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Updated: Jul 31, 2025

Author Spotlight: Exploring the Relationship Between Lipotoxicity and HFpEF
Published on: March 29, 2024
Western Diet Causes Heart Failure With Reduced Ejection Fraction and Metabolic Shifts After Diastolic Dysfunction and
Santosh K Maurya1, Andrew N Carley1, Chandan K Maurya1
1Department of Internal Medicine, Ohio State University College of Medicine, Columbus, Ohio, USA.
Abstract:
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.
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