COBRE in Mesenchymal and Neural Regulation of Metabolic Networks - Metabolic Phenotyping Equipment

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Abstract Whole body metabolism is regulated by integration of multiple tissues, including adipose tissue, the skeleton, and bone marrow. Imbalanced regulation of these tissues leads to prevalent, chronic disorders, obesity and osteoporosis. Adipocyte precursors and osteoprogenitor cells share a common mesenchymal precursor, and are highly regulated during aging, under nutritional stress, and in temperature regulation. There is growing appreciation that the sympathetic nervous system plays a unique role in metabolic regulation in normal health and disease, although mechanisms are just starting to be uncovered. Our program goal is to define specific molecular and signaling pathways that integrate brain, bone, and adipose tissue regulation of metabolic networks. This COBRE was initiated with four projects that test complementary aspects of adipocyte and skeletal metabolic function, and their regulation by central nervous system input. Project 1 (A. Brown) studies the role of BMP signaling in brown adipogenesis and thermogenic activity, and is optimizing thermogenic capacity in human iPS-derived brown adipocytes. Project 2 (M. Reagan) addressed bone marrow adipose tissue, a depot that is regulated during osteoporosis and obesity. Dr. Reagan has graduated with her own independent R37 funding. Her project was replaced by A. Guntur, who studies mechanisms of mitophagy and cellular bioenergetics in osteoblast differentiation. Project 3 (C. Duarte) is a translational project addressing the consequences of atypical antipsychotics on bone fracture risk. Project 4 (K. Motyl) is complementary to Project 3, and uses mouse models to test the novel hypothesis that risperidone acts on the central nervous system to target bone loss directly or via activation of brown adipose tissue. Dr. Motyl will be graduating this year, as she will be receiving her first R01. Two new junior investigator recruits are in process, and COBRE unobligated funds have been set aside for these recruitments. The COBRE projects are supported by an Administrative and Professional Development Core that oversees a pilot project program. Our successful pilot project program has supported investigators who have gone on to acquire NIH funding. We also support the scientific cores: (i) Proteomics and Lipidomics Core (C. Vary), (ii) Histopathology and Histomorphometry Core (V. Lindner), and (iii) Physiology Core (C. Rosen). This administrative supplement request is for a Promethion 8 cage multiplexed metabolic and behavioral monitoring system with temperature cabinet from Sable Systems, which will enhance our current 16 cage system and address the high demand, which is causing a bottleneck in research productivity. In addition, this acquisition will allow for the implementation of a treadmill and temperature controlled studies as part of the metabolic and behavioral capacity of this core facility.