SMUG1 regulates fat homeostasis leading to a fatty liver phenotype in mice.
DNA Repair (Amst)
; 120: 103410, 2022 12.
Article
em En
| MEDLINE
| ID: mdl-36244177
ABSTRACT
Fatty liver diseases are a major health threat across the western world, leading to cirrhosis and premature morbidity and mortality. Recently, a correlation between the base excision repair enzyme SMUG1 and metabolic homeostasis was identified. As the molecular mechanisms remain unknown, we exploited a SMUG1-knockout mouse model to gain insights into this association by characterizing the liver phenotype in young vs old SMUG1-null mice. We observed increased weight and fat content in one-year old animals, with altered activity of enzymes important for fatty acids influx and uptake. Consistently, lipidomic profiling showed accumulation of free fatty acids and triglycerides in SMUG1-null livers. Old SMUG1-knockout mice also displayed increased hepatocyte senescence and DNA damage at telomeres. Interestingly, RNA sequencing revealed widespread changes in the expression of lipid metabolic genes already in three months old animals. In summary, SMUG1 modulates fat metabolism favouring net lipogenesis and resulting in development of a fatty liver phenotype.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Uracila-DNA Glicosidase
/
Fígado Gorduroso
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article