Western Diet Causes Heart Failure With Reduced Ejection Fraction and Metabolic Shifts After Diastolic Dysfunction and Novel Cardiac Lipid Derangements

Santosh K Maurya; Andrew N Carley; Chandan K Maurya; E Douglas Lewandowski

doi:10.1016/j.jacbts.2022.10.009

Western Diet Causes Heart Failure With Reduced Ejection Fraction and Metabolic Shifts After Diastolic Dysfunction and Novel Cardiac Lipid Derangements

JACC Basic Transl Sci. 2023 Jan 25;8(4):422-435. doi: 10.1016/j.jacbts.2022.10.009. eCollection 2023 Apr.

Authors

Santosh K Maurya¹, Andrew N Carley¹, Chandan K Maurya¹, E Douglas Lewandowski¹

Affiliation

¹ Department 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.

Keywords: HFpEF; HFrEF; Western diet; metabolism; triglyceride turnover.

Abstract

Grants and funding