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.
References
[1]
Matsuzawa Y (2006) Therapy Insight: adipocytokines in metabolic syndrome and related cardiovascular disease. Nat Clin Pract Cardiovasc 3: 35–42. doi: 10.1038/ncpcardio0380
[2]
Okubo K, Hori N, Matoba R, Niiyama T, Fukushima A, et al. (1992) Large scale cDNA sequencing for analysis of quantitative and qualitative aspects of gene expression. Nat Genet 2: 173–179. doi: 10.1038/ng1192-173
[3]
Maeda K, Okubo K, Shimomura I, Mizuno K, Matsuzawa Y, et al. (1997) Analysis of an expression profile of genes in the human adipose tissue. Gene 1190: 227–235. doi: 10.1016/s0378-1119(96)00730-5
[4]
Maeda K, Okubo K, Shimomura I, Funahashi T, Matsuzawa Y, et al. (1996) cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (AdiPose Most abundant Gene transcript 1). Biochem Biophys Res Commun 221: 286–289. doi: 10.1006/bbrc.1996.0587
[5]
Yamaoka M, Maeda N, Nakamura S, Kashine S, Nakagawa Y, et al. (2012) A pilot investigation of visceral fat adiposity and gene expression profile in peripheral blood cells. PLoS One 7: e47377. doi: 10.1371/journal.pone.0047377
[6]
Yamaoka M, Maeda N, Nakamura S, Mori T, Inoue K, et al. (2013) Gene expression levels of S100 protein family in blood cells are associated with insulin resistance and inflammation. Biochem Biophys Res Commun 433: 450–455. doi: 10.1016/j.bbrc.2013.02.096
[7]
Williams JM, Chen GC, Zhu L, Rest RF (1998) Using the yeast two-hybrid system to identify human epithelial cell proteins that bind gonococcal Opa proteins: intracellular gonococci bind pyruvate kinase via their Opa proteins and require host pyruvate for growth. Mol Microbiol 27: 171–186. doi: 10.1046/j.1365-2958.1998.00670.x
[8]
Nakamura Y, Tanaka F, Nagahara H, Ieta K, Haraguchi N, et al. (2007) Opa interacting protein 5 (OIP5) is a novel cancer-testis specific gene in gastric cancer. Ann Surg Oncol 14: 885–892. doi: 10.1245/s10434-006-9121-x
[9]
Chun HK, Chung KS, Kim HC, Kang JE, Kang MA, et al. (2010) OIP5 is a highly expressed potential therapeutic target for colorectal and gastric cancers. BMB Rep 43: 349–354. doi: 10.3858/bmbrep.2010.43.5.349
[10]
Koinuma J, Akiyama H, Fujita M, Hosokawa M, Tsuchiya E, et al. (2012) Characterization of an Opa interacting protein 5 involved in lung and esophageal carcinogenesis. Cancer Sci 103: 577–586. doi: 10.1111/j.1349-7006.2011.02167.x
[11]
Yazarloo F, Shirkoohi R, Mobasheri MB, Emami A, Modarressi MH (2013) Expression analysis of four testis-specific genes AURKC, OIP5, PIWIL2 and TAF7L in acute myeloid leukemia: a gender-dependent expression pattern. Med Oncol 30: 368. doi: 10.1007/s12032-012-0368-8
[12]
Gong M, Xu Y, Dong W, Guo G, Ni W, et al.. (2013) Expression of Opa interacting protein 5 (OIP5) is associated with tumor stage and prognosis of clear cell renal cell carcinoma. Acta Histochem In press.
[13]
Fujita Y, Hayashi T, Kiyomitsu T, Toyoda Y, Kokubu A, et al. (2007) Priming of centromere for CENP-A recruitment by human hMis18alpha, hMis18beta, and M18BP1. Dev Cell 12: 17–30. doi: 10.1016/j.devcel.2006.11.002
[14]
Maeda N, Takahashi M, Funahashi T, Kihara S, Nishizawa H, et al. (2001) PPARgamma ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein. Diabetes 50: 2094–2099. doi: 10.2337/diabetes.50.9.2094
[15]
Ito A, Suganami T, Miyamoto Y, Yoshimasa Y, Takeya M, et al. (2007) Role of MAPK phosphatase-1 in the induction of monocyte chemoattractant protein-1 during the course of adipocyte hypertrophy. J Biol Chem 282: 25445–25452. doi: 10.1074/jbc.m701549200
[16]
Hosono T, Mizuguchi H, Katayama K, Koizumi N, Kawabata K, et al. (2005) RNA interference of PPARgamma using fiber-modified adenovirus vector efficiently suppresses preadipocyte-to-adipocyte differentiation in 3T3-L1 cells. Gene 348: 157–165. doi: 10.1016/j.gene.2005.01.005
[17]
Hiuge-Shimizu A, Maeda N, Hirata A, Nakatsuji H, Nakamura K, et al. (2011) Dynamic changes of adiponectin and S100A8 levels by the selective peroxisome proliferator-activated receptor-gamma agonist rivoglitazone. Arterioscler Thromb Vasc Biol 31: 792–799. doi: 10.1161/atvbaha.110.221747
[18]
Spalding KL, Arner E, Westermark PO, Bernard S, Buchholz BA, et al. (2008) Dynamics of fat cell turnover in humans. Nature 453: 783–787. doi: 10.1038/nature06902
[19]
Rosen ED, MacDougald OA (2006) Adipocyte differentiation from the inside out. Nat Rev Mol Cell Biol 7: 885–896. doi: 10.1038/nrm2066
[20]
Rodeheffer MS, Birsoy K, Friedman JM (2008) Identification of white adipocyte progenitor cells in vivo. Cell 135: 240–249. doi: 10.1016/j.cell.2008.09.036
[21]
Tang W, Zeve D, Suh JM, Bosnakovski D, Kyba M, et al. (2008) White fat progenitor cells reside in the adipose vasculature. Science 322: 583–586. doi: 10.1126/science.1156232
[22]
Arner P, Spalding KL (2010) Fat cell turnover in humans. Biochem Biophys Res Commun 396: 101–104. doi: 10.1016/j.bbrc.2010.02.165
[23]
Arner E, Westermark PO, Spalding KL, Britton T, Rydén M, et al. (2010) Adipocyte turnover: relevance to human adipose tissue morphology. Diabetes 59: 105–109. doi: 10.2337/db09-0942
[24]
Abella A, Dubus P, Malumbres M, Rane SG, Kiyokawa H, et al. (2005) Cdk4 promotes adipogenesis through PPARgamma activation. Cell Metab 2: 239–249. doi: 10.1016/j.cmet.2005.09.003
[25]
Naaz A, Holsberger DR, Iwamoto GA, Nelson A, Kiyokawa H, et al. (2004) Loss of cyclin-dependent kinase inhibitors produces adipocyte hyperplasia and obesity. FASEB J 18: 1925–1927. doi: 10.1096/fj.04-2631fje
[26]
Sakai T, Sakaue H, Nakamura T, Okada M, Matsuki Y, et al. (2007) Skp2 controls adipocyte proliferation during the development of obesity. J Biol Chem 282: 2038–2046. doi: 10.1074/jbc.m608144200
[27]
Nagayama M, Uchida T, Gohara K (2007) Temporal and spatial variations of lipid droplets during adipocyte division and differentiation. J Lipid Res 48: 9–18. doi: 10.1194/jlr.m600155-jlr200
[28]
Young P, Arch JR, Ashwell M (1984) Brown adipose tissue in the parametrial fat pad of the mouse. FEBS Lett 167: 10–14. doi: 10.1016/0014-5793(84)80822-4
[29]
Cousin B, Cinti S, Morroni M, Raimbault S, Ricquier D, et al. (1992) Occurrence of brown adipocytes in rat white adipose tissue: molecular and morphological characterization. J Cell Sci 103: 931–942.
[30]
Himms-Hagen J, Cui J, Danforth E Jr, Taatjes DJ, Lang SS, et al. (1994) Effect of CL-316,243, a thermogenic beta 3-agonist, on energy balance and brown and white adipose tissues in rats. Am J Physiol 266: R1371–R1382.
[31]
Nagase I, Yoshida T, Kumamoto K, Umekawa T, Sakane N, et al. (1996) Expression of uncoupling protein in skeletal muscle and white fat of obese mice treated with thermogenic beta 3-adrenergic agonist. J Clin Invest 97: 2898–2904. doi: 10.1172/jci118748
[32]
Bogacka I, Xie H, Bray GA, Smith SR (2005) Pioglitazone induces mitochondrial biogenesis in human subcutaneous adipose tissue in vivo. Diabetes 54: 1392–1399. doi: 10.2337/diabetes.54.5.1392
[33]
Wu J, Bostr？m P, Sparks LM, Ye L, Choi JH, et al. (2012) Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell 150: 366–376. doi: 10.1016/j.cell.2012.05.016
[34]
Okuno A, Tamemoto H, Tobe K, Ueki K, Mori Y, et al. (1998) Troglitazone increases the number of small adipocytes without the change of white adipose tissue mass in obese Zucker rats. J Clin Invest 101: 1354–1361. doi: 10.1172/jci1235
[35]
Fukui Y, Masui S, Osada S, Umesono K, Motojima K (2000) A new thiazolidinedione, NC-2100, which is a weak PPAR-gamma activator, exhibits potent antidiabetic effects and induces uncoupling protein 1 in white adipose tissue of KKAy obese mice. Diabetes 49: 759–767. doi: 10.2337/diabetes.49.5.759
