Does a Western diet cause HFrEF and metabolic shifts in mice?
A Western diet in mice causes deranged cardiac lipid dynamics and slowed triglyceride turnover, leading to diastolic dysfunction and eventually HFrEF.
Western diet (WD) impairs glucose tolerance and cardiac lipid dynamics, preceding heart failure with reduced ejection fraction (HFrEF) in mice. Unlike diabetic db/db mice with high cardiac triglyceride (TG) and rapid TG turnover, WD mice had high TG but slowed turnover, reducing lipolytic PPAR⍺ activation. WD deranged cardiac TG dynamics by imbalancing synthesis and lipolysis, with low cardiac TG lipase (ATGL), low ATGL co-activator, and high ATGL inhibitory peptide. By 24 weeks of WD, hearts shifted from diastolic dysfunction to diastolic dysfunction with HFrEF with decreases in GLUT4 and exogenous glucose oxidation and elevated β-hydroxybutyrate dehydrogenase 1 without increasing ketone oxidation.
Maurya et al. (Wed,) studied this question.