Contribution of Organ Size to Adaptive Thermogenesis during Caloric Restriction

St. Luke'S-Roosevelt Inst For Hlth Scis, New York NY

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Abstract

DESCRIPTION (provided by applicant): Adaptive thermogenesis is defined as the decrease in resting energy expenditure (REE) with caloric restriction beyond that which is expected based on changes in body mass and composition. Accurate quantification of adaptive thermogenesis requires precise measurements of heterogeneous body composition components. Most commonly used models designed to predict REE group body components into fat mass and fat free mass (FFM). However, the constituents of FFM have a wide range of specific metabolic rates. For example, the metabolic rate of the kidneys and the liver are 33-fold and 15-fold higher than that of skeletal muscle. Organ size based REE prediction models are more accurate than FFM based models. Most previous weight loss studies that have investigated adaptive thermogenesis use FFM predicted energy expenditure. To date only one study has examined organ size change in short term weight loss (i.e., 3 months); it is currently unknown whether adaptive thermogenesis still exists in long term caloric restriction and weight stable conditions. Using the CALERIE dataset, it is possible for the first time to evaluate adaptive thermogenesis during long term caloric restriction both with weight loss (i.e., at year 1) and under weight stabl conditions (i.e., at year 2). In the CALERIE dataset of the Pennington Biomedical Research Center, the availability of both cellular level and tissue-organ level data related to adaptive thermogenesis allows for the translation of cellular findings to higher biological levels of organization. We will use whole body high resolution contiguous magnetic resonance imaging (MRI) to measure volumes of high-metabolic-rate organs including the brain, liver, spleen, pancreas, kidneys, heart, and digestive tracts. This accurate quantification of organ masses will allow for a more precise characterization of adaptive thermogenesis at the tissue-organ level. Furthermore, the availability of liver fat by in vivo magnetic resonance spectroscopy will allow the quantification of fat free liver mass. This is critical to warrant accurate quantification ofthe metabolically active liver mass. This study will, for the first time, unite the cellular level evidnce with the tissue-organ level evidence of adaptive thermogenesis during long term caloric restriction. The proposed analyses will answer a question put forth by many investigators in obesity and aging research - what is the contribution of the different organs and tissues to the changes in energy expenditure at a new body weight equilibrium after weight loss. The present study will uniquely make an important contribution to one of the major proposed mechanisms for the increase in lifespan with a reduction of oxidative damage. The knowledge gained will pave the way for future studies to accurately evaluate mechanisms of adaptive thermogenesis independent of organ and tissue size. This collected knowledge will contribute to developing interventions and strategies that can sustain weight loss and improve lifespan.