Key result
End-stage HFrEF is linked to elevated inflammatory exerkines and reduced muscle integrity proteins versus healthy controls.
Why the study?
The role of exerkines in advanced HFrEF and their relationship with adiposity and skeletal muscle characteristics remain poorly understood.
Observational (n=89)
No
Advanced HFrEF is characterized by a dysregulated exerkine network linking adiposity, skeletal muscle quality, and functional performance, identifying candidate molecular mediators of sarcopenia and functional decline.
Answers are grounded in this paper and cite their sources.
May link exerkine dysregulation to sarcopenia in HFrEF; hypothesis-generating and requires prospective validation.
Background Heart failure with reduced ejection fraction (HFrEF) is associated with profound alterations in body composition, skeletal muscle dysfunction, and impaired exercise capacity. Exerkines representing exercise-responsive signaling molecules released by skeletal muscle, adipose tissue, and other organs may mediate systemic metabolic communication between tissues. However, their role in advanced HFrEF and their relationship with adiposity and skeletal muscle characteristics remain poorly understood. Methods We studied 73 patients with end-stage HFrEF and 16 healthy controls. Body composition was assessed using computed tomography, including visceral (VAT), subcutaneous (SAT), and epicardial adipose tissue (EAT), as well as skeletal muscle quantity (psoas muscle index, PMI) and quality (psoas muscle density, PMD). Functional performance was evaluated using handgrip strength (HGT) and the 6-min walk test (6MWT). Circulating exerkines were quantified using the Olink technology. Associations between proteins and clinical variables were assessed using age- and creatinine-adjusted linear models with false discovery rate correction. Results Among patients with HFrEF, 36% were obese and 38% exhibited central obesity independent of BMI. Muscle strength and muscle quality were strongly associated with functional capacity. VAT correlated with muscle mass but not with muscle quality or performance. Compared with controls, HFrEF patients demonstrated elevated inflammatory and metabolic stress-related exerkines including CXCL8, CCL2, IL-6, TNF, IL-15, GDF15, FGF21, ANGPTL4, CTSB, DCN, and resistin. In contrast, proteins associated with muscle integrity and regenerative signaling (myostatin, BDNF, IL-7, SPARC) were significantly reduced. In HFrEF patients leptin strongly correlated with adiposity measures. Metabolic stress mediators (GDF15, IL-15, FGF21, CTSB) were inversely associated with muscle quality and functional performance, whereas myostatin positively correlated with muscle quality, strength, and exercise capacity. BDNF was inversely associated with frailty. Conclusions Advanced HFrEF is characterized by a dysregulated exerkine network linking adiposity, skeletal muscle quality, and functional performance. Four biologically coherent axes were identified: a leptin-driven adiposity axis, a metabolic stress–muscle quality axis, a myostatin-related muscle function axis, and a neurotrophic frailty axis. These findings support the presence of a systemic cardio–adipose–muscle signaling network in end-stage HFrEF and identify candidate molecular mediators of sarcopenia and functional decline.
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Załęska-Kocięcka et al. (2026) conducted an observational in End-stage heart failure with reduced ejection fraction (HFrEF) (n=89). End-stage HFrEF vs. Healthy controls was evaluated on Circulating exerkine levels. Patients with end-stage HFrEF demonstrated elevated inflammatory and metabolic stress-related exerkines and reduced muscle integrity proteins compared to healthy controls.
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