Transplantation of committed pre-adipocytes from brown adipose tissue improves whole-body glucose homeostasis

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; Kristin I Stanford

doi:10.1016/j.isci.2024.108927

Transplantation of committed pre-adipocytes from brown adipose tissue improves whole-body glucose homeostasis

iScience. 2024 Jan 17;27(2):108927. doi: 10.1016/j.isci.2024.108927. eCollection 2024 Feb 16.

Authors

Revati S Dewal¹, Felix T Yang^{1

2}, Lisa A Baer^{1

2}, Pablo Vidal^{1

2}, Diego Hernandez-Saavedra¹, Nickolai P Seculov¹, Adhideb Ghosh³, Falko Noé³, Olivia Togliatti¹, Lexis Hughes¹, Megan K DeBari⁴, Michael D West⁵, Richard Soroko⁵, Hal Sternberg⁵, Nafees N Malik⁵, Estella Puchulu-Campanella⁶, Huabao Wang⁶, Pearlly Yan^{6

7}, Christian Wolfrum³, Rosalyn D Abbott⁴, Kristin I Stanford^{1

2}

Affiliations

¹ Department of Physiology and Cell Biology, College of Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA.
² Department of Surgery, College of Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA.
³ Laboratory of Translational Nutritional Biology, Institute of Food, Nutrition and Health, ETH Zurich, 8603 Schwerzenbach, Switzerland.
⁴ Department of Biomedical Engineering, College of Engineering, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
⁵ AgeX Therapeutics, Inc., 1101 Marina Village Parkway, Suite 201, Alameda, CA 94501, USA.
⁶ Genomics Shared Resource, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
⁷ Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA.

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.

Abstract

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