Key result
Long-term Western diet reduces LVEF to ~42% vs normal diet in male mice.
Why the study?
Long-term Western Diet consumption is an established CVD risk factor, but studies on its long-term effects on CVD pathophysiology and sex-specific responses are lacking.
Does a Western diet induce sex-specific pathophysiological changes in left ventricular function and transcriptomic signatures in C57BL/6J mice?
Does a Western diet induce sex-specific pathophysiological changes in left ventricular function and transcriptomic signatures in C57BL/6J mice?
Long-term Western diet consumption induces sex-specific cardiac phenotypes in mice, causing HFrEF-like changes in males and HFpEF-like structural remodeling in females.
Answers are grounded in this paper and cite their sources.
Western diet may induce sex-specific HF phenotypes in mice; hypothesis-generating and should not yet inform clinical practice.
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.
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Stepanyan et al. (2024) studied Cardiovascular disease (n=80). Western Diet vs. Normal diet was evaluated on Left ventricular ejection fraction (LVEF) at 750 days in male mice (p=0.0005). Long-term consumption of a Western diet in male mice significantly reduced left ventricular ejection fraction to 42% compared to 60% in normal diet-fed controls at 750 days of age.
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