The Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction: A Novel Framework to Explain Pathogenesis and Guide Treatment

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Hypothesis The paper proposes a novel unifying hypothesis-that heart failure with preserved ejection fraction (HFpEF) arises primarily from the expansion and dysfunctional transformation of visceral adipose tissue, leading to the secretion of altered suite of signaling molecules (adipokines), which causes systemic inflammation, plasma volume expansion, and cardiac hypertrophy and fibrosis. Elements of the framework The framework groups adipokines into 3 domains. Domain I adipokines are cardioprotective molecules but are suppressed in patients with excess adiposity. Domain II adipokines are cardioprotective molecules that are up-regulated by adiposity as a compensatory response mechanism. Domain III adipokines, whose secretion is heightened in adiposity, have proinflammatory, prohypertrophic, profibrotic, and antinatriuretic effects. HFpEF results from an adiposity-driven imbalance that promotes Domain III adipokines but suppresses Domain I adipokines, with Domain II adipokines representing an inadequate counter-regulatory response. Key lines of evidence 1) Obesity and dietary nutrient excess are the major drivers of experimental HFpEF; 2) changes in visceral adiposity and circulating adipokines are observed years before and predict the diagnosis of HFpEF (but not heart failure with a reduced ejection fraction) in the general community; 3) central obesity or visceral adiposity i

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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