Metabolic Adaptations to Acute and Chronic Exercise

/Abstract Obesity is a major contributor to the development of cardiovascular diseases (CVD), including cardiomyopathy and heart failure. The cardiometabolic profile of the obese heart demonstrates an imbalance between lipid uptake and oxidation, representative of “cardiac lipotoxicity”, which is a potential culprit in the development of cardiomyopathy. While exercise training is a recommended non-pharmalogical intervention for primary and secondary prevention of both obesity and CVD, the cardiometabolic adaptations that occur in response to chronic exercise training remain elusive. There are a number of potential concerns that contribute to the inconsistencies in the literature including the time after the last exercise session that metabolism was assessed, the methodologies used to evaluate metabolism, and the exercise training protocols utilized in the studies. Furthermore, studies that specifically explore sex differences are limited. Therefore, the main objective of this project is to identify and understand the cardiometabolic adaptations in male and female mice in response to acute and chronic exercise. The proposed project will accomplish the objective through three specific aims: 1) to identify the time course of the metabolic response to acute exercise in male and female mice; 2) to identify the adaptations in cardiac substrate utilization and metabolic pathways in response to chronic treadmill running and voluntary wheel running; and 3) to evaluate the ability of exercise training to modulate cardiac metabolism in the obese heart. Within each aim, these three working hypotheses are proposed: 1) the metabolic responses to acute exercise will require greater than 24 hours to return to baseline and will exhibit sex specific differences; 2) chronic exercise training will enhance fatty acid and ketone body oxidation in an intensity dependent manner; and 3) chronic exercise training will restore the balance of lipid uptake and fatty acid oxidation and improve ketone body oxidation in obese hearts. Overall, the findings from this project have the potential to contribute to the fields of cardiac metabolism and exercise physiology as well as enhance the understanding of the role of exercise training in promoting cardiometabolic health particularly in the setting of obesity and improve the knowledge gap regarding sex as a biological variable. Furthermore, the proposed project will provide meaningful experiences in basic research to undergraduate students and allow them to be highly competitive for entry into graduate programs and medical school as well as to pursue careers in biomedical sciences. Project Number: 1R15HL177624-01A1 | Fiscal Year: 2025 | NIH Institute/Center: National Heart Lung and Blood Institute (NHLBI) | Principal Investigator: Stephen Kolwicz | Institution: URSINUS COLLEGE, COLLEGEVILLE, PA | Award Amount: $349,728 | Activity Code: R15 | Study Section: Special Emphasis Panel[ZRG1 RCCS-C (80)] View on NIH RePORTER: https://reporter.nih.gov/project-details/1R15HL17762401A1