ThermoMouse: An In Vivo Model to Identify Modulators of UCP1 Expression in Brown Adipose Tissue

Andrea Galmozzi, Si B. Sonne, Svetlana Altshuler-Keylin, Yutaka Hasegawa, Kosaku Shinoda, Ineke H.N. Luijten, Jae Won Chang, Louis Z. Sharp, Benjamin F. Cravatt, Enrique Saez, Shingo Kajimura

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1584-1594
Number of pages11
JournalCell Reports
Volume9
Issue number5
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

Fingerprint

Brown Adipose Tissue
Modulators
Tissue
Energy Metabolism
Thermogenesis
Proteins
Obesity
Adrenergic Agents
Molecules
Brown Adipocytes
Pharmacology
Uncoupling Protein 1
Energy Intake
Luciferases
Libraries
Energy dissipation
Screening
Hot Temperature
Chemical activation
Fats

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Galmozzi, A., Sonne, S. B., Altshuler-Keylin, S., Hasegawa, Y., Shinoda, K., Luijten, I. H. N., ... Kajimura, S. (2014). ThermoMouse: An In Vivo Model to Identify Modulators of UCP1 Expression in Brown Adipose Tissue. Cell Reports, 9(5), 1584-1594. https://doi.org/10.1016/j.celrep.2014.10.066

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.

In: Cell Reports, Vol. 9, No. 5, 01.01.2014, p. 1584-1594.

Research output: Contribution to journalArticle

Galmozzi, A, Sonne, SB, Altshuler-Keylin, S, Hasegawa, Y, Shinoda, K, Luijten, IHN, Chang, JW, Sharp, LZ, Cravatt, BF, Saez, E & Kajimura, S 2014, 'ThermoMouse: An In Vivo Model to Identify Modulators of UCP1 Expression in Brown Adipose Tissue', Cell Reports, vol. 9, no. 5, pp. 1584-1594. https://doi.org/10.1016/j.celrep.2014.10.066
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. / ThermoMouse : An In Vivo Model to Identify Modulators of UCP1 Expression in Brown Adipose Tissue. In: Cell Reports. 2014 ; Vol. 9, No. 5. pp. 1584-1594.
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