Expression of genes involved with the maintenance of skeletal muscle phenotype in aged rats submitted to perinatal malnutrition

Abstract

Some perinatal events, such as nutritional restriction in the intrauterine period and lactation, may promote irreversible physiological adaptations for the fetus, a process called fetal programming. Studies show that intrauterine and/or perinatal malnutrition is related to low pup weight at birth, with risks of cardiovascular and metabolic diseases in adults; also promotes changes in myogeny and postnatal muscle growth, processes regulated by various signaling pathways, such as the transcriptional factors of myogenic regulation (MRFs) and IGF-1 (anabolism), the ubiquitin proteasome system (catabolism), and the expression of myofrogenic Myostatin (MSTN), a negative regulator of muscle growth; These changes may compromise the establishment and maintenance of muscle phenotype, longevity, and quality of life of adults. This condition presents aggravating factors during aging, when muscle loss (sarcopenia) occurs. Although it has been observed that nutritional restriction in the intrauterine period may accelerate muscle aging, the cellular and molecular mechanisms involved in these changes are not well established. The hypothesis of our study is that intrauterine malnutrition and lactation alters the pattern of gene expression involved in the maintenance of the skeletal muscle phenotype of aged rats. The objective of this work is to analyze the expression of genes involved in the maintenance of the skeletal muscle phenotype in aged rats submitted to perinatal protein malnutrition. It will be employed Sprague-Dawley rats (CEEA-573), evaluated in a 540-day period (material already collected), from two mother groups submitted to different diets (hypoproteic: 6% protein, and standard: 17% protein) during the entire gestational period and lactation. At the end of the experiment, the animals were weighed and euthanized to collect samples of the soleus muscles (SOL) with oxidative metabolism/slow contraction, and Long Finger Extension (EDL) with glycolytic metabolism/rapid contraction for morphological and molecular analyzes (N = 8). Hematoxylin-Eosin (HE) staining will be used for the measurement of the cross-sectional area (AST) of muscle, Immunohistochemistry for characterization of muscle fiber types, and RTqPCR gene expression of the myogenic regulation factors MyoD and Myogenin, IGF- 1, of the atrogenes Murf1 and MAFBx, and of the myostatin growth factor. Results will be submitted to appropriate statistical analysis. (AU)