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

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.

[1]  Yan Wang,et al.  Expression of Opa interacting protein 5 (OIP5) is associated with tumor stage and prognosis of clear cell renal cell carcinoma. , 2013, Acta histochemica.

[2]  T. Funahashi,et al.  Gene expression levels of S100 protein family in blood cells are associated with insulin resistance and inflammation (Peripheral blood S100 mRNAs and metabolic syndrome). , 2013, Biochemical and biophysical research communications.

[3]  R. Shirkoohi,et al.  Expression analysis of four testis-specific genes AURKC, OIP5, PIWIL2 and TAF7L in acute myeloid leukemia: a gender-dependent expression pattern , 2013, Medical Oncology.

[4]  T. Funahashi,et al.  A Pilot Investigation of Visceral Fat Adiposity and Gene Expression Profile in Peripheral Blood Cells , 2012, PloS one.

[5]  B. Spiegelman,et al.  Beige Adipocytes Are a Distinct Type of Thermogenic Fat Cell in Mouse and Human , 2012, Cell.

[6]  Yusuke Nakamura,et al.  Characterization of an Opa interacting protein 5 involved in lung and esophageal carcinogenesis , 2012, Cancer science.

[7]  S. Kihara,et al.  Dynamic Changes of Adiponectin and S100A8 Levels by the Selective Peroxisome Proliferator–Activated Receptor-&ggr; Agonist Rivoglitazone , 2011, Arteriosclerosis, thrombosis, and vascular biology.

[8]  Seon-Young Kim,et al.  OIP5 is a highly expressed potential therapeutic target for colorectal and gastric cancers. , 2010, BMB reports.

[9]  P. Arner,et al.  Fat cell turnover in humans. , 2010, Biochemical and biophysical research communications.

[10]  S. Bernard,et al.  Adipocyte Turnover: Relevance to Human Adipose Tissue Morphology , 2009, Diabetes.

[11]  R. Hammer,et al.  White Fat Progenitor Cells Reside in the Adipose Vasculature , 2008, Science.

[12]  J. Friedman,et al.  Identification of White Adipocyte Progenitor Cells In Vivo , 2008, Cell.

[13]  Tom Britton,et al.  Dynamics of fat cell turnover in humans , 2008, Nature.

[14]  Y. Kamei,et al.  Role of MAPK Phosphatase-1 in the Induction of Monocyte Chemoattractant Protein-1 during the Course of Adipocyte Hypertrophy* , 2007, Journal of Biological Chemistry.

[15]  K. Mimori,et al.  Opa Interacting Protein 5 (OIP5) Is a Novel Cancer-testis Specific Gene in Gastric Cancer , 2007, Annals of Surgical Oncology.

[16]  Y. Matsuki,et al.  Skp2 Controls Adipocyte Proliferation during the Development of Obesity* , 2007, Journal of Biological Chemistry.

[17]  O. MacDougald,et al.  Adipocyte differentiation from the inside out , 2006, Nature Reviews Molecular Cell Biology.

[18]  M. Barbacid,et al.  Cdk4 promotes adipogenesis through PPARgamma activation. , 2005, Cell metabolism.

[19]  G. Bray,et al.  Pioglitazone induces mitochondrial biogenesis in human subcutaneous adipose tissue in vivo. , 2005, Diabetes.

[20]  S. Nakagawa,et al.  RNA interference of PPARγ using fiber-modified adenovirus vector efficiently suppresses preadipocyte-to-adipocyte differentiation in 3T3-L1 cells , 2005 .

[21]  G. Iwamoto,et al.  Loss of cyclin‐dependent kinase inhibitors produces adipocyte hyperplasia and obesity , 2004, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[22]  M. Matsuda,et al.  PPARgamma ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein. , 2001, Diabetes.

[23]  K. Umesono,et al.  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. , 2000, Diabetes.

[24]  K. Umesono,et al.  Troglitazone increases the number of small adipocytes without the change of white adipose tissue mass in obese Zucker rats. , 1998, The Journal of clinical investigation.

[25]  R. Rest,et al.  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 , 1998, Molecular microbiology.

[26]  Y. Matsuzawa,et al.  Analysis of an expression profile of genes in the human adipose tissue. , 1997, Gene.

[27]  K. Kumamoto,et al.  Expression of uncoupling protein in skeletal muscle and white fat of obese mice treated with thermogenic beta 3-adrenergic agonist. , 1996, The Journal of clinical investigation.

[28]  T. Funahashi,et al.  cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (AdiPose Most abundant Gene transcript 1). , 1996, Biochemical and biophysical research communications.

[29]  J. Himms-Hagen,et al.  Effect of CL-316,243, a thermogenic beta 3-agonist, on energy balance and brown and white adipose tissues in rats. , 1994, The American journal of physiology.

[30]  L. Pénicaud,et al.  Occurrence of brown adipocytes in rat white adipose tissue: molecular and morphological characterization. , 1992, Journal of cell science.

[31]  Kousaku Okubo,et al.  Large scale cDNA sequencing for analysis of quantitative and qualitative aspects of gene expression , 1992, Nature Genetics.

[32]  M. Ashwell,et al.  Brown adipose tissue in the parametrial fat pad of the mouse , 1984, FEBS letters.

[33]  S. Bernard,et al.  Adipocyte Turnover: Relevance to Human Adipose Tissue , 2010 .

[34]  R. Hammer,et al.  Vasculature White Fat Progenitor Cells Reside in the Adipose , 2008 .

[35]  Yusuke Toyoda,et al.  Priming of centromere for CENP-A recruitment by human hMis18alpha, hMis18beta, and M18BP1. , 2007, Developmental cell.

[36]  Yusuke Toyoda,et al.  Priming of Centromere for CENP-A Recruitment by Human hMis18α, hMis18β, and M18BP1 , 2007 .

[37]  Y. Matsuzawa.  Therapy Insight: adipocytokines in metabolic syndrome and related cardiovascular disease , 2006, Nature Clinical Practice Cardiovascular Medicine.

[38]  S. Nakagawa,et al.  RNA interference of PPARgamma using fiber-modified adenovirus vector efficiently suppresses preadipocyte-to-adipocyte differentiation in 3T3-L1 cells. , 2005, Gene.