Cited by 788Adipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and MetabolismPeroxisome Proliferator-Activated Receptors

The DOI matches its Crossref record; 23 of the 23 references it cites were found in a registry or an index.

Irisin Is Expressed and Produced by Human Muscle and Adipose Tissue in Association With Obesity and Insulin Resistance

Moreno-Navarrete, José María, Ortega, Francisco, Serrano, Marta, Guerra, Ester, Pardo, Gerard, Tinahones, Francisco, Ricart, Wifredo, Fernández-Real, José Manuel·2013·The Journal of Clinical Endocrinology & Metabolism

DOI 10.1210/jc.2012-2749

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Abstract

CONTEXT: Recently irisin (encoded by Fndc5 gene) has been reported to stimulate browning and uncoupling protein 1 expression in sc adipose tissue of mice. OBJECTIVE: The objective of the study was to investigate FNDC5 gene expression in human muscle and adipose tissue and circulating irisin according to obesity, insulin sensitivity, and type 2 diabetes. DESIGN, PATIENTS, AND MAIN OUTCOME MEASURE: Adipose tissue FNDC5 gene expression and circulating irisin (ELISA) were analyzed in 2 different cohorts (n = 125 and n = 76); muscle FNDC5 expression was also evaluated in a subcohort of 34 subjects. In vitro studies in human preadipocytes and adipocytes and in induced browning of 3T3-L1 cells (by means of retinoblastoma 1 silencing) were also performed. RESULTS: In both sc and visceral adipose tissue, FNDC5 gene expression decreased significantly in association with obesity and was positively associated with brown adipose tissue markers, lipogenic, insulin pathway-related, mitochondrial, and alternative macrophage gene markers and negatively associated with LEP, TNFα, and FSP27 (a known repressor of brown genes). Circulating irisin and irisin levels in adipose tissue were significantly associated with FNDC5 gene expression in adipose tissue. In muscle, the FNDC5 gene was 200-fold more expressed than in adipose tissue, and its expression was associated with body mass index, PGC1α, and other mitochondrial genes. In obese participants, FNDC5 gene expression in muscle was significantly decreased in association with type 2 diabetes. Interestingly, muscle FNDC5 gene expression was significantly associated with FNDC5 and UCP1 gene expression in visceral adipose tissue. In men, circulating irisin levels were negatively associated with obesity and insulin resistance. Irisin was secreted from human adipocytes into the media, and the induction of browning in 3T3-L1 cells led to increased secreted irisin levels. CONCLUSIONS: Decreased circulating irisin concentration and FNDC5 gene expression in adipose tissue and muscle from obese and type 2 diabetic subjects suggests a loss of brown-like characteristics and a potential target for therapy.

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Additional file 2 of Irisin mediates beiging of adipose-derived mesenchymal stem cells through binding to TRPC3
Xue, C., Li, X., Ba, L., Shen, Y., Sun, Z., Gu, J., Yang, Y., Han, Q., & Zhao, R. C. (2022) · Figshare · doi:10.6084/m9.figshare.19695969
Additional file 1 of Irisin deletion induces a decrease in growth and fertility in mice
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Additional file 2 of Association between irisin and metabolic parameters in nondiabetic, nonobese adults: a meta-analysis
Li, Y., & Xu, Z. (2022) · Figshare · doi:10.6084/m9.figshare.21382569
Additional file 1 of Irisin mediates beiging of adipose-derived mesenchymal stem cells through binding to TRPC3
Xue, C., Li, X., Ba, L., Shen, Y., Sun, Z., Gu, J., Yang, Y., Han, Q., & Zhao, R. C. (2022) · Figshare · doi:10.6084/m9.figshare.19695966
Additional file 6 of Association between irisin and metabolic parameters in nondiabetic, nonobese adults: a meta-analysis
Li, Y., & Xu, Z. (2022) · Figshare · doi:10.6084/m9.figshare.21382581
Additional file 1 of Association between irisin and metabolic parameters in nondiabetic, nonobese adults: a meta-analysis
Li, Y., & Xu, Z. (2022) · Figshare · doi:10.6084/m9.figshare.21382566
Additional file 5 of Irisin mediates beiging of adipose-derived mesenchymal stem cells through binding to TRPC3
Xue, C., Li, X., Ba, L., Shen, Y., Sun, Z., Gu, J., Yang, Y., Han, Q., & Zhao, R. C. (2022) · Figshare · doi:10.6084/m9.figshare.19695978
Additional file 5 of Association between irisin and metabolic parameters in nondiabetic, nonobese adults: a meta-analysis
Li, Y., & Xu, Z. (2022) · Figshare · doi:10.6084/m9.figshare.21382578
Additional file 4 of Association between irisin and metabolic parameters in nondiabetic, nonobese adults: a meta-analysis
Li, Y., & Xu, Z. (2022) · Figshare · doi:10.6084/m9.figshare.21382575
Additional file 4 of Irisin mediates beiging of adipose-derived mesenchymal stem cells through binding to TRPC3
Xue, C., Li, X., Ba, L., Shen, Y., Sun, Z., Gu, J., Yang, Y., Han, Q., & Zhao, R. C. (2022) · Figshare · doi:10.6084/m9.figshare.19695975
Additional file 3 of Association between irisin and metabolic parameters in nondiabetic, nonobese adults: a meta-analysis
Li, Y., & Xu, Z. (2022) · Figshare · doi:10.6084/m9.figshare.21382572
Additional file 6 of Irisin mediates beiging of adipose-derived mesenchymal stem cells through binding to TRPC3
Xue, C., Li, X., Ba, L., Shen, Y., Sun, Z., Gu, J., Yang, Y., Han, Q., & Zhao, R. C. (2022) · Figshare · doi:10.6084/m9.figshare.19695981
Additional file 3 of Irisin mediates beiging of adipose-derived mesenchymal stem cells through binding to TRPC3
Xue, C., Li, X., Ba, L., Shen, Y., Sun, Z., Gu, J., Yang, Y., Han, Q., & Zhao, R. C. (2022) · Figshare · doi:10.6084/m9.figshare.19695972
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Rouquet, T. (2015) · theses.fr (ABES) · doi:10.70675/680971a6z149ez4296z9c76z5ee9dfd53ce5
FNDC4 and FNDC5 Attenuate SARS‐CoV‐2 S1‐Induced Inflammatory Responses in Human Adipose Tissue
Neira, G., Hernández‐Castañeda, J., Catalán, V., Becerril, S., Martín, M., Valentí, V., Moncada, R., Silva, C., Gómez‐Ambrosi, J., Escalada, J., et al. (2026) · European Journal of Clinical Investigation · doi:10.1111/eci.70215
Multimodal evidence for the association between muscle mass and NAFLD: insights from hospital-based data, NHANES and mendelian randomization
Xie, W., Li, S. X., & Han, S. (2026) · Frontiers in Genetics · doi:10.3389/fgene.2026.1821445
Adipose Tissue–Brain Crosstalk: The Role of Adipokines in the Regulation of Cognitive Function
Żołyniak, M., Soczyńska, J., Kania, K., Szwach, J., Kurowski, M., Gawełczyk, W., & Woźniak, S. (2026) · Obesities · doi:10.3390/obesities6030032
“Similarly, irisin, originally characterised as a myokine, has also been detected in adipose tissue and is increasingly considered an adipomyokine, reflecting its involvement in systemic energy homeostasis and metabolic regulation [63,64].”
Change in circulating irisin level and its association with lipid metabolism after exenatide treatment in patients with type 2 diabetes mellitus
Gao, Y., Hong, X., Yang, K., Le, Y., Wei, R., Yang, J., Hong, T., & Tian, Q. (2026) · Journal of Clinical & Translational Endocrinology · doi:10.1016/j.jcte.2026.100447
“Elevated irisin level in individuals with obesity has been indicated to reflect a compensatory mechanism against metabolic stress and it is possibly driven by an increased secretion from white adipose tissue [23,24].”
Irisin Potentiates 5-fluorouracil Cytotoxicity in HT-29 Colon Cancer Cells through Enhanced Apoptosis and Transcriptional Modulation of Adenosine Monophosphate-activated Protein Kinase/Mammalian Target of Rapamycin Signaling
Refaat, B. (2026) · International Journal of Applied and Basic Medical Research · doi:10.4103/ijabmr.ijabmr_477_25
“[30,31] In light of this variability, the lower concentrations (2 and 20 ng/mL) were selected to approximate reported systemic levels, whereas the higher dose (200 ng/mL) was included to evaluate potential dose dependent and pharmacological effects in a controlled in vitro setting.”
Irisin and anxiety-like behaviors: Mechanistic integration of peripheral–central crosstalk, neuroinflammation, and neural plasticity
Li, H., Song, S., Tang, D., Zhu, Y., Zhang, X., Wang, C., Zhang, Y., Du, M., Liu, C., & Hu, Y. (2026) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2026.106847
Exercise-induced myokine irisin protects against obesity-associated ischemic stroke via integrin αVβ5 signaling
Ma, E. B., Hong, S. J., Kang, H., Sohn, E., Choi, K., & Huh, J. Y. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1893339
The exercise-induced irisin–BDNF axis: a systematic review of evidence and translational implications
Ersever, E. M. (2026) · Muscles Ligaments and Tendons Journal · doi:10.32098/mltj_2026_6329
“This signaling pathway is crucial for the release of irisin, a hormone that may promote BDNF expression in the brain [27-30] .”
Exercise-induced irisin–BDNF signaling in aging: implications for cognitive decline, sarcopenia, and neurodegeneration. A narrative review
Ersever, E. M. (2026) · European Journal of Translational Myology · doi:10.4081/ejtm.2026.15846
“15-17 Sedentary older adults exhibited significantly lower circulating irisin and BDNF levels, paralleling impairments in metabolic health (increased insulin resistance, reduced thermogenesis) and cognitive performance.”
Exercise‐Regulated Irisin Signaling in Glucose Homeostasis and Diabetes: The Myogenic Benefits for Metabolic Health
Gao, R., Zhang, Y., & Quan, L. (2026) · Comprehensive physiology · doi:10.1002/cph4.70248
Sex-Dependent Effects of Exogenous Irisin on Pancreatic Endocrine-Cell Immunophenotype in Post-Weaning Wistar Rats
Osiak-Wicha, C., Manastyrska-Stolarczyk, M., Muszyński, S., Kras, K., Dajnowska, A., Hiżewska, L., Woźniak, K., Tomaszewska, E., Słowik, T., Dobrowolski, P., et al. (2026) · Current Issues in Molecular Biology · doi:10.3390/cimb48090967
Acute effects of a strength exercise session on inflammatory and lipid markers in overweight men
Moreira, A. R. S., Vieira, É. L. M., Fortes, Y. M., de Moura, S. S., Barroso, L. S. S., Galdino, G., Furtado, G., Fernandes, H. D. B., de Miranda, A. S., Martins-Costa, H. C., et al. (2026) · Brain Behavior and Immunity Integrative · doi:10.1016/j.bbii.2026.100202
Association of Circulating Irisin with Adiposity, Sarcopenia-Related Indices, and Phenotypes in Premenopausal and Postmenopausal Women
Aljawini, N., Habib, S. S., & Al-Regaiey, K. (2026) · Nutrients · doi:10.3390/nu18213531

Authors: Moreno-Navarrete, J. M., Ortega, F., Serrano, M., Guerra, E., Pardo, G., Tinahones, F., Ricart, W., & Fernández-Real, J. M.
Affiliations: Department of Diabetes, Endocrinology, and Nutrition (J.M.M.-N., F.O., M.S., E.G., G.P., W.R., J.M.-F.-R.), Hospital Dr. Josep Trueta de Girona, Spain, Institut d'Investigació Biomèdica de Girona, Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERobn) (CB06/03/010), and Instituto de Salud Carlos III, 17007 Girona, Spain, Department of Endocrinology and Nu
Instituto de Salud Carlos III (ES)
ORCID: Ortega, Francisco
Serrano, Marta
Tinahones, Francisco
Ricart, Wifredo
Venue: The Journal of Clinical Endocrinology & Metabolism
Publisher: The Endocrine Society
Published: 2013-04-01
Volume: 98
Issue: 4
Pages: E769-E778
ISSN: 0021-972X (ISSN-L)
1945-7197
DOI: 10.1210/jc.2012-2749
OpenAlex: W2046500896
Cited by: 788
References: 23
Citations by year: 2026: 23 · 2025: 29 · 2024: 39 · 2023: 46 · 2022: 84 · 2021: 63 · 2020: 78 · 2019: 62 · 2018: 62 · 2017: 63 · 2016: 63 · 2015: 75 · 2014: 67 · 2013: 34
FWCI: 58.02
Type: journal article
Language: en
Open access: closed
Locations: The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
PubMed (publishedVersion)
RISalud Institutional Health Repository of Andalucía (submittedVersion)
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: irisin, FNDC5, obesity, insulin resistance, type 2 diabetes, brown adipose tissue, adipose tissue browning, skeletal muscle, UCP1, PGC-1α, adipocytes, mitochondrial genes, macrophage markers, FSP27, retinoblastoma 1
MeSH terms: Adipose Tissue, Adult, Aged, Animals, Cells, Cultured, Diabetes Mellitus, Type 2, Female, Fibronectins, Humans, Insulin Resistance, Male, Middle Aged, Obesity, Gene Expression, Muscle, Skeletal, 3T3-L1 Cells, Mice, Genetic Association Studies

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Irisin Is Expressed and Produced by Human Muscle and Adipose Tissue in Association With Obesity and Insulin Resistance

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