Berberine improves dietary-induced cardiac remodeling by upregulating Kruppel-like factor 4-dependent mitochondrial...

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Obesity Research

Background:

• Berberine demonstrates cardioprotective effects, particularly in obesity-associated cardiomyopathy.
• The precise molecular mechanisms underlying berberine's benefits in cardiac remodeling remain incompletely understood.
• Kruppel-like factor 4 (KLF4) is a key transcription factor implicated in various cardiac injuries.

Purpose of the Study:

• To investigate whether KLF4 mediates the cardioprotective effects of berberine in a mouse model of diet-induced obesity.
• To elucidate the role of KLF4 in berberine's impact on cardiac structure, function, and mitochondrial health.

Main Methods:

• Diet-induced obese mice were administered berberine, with or without lentivirus-mediated KLF4 knockdown.
• Cardiac function, structure, fibrosis, inflammation, oxidative stress, and mitochondrial parameters were assessed.
• Molecular analyses were performed to evaluate KLF4 expression and its downstream effects.

Main Results:

• Berberine administration significantly increased cardiac KLF4 levels, correlating with improved cardiac function.
• KLF4 knockdown abolished berberine's protective effects, exacerbating cardiac hypertrophy, fibrosis, inflammation, and oxidative stress.
• Berberine enhanced mitochondrial biogenesis and activity, effects that were diminished by KLF4 silencing.

Conclusions:

• Berberine confers cardioprotection against diet-induced obesity by modulating cardiac KLF4 signaling.
• Cardiac KLF4 is essential for berberine's ability to improve mitochondrial function and prevent cardiac remodeling.
• KLF4 represents a potential therapeutic target for managing obesity-related cardiac complications.