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White, Andrew

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White

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Andrew

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White, Andrew

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2013 - 20173

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Author's Publications: search.filters.isAuthorOfPublication.d59d7c0e-0afd-4d19-b074-546290f66496

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Now showing 1 - 3 of 3
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    Anatomical Localization, Gene Expression Profiling, and Functional Characterization of Adult Human Neck Brown Fat
    (2013) Cypess, Aaron; White, Andrew; Vernochet, Cecile; Schulz, Tim J.; Xue, Ruidan; Sass, Christina A.; Huang, Tian Liang; Roberts-Toler, Carla; Weiner, Lauren S.; Sze, Cathy; Chacko, Aron T.; Deschamps, Laura N.; Herder, Lindsay M.; Truchan, Nathan; Glasgow, Allison L.; Holman, Ashley R.; Gavrila, Alina; Hasselgren, Per-Olof; Mori, Marcelo A.; Molla, Michael; Tseng, Yu-Hua
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    Clonal analyses and gene profiling identify genetic biomarkers of human brown and white preadipocyte thermogenic potential
    (2015) Xue, Ruidan; Lynes, Matthew; Dreyfuss, Jonathan M.; Shamsi, Farnaz; Schulz, Tim J.; Zhang, Hongbin; Huang, Tian Lian; Townsend, Kristy L.; Li, Yiming; Takahashi, Hirokazu; Weiner, Lauren S.; White, Andrew; Lynes, Maureen S.; Rubin, Lee; Goodyear, Laurie; Cypess, Aaron M.; Tseng, Yu-Hua
    Targeting brown adipose tissue (BAT) content or activity has therapeutic potential for treating obesity and the metabolic syndrome by increasing energy expenditure. Both inter- and intra-individual differences contribute to heterogeneity in human BAT and potentially to differential thermogenic capacity in human populations. Here, we demonstrated the generated clones of brown and white preadipocytes from human neck fat of four individuals and characterized their adipogenic differentiation and thermogenic function. Combining an uncoupling protein 1(UCP1) reporter system and expression profiling, we defined novel sets of gene signatures in human preadipocytes that could predict the thermogenic potential of the cells once they were maturated in culture. Knocking out the positive UCP1 regulators identified by this approach, PREX1 and EDNRB in brown preadipocytes using CRISPR/Cas9 markedly abolished the high level of UCP1 in brown adipocytes differentiated from the preadipocytes. Finally, we were able to prospectively isolate adipose progenitors with great thermogenic potential using cell surface marker CD29. These data provide new insights into the cellular heterogeneity in human fat and offer the identification of possible biomarkers of thermogenically competent preadipocytes.
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    Optical visualisation of thermogenesis in stimulated single-cell brown adipocytes
    (Nature Publishing Group UK, 2017) Kriszt, Rókus; Arai, Satoshi; Itoh, Hideki; Lee, Michelle H.; Goralczyk, Anna G.; Ang, Xiu Min; Cypess, Aaron M.; White, Andrew; Shamsi, Farnaz; Xue, Ruidan; Lee, Jung Yeol; Lee, Sung-Chan; Hou, Yanyan; Kitaguchi, Tetsuya; Sudhaharan, Thankiah; Ishiwata, Shin’ichi; Lane, E. Birgitte; Chang, Young-Tae; Tseng, Yu-Hua; Suzuki, Madoka; Raghunath, Michael
    The identification of brown adipose deposits in adults has led to significant interest in targeting this metabolically active tissue for treatment of obesity and diabetes. Improved methods for the direct measurement of heat production as the signature function of brown adipocytes (BAs), particularly at the single cell level, would be of substantial benefit to these ongoing efforts. Here, we report the first application of a small molecule-type thermosensitive fluorescent dye, ERthermAC, to monitor thermogenesis in BAs derived from murine brown fat precursors and in human brown fat cells differentiated from human neck brown preadipocytes. ERthermAC accumulated in the endoplasmic reticulum of BAs and displayed a marked change in fluorescence intensity in response to adrenergic stimulation of cells, which corresponded to temperature change. ERthermAC fluorescence intensity profiles were congruent with mitochondrial depolarisation events visualised by the JC-1 probe. Moreover, the averaged fluorescence intensity changes across a population of cells correlated well with dynamic changes such as thermal power, oxygen consumption, and extracellular acidification rates. These findings suggest ERthermAC as a promising new tool for studying thermogenic function in brown adipocytes of both murine and human origins.