Article open access publication

Human adipose glycerol flux is regulated by a pH gate in AQP10

Nature Communications, Springer Nature, ISSN 2041-1723

Volume 9, 1, 2018

DOI:10.1038/s41467-018-07176-z, Dimensions: pub.1108060295, PMC: PMC6232157, PMID: 30420639,

Affiliations

Organisations

  1. (1) University of Copenhagen, grid.5254.6, KU
  2. (2) University of Lisbon, grid.9983.b
  3. (3) Technical University of Denmark, grid.5170.3, DTU
  4. (4) Aquaporin A/S, Nymøllevej 78, DK-2800, Lyngby, Denmark
  5. (5) University of Pavia, grid.8982.b
  6. (6) Lund University, grid.4514.4

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Denmark

Sweden

Portugal

Italy

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Europe

Description

Obesity is a major threat to global health and metabolically associated with glycerol homeostasis. Here we demonstrate that in human adipocytes, the decreased pH observed during lipolysis (fat burning) correlates with increased glycerol release and stimulation of aquaglyceroporin AQP10. The crystal structure of human AQP10 determined at 2.3 Å resolution unveils the molecular basis for pH modulation-an exceptionally wide selectivity (ar/R) filter and a unique cytoplasmic gate. Structural and functional (in vitro and in vivo) analyses disclose a glycerol-specific pH-dependence and pinpoint pore-lining His80 as the pH-sensor. Molecular dynamics simulations indicate how gate opening is achieved. These findings unravel a unique type of aquaporin regulation important for controlling body fat mass. Thus, targeting the cytoplasmic gate to induce constitutive glycerol secretion may offer an attractive option for treating obesity and related complications.

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NORA University Profiles

University of Copenhagen

Technical University of Denmark

Danish Open Access Indicator

2018: Realized

Research area: Science & Technology

Danish Bibliometrics Indicator

2018: Level 2

Research area: Science & Technology

Dimensions Citation Indicators

Times Cited: 21

Field Citation Ratio (FCR): 6.69

Relative Citation ratio (RCR): 1.73

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