GPAT3 deficiency alleviates insulin resistance and hepatic steatosis in a mouse model of severe congenital generalized lipodystrophy.
Hum Mol Genet
; 29(3): 432-443, 2020 02 01.
Article
em En
| MEDLINE
| ID: mdl-31873720
ABSTRACT
Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) is the most severe form of human lipodystrophy and is caused by loss-of-function mutations in the BSCL2/seipin gene. Exactly how seipin may regulate adipogenesis remains unclear. A recent study in vitro suggested that seipin may function to inhibit the activity of glycerol-3-phosphate acyltransferases (GPATs), and increased GPAT activity may be responsible for the defective adipogenesis under seipin deficiency. Here we generated Seipin-/-Gpat3-/- mice, which had mild but significant recovery of white adipose tissue mass over Seipin-/- mice. The mass of brown adipose tissue (BAT) of the Seipin-/-Gpat3-/- mice was almost completely restored to normal level. Importantly, the Seipin-/-Gpat3-/- mice showed significant improvement in liver steatosis and insulin sensitivity over Seipin-/- mice, which is attributable to the increased BAT mass and to the enhanced browning of the subcutaneous fat of the Seipin-/-Gpat3-/- mice. Together, our results establish a functional link between seipin and GPAT3 in vivo and suggest that GPAT inhibitors may have beneficial effects on BSCL2 patients.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Resistência à Insulina
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Subunidades gama da Proteína de Ligação ao GTP
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Modelos Animais de Doenças
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1-Acilglicerol-3-Fosfato O-Aciltransferase
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Adipogenia
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Lipodistrofia Generalizada Congênita
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Fígado Gorduroso
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article