Acute and chronic increases of circulating FSTL1 normalize energy substrate metabolism in pacing-induced heart failure
Open accessAbstract
BACKGROUND: FSTL1 (follistatin-like protein 1) is an emerging cardiokine/myokine that is upregulated in heart failure (HF) and is found to be cardioprotective in animal models of cardiac injury. We tested the hypothesis that circulating FSTL1 can affect cardiac function and metabolism under baseline physiological conditions and in HF. METHODS AND RESULTS: C-glucose were infused to track the metabolic fate of free fatty acids and glucose. Cardiac uptake of lactate and ketone bodies and systemic respiratory quotient were also measured. HF caused a shift from prevalent cardiac and systemic fat to carbohydrate oxidation. Although acute FSTL1 administration caused minimal hemodynamic changes at baseline, in HF dogs it enhanced cardiac oxygen consumption and transiently reversed the changes in free fatty acid and glucose oxidation and systemic respiratory quotient. In HF, chronic FSTL1 infusion stably normalized cardiac free fatty acid, glucose, ketone body consumption, and systemic respiratory quotient, while moderately improving diastolic and contractile function. Consistently, FSTL1 prevented the downregulation of medium-chain acyl-CoA dehydrogenase-a representative enzyme of the free fatty acid oxidation pathway. Complementary in vitro experiments in primary cardiac and skeletal muscle myocytes showed that FSTL1 stimulated oxygen consumption through AMPK (AMP-activated kinase) activation. CONCLUSIONS: These findings support a novel function for FSTL1 and provide the first direct evidence that a circulating cardiokine/myokine can alter myocardial and systemic energy substrate metabolism, in vivo.
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FSTL1 can positively regulate myocardial substrate metabolism in vivo in a dog model.
“Using a dog model, it was recently shown that FSTL1 can positively regulate myocardial substrate metabolism, in vivo (199).”
From Muscle–Organ Crosstalk: The Emerging Roles of Myokines (2020) · cites this paper as [199]
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- Authors
- Seki, M., Powers, J. C., Maruyama, S., Zuriaga, M. A., Wu, C.-L., Kurishima, C., Kim, L., Johnson, J., Poidomani, A., Wang, T., Muñoz, E., Rajan, S., Park, J. Y., Walsh, K., & Recchia, F. A.
- Affiliations
- Boston University (US)
- From the Cardiovascular Research Center (M.S., J.C.P., C.K., L.K., J.J., A.P., T.W., E.M., J.Y.P., F.A.R.) and the Center for Translational Medicine (S.R.), Lewis Katz School of Medicine at Temple University, Philadelphia, PA; Molecular Cardiology, Whitaker Cardiovascular Institute, Boston University School of Medicine, MA (S.M., M.A.Z., C.-L.W., K.W.); Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy (F.A.R.); and Fondazione Toscana Gabriele Monasterio, Pisa, Italy (F.A.R.).
- ORCID
- Venue
- Circulation Heart Failure
- Published
- 2018-01
- Volume
- 11
- Issue
- 1
- Pages
- e004486-e004486
- ISSN
- 1941-3289 (ISSN-L)
- 1941-3297
- PMC
- PMC5765881
- OpenAlex
- W2782755088
- Cited by
- 59
- References
- 34
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 8 · 2023: 10 · 2022: 8 · 2021: 8 · 2020: 5 · 2019: 6 · 2018: 2
- FWCI
- 3.97
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Circulation Heart Failure (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- CINECA IRIS Institutional Research Information System (Sant'Anna School of Advanced Studies) (submittedVersion)
- Funders
- National Institute on Aging (R21AG052160)
- National Heart, Lung, and Blood Institute (R01HL131006, R01HL129120, R01HL126952)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Keywords
- FSTL1, follistatin-like protein 1, heart failure, pacing-induced heart failure, cardiokines, myokines, substrate metabolism, free fatty acid oxidation, glucose oxidation, ketone oxidation, respiratory quotient, myocardial oxygen consumption, medium-chain acyl-CoA dehydrogenase, AMPK, cardiac contractile function, diastolic function, cardiomyocytes, skeletal muscle fibers
- MeSH terms
- Animals, Blood Pressure, Cardiac Pacing, Artificial, Disease Models, Animal, Dogs, Drug Administration Schedule, Fatty Acids, Nonesterified, Glucose, Heart Failure, Ketone Bodies, Male, Oxygen Consumption, Vascular Resistance, Follistatin-Related Proteins
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