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This study explored the role of mitochondria\u2010related gene Enoyl\u2010CoA hydratase and 3\u2010hydroxyacyl CoA dehydrogenase (EHHADH) in DCM. Mitochondria\u2010related differentially expressed genes(Mito DEGs) were screened from DCM and mitochondrial datasets. Protein\u2010protein interaction (PPI) network and CytoHubba were applied to identify hub Mito DEGs. Hub gene expression in vivo and vitro DCM models was verified by western blot and RT\u2010qPCR. H9C2 cell apoptosis was detected by Tunel and flow cytometry, lipid accumulation was clarified by oil red O staining, oxidative stress was assessed by detecting ROS, BODIPY\u2010C11 and malondialdehyde(MDA). Mitochondrial function was determined by JC\u20101 staining and ATP levels. After adding Fenofibrate(FNB), apoptosis proteins were detected by western blot. DCM genes are enriched in fatty acid metabolism pathway. EHHADH is the most critical hub gene in all hub Mito DEGs and upregulated in vivo and vitro DCM models. EHHADH knockdown aggravate high glucose and palmitic acid (HGHP)\u2010treated H9C2 cell apoptosis, oxidative stress, lipid peroxidation, and lipid accumulation, which are associated with mitochondrial functional damage. FNB promoted EHHADH expression, thereby reducing apoptosis, lipid accumulation, and mitochondrial damage in myocardial cells. EHHADH exerts a protective effect in DCM by reducing mitochondrial damage, oxidative stress, lipid accumulation, and cardiomyocyte apoptosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cbin.70212","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T10:48:19Z","timestamp":1789987699000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Potential Protective Effects of Mitochondria\u2010Related Gene EHHADH on Diabetic Cardiomyopathy"],"prefix":"10.1002","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1471-6622","authenticated-orcid":false,"given":"Han","family":"Sun","sequence":"first","affiliation":[{"name":"Qingdao Medical College Qingdao University Qingdao China"},{"name":"Department of Cardiology Yantai Yuhuangding Hospital Yantai 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