Long-Term Impact of Western Diet on Right Ventricular Transcriptome: Uncovering Sex-Specific Patterns in C57BL/6J Mice

The Western diet (WD) has been linked to various structural and functional alterations in the left ventricle (LV), but the molecular response of the right ventricle (RV) remains largely unknown. Given the RV's distinct anatomical and functional characteristics, it is crucial to understand how long-term WD exposure affects RV gene expression, especially in a sex-specific context. Our objective was to perform gene expression profiling of the RV late responses to WD in wild-type mice. Male and female C57BL/6J mice were fed a WD for 125 days from 300 to 425 days of age, and RV tissues were collected at 530 and 640/750 (female/male) days. mRNA sequencing was performed on RV tissues to identify differentially expressed genes (DEGs) between WD-fed and normal diet (ND)-fed groups. Data processing and analysis were conducted using the STAR aligner and DESeq2. WD-induced RV transcriptomic changes were characterized by differential expression of genes associated with cardiac remodeling and transcriptional regulation in both sexes. In females, additional genes showing altered expression were associated with immune response, whereas in males, changes were more limited, primarily involving genes related to circadian rhythm and cardiac remodeling. Echocardiography revealed modest, sex-specific differences: WD-fed females showed a decrease in right-ventricular internal diameter in diastole and a trend toward increased pulmonary trunk diameter, whereas males showed no notable changes. These exploratory results suggest that WD is associated with modest transcriptomic changes in the RV in both sexes, with only minor structural differences observed in females, indicating subtle sex-specific effects after a switch to normal chow.