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Inhibition of SOCS-3 in adipocytes of rats with diet-induced obesity increases leptin-mediated fatty acid oxidation

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Abstract

Rats with diet-induced obesity (DIO) usually experience hyperleptinemia. Thus, leptin produced by adipocytes does not deplete adipocyte fat, which implying a leptin resistance in adipocytes during overnutrition. Here, we induced hyperleptinemia in rats by feeding them a diet consisting of 45% fat. In epididymal adipose tissues, the mRNA and protein levels of a putative leptin resistant factor, suppressor of cytokine signaling 3 (SOCS-3), were increased. The mRNA levels of SOCS-3 in adipocytes differentiated from adipose-derived stromal cells (ADSCs) were higher in DIO rats than in rats on a 10% fat diet. Using SOCS-3 short hairpin RNA lentivirus interference, we found decreased expression of acetyl-CoA carboxylase mRNA (a marker of de novo lipogenesis) and increased expression of acetyl-CoA oxidase mRNA (a marker of fat oxidation) in SOCS-3-knockdown adipocytes after incubation with 50 nM leptin for 6 h. We conclude that the SOCS-3 knockdown may have increased the leptin-mediated in situ fatty acid oxidation in the DIO adipocytes, and therefore, SOCS-3 might be an excellent target for therapeutic intervention for obesity.

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References

  1. P.J. Enriori, A.E. Evans, P. Sinnayah, E.E. Jobst, L. Tonelli-Lemos, S.K. Billes, M.M. Glavas, B.E. Grayson, M. Perello, E.A. Nillni, K.L. Grove, M.A. Cowley, Cell Metab. 5, 181–194 (2007)

    Article  CAS  PubMed  Google Scholar 

  2. H. Munzberg, J.S. Flier, C. Bjorbaek, Endocrinology 145, 4880–4889 (2004)

    Article  PubMed  Google Scholar 

  3. K. El-Haschimi, D.D. Pierroz, S.M. Hileman, C. Bjorbaek, J.S. Flier, J. Clin. Invest. 105, 1827–1832 (2000)

    Article  CAS  PubMed  Google Scholar 

  4. M. Van Heek, D.S. Compton, C.F. France, R.P. Tedesco, A.B. Fawzi, M.P. Graziano, E.J. Sybertz, C.D. Strader, H.R. Davis Jr., J. Clin. Invest. 99, 385–390 (1997)

    Article  PubMed  Google Scholar 

  5. S.L. Dunn, M. Bjornholm, S.H. Bates, Z. Chen, M. Seifert, M.G. Myers Jr., Mol. Endocrinol. 19, 925–938 (2005)

    Article  CAS  PubMed  Google Scholar 

  6. C. Kloek, A.K. Haq, S.L. Dunn, H.J. Lavery, A.S. Banks, M.G. Myers Jr., J. Biol. Chem. 277, 41547–41555 (2002)

    Article  CAS  PubMed  Google Scholar 

  7. C. Bjorbaek, K. El-Haschimi, J.D. Frantz, J.S. Flier, J. Biol. Chem. 274, 30059–30065 (1999)

    Article  CAS  PubMed  Google Scholar 

  8. C. Bjorbaek, J.K. Elmquist, J.D. Frantz, S.E. Shoelson, J.S. Flier, Mol. Cell. 1, 619–625 (1998)

    Article  CAS  PubMed  Google Scholar 

  9. J.N. Huan, J. Li, Y. Han, K. Chen, N. Wu, A.Z. Zhao, J. Biol. Chem. 278, 45638–45650 (2003)

    Article  CAS  PubMed  Google Scholar 

  10. Z.W. Wang, Y.T. Zhou, Y. Lee, M. Higa, S.P. Kalra, R.H. Unger, Biochem. Biophys. Res. Commun. 260, 653–657 (1999)

    Article  CAS  PubMed  Google Scholar 

  11. C.A. Siegrist-Kaiser, V. Pauli, C.E. Juge-Aubry, O. Boss, A. Pernin, W.W. Chin, I. Cusin, F. Rohner-Jeanrenaud, A.G. Burger, J. Zapf, C.A. Meier, J. Clin. Invest. 100, 2858–2864 (1997)

    Article  CAS  PubMed  Google Scholar 

  12. G.M. Fruhbeck, M. Aguado, J.A. Martinez, Biochem. Biophys. Res. Commun. 240, 590–594 (1997)

    Article  CAS  PubMed  Google Scholar 

  13. M.Y. Wang, Y. Lee, R.H. Unger, J. Biol. Chem. 274, 17541–17544 (1999)

    Article  CAS  PubMed  Google Scholar 

  14. G. Muller, J. Ertl, M. Gerl, G. Preibisch, J. Biol. Chem. 272, 10585–10593 (1997)

    Article  CAS  PubMed  Google Scholar 

  15. B.E. Levin, J. Triscari, A.C. Sullivan, Am. J. Physiol. 244, R347–R355 (1983)

    CAS  PubMed  Google Scholar 

  16. C. Perez, C. Fernandez-Galaz, T. Fernandez-Agullo, C. Arribas, A. Andres, M. Ros, J.M. Carrascosa, Diabetes 53, 347–353 (2004)

    Article  CAS  PubMed  Google Scholar 

  17. L. Orci, W.S. Cook, M. Ravazzola, M.Y. Wang, B.H. Park, R. Montesano, R.H. Unger, Proc. Natl. Acad. Sci. USA 101, 2058–2063 (2004)

    Article  CAS  PubMed  Google Scholar 

  18. Y. Lee, M.Y. Wang, T. Kakuma, Z.W. Wang, E. Babcock, K. McCorkle, M. Higa, Y.T. Zhou, R.H. Unger, J. Biol. Chem. 276, 5629–5635 (2001)

    Article  CAS  PubMed  Google Scholar 

  19. P.J. Havel, S. Kasim-Karakas, W. Mueller, P.R. Johnson, R.L. Gingerich, J.S. Stern, J. Clin. Endocrinol. Metab. 81, 4406–4413 (1996)

    Article  CAS  PubMed  Google Scholar 

  20. M.Y. Wang, L. Orci, M. Ravazzola, R.H. Unger, Proc. Natl. Acad. Sci. USA 102, 18011–18016 (2005)

    Article  CAS  PubMed  Google Scholar 

  21. L. Liu, H. Gu, Y. Zhao, F. Yu, Wei Sheng Yan Jiu 37, 40–42 (2008)

    PubMed  Google Scholar 

  22. H. Shi, I. Tzameli, C. Bjorbaek, J.S. Flier, J. Biol. Chem. 279, 34733–34740 (2004)

    Article  CAS  PubMed  Google Scholar 

  23. Z. Wang, Y.T. Zhou, T. Kakuma, Y. Lee, S.P. Kalra, P.S. Kalra, W. Pan, R.H. Unger, Biochem. Biophys. Res. Commun. 277, 20–26 (2000)

    Article  CAS  PubMed  Google Scholar 

  24. G.R. Steinberg, D.J. Dyck, Am. J. Physiol. Endocrinol. Metab. 279, E1374–E1382 (2000)

    CAS  PubMed  Google Scholar 

  25. J.E. Novakofski, in Biology of the Adipocyte: Research Approached, ed. by G.J. Hausman, R. Martin (Van Nostrand Reinhold, New York, 1987)

    Google Scholar 

  26. G.J. Hausman, J. Anim. Sci. 70, 106–114 (1992)

    CAS  PubMed  Google Scholar 

  27. F. Samad, M. Pandey, D.J. Loskutoff, Proc. Natl. Acad. Sci. USA 95, 7591–7596 (1998)

    Article  CAS  PubMed  Google Scholar 

  28. G. Shillabeer, D.C. Lau, J. Lipid Res. 35, 592–600 (1994)

    CAS  PubMed  Google Scholar 

  29. Y.T. Zhou, Z.W. Wang, M. Higa, C.B. Newgard, R.H. Unger, Proc. Natl. Acad. Sci. USA 96, 2391–2395 (1999)

    Article  CAS  PubMed  Google Scholar 

  30. L. Liu, H. Gu, J. Yang, F. Yu, Wei Sheng Yan Jiu 38, 160–162 (2009)

    PubMed  Google Scholar 

  31. Y. Bai, S. Zhang, K.S. Kim, J.K. Lee, K.H. Kim, J. Biol. Chem. 271, 13939–13942 (1996)

    Article  CAS  PubMed  Google Scholar 

  32. A.Z. Zhao, J.N. Huan, S. Gupta, R. Pal, A. Sahu, Nat. Neurosci. 5, 727–728 (2002)

    CAS  PubMed  Google Scholar 

  33. K.D. Niswender, G.J. Morton, W.H. Stearns, C.J. Rhodes, M.G. Myers Jr., M.W. Schwartz, Nature 413, 794–795 (2001)

    Article  CAS  PubMed  Google Scholar 

  34. Y.B. Kim, S. Uotani, D.D. Pierroz, J.S. Flier, B.B. Kahn, Endocrinology 141, 2328–2339 (2000)

    Article  CAS  PubMed  Google Scholar 

  35. G.R. Steinberg, A.J. McAinch, M.B. Chen, P.E. O’Brien, J.B. Dixon, D. Cameron-Smith, B.E. Kemp, J. Clin. Endocrinol. Metab. 91, 3592–3597 (2006)

    Article  CAS  PubMed  Google Scholar 

  36. L. Liu, H. Gu, J. Yang, S. Ma, F. Yu, Y. Ren, L. An, Mol. Biol. Rep. doi:10.1007/s11033-009-9757-2

  37. S.P. Zielske, M. Stevenson, J. Virol. 79, 11541–11546 (2005)

    Article  CAS  PubMed  Google Scholar 

  38. R. Pullmann Jr., M. Juhaszova, I. Lopez de Silanes, T. Kawai, K. Mazan-Mamczarz, M.K. Halushka, M. Gorospe, J. Biol. Chem. 280, 22819–22826 (2005)

    Article  CAS  PubMed  Google Scholar 

  39. G. Tiscornia, O. Singer, I.M. Verma, Nat. Protoc. 1, 241–245 (2006)

    Article  CAS  PubMed  Google Scholar 

  40. D.B. Hausman, H.J. Park, G.J. Hausman, Methods Mol. Biol. 456, 201–219 (2008)

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Mr. Y. Zhao for his technical assistance. This work was supported by the National Natural Science Foundation of China (Grant No. 30500409).

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Authors and Affiliations

  1. Department of Orthopaedics, Shengjing Hospital, China Medical University, Shenyang, 110004, People’s Republic of China

    Hailun Gu

  2. Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, No. 92 Beier Road, Heping District, Shenyang, Liaoning Province, 110001, People’s Republic of China

    Li Liu, Shuang Ma, Yahao Ren, Fei Yu, Li An & Jun Yang

  3. College of Profession and Technology, Liaoning University of Traditional Chinese Medicine, Shenyang, 110032, People’s Republic of China

    Yali Liu

  4. Department of Child and Adolescent Health, School of Public Health, China Medical University, Shenyang, 110001, People’s Republic of China

    Lingling Zhai

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  1. Hailun Gu
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Correspondence to Li Liu.

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Gu, H., Liu, L., Ma, S. et al. Inhibition of SOCS-3 in adipocytes of rats with diet-induced obesity increases leptin-mediated fatty acid oxidation. Endocr 36, 546–554 (2009). https://doi.org/10.1007/s12020-009-9253-4

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  • DOI: https://doi.org/10.1007/s12020-009-9253-4

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