Serum Brain-Derived Neurotrophic Factor Levels Are Associated with Skeletal Muscle Function but Not with Muscle Mass in Patients with Heart Failure

Abstract

Heart failure (HF) is associated with aberrant skeletal muscle impairments, which are closely linked to the severity of HF. A low level of brain-derived neurotrophic factor (BDNF), a myokine produced in the skeletal muscle, is known to be involved in reduced exercise capacity and poor prognosis in HF. However, little is known about the factors or conditions of skeletal muscle associated with BDNF levels. We investigated the association between serum BDNF levels and the skeletal muscle mass and function in HF patients (n = 60, 63 ± 13 years) and age-matched controls (n = 29, 61 ± 16 years). The serum BDNF level was significantly lower in the HF patients compared to the controls (24.9 ± 0.9 versus 28.6 ± 1.3, P = 0.021). In a univariate analysis, BDNF was significantly correlated with the peak oxygen uptake, estimated glomerular filtration rate, 10-m gait speed, and muscle strength, but not with the body mass index or lean mass in the HF group. A multiple linear regression analysis revealed that BDNF was independently associated with muscle strength (β-coefficient = 2.80, 95%CI: 1.89-11.8, P = 0.008). Serum BDNF levels were associated with exercise capacity and skeletal muscle function, but not with muscle mass. These novel findings may suggest that BDNF production is controlled by muscle function and activity and consequently regulates exercise capacity, highlighting the importance of adequate training regarding skeletal muscle in HF patients.

High-intensity interval training is superior to moderate intensity training on aerobic capacity in rats: Impact on hippocampal plasticity markers

“…Our results are thus in line with those who found a higher increase of hippocampal BDNF after HIIT compared to MICT in healthy rats [5] while other studies found opposite results by using different ways to compare intense and moderate intensity exercises [4,11]. The correlation between the PGC-1α and TrkB upregulation with improvements in SLT and Smax is in line with those showing in humans that the serum BDNF level was related to VO2peak and the first ventilatory threshold [41]. It is thus suggested with caution that aerobic fitness improvements might be associated with an upregulation of neurotrophic activity in the hippocampus.…”

Brain-derived neurotrophic factor gene polymorphism in post-ST-elevation myocardial infarction patients undergoing primary percutaneous intervention

“…Probably, BDNF can be released from skeletal muscle, and skeletal muscle dysfunction (rather than loss of skeletal muscle mass) in HF patients may explain lowered levels of circulating BDNF in HFrEF. However, it does not determine declining levels of the peptide in post-STEMI patients with adverse cardiac remodeling, HF with preserved EF, nor recurrent CV events [38][39][40][41] . Whether BDNF production is under control by myocardial function and exercise is not well-understood.…”

“…Brain-derived neurotropic factor (BDNF) was previously found as one of the neurotrophins with proliferative, cholinergic, serotoninergic and dopaminergic activities, and is predominantly synthesized in central and peripheral neurons 12 . Later, an expression of mRNA BDNF was found in myocardium, vessel vasculature, skeletal muscles, parenchymal organs (including lung, spleen and kidney), visceral epithelial cells, and mature and progenitor endothelial cells [13][14][15] . Previous animal and clinical studies have revealed that BDNF through an activation of nuclear factor kB receptors mediates endothelial cell survival and neoangiogenesis, reduces p75-mediated apoptosis of cardiac myocytes, enhances endothelial function, regulates blood flow in ischemic myocardium, and improves LV function after ischemic injury, thereby providing cardioprotective effects 16,17 .…”

Physical Exercise and Myokines: Relationships with Sarcopenia and Cardiovascular Complications

“…BDNF levels are reduced in heart failure patients and are positively correlated with the peak of oxygen uptake (VO 2 ). Furthermore, reduced serum levels of BDNF were associated with all-cause cardiac death and readmission in heart failure patients, suggesting that this myokine could be a less invasive biomarker that shows the severity of heart failure and can work as a predictor of prognosis in these patients [106].…”