Diet, exercise and disease
Our clinical and animal projects are closely interrelated in that we attempt to understand our human findings by studying cellular mechanisms in animal models of common cardiac diseases, including diabetes and heart failure. We use magnetic resonance (MR) techniques with biochemical, physiological and molecular techniques to detect energetic and functional changes in heart and skeletal muscle and determine whether interventions, such as diet and exercise, reverse the abnormalities.
We work in the Department of Physiology, Anatomy and Genetics and at the Oxford Centre for Clinical Magnetic Resonance Research (OCMR) at the John Radcliffe Hospital.
Insulin resistance and abnormal cardiac and skeletal muscle energetics are found in heart failure patients and, we propose, reflect the same underlying pathogenic mechanism: energy substrate depletion. Our patient studies define the links between insulin resistance, abnormal muscle function and energetics. We use methods that are known to decrease insulin resistance, such as exercise, to determine whether heart and/or skeletal muscle function and/or energetics improve. In our animal studies we study the chronically failing rat heart, and mice with defined mutations, to determine the impact of each mutation on cardiac energetics, contractile function and efficiency. We believe that the transition to failure involves changes in fatty acid oxidation, nuclear transcription factors, mitochondrial uncoupling, ATP synthesis and glycolysis, with energy substrate depletion the outcome.
My own research is focussed on the effect on physical performance and cognitive function of mild ketosis. During periods of stress, elevated catecholamines, steroids and cytokines increase the metabolism of stored fat in the body. The increase in circulating free fatty acids causes insulin resistance, decreases skeletal and cardiac muscular efficiency and may decrease metabolic fuel for the brain, which cannot metabolize fat, but can metabolize ketones. Ketone bodies contain more recoverable metabolic energy than fatty acids and yield 28% more energy on combustion than glucose. We are testing whether the negative effects of elevated free fatty acids can be overcome by mild ketosis using a diet containing ketone bodies. We are also testing the metabolic mechanism underlying the effects of the ketone body diet on exercise. Endurance and cognitive function, tested in rats using treadmill exercise and a maze test, respectively, were found to be increased by the ketosis. We have further tested the ketone diet during endurance exercise, in a blinded placebo-controlled cross-over studies of rowing and cycling in elite athletes. Exercise, cognitive function and skeletal and cardiac muscle energetics were followed using non-invasive MRI of brain and muscle during exercise. The diet can also be used to treat metabolic diseases, such as obesity, Alzheimer’s and Parkinson’s diseases. Such studies have started recently.
For further information on the separate areas of research covered within CMRG, please use the following links: