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

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2014 Dec 4

PMID 25466254

Citations 63

Authors

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

Affiliations

Soon will be listed here.

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.

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