Exerkine dysregulation links visceral adiposity to skeletal muscle impairment in end-stage heart failure with reduced ejection fraction: proteomic evidence for a cardio–adipose–muscle axis
Authors' conclusion
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.
Study context
- Population
- Patients with end-stage heart failure with reduced ejection fraction (HFrEF) and healthy controls; body composition by CT (VAT, SAT, epicardial adipose tissue (EAT), psoas muscle index and density), handgrip strength and 6-min walk test
- Participants
- 73 vs 16
- Exposure
- End-stage HFrEF vs healthy controls
- HFrEFn = 73
- Healthy controlsn = 16reference
- Outcome
- Circulating exerkines, HFrEF vs controls
Methodological detailscase-control comparison, proteomic (Olink), age- and creatinine-adjusted linear models with false discovery rate correction
- Case-control comparison
- Proteomic (Olink)
- Age- and creatinine-adjusted linear models with false discovery rate correction
Main finding
As reported in the abstract
- Elevated in HFrEF: inflammatory and metabolic stress-related exerkines CXCL8, CCL2, IL-6, TNF, IL-15, GDF15, FGF21, ANGPTL4, CTSB, DCN and resistin
- Significantly reduced in HFrEF: proteins of muscle integrity and regenerative signaling (myostatin, BDNF, IL-7, SPARC)
Observational data: associations, not effects.
Further findings
Obesity in HFrEF
- Obese
- 36%
- Central obesity independent of BMI
- 38%
Body composition and function in HFrEF
- Muscle strength and muscle quality strongly associated with functional capacity
- VAT correlated with muscle mass but not with muscle quality or performance
Exerkine associations in HFrEF
- Leptin strongly correlated with adiposity measures
- GDF15, IL-15, FGF21, CTSB inversely associated with muscle quality and functional performance
- Myostatin positively correlated with muscle quality, strength and exercise capacity
- BDNF inversely associated with frailty
Original publication
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