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May 14, 2026Physiology

Mineralocorticoid receptor blockade prevents cardiac metabolic remodeling in obese Ossabaw swine

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Why the study?

Whether mineralocorticoid receptor signaling contributes to altered cardiac metabolism and metabolic inflexibility in obesity is unclear.

Does spironolactone improve cardiac glucose uptake and prevent cardiac metabolic remodeling in obese Ossabaw swine?

Population

Lean and obese Ossabaw swine

Comparison

Obese swine treated with spironolactone (25 mg/d) vs untreated obese swine vs lean swine

Design

Preclinical animal study

Key result

Chronic mineralocorticoid receptor blockade with spironolactone prevented the reduction in myocardial glucose uptake and metabolic remodeling in obese Ossabaw swine.

Authors

SBS.B. BenderRLRachel Lopez‐SchenkCBChastidy Bailey

Discussion

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Overview

Whether MR signaling drives cardiac metabolic inflexibility in obesity remains unclear; this leaves open whether MR antagonists could restore myocardial glucose oxidation.

Key Points

  • The study aims to determine if mineralocorticoid receptor blockade with spironolactone can improve cardiac metabolism in obese Ossabaw swine.
  • Used lean swine, obese swine on a high-fat, high-fructose diet, and obese swine treated with spironolactone (25 mg/d).
  • Assessed myocardial glucose delivery during hypoxemic coronary vasodilation with an extracorporeal perfusion system.
  • Conducted myocardial metabolomic analysis and cardiac RNA sequencing to evaluate metabolic and transcriptomic changes.
  • In obese swine, myocardial glucose uptake was significantly reduced compared to lean swine, but spironolactone treatment prevented this reduction.
  • Metabolomic analysis indicated pronounced remodeling in obese hearts, notably in phenylalanine, tyrosine, and tryptophan biosynthesis; spironolactone largely prevented such alterations.
  • Cardiac RNA sequencing revealed reduced cholesterol biosynthesis and glycation signaling in obese hearts, which were normalized by MR blockade.

Structured PICO

Does spironolactone improve cardiac glucose uptake and prevent cardiac metabolic remodeling in obese Ossabaw swine?

P
Population
Ossabaw swine model including lean swine and obese swine fed a high-fat, high-fructose diet
I
Intervention
Spironolactone 25 mg/d
C
Comparator
Untreated obese swine and lean swine
O
Outcome
Myocardial glucose uptake during hypoxemic coronary vasodilationsurrogate

In an obese swine model, mineralocorticoid receptor blockade with spironolactone prevents cardiac metabolic inflexibility and transcriptomic changes associated with cardiomyopathy.

Cite This Study

Bender et al. (2026) studied Obesity-associated cardiac metabolic remodeling. Spironolactone vs. Lean swine and untreated obese swine was evaluated on Myocardial glucose uptake and metabolic remodeling. Chronic mineralocorticoid receptor blockade with spironolactone prevented the reduction in myocardial glucose uptake and metabolic remodeling in obese Ossabaw swine.

synapsesocial.com/papers/6a05684ea550a87e60a20c03https://doi.org/10.1152/physiol.2026.41.s1.2346592
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