Differential Lipolytic Regulation in Human Embryonic Stem Cell–derived Adipocytes

Abstract

Human embryonic stem cells (hESCs) have raised great hopes for future clinical applications. Several groups have succeeded in differentiating hESCs into adipocytes, as determined by morphology, mRNA expression, and protein secretion. However, determination of lipolytic response, the most important characteristic of adipocytes, has not been performed. This work was intended to study adipogenic conversion of hESCs by functional assessment of differentiation. Single undifferentiated colonies were allowed to transform into embryonic bodies. mRNA expression for a set of adipocyte-specific genes and leptin/adiponectin secretion and lipolysis were assessed at different time-points after differentiation. In contrast to primary human adipocytes, hESC-derived adipocytes showed a very small response to classical beta-adrenergic agonists, although they expressed the major genes in the lipolytic cascade. In contrast, there was a significant lipolytic response to atrial natriuretic peptide. Although hESC-derived adipocytes seem to be morphologically and expressionally similar to mature adipocytes, there are important functional differences that could depend on their early developmental origin. We conclude that, in contrast to mature adipocytes, hESC-derived adipocytes display a differential response to atrial natriuretic peptide and catecholamines.