Locomotion is a key element of the lives of all animals, including human beings. Locomotor abilities (performance capacities) set limits within which normal behaviors must be accomplished, including finding food, avoiding predators, and seeking mates. Locomotor activity can be costly in terms of energy and so it can be a major component of the overall daily energy budget of an animal, with important implications for the regulation of body weight. Much of the locomotor activity that animals exhibit may be considered voluntary, yet biologists and psychologists do not understand how and why voluntary exercise varies so widely among species of animals in the wild or among individual humans. Prior NSF support was used to develop a novel mouse model for the study of voluntary exercise. More than 55 generations of selective breeding for high voluntary wheel running have produced 4 replicate High-Runner (HR) lines that run 3-fold farther per day than 4 non-selected control (C) lines. A striking result is a plateau in running performance since about generation 16, that is, a limit to selection despite continuing to select for high voluntary wheel running. This project stems from the remarkable finding that a high-fat diet (HFD) increases daily wheel-running distances of HR mice up to 75%, with little effect on C mice. Three hypotheses about the mechanisms that cause this increase in individual performance of mice at the selection limit will be tested: 1) HFD increases endurance ability of HR mice by altering components of their unique physiology; 2) HFD increases motivation for wheel running via interaction with their altered brain reward system; 3) HFD increases thermal tolerance and/or alters the thermo-regulatory set point of HR mice. Following these studies, the nutritional environment will be altered for half of the lines (2 HR and 2 C) by administering HFD from weaning through wheel testing, while the standard selection protocol is applied. This aspect of the study will provide a direct test of whether feeding a high-fat diet will make it possible to increase running performance beyond what has been observed, a cross-generational evolutionary change that will break the selection limit. Results will lead to comprehensive understanding of voluntary activity levels and will have biomedical relevance for fat dynamics and obesity, the motivational basis of voluntary exercise, and the regulation of activity levels. Animals, tissues, and data will be made available to other researchers for projects not covered in this proposal. Research will emphasize training of graduate and undergraduate students, including women and under-represented groups, and will involve collaborations with at least 6 other faculty and 3 other universities. Working with a local middle-school teacher, digital research photographs of skeletal elements will be used to develop a middle-school science lesson plan designed to illustrate methods of scientific inquiry in conjunction with fundamental evolutionary principles through inquiry-based learning.

National Science Foundation (NSF)
Division of Integrative Organismal Systems (IOS)
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William E. Zamer
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University of California Riverside
United States
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