Meteorin-like protein elevation post-exercise improved vascular inflammation among coronary artery disease patients by downregulating NLRP3 inflammasome activity
Open accessAbstract
BACKGROUND: Coronary artery disease (CAD) has become the most common cause of death worldwide. However, the negative effects of CAD are able to be alleviated via exercises, possibly via increased production of meteorin-like protein (Metrnl). In this study, we aim to evaluate the connection between Metrnl production during exercise with lowered CAD risk and severity. METHODS: Two age and gender-matched groups of 60 human patients, one with CAD, and one without were randomly recruited. The CAD group were subjected to continuous training exercises. Mice were exercised by using a treadmill, establishing an animal exercise model. ELISA was used to measure plasma Metrnl and inflammatory factors. To determine the impact of Metrnl on glucose metabolism, oxygen consumption and extracellular acid rates were taken for untreated, palmitic acid (PA)-treated, and PA+Metrnl co-treated human umbilical vein endothelial cells. Western blot was used to measure expression levels for the NLR family pyrin domain containing 3 inflammasome. RESULTS: CAD patients had lower Metrnl levels compared to non-CAD controls. Furthermore, higher Metrnl levels post-exercise were inversely associated with LDL, inflammatory cytokines, and CAD severity, as well as being positively associated with HDL. Metrnl was able to counteract against PA-induced HUVEC glucose metabolic dysfunction via reducing ROS production, which in turn lowered NLRP3 inflammasome expression, thereby serving as the basis behind the inverse correlation between Metrnl and inflammatory cytokines. CONCLUSIONS: Exercise was able to increase Metrnl production from skeletal muscle among CAD patients, and subsequently improve patient atherosclerosis via counteracting against endothelial metabolic dysfunction and pro-inflammatory activities.
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Sustained exercise training leads to stable elevations in both Metrnl expression and its circulating concentration.
“In contrast, sustained exercise training leads to stable elevations in both Metrnl expression and its circulating concentration. Long-term exercise training can also increase circulating Metrnl levels and muscle mRNA expression in human [27,28,66].”
From Exercise-Induced Myokines in Obesity-Related Metabolic Disorders and Cardiovascular Protection: A Narrative Review (2026) · cites this paper as [66]
The Results section reports higher plasma Metrnl in CAD patients after 12 weeks of exercise and higher plasma and skeletal-muscle Metrnl in exercised mice. These findings support elevations after sustained training, but the paper does not establish that the elevations remained stable over time. (LLM, conf=0.86)
Experimental — accuracy not yet measuredHIIT has been associated with rapid and pronounced peaks of IL-6 and robust induction of Metrnl, suggesting potential benefits for enhancing acute anti-inflammatory responses and improving myocardial metabolism.
“High-intensity interval training (HIIT) has been associated with rapid and pronounced peaks of IL-6 and robust induction of Metrnl, suggesting potential benefits for enhancing acute anti-inflammatory responses and improving myocardial metabolism [27,28,66].”
From Exercise-Induced Myokines in Obesity-Related Metabolic Disorders and Cardiovascular Protection: A Narrative Review (2026) · cites this paper as [66]
The Results section (page unavailable) reports increased Metrnl and reduced inflammation after 12 weeks of moderate-intensity continuous training in patients with coronary artery disease, supporting the broader exercise–Metrnl–inflammation link. The paper does not establish those effects for HIIT or report rapid IL-6 peaks; its Conclusions associate higher Metrnl with lower IL-6 and improved endothelial, not myocardial, metabolism. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe intense metabolic stress induced by HIIT triggers a pulsatile IL-6 release that activates anti-inflammatory cascades, while Metrnl upregulation has been associated with improved cardiac function in human studies.
“The intense metabolic stress induced by HIIT triggers a pulsatile IL-6 release that activates anti-inflammatory cascades [14,34], while Metrnl upregulation has been associated with improved cardiac function in human studies [66].”
From Exercise-Induced Myokines in Obesity-Related Metabolic Disorders and Cardiovascular Protection: A Narrative Review (2026) · cites this paper as [66]
The Results section reports increased plasma Metrnl and reduced inflammatory markers after 12 weeks of moderate-intensity continuous training in patients with coronary artery disease. The Discussion proposes improved patient functioning and describes improved endothelial function, but the cited study does not report a measured improvement in cardiac function. The HIIT and IL-6 clause is attached to other citations, not this one. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIn patients with coronary artery disease, training-induced augmentation of skeletal muscle-derived Metrnl coincides with mitigated atherosclerosis, characterized by improved endothelial metabolism and reduced pro-inflammatory activity.
“Exercise-mediated increases in Metrnl reinforce its protective character; in patients with coronary artery disease, training-induced augmentation of skeletal muscle-derived Metrnl coincides with mitigated atherosclerosis, characterized by improved endothelial metabolism and reduced pro-inflammatory activity [66].”
From Exercise-Induced Myokines in Obesity-Related Metabolic Disorders and Cardiovascular Protection: A Narrative Review (2026) · cites this paper as [66]
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Zhang, Y., & Qiu, Y. (2026) · Sports · doi:10.3390/sports14050212 · Cited by 3 · see citing works
“Long-term https://doi.org/10.3390/sports14050212 exercise training can also increase circulating Metrnl levels and muscle mRNA expression in human [27,28,66].”
Influential
- Authors
- Liu, J., Diao, L., Xia, W., Zeng, X., Li, W., Zou, J., Liu, T., Pang, X., & Wang, Y.
- Affiliations
- Jinan University (CN)
- University of Chinese Academy of Sciences (CN)
- Hong Kong Polytechnic University (HK)
- Corresponding author
- Pang, Xinli
- Wang, Yongshun
- Venue
- Aging
- Publisher
- Impact Journals, LLC
- Published
- 2023-12-04
- Volume
- 15
- Issue
- 24
- Pages
- 14720-14732
- ISSN
- 1945-4589 (ISSN-L)
- PMC
- PMC10781447
- OpenAlex
- W4389323485
- Cited by
- 28
- References
- 38
- Citations by year
- 2026: 13 · 2025: 7 · 2024: 8
- FWCI
- 2.50
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Aging (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Guangdong Medical Research Foundation
- Sanming Project of Medicine in Shenzhen (SZSM201412012)
- Basic and Applied Basic Research Foundation of Guangdong Province (2021A1515111145)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Keywords
- meteorin-like protein, Metrnl, coronary artery disease, physical activity, vascular inflammation, NLRP3 inflammasome, endothelial dysfunction, palmitic acid, reactive oxygen species, glucose metabolism, inflammatory cytokines, atherosclerosis, skeletal muscle, treadmill exercise
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Animals, Coronary Artery Disease, Humans, Inflammation, Cytokines, Mice, Inflammasomes, Human Umbilical Vein Endothelial Cells
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