Transplantation of committed pre-adipocytes from brown adipose tissue improves whole-body glucose homeostasis
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Date
2024-02-16
Publication Type
Journal Article
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yes
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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.
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published
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Journal / series
Volume
27 (2)
Pages / Article No.
108927
Publisher
Cell Press
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Edition / version
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Subject
Health sciences; Endocrinology; Natural sciences; Biological sciences; Physiology
Organisational unit
03819 - Wolfrum, Christian (ehemalig) / Wolfrum, Christian (former)
03819 - Wolfrum, Christian (ehemalig) / Wolfrum, Christian (former)
02207 - Functional Genomics Center Zurich / Functional Genomics Center Zurich