Maternal environments are critical factors in determining risk for obesity and diabetes in both first generation (F1) and second generation (F2) offspring. Maternal exercise in mice has been shown to improve metabolic health in F1, including prevention of the detrimental effects of maternal high-fat feeding on F1 offspring. Whether the beneficial effects of maternal exercise can be transmitted to the F2 generation (grand-offspring) is not known. To test this, C57BL/6 females were fed a chow or high fat diet (60% fat) and grouped by housing in cages with (Exercise Trained) or without (Sedentary) running wheels for 2 weeks before breeding (7.04±0.5 km/day) and during gestation (2.2±0.3 km/day). Females were bred with chow-fed, sedentary males. F1 offspring were sedentary and chow-fed. At 8 weeks of age, two male mice (F1) from each litter (selected based on average body weight of the litter), were bred with age-matched female mice from untreated parents. Thus, four groups of F2 offspring resulted based on grand-maternal treatment: sedentary and chow-fed; sedentary and high fat-fed; trained and chow-fed; trained and high fat-fed (n=5-10 litters/group). F2 offspring were sedentary and chow-fed post-weaning. Unexpectedly, there was no effect of grand-maternal high fat diet on F2 glucose tolerance at any age. There was also no effect of grand-maternal exercise on glucose tolerance in offspring at 16 or 24 weeks of age. However, grand-maternal exercise resulted in a tendency for improvement in glucose tolerance in 36-week-old offspring (P=0.07), and a significant improvement at 52 weeks (males: P=0.03; females: P=0.0001). Male and female body weights were not different among F2 groups. F2 offspring from exercise-trained grand-mothers had decreased % fat mass (males: P=0.04; females: P=0.05) and increased % lean mass in males (P=0.04), with a tendency to increase in females (P=0.06) at 52 weeks of age.

In conclusion, grand-maternal exercise training has beneficial effects in the metabolic health of adult male and female F2 offspring.


A.B.A. Wagner: None. J. Kusuyama: None. P. Nigro: None. M.F. Hirshman: Stock/Shareholder; Self; Abbott Laboratories, AbbVie Inc., Amgen Inc., Colgate-Palmolive Company, Medtronic. L.J. Goodyear: None.


American Diabetes Association (1-17-PMF-009 to A.B.A.W.); National Institutes of Health (R01DK101043)

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