NYMC Faculty Publications
Evaluating Sex-Specific Responses to Western Diet Across the Lifespan: Impact on Cardiac Function and Transcriptomic Signatures in C57BL/6J Mice at 530 and 640/750 Days of Age
Author Type(s)
Faculty
DOI
10.1186/s12933-024-02565-9
Journal Title
Cardiovascular Diabetology
Document Type
Article
Publication Date
12-1-2024
Department
Cell Biology and Anatomy
Keywords
Cardiovascular, Heart, RNA sequencing, Sex, Western Diet
Disciplines
Medicine and Health Sciences
Abstract
Background: Long-term consumption of Western Diet (WD) is a well-established risk factor for the development of cardiovascular disease (CVD); however, there is a paucity of studies on the long-term effects of WD on the pathophysiology of CVD and sex-specific responses. Methods: Our study aimed to investigate the sex-specific pathophysiological changes in left ventricular (LV) function using transthoracic echocardiography (ECHO) and LV tissue transcriptomics in WD-fed C57BL/6 J mice for 125 days, starting at the age of 300 through 425 days. Results: In female mice, consumption of the WD diet showed long-term effects on LV structure and possible development of HFpEF-like phenotype with compensatory cardiac structural changes later in life. In male mice, ECHO revealed the development of an HFrEF-like phenotype later in life without detectable structural alterations. The transcriptomic profile revealed a sex-associated dichotomy in LV structure and function. Specifically, at 530-day, WD-fed male mice exhibited differentially expressed genes (DEGs), which were overrepresented in pathways associated with endocrine function, signal transduction, and cardiomyopathies. At 750 days, WD-fed male mice exhibited dysregulation of several genes involved in various lipid, glucagon, and glutathione metabolic pathways. At 530 days, WD-fed female mice exhibited the most distinctive set of DEGs with an abundance of genes related to circadian rhythms. At 640 days, altered DEGs in WD-fed female mice were associated with cardiac energy metabolism and remodeling. Conclusions: Our study demonstrated distinct sex-specific and age-associated differences in cardiac structure, function, and transcriptome signature between WD-fed male and female mice.
Recommended Citation
Stepanyan, A., Brojakowska, A., Zakharyan, R., Hakobyan, S., Davitavyan, S., Sirunyan, T., Khachatryan, G., Khlgatian, M., Bisserier, M., Zhang, S., Sahoo, S., Hadri, L., Rai, A., Garikipati, V., Arakelyan, A., & Goukassian, D. (2024). Evaluating Sex-Specific Responses to Western Diet Across the Lifespan: Impact on Cardiac Function and Transcriptomic Signatures in C57BL/6J Mice at 530 and 640/750 Days of Age. Cardiovascular Diabetology, 23 (1). https://doi.org/10.1186/s12933-024-02565-9
