Linking Fatty Acid Metabolism to Diabetic Cardiomyopathy: The Role of Mitochondrial Dysfunction and Immune Microenvironment Alterations, a Bioinformatics Approach

Abstract Background Diabetic cardiomyopathy (DCM) stands as a prevalent cardiovascular complication of diabetes and a primary contributor to mortality among diabetic patients. The pathogenesis of DCM is intricately linked to both fatty acid metabolism (Facm) and immune-inflammation; however, the interplay between these factors in the context of DCM remains a subject of ongoing inquiry. This study seeks to delineate the unique contributions of fatty acid metabolism and the immune microenvironment, as well as their interconnectedness in the progression of DCM, utilizing bioinformatics methodologies. Methods The RNA expression dataset for DCM was acquired from the NCBI GEO database. Following data preprocessing, differentially expressed genes (DEGs) between the DCM and control group were identified and overlapped with genes related to fatty acid metabolism genes (Facms). The CIBERSORT algorithm was employed to assess immune infiltration within the cardiac tissue. Finally, validation analysis was carried out using animal and cell models. A mice DCM models was developed to authenticate the expression of hub FacmDEGs and their correlation with cardiac function. Results Five hub FacmDEGs (Acot2, Eci1, Ehhadh, Acaa2 and Hadha) were identified as closely linked to DCM. Despite the absence of significant differences in immune cell infiltration demonstrated between the DCM and control (CON) groups in myocardial tissue, the results of immune infiltration analysis revealed a close association of the five hub FacmDEGs with immune cells, especially Th1 Cells and DC Active cell. In the animal and cell experiment, the expression of Acot2 and Eci1 were found to be in accordance with the results of the bioinformatics analysis. Furthermore, the up-regulation of Acot2 and Eci1 was distinctly associated with mitochondrial dysfunction and cardiac dysfunction. Conclusions This study has unveiled the complicated interaction between fatty acid metabolism and the immune microenvironment in DCM through the lens of mitochondrial dysfunction, providing novel insights into the underlying pathogenesis of DCM and opening avenues for exploring new targets for pharmacological interventions.