of metabolic responses to exercise training in adult sheep offspring of placentally-restricted pregnancies (#224)

Kathryn L Gatford 1 , Amy L Wooldridge 1 , Manpreet Kaur 1 , Jennifer Rice 1 , Anna Le-Ber 1 , Filippe Falcao-Tebas 2 , Jarrod Kerris 2 , Evelyn Marin 2 , Glenn K McConell 2
  1. Robinson Research Institute and School of Medicine, University of Adelaide, University of Adelaide, Adelaide, SA, Australia
  2. Institute of Sport, Exercise and Active Living, Victoria Unversity, Melbourne, VIC, Australia

Exercise training improves glucose homeostasis, improving insulin sensitivity and secretion, which are both impaired after intrauterine growth restriction (IUGR). There is mixed and limited evidence that responses to exercise training are blunted after IUGR. We therefore measured glucose tolerance and insulin secretion during an intravenous glucose tolerance test, and insulin sensitivity by hyperinsulinameic euglycaemic clamp in one year-old (adult) progeny from multi-fetal control (CON: n=5 M, 9 F) and placentally-restricted (PR: n=9 M, 10 F) pregnancies. Sheep were re-tested after 33 d of exercise training (~3.4 km running each day in same-sex groups, average speed 5.7 ± 0.06 km/h). Effects of training, treatment, and sex were analysed using a repeated measures model, including the dam as a random factor to account for maternal environment in twins. Training profoundly reduced the increase in circulating lactate after daily exercise, similarly in all animals. Glucose tolerance improved by ~10% after training in CON (P=0.028) but did not change in PR progeny. The insulin secretion response to glucose increased >40% overall after training (P=0.009), and this training response occurred in CON (P=0.005) but not PR animals when analysed separately. Surprisingly, whole-body insulin sensitivity did not increase after training, although preliminary data confirms an increase in skeletal muscle GLUT4 expression. In conclusion, PR impaired the exercise training-induced improvement in glucose tolerance and insulin secretion, particularly in males. Enhanced insulin secretion appears to underlie training-induced improvements in glucose tolerance in CON but not PR progeny. Our results suggest that individuals subjected to a restricted environment before birth may have impaired capacity to respond to adult exercise. We hypothesise that interventions to reprogram metabolism and reverse or prevent adverse metabolic effects of IUGR that develop with aging may need to be targeted to earlier ages, during periods of greater plasticity.