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

• DOI: 10.1038/s41467-018-07176-z
• Publication Date: 2018-11-06T11:39:16Z
• Authors: Kamil Gotfryd; Andreia Filipa Mósca; Julie Winkel Missel; Sigurd Friis True...; Kaituo Wang; Mariana Spulber; Simon Krabbe; Claus Hélix-Nielsen; Umberto Laforenza; Graça Soveral; Per Amstrup Pedersen; Pontus Gourdon
• Keywords: Glycerol; Male; 0301 basic medicine; 570; Principal Component Analysis; Science; Q; 610; Hydrogen-Ion Concentration; Middle Aged; Molecular Dynamics Simulation; Aquaporins; Article; 03 medical and health sciences; Adipose Tissue; Adipocytes; Humans; Female; /dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being; name=SDG 3 - Good Health and Well-being; Ion Channel Gating; Aged

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 increased release stimulation of aquaglyceroporin AQP10. The crystal structure AQP10 determined at 2.3 Å resolution unveils molecular basis for modulation-an exceptionally wide selectivity (ar/R) filter unique cytoplasmic gate. Structural functional (in vitro vivo) analyses disclose glycerol-specific pH-dependence pinpoint pore-lining His80 as pH-sensor. Molecular dynamics simulations indicate how gate opening achieved. These findings unravel type aquaporin regulation important controlling body fat mass. Thus, targeting induce constitutive secretion may offer an attractive option treating obesity related complications.