The action of obestatin in skeletal muscle repair: stem cell expansion, muscle growth, and microenvironment remodeling

The development of therapeutic strategies for skeletal muscle diseases, such as physical injuries and myopathies, depends on the knowledge of regulatory signals that control the myogenic process. The obestatin/GPR39 system operates as an autocrine signal in the regulation of skeletal myogenesis. Using a mouse model of skeletal muscle regeneration after injury and several cellular strategies, we explored the potential use of obestatin as a therapeutic agent for the treatment of trauma-induced muscle injuries. Our results evidenced that the overexpression of the preproghrelin, and thus obestatin, and GPR39 in skeletal muscle increased regeneration after muscle injury. More importantly, the intramuscular injection of obestatin significantly enhanced muscle regeneration by simulating satellite stem cell expansion as well as myofiber hypertrophy through a kinase hierarchy. Added to the myogenic action, the obestatin administration resulted in an increased expression of VEGF/VEGFR2 and the consequent microvascularization, with no effect on collagen deposition in skeletal muscle. Furthermore, the potential inhibition of myostatin during obestatin treatment might contribute to its myogenic action improving muscle growth and regeneration. Taken together, our data demonstrate successful improvement of muscle regeneration, indicating obestatin is a potential therapeutic agent for skeletal muscle injury and would benefit other myopathies related to muscle regeneration

Decreased serum obestatin consequent upon <it>TRIB3</it> Q84R polymorphism exacerbates carotid atherosclerosis in subjects with metabolic syndrome

<p>Abstract</p> <p>Background</p> <p>Functional <it>TRIB3</it> Q84R polymorphism has been associated with insulin resistance. Obestatin, improving insulin resistance, exerts obscure effects on metabolic syndrome (MetS) and carotid atherosclerosis. Aims to investigate whether the prevalent <it>TRIB3</it> Q84R polymorphism has profound implications for alterations of serum obestatin and what effect obestatin exerts on carotid atherosclerosis.</p> <p>Methods</p> <p>A total of 518 unrelated Chinese subjects consisted of control (n = 258) and MetS (n = 260) groups. Clinical and biochemical characteristics were collected. The level of serum obestatin was measured. Genotype the functional <it>TRIB3</it> Q84R polymorphism. All subjects underwent ultrasonography to determine carotid intima-media thickness (IMT).</p> <p>Results</p> <p>Serum obestatin was significantly decreased in MetS as compared with the control group (<it>P</it> = 0.042). Among the MetS group participants possessing RR84 genotype had significantly lower levels of serum obestatin than those with QQ84 or QR84 genotypes (<it>P</it> = 0.008, <it>P</it> = 0.043) with similar significant difference among the control group. Factorial analyses showed statistically significant interactions between MetS and RR84 genotype (<it>P</it> = 0.009 for interaction for obestatin). On correlation analysis, obestatin correlated negatively with homeostasis model assessment insulin resistance (<it>r</it> = -0.163, <it>P</it> = 0.010) and IMT (<it>r</it> = -0.256, <it>P</it> = 0.011). On partial analyses, obestatin negatively correlated with IMT(<it>r</it> = -0.259, <it>P</it> = 0.024) after controlling for the confounding factors.</p> <p>Conclusion</p> <p>MetS individuals with <it>TRIB3</it> RR84 genotype demonstrated further decreased serum obestatin. Decreased serum obestatin might in part exacerbate insulin resistance and carotid atherosclerosis.</p

The SHP-1 protein tyrosine phosphatase negatively modulates Akt signaling in the ghrelin/GHSR1a system

The SHP-1 tyrosine phosphatase is a negative regulator of ghrelin activity, being a critical signaling component for proper regulation of Akt-dependent processes. Based on the SHP-1 expression pattern in white adipose tissue (WAT) and its regulation in a positive energy balance situation, it is possible to speculate about its role in the enlargement of WAT in obesity