EXAMINING THE EFFECTS OF EXERCISE ANCESTRY ON TWO GENERATIONS OF MOUSE OFFSPRING
Guth, Lisa Marie
Roth, Stephen M
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This dissertation research is comprised of three projects examining the effect of voluntary parental exercise on health-related phenotypes in two generations of mouse offspring. We developed a novel model of exercise ancestry where C57BL/6 mice (F0) were exposed to voluntary exercise (EX) or a sedentary (SED) lifestyle and were bred with like-exposed mates to produce first-generation (F1) offspring; F1 offspring were bred with like-exposed offspring to produce second-generation offspring (F2). F0 mice exercised before breeding and continuously through gestation and lactation; all offspring remained sedentary after weaning, thus F0 exercise exposure was the only distinguishing factor between offspring. The first project examined whole body and tissue masses, glucose tolerance, and skeletal muscle gene expression in two generations of 8-week old offspring of exercised vs. sedentary parents. F1 EX females were lighter with less fat mass compared to F1 SED females. F2 EX females had lower baseline blood glucose and impaired glucose tolerance. Further, skeletal muscle lipogenic gene expression was downregulated in females with exercise ancestry, while it was upregulated in males with exercise ancestry. The second study further examined these phenotypes in two generations of adult (28 week) offspring. Parental exercise did not influence offspring body mass or glucose tolerance in 28 week-old offspring, though F1 EX females had higher baseline glucose. Additionally, while some differences in skeletal muscle gene expression were observed, the effect of parental exercise on offspring was blunted at 28 compared to 8 weeks of age. The third study further examined the effects of parental exercise in skeletal muscle as well as adipose and hepatic tissue with regards to metabolite content and gene expression. Exercise ancestry did not affect offspring skeletal muscle or liver triglyceride or glycogen content. Further, there were no effects of exercise ancestry on gene expression levels of glycogen- or triglyceride-related enzymes in skeletal muscle, liver, or adipose tissue. Overall, these studies suggest no adverse effects of parental exercise on metabolic health in multiple generations of mouse offspring.