Possible Involvement of Opa-Interacting Protein 5 in Adipose Proliferation and Obesity

Kana Inoue,Hitoshi Nishizawa,Yoshihiro Ogawa,Yu Tsushima,Takuya Mori,Takayoshi Suganami,Iichiro Shimomura,Keisuke Matsuda,Norikazu Maeda,Ryohei Sekimoto,Tohru Funahashi,Masaya Yamaoka,Xiaoli Chen

doi:10.1371/journal.pone.0087661

Kana Inoue, Hitoshi Nishizawa + Show 11 more

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https://doi.org/10.1371/journal.pone.0087661

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Journal: PloS one	Publication Date: Feb 6, 2014
Citations: 41	License type: CC BY 4.0

Affiliation: Osaka University, Tokyo Medical and Dental University

Abstract

Obesity is an epidemic matter increasing risk for cardiovascular diseases and metabolic disorders such as type 2 diabetes. We recently examined the association between visceral fat adiposity and gene expression profile of peripheral blood cells in human subjects. In a series of studies, Opa (Neisseria gonorrhoeae opacity-associated)-interacting protein 5 (OIP5) was nominated as a molecule of unknown function in adipocytes and thus the present study was performed to investigate the role of OIP5 in obesity. Adenovirus overexpressing Oip5 (Ad-Oip5) was generated and infected to 3T3-L1 cells stably expressing Coxsackie-Adenovirus Receptor (CAR-3T3-L1) and to mouse subcutaneous fat. For a knockdown experiment, siRNA against Oip5 (Oip5-siRNA) was introduced into 3T3-L1 cells. Proliferation of adipose cells was measured by BrdU uptake, EdU-staining, and cell count. Significant increase of Oip5 mRNA level was observed in obese white adipose tissues and such increase was detected in both mature adipocytes fraction and stromal vascular cell fraction. Ad-Oip5-infected CAR-3T3-L1 preadipocytes and adipocytes proliferated rapidly, while a significant reduction of proliferation was observed in Oip5-siRNA-introduced 3T3-L1 preadipocytes. Fat weight and number of adipocytes were significantly increased in Ad-Oip5-administered fat tissues. Oip5 promotes proliferation of pre- and mature-adipocytes and contributes adipose hyperplasia. Increase of Oip5 may associate with development of obesity.

Highlights

Obesity, especially visceral fat-accumulated obesity, is an important aspect of the metabolic syndrome, diabetes, and atherosclerosis [1]
Signal intensity levels of OIP5 mRNA in peripheral blood cells positively correlated with the estimated visceral fat area in human subjects (Figure S4)
Oip5 mRNA was detected in epididymal (Epi) and subcutaneous (Sub) white adipose tissue (WAT)

Summary

Introduction

Especially visceral fat-accumulated obesity, is an important aspect of the metabolic syndrome, diabetes, and atherosclerosis [1]. In the Human Body Map project [2], our group for the first time provided evidence for the endocrine function of adipose tissue [3]. Our group reported recently the association between visceral fat adiposity and gene expression profile of peripheral blood cells in human subjects [5,6]. We hypothesized that the visceral fat status may affect and reflect the gene expression profile in peripheral blood cells. In a series of exploratory research studies, we searched for genes of unknown function in adipocytes and adipose tissues by comparing the cDNA microarray-based gene expression patterns of mouse adipose tissues and human peripheral blood cells. The transfected cells were incubated for 24 hrs and reseeded to match the number of 3T3-L1 preadipocytes between Oip5-siRNA and Cont-siRNA groups. Cell number was counted at 24, 48 or 72 hrs after reseeding.

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