Exercise-mimicking treatment fails to increase Fndc5 mRNA &amp; irisin secretion in primary human myotubes

Kurdiová, Tímea; Baláž, Miroslav; Mayer, Alexander; Máderová, Denisa; Белан, В. Н.; Wolfrum, Christian; Ukropec, Jozef; Ukropcová, Barbara

doi:10.1016/j.peptides.2014.03.003

Cited by 49 publications

(48 citation statements)

References 23 publications

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“…For instance, it was reported that exercise-mimicking treatment failed to increase Fndc5 expression in myotubes [34]. Adrenaline stimulation also showed no significant effects on Fndc5 expression in cultured myotubes [17].…”

Section: Discussionmentioning

confidence: 99%

Interaction of CREB and PGC-1α Induces Fibronectin Type III Domain-Containing Protein 5 Expression in C2C12 Myotubes

Yang

Tse

et al. 2018

Cell Physiol Biochem

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Background/Aims: Fibronectin type III domain-containing protein 5 (FNDC5), also known as irisin, is a myokine secreted from muscle in response to exercise. However, the molecular mechanisms that regulate FNDC5 expression and the functional significance of irisn in skeletal muscle remain unknown. In this study, we explored the potential pathways that induce FNDC5 expression and delineated the metabolic effects of irisin on skeletal muscle. Methods: C2C12 myotubes were treated with drugs at various concentrations and durations. The expression and activation of genes were measured by real-time polymerase chain reaction (qRT-PCR) and Western blotting. Oxidative phosphorylation was quantified by measuring the oxygen consumption rate (OCR). Results: We found that the exercise-mimicking treatment (cAMP, forskolin and isoproterenol) increased Fndc5 expression in C2C12 myotubes. CREB over-expressed C2C12 myotubes displayed higher Fndc5 expression. CREB over-expression also promoted peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) expression. PGC-1α-induced Fndc5 expression was blocked when the dominant negative form of CREB (S133A) was present. PGC-1α mutation (S570A) also decreased Fndc5 expression. Immunoprecipitation showed that overexpressed PGC-1α complexed with CREB in HEK293 cells. C2C12 myotubes treated with forskolin also increased endogenous CREB and PGC-1α binding. Functionally, irisin treatment increased mitochondrial respiration, enhanced ATP production, promoted fatty acid oxidation but decreased glycolysis in myotubes. Conclusion: Our observation indicates that cAMP-mediated PGC-1α/CREB interaction triggers Fndc5 expression, which acts as an autocrine/paracrine to shape the metabolic phenotype of myotubes.

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Section: Discussionmentioning

confidence: 99%

Interaction of CREB and PGC-1α Induces Fibronectin Type III Domain-Containing Protein 5 Expression in C2C12 Myotubes

Yang

Tse

et al. 2018

Cell Physiol Biochem

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“…It was further observed that in the Pgc-1α knockdown, the level of FNDC5 expression was significantly decreased by 86%, supporting the view that FNDC5 expression is mediated via the PGC-1α pathway. However, when using forskolin, ionomycin, or caffeine to activate PGC-1α expression in vitro, FNDC5 levels were unchanged (Kurdiova et al, 2014). Moreover, when treated C2C12 cells with free fatty acids alone and combined with exercise mimetics, showed no significant effects on irisin secretion (Sanchez et al, 2013).…”

Section: Dihydromyricetin Stimulates Fndc5/pgc-1α Expression In Vitromentioning

confidence: 97%

Dihydromyricetin stimulates irisin secretion partially via the PGC-1α pathway

Zhou

Chen

Liu

et al. 2015

Molecular and Cellular Endocrinology

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“…As one of the important triggers of PPARGC1A expression is exercise, many studies have investigated the effect of exercise on irisin secretion and have reported contradictory results. For example, two studies did not find an association between levels of PGC1α, FNDC5, irisin and exercise 21,38 . In vitro exercise-mimicking treatment with forskolin and ionomycin in human primary muscle cell cultures stimulated expression of PGC1α but decreased expression of FNDC5 and irisin secretion 38 .…”

Section: Physiology Of Irisinmentioning

confidence: 99%

Physiology and role of irisin in glucose homeostasis

et al. 2017

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Irisin is a myokine that leads to increased energy expenditure by stimulating the ‘browning’ of white adipose tissue. In the first description of this hormone, increased levels of circulating irisin, which is cleaved from its precursor fibronectin type III domain-containing protein 5, were associated with improved glucose homeostasis by reducing insulin resistance. Consequently, several studies attempted to characterize the role of irisin in glucose regulation, but contradictory results have been reported, and even the existence of this hormone has been questioned. In this Review, we present the current knowledge on the physiology of irisin and its role in glucose homeostasis. We describe the mechanisms involved in the synthesis, secretion, circulation and regulation of irisin, and the controversies regarding the measurement of irisin. We also discuss the direct effects of irisin on glucose regulatory mechanisms in different organs, the indirect effects and interactions with other hormones, and the important open questions with regard to irisin in those organs. Finally, we present the results from animal interventional studies and from human clinical studies investigating the association of irisin with obesity, insulin resistance, type 2 diabetes mellitus and the metabolic syndrome.

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Exercise-mimicking treatment fails to increase Fndc5 mRNA & irisin secretion in primary human myotubes

Cited by 49 publications

References 23 publications

Interaction of CREB and PGC-1α Induces Fibronectin Type III Domain-Containing Protein 5 Expression in C2C12 Myotubes

Interaction of CREB and PGC-1α Induces Fibronectin Type III Domain-Containing Protein 5 Expression in C2C12 Myotubes

Dihydromyricetin stimulates irisin secretion partially via the PGC-1α pathway

Physiology and role of irisin in glucose homeostasis

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