The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
FNDC5 overexpression and irisin ameliorate glucose/lipid metabolic derangements and enhance lipolysis in obesity
Open accessAbstract
Irisin is a cleaved and secreted fragment of fibronectin type III domain containing 5 (FNDC5), and contributes to the beneficial effects of exercise on metabolism. Here we report the therapeutical effects of FNDC5/irisin on metabolic derangements and insulin resistance in obesity, and show the lipolysis effect of irisin and its signal molecular mechanism. In obese mice, lentivirus mediated-FNDC5 overexpression enhanced energy expenditure, lipolysis and insulin sensitivity, and reduced hyperlipidemia, hyperglycemia, hyperinsulinism, blood pressure and norepinephrine levels; it increased hormone-sensitive lipase (HSL) expression and phosphorylation, and reduced perilipin level and adipocyte diameter in adipose tissues. Subcutaneous perfusion of irisin reduced hyperlipidemia and hyperglycemia, and improved insulin resistance. Either FNDC5 overexpression or irisin perfusion only induced a tendency toward a slight decrease in body weight in obese mice. In 3T3-L1 adipocytes, irisin enhanced basal lipolysis rather than isoproterenol-induced lipolysis, which were prevented by inhibition of adenylate cyclase or PKA; irisin increased the HSL and perilipin phosphorylation; it increased PKA activity, and cAMP and HSL mRNA levels, but reduced perilipin expression. These results indicate that FNDC5/irisin ameliorates glucose/lipid metabolic derangements and insulin resistance in obese mice, and enhances lipolysis via cAMP-PKA-HSL/perilipin pathway. FNDC5 or irisin can be taken as an effective therapeutic strategy for metabolic disorders.
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“Irisin was described to stimulate lipolysis via HSL and to inhibit lipid accumulation in adipocytes [58,64].”
In the citing paper
“For instance, irisin [58], IL-15 [89], and IL-6 [75] have shown to directly induce lipolysis in adipocytes (2a)”
Citations
Cites
1 retracted
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FNDC5/irisin is not only a myokine but also an adipokine
Roca-Rivada, A., Castelao, C., Senin, L. L., Landrove, M. O., Baltar, J., Crujeiras, A. B., Seoane, L. M., Casanueva, F. F., & Pardo, M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0060563 · Cited by 612
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- Muller, 2010, Is there evidence for a set point that regulates human body weight?, F1000, Med. Rep., 2, 59
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Physiology and role of irisin in glucose homeostasis
Perakakis, N., Triantafyllou, G. A., Fernández-Real, J. M., Huh, J. Y., Park, K. H., Seufert, J., & Mantzoros, C. S. (2017) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.221 · Cited by 621
Cheng, L., Wang, J., Dai, H., Duan, Y., An, Y., Shi, L., Lv, Y., Li, H., Wang, C., Ma, Q., et al. (2021) · Adipocyte · doi:10.1080/21623945.2020.1870060 · Cited by 404
Bi, J., Zhang, J., Ren, Y., Du, Z., Li, Q., Wang, Y., Wei, S., Yang, L., Zhang, J., Liu, C., et al. (2018) · Redox Biology · doi:10.1016/j.redox.2018.10.019 · Cited by 284
Gonzalez-Gil, A. M., & Elizondo-Montemayor, L. (2020) · Nutrients · doi:10.3390/nu12061899 · Cited by 278
“For instance, irisin [58], IL-15 [89], and IL-6 [75] have shown to directly induce lipolysis in adipocytes (2a), while irisin exerts a dual effect by also inhibiting myostatin [44] (2b), reducing myostatin-mediated inhibition of WAT lipolysis [132].”
BackgroundPolyzos, S. A., Anastasilakis, A. D., Efstathiadou, Z. A., Makras, P., Perakakis, N., Kountouras, J., & Mantzoros, C. S. (2018) · Endocrine · doi:10.1007/s12020-017-1476-1 · Cited by 262
Metadata
- Authors
- Xiong, X.-Q., Chen, D., Sun, H.-J., Ding, L., Wang, J.-J., Chen, Q., Li, Y.-H., Zhou, Y.-B., Han, Y., Zhang, F., Gao, X.-Y., Kang, Y.-M., & Zhu, G.-Q.
- Affiliations
- Nanjing Medical University (CN)
- Xi'an Jiaotong University (CN)
- Corresponding author
- Zhu, Guo-Qing
- ORCID
- Venue
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
- Publisher
- Elsevier BV
- Published
- 2015-09
- Volume
- 1852
- Issue
- 9
- Pages
- 1867-1875
- ISSN
- 0925-4439 (ISSN-L)
- OpenAlex
- W1931609017
- Cited by
- 242
- References
- 37
- Citations by year
- 2026: 8 · 2025: 23 · 2024: 23 · 2023: 13 · 2022: 43 · 2021: 38 · 2020: 23 · 2019: 23 · 2018: 18 · 2017: 13 · 2016: 15 · 2015: 1
- FWCI
- 12.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (31171095, 31271213, 91439120)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- FNDC5, irisin, obesity, insulin resistance, lipolysis, hyperlipidemia, hyperglycemia, hormone-sensitive lipase, perilipin, cAMP/PKA signaling, energy expenditure, adipocytes, exercise metabolism
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