Skip to main content
Log in

Alterations in niban gene expression as a response to stress conditions in 3T3-L1 adipocytes

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Adipocyte death is important in obesity development. Understanding and prevention of adipocyte deaths may be a molecular approach in the treatment. In the study, we aimed to understand role of Niban gene, which acts as an anti-apoptotic molecule as a response to stress conditions, in adipocytes. 3T3-L1 adipocytes were treated with different doses of linoleic acid, hydrogen peroxide and ethanol; and proliferation of the cells examined with real time monitoring iCELLingence system. Gene expression levels were measured by q-PCR. As a response to 24h 480 µM linoleic acid treatment, Niban gene expression was found to be higher than control group (p = 0.008), whereas 24 h 90 mM ethanol treatment was determined to be lower than control group (p = 0.008). The highest value of Niban gene expression among H2O2 treatment groups was detected in 4h 600µM H2O2 in comparison to control group (p = 0.008). To understand role of Niban in adipogenesis, Niban gene expressions were compared between pre-adipocytes and advanced fat accumulated adipocytes and determined to be significantly different (p = 0.042). Our results suggest that Niban might be involved in stress response process in adipocytes. However, the exact molecular role of Niban needs to be investigated in further studies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Cao Y (2010) Adipose tissue angiogenesis as a therapeutic target for obesity and metabolic diseases. Nat Rev Drug Discov 9:107–115. https://doi.org/10.1038/nrd3055

    Article  CAS  PubMed  Google Scholar 

  2. Eckel RH (2003) Obesity: mechanisms and clinical management. Lippincott Williams & Wilkins, Philadelphia (PA)

    Google Scholar 

  3. Ozcan U, Cao Q, Yilmaz E, Lee AH, Iwakoshi NN, Ozdelen E, Tuncman G, Gorgun C, Glimcher LH, Hotamisligil GS (2004) Endoplasmic reticulum stress links obesity insulin action and type2 diabetes. Science 306:457–461. https://doi.org/10.1126/science.1103160

    Article  CAS  PubMed  Google Scholar 

  4. Hirosumi J, Tuncman G, Chang L, Görgün CZ, Uysal KT, Maeda K, Karin M, Hotamisligil GS (2002) A central role for JNK in obesity and insulin resistance. Nature 420:333–6. https://doi.org/10.1038/nature01137

    Article  CAS  PubMed  Google Scholar 

  5. Yuan M, Konstantopoulos N, Lee J, Hansen L, Li ZW, Karin M, Shoelson SE (2001) Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkβ. Science 293:1673–7. https://doi.org/10.1126/science.1061620

    Article  CAS  PubMed  Google Scholar 

  6. Alkhouri N, Gornicka A, Berk MP, Thapaliya S, Dixon LJ, Kashyap S, Schauer PR, Feldstein AE (2010) Adipocyte apoptosis, a link between obesity, insulin resistance, and hepatic steatosis. J Biol Chem 285:3428–3438. https://doi.org/10.1074/jbc.M109.074252

    Article  CAS  Google Scholar 

  7. Adachi H, Majima S, Kon S et al (2004) Niban gene is commonly expressed in the renal tumors: a new candidate marker for renal carcinogenesis. Oncogene 23:3495–3500. https://doi.org/10.1038/sj.onc.1207468

    Article  CAS  PubMed  Google Scholar 

  8. Majima S, Kajino K, Fukuda T, Otsuka F, Hino O (2000) A novel gene ‘Niban’ upregulated in renal carcinogenesis: cloning by the cDNA amplified fragment length polymorphism approach. Jpn J Canc Res 91:869–874. https://doi.org/10.1111/j.1349-7006.2000.tb01027.x

    Article  CAS  Google Scholar 

  9. Matsumoto F, Fujii H, Abe M, Kajino K, Kobayashi T, Matsumoto T, Ikeda K, Hino O (2006) A novel tumor marker, Niban, is expressed in subsets of thyroid tumors and Hashimoto’sthyroiditis. Hum Pathol 37:1592–1600. https://doi.org/10.1016/j.humpath.2006.06.022

    Article  CAS  PubMed  Google Scholar 

  10. Sun GD, Kobayashi T, Abe M, Tada N, Adachi H, Shiota A, TotsukaY Hino O (2007) The endoplasmic reticulum stress-inducible protein Niban regulates eIF2α and S6K1/4E-BP1 phosphorylation. Biochem Biophys Res Commun 360:181–187. https://doi.org/10.1016/j.bbrc.2007.06.021

    Article  CAS  PubMed  Google Scholar 

  11. Ji H, Ding Z, Hawke D, Xing D, Jiang BH, Mills GB, Lu Z (2012) AKT-dependent phosphorylation of Niban regulates nucleophosmin- and MDM2-mediated p53 stability and cell apoptosis. EMBO Rep 13:554–560. https://doi.org/10.1038/embor.2012.53

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Feng X, Yan N, Sun W et al (2019) miR-4521-FAM129A axial regulation on ccRCC progression through TIMP-1/MMP2/MMP9 and MDM2/p53/Bcl2/Bax pathways. Cell Death Discov 5:89. https://doi.org/10.1038/s41420-019-0167-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Nozima BH, Mendes TB, Pereira G, Araldi RP, Iwamura ESM, Smaili SS, Carvalheira GMG, Cerutti JM (2019) FAM129A regulates autophagy in thyroid carcinomas in an oncogene-dependent manner. Endocr Relat Cancer 26:227–238. https://doi.org/10.1530/ERC-17-0530

    Article  CAS  PubMed  Google Scholar 

  14. Pallmann N, Livgård M, Tesikova M, Nenseth HZ, Akkus E, Sikkeland J, Jin Y, Koc D, Kuzu OF, Pradhan M, Danielsen HE, Kahraman N, Mokhlis HM, Ozpolat B, Banerjee PP, Uren A, Fazli L, Rennie PS, Jin Y, Saatcioglu F (2019) Regulation of the unfolded protein response through ATF4 and FAM129A in prostate cancer. Oncogene 38:6301–6318. https://doi.org/10.1038/s41388-019-0879-2

    Article  CAS  PubMed  Google Scholar 

  15. Volkmar M, Dedeurwaerder S, Cunha DA, Ndlovu MN, Defrance M, Deplus R, Del Guerra S (2012) DNA methylation profiling identifies epigenetic dysregulation in pancreatic islets from type 2 diabetic patients. EMBO J 31:1405–1426. https://doi.org/10.1038/emboj.2011.503

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y, Nakayama O, Makishima M, Matsuda M, Shimomura I (2004) Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest 114:1752–1761. https://doi.org/10.1172/JCI21625

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Cnop M, Foufelle F, Velloso LA (2012) Endoplasmic reticulum stress, obesity and diabetes. Trends Mol Med 18:59–68. https://doi.org/10.1016/j.molmed.2011.07.010

    Article  CAS  PubMed  Google Scholar 

  18. Jiao P, Ma J, Feng B, Zhang H, Alan-Diehl J, Eugene-Chin Y, Xu H (2011) FFA-induced adipocyte inflammation and insulin resistance: involvement of ER stress and IKKβ pathways. Obesity 19:483–491. https://doi.org/10.1038/oby.2010.200

    Article  CAS  PubMed  Google Scholar 

  19. Ozcan U, Yilmaz E, Ozcan L, Furuhashi M, Vaillancourt E, Smith RO, Gorgun CZ, Hotamisligil GS (2006) Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes. Science 313:1137–1140. https://doi.org/10.1126/science.1128294

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Miard S, Dombrowski L, Carter S, Boivin L, Picard F (2009) Aging alters PPARgamma in rodent and human adipose tissue by modulating the balance in steroid receptor coactivator-1. Aging Cell 8:449–59. https://doi.org/10.1111/j.1474-9726.2009.00490.x

    Article  CAS  PubMed  Google Scholar 

  21. Chavez JA, Holland WL, Bar J, Sandhoff K, Summers SA (2005) Acid ceramidase overexpression prevents the inhibitory effects of saturated fatty acids on insulin signaling. J Biol Chem 280:20148–20153. https://doi.org/10.1074/jbc.M412769200

    Article  CAS  PubMed  Google Scholar 

  22. Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29(9):45. https://doi.org/10.1093/nar/29.9.e45

    Article  Google Scholar 

  23. Morrison RF, Farmer SR (2000) Hormonal signaling and transcriptional control of adipocyte differentiation. J Nutr 130:3116S-3121S. https://doi.org/10.1093/jn/130.12.3116S

    Article  CAS  PubMed  Google Scholar 

  24. Bays HE, González-Campoy JM, Bray GA, Kitabchi AE, Bergman DA, Schorr AB, Rodbard HW, Henry RR (2008) Pathogenic potential of adipose tissue and metabolic consequences of adipocyte hypertrophy and increased visceral adiposity. Expert Rev Cardiovasc Ther 6:343–368. https://doi.org/10.1586/14779072.6.3.343

    Article  CAS  PubMed  Google Scholar 

  25. Ye F, Than A, Zhao YY, Goh KH, Chen P (2010) Vesicular storage, vesicle trafficking, and secretion of leptin and resistin: the similarities, differences, and interplays. J Endocrinol 206:27–36. https://doi.org/10.1677/JOE-10-0090

    Article  CAS  PubMed  Google Scholar 

  26. Ye F, Zhang H, Yang YX, Hu HD, Sze SK, Meng W, Qian J, Ren H, Yang BL, Luo MY, Wu X, Zhu W, Cai WJ, Tong JB (2011) Comparative proteome analysis of 3T3-L1 adipocyte differentiation using iTRAQ-coupled 2D LC-MS/MS. J Cell Biochem 112:3002–3014. https://doi.org/10.1002/jcb.23223

    Article  CAS  PubMed  Google Scholar 

  27. Andreoli MF, Illesca PG, Gonzalez MA, Bernal CA (2010) Conjugated linoleic acid reduces hepatic steatosis and restores liver triacylglycerol secretion and the fatty acid profi le during protein repletion in rats. Lipids 45:1035–1045. https://doi.org/10.1007/s11745-010-3466-4

    Article  CAS  PubMed  Google Scholar 

  28. Terpstra AH, Beynen A, Everts H, Kocsis S, Katan M, Zock P (2002) The decrease in body fat in mice fed conjugated linoleic acid is due to increases in energy expenditure and energy loss in the excreta. J Nutr 132:940–945. https://doi.org/10.1093/jn/132.5.940

    Article  CAS  PubMed  Google Scholar 

  29. Kennedy A, Martinez K, Schmidt S, Mandrup S, LaPoint K, McIntosh M (2010) Antiobesity mechanisms of action of conjugated linoleic acid. J Nutr Biochem 21:171–179. https://doi.org/10.1016/j.jnutbio.2009.08.003

    Article  CAS  PubMed  Google Scholar 

  30. Park Y, Storkson JM, Albright KJ, Liu W, Pariza MW (1999) Evidence that the trans-10, cis-12 isomer of conjugated linoleic acid induces body composition changes in mice. Lipids 34:235–41. https://doi.org/10.1007/s11745-999-0358-8

    Article  CAS  PubMed  Google Scholar 

  31. Brown JM, Halvorsen YD, Lea-Currie YR, Geigerman C, McIntosh M (2001) Trans-10, cis-12, but not cis-9, trans-11, conjugated linoleic acid attenuates lipogenesis in primary cultures of stromal vascular cells from human adipose tissue. J Nutr 131:2316–21. https://doi.org/10.1093/jn/131.9.2316

    Article  CAS  PubMed  Google Scholar 

  32. Granlund L, Pedersen JI, Nebb HI (2005) Impaired lipid accumulation by trans10, cis12 CLA during adipocyte differentiation is dependent on timing and length of treatment. Biochim Biophys Acta 1687:11–22. https://doi.org/10.1016/j.bbalip.2004.08.018

    Article  CAS  PubMed  Google Scholar 

  33. LaRosa PC, Riethoven JM, Chen H, Xia Y, ZhouY Chen M, Miner J, Fromm ME (2007) Trans-10, cis-12 conjugated linoleic acid activates the integrated stress response pathway in adipocytes. Physiol Genomics 31:544–53. https://doi.org/10.1152/physiolgenomics.00156.2007

    Article  CAS  PubMed  Google Scholar 

  34. Riserus U, Berglund L, Vessby B (2001) Conjugated linoleic acid (CLA) reduced abdominal adipose tissue in obese middle-aged men with signs of the metabolic syndrome: a randomised controlled trial. Int J Obes Relat Metab Disord 25:1129–1135. https://doi.org/10.1038/sj.ijo.0801659

    Article  CAS  PubMed  Google Scholar 

  35. Kanter JE, Goodspeed L, Wang S, Kramer F, Wietecha T, Gomes-Kjerulf D, Den Hartigh LJ (2018) 10, 12 conjugated linoleic acid-driven weight loss is protective against atherosclerosis in mice and is associated with alternative macrophage enrichment in perivascular adipose tissue. Nutrients 10:1416. https://doi.org/10.3390/nu10101416

    Article  CAS  PubMed Central  Google Scholar 

  36. den Hartigh LJ, Wang S, Goodspeed L, Wietecha T, Houston B, Omer M, Kaiyala KJ (2018) Metabolically distinct weight loss by 10, 12 CLA and caloric restriction highlight the importance of subcutaneous white adipose tissue for glucose homeostasis in mice. PLoS One 12:e0172912. https://doi.org/10.1371/journal.pone.0172912

    Article  CAS  Google Scholar 

  37. Tsuboyama-Kasaoka N, Takahashi M, Tanemura K, Kim HJ, Tange T, Okuyama H, Kasai M, Ikemoto S, Ezaki O (2000) Conjugated linoleic acid supplementation reduces adipose tissue by apoptosis and develops. Diabetes 49:1534–1542. https://doi.org/10.2337/diabetes.49.9.1534

    Article  CAS  PubMed  Google Scholar 

  38. Churruca I, Ferna´ndez-Quintela A, Portillo MO (2009) Conjugated linoleic acid isomers: differences in metabolism and biological effects. IUBMB Life 35:105–111. https://doi.org/10.1002/biof.13

    Article  CAS  Google Scholar 

  39. Roz AE, Barda JM, Huvelin JM, Nazih H (2013) The anti-proliferative and pro-apoptotic effects of the trans9, trans11 conjugated linoleic acid isomer on MCF-7 breast cancer cells are associated with LXR activation. Prostaglandins Leukot Essent Fatty Acids (PLEFA) 88:265–272. https://doi.org/10.1016/j.plefa.2012.12.006

    Article  CAS  Google Scholar 

  40. Ryter SW, Kim HP, Hoetzel A, Park JW, Nakahira K, Wang X, Choi AM (2007) Mechanisms of cell death in oxidative stress. Antioxid Redox Sign 9:49–89. https://doi.org/10.1089/ars.2007.9.49

    Article  CAS  Google Scholar 

  41. Escargueil-Blanc I, Salvayre R, Negre-Salvayre A (1994) Necrosis and apoptosis induced by oxidized low density lipoproteins occur through two calcium-dependent pathways in lymphoblastoid cells. FASEB J 8:1075–1080. https://doi.org/10.1096/fasebj.8.13.7926374

    Article  CAS  PubMed  Google Scholar 

  42. Gardner AM, Xu FH, Fady C, Jacoby FJ, Duffey DC, Tu Y, Lichtenstein A (1997) Apoptotic vs. nonapoptotic cytotoxicity induced by hydrogen peroxide. Free Radic Biol Med 22:73–83. https://doi.org/10.1016/S0891-5849(96)00235-3

    Article  CAS  PubMed  Google Scholar 

  43. Wei H, Li Z, Hu S, Chen X, Cong X (2010) Apoptosis of mesenchymal stem cells induced by hydrogen peroxide concerns both endoplasmic reticulum stress and mitochondrial death pathway through regulation of caspases, p38 and JNK. J Cell Biochem 111(4):967–78. https://doi.org/10.1002/jcb.22785

    Article  CAS  PubMed  Google Scholar 

  44. Yoon SO, Kim MM, Park SJ, Kim D, Chung J, Chung AS (2002) Selenite suppresses hydrogen peroxide-induced cell apoptosis through inhibition of ASK1/JNK and activation of PI3-K/Akt pathways. FASEB Journals 16(1):111–3. https://doi.org/10.1096/fj.01-0398fje

    Article  CAS  Google Scholar 

  45. Cherian PP, Schenker S, Henderson GI (2008) Ethanol-mediated DNA damage and PARP-1 apoptotic responses in cultured fetal cortical neurons. Alcohol Clin Exp Res 32:1884–1892. https://doi.org/10.1111/j.1530-0277.2008.00769.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Chen G, Ma C, Bower KA, Shi X, Ke Z, Luo J (2008) Ethanol promotes endoplasmic reticulum stress-induced neuronal death: involvement of oxidative stress. J Neurosci Res 86:937–946. https://doi.org/10.1002/jnr.21540

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Das SK, Vasudevan DM (2007) Alcohol-induced oxidative stress. Life Sci 81:177–187. https://doi.org/10.1016/j.lfs.2007.05.005

    Article  CAS  PubMed  Google Scholar 

  48. Plante MK, Arscott WT, Folsom JB, Tighe SW, Dempsey RJ, Wesley UV (2013) Ethanol promotes cytotoxic effects of tumor necrosis factor-related apoptosis-inducing ligand through induction of reactive oxygen species in prostate cancer cells. Prostate Cancer Prostatic Dis 16:16–22. https://doi.org/10.1038/pcan.2012.37

    Article  CAS  PubMed  Google Scholar 

  49. Vaculova A, Hofmanova J, Soucek K, Andera L, Kozubık A (2004) Ethanol acts as a potent agent sensitizing colon cancer cells to the TRAIL-induced apoptosis. FEBS Lett 577:309–313. https://doi.org/10.1016/j.febslet.2004.10.013

    Article  CAS  PubMed  Google Scholar 

  50. Higuchi H, Kurose I, Kato S, Miura S, Ishii H (1996) Ethanol-induced apoptosis and oxidative stress in hepatocytes. Alcohol Clin Exp Res 20:340–6. https://doi.org/10.1111/j.1530-0277.1996.tb01804.x

    Article  Google Scholar 

Download references

Acknowledgements

This study was supported by Marmara University Scientific Research Projects Coordination Unit. Project No: FEN-C-YLP-080415-0125. Additionally, we would like to thank the Scientific and Technological Research Council of Turkey (TUBITAK) for supporting education of young scientists (M. Cevik) with 2210-C master program.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Belgin Susleyici.

Ethics declarations

Conflict of interest

The author declares that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cevik, M., Gunduz, M.K., Deliorman, G. et al. Alterations in niban gene expression as a response to stress conditions in 3T3-L1 adipocytes. Mol Biol Rep 47, 9399–9408 (2020). https://doi.org/10.1007/s11033-020-05992-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-020-05992-5

Keywords

Navigation