ThermoMouse: An In Vivo Model to Identify Modulators of UCP1 Expression in Brown Adipose Tissue
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ThermoMouse : An In Vivo Model to Identify Modulators of UCP1 Expression in Brown Adipose Tissue. / Galmozzi, Andrea; Sonne, Si B.; Altshuler-Keylin, Svetlana; Hasegawa, Yutaka; Shinoda, Kosaku; Luijten, Ineke H.N.; Chang, Jae Won; Sharp, Louis Z.; Cravatt, Benjamin F.; Saez, Enrique; Kajimura, Shingo.
I: Cell Reports, Bind 9, Nr. 5, 2014, s. 1584-1593.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - ThermoMouse
T2 - An In Vivo Model to Identify Modulators of UCP1 Expression in Brown Adipose Tissue
AU - Galmozzi, Andrea
AU - Sonne, Si B.
AU - Altshuler-Keylin, Svetlana
AU - Hasegawa, Yutaka
AU - Shinoda, Kosaku
AU - Luijten, Ineke H.N.
AU - Chang, Jae Won
AU - Sharp, Louis Z.
AU - Cravatt, Benjamin F.
AU - Saez, Enrique
AU - Kajimura, Shingo
N1 - Publisher Copyright: © 2014 The Authors.
PY - 2014
Y1 - 2014
N2 - Obesity develops when energy intake chronically exceeds energy expenditure. Because brown adiposetissue (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. Pharmacological activation of brown adipose tissue (BAT) thermogenesis and energy dissipation, a process mediated by UCP1, may be useful to counter the energy imbalance that engenders obesity. Galmozzi etal. have developed an invivo model to monitor UCP1 expression in real time and identified a small molecule that increases UCP1 levels. Mice treated with this molecule show greater energy expenditure upon adrenergic stimulation. Discovery of compounds with this ability is an important stride toward enhancing BAT function in obese individuals.
AB - Obesity develops when energy intake chronically exceeds energy expenditure. Because brown adiposetissue (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. Pharmacological activation of brown adipose tissue (BAT) thermogenesis and energy dissipation, a process mediated by UCP1, may be useful to counter the energy imbalance that engenders obesity. Galmozzi etal. have developed an invivo model to monitor UCP1 expression in real time and identified a small molecule that increases UCP1 levels. Mice treated with this molecule show greater energy expenditure upon adrenergic stimulation. Discovery of compounds with this ability is an important stride toward enhancing BAT function in obese individuals.
U2 - 10.1016/j.celrep.2014.10.066
DO - 10.1016/j.celrep.2014.10.066
M3 - Journal article
C2 - 25466254
AN - SCOPUS:84915820023
VL - 9
SP - 1584
EP - 1593
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 5
ER -
ID: 375199903