Related Experiment Video

Updated: May 14, 2026

Lumped-Parameter and Finite Element Modeling of Heart Failure with Preserved Ejection Fraction
09:20

Lumped-Parameter and Finite Element Modeling of Heart Failure with Preserved Ejection Fraction

Published on: February 13, 2021

A Translational Model of MASLD-Associated HFpEF Defines Mitochondrial Dysfunction and Cardiac Plasticity During

Souradipta Ganguly1,2, Betul Gunes2, Yusu Gu2

  • 1Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.

Biorxiv : the Preprint Server for Biology
|May 13, 2026
PubMed

Insights

Metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (MASH) drive heart failure with preserved ejection fraction (HFpEF). Reversing diet improved liver and heart function, revealing mitochondrial dysfunction as a key mediator.

Area of Science:

  • Cardiovascular Medicine
  • Hepatology
  • Mitochondrial Biology

Background:

  • Metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form, MASH, are linked to heart failure with preserved ejection fraction (HFpEF).
  • Mechanisms and reversibility of MASLD-associated HFpEF are poorly understood due to a lack of robust preclinical models.
  • The liver and heart are rarely studied as a coordinated system in MASLD/MASH-associated HFpEF.

Purpose of the Study:

  • To establish a translational preclinical model of MASLD-associated HFpEF.
  • To define the mechanisms underlying cardiac dysfunction and its reversibility in MASLD/MASH.
  • To investigate the liver-heart axis in the context of metabolic dysfunction.

Main Methods:

  • Utilized *Alms1*-/- (Foz/Foz) mice fed a Western diet to induce MASH and HFpEF.
  • Assessed cardiac function via echocardiography, invasive hemodynamics, and cardiomyocyte contractility.
  • Analyzed left ventricular transcriptomes and utilized electron microscopy for mechanistic insights.

Main Results:

  • Foz/Foz mice on Western diet developed MASH, advanced liver fibrosis, and HFpEF with preserved ejection fraction.
  • Liver fibrosis strongly predicted cardiac dysfunction.
  • Dietary reversal normalized liver and cardiac function, improving survival and demonstrating liver-heart axis plasticity.
  • Transcriptomic and ultrastructural analyses revealed coordinated mitochondrial dysfunction and extracellular matrix remodeling in the left ventricle.

Conclusions:

  • Mitochondrial dysfunction and fibroinflammatory remodeling are central mediators of MASLD-associated HFpEF.
  • Dietary intervention can reverse hepatic and cardiac phenotypes, highlighting the liver-heart axis's plasticity.
  • The Foz/Foz model serves as a robust platform for mechanistic and therapeutic discovery targeting MASLD-associated HFpEF.
Keywords:
Disease RegressionHFpEFLV DysfunctionLifestyle ModificationLiver-Heart AxisMASHMetabolic Dysfunction associated steatotic liver disease (MASLD)

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