title: Metabolically active human brown adipose tissue derived stem cells.
abstract: Brown adipose tissue (BAT) plays a key role in the evolutionarily conserved mechanisms underlying energy homeostasis in mammals. It is characterized by fat vacuoles 5-10 µm in diameter and expression of uncoupling protein one, central to the regulation of thermogenesis. In the human newborn, BAT depots are typically grouped around the vasculature and solid organs. These depots maintain body temperature during cold exposure by warming the blood before its distribution to the periphery. They also ensure an optimal temperature for biochemical reactions within solid organs. BAT had been thought to involute throughout childhood and adolescence. Recent studies, however, have confirmed the presence of active BAT in adult humans with depots residing in cervical, supraclavicular, mediastinal, paravertebral, and suprarenal regions. While human pluripotent stem cells have been differentiated into functional brown adipocytes in vitro and brown adipocyte progenitor cells have been identified in murine skeletal muscle and white adipose tissue, multipotent metabolically active BAT-derived stem cells from a single depot have not been identified in adult humans to date. Here, we demonstrate a clonogenic population of metabolically active BAT stem cells residing in adult humans that can: (a) be expanded in vitro; (b) exhibit multilineage differentiation potential; and (c) functionally differentiate into metabolically active brown adipocytes. Our study defines a new target stem cell population that can be activated to restore energy homeostasis in vivo for the treatment of obesity and related metabolic disorders.
authors.affiliation: Department of Surgery, Division of Cardiothoracic Surgery, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Silva
authors.forename: Dolly J
authors.initials: DJ
authors.lastname: Holt
authors.forename: Vanessa
authors.initials: V
authors.lastname: Vargas
authors.forename: James
authors.initials: J
authors.lastname: Yockman
authors.forename: Sihem
authors.initials: S
authors.lastname: Boudina
authors.forename: Donald
authors.initials: D
authors.lastname: Atkinson
authors.forename: David W
authors.initials: DW
authors.lastname: Grainger
authors.forename: Monica P
authors.initials: MP
authors.lastname: Revelo
authors.forename: Warren
authors.initials: W
authors.lastname: Sherman
authors.forename: David A
authors.initials: DA
authors.lastname: Bull
authors.forename: Amit N
authors.initials: AN
authors.lastname: Patel
mesh_terms: D002001:Adipose Tissue, Brown / Q000166:cytology*; D052436:Adipose Tissue, White / Q000166:cytology; D000818:Animals; D005075:Biological Evolution; D002454:Cell Differentiation / Q000235:genetics*; D004734:Energy Metabolism / Q000235:genetics; D006801:Humans; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D009765:Obesity / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D022722:Thermogenesis
keywords: Adipose; Brown adipose tissue; Diabetes; Obesity; Scaffolds; Stem cells