Effect of obesity and exercise on the expression of the novel myokines, Myonectin and Fibronectin type III domain containing 5
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Abstract
Metabolic dysfunction in skeletal muscle is a major contributor to the development of type 2 diabetes. Endurance exercise training has long been established as an effective means to directly restore skeletal muscle glucose and lipid uptake and metabolism. However, in addition to the direct effects of skeletal muscle on glucose and lipids, there is renewed interest in the ability of skeletal muscle to coordinate metabolic activity of other tissues, such as adipose tissue and liver. The purpose of this study was to examine the effects of endurance exercise on the expression level of two novel muscle-derived secreted factors, or myokines, Myonectin and Fibronectin type III domain containing 5 (FNDC5), the precursor for Irisin. Methods. We performed immunoblot analysis and quantitative real-time PCR analysis of Myonectin and FNDC5 in the diaphragm muscles of obese Zucker rat (OZR) and lean Zucker rat (LZR) with 9 weeks of aerobic training on a motorized treadmill. Results. We show that myonectin gene expression is increased in the OZR model of obesity and decreases with exercise in both lean and obese Zucker rats. Conversely, myonectin protein concentration was elevated with exercise. Similarly, FNDC5 mRNA levels are significantly higher in the OZR, however exercise training had no effect on the expression level of FNDC5 in either the LZR or OZR. We did not observe any difference in muscle protein content of Irisin with obesity or exercise. Conclusion. Our data shows that exercise training does not increase either FNDC5 or myonectin gene expression, indicating that increased transcriptional regulation of these myokines is not induced by exercise. However, our data also indicates a yet to be explored disconnect between myonectin gene expression and protein content. Further, this report highlights the importance of verifying reference genes when completing gene expression analysis. We found that many commonly used reference genes varied significantly by obesity and/or exercise and would have skewed the results of this study if used to normalize gene expression data. The unstable reference genes include: beta-Actin, beta-2-microglobulin, Non-POU domain containing, octamer-binding, Peptidylprolyl isomerase H, 18S ribosomal RNA, TATA box binding protein and Transferrin receptor.
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In other studies, the relationship between myonectin expression and physical exercise is contradictory.
“although in other studies the relationship between the expression of myonectin and physical exercise is contradictory (Peterson et al., 2014).”
From Physical Exercise-Induced Myokines and Muscle-Adipose Tissue Crosstalk: A Review of Current Knowledge and the Implications for Health and Metabolic Diseases (2018) · cites this paper as Peterson et al., 2014
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Hekmatikar, A. H. A., Bettariga, F., López-Llorente, Á., Fernández‐Lázaro, D., Suzuki, K., & Daud, D. M. A. (2026) · Cancers · doi:10.3390/cancers18142343 · Cited by 1 · see citing works
Placenta Previa with history of Previous Caesarean Delivery – an obstetrician's nightmare
Mazumder, U., Rouf, S., & Sarkar, S. (2015) · Journal of Woman s Reproductive Health · doi:10.14302/issn.2381-862x.jwrh-17-1750 · Cited by 1 · see citing works
Jouzi, Z., & Omidi, M. (2023) · Modern Care Journal · doi:10.5812/mcj-142039 · Cited by 1 · see citing works
Khademi, S., اهواز, د. ش. چ., Ranjbar, R., اهواز, د. ش. چ., Ghanbarzadeh, M., & اهواز, د. ش. چ. (2015) · Research in Sport Medicine and Technology · doi:10.18869/acadpub.jsmt.13.10.91
Associations Of Betatrophin Levels With Fasting Blood Glucose In Obese Females
Baskara, P. G., Herawati, L., & Rejeki, P. S. (2020) · STRADA JURNAL ILMIAH KESEHATAN · doi:10.30994/sjik.v9i1.271
Waritsu, C., Utomo, D. N., & Sari, G. M. (2020) · STRADA JURNAL ILMIAH KESEHATAN · doi:10.30994/sjik.v9i2.314
Serum Myonectin and Adropin Levels in Predicting Diabetes
Gökmen, E. S., Durcan, E., Dağ, İ., & Dinç, M. (2023) · Artuklu International Journal of Health Sciences · doi:10.58252/artukluder.1243870
Safarpour, H., Safarzade, A., & Delpisheh, A. (2024) · Jentashapir Journal of Cellular and Molecular Biology · doi:10.5812/jjcmb-149169
Yousefvand, Z., Rahmati, M., & Mirnasuri, R. (2024) · مجله دانشگاه علوم پزشکی اراک · doi:10.61186/jams.27.3.164
İrisin Hormonunun Sağlık ve Enerji Homeostazı Üzerine Etkileri
Kartal, M. E., & Baran, Ö. (2024) · Turkish Journal of Diabetes and Obesity · doi:10.25048/tudod.1516025
Physical exercise and irisin: managing obesity and related comorbidities
Negroiu, C. E., Tudorașcu, I., Dănoiu, S., Pădureanu, V., Godeanu, S., Dănoiu, R., Ungureanu, A., Beznă, M. C., & Moise, C. G. (2025) · Romanian Journal of Morphology and Embryology · doi:10.47162/rjme.66.2.05 · Cited by 1 · see citing works
Myokines and mitochondrial function in cardiometabolic diseases
Saavedra, J. E., Gallo-Villegas, J., & Calderón, J. C. (2026) · Journal of physiology and biochemistry · doi:10.1007/s13105-026-01233-8
- Authors
- Peterson, J. M., Mart, R., & Bond, C. E.
- Affiliations
- East Tennessee State University (US)
- Venue
- PeerJ
- Publisher
- PeerJ
- Published
- 2014-09-30
- Volume
- 2
- Pages
- e605
- ISSN
- 2167-8359 (ISSN-L)
- PMC
- PMC4184026
- OpenAlex
- W2162744978
- Cited by
- 64
- References
- 36
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 6 · 2023: 7 · 2022: 5 · 2021: 7 · 2020: 14 · 2019: 3 · 2018: 8 · 2017: 5 · 2015: 4
- FWCI
- 2.91
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- PeerJ (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Commons - East Tennessee State University (East Tennessee State University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- myokines, myonectin, FNDC5, irisin, obesity, endurance training, skeletal muscle, diaphragm, gene expression, reference genes, gene normalization, type 2 diabetes, metabolic dysfunction, Zucker rats
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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