Asian-Australasian Journal of Animal Sciences

Asian Australasian Association of Animal Production Societies (아세아태평양축산학회)
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Proteomic Functional Characterization of Bovine Stromal Vascular Cells from Omental, Subcutaneous and Intramuscular Adipose Depots

  • Rajesh, Ramanna Valmiki (Division of Animal Genomics and Bioinformatics, National Institute of Animal Science, Rural Development Administration) ;
  • Kim, Seong-Kon (Division of Animal Genomics and Bioinformatics, National Institute of Animal Science, Rural Development Administration) ;
  • Park, Mi-Rim (Division of Animal Genomics and Bioinformatics, National Institute of Animal Science, Rural Development Administration) ;
  • Nam, Jin-Seon (Division of Animal Genomics and Bioinformatics, National Institute of Animal Science, Rural Development Administration) ;
  • Kim, Nam-Kuk (Division of Animal Genomics and Bioinformatics, National Institute of Animal Science, Rural Development Administration) ;
  • Kwon, Seulemina (Division of Animal Genomics and Bioinformatics, National Institute of Animal Science, Rural Development Administration) ;
  • Yoon, Du-Hak (Division of Animal Genomics and Bioinformatics, National Institute of Animal Science, Rural Development Administration) ;
  • Kim, Tae-Hun (Division of Animal Genomics and Bioinformatics, National Institute of Animal Science, Rural Development Administration) ;
  • Lee, Hyun-Jeong (Division of Animal Genomics and Bioinformatics, National Institute of Animal Science, Rural Development Administration)
  • Received : 2010.03.22
  • Accepted : 2010.05.18
  • Published : 2011.01.01
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Abstract

Anatomically separate fat depots differ in size, function, and contribution to pathological states such as the metabolic syndrome. We isolated pre-adipocytes from different adipose depots, omental, subcutaneous and intramuscular, of beef cattle, and cultured in vitro to determine the basis for the variations and attribute these variations to the inherent properties of adipocyte progenitors. The proliferating cells from all depots before the confluence were harvested and the proteome was analyzed by a functional proteomic approach, involving 2-DE and MALDI-TOF/TOF. More than 252 protein spots were identified, selected and analyzed by Image Master (ver 7.0) and MALDI-TOF/TOF. Further, our analysis showed that there were specific differences in proteome expression patterns among proliferating precursor cells from the three depots. Sixteen proteins were found to be differentially expressed and these were identified as proteins involved in cellular processes, heat shock/chaperones, redox proteins, cytoskeletal proteins and metabolic enzymes. The results also enabled us to understand the basic roles of these proteins in different inherent properties exhibited by adipose tissue depots.

Keywords

References

  1. Aboulaich, N., J. P. Vainonen, P. Stralfors and A. V. Vener. 2004. Vectorial proteomics reveal targeting, phosphorylation and specific fragmentation of PTRF (polymerase I and transcript release factor) at the surface of caveolae in human adipocytes. Biochem. J. 383:237-248. https://doi.org/10.1042/BJ20040647
  2. Adachi, J., C. Kumar, Y. Zhang and M. Mann. 2007. In-depth analysis of the adipocyte proteome by mass spectrometry and bioinformatics. Mol. Cell Proteomics 6:1257-1273. https://doi.org/10.1074/mcp.M600476-MCP200
  3. Adams, M., M. J. Reginato, D. Shao, M. A. Lazar and V. Krishna Chatterjee. 1997. Transcriptional activation by peroxisome proliferator-activated receptor is inhibited by phosphorylation at a consensus mitogen-activated protein kinase site. J. Biol. Chem. 272:5128-5132. https://doi.org/10.1074/jbc.272.8.5128
  4. Ahmed, M. and P. Bergsten. 2005. Glucose-induced changes of multiple mouse islet proteins analysed by two-dimensional gel electrophoresis and mass spectrometry. Diabetologica 48:477-485. https://doi.org/10.1007/s00125-004-1661-7
  5. Arner, P. 1997. Regional adiposity in man. J. Endocrinol. 155:191-192. https://doi.org/10.1677/joe.0.1550191
  6. Barcelo-Batllori, S. and R. Gomis. 2009. Proteomics in obesity. Proteomics Clin. Appl. 3:263-278. https://doi.org/10.1002/prca.200800178
  7. Caserta, F., T. Tchkonia, V. Civelekm, M. Prentki, N. F. Brown, J. D. McGarry, R. A. Forse, B. E. Corkey, J. A. Hamilton and J. L. Kirkland. 2001. Fat depot origin affects fatty acid handling in cultured rat and human preadipocytes. Am. J. Physiol. Endocrinol. Metab. 280:E238-E247.
  8. Cherian, M. and E. C. Abraham. 1995. Diabetes affects ${\alpha}-crystallin$ chaperone function. Biochem. Biophys. Res. Commun. 212:184-189. https://doi.org/10.1006/bbrc.1995.1954
  9. Choi, K. C., S. G. Roh, D. Hishikawa, H. Miyahara, M. Kuno, H. Tsuzuki, A. Tomimatsu, Y. H. Hong, K. K. Cho, K. H. Han and S. Sasaki. 2003. Differential expression of the nonmuscle-type cofilin gene between subcutaneous and visceral adipose tissue. Biosci. Biotechnol. Biochem. 67:2262-2265. https://doi.org/10.1271/bbb.67.2262
  10. Chouchane, L., J. Danguir, C. Beji, K. Bouassida, L. Camoin, H. Sfar, S. Gabbouj and A. D. Strosberg. 2001. Genetic variation in the stress protein hsp70-2 gene is highly associated with obesity. Int. J. Obes. Relat. Metab. Disord. 25:462-466. https://doi.org/10.1038/sj.ijo.0801545
  11. Cianzio, D., D. G. Topel, G. Whitehurst, D. C. Beitz and H. L. Slef. 1982. Adipose tissue growth in cattle representing two frame sizes: Distribution among depots. J. Anim. Sci. 55:305-312.
  12. Cornelius, P., O. A. MacDougald and M. D. Lane. 1994. Regulation of adipocyte development. Annu. Rev. Nutr. 14:99-129. https://doi.org/10.1146/annurev.nu.14.070194.000531
  13. Cryer, A., S. E. Williams and J. Cryer. 1992. Dietary and other factors involved in the proliferation, determination and differentiation of adipocyte precursor cells. Proc. Nutr. Soc. 51:379-385. https://doi.org/10.1079/PNS19920051
  14. Cryer, J., B. G. Woodhead and A. Cryer. 1987. The isolation and characterization of a putative adipocyte precursor cell type from the white adipose tissue of the chicken (Gallus domesticus). Comp. Biochem. Physiol. 86A:515-520.
  15. Darlington, G. J., S. E. Ross and O. A. MacDougald. 1998. The role of C/EBP genes in adipocyte differentiation. J. Biol. Chem. 273:30057-30060. https://doi.org/10.1074/jbc.273.46.30057
  16. Djian, P., D. A. K. Roncari and C. H. Hollenberg. 1993. Influence of anatomic site and age on the replication and differentiation of rat adipocyte precursors in culture. J. Clin. Invest. 72:1200-1208.
  17. Dubios, T., J. P. Mira, D. Feliers, E. Solito, F. Russo-Marie and J. P. Oudinet. 1998. Annexin V inhibits protein kinase C activity via a mechanism of phospholipid sequestration. Biochem. J. 330:1277-1282.
  18. Edens, N. K., S. K. Fried, J. G. Kral, J. Hirsch and R. L. Leibel. 1993. In vitro lipid synthesis in human adipose tissue from three abdominal sites. Am. J. Physiol. Endocrinol. Metab. 265: E374-E379.
  19. Fasshauera, M., J. Kleinb, S. Neumanna, M. Eszlingera and R. Paschke. 2002. Hormonal regulation of adiponectin gene expression in 3T3-L1 adipocytes. Biochem. Biophys. Res. Commun. 290:1084-1089. https://doi.org/10.1006/bbrc.2001.6307
  20. Fleming, I., S. J. MacKenzie, R. G. Vernon, N. G. Anderson, M. D. Houslay and E. Kilgour. 1999. Protein kinase C isoform play differential roles in the regulation of adipocyte differentiation. Biochem. J. 333:719-727.
  21. Fried, S. K., C. D. Russell, N. L. Grauso and R. E. Brolin. 1993. Lipoprotein lipase regulation by insulin and glucocorticoid in subcutaneous and omental adipose tissues of obese women and men. J. Clin. Invest. 92:2191-2198. https://doi.org/10.1172/JCI116821
  22. Gao, G. and G. Serrero. 1990. Phospholipase $A_2$ is a differentiation-dependent enzymatic activity for adipogenic cell line and adipocyte precursors in primary culture. J. Biol. Chem. 265:2431-2434.
  23. Gregoire, F., G. Todoroff, N. Hauser and C. Remacle. 1990. The stromal vascular fraction of rat inguinal and epididymal adipose tissue and the adipoconversion of fat cell precursors in primary culture. Biol. Cell. 69:215-222. https://doi.org/10.1016/0248-4900(90)90348-7
  24. Hache, R. J., R. Tse, T. Reich, J. G. Savory and Y. A. Lefebure. 1999. Nucleocytoplasmic trafficking of steroid-free glucocorticoid receptor. J. Biol. Chem. 274:1432-1439. https://doi.org/10.1074/jbc.274.3.1432
  25. Hartman, A. D. 1985. Adipocyte fatty acid mobilization in vivo: effects of age and anatomical location. Lipids 20:255-261. https://doi.org/10.1007/BF02534256
  26. Hauner, H. and G. Entenmann. 1991. Regional variation of adipose differentiation in cultured stromal-vascular cells from the abdominal and femoral adipose tissue of obese women. Int. J. Obes. 15:121-126.
  27. Hausman, D. B., M. DiGirolamo, T. J. Bartness, G. J. Hausman and R. J. Martin. 2001. The biology of white adipocyte proliferation. Obes. Rev. 2:239-254. https://doi.org/10.1046/j.1467-789X.2001.00042.x
  28. Hellmann, U., C. Wemstedt, J. Gonez and C. H. Heldin. 1995. Improvement of an "In-gel" digestion procedure for the micropreparation of internal protein fragments for amino acid sequencing. Anal. Biochem. 224:451-455. https://doi.org/10.1006/abio.1995.1070
  29. Hoehn, B., M. A. Yenari, R. M. Sapolsky and G. K. Steinberg. 2003. Glutathione peroxidase overexpression inhibits cytochrome c release and proapoptotic mediators to protect neurons from experimental stroke. Stroke. 34:2489-2449. https://doi.org/10.1161/01.STR.0000091268.25816.19
  30. Hube, F., U. Lietz, M. Igel, P. B. Jensen, H. Tornqvist, H. G. Joost and H. Hauner. 1996. Difference in leptin mRNA levels between omental and subcutaneous abdominal adipose tissue from obese humans. Horm. Metab. Res. 28:690-693. https://doi.org/10.1055/s-2007-979879
  31. James, P., Z. DeLany, E. Floyd, S. Zvonic, A. Gravois, E. Reiners, X. Wu, G. Kilroy, M. Lefevre and J. M. Gimble. 2005. Proteomic analysis of primary cultures of human adipose-derived stem cells. Mol. Cell. Proteomics 4:731-740. https://doi.org/10.1074/mcp.M400198-MCP200
  32. Jin, D. Y., H. Z. Chae, S. G. Rhee and K. T. Jeang. 1997. Regulatory role for a novel human thioredoxin peroxidase in $NF-{\kappa}B$ activation. J. Biol. Chem. 272:30952-30961. https://doi.org/10.1074/jbc.272.49.30952
  33. Kaul, S. C., R. R. Reddel, Y. Mitsui and R. Wadhwa. 2001. An N-terminal region of mot-2 binds to p53 in vitro. Neoplasia 3:110-114. https://doi.org/10.1038/sj.neo.7900139
  34. Kirkland, J. and P. M. Harris. 1980. Changes in adipose tissue of the rat due to early under nutrition followed by rehabilitation. 3. Changes in cell replication studies with tritiated thymidine. Br. J. Nutr. 43:33-43. https://doi.org/10.1079/BJN19800062
  35. Kirkland, J. L. and E. M. Dax. 1984. Adipose hormone responsiveness and aging in the rat. J. Am. Geriatr. Soc. 32:1219-228.
  36. Kirkland, J. L., C. H. Hollenberg and W. S. Gillon. 1996. Effects of fat depot site on differentiation-dependent gene expression in rat preadipocytes. Int. J. Obes. 20:S102-S107.
  37. Kirkland, J. L., C. H. Hollenberg, W. Gillon and S. Kindler. 1992. Effect of hypophysectomy on rat preadipocyte replication and differentiation. Endocrinology 131:2769-2773. https://doi.org/10.1210/en.131.6.2769
  38. Kirkland, J. L., P. Cummins, C. Steppan, D. E. Dobson and M. H. Cladaras. 1997. Decreasing preadipocyte differentiation capacity with aging is associated with blunted expression of the transcription factor, CCAAT enhancer binding protein ${\alpha}$. Obes. Res. 5 (Suppl 1):22S.
  39. Kumar, M. S., P. Y. Reddy, P. A. Kumar, I. Surolia and G. B. Reddy. 2004. Effect of dicarbonyl-induced browning on ${\alpha}-crystallin$ chaperone like activity: physiological significance and caveats of in vitro aggregation assays. Biochem. J. 379:273-282. https://doi.org/10.1042/BJ20031633
  40. Kurucz, I., A. Morva, A. Vaag, K. Eriksson, X. Huang, L. Group and L. Koranyi. 2002. Decreased expression of heat shock protein 72 in skeletal muscle of patients with type 2 diabetes correlates with insulin resistance. Diabetes 51:1102-1109. https://doi.org/10.2337/diabetes.51.4.1102
  41. Lacasa, D., E. Garcia, B. Agli and Y. Giudicelli. 1997. Control of rat preadipocytes adipose conversion by ovarian status: regional specificity and possible involvement of the mitogenactivated protein kinase-dependent and c-fos signaling pathways. Endocrinology 138:2729-2734. https://doi.org/10.1210/en.138.7.2729
  42. Landry, F., C. R. Lombardo and J. W. Smith. 2000. A method for application of samples to Matrix-Assisted Laser Desorption Ionization Time-of-Flight targets that enhances peptide detection. Anal. Biochem. 279:1-8. https://doi.org/10.1006/abio.1999.4468
  43. Litthauer, D. and G. Serrero. 1992. The primary culture of mouse adipocyte precursor cells in defined medium. Comp. Biochem. Physiol. A Comp. Physiol. 101:59-64. https://doi.org/10.1016/0300-9629(92)90628-4
  44. Loffler, G. and H. Hauner. 1987. Adipose tissue development: the role of precursor cells and adipogenic factors. Part II. The regulation of the adipogenic conversion by hormones and serum factors. Klin. Wochenschr. 65:812-817. https://doi.org/10.1007/BF01727475
  45. Luegmayr, E., F. Varga, T. Frank, P. Roschger and K. Klaushofer. 1996. Effects of triiodothyronine on morphology, growth behavior, and the actin cytoskeleton in mouse osteoblastic cells (MC3T3-E1). Bone 18:591-599. https://doi.org/10.1016/8756-3282(96)00068-3
  46. Mayr, M., R. Siow, Y. L. Chung, U. Mayr, J. R. Griffiths and Q. Xu. 2004. Proteomic and metabolomic analysis of vascular smooth muscle cells. Circ. Res. 94:e87-e96. https://doi.org/10.1161/01.RES.0000131496.49135.1d
  47. McBeath, R., D. M. Pirone, C. M. Nelson, K. Bhadriraju and C. S. Chen. 2004. Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev. Cell 6:483-495. https://doi.org/10.1016/S1534-5807(04)00075-9
  48. Mira, J. P., T. Dubois, J. P. Oudinet, S. Lukowski, F. Russo-Marie and B. Geny. 1997. Inhibition of cytosolic phospholipase $A_2$ by Annexin V in differentiated permeabilized HL-60 cells. J. Biol. Chem. 272:10474-10482. https://doi.org/10.1074/jbc.272.16.10474
  49. Niesler, C. U., K. Siddle and B. Prins. 1998. Human preadipocytes displays a depot-specific susceptibility to apoptosis. Diabetes 47:1365-1368. https://doi.org/10.2337/diabetes.47.8.1365
  50. Niesler, C. U., K. Siddle and J. B. Prins. 1998. Human preadipocytes display a depot-specific susceptibility to apoptosis. Diabetes 47:1365-1368. https://doi.org/10.2337/diabetes.47.8.1365
  51. Novakofski, J. and C. Y. Hu. 1987. Culture of isolated adipose tissue cells. J. Anim. Sci. 65:12-24.
  52. Ozcan, U., Q. Cao, E. Yilmaz, A. H. Lee, N.N. Iwakoshi, E. Ozdelen, G. Tuncman, C. Gorgun, L. H. Glimcher and G. S. Hotamisligil. 2004. Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science 306:457-461. https://doi.org/10.1126/science.1103160
  53. Pan, L., P. C. L. Beverley and P. G. Isaacson. 1991. Lactate dehydrogenase (LDH) isoenzymes and proliferative activity of lymphoid cells - an immunocytochemical study. Clin. Exp. Immunol. 86:240-245.
  54. Perez-Perez, R., F. J. Ortega-Delgado, E. Garcia-Santos, J. A. Lopez, E. Camafeita, W. Ricart, J. M. Fernandez-Real and B. Peral. 2009. Differential proteomics of omental and subcutaneous adipose tissue reflects their unalike biochemical and metabolic properties. J. Proteome Res. 8:1682-1693. https://doi.org/10.1021/pr800942k
  55. Petrak, J., R. Ivanek, O. Toman, R. Cmejla, J. Cmejlova, D. Vyoral, J. Zivny, C. D. Vulpe, Deja vu in proteomics. 2008. A hit parade of repeatedly identified differentially expressed proteins. Proteomics 8:1744-1749. https://doi.org/10.1002/pmic.200700919
  56. Prins, J. B. and S. O'Rahilly. 1997. Regulation of adipose cell number in man. Clin. Sci. 92:3-11.
  57. Prosperi, M. T., D. Ferbus, D. Rouillard and G. Goubin. 1998. The pag gene product, a physiological inhibitor of c-abl tyrosine kinase, is overexpressed in cells entering S phase and by contact with agents including oxidative stress. FEBS Lett. 423:39-44. https://doi.org/10.1016/S0014-5793(98)00057-X
  58. Rahman, A., S. G. Kumar, S. W. Kim, H. J. Hwang, M. B. Yu, S. K. Lee, H. S. Hwang, Y. H. Shon, K. S. Nam and J. W. Yun. 2008. Proteomic analysis for inhibitory effect of chitosan oligosaccharides on 3T3-L1 adipocyte differentiation. Proteomics 8:569-581. https://doi.org/10.1002/pmic.200700888
  59. Ramsay, T. G., S. V. Rao and C. K. Wolverton. 1993. In vitro systems for the analysis of the development of adipose tissue in domestic animals. J. Nutr. 122:806-817.
  60. Rane, M. J., Y. Pan, S. Singh, D. W. Powell, R. Wu, T. Cummins, Q. Chen, K. R. McLeish and J. B. Klein. 2003. Heat shock protein 27 controls apoptosis by regulating Akt activation. J. Biol. Chem. 278:27828-27835. https://doi.org/10.1074/jbc.M303417200
  61. Renes, J., F. Bouwman, J. P. Noben, C. Evelo, J. Robben and E. Mariman. 2005. Protein profiling of 3T3-L1 adipocyte differentiation and (tumor necrosis factor alpha-mediated) starvation. Cell. Mol. Life Sci. 62:492-503. https://doi.org/10.1007/s00018-004-4498-9
  62. Samulin, J., S. Lien, E. Grindflek, I. Berget, B. Ruyter and H. Sundvold. 2008. Depot specific differences during adipogenesis of porcine stromal-vascular cells. Cell Biol. Int. 32:525-531. https://doi.org/10.1016/j.cellbi.2008.01.001
  63. Sezen, D., A. Bongiovanni, S. Gelber, U. Perni, J. Hutson, D. Skupski and S. Witkin. 2009. Gelsolin down-regulates lipopolysaccharide-inducedintraamniotic tumor necrosis factor-α production in the midtrimester of pregnancy. Am. J. Obstet. Gynecol. 200:191-192.
  64. Sha, H., Y. He, H. Chen, C. Wang, A. Zenno, H. Shi, X. Yang, X. Zhang and L. Qi. 2009. The IRE1a-XBP1 pathway of the unfolded protein response is required for adipogenesis. Cell Metab. 9:556-564. https://doi.org/10.1016/j.cmet.2009.04.009
  65. Shan, Y., T. L. Yang, R. Mestril and P. H. Wang. 2003. Hsp10 and Hsp60 suppress ubiquitination of insulin-like growth factor-1 receptor and augment insulin-like growth factor-1 receptor signaling in cardiac muscle. J. Biol. Chem. 278:45492-45498. https://doi.org/10.1074/jbc.M304498200
  66. Shi, Y., K. Porter, N. Parameswaran and H. K. Bae. 2009. Role of GRP78/BiP degradation and ER stress in deoxynivalenolinduced interleukin-6 upregulation in the macrophage. Toxicol. Sci. 109:247-255. https://doi.org/10.1093/toxsci/kfp060
  67. Smyth, M. J., R. L. Sparks and W. Wharton. 1993. Proadipocyte cell lines: models of cellular proliferation and differentiation. J. Cell. Sci. 106:1-9.
  68. Takenouchi, T., N. Miyashita, K. Ozutsumi, M. T. Rose and H. Aso. 2004. Role of caveolin-1 and cytoskeletal proteins, actin and vimentinm in adipogenesis of bovine intramuscular preadipocytes cells. Cell Biol. Int. 28:615-623. https://doi.org/10.1016/j.cellbi.2004.05.003
  69. Tchkonia, T., N. Giorgadze, T. Pirtskhalava, Y. Tchoukalova, I. Karagiannides and R. A. Forse. 2002. Fat depot origin affects adipogenesis in primary cultured and cloned human preadipocytes. Am. J. Physiol. Regul. Integr. Comp. Physiol. 282:R1286-1296.
  70. Van Harmelen, V., K. Rohrig and H. Hauner. 2004. Comparison of proliferation and differentiation capacity of human adipocyte precursor cells from omental and subcutaneous adipose tissue depot of obese subjects. Metab. Clin. Exp. 53:632-637. https://doi.org/10.1016/j.metabol.2003.11.012
  71. Villani, P., P. L. Altavista, L. Castaldi, G. Leter and E. Cordelli. 2000. Analysis of DNA oxidative damage related to cell proliferation. Mutat. Res. 464:229-237. https://doi.org/10.1016/S1383-5718(99)00192-8
  72. Wadhwa, R., S. Takano, M. Robert, A. Yoshida, H. Nomura, R. R. Reddel, Y. Mitusui and S. C. Kaul. 1998. Inactivation of tumor suppressor p53 by mot-2, a hsp70 family member. J. Biol. Chem. 273:29586-29591. https://doi.org/10.1074/jbc.273.45.29586
  73. Wang, P., F. G. Bouwman and E. C. Mariman. 2009. Generally detected proteins in comparative proteomics-a matter of cellular stress response? Proteomics 9:2955-2966. https://doi.org/10.1002/pmic.200800826
  74. Webb, P. R., Doyle and C. N. G. Anderson. 2003. Protein kinase $C-{\varepsilon}$ promotes adipogenic commitment and is essential for terminal differentiation of 3T3-F442A preadipocytes. Cell. Mol. Life. Sci. 60:1504-1512. https://doi.org/10.1007/s00018-003-2337-z
  75. Weil, C., N. Sabin, J. Bugeon, G. Paboeuf and F. Lefevre. 2009. Differentially expressed proteins in rainbow trout adipocytes isolated from visceral and subcutaneous tissues. Comp. Biochem. Physiol. Part D Genomics Proteomics 4:235-241. https://doi.org/10.1016/j.cbd.2009.05.002
  76. Yeh, W. C., T. K. Li, B. E. Bierer and S. L. McKnight. 1995. Identification and characterization of an immunophilin expressed during the clonal expansion phase of adipocyte differentiation. Proc. Natl. Acad. Sci. USA 92:11081-11085. https://doi.org/10.1073/pnas.92.24.11081
  77. Young, J. C., V. R. Agashe, K. Siegers and F. U. Hartl. 2005. Pathways of chaperone-mediated protein folding in the cytosol. Nat. Rev. Mol. Cell. Biol. 5:781-791.
  78. Ziouzenkova, O., G. Orasanu, M. Sharlach, T. E Akiyama, J. P. Berger, J. Viereck, J. A. Hamilton, G. Tang, G. G. Dolnikowski, S. Vogel, G. Duester and J. Plutzky. 2007. Retinaldehyde represses adipogenesis and diet-induced obesity. Nat. Med. 13:695-702. https://doi.org/10.1038/nm1587
  79. Zouari Bouassida, K., L. Chouchane, K. Jellouli, S. Cherif, S. Haddada, S. Gabboujb and J. Danguir. 2004. Polymorphism of stress protein HSP70-2 gene in Tunisians: susceptibility implications in type 2 diabetes and obesity. Diabetes Metab. 30:175-180. https://doi.org/10.1016/S1262-3636(07)70104-0