title: ThermoMouse: an in vivo model to identify modulators of UCP1 expression in brown adipose tissue.
abstract: Obesity develops when energy intake chronically exceeds energy expenditure. Because brown adipose tissue (BAT) dissipates energy in the form of heat, increasing energy expenditure by augmenting BAT-mediated thermogenesis may represent an approach to counter obesity and its complications. The ability of BAT to dissipate energy is dependent on expression of mitochondrial uncoupling protein 1 (UCP1). To facilitate the identification of pharmacological modulators of BAT UCP1 levels, which may have potential as antiobesity medications, we developed a transgenic model in which luciferase activity faithfully mimics endogenous UCP1 expression and its response to physiologic stimuli. Phenotypic screening of a library using cells derived from this model yielded a small molecule that increases UCP1 expression in brown fat cells and mice. Upon adrenergic stimulation, compound-treated mice showed increased energy expenditure. These tools offer an opportunity to identify pharmacologic modulators of UCP1 expression and uncover regulatory pathways that impact BAT-mediated thermogenesis.
authors.affiliation: Department of Chemical Physiology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Galmozzi
authors.affiliation: UCSF Diabetes Center, Department of Cell and Tissue Biology, University of California, San Francisco, 35 Medical Center Way, San Francisco, CA 94143, USA.
authors.forename: Si B
authors.initials: SB
authors.lastname: Sonne
authors.affiliation: UCSF Diabetes Center, Department of Cell and Tissue Biology, University of California, San Francisco, 35 Medical Center Way, San Francisco, CA 94143, USA.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Altshuler-Keylin
authors.affiliation: UCSF Diabetes Center, Department of Cell and Tissue Biology, University of California, San Francisco, 35 Medical Center Way, San Francisco, CA 94143, USA.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hasegawa
authors.affiliation: UCSF Diabetes Center, Department of Cell and Tissue Biology, University of California, San Francisco, 35 Medical Center Way, San Francisco, CA 94143, USA.
authors.forename: Kosaku
authors.initials: K
authors.lastname: Shinoda
authors.affiliation: UCSF Diabetes Center, Department of Cell and Tissue Biology, University of California, San Francisco, 35 Medical Center Way, San Francisco, CA 94143, USA.
authors.forename: Ineke H N
authors.initials: IHN
authors.lastname: Luijten
authors.affiliation: Department of Chemical Physiology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Jae Won
authors.initials: JW
authors.lastname: Chang
authors.affiliation: UCSF Diabetes Center, Department of Cell and Tissue Biology, University of California, San Francisco, 35 Medical Center Way, San Francisco, CA 94143, USA.
authors.forename: Louis Z
authors.initials: LZ
authors.lastname: Sharp
authors.affiliation: Department of Chemical Physiology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Benjamin F
authors.initials: BF
authors.lastname: Cravatt
authors.affiliation: Department of Chemical Physiology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: esaez@scripps.edu.
authors.forename: Enrique
authors.initials: E
authors.lastname: Saez
authors.affiliation: UCSF Diabetes Center, Department of Cell and Tissue Biology, University of California, San Francisco, 35 Medical Center Way, San Francisco, CA 94143, USA. Electronic address: skajimura@diabetes.ucsf.edu.
authors.forename: Shingo
authors.initials: S
authors.lastname: Kajimura
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D004734:Energy Metabolism; D015870:Gene Expression; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008822:Mice, Transgenic; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism; D015398:Signal Transduction; D022722:Thermogenesis; D015533:Transcriptional Activation / Q000187:drug effects*; D000071256:Uncoupling Protein 1
chemical_list: D019440:Anti-Obesity Agents; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1