Back in 2003, laboratories around the world were busy identifying a dizzying array of factors secreted by fat cells. Ever since the discovery of leptin, adipose tissue had become well established as an ‘endocrine organ’ that secreted a range of molecules commonly now referred to as ‘adipokines’.
In a paper published in 2003 in Hormone and Metabolic Research, we reported that endothelial cell specific molecule (ESM)-1, originally identified in lung and kidney endothelial cells, where its expression is regulated by cytokines, was also expressed in fat cells.
Previous in vitro studies had shown that ESM-1 interferes with the molecular mechanisms of immune cell migration by binding to adhesion molecules.
In our study, we explored the expression of ESM-1 in isolated human adipocytes and in rat adipose tissue depots. Human primary adipocytes were cultivated after collagenase digestion and used for in vitro incubation studies. Adipocytes were also isolated from different fat depots of Sprague-Dawley rats.
Using gene expression techniques and confocal microscopy, we demonstrated that ESM-1 was expressed in both human and rat adipose tissue and showed that its expression was stimulated by phorbol ester, an activator of protein kinase C, and by retinoic acid, an activator of nuclear receptors.
The highest expression was found in subcutaneous rat adipose tissue – two-fold compared to epididymal and six-fold compared to intrascapular brown adipose tissue.
Based on the emerging evidence that obesity is related to systemic inflammation, we speculated that the formation of ESM-1 in adipocytes and its activation by protein kinase C may play a role in the regulation of inflammatory processes in fat tissue.
Judging by the rather modest 17 citations of this paper, our finding of ESM-1 in fat tissue may not have been quite that important a discovery after all.