Maternal and Paternal Exercise Regulates Offspring Metabolic Health and Beta-Cell Phenotype

Abstract

Maternal and paternal environment are critical factors in determining risk for obesity and diabetes in offspring. Maternal exercise in mice can prevent the detrimental effects of maternal high-fat feeding on offspring metabolic health, whereas the effects of paternal exercise on offspring are less clear. Little is also known about the effects of maternal or paternal exercise on offspring beta cells, a major factor in glucose homeostasis. We determined the effects of maternal, paternal and maternal+paternal exercise on offspring glucose tolerance and beta cell morphology. Male sires were housed ± running wheels for 3 weeks before breeding (4.4±0.8 km/day) and dams were housed ± running wheels for 2 weeks before breeding (8.4±0.5 km/day) and during gestation (4.7±0.5 km/day). All male and female breeders were fed a high-fat diet. Four groups of male offspring were studied: both parents sedentary (Sed); maternal exercise only (Mat Ex); paternal exercise only (Pat Ex); maternal+paternal exercise (Mat+Pat Ex) (n=5-8 litters/group). Offspring were sedentary and separate cohorts were studied at weaning, 52, and 80 weeks. Post-weaning, offspring were fed a chow diet. There was no effect of parental exercise on offspring glucose tolerance at weaning. At 52 weeks, offspring of exercised parents had ∼25% lower fasting blood glucose concentrations vs. Sed (all p<0.01), and glucose tolerance was improved in Mat Ex (33%), Pat Ex (35%), and Mat+Pat Ex (50%) vs. Sed (p<0.001). Mat Ex, Pat Ex and Mat+Pat Ex had decreased beta cell size (40%) and mass (40%), whereas islet size and density were only decreased in offspring from Mat+Pat Ex parents (28% and 40%, respectively). Older offspring (80 weeks) from all three parental exercise treatments displayed improved glucose tolerance (p<0.05). Maternal and paternal exercise in high-fat fed parents has profound positive effects on offspring glucose tolerance during adulthood and older age that may be linked to adaptations in the endocrine pancreas. Disclosure J. Zheng: None. A.B.A. Wagner: None. N.B. Prince: None. K. So: None. J. Mul: None. E. Dirice: None. M.F. Hirshman: None. K.I. Stanford: None. R. Kulkarni: None. L.J. Goodyear: None.