FNDC5/Irisin inhibits pathological cardiac hypertrophy

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Endocrinology

Background:

• Cardiac hypertrophy is a significant cardiovascular disease lacking effective treatments.
• Irisin, a myokine from skeletal muscle, regulates energy metabolism and may impact cardiac function.
• Current therapeutic options for cardiac hypertrophy are limited.

Purpose of the Study:

• To investigate the role of irisin in cardiac hypertrophy.
• To explore the therapeutic potential of irisin in pressure overload-induced cardiac hypertrophy.
• To elucidate the molecular mechanisms underlying irisin's effects on cardiac hypertrophy.

Main Methods:

• In vitro studies using angiotensin II-induced cardiomyocyte hypertrophy models.
• In vivo studies using transverse aortic constriction (TAC)-induced cardiac hypertrophy in mice.
• Echocardiography to assess cardiac function.
• Western blotting to analyze protein expression and signaling pathways (AMPK, mTOR).
• Investigation of FNDC5 cleavage by ADAM family proteases.

Main Results:

• Irisin expression was elevated in hypertrophic murine hearts and serum.
• Irisin administration attenuated cardiomyocyte hypertrophy in vitro and cardiac hypertrophy and fibrosis in vivo.
• Irisin treatment improved cardiac function in TAC-induced mice.
• Irisin activates AMP-activated protein kinase (AMPK), subsequently inhibiting mammalian target of rapamycin (mTOR) signaling.
• FNDC5 cleavage into irisin is dependent on the ADAM family, particularly ADAM10.
• AMPK inhibition abolished the protective effects of irisin.

Conclusions:

• Irisin is secreted via ADAM family proteases (including ADAM10).
• Irisin treatment effectively attenuates pressure overload-induced cardiac hypertrophy and fibrosis.
• Irisin exerts protective effects by activating the AMPK-mTOR signaling pathway.
• Irisin represents a potential therapeutic agent for cardiac hypertrophy and related cardiovascular diseases.