Irisin is expressed and produced by human muscle and adipose tissue in association with obesity and insulin resistance
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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Irisin is known to be downregulated by glucotoxic, lipotoxic, and inflammatory conditions.
“and possibly irisin, which is known to be downregulated by glucotoxic, lipotoxic [47,48], and inflammatory conditions [45].”
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- 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)
- 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
- 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 › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › 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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