iScience (Feb 2024)
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
Affiliations
- Revati S. Dewal
- Department of Physiology and Cell Biology, College of Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA
- Felix T. Yang
- Department of Physiology and Cell Biology, College of Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA; Department of Surgery, College of Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA
- Lisa A. Baer
- Department of Physiology and Cell Biology, College of Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA; Department of Surgery, College of Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA
- Pablo Vidal
- Department of Physiology and Cell Biology, College of Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA; Department of Surgery, College of Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA
- Diego Hernandez-Saavedra
- Department of Physiology and Cell Biology, College of Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA
- Nickolai P. Seculov
- Department of Physiology and Cell Biology, College of Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA
- Adhideb Ghosh
- Laboratory of Translational Nutritional Biology, Institute of Food, Nutrition and Health, ETH Zurich, 8603 Schwerzenbach, Switzerland
- Falko Noé
- Laboratory of Translational Nutritional Biology, Institute of Food, Nutrition and Health, ETH Zurich, 8603 Schwerzenbach, Switzerland
- Olivia Togliatti
- Department of Physiology and Cell Biology, College of Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA
- Lexis Hughes
- Department of Physiology and Cell Biology, College of Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA
- Megan K. DeBari
- Department of Biomedical Engineering, College of Engineering, Carnegie Mellon University, Pittsburgh, PA 15213, USA
- Michael D. West
- AgeX Therapeutics, Inc., 1101 Marina Village Parkway, Suite 201, Alameda, CA 94501, USA
- Richard Soroko
- AgeX Therapeutics, Inc., 1101 Marina Village Parkway, Suite 201, Alameda, CA 94501, USA
- Hal Sternberg
- AgeX Therapeutics, Inc., 1101 Marina Village Parkway, Suite 201, Alameda, CA 94501, USA
- Nafees N. Malik
- AgeX Therapeutics, Inc., 1101 Marina Village Parkway, Suite 201, Alameda, CA 94501, USA
- Estella Puchulu-Campanella
- Genomics Shared Resource, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA
- Huabao Wang
- Genomics Shared Resource, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA
- Pearlly Yan
- Genomics Shared Resource, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA; Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA
- Christian Wolfrum
- Laboratory of Translational Nutritional Biology, Institute of Food, Nutrition and Health, ETH Zurich, 8603 Schwerzenbach, Switzerland
- Rosalyn D. Abbott
- Department of Biomedical Engineering, College of Engineering, Carnegie Mellon University, Pittsburgh, PA 15213, USA
- Kristin I. Stanford
- Department of Physiology and Cell Biology, College of Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA; Department of Surgery, College of Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA; Corresponding author
- Journal volume & issue
-
Vol. 27,
no. 2
p. 108927
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.
