Transplantation of committed pre-adipocytes from brown adipose tissue improves whole-body glucose homeostasis
- PMID: 38327776
- PMCID: PMC10847743
- DOI: 10.1016/j.isci.2024.108927
Transplantation of committed pre-adipocytes from brown adipose tissue improves whole-body glucose homeostasis
Abstract
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.
Keywords: Biological sciences; Endocrinology; Health sciences; Natural sciences; Physiology.
© 2024 The Author(s).
Conflict of interest statement
M.D.W., R.S., H.S., and N.N.M. are employed by AgeX Therapeutics.
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