New Insights on the Role of Connexins and Gap Junctions Channels in Adipose Tissue and Obesity

Abstract

Due to the inability to curb the excessive increase in the prevalence of obesity and overweight, it is necessary to comprehend in more detail the factors involved in the pathophysiology and to appreciate more clearly the biochemical and molecular mechanisms of obesity. Thus, understanding the biological regulation of adipose tissue is of fundamental relevance. Connexin, a protein that forms intercellular membrane channels of gap junctions and unopposed hemichannels, plays a key role in adipogenesis and in the maintenance of adipose tissue homeostasis. The expression and function of Connexin 43 (Cx43) during the different stages of the adipogenesis are differentially regulated. Moreover, it has been shown that cell–cell communication decreases dramatically upon differentiation into adipocytes. Furthermore, inhibition of Cx43 degradation or constitutive overexpression of Cx43 blocks adipocyte differentiation. In the first events of adipogenesis, the connexin is highly phosphorylated, which is likely associated with enhanced Gap Junction (GJ) communication. In an intermediate state of adipocyte differentiation, Cx43 phosphorylation decreases, as it is displaced from the membrane and degraded through the proteasome; thus, Cx43 total protein is reduced. Cx is involved in cardiac disease as well as in obesity-related cardiovascular diseases. Different studies suggest that obesity together with a high-fat diet are related to the production of remodeling factors associated with expression and distribution of Cx43 in the atrium.

Full-Length Transcriptome and Gene Expression Analysis of Different Ovis aries Adipose Tissues Reveals Transcript Variants Involved in Lipid Biosynthesis

“…During the initial process of fat formation, connexins are highly phosphorylated. In the intermediate state of adipocyte differentiation, Cx43 is translocated from the membrane and phosphorylation is reduced by proteasome degradation [ 52 ]. In the DEI PPI networks of TF and SF, the hub isoforms, including XM_012180724.3, NC_056054.1.4780.11, NC_056064.1.197.5, NC_056064.1.1711.2, and isoforms XM_012180724.3, NC_056054.1.4780.11, NC_056064.1.1711.2, and Xm_015093599.3, were all enriched in the Proteasome KEGG pathway.…”

Biofabrication of 3D adipose tissue via assembly of composite stem cell spheroids containing adipo-inductive dual-signal delivery nanofibers

“…In previous studies, adipogenic differentiation has been shown to trigger the formation of lipid droplets, significantly reducing the cellular cytoplasmic space and leading to morphological hypertrophy [52,53]. Cells in this hypertrophic state exhibited a weakened response to shear stress and external stimulation, with notable reductions in the expression of junction proteins such as Connexin 43 on the cell surface, resulting in diminished adhesive capacity and very low host tissue integration [54]. Moreover, adipogenesis down-regulates RhoA activity, inducing the depolymerization of stress fibers into the G-actin monomer state [14].…”

The proarrhythmogenic role of autonomics and emerging neuromodulation approaches to prevent sudden death in cardiac ion channelopathies

“…Adiponectin is not the only promising target with other metabolic targets involved in connexin and gap junction signalling already highlighted. 157 Yet, overall, the highly complex metabolic–immunological–autonomic cardiac interactions and their contribution to ventricular arrhythmogenesis are still poorly understood.…”