Adipose tissue is a major source of mesenchymal stem cells (MSCs), which possess a variety of properties that make them ideal candidates for regenerative and immunomodulatory therapies. Here, we compared the immunophenotypic profile of human adipose-derived stem cells (hASCs) from lean and obese individuals, and explored its relationship with the apparent altered plasticity of hASCs. We also hypothesized that persistent hypoxia treatment of cultured hASCs may be necessary but not sufficient to drive significant changes in mature adipocytes. hASCs were obtained from subcutaneous adipose tissue of healthy, adult, female donors undergoing abdominal plastic surgery: lean (n = 8; body mass index [BMI]: 23 6 1 kg/m 2 ) and obese (n = 8; BMI: 35 6 5 kg/m 2 ). Cell surface marker expression, proliferation and migration capacity, and adipogenic differentiation potential of cultured hASCs at two different oxygen conditions were studied. Compared with lean-derived hASCs, obese-derived hASCs demonstrated increased proliferation and migration capacity but decreased lipid droplet accumulation, correlating with a higher expression of human leukocyte antigen (HLA)-II and cluster of differentiation (CD) 106 and lower expression of CD29. Of interest, adipogenic differentiation modified CD106, CD49b, HLA-ABC surface protein expression, which was dependent on the donor's BMI. Additionally, low oxygen tension increased proliferation and migration of lean but not obese hASCs, which correlated with an altered CD36 and CD49b immunophenotypic profile. In summary, the differences observed in proliferation, migration, and differentiation capacity in obese hASCs occurred in parallel with changes in cell surface markers, both under basal conditions and during differentiation. Therefore, obesity is an important determinant of stem cell function independent of oxygen tension. STEM CELLS TRANSLATIONAL MEDICINE 2016;5:464-475 SIGNIFICANCEThe obesity-related hypoxic environment may have latent effects on human adipose tissue-derived mesenchymal stem cells (hASCs) with potential consequences in mature cells. This study explores the immunophenotypic profile of hASCs obtained from lean and obese individuals and its potential relationship with the altered plasticity of hASCs observed in obesity. In this context, an altered pattern of cell surface marker expression in obese-derived hASCs in both undifferentiated and differentiated stages is demonstrated. Differences in proliferation, migration, and differentiation capacity of hASCs from obese adipose tissue correlated with alterations in cell surface expression. Remarkably, altered plasticity observed in obese-derived hASCs was maintained in the absence of hypoxia, suggesting that these cells might be obesity conditioned.

. contributed equally to this manuscript. BACKGROUND AND PURPOSEGlucagon-like peptide-1 (GLP-1) analogues improve glycaemic control in type 2 diabetic (T2D) patients and cause weight loss in obese subjects by as yet unknown mechanisms. We recently demonstrated that the GLP-1 receptor, which is present in adipocytes and the stromal vascular fraction of human adipose tissue (AT), is up-regulated in AT of insulin-resistant morbidly obese subjects compared with healthy lean subjects. The aim of this study was to explore the effects of in vitro and in vivo administration of GLP-1 and its analogues on AT and adipocyte functions from T2D morbidly obese subjects. EXPERIMENTAL APPROACHWe analysed the effects of GLP-1 on human AT and isolated adipocytes in vitro and the effects of GLP-1 mimetics on AT of morbidly obese T2D subjects in vivo. KEY RESULTSGLP-1 down-regulated the expression of lipogenic genes when administered during in vitro differentiation of human adipocytes from morbidly obese patients. GLP-1 also decreased the expression of adipogenic/lipogenic genes in AT explants and mature adipocytes, while increasing that of lipolytic markers and adiponectin. In 3T3-L1 adipocytes, GLP-1 decreased free cytosolic Ca 2+ concentration ([Ca 2+ ] i ). GLP-1-induced responses were only partially blocked by GLP-1 receptor antagonist exendin (9-39). Moreover, administration of exenatide or liraglutide reduced adipogenic and inflammatory marker mRNA in AT of T2D obese subjects. CONCLUSIONS AND IMPLICATIONSOur data suggest that the beneficial effects of GLP-1 are associated with changes in the adipogenic potential and ability of AT to expand, via activation of the canonical GLP-1 receptor and an additional, as yet unknown, receptor.Abbreviations ADRP, adipocyte differentiation-related protein; AT, adipose tissue; ATGL, adipose triglyceride lipase; BMI, body mass index; FABP4, fatty acid binding protein 4; FASN, fatty acid synthase; GLP-1, glucagon-like peptide-1; HSL, hormone-sensitive lipase; LPL, lipoprotein lipase; MO, morbidly obese; SAT, subcutaneous AT; SREBP1, sterol regulatory element-binding transcription factor 1; T2D, type 2 diabetic; VAT, visceral AT