Cited by 242Adipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and MetabolismPeroxisome Proliferator-Activated Receptors

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FNDC5 overexpression and irisin ameliorate glucose/lipid metabolic derangements and enhance lipolysis in obesity

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Xiong, Xiao-Qing, Chen, Dan, Sun, Hai-Jian, Ding, Lei, Wang, Jue-Jin, Chen, Qi, Li, Yue-Hua, Zhou, Ye-Bo, Han, Ying, Zhang, Feng, Gao, Xing-Ya, Kang, Yu-Ming, Zhu, Guo-Qing·2015·Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

DOI 10.1016/j.bbadis.2015.06.017

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Abstract

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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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: Xiong, Xiao-Qing
Chen, Dan
Sun, Hai-Jian
Ding, Lei
Wang, Jue-Jin
Chen, Qi
Zhou, Ye-Bo
Han, Ying
Kang, Yu-Ming
Zhu, Guo-Qing
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)
DOI: 10.1016/j.bbadis.2015.06.017
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 366 d)
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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FNDC5 overexpression and irisin ameliorate glucose/lipid metabolic derangements and enhance lipolysis in obesity

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