Metabolic Coordination Structures Contribute to Diabetic Myocardial Dysfunction

作者：Teng Wu, Tongsheng Huang, Honglin Ren, Conghui Shen, Qian Jiang, Xinlu Fu, Shang-Yuan Liu, Chengshu Xie, Xi Lin, Junhong Wan, Shijie Xiong, yuanjun ji, Mengying Liu, Huiting Zheng, Ting Liang, Wenyi Liu, Yan Zou, Jingwei Li, Maoquan Yang, Ze-Yi Song, Peixuan Lan, Xinghui Li, Yandi Wu, Ming Yang, Hui Li, Xuezhe Huang, Hui Chen, Jing Tan, Weibin Cai · 发表于：Circulation Research · 年份：2025 · DOI：10.1161/circresaha.124.326044 · 被引用次数：20 · 研究领域：Cardiovascular Function and Risk Factors、Peroxisome Proliferator-Activated Receptors、Mitochondrial Function and Pathology

BACKGROUND: Individuals with diabetes are susceptible to cardiac dysfunction and heart failure, potentially resulting in mortality. Metabolic disorders frequently occur in patients with diabetes, and diabetes usually leads to remodeling of heart structure and cardiac dysfunction. However, the contribution and underlying mechanisms of metabolic and structural coupling in diabetic cardiac dysfunction remain elusive. METHODS: Two mouse models of type 2 diabetes (T2DM) were used to assess alterations in glucose/lipid metabolism and cardiac structure. The potential metabolic-structural coupling molecule ACBP (acyl–coenzyme A–binding protein) was screened from 4 published datasets of T2DM-associated heart disease. In vivo loss-of-function and gain-of-function approaches were used to investigate the role of ACBP in diabetic cardiac dysfunction. The underlying mechanisms of metabolic and structural coupling were investigated by stable-isotope tracing metabolomics, coimmunoprecipitation coupled with mass spectrometry, and chromatin immunoprecipitation sequencing. RESULTS: Diabetic mouse hearts exhibit enhanced lipid metabolism and impaired ultrastructure with marked cardiac systolic and diastolic dysfunction. Analysis of 4 T2DM public datasets revealed that Acbp was a significant lipid metabolism gene whose expression was upregulated. Consistently, ACBP expression levels were markedly elevated in the hearts of patients with diabetes and diabetic mice. Moreover, we constructed cardiomy...