Autophagic control of cardiac steatosis through FGF21 in obesity-associated cardiomyopathy

Area of Science:

• Cardiovascular Biology
• Metabolic Disease Research
• Molecular Mechanisms of Cardiac Dysfunction

Background:

• High-fat diet-induced obesity is linked to cardiac hypertrophy and heart failure via unclear molecular pathways.
• Fibroblast growth factor-21 (FGF21), produced by the heart, offers protection against cardiac hypertrophy and oxidative stress.
• Understanding FGF21's role is crucial for addressing obesity-related cardiomyopathy.

Purpose of the Study:

• To investigate the impact of FGF21 on cardiomyopathy development in the context of obesity.
• To elucidate the molecular mechanisms by which FGF21 influences cardiac health during high-fat diet consumption.

Main Methods:

• Utilized Fgf21 knockout (Fgf21-/-) and wild-type (wt) mice fed a high-fat diet.
• Assessed cardiac hypertrophy using heart weight/tibia length ratios and echocardiography.
• Analyzed cardiomyocyte size, cardiac oxidative stress, lipid droplet accumulation (Oil-red O staining), and cardiac autophagy/lipophagy markers.

Main Results:

• Fgf21-/- mice exhibited significantly increased cardiac hypertrophy and cardiomyocyte size compared to wt mice on a high-fat diet.
• Absence of FGF21 led to elevated fatty acid oxidation, increased cardiac oxidative stress, and greater lipid droplet accumulation in the heart.
• Fgf21-/- mice displayed impaired cardiac autophagy and reduced lipophagy, indicating FGF21's role in promoting these processes.

Conclusions:

• FGF21 deficiency exacerbates susceptibility to obesity-related cardiomyopathy.
• Cardiac dysfunction in FGF21-deficient mice is associated with detrimental lipid accumulation in the heart.
• Impaired FGF21-mediated autophagy and lipophagy contribute to lipid buildup and cardiac abnormalities in diet-induced obesity.