Leptin and heart failure: the chicken or the egg?

Area of Science:

• Cardiology
• Endocrinology
• Metabolic Syndrome

Background:

• Leptin, a hormone regulating appetite and metabolism, exhibits a complex, dual role in heart failure (HF).
• Its function varies significantly between HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF).
• Understanding these distinct roles is crucial for developing targeted therapeutic strategies.

Purpose of the Study:

• To elucidate the differential roles of leptin in HFpEF and HFrEF.
• To explore the potential therapeutic implications of targeting leptin signaling in various HF subtypes.
• To emphasize the need for individualized treatment approaches based on HF pathophysiology.

Main Methods:

• Review and synthesis of existing literature on leptin's involvement in cardiovascular disease.
• Analysis of leptin's mechanistic pathways in HFpEF, including inflammation, metabolic dysfunction, and cardiac remodeling.
• Comparative analysis of leptin's role as a primary driver in HFpEF versus a secondary exacerbating factor in HFrEF.

Main Results:

• In HFpEF, chronic hyperleptinemia is a key driver, linked to obesity and metabolic dysfunction, promoting inflammation, arterial stiffness, and diastolic dysfunction.
• In HFrEF, elevated leptin is a consequence of cardiac dysfunction and inflammation, amplifying adverse neurohormonal activation and remodeling.
• Interventions like weight loss and specific medications show promise in HFpEF by mitigating hyperleptinemia.

Conclusions:

• Leptin acts as an initiator in HFpEF and an exacerbator in HFrEF, necessitating distinct therapeutic strategies.
• Targeting leptin signaling warrants investigation, particularly in cardiometabolic HFpEF.
• Integrated treatment addressing both metabolic and cardiovascular aspects is key to improving outcomes in all HF patients.