Energy Allocation to Adolescent Skeletal Growth: Impacts of Insulin and Physical Activity

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URL: https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37368324

Abstract

Life history theory dictates that organisms should precisely allocate investment of their limited resources, including energy, to a variety of tasks to serve natural selection’s ultimate goal: reproduction. In adolescence, menarche occurs as growth velocity is tapering off, providing direct support for a trade-off in energy allocation. However, the hormonal mechanisms regulating this trade-off are not well-delineated. Insulin, one of the body’s most potent anabolic hormones, has previously been implicated as one potential agent of life history trade-offs and its candidate role in adolescence is previously supported by empirical data demonstrating that children go through a transient period of insulin resistance during puberty that coincides with the greatest gains in linear growth. Here, we test the association between insulin and adolescent growth in three ways. In Chapter I, we utilize a natural experiment to test the role of energetic environment in regulating linear growth gains. We find positive correlations between c-peptide, a urinary biomarker of insulin, and biomarkers of bone turnover and as well as estradiol, strongly suggesting insulin promotes skeletal growth in addition to gonadal development. In Chapter II, we utilize a model organism experiment to test whether insulin sensitivity in the growth plate responds to high glycemic index feeding, finding evidence suggesting that diet-induced obesity reduces insulin sensitivity in the growth plate. In Chapter III, we explore the effects of exercise in regulating bone mineral accrual and bone fragility during adolescence by utilizing a different natural experiment: polycystic ovary syndrome (PCOS). PCOS is characterized by dysregulated insulin and is associated with poor bone outcomes in young, lean women. Here we use a retrospective analysis to demonstrate that young athletes with PCOS are less likely to suffer bone stress injuries than eumenorrheic athletes. Altogether, the results from these studies indicate that insulin influences linear skeletal growth at adolescence, insulin sensitivity in the growth plate is sensitive to diet-induced obesity, and that exercise may ameliorate the effects of PCOS on bone mineral accrual and promote bone strength.

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