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Human induced pluripotent stem (iPS) and embryonic stem (ES) cells can differentiate into a variety of cell types. We reported on adipogenic potential of human iPS and ES cells in vitro. In the present study, we investigate the survival and maintenance of adipocytes differentiated in vitro from human iPS and ES cells after transplantation. Following adipogenic induction in vitro, the differentiated cells exhibited functional properties of adipocytes such as lipid storage, lipolysis, and insulin responsiveness. Subsequently, Matrigel containing the differentiated human iPS and ES cells was transplanted into the subcutaneous tissue of nude mice. After 1-4 weeks, the cells with adipocyte-like features were observed in transplanted Matrigel by histological analysis. The human origin of the cells, their lipid accumulation, and gene expression of adipocyte markers in transplanted cells were then confirmed, suggesting the presence of adipocytes in transplanted Matrigel. When the relative areas of these cells were calculated by dividing the adipocyte areas by the total Matrigel areas, we found that they peaked at 2 weeks after transplantation, and that the adipocytes persisted at 4 weeks. The present study demonstrates that human iPS and ES cells can differentiate into adipocytes with functional properties and that adipocytes derived from human iPS and ES cells can survive and maintain the differentiated properties of adipocytes for at least 4 weeks after transplantation. Adipocytes derived from human iPS and ES cells thus have the potential to open new avenues for stem cell-based research into metabolic diseases and future therapeutic applications. [ABSTRACT FROM AUTHOR]

Leptin may reduce pancreatic lipid deposition, which increases with progression of obesity and can impair β-cell function. The insulinotropic effect of glucagon-like peptide-1 (GLP-1) and the efficacy of GLP-1 receptor agonist are reduced associated with impaired β-cell function. In this study, we examined whether leptin could restore the efficacy of exenatide, a GLP-1 receptor agonist, in type 2 diabetes with increased adiposity. We chronically administered leptin (500 μg·kg-1·day-1) and/or exenatide (20 μg·kg-1·day-1) for 2 wk in a mouse model of type 2 diabetes with increased adiposity induced by streptozotocin and high-fat diet (STZ/HFD mice). The STZ/HFD mice exhibited hyperglycemia, overweight, increased pancreatic triglyceride level, and reduced glucose-stimulated insulin secretion (GSIS); moreover, the insulinotropic effect of exenatide was reduced. However, leptin significantly reduced pancreatic triglyceride level, and adding leptin to exenatide (LEP/EX) remarkably enhanced GSIS. These results suggested that the leptin treatment restored the insulinotropic effect of exenatide in the mice. In addition, LEP/EX reduced food intake, body weight, and triglyceride levels in the skeletal muscle and liver, and corrected hyperglycemia to a greater extent than either monotherapy. The pair-feeding experiment indicated that the marked reduction of pancreatic triglyceride level and enhancement of GSIS by LEP/EX occurred via mechanisms other than calorie restriction. These results suggest that leptin treatment may restore the insulinotropic effect of exenatide associated with the reduction of pancreatic lipid deposition in type 2 diabetes with increased adiposity. Combination therapy with leptin and exenatide could be an effective treatment for patients with type 2 diabetes with increased adiposity. [ABSTRACT FROM AUTHOR]