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The Capital Region of Denmark - a part of Copenhagen University Hospital
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Gamma-Aminobutyric Acid Signaling in Brown Adipose Tissue Promotes Systemic Metabolic Derangement in Obesity

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  1. ERG Controls B Cell Development by Promoting Igh V-to-DJ Recombination

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  2. Single mRNP Analysis Reveals that Small Cytoplasmic mRNP Granules Represent mRNA Singletons

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  3. De Novo Sequence and Copy Number Variants Are Strongly Associated with Tourette Disorder and Implicate Cell Polarity in Pathogenesis

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  4. Nodal Signaling Regulates Germ Cell Development and Establishment of Seminiferous Cords in the Human Fetal Testis

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  5. Differences in Cell Cycle Status Underlie Transcriptional Heterogeneity in the HSC Compartment

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  1. Proteomics-Based Comparative Mapping of the Secretomes of Human Brown and White Adipocytes Reveals EPDR1 as a Novel Batokine

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  2. Sex influences DNA methylation and gene expression in human skeletal muscle myoblasts and myotubes

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  3. Adipogenesis in Primary Cell Culture

    Research output: Chapter in Book/Report/Conference proceedingBook chapterResearchpeer-review

  4. Local recurrence rate in a national Danish patient cohort after curative treatment for rectal cancer

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Brown adipose tissue (BAT) is a metabolically active organ that contributes to the maintenance of systemic metabolism. The sympathetic nervous system plays important roles in the homeostasis of BAT and promotes its browning and activation. However, the role of other neurotransmitters in BAT homeostasis remains largely unknown. Our metabolomic analyses reveal that gamma-aminobutyric acid (GABA) levels are increased in the interscapular BAT of mice with dietary obesity. We also found a significant increase in GABA-type B receptor subunit 1 (GABA-BR1) in the cell membranes of brown adipocytes of dietary obese mice. When administered to obese mice, GABA induces BAT dysfunction together with systemic metabolic disorder. Conversely, the genetic inactivation or inhibition of GABA-BR1 leads to the re-browning of BAT under conditions of metabolic stress and ameliorated systemic glucose intolerance. These results indicate that the constitutive activation of GABA/GABA-BR1 signaling in obesity promotes BAT dysfunction and systemic metabolic derangement.

Original languageEnglish
JournalCell Reports
Volume24
Issue number11
Pages (from-to)2827-2837.e5
DOIs
Publication statusPublished - 11 Sep 2018

ID: 56585794