Myostatin HMP 1mg

Myostatin HMP 1mg


Myostatin HMP 1mg  Mexico Supreme Peptides

La miostatina es una proteína perteneciente a la familia del factor de crecimiento de transformación (TGF)-ß, que desempeña un papel fundamental en el control del desarrollo muscular. Como ocurre con el resto de miembros de la familia del TGF-ß, la miostatina se sintetiza en forma de un precursor inactivo que ha de tener un procesamiento proteolítico para dar lugar a la forma madura. La miostatina se expresa de forma casi exclusiva en el músculo esquelético donde actúa de forma autocrina/paracrina al inhibir el desarrollo muscular. En ratones, el bloqueo de la miostatina produce un marcado aumento de la masa muscular y una disminución de la adiposidad. Este efecto sobre el tejido adiposo es tan marcado que el bloqueo de la miostatina es incluso capaz de revertir la obesidad en diversas cepas de ratones. Debido a estas acciones, se está comenzando a estudiar el uso de fármacos capaces de bloquear la miostatina para la prevención y el tratamiento de la obesidad, la diabetes tipo 2.


The TGFβ family member myostatin (growth/differentiation factor-8) is a negative regulator of skeletal muscle growth. The hypermuscular Compact mice carry the 12-bp Mstn(Cmpt-dl1Abc) deletion in the sequence encoding the propeptide region of the precursor promyostatin, and additional modifier genes of the Compact genetic background contribute to determine the full expression of the phenotype. In this study, by using mice strains carrying mutant or wild-type myostatin alleles with the Compact genetic background and nonmutant myostatin with the wild-type background, we studied separately the effect of the Mstn(Cmpt-dl1Abc) mutation or the Compact genetic background on morphology, metabolism, and signaling. We show that both the Compact myostatin mutation and Compact genetic background account for determination of skeletal muscle size. Despite the increased musculature of Compacts, the absolute size of heart and kidney is not influenced by myostatin mutation; however, the Compact genetic background increases them. Both Compact myostatin and genetic background exhibit systemic metabolic effects. The Compact mutation decreases adiposity and improves whole body glucose uptake, insulin sensitivity, and 18FDG uptake of skeletal muscle and white adipose tissue, whereas the Compact genetic background has the opposite effect. Importantly, the mutation does not prevent the formation of mature myostatin; however, a decrease in myostatin level was observed, leading to altered activation of Smad2, Smad1/5/8, and Akt, and an increased level of p-AS160, a Rab-GTPase-activating protein responsible for GLUT4 translocation. Based on our analysis, the Compact genetic background strengthens the effect of myostatin mutation on muscle mass, but those can compensate for each other when systemic metabolic effects are compared.

myostatin [growth/differentiation factor-8 (GDF-8)] is a member of the TGFβ superfamily and is expressed predominantly in skeletal muscle (31). Myostatin is synthesized as a precursor protein, promyostatin, which undergoes dimerization and proteolytic processing; promyostatin dimer is cleaved by furin proteases to NH2-terminal propeptide fragments and COOH-terminal disulfide-linked myostatin dimer (24). However, the propeptides can still associate with myostatin dimer via noncovalent bonds to form a latent complex that sequesters functional myostatin by preventing its binding to the receptor (24, 45). Myostatin acts through activin type IIB receptor (ActRIIB) (24), and the signaling involves Smad2/3 transcription factors (23, 57); furthermore, it influences the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, which is the key regulator of the anabolic and catabolic responses in skeletal muscle (53).

Myostatin regulates the proliferation and differentiation of myoblasts (23, 46); moreover, it also controls the activation and proliferation of satellite cells, the stem cells of skeletal muscle (29). Homozygous disruption of the myostatin gene (31), administration of myostatin propeptide (25), or naturally occurring myostatin gene mutations, e.g., in humans (38), mouse (42), cattle (20), or sheep (10), result in widespread increase of skeletal muscle mass (“double-muscled” phenotype). However, the effect of myostatin is not restricted to skeletal muscle. Beside the autocrine and paracrine effects, it can serve as an endocrine factor. Myostatin was reported to influence the synthesis and secretion of IGF-1 (insulin-like growth factor-1) in the liver, thereby regulating the amount of circulating IGF-1 (51).

Several studies suggest that loss of myostatin or reduction in active myostatin levels leads to increased insulin sensitivity. Myostatin-null mice have increased muscle mass and reduced body fat (14, 26, 32) and exhibit increased insulin sensitivity (14), which depends on AMP-activated protein kinase (55). Transgenic expression of myostatin propeptide prevents diet-induced obesity and insulin resistance (56), and the overexpression of follistatin-like 3, an inhibitor of members of the TGFβ family (6), or inhibition of myostatin by dominant-negative myostatin receptor (13) improves insulin sensitivity. Furthermore, increased serum and muscle myostatin levels were shown in insulin-resistant human individuals (17).

The naturally occurring Compact mutation of the myostatin gene arose in a selection program on protein amount and hypermuscularity conducted at the Technical University of Berlin (7, 8). Genetic analysis of the Hungarian subpopulation of the hypermuscular Compact mice identified a 12-bp deletion, denoted Mstn(Cmpt-dl1Abc), in the propeptide of the promyostatin (42). The biologically active growth factor domain of myostatin is unaffected by Compact mutation; therefore, the loss of myostatin activity cannot be explained by disruption of the growth factor bioactive domain. However, the mutation can lead to misfolding or defect in secretion and mistargeting of mature myostatin (42). Additional modifier genes should be present to determine the full expression of the Compact phenotype; however, these modifier genes of the special Compact genetic background have not yet been identified (47, 48). Furthermore, the molecular consequences of Compact myostatin mutation, which can regulate muscle size and metabolism, have not been examined. In this study, by using a congenic wild-type mice strain with wild-type myostatin and Compact genetic background, we could separately study the effect of Compact myostatin mutation and genetic background on morphology, metabolism, and signaling. The Compact mice show several similarities compared with myostatin knockout animals; however, numerous alterations exist. The Compact mutation decreased adiposity and improved insulin sensitivity and glucose uptake, whereas the genetic background exhibited the opposite effect. Importantly, here we show that the mature myostatin protein is present in Compact mice, and the 12-bp deletion in the sequence encoding the propeptide decreased the formation of mature myostatin in accordance with increased muscle mass.



The Compact line carrying the 12-bp deletion in the propeptide of promyostatin (Fig. 1A) was selected and inbred in a long-term selection experiment in Berlin, Germany (8, 50). The origin of the Hungarian subpopulation of the Compact line was described earlier (3, 22). The BALB/c mice carrying wild-type myostatin were obtained from the Biological Research Centre of the Hungarian Academy of Sciences (Szeged, Hungary).

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