Skip to main content
SpringerLink
Log in

NYGGF4 homologous gene expression in 3T3-L1 adipocytes: regulation by FFA and adipokines

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

NYGGF4 is a novel gene that is abundantly expressed in the adipose tissue of obese subjects and is involved in insulin resistance. In the present study, the mRNA expression of NYGGF4 homologous genes was examined in the 3T3-L1 cell line. The NYGGF4 mRNAs were expressed at low levels in the 3T3-L1 preadipocytes. During the conversion of 3T3-L1 preadipocytes to adipocytes, the expression of NYGGF4 mRNA was upregulated. On the 8th day after induction of differentiation, the NYGGF4 mRNA levels peaked and remained high. Free fatty acids (FFA) and tumor necrosis factor-α (TNFα) could upregulate NYGGF4 mRNA expression in 3T3-L1 adipocytes, while interleukin-6 (IL-6), leptin, and resistin exerted an inhibitory effect. The results suggest that the expression of NYGGF4 mRNA is affected by a variety of factors that are related to insulin sensitivity. It is likely that NYGGF4 may be an important mediator in the development of obesity-related insulin resistance.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Jeffery RW, Sherwood NE (2008) Is the obesity epidemic exaggerated? No. Br Med J 336:244–246. doi:10.1136/bmj.39458.495127.AD

    Article  Google Scholar 

  2. Kopelman PG (2000) Obesity as a medical problem. Nature 404:635–643

    CAS  PubMed  Google Scholar 

  3. Spiegelman BM, Flier JS (2001) Obesity and the regulation of energy balance. Cell 104:531–543. doi:10.1016/S0092-8674(01)00240-9

    Article  CAS  PubMed  Google Scholar 

  4. Qiu J, Ni YH, Gong HX, Fei L, Pan XQ, Guo M, Chen RH, Guo XR (2007) Identification of differentially expressed genes in omental adipose tissues of obese patients by suppression subtractive hybridization. Biochem Biophys Res Commun 352:469–478. doi:10.1016/j.bbrc.2006.11.049

    Article  CAS  PubMed  Google Scholar 

  5. Wang B, Zhang M, Ni YH, Liu F, Fan HQ, Fei L, Pan XQ, Guo M, Chen RH, Guo XR (2006) Identification and characterization of NYGGF4, a novel gene containing a phosphotyrosine-binding (PTB) domain that stimulates 3T3–L1 preadipocytes proliferation. Gene 379:132–140. doi:10.1016/j.gene.2006.05.008

    Article  CAS  PubMed  Google Scholar 

  6. Zhang CM, Chen XH, Wang B, Liu F, Chi X, Tong ML, Ni YH, Chen RH, Guo XR (2009) Over-expression of NYGGF4 inhibits glucose transport in 3T3–L1 adipocytes via attenuated phosphorylation of IRS-1 and Akt. Acta Pharmacol Sin 30:120–124. doi:10.1038/aps.2008.9

    Article  PubMed  Google Scholar 

  7. Caratù G, Allegra D, Bimonte M, Schiattarella GG, D’Ambrosio C, Scaloni A, Napolitano M, Russo T, Zambrano N (2007) Identification of the ligands of protein interaction domains through a functional approach. Mol Cell Proteomics 6:333–345. doi:10.1074/mcp.M600289-MCP200

    PubMed  Google Scholar 

  8. Goossens GH (2008) The role of adipose tissue dysfunction in the pathogenesis of obesity-related insulin resistance. Physiol Behav 94:206–218. doi:10.1016/j.physbeh.2007.10.010

    Article  CAS  PubMed  Google Scholar 

  9. Boden G (1997) Role of fatty acids in the pathogenesis of insulin resistance and NIDDM. Diabetes 46:3–10. doi:10.2337/diabetes.46.1.3

    Article  CAS  PubMed  Google Scholar 

  10. Hotamisligil GS, Shargill NS, Spiegelman BM (1993) Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 259:87–91. doi:10.1126/science.7678183

    Article  CAS  PubMed  Google Scholar 

  11. Vozarova B, Weyer C, Hanson K, Tataranni PA, Bogardus C, Pratley RE (2001) Circulating interleukin-6 in relation to adiposity, insulin action, and insulin secretion. Obes Res 9:414–417. doi:10.1038/oby.2001.54

    Article  CAS  PubMed  Google Scholar 

  12. Maffei M, Halaas J, Ravussin E, Pratley RE, Lee GH, Zhang Y, Fei H, Kim S, Lallone R, Ranganathan S (1995) Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med 1:1155–1161. doi:10.1038/nm1195-1155

    Article  CAS  PubMed  Google Scholar 

  13. Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS, Lazar MA (2001) The hormone resistin links obesity to diabetes. Nature 409:307–312. doi:10.1038/35053000

    Article  CAS  PubMed  Google Scholar 

  14. Student AK, Hsu RY, Lane MD (1980) Induction of fatty acid synthetase synthesis in differentiating 3T3–L1 preadipocytes. J Biol Chem 255:4745–4750

    CAS  PubMed  Google Scholar 

  15. Bergman RN, Ader M (2000) Free fatty acids and pathogenesis of type 2 diabetes mellitus. Trends Endocrinol Metab 11:351–356. doi:10.1016/S1043-2760(00)00323-4

    Article  CAS  PubMed  Google Scholar 

  16. Dresner A, Laurent D, Marcucci M, Griffin ME, Dufour S, Cline GW, Slezak LA, Andersen DK, Hundal RS, Rothman DL, Petersen KF, Shulman GI (1999) Effects of free fatty acids on glucose transport and IRS-1-associated phosphatidylinositol 3-kinase activity. J Clin Invest 103:253–259. doi:10.1172/JCI5001

    Article  CAS  PubMed  Google Scholar 

  17. Gao Z, Zhang X, Zuberi A, Hwang D, Quon MJ, Lefevre M, Ye J (2004) Inhibition of insulin sensitivity by free fatty acids requires activation of multiple serine kinases in 3T3–L1 adipocytes. Mol Endocrinol 18:2024–2034. doi:10.1210/me.2003-0383

    Article  CAS  PubMed  Google Scholar 

  18. Moller DE (2000) Potential role of TNF-alpha in the pathogenesis of insulin resistance and type 2 diabetes. Trends Endocrinol Metab 11:212–217. doi:10.1016/S1043-2760(00)00272-1

    Article  CAS  PubMed  Google Scholar 

  19. Stephens JM, Lee J, Pilch PF (1997) Tumor necrosis factor-alpha-induced insulin resistance in 3T3–L1 adipocytes is accompanied by a loss of insulin receptor substrate-1 and GLUT4 expression without a loss of insulin receptor-mediated signal transduction. J Biol Chem 272:971–976. doi:10.1074/jbc.272.2.971

    Article  CAS  PubMed  Google Scholar 

  20. Ozes ON, Akca H, Mayo LD, Gustin JA, Maehama T, Dixon JE, Donner DB (2001) A phosphatidylinositol 3-kinase/Akt/mTOR pathway mediates and PTEN antagonizes tumor necrosis factor inhibition of insulin signaling through insulin receptor substrate-1. Proc Natl Acad Sci USA 98:4640–4645. doi:10.1073/pnas.051042298

    Article  CAS  PubMed  Google Scholar 

  21. Bastard JP, Maachi M, Van Nhieu JT, Jardel C, Bruckert E, Grimaldi A, Robert JJ, Capeau J, Hainque B (2002) Adipose tissue IL-6 content correlates with resistance to insulin activation of glucose uptake both in vivo and in vitro. J Clin Endocrinol Metab 87:2084–2089. doi:10.1210/jc.87.5.2084

    Article  CAS  PubMed  Google Scholar 

  22. Rotter V, Nagaev I, Smith U (2003) Interleukin-6 (IL-6) induces insulin resistance in 3T3–L1 adipocytes and is, like IL-8 and tumor necrosis factor-alpha, overexpressed in human fat cells from insulin-resistant subjects. J Biol Chem 278:45777–45784. doi:10.1074/jbc.M301977200

    Article  CAS  PubMed  Google Scholar 

  23. Stouthard JM, Oude Elferink RP, Sauerwein HP (1996) Interleukin-6 enhances glucose transport in 3T3–L1 adipocytes. Biochem Biophys Res Commun 220:241–245. doi:10.1006/bbrc.1996.0389

    Article  CAS  PubMed  Google Scholar 

  24. Steensberg A, Fischer CP, Sacchetti M, Keller C, Osada T, Schjerling P, van Hall G, Febbraio MA, Pedersen BK (2003) Acute interleukin-6 administration does not impair muscle glucose uptake or whole-body glucose disposal in healthy humans. J Physiol 548:631–638. doi:10.1113/jphysiol.2002.032938

    Article  CAS  PubMed  Google Scholar 

  25. Glund S, Deshmukh A, Long YC, Moller T, Koistinen HA, Caidahl K, Zierath JR, Krook A (2007) Interleukin-6 directly increases glucose metabolism in resting human skeletal muscle. Diabetes 56:1630–1637. doi:10.2337/db06-1733

    Article  CAS  PubMed  Google Scholar 

  26. Friedman JM, Halaas JL (1998) Leptin and the regulation of body weight in mammals. Nature 395:763–770. doi:10.1038/27376

    Article  CAS  PubMed  Google Scholar 

  27. Luoh SM, Di Marco F, Levin N, Armanini M, Xie MH, Nelson C, Bennett GL, Williams M, Spencer SA, Gurney A, de Sauvage FJ (1997) Cloning and characterization of a human leptin receptor using a biologically active leptin immunoadhesin. J Mol Endocrinol 18:77–85. doi:10.1677/jme.0.0180077

    Article  CAS  PubMed  Google Scholar 

  28. Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS, Lazar MA (2001) The hormone resistin links obesity to diabetes. Nature 409:307–312. doi:10.1038/35053000

    Article  CAS  PubMed  Google Scholar 

  29. Juan CC, Au LC, Fang VS, Kang SF, Ko YH, Kuo SF, Hsu YP, Kwok CF, Ho LT (2001) Suppressed gene expression of adipocyte resistin in an insulin-resist ant rat model probably by elevated free fatty acids. Biochem Biophys Res Commun 289:1328–1333. doi:10.1006/bbrc.2001.6132

    Article  CAS  PubMed  Google Scholar 

  30. Le Lay S, Boucher J, Rey A, Castan-Laurell I, Krief S, Ferre P, Valet P, Dugail I (2001) Decreased resistin expression in mice with different sensitivities to a high-fat diet. Biochem Biophys Res Commun 289:564–567. doi:10.1006/bbrc.2001.6015

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (Grant Number: 30973231) and Program of Medical Leading Talent in Jiangsu Province (Grant Number: LJ200624)

Author information

Authors and Affiliations

  1. Department of Endocrinology, The 82th Hospital of the People’s Liberation Army, 223001, Huaian, China

    Ya-ping Zhao & Jia-lin Wang

  2. Department of Pediatrics, Nanjing Maternal and Child Health Hospital of Nanjing Medical University, 210004, Nanjing, China

    Chun-mei Zhang, Chun Zhu, Xiao-hui Chen, Chen-bo Ji, Xia Chi, Qin Hong, Yu-zhu Peng & Xi-rong Guo

Authors
  1. Ya-ping Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chun-mei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chun Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiao-hui Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jia-lin Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Chen-bo Ji
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xia Chi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Qin Hong
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yu-zhu Peng
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Xi-rong Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Yu-zhu Peng or Xi-rong Guo.

Additional information

Ya-ping Zhao and Chun-mei Zhang contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhao, Yp., Zhang, Cm., Zhu, C. et al. NYGGF4 homologous gene expression in 3T3-L1 adipocytes: regulation by FFA and adipokines. Mol Biol Rep 37, 3291–3296 (2010). https://doi.org/10.1007/s11033-009-9914-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-009-9914-7

Keywords

Search

Navigation