PROJECT SUMMARY/ABSTRACT – Overview: The overarching goal of the UTSW NORC is to enhance research efforts in nutrition and obesity by facilitating interdisciplinary interactions to speed translation of basic scientific discoveries into clinically relevant interventions in humans that improve public health. We have assembled a highly interactive and collaborative interdisciplinary team of investigators at UT Southwestern that harnesses expertise from diverse disciplines, with a goal of defining the behavioral, metabolic, genetic, and molecular mechanisms contributing to obesity and obesity-induced disease. The UTSW NORC research base consists of 158 investigators from 27 different Departments. These investigators have 230 extramurally funded nutrition/obesity-related research grants that total more than $74 million/yr in direct costs. To facilitate interdisciplinary research and the exchange of ideas, our NORC has created the following thematically related Teams: Team 1: Central Regulation of Energy Metabolism; Team 2: Adipocyte Biology and Energy Metabolism; Team 3: Obesity-induced Peripheral Organ Disease; and Team 4: Nutrition, Obesity, and Cancer. Within each team, we have integrated scientists from a wide spectrum of disciplines to comprehensively address the biochemical, metabolic, and clinical consequences of obesity and related diseases. Each Team has a mixture of senior, mid-level, and junior scientists, which will enhance the development of junior scientists and increase the likelihood of successful collaborations. The P&F program will support four new investigators/year who will also be assigned to one of the four research Teams. To support our research efforts, we have established four cores and a Clinical Element to provide state-of- the art services that exceed the capabilities, availability and/or budgets of individual NORC investigators. The Animal Phenotyping/Metabolism Core provides an extensive array of blood metabolites and hormones, 50+ metabolic cages, telemetry measurements of blood pressure, heart rate, core body temperature, and activity, multiple imaging modalities to characterize fat distribution, and hyperinsulinemic-euglycemic clamps and primary cell isolation. The Lipid Mass Spectrometry Core provides comprehensive quantification of lipids in cells, tissues, and blood. The Quantitative Metabolism and Imaging Core provides sophisticated flux measurements of metabolic pathways in vivo and 1H imaging and spectroscopy to characterize skeletal muscle and liver lipid content in humans. The Genetics, Single Cell Sequencing & RNA seq core provides exome sequencing and gene expression and analysis. All cores provide services for animal and human research, supporting the ability to translate findings more rapidly from animal models into testable hypothesis in humans. The UTSW NORC provides an important mechanism for a large group of diverse investigators to coalesce and focus their research efforts related to nutrition and ...