Jorge Calles-Escandon, M.D., (PI) is a graduate from the National University of Mexico who received training at Yale University and at the University of Vermont in metabolism and nutrition. He is strongly committed to nutrition research. His personal interest is the investigation of determinants of energy metabolism in man, using as models the closely related syndromes of obesity and Type II diabetes. This proposal will study the role of substrate cycles in regulation of energy metabolism, as well as their contribution to the distorted rates of energy metabolism of obesity and Type II diabetes. The underlying hypothesis is that either the magnitude and/or the regulation of substrate cycles will explain the absolute basal high rates of energy expenditure in the obese and diabetic states. We plan to measure substrate cycles for the glucose and lipid systems, involving thus 2 key insulin sensitive organs: the liver and the adipose tissue.l The project will encompass a comprehensive approach that will include state of the art techniques for: 1) energy metabolism (indirect calorimetry),k 2) tracer methodology (stable and radioactive isotopes) and, 3) physiological perturbations. Thermodynamically, substrate cycles operate at a low level in basal conditions, thus we will not limit our observations to the resting non- stimulated state but will also examine the response of the cycles under metabolic challenges: a) glucagon infusion,l b) epinephrine administration, and c) combination of glucagon and epinephrine. A detailed topographic characterization of our volunteers will let us define the importance of intra-abdominal fat as a correlate of distorted energy and fuel metabolism. This particular issue will help clarify discordant data in the literature regarding energy expenditure and metabolic abnormalities among obese patients. These studies will help to understand the basic mechanisms of the obese state and will provide insight into possible biochemical abnormalities that help explain the link between obesity and Type II diabetes. All the studies will be carried out at the Clinical Research Center of the University of Vermont. The Metabolic Unit is recognized as a leader group in obesity research. The environment is highly conductive to research, with interaction among the several members of the Unit as well as with close links with other departments. Techniques available include, among others, state of the art method to measure energy expenditure and the Biomedical Mass Spectrometry facility that enables the application of sophisticated stable isotope techniques to metabolic research in human beings.
