Human adipose glycerol flux is regulated by a pH gate in AQP10.
Nat Commun
; 9(1): 4749, 2018 11 12.
Article
em En
| MEDLINE
| ID: mdl-30420639
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
2_ODS3
Base de dados:
MEDLINE
Assunto principal:
Tecido Adiposo
/
Aquaporinas
/
Glicerol
Limite:
Aged
/
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Nat Commun
Ano de publicação:
2018
Tipo de documento:
Article