title: Pharmacological Activation of Thyroid Hormone Receptors Elicits a Functional Conversion of White to Brown Fat.
abstract: The functional conversion of white adipose tissue (WAT) into a tissue with brown adipose tissue (BAT)-like activity, often referred to as "browning," represents an intriguing strategy for combating obesity and metabolic disease. We demonstrate that thyroid hormone receptor (TR) activation by a synthetic agonist markedly induces a program of adaptive thermogenesis in subcutaneous WAT that coincides with a restoration of cold tolerance to cold-intolerant mice. Distinct from most other browning agents, pharmacological TR activation dissociates the browning of WAT from activation of classical BAT. TR agonism also induces the browning of white adipocytes in vitro, indicating that TR-mediated browning is cell autonomous. These data establish TR agonists as a class of browning agents, implicate the TRs in the browning of WAT, and suggest a profound pharmacological potential of this action.
authors.affiliation: Diabetes and Metabolic Disease Program, Houston Methodist Research Institute, Houston, TX 77030, USA; Center for Nuclear Receptors and Cell Signaling, University of Houston, Houston, TX 77004, USA.
authors.forename: Jean Z
authors.initials: JZ
authors.lastname: Lin
authors.affiliation: Diabetes and Metabolic Disease Program, Houston Methodist Research Institute, Houston, TX 77030, USA; Escuela de Biotecnología y Alimentos, Instituto Tecnológico y de Estudios Superiores de Monterrey, 64849 Monterrey, NL, Mexico.
authors.forename: Alexandro J
authors.initials: AJ
authors.lastname: Martagón
authors.affiliation: Diabetes and Metabolic Disease Program, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Cimini
authors.affiliation: Diabetes and Metabolic Disease Program, Houston Methodist Research Institute, Houston, TX 77030, USA; Escuela de Biotecnología y Alimentos, Instituto Tecnológico y de Estudios Superiores de Monterrey, 64849 Monterrey, NL, Mexico.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Gonzalez
authors.affiliation: Comparative Medicine Program, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Tinkey
authors.affiliation: Diabetes and Metabolic Disease Program, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors.forename: Amadeo
authors.initials: A
authors.lastname: Biter
authors.affiliation: Diabetes and Metabolic Disease Program, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Baxter
authors.affiliation: Diabetes and Metabolic Disease Program, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Webb
authors.affiliation: Diabetes and Metabolic Disease Program, Houston Methodist Research Institute, Houston, TX 77030, USA; Center for Nuclear Receptors and Cell Signaling, University of Houston, Houston, TX 77004, USA.
authors.forename: Jan-Åke
authors.initials: JÅ
authors.lastname: Gustafsson
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Sean M
authors.initials: SM
authors.lastname: Hartig
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: kevinp@bcm.edu.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Phillips
mesh_terms: D052437:Adipocytes, Brown / Q000378:metabolism; D052438:Adipocytes, White / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D004734:Energy Metabolism / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D022722:Thermogenesis / Q000502:physiology
chemical_list: D011988:Receptors, Thyroid Hormone