BDH1 overexpression alleviates diabetic cardiomyopathy through inhibiting H3K9bhb-mediated transcriptional activation of LCN2.

ABSTRACT:

Background

Diabetic cardiomyopathy (DbCM) is one of the common complications in diabetic patients, but there is no effective treatment for it up to now. Ketone bodies such as β-OHB have been widely reported to be beneficial for metabolic diseases including various diabetic complications. However, the role of ketone metabolism, especially the relevant enzymes, in the pathogenesis of DbCM is poorly understood.

Methods and results

In this study, we firstly observed BDH1, the rate-limiting enzyme of ketone metabolism, was markedly diminished in cardiac tissues from db/db mice and diabetic patients, as well as in H9C2 cells treated with palmitic acid. Genetic deletion of BDH1 aggravated, whereas AAV-mediated BDH1 overexpression attenuated, the diastolic dysfunction and pathogenic

SUBMITTER: Xu BT 

PROVIDER: S-EPMC11871690 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature