SMAD3 Negatively Regulates Serum Irisin and Skeletal Muscle FNDC5 and Peroxisome Proliferator-activated Receptor γ Coactivator 1-α (PGC-1α) during Exercise

Tiano, Joseph P.; Springer, Danielle; Rane, Sushil G.

doi:10.1074/jbc.m114.617399

Cited by 78 publications

(62 citation statements)

References 66 publications

(81 reference statements)

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“…By now, there are around 50 papers published that investigate the FNDC5 and/or irisin in exercise in rodent studies and clinical trials in humans. Induction of Fndc5 mRNA in skeletal by endurance exercise has been confirmed in several studies in mice (Quinn et al, 2015; Tiano et al, 2015; Wrann et al, 2013) and humans (Albrecht et al, 2015; Lecker et al, 2012; Norheim et al, 2014) using QPCR or RNA sequencing. As with all clinical studies, there are a lot of variables to consider, such as retrospective studies vs. intervention trial, age and fitness level of the subjects and most importantly the type of exercise protocol used and time point of sampling.…”

Section: Fndc5/irisin In Exercisementioning

confidence: 67%

“…In neurons its regulatory partner has been suggested to be ERRα, based on bioinformatical analysis of the murine Fndc5 promoter, which contains ERRα transcription factor binding sites, and biochemical experiments using an inverse pharmacological agonist and RNAi-mediated knock-down (Wrann et al, 2013). One report identifies SMAD3 as negative regulator of serum Irisin and skeletal muscle FNDC5 and PGC-1α during exercise (Tiano et al, 2015). …”

Section: Transcriptional Regulation Of Fndc5 Expressionmentioning

confidence: 99%

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FNDC5/Irisin – Their Role in the Nervous System and as a Mediator for Beneficial Effects of Exercise on the Brain

Wrann

2015

BPL

107

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Exercise can improve cognitive function and the outcome of neurodegenerative diseases, like Alzheimer’s disease. This effect has been linked to the increased expression of brain-derived neurotrophic factor (BDNF). However, the underlying molecular mechanisms driving the elevation of this neurotrophin remain unknown. Recently, we have reported a PGC-1α-FNDC5/irisin pathway, which is activated by exercise in the hippocampus in mice and induces a neuroprotective gene program, including Bdnf. This review will focus on FNDC5 and its secreted form “irisin”, a newly discovered myokine, and their role in the nervous system and its therapeutic potential. In addition, we will briefly discuss the role of other exercise-induced myokines on positive brain effects.

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Section: Fndc5/irisin In Exercisementioning

confidence: 67%

Section: Transcriptional Regulation Of Fndc5 Expressionmentioning

confidence: 99%

FNDC5/Irisin – Their Role in the Nervous System and as a Mediator for Beneficial Effects of Exercise on the Brain

Wrann

2015

BPL

107

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“…By contrast, the transforming growth factor β (TGFβ) effector protein SMAD3 might suppress the production of irisin 54,55 . Smad3 −/− mice demonstrate increased energy expenditure due to browning of WAT 56 .…”

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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“…TGFβ has been demonstrated to influence energy expenditure and adipogenesis, and thereby whole body adiposity [15, 26, 27, 29, 30]. Serum TGFβ positively correlates with BMI, reducing TGFβ signaling results in leaner mice, and TGFβ blockade can protect mice against diet-induced obesity/diabetes.…”

Section: Introductionmentioning

confidence: 99%

Characterization of metabolic health in mouse models of fibrillin-1 perturbation

et al. 2016

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Mutations in the microfibrillar protein fibrillin-1 or the absence of its binding partner microfibrilassociated glycoprotein (MAGP1) lead to increased TGFβ signaling due to an inability to sequester latent or active forms of TGFβ, respectively. Mouse models of excess TGFβ signaling display increased adiposity and predisposition to type-2 diabetes. It is therefore interesting that individuals with Marfan syndrome, a disease in which fibrillin-1 mutation leads to aberrant TGFβ signaling, typically present with extreme fat hypoplasia. The goal of this project was to characterize multiple fibrillin-1 mutant mouse strains to understand how fibrillin-1 contributes to metabolic health. The results of this study demonstrate that fibrillin-1 contributes little to lipid storage and metabolic homeostasis, which is in contrast to the obesity and metabolic changes associated with MAGP1 deficiency. MAGP1 but not fibrillin-1 mutant mice had elevated TGFβ signaling in their adipose tissue, which is consistent with the difference in obesity phenotypes. However, fibrillin-1 mutant strains and MAGP1-deficient mice all exhibit increased bone length and reduced bone mineralization which are characteristic of Marfan syndrome. Our findings suggest Marfan-associated adipocyte hypoplasia is likely not due to microfibril-associated changes in adipose tissue, and provide evidence that MAGP1 may function independently of fibrillin in some tissues.

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SMAD3 Negatively Regulates Serum Irisin and Skeletal Muscle FNDC5 and Peroxisome Proliferator-activated Receptor γ Coactivator 1-α (PGC-1α) during Exercise

Cited by 78 publications

References 66 publications

FNDC5/Irisin – Their Role in the Nervous System and as a Mediator for Beneficial Effects of Exercise on the Brain

FNDC5/Irisin – Their Role in the Nervous System and as a Mediator for Beneficial Effects of Exercise on the Brain

Physiology and role of irisin in glucose homeostasis

Characterization of metabolic health in mouse models of fibrillin-1 perturbation

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