Adipocytes in both brown and white adipose tissue of adult mice are functionally connected via gap junctions: implications for Chagas disease

Abstract

Adipose tissue serves as a host reservoir for the protozoan Trypanosoma cruzi, the causative organism in Chagas disease. Gap junctions interconnect cells of most tissues, serving to synchronize cell activities including secretion in glandular tissue, and we have previously demonstrated that gap junctions are altered in various tissues and cells infected with T. cruzi. Herein, we examined the gap junction protein connexin 43 (Cx43) expression in infected adipose tissues. Adipose tissue is the largest endocrine organ of the body and is also involved in other physiological functions. In mammals, it is primarily composed of white adipocytes. Although gap junctions are a prominent feature of brown adipocytes, they have not been explored extensively in white adipocytes, especially in the setting of infection. Thus, we examined functional coupling in both white and brown adipocytes in mice. Injection of electrical current or the dye Lucifer Yellow into adipocytes within fat tissue spread to adjacent cells, which was reduced by treatment with agents known to block gap junctions. Moreover, Cx43 was detected in both brown and white fat tissue. At thirty and ninety days post-infection, Cx43 was downregulated in brown adipocytes and upregulated in white adipocytes. Gap junction-mediated intercellular communication likely contributes to hormone secretion and other functions in white adipose tissue and to nonshivering thermogenesis in brown fat, and modulation of the coupling by T. cruzi infection is expected to impact these functions.

Connexin 43 Mediates White Adipose Tissue Beiging by Facilitating the Propagation of Sympathetic Neuronal Signals

“…These data agree with previous studies that identified Cx43 as the most abundant connexin gene in the adipose tissue (Burke et al, 2014). Using qPCR assays, we verified that cold induces Cx43 gene expression 15-fold, a much higher de facto increase than the 2.90-fold change indicated by our microarray study.…”

“…The experimental procedure was adapted from a previous publication (Burke et al, 2014). Briefly, experiments were performed using an upright microscope (Nikon Eclipse FN1) equipped with a fixed stage and a QuantEM:512SC electron-multiplying charge-coupled device camera, connected to a computer running NIS-Elements AR 3.2 proprietary imaging software.…”

“…Several reports describe that gap junction function is tightly modulated during WAT and BAT development (Schneider-Picard et al, 1980; Yanagiya et al, 2007). Adipocytes in BAT of adult mice seem functionally connected via gap junctions, whereas adipocytes in WAT appear to be connected much less effectively (Burke et al, 2014). …”

Adipose Tissue: A Safe Haven for Parasites?

“…Both BAT and WAT obtained from T. cruz i-infected mice display increased markers of oxidative stress, findings consistent with the persistent inflammatory state observed [38]. T. cruzi infection of AT alters the expression and function of the connexin-43 gap junction protein, which may have widespread implications for intercellular communication in AT [39]. Caradonna and colleagues have demonstrated that the pre-replication phase of the T. cruzi infection cycle is predominantly affected by host cell signaling pathways and cytoskeletal regulators.…”

<b>Participação da conexina 32 na fisiopatogênese da doença hepática gordurosa não alcoólica em camundongos</b>

“…Há relatos de junções comunicantes interligando adipócitos da gordura marrom (REVEL; SHERIDAN, 1968;LINCK et al, 1974), mas sobre a gordura branca pouco se sabe. Burke et al(2014) (MATSUDA et al, 2009;WANG et al, 2011).…”