Inhibition of Myostatin Signaling through Notch Activation following Acute Resistance Exercise

MacKenzie, Matthew G.; Hamilton, D. Lee; Pepin, Mark E; Patton, Amy; Baar, Keith

doi:10.1371/journal.pone.0068743

Cited by 58 publications

(56 citation statements)

References 37 publications

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“…[25][26][27] Notably, change in the expression myostatin, also released from skeletal muscle, undergoes opposite direction to Irisin release following exercise, as it has been shown that myostatin signaling is inhibited by acute resistance exercise. 28 In addition, myostatin knock out mice displayed BATexpansion, an effect mediated by the AMPK-PGC1a-FNDC5 pathway in skeletal muscle. 29 As well recognized, myostatin, besides being a critical autocrine/paracrine inhibitor of skeletal muscle growth, negatively regulates bone metabolism.…”

Section: Irisin the Messenger Of Healthy Bone-muscle Unitmentioning

confidence: 99%

Role of Irisin on the bone–muscle functional unit

Colaianni

Grano

2015

BoneKEy Reports

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Irisin was originally recognized as a hormone-like myokine secreted as a product of fibronectin type III domain containing 5 from skeletal muscle in response to exercise both in mice and humans. The first role attributed to Irisin was its ability to induce trans-differentiation of white adipose tissue into brown, but we recently demonstrated that Irisin also has a central role in the control of bone mass, even at lower concentration than required to induce the browning response. Considering how physical exercise is important for the development of an efficient load-bearing skeleton, we can now consider this myokine as one of the molecules responsible for the positive correlation between exercise and healthy bone, linking to the well-established relationship between muscle and bone. Recombinant Irisin (r-Irisin), administered at low dose in young mice, increases cortical bone mineral density and positively modifies bone geometry. Irisin exerts its effect prevalently on osteoblast lineage by enhancing differentiation and activity of bone-forming cells, through the increase in activating transcription factor 4 expression. Low-dose r-Irisin also increases osteopontin and decreases sclerostin synthesis but did not affect Uncoupling protein 1 expression in white adipose tissue, whose upregulation is known to cause browning of fat, when Irisin is administered at a higher dose. These findings offer an explanation to the positive outcome on the skeleton triggered by skeletal muscle during physical activity and prove that the bone tissue is more sensitive than the adipose tissue to the Irisin action.

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Section: Irisin the Messenger Of Healthy Bone-muscle Unitmentioning

confidence: 99%

Role of Irisin on the bone–muscle functional unit

Colaianni

Grano

2015

BoneKEy Reports

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“…Hence, Irisin and myostatin, both produced by skeletal muscle, are opposite actors in the functional bonemuscle unit. Moreover, their secretion is inversely regulated by physical activity that, while increasing Irisin, downregulates myostatin synthesis [36].…”

Section: Irisin and The Musclementioning

confidence: 99%

Crosstalk Between Muscle and Bone Via the Muscle-Myokine Irisin

Colaianni

Mongelli

Colucci

et al. 2016

Curr Osteoporos Rep

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Several lines of evidence have recently established that skeletal muscle is an endocrine organ producing and releasing myokines acting in a paracrine or endocrine fashion. Among these, the newly identified myokine Irisin, produced by skeletal muscle after physical exercise, was originally described as molecule able to promote energy expenditure in white adipose tissue. Recently, it has been shown that the myokine Irisin affects skeletal metabolism in vivo. Thus, mice treated with a micro-dose of r-Irisin displayed improved cortical bone mass, geometry and strength, resembling the effect of physical activity in developing an efficient load-bearing skeleton. Further studies highlighted the autocrine effect of Irisin on skeletal muscle, and research performed in humans has definitively established that Irisin is a circulating hormone-like myokine, increased by physical activity. Albeit there are still few, since Irisin has been very recently discovered, herein are summarized the most relevant research findings published on this topic.

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“…As described above, myostatin mRNA levels do not predict load-induced skeletal muscle hypertrophy [57]. Furthermore, we have not seen changes in Smad2/3 [130] or Smad1/5/8 (Aguirre et al in preparation) phosphorylation following resistance exercise. In spite of the absence of differences in Smad phosphorylation, the expression of a Smad2/3 inhibited mRNA increases in proportion to the degree of muscle hypertrophy following training [130].…”

Section: Molecular Signals Underlying Load-induced Skeletal Muscle Hymentioning

confidence: 50%

The Molecular Basis for Load-Induced Skeletal Muscle Hypertrophy

2014

Self Cite

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In a mature (weight neutral) animal, an increase in muscle mass only occurs when the muscle is loaded sufficiently to cause an increase in myofibrillar protein balance. A tight relationship between muscle hypertrophy, acute increases in protein balance, and the activity of the mechanistic target of rapamycin complex 1 (mTORC1) was demonstrated 15 years ago. Since then, our understanding of the signals that regulate load-induced hypertrophy has evolved considerably. For example, we now know that mechanical load activates mTORC1 in the same way as growth factors, by moving TSC2 (a primary inhibitor of mTORC1) away from its target (the mTORC activator) Rheb. However, the kinase that phosphorylates and moves TSC2 is different in the two processes. Similarly, we have learned that a distinct pathway exists whereby amino acids activate mTORC1 by moving it to Rheb. While mTORC1 remains at the forefront of load-induced hypertrophy, the importance of other pathways that regulate muscle mass are becoming clearer. Myostatin, is best known for its control of developmental muscle size. However, new mechanisms to explain how loading regulates this process are suggesting that it could play an important role in hypertrophic muscle growth as well. Lastly, new mechanisms are highlighted for how β2 receptor agonists could be involved in load-induced muscle growth and why these agents are being developed as non-exercise-based therapies for muscle atrophy. Overall, the results highlight how studying the mechanism of load-induced skeletal muscle mass is leading the development of pharmaceutical interventions to promote muscle growth in those unwilling or unable to perform resistance exercise.

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Inhibition of Myostatin Signaling through Notch Activation following Acute Resistance Exercise

Cited by 58 publications

References 37 publications

Role of Irisin on the bone–muscle functional unit

Role of Irisin on the bone–muscle functional unit

Crosstalk Between Muscle and Bone Via the Muscle-Myokine Irisin

The Molecular Basis for Load-Induced Skeletal Muscle Hypertrophy

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