Urolithin A Attenuates Diabetes-Associated Cognitive Impairment by Ameliorating Intestinal Barrier Dysfunction via N-glycan Biosynthesis Pathway.
Mol Nutr Food Res
; 66(9): e2100863, 2022 05.
Article
em En
| MEDLINE
| ID: mdl-35184377
ABSTRACT
SCOPE This study aims to investigate the effect of Urolithin A (UA) on diabetes-associated cognitive impairment in type 2 diabetes mellitus (T2DM) mouse model induced by high-fat diet (HFD) and streptozotocin (STZ). METHODS AND RESULTS:
The UA-treated T2DM mice display an attenuated cognitive impairment as well as reduced levels of metabolic endotoxemia and proinflammatory cytokines in serum. A systemic restraint of gut/brain inflammation in UA-treated T2DM mice is also observed as the downregulation of TLR4 and Myd88 in colon along with the inhibition of GFAP, Iba-1, NLRP3, and inflammation-related genes in brain. Moreover, UA ameliorates gut barrier dysfunction by upregulating tight-junction proteins levels. Furthermore, UA restores the hyperglycemia-mediated downregulation of genes involved in N-glycan biosynthesis both in vivo and in vitro, which plays a crucial role in barrier integrity. Although UA shares similar beneficial effects on diabetes with metformin, unlike metformin, the effect of UA is independent of gut microbiome and short chain fatty acids. Taken together, these data suggest that feeding UA can attenuate diabetes-associated cognitive impairment by ameliorating systemic inflammation and intestinal barrier dysfunction via N-glycan biosynthesis pathway. The study implies UA as a potential novel pharmaceutic target for diabetes therapy via manipulating gut-brain axis and N-glycan metabolism.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Diabetes Mellitus Tipo 2
/
Disfunção Cognitiva
/
Enteropatias
/
Metformina
Tipo de estudo:
Etiology_studies
/
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Mol Nutr Food Res
Ano de publicação:
2022
Tipo de documento:
Article