Brown-Like Adipocyte Progenitors Derived from Human iPS Cells: A New Tool for Anti-obesity Drug Discovery and Cell-Based Therapy?

Abstract

Alternative strategies are urgently required to fight obesity and associated metabolic disorders including diabetes and cardiovascular diseases. Brown and brown-like adipocytes (BAs) store fat, but in contrast to white adipocytes, activated BAs are equipped to dissipate energy stored. Therefore, BAs represent promising cell targets to counteract obesity. However, the scarcity of BAs in adults is a major limitation for a BA-based therapy of obesity, and the notion to increase the BA mass by transplanting BA progenitors (BAPs) in obese patients recently emerged. The next challenge is to identify an abundant and reliable source of BAPs. In this chapter, we describe the capacity of human-induced pluripotent stem cells (hiPSCs) to generate BAPs able to differentiate at a high efficiency with no gene transfer. This cell model represents an unlimited source of human BAPs that in a near future may be a suitable tool for both therapeutic transplantation and for the discovery of novel efficient and safe anti-obesity drugs. The generation of a relevant cell model, such as hiPSC-BAs in 3D adipospheres enriched with macrophages and endothelial cells to better mimic the microenvironment within the adipose tissue, will be the next critical step.

Delta-Tocopherol Suppresses the Dysfunction of Thermogenesis due to Inflammatory Stimulation in Brown Adipocytes

“…The effects of vitamin E analogs on macrophage invasion and inflammatory signals in vivo in BAT warrant further investigation. Recent studies have made it possible to induce differentiation from ES cells and iPS cells to brown adipocytes 25,26) . The effects of food ingredients on the function of human brown adipocytes will be further investigated in the future.…”

Stem Cell Research Tools in Human Metabolic Disorders: An Overview

“…Another interesting aspect related to stem cell application in the treatment of obesity is the potential of ex vivo differentiation into brown adipocytes, which is reported to improve obesity in animals and humans [79][80][81][82]. In this case, interesting results were obtained by the use of induced pluripotent stem cells (iPSCs) which can be easily collected and engineered ex vivo for being retransplanted into the original donor [83]. Transplantation of induced brown adipocytes (iBAs)-differentiated from epidermal-derived iPSCs-showed a strong ability to ameliorate the obese phenotype, by reducing body weight and ameliorating glucose tolerance and dyslipidemia [84].…”