Increased α-HB links colorectal cancer and diabetes by potentiating NF-κB signaling.
Mol Metab
; 75: 101766, 2023 09.
Article
em En
| MEDLINE
| ID: mdl-37406987
ABSTRACT
Sufficient evidence has linked many different types of cancers and T2D through shared risk factors; however, the underlying mechanisms are not fully understood. α-Hydroxybutyrate (α-HB), a byproduct metabolite increased in diabetes and cancer, including colorectal cancer (CRC), triggers lactate dehydrogenase A (LDHA) nuclear translocation. Nuclear LDHA markedly extends NF-κB nuclear retention by interacting with phosphorylated p65, leading to an increase in TNF-α production, impaired insulin secretion and the exacerbation of azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced CRC and high-fat diet (HFD)-induced type 2 diabetes. Furthermore, metformin interrupted this process by inhibiting the transcription of FOXM1 and c-MYC, the resultant downregulation of LDHA expression and α-HB-induced LDHA nuclear translocation. Thus, the results reveal the elevated α-HB level could be a novel shared risk factor of linking CRC, diabetes and the use of metformin treatment, as well as highlight the importance of preventing NF-κB activation for protecting against cancer and diabetes.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
/
Diabetes Mellitus Tipo 2
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Mol Metab
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China