Fatty Acid Oxidation Disorders & Body Weight Regulation

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DESCRIPTION (provided by applicant): This application proposes a training program to transition Melanie B. Gillingham, PhD from a post-doctoral to a faculty position and independent clinical investigator. Dr. Gillingham is completing her fourth year of post-doctoral training in Medical and Molecular Genetics at OHSU. She has accepted an position as an assistant professor in the graduate Clinical Nutrition program, Division of Endocrinology, Diabetes and Clinical Nutrition. The primary goal of this program will be for Dr. Gillingham to achieve independence as a clinical investigator in all respects. The mentored career development plan consists of a two-tiered approach: a focused didactic and experitential learning program in a new area of interest and a mentored clinical research experiance. The learning program will consist of didactic training in neuroendocrine body weight regulation and stable isotope techniques and learning a new laboratory method, isotope ratio mass spectroscopy (IRMS) under the direction of Dr. Dale Schoeller at the University of Wisconsin-Madison. The mentored research will be conduced under the direction of Jonathan Purnell, MD and Cary O. Harding, MD. The goal of the research is to investigate the effects of fatty acid oxidation (FAO) on body composition and weight regulation using the following long-chain FAO disorders as models: inherited deficiency of trifunctional protein and very long-chain acyl-CoA dehydrogenase. Fatty acid beta-oxidation is an important regulatory element in the regulation of food intake and body weight, as well as in the expression of insulin resistance and dyslipidemia. Children with long-chain FAO disorders lack an ability to oxidize fatty acids for energy. They have elevated de novo lipogenesis, and increased body fat. Ectopic fat deposition in the liver and muscle is closely associated with insulin resistance and cardiovascular disease, but the relationship between fatty acid oxidation, energy balance and ectopic fat deposition is not fully understood. We propose to study the regulation of body composition and macronutrient metabolism in children with long-chain FAO disorders compared to normal controls. We also propose to determine the effects of an increased protein, low fat diet on body composition in children with long-chain FAO disorders. Results from these studies will enhance our understanding of the role of FAO in body composition and insulin resistance, and may provide a new dietary treatment to prevent obesity in children with long-chain FAO disorders.