Adipose tissue is a dynamic endocrine organ with a central role in metabolism regulation. Functional differences in adipose tissue seem associated with the regional distribution of fat depots, in particular in subcutaneous and visceral omental pads. Here, we report for the first time the isolation of human adipose-derived adult stem cells from visceral omental and subcutaneous fat (V-ASCs and S-ASCs, respectively) from the same subject. Immunophenotyping shows that plastic culturing selects homogeneous cell populations of V-ASCs and S-ASCs from the corresponding stromal vascular fractions (SVFs), sharing typical markers of mesenchymal stem cells. Electron microscopy and electrophysiological and real-time RT-PCR analyses confirm the mesenchymal stem nature of both V-ASCs and S-ASCs, while no significant differences in a limited pattern of cytokine/chemokine expression can be detected. Similar to S-ASCs, V-ASCs can differentiate in vitro toward adipogenic, osteogenic, chondrogenic, muscular, and neuronal lineages, as demonstrated by histochemical, immunofluorescence, real-time RT-PCR, and electrophysiological analyses, suggesting the multipotency of such adult stem cells. Our data demonstrate that both visceral and subcutaneous adipose tissues are a source of pluripotent stem cells with multigermline potential. However, the visceral rather than the subcutaneous ASC could represent a more appropriate in vitro cell model for investigating the molecular mechanisms implicated in the pathophysiology of metabolic disorders such as obesity.

We identified a novel Src isoform in human spermatozoa, which appears to be involved in regulating sperm capacitation, calcium fluxes, tyrosine phosphorylation and acrosome reaction.

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Objective-Microvascular endothelium is one of the main targets of the inflammatory response. On specific activation, endothelial cells recruit Th1-lymphocytes at the inflammatory site. We investigated the intracellular signaling mediating tumor necrosis factor (TNF)-␣ and interferon (IFN)-␥ inflammatory response in human microvascular endothelial cells (HMEC-1) and the interfering effects of the peroxisome-proliferator-activated-receptor (PPAR␥) agonist, rosiglitazone (RGZ). Methods and Results-TNF␣ and IFN␥, mainly when combined, stimulate IFN␥-inducible protein of 10 kDa (IP10) and fractalkine production evaluated by ELISA and TaqMan analyses. This effect is not only mediated by activation of the NFkB and Stat1 classic pathways, but also involves a rapid increase in phosphorylation and activation of extracellular signal-regulated kinases (ERK1/2) as measured by Western blot. RGZ interferes with TNF␣ and IFN␥ stimulation of IP10, fractalkine, and adhesion molecule through a novel rapid mechanism which involves the blocking of ERK activation. Key Words: thiazolidinediones Ⅲ MAPK Ⅲ CXCL10 Ⅲ endothelium Ⅲ Th1-response T umor necrosis factor (TNF)-␣ and interferon (IFN)-␥ are the pivotal cytokines coordinating interactions between infiltrating lymphocytes/macrophages and resident cells during the vascular inflammatory Th1-response. Th1-oriented immune responses are implicated in several systemic pathologies such as autoimmune diseases, atherogenesis, type 2 diabetes (T2D), and they also play a major role in the development of acute and chronic rejection as well as in chronic allograft nephropathy. 1 IFN␥, primarily secreted by activated T-lymphocytes, represents the cardinal Th1-cytokine whereas TNF␣, secreted by monocytes, macrophages, and resident cells, is considered a pleiotropic cytokine involved in a general inflammatory response. Both cytokines modulate the expression of cellular adhesion molecules (CAM) in endothelial cells (ECs). A synergistic action of TNF␣ and IFN␥ in promoting inflammatory response through chemokine secretion has been described. 2 In particular, IFN␥ induces ECs to secret CXC chemokines, such as fractalkine, IFN␥-inducible T-cell ␣-chemoattractant, monokine-induced by IFN␥ and IFN␥-inducible protein of 10 kDa (IP10). Both IP10 and fractalkine chemoattractant activity is directed toward Th1-lymphocytes. 1,3 Thiazolidinediones (TZD) are a pharmacological class of drugs currently used in T2D to improve glucose homeostasis by increasing insulin sensitivity. Besides their well established effects on lipid metabolism and glucose homeostasis, a novel role of TZD in regulating the inflammatory response 4 through a direct action on cells of natural and induced immunity is recently emerging, both in vitro and in animal models of human inflammatory disorders. 5,6 Experimental evidence suggests that the TZD receptor, PPAR␥, interferes with cytokine-induced chemokine secretion in monocytes, 7 macrophages, 8 and venous endothelial cells. 9 TZD action seems to be mainly attributable to their ability ...