Dissertation Defence: Substrate Utilization in the Brain and Skeletal Muscle During Environmental and Energetic Stress in Humans

Hannah Caldwell, supervised by Dr. Phil Ainslie, will defend their dissertation titled “Substrate Utilization in the Brain and Skeletal Muscle During Environmental and Energetic Stress in Humans” in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Kinesiology.

An abstract for Hannah Caldwell’s dissertation is included below.

Examinations are open to all members of the campus community as well as the general public. Registration is not required for in person defences.

---

ABSTRACT

Metabolism describes the sum of biochemical reactions that take place within a living organism which provide energy for vital processes; this can be studied at the whole-body, organ specific, or cellular level. Energy availability, which is determined by the difference between energy intake and exercise energy expenditure, is affected by environmental and energetic stresses (e.g., high-altitude, exercise, diet/nutrition). Systemic energy deficits have implications for the regulation of organ-specific substrate utilization and function. The aim of this thesis was to integrate brain, skeletal muscle, and systemic substrate oxidation and relative fuel utilization in the context of selected environmental and energetic stress (e.g., high-altitude, exercise, nutritional caloric deficits). Study 1 addressed a fundamental question for integrative cerebrovascular physiology: How are the cerebral metabolic rates of oxygen and glucose utilization (CMRO2 and CMRGlu, respectively) affected by alterations in arterial PCO2 (PaCO2)? The results of this study indicate that cerebral oxidative metabolism (i.e., CMRO2) is altered by approximately 1 % per mmHg change in PaCO2. These changes, in part, are explained by an increased compensatory contribution of anaerobic metabolic pathways. Study 2 investigated the research question: How does systemic fuel utilization at high-altitude affect the brain inflammatory response to exercise? The results of this study provide new evidence that 6-8 days of acclimatization at 3,800 m does not provoke immune suppression or exacerbate systemic pro-inflammatory responses at rest or with maximal exercise. Further, altitude-induced alterations in systemic inflammatory responses did not translate to any uptake/release of any cytokines by the brain with maximal exercise. Study 3A showed that 14-days low energy availability (LEA) – involving effectively 50% daily caloric restriction – in endurance-trained females provokes immunological stress, systemic inflammation and impairs exercise performance. Study 3B further revealed that 14-days LEA in these same females provokes an increased reliance on fat oxidation to total energy expenditure during submaximal exercise that was independent of any changes in resting metabolic rate, insulin sensitivity, and skeletal muscle mitochondrial respiratory capacity. This dissertation advances our understanding of integrative brain, skeletal muscle, and systemic substrate oxidation and relative fuel utilization in the context of environmental and energetic stress.