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Perilipin Overexpression in White Adipose Tissue Induces a Brown Fat-Like Phenotype

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Title: Perilipin Overexpression in White Adipose Tissue Induces a Brown Fat-Like Phenotype
Authors: Sawada, Takashi Browse this author
Miyoshi, Hideaki Browse this author →KAKEN DB
Shimada, Kohei Browse this author
Suzuki, Akira Browse this author
Okamatsu-Ogura, Yuko Browse this author →KAKEN DB
Perfield, James W., II Browse this author
Kondo, Takuma Browse this author
Nagai, So Browse this author →KAKEN DB
Shimizu, Chikara Browse this author →KAKEN DB
Yoshioka, Narihito Browse this author →KAKEN DB
Greenberg, Andrew S. Browse this author
Kimura, Kazuhiro Browse this author →KAKEN DB
Koike, Takao Browse this author →KAKEN DB
Issue Date: 16-Nov-2010
Publisher: Public Library of Science
Journal Title: PLoS One
Volume: 5
Issue: 11
Start Page: e14006
Publisher DOI: 10.1371/journal.pone.0014006
Abstract: Background: Perilipin A (PeriA) exclusively locates on adipocyte lipid droplets and is essential for lipid storage and lipolysis. Previously, we reported that adipocyte specific overexpression of PeriA caused resistance to diet-induced obesity and resulted in improved insulin sensitivity. In order to better understand the biological basis for this observed phenotype, we performed additional studies in this transgenic mouse model. Methodology and Principal Findings: When compared to control animals, whole body energy expenditure was increased in the transgenic mice. Subsequently, we performed DNA microarray analysis and real-time PCR on white adipose tissue. Consistent with the metabolic chamber data, we observed increased expression of genes associated with fatty acid β-oxidation and heat production, and a decrease in the genes associated with lipid synthesis. Gene expression of Pgc1a, a regulator of fatty acid oxidation and Ucp1, a brown adipocyte specific protein, was increased in the white adipose tissue of the transgenic mice. This observation was subsequently verified by both Western blotting and histological examination. Expression of RIP140, a regulator of white adipocyte differentiation, and the lipid droplet protein FSP27 was decreased in the transgenic mice. Importantly, FSP27 has been shown to control gene expression of these crucial metabolic regulators. Overexpression of PeriA in 3T3-L1 adipocytes also reduced FSP27 expression and diminished lipid droplet size. Conclusions: These findings demonstrate that overexpression of PeriA in white adipocytes reduces lipid droplet size by decreasing FSP27 expression and thereby inducing a brown adipose tissue-like phenotype. Our data suggest that modulation of lipid droplet proteins in white adipocytes is a potential therapeutic strategy for the treatment of obesity and its related disorders.
Type: article
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 澤田 享

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