Circulating Sclerostin and Irisin Are Related and Interact with Gender to Influence Adiposity in Adults with Prediabetes

Mongelli

Colucci

et al. 2016

Curr Osteoporos Rep

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.

Section: Irisin and The Bonesupporting

confidence: 77%

Crosstalk Between Muscle and Bone Via the Muscle-Myokine Irisin

Mongelli

Colucci

et al. 2016

Curr Osteoporos Rep

“…Load-induced decreases in Sost expression have been associated with increased bone formation (43). Furthermore, and interestingly, serum irisin levels in people are inversely correlated with serum sclerostin levels independently of age or sex (44). There is also an inverse correlation between serum irisin levels and vertebral fragility fractures in postmenopausal women (45,46).…”

Section: Discussionmentioning

confidence: 99%

The myokine irisin increases cortical bone mass

Proc. Natl. Acad. Sci. U.S.A.

Cuscito

Mongelli

et al. 2015

404

399

It is unclear how physical activity stimulates new bone synthesis. We explored whether irisin, a newly discovered myokine released upon physical activity, displays anabolic actions on the skeleton. Young male mice were injected with vehicle or recombinant irisin (r-irisin) at a low cumulative weekly dose of 100 µg kg(-1). We observed significant increases in cortical bone mass and strength, notably in cortical tissue mineral density, periosteal circumference, polar moment of inertia, and bending strength. This anabolic action was mediated primarily through the stimulation of bone formation, but with parallel notable reductions in osteoclast numbers. The trabecular compartment of the same bones was spared, as were vertebrae from the same mice. Higher irisin doses (3,500 µg kg(-1) per week) cause browning of adipose tissue; this was not seen with low-dose r-irisin. Expectedly, low-dose r-irisin modulated the skeletal genes, Opn and Sost, but not Ucp1 or Pparγ expression in white adipose tissue. In bone marrow stromal cell cultures, r-irisin rapidly phosphorylated Erk, and up-regulated Atf4, Runx2, Osx, Lrp5, β-catenin, Alp, and Col1a1; this is consistent with a direct receptor-mediated action to stimulate osteogenesis. We also noted that, although the irisin precursor Fndc5 was expressed abundantly in skeletal muscle, other sites, such as bone and brain, also expressed Fndc5, albeit at low levels. Furthermore, muscle fibers from r-irisin-injected mice displayed enhanced Fndc5 positivity, and irisin induced Fdnc5 mRNA expression in cultured myoblasts. Our data therefore highlight a previously unknown action of the myokine irisin, which may be the molecular entity responsible for muscle-bone connectivity

“…With regard to the skeleton, Irisin levels were found inversely correlated with serum sclerostin levels in adults, independent of age or gender. 43 Likewise, post-menopausal women showed inverse correlation between Irisin levels and vertebral fragility fractures. 44,45 Conversely, Irisin measured in athletes was positively associated with bone density and strength, 46 supporting the idea that Irisin could have a protective role on bone health.…”

Section: Irisin Synthesis Beyond the Muscle And Its Autocrine Actionmentioning

confidence: 98%

Role of Irisin on the bone–muscle functional unit

Grano

2015

BoneKEy Reports

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.