The Role of Interventional Irisin on Heart Molecular Physiology

Abstract

Irisin, encoded by the FNDC5 (fibronectin type III domain containing 5) gene, is a novel myokine that has been implicated as an essential mediator of exercise benefits. Effects of irisin on heart physiology is still ambiguous. This study aimed to evaluate the impact of exogenous administration of irisin on heart physiology and the pharmacokinetic profile of pump-administered irisin. To do so, Sprague Dawley rats were implanted with an irisin-loaded osmotic pump (5 μg/kg/day) for 42 days, and other animals were administered with single bolus subcutaneous injections of irisin (5 µg/kg). Body weights and blood samples were collected weekly for 42 days for serum irisin quantification and histopathology. Clinical biochemistry analyses were performed. Heart mRNA expression was assessed in 26 selected genes. Chronic interventional exogenous irisin significantly reduced body weight without affecting the heart myocyte size and significantly reduced creatine kinase enzyme level. Blood CBC, serum biochemistry, and heart morphology were normal. Gene expression of FNCD5, Raf1, CPT1, IGF-1, and CALCIN, encoding for heart physiology, increased while PGC1, Nox4, and Mfn1 significantly decreased. Nevertheless, irisin increased the expression of cardioprotective genes and inhibited some genes that harm heart physiology. Administration of irisin promotes myocardial functions and could be translated into clinical settings after preclinical profiling.

Impact of Sustained Exogenous Irisin Myokine Administration on Muscle and Myocyte Integrity in Sprague Dawley Rats

“…A peak in irisin levels was detected in serum 1 h after dosing (58.5 ng/mL), as shown in Figure 2 . The presented data are briefly described in a previous publication [ 7 ]. As shown in Figure 2 b, levels of irisin increased after 14 days and returned to normal at day 42; such results are in line with the pump’s design, which is intended to deliver its contents for up to 42 days, as labelled by the manufacturer.…”

“…Animals were acclimated and then separated into two groups ( n = 10): a sham group receiving a bare surgery and another receiving an ALZET Osmotic Pump 2006 (Cupertino, CA, USA) loaded with recombinant human irisin (FNDC5) (CusaBio, Houston, TX, USA) at a concentration of 0.25 μg/μL. The surgery and implantation occurred at the rats’ dorsal area under anesthesia using isoflurane (Hikma Pharmaceuticals, Amman, Jordan), as described briefly in a previous publication [ 7 ].…”

“…The WinNonlin noncompartmental analysis program (Version 5.2) was used for the analysis. Representative figures for the results were retrieved from the original published article [ 7 ].…”

“…Thereafter, RNA samples were reverse transcribed and run in RTq-PCR to analyse target genes. Gene analysis parameters and selected primer sequences were as described elsewhere [ 7 ].…”

Neuroplasticity to autophagy cross-talk in a therapeutic effect of physical exercises and irisin in ADHD

“…Another example is the positive effect of irisin on the cardiac muscle. As had been shown, irisin has effect on expression of gene with cardioprotective functions ( Alzoughool et al, 2022 ), improves heart conditions in a model of aging in mice ( Hu et al, 2022 ), and works as cardiomyocyte protector both in vitro and in vivo ( Cao et al, 2022 ). An overall expected therapeutic effect is stabilization of heart contractile activity and an adequate regulation of cardiac output.…”