Inoue Kana, Maeda Norikazu, Mori Takuya, Sekimoto Ryohei, Tsushima Yu, Matsuda Keisuke, Yamaoka Masaya, Suganami Takayoshi, Nishizawa Hitoshi, Ogawa Yoshihiro, Funahashi Tohru, Shimomura Iichiro
Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
Department of Organ Network and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
PLoS One. 2014 Feb 6;9(2):e87661. doi: 10.1371/journal.pone.0087661. eCollection 2014.
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.
肥胖是一个流行问题,它增加了患心血管疾病和代谢紊乱(如2型糖尿病)的风险。我们最近研究了人类受试者内脏脂肪肥胖与外周血细胞基因表达谱之间的关联。在一系列研究中,淋病奈瑟菌opacity相关相互作用蛋白5(OIP5)被确定为脂肪细胞中功能未知的分子,因此进行本研究以探究OIP5在肥胖中的作用。构建了过表达Oip5的腺病毒(Ad - Oip5),并将其感染稳定表达柯萨奇 - 腺病毒受体的3T3 - L1细胞(CAR - 3T3 - L1)以及小鼠皮下脂肪。对于敲低实验,将针对Oip5的小干扰RNA(Oip5 - siRNA)导入3T3 - L1细胞。通过BrdU摄取、EdU染色和细胞计数来测量脂肪细胞的增殖。在肥胖白色脂肪组织中观察到Oip5 mRNA水平显著升高,并且在成熟脂肪细胞组分和基质血管细胞组分中均检测到这种升高。Ad - Oip5感染的CAR - 3T3 - L1前脂肪细胞和脂肪细胞迅速增殖,而在导入Oip5 - siRNA的3T3 - L1前脂肪细胞中观察到增殖显著降低。给予Ad - Oip5的脂肪组织中脂肪重量和脂肪细胞数量显著增加。Oip5促进前脂肪细胞和成熟脂肪细胞的增殖,并导致脂肪组织增生。Oip5的增加可能与肥胖的发生有关。