title: Depletion of white adipocyte progenitors induces beige adipocyte differentiation and suppresses obesity development.
abstract: Overgrowth of white adipose tissue (WAT) in obesity occurs as a result of adipocyte hypertrophy and hyperplasia. Expansion and renewal of adipocytes relies on proliferation and differentiation of white adipocyte progenitors (WAP); however, the requirement of WAP for obesity development has not been proven. Here, we investigate whether depletion of WAP can be used to prevent WAT expansion. We test this approach by using a hunter-killer peptide designed to induce apoptosis selectively in WAP. We show that targeted WAP cytoablation results in a long-term WAT growth suppression despite increased caloric intake in a mouse diet-induced obesity model. Our data indicate that WAP depletion results in a compensatory population of adipose tissue with beige adipocytes. Consistent with reported thermogenic capacity of beige adipose tissue, WAP-depleted mice display increased energy expenditure. We conclude that targeting of white adipocyte progenitors could be developed as a strategy to sustained modulation of WAT metabolic activity.
authors.affiliation: Center for Metabolic and Degenerative Diseases, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
authors.forename: A C
authors.initials: AC
authors.lastname: Daquinag
authors.affiliation: Center for Metabolic and Degenerative Diseases, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
authors.forename: C
authors.initials: C
authors.lastname: Tseng
authors.affiliation: Center for Metabolic and Degenerative Diseases, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
authors.forename: A
authors.initials: A
authors.lastname: Salameh
authors.affiliation: Center for Metabolic and Degenerative Diseases, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Center for Metabolic and Degenerative Diseases, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
authors.forename: F
authors.initials: F
authors.lastname: Amaya-Manzanares
authors.affiliation: Center for Metabolic and Degenerative Diseases, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
authors.forename: A
authors.initials: A
authors.lastname: Dadbin
authors.affiliation: Center for Metabolic and Degenerative Diseases, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
authors.forename: F
authors.initials: F
authors.lastname: Florez
authors.affiliation: Center for Metabolic and Degenerative Diseases, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Center for Metabolic and Degenerative Diseases, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Tong
authors.affiliation: Center for Metabolic and Degenerative Diseases, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
authors.forename: M G
authors.initials: MG
authors.lastname: Kolonin
mesh_terms: D052437:Adipocytes, Brown / Q000378:metabolism*; D052438:Adipocytes, White / Q000378:metabolism*; D050156:Adipogenesis; D002001:Adipose Tissue, Brown / Q000166:cytology; D052436:Adipose Tissue, White / Q000166:cytology; D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D004195:Disease Models, Animal; D004734:Energy Metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism*