1. Transplantation of committed pre-adipocytes from brown adipose tissue improves whole-body glucose homeostasis
- Author
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Revati S. Dewal, Felix T. Yang, Lisa A. Baer, Pablo Vidal, Diego Hernandez-Saavedra, Nickolai P. Seculov, Adhideb Ghosh, Falko Noé, Olivia Togliatti, Lexis Hughes, Megan K. DeBari, Michael D. West, Richard Soroko, Hal Sternberg, Nafees N. Malik, Estella Puchulu-Campanella, Huabao Wang, Pearlly Yan, Christian Wolfrum, Rosalyn D. Abbott, and Kristin I. Stanford
- Subjects
Health sciences ,Endocrinology ,Natural sciences ,Biological sciences ,Physiology ,Science - Abstract
Summary: Obesity and its co-morbidities including type 2 diabetes are increasing at epidemic rates in the U.S. and worldwide. Brown adipose tissue (BAT) is a potential therapeutic to combat obesity and type 2 diabetes. Increasing BAT mass by transplantation improves metabolic health in rodents, but its clinical translation remains a challenge. Here, we investigated if transplantation of 2–4 million differentiated brown pre-adipocytes from mouse BAT stromal fraction (SVF) or human pluripotent stem cells (hPSCs) could improve metabolic health. Transplantation of differentiated brown pre-adipocytes, termed “committed pre-adipocytes” from BAT SVF from mice or derived from hPSCs improves glucose homeostasis and insulin sensitivity in recipient mice under conditions of diet-induced obesity, and this improvement is mediated through the collaborative actions of the liver transcriptome, tissue AKT signaling, and FGF21. These data demonstrate that transplantation of a small number of brown adipocytes has significant long-term translational and therapeutic potential to improve glucose metabolism.
- Published
- 2024
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