The initial reports about human BAT distribution and lack of plasma biomarkers indicated that it would be a particularly challenging organ to study. An acute need was the precise anatomical localization of the tissue and the availability of human-derived brown and white fat progenitor cell models to understand its distinct physiology. In collaboration with Yu-Hua Tseng, my group first reported the anatomical localization of the tissue and showed that human neck BAT shared the same developmental lineage as rodent interscapular BAT, the principal model system used for more than half a century. In collaboration with C. Ronald Kahn, we identified cell surface markers of white, brown, and beige human adipocytes that could be used to isolate and study the different adipocyte lineages. In parallel, Dr. Tsengs group generated clonal cell lines from human neck fat and characterized their adipogenic differentiation and metabolic function in vitro and in vivo after transplantation into immune deficient nude mice. Using clonal analysis and gene expression profiling, we identified unique sets of gene signatures in human preadipocytes that could predict the thermogenic potential of these cells once matured in culture into adipocytes. These data highlight the cellular heterogeneity in human BAT and WAT and provide novel gene targets to prime preadipocytes for thermogenic differentiation. Additional discoveries included the demonstration that altered miRNA processing disrupts brown/white adipocyte determination and associates with lipodystrophy; HIV-infected subjects with metabolic complications demonstrate increases in FGF21 in relationship to BAT gene expression; and IRF4 is a transcriptional driver of a program of thermogenic gene expression and energy expenditure. In collaboration with Kong Chen, Acting Chief of the Energy Metabolism Section, and Peter Herscovitch, Chief of the Positron Emission Tomography Department in the CRC, we have completed the first version of an PET/CT-based atlas of human BAT known as the BATlas 1.0. Anatomical and functional information about each depot is being catalogued as part of the larger effort of understanding the function and structure of the human brown and white adipose tissue mass. We are now in the process of expanding this collaboration with Bradford Wood, Director of NIH Center for Interventional Oncology, to be able to collect ultrasound-guided biopsies of the BAT.

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4
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2018
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U.S. National Inst Diabetes/Digst/Kidney
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Lynes, Matthew D; Shamsi, Farnaz; Sustarsic, Elahu Gosney et al. (2018) Cold-Activated Lipid Dynamics in Adipose Tissue Highlights a Role for Cardiolipin in Thermogenic Metabolism. Cell Rep 24:781-790
Wankhade, Umesh D; Lee, Ji-Hyeon; Dagur, Pradeep K et al. (2018) TGF-? receptor 1 regulates progenitors that promote browning of white fat. Mol Metab 16:160-171
Baskin, Alison S; Linderman, Joyce D; Brychta, Robert J et al. (2018) Regulation of Human Adipose Tissue Activation, Gallbladder Size, and Bile Acid Metabolism by a ?3-Adrenergic Receptor Agonist. Diabetes 67:2113-2125
Ran, Chongzhao; Albrecht, Daniel S; Bredella, Miriam A et al. (2018) PET Imaging of Human Brown Adipose Tissue with the TSPO Tracer [11C]PBR28. Mol Imaging Biol 20:188-193
Lynes, Matthew D; Leiria, Luiz O; Lundh, Morten et al. (2017) Corrigendum: The cold-induced lipokine 12,13-diHOME promotes fatty acid transport into brown adipose tissue. Nat Med 23:1384
Lynes, Matthew D; Leiria, Luiz O; Lundh, Morten et al. (2017) The cold-induced lipokine 12,13-diHOME promotes fatty acid transport into brown adipose tissue. Nat Med 23:631-637
Kriszt, Rókus; Arai, Satoshi; Itoh, Hideki et al. (2017) Optical visualisation of thermogenesis in stimulated single-cell brown adipocytes. Sci Rep 7:1383
Hiraike, Yuta; Waki, Hironori; Yu, Jing et al. (2017) NFIA co-localizes with PPAR? and transcriptionally controls the brown fat gene program. Nat Cell Biol 19:1081-1092
Torriani, Martin; Srinivasa, Suman; Fitch, Kathleen V et al. (2016) Dysfunctional Subcutaneous Fat With Reduced Dicer and Brown Adipose Tissue Gene Expression in HIV-Infected Patients. J Clin Endocrinol Metab 101:1225-34
Xue, Ruidan; Lynes, Matthew D; Dreyfuss, Jonathan M et al. (2015) Clonal analyses and gene profiling identify genetic biomarkers of the thermogenic potential of human brown and white preadipocytes. Nat Med 21:760-8

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