Muscle, a multinucleate syncytium formed by the fusion of mononuclear myoblasts, arises from quiescent progenitors (satellite cells) via activation of muscle-specific transcription factors (MyoD, Myf5, myogenin: MYOG, and MRF4). Subsequent to a decline in Pax7, induction in the expression of MYOG is a hallmark of myoblasts that have entered the differentiation phase following cell cycle withdrawal. It is evident that MYOG function cannot be compensated by any other myogenic regulatory factors (MRFs). Despite a plethora of information available regarding MYOG, the mechanism by which MYOG regulates muscle cell differentiation has not yet been identified. Using an RNA-Seq approach, analysis of MYOG knock-down muscle satellite cells (MSCs) have shown that genes associated with cell cycle and division, DNA replication, and phosphate metabolism are differentially expressed. By constructing an interaction network of differentially expressed genes (DEGs) using GeneMANIA, cadherin-associated protein (CTNNA2) was identified as the main hub gene in the network with highest node degree. Four functional clusters (modules or communities) were identified in the network and the functional enrichment analysis revealed that genes included in these clusters significantly contribute to skeletal muscle development. To confirm this finding, in vitro studies revealed increased expression of CTNNA2 in MSCs on day 12 compared to day 10. Expression of CTNNA2 was decreased in MYOG knock-down cells. However, knocking down CTNNA2, which leads to increased expression of extracellular matrix (ECM) genes (type I collagen α1 and type I collagen α2) along with myostatin (MSTN), was not found significantly affecting the expression of MYOG in C2C12 cells. We therefore propose that MYOG exerts its regulatory effects by acting upstream of CTNNA2, which in turn regulates the differentiation of C2C12 cells via interaction with ECM genes. Taken together, these findings highlight a new mechanism by which MYOG interacts with CTNNA2 in order to promote myoblast differentiation.
Obesity and obesity-related comorbidities have transformed into a global epidemic. The number of people suffering from obesity has increased dramatically within the past few decades. This rise in obesity cannot alone be explained by genetic factors; however, diet, environment, lifestyle, and presence of other diseases undoubtedly contribute towards obesity etiology. Nevertheless, evidence suggests that alterations in the gut microbial diversity and composition have a role to play in energy assimilation, storage, and expenditure. In this review, the impact of gut microbiota composition on metabolic functionalities, and potential therapeutics such as gut microbial modulation to manage obesity and its associated comorbidities are highlighted. Optimistically, an understanding of the gut microbiome could facilitate the innovative clinical strategies to restore the normal gut flora and improve lifestyle-related diseases in the future.