Instructions for use Title Perilipin Overexpression in White Adipose Tissue Induces a Brown Fat-Like Phenotype

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 boxidation 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. Citation: Sawada T, Miyoshi H, Shimada K, Suzuki A, Okamatsu-Ogura Y, et al. (2010) Perilipin Overexpression in White Adipose Tissue Induces a Brown Fat-Like Phenotype. PLoS ONE 5(11): e14006. doi:10.1371/journal.pone.0014006 Editor: Massimo Federici, University of Tor Vergata, Italy Received May 4, 2010; Accepted October 26, 2010; Published November 16, 2010 Copyright: 2010 Sawada et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by grants from the Japanese Ministry of Education, Culture, Sports, Science, and Technology Foundation (http://www.mext. go.jp/), Takeda Science Foundation (http://www.takeda-sci.or.jp/), Kanae Foundation for the Promotion of Medical Science (http://kanae.sanofi-aventis.co.jp/), and Kissei Pharmaceutical Foundation (http://www.kissei.co.jp/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: [email protected]