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

Increment at molt for the Norway lobster (Nephrops norvegicus) from the south coast of Portugal

The increment at molt for Nephrops norvegicus was studied with the objective of obtaining a model for prediction of post-molt size based on pre-molt size for the population from the south coast of Portugal. Wild animals were maintained in a specially prepared laboratory facility until they malted. Individual values of increment at molt were obtained and used to evaluate alternative models and estimate their parameters. Six alternative models, used previously by several authors to relate pre- and post-molt size, were modified so that increment at molt was the dependent variable and pre-molt size the independent variable. These included the linear relationship of the growth factor (GF) on pre-molt size, the Hiatt equation, post-molt size a power function of pre-molt size, the hyperbolic function, GF exponential function of pre-molt size and the Misra equation. The analysis of the data showed that none of the models could be used to predict increment at molt for either sex. The distribution of the increment at molt was a random normal variable, with mean values not significantly different between sexes, 2.78 mm for males and 2.26 mm for females, variances 0.47 and 0.59, respectively. An analysis of the models suggests that using post-molt size or the GF as dependent variables may lead to a misinterpretation of the dependency of these variables on pre-molt size. It is suggested that the increment at molt should be the variable of interest for predicting post-molt size. The choice of a mathematical formulation should, besides having biological meaning, have the capacity of expressing a true relationship between increment at molt and pre-molt carapace length, namely, be able to model several options for the increment at molt after maturity, including a steady increase of the increment through life, the stabilization of the increment after maturity or the decrease of the increment for larger sizes. (C) 2003 International Council for the Exploration of the Sea. Published by Elsevier Ltd. All rights reserved.info:eu-repo/semantics/publishedVersio

Role of AMP-activated protein kinase in adipose tissue metabolism and inflammation

AMPK (AMP-activated protein kinase) is a key regulator of cellular and whole-body energy balance. AMPK phosphorylates and regulates many proteins concerned with nutrient metabolism, largely acting to suppress anabolic ATP-consuming pathways while stimulating catabolic ATP-generating pathways. This has led to considerable interest in AMPK as a therapeutic target for the metabolic dysfunction observed in obesity and insulin resistance. The role of AMPK in skeletal muscle and the liver has been extensively studied, such that AMPK has been demonstrated to inhibit synthesis of fatty acids, cholesterol and isoprenoids, hepatic gluconeogenesis and translation while increasing fatty acid oxidation, muscle glucose transport, mitochondrial biogenesis and caloric intake. The role of AMPK in the other principal metabolic and insulin-sensitive tissue, adipose, remains poorly characterized in comparison, yet increasing evidence supports an important role for AMPK in adipose tissue function. Obesity is characterized by hypertrophy of adipocytes and the development of a chronic sub-clinical pro-inflammatory environment in adipose tissue, leading to increased infiltration of immune cells. This combination of dysfunctional hypertrophic adipocytes and a pro-inflammatory environment contributes to insulin resistance and the development of Type 2 diabetes. Exciting recent studies indicate that AMPK may not only influence metabolism in adipocytes, but also act to suppress this pro-inflammatory environment, such that targeting AMPK in adipose tissue may be desirable to normalize adipose dysfunction and inflammation. In the present review, we discuss the role of AMPK in adipose tissue, focussing on the regulation of carbohydrate and lipid metabolism, adipogenesis and pro-inflammatory pathways in physiological and pathophysiological conditions

A longitudinal study of gene expression in first-episode schizophrenia; exploring relapse mechanisms by co-expression analysis in peripheral blood

Little is known about the pathophysiological mechanisms of relapse in first-episode schizophrenia, which limits the study of potential biomarkers. To explore relapse mechanisms and identify potential biomarkers for relapse prediction, we analyzed gene expression in peripheral blood in a cohort of first-episode schizophrenia patients with less than 5 years of evolution who had been evaluated over a 3-year follow-up period. A total of 91 participants of the 2EPs project formed the sample for baseline gene expression analysis. Of these, 67 provided biological samples at follow-up (36 after 3 years and 31 at relapse). Gene expression was assessed using the Clariom S Human Array. Weighted gene co-expression network analysis was applied to identify modules of co-expressed genes and to analyze their preservation after 3 years of follow-up or at relapse. Among the 25 modules identified, one module was semi-conserved at relapse (DarkTurquoise) and was enriched with risk genes for schizophrenia, showing a dysregulation of the TCF4 gene network in the module. Two modules were semi-conserved both at relapse and after 3 years of follow-up (DarkRed and DarkGrey) and were found to be biologically associated with protein modification and protein location processes. Higher expression of DarkRed genes was associated with higher risk of suffering a relapse and early appearance of relapse (p = 0.045). Our findings suggest that a dysregulation of the TCF4 network could be an important step in the biological process that leads to relapse and suggest that genes related to the ubiquitin proteosome system could be potential biomarkers of relapse. © 2021, The Author(s)

Growth at moult, intermoult period, and moulting seasonality of the spider crab Maja brachydactyla: combining information from mark-recapture and experimental studies

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