, Volume 49, Issue 1, pp 119–129 | Cite as

Recombinant murine fibroblast growth factor 21 ameliorates obesity-related inflammation in monosodium glutamate-induced obesity rats

  • Wen-Fei Wang
  • Si-Ming Li
  • Gui-Ping Ren
  • Wei Zheng
  • Yu-Jia Lu
  • Yin-Hang Yu
  • Wen-Juan Xu
  • Tian-He Li
  • Li-Hong Zhou
  • Yan Liu
  • De-Shan Li
Original Article


The aim of this study is to investigate the role of FGF21 in obesity-related inflammation in livers of monosodium glutamate (MSG)-induced obesity rats. The MSG rats were injected with recombinant murine fibroblast growth factor 21(FGF21) or equal volumes of vehicle. Metabolic parameters including body weight, Lee’s index, food intake, visceral fat and liver weight, intraperitoneal glucose tolerance, glucose, and lipid levels were dynamically measured at specific time points. Liver function and routine blood test were also analyzed. Further, systemic inflammatory cytokines such as glucose transporter 1 (GLUT-1), leptin, TNF-α, and IL-6 mRNAs were determined by real-time PCR. FGF21 independently decreased body weight and whole-body fat mass without reducing food intake in the MSG rats. FGF21 reduced blood glucose level, Lee’s index, visceral fat, and liver weight, and improved glucose tolerance, lipid metabolic spectrum, and hepatic steatosis in the MSG-obesity rats. Liver function parameters including AST, ALT, ALP, TP, T.Bili, and D.Bili levels significantly reduced in the FGF21-treated obesity rats compared to the controls. Further, FGF21 ameliorated the total and differential white blood cell (WBC) count, serum C-reactive protein (CRP), IL-6, and TNF-α levels in adipose tissues of the obesity rats, suggesting inflammation amelioration in the in the obesity rats by FGF21. FGF21 improves multiple metabolic disorders and ameliorates obesity-related inflammation in the MSG-induced obesity rats.


Obesity Monosodium glutamate Fibroblast growth factor 21 Inflammation Rat 



This study was supported by the National Natural Science Foundation of China (Nos.81172741 and 30972537).

Conflict of interest

The authors declare that there is no conflict of interest in this study.


  1. 1.
    N. Itoh, D.M. Ornitz, Evolution of the Fgf and Fgfr gene families. Trends. Genet. 20, 563–569 (2004)CrossRefPubMedGoogle Scholar
  2. 2.
    T. Nishimura, Y. Nakatake, M. Konishi, N. Itoh, Identification of a novel FGF, FGF-21, preferentially expressed in the liver. Biochim. Biophys. Acta 1492, 203–206 (2000)CrossRefPubMedGoogle Scholar
  3. 3.
    A. Kharitonenkov, T.L. Shiyanova, A. Koester, A.M. Ford, R. Micanovic, E.J. Galbreath et al., FGF-21 as a novel metabolic regulator. J Clin Invest. 115, 1627–1635 (2005)CrossRefPubMedCentralPubMedGoogle Scholar
  4. 4.
    J. Xu, D.J. Lloyd, C. Hale, S. Stanislaus, M. Chen, G. Sivits et al., FGF21 reverses hepatic steatosis, increases energy expenditure and improves insulin sensitivity in diet-induced obese mice. Diabetes 58, 250–259 (2008)CrossRefPubMedGoogle Scholar
  5. 5.
    T. Coskun, H.A. Bina, M.A. Schneider, J.D. Dunbar, C.C. Hu, Y. Chen et al., FGF21 corrects obesity in mice. Endocrinology 149, 6018–6127 (2008)CrossRefPubMedGoogle Scholar
  6. 6.
    A. Kharitonenkov, V.J. Wroblewski, A. Koester, Y.F. Chen, C.K. Clutinger, X.T. Tigno et al., The metabolic state of diabetic monkeys is regulated by fibroblast growth factor-21. Endocrinology 148, 774–781 (2007)CrossRefPubMedGoogle Scholar
  7. 7.
    A.H. Goris, K.R. Westerterp, Physical activity, fat intake and body fat. Physiol. Behav. 94, 164–168 (2008)CrossRefPubMedGoogle Scholar
  8. 8.
    R.H. Unger, P.E. Scherer, Gluttony, sloth and the metabolic syndrome: a roadmap to lipotoxicity. Trends Endocrinol. Metab. 21, 345–352 (2010)CrossRefPubMedCentralPubMedGoogle Scholar
  9. 9.
    M. Nagata, W. Suzuki, S. Iizuka, M. Tabuchi, H. Maruyama et al., Type 2 diabetes mellitus in obese mouse model induced by monosodium glutamate. Exp. Anim. 55, 109–115 (2006)CrossRefPubMedGoogle Scholar
  10. 10.
    Y. Nakanishi, K. Tsuneyama, M. Fujimoto, T.L. Salunga, K. Nomoto, J.L. An et al., Monosodium glutamate (MSG): a villain and promoter of liver inflammation and dysplasia. J. Autoimmun. 30, 42–50 (2008)CrossRefPubMedGoogle Scholar
  11. 11.
    N. Aoi, M. Soma, T. Nakayama, D. Rahmutula, K. Kosuge, Y. Izumi et al., Variable number of tandem repeat of the 5’-flanking region of type-C human natriuretic peptide receptor gene influences blood pressure levels in obesity-associated hypertension. Hypertens. Res. 27, 711–716 (2004)CrossRefPubMedGoogle Scholar
  12. 12.
    K. Kosuge, M. Soma, T. Nakayama, N. Aoi, M. Sato, A. Haketa et al., Human uncoupling protein 2 and 3 genes are associated with obesity in Japanese. Endocrine 34, 87–95 (2008)CrossRefPubMedGoogle Scholar
  13. 13.
    K. Strohacker, B.K. McFarlin, Influence of obesity, physical inactivity, and weight cycling on chronic inflammation. Front Biosci (Elite Ed). 2, 98–104 (2010)CrossRefPubMedGoogle Scholar
  14. 14.
    I. Majumdar, L.D. Mastrandrea, Serum sphingolipids and inflammatory mediators in adolescents at risk for metabolic syndrome. Endocrine 41, 442–449 (2012)CrossRefPubMedGoogle Scholar
  15. 15.
    P. Marzullo, A. Minocci, P. Giarda, C. Marconi, A. Tagliaferri, G.E. Walker, M. Scacchi, G. Aimaretti, A. Liuzzi, Lymphocytes and immunoglobulin patterns across the threshold of severe obesity. Endocrine 45, 392–400 (2014)CrossRefPubMedGoogle Scholar
  16. 16.
    M. Rondanelli, A. Opizzi, S. Perna, M. Faliva, S.B. Solerte, M. Fioravanti, C. Klersy, E. Cava, M. Paolini, L. Scavone, P. Ceccarelli, E. Castellaneta, C. Savina, L.M. Donini, Improvement in insulin resistance and favourable changes in plasma inflammatory adipokines after weight loss associated with two months’ consumption of a combination of bioactive food ingredients in overweight subjects. Endocrine 44, 391–401 (2013)CrossRefPubMedCentralPubMedGoogle Scholar
  17. 17.
    T. Inagaki, P. Dutchak, G. Zhao, X. Ding, L. Gautron, V. Parameswara et al., Endocrine regulation of the fasting response by PPARalpha-mediated induction of fibroblast growth factor 21. Cell Metab. 5, 415–425 (2007)CrossRefPubMedGoogle Scholar
  18. 18.
    A. Kharitonenkov, A.B. Shanafelt, Fibroblast growth factor-21 as a therapeutic agent for metabolic diseases. BioDrugs. 22, 37–44 (2008)CrossRefPubMedGoogle Scholar
  19. 19.
    T. Nakagawa, K. Ukai, T. Ohyama, Y. Gomita, H. Okamura, Effects of chronic administration of sibutramine on body weight, food intake and motor activity in neonatally monosodium glutamate-treated obese female rats: relationship of antiobesity effect with monoamines. Exp. Anim. 49, 239–249 (2000)CrossRefPubMedGoogle Scholar
  20. 20.
    M. Nagata, W. Suzuki, S. Iizuka, M. Tabuchi, H. Maruyama, S. Takeda et al., Type 2 diabetes mellitus in obese mouse model induced by monosodium glutamate. Exp. Anim. 55, 109–115 (2006)CrossRefPubMedGoogle Scholar
  21. 21.
    S.M. Kang, J.W. Yoon, H.Y. Ahn, S.Y. Kim, K.H. Lee, H. Shin et al., Android fat depot is more closely associated with metabolic syndrome than abdominal visceral fat in elderly people. PLoS ONE 6, e27694 (2011)CrossRefPubMedCentralPubMedGoogle Scholar
  22. 22.
    J. Liu, F. Zhang, C. Li, M. Lin, M.R. Briggs, Synergistic activation of human LDL receptor expression by SCAP ligand and cytokine oncostatin M. Arterioscler. Thromb. Vasc. Biol. 23, 90–96 (2003)CrossRefPubMedGoogle Scholar
  23. 23.
    S.M. Grundy, Statin trials and goals of cholesterol-lowering therapy. Circulation 97, 1436–1439 (1998)CrossRefPubMedGoogle Scholar
  24. 24.
    E.D. Berglund, C.Y. Li, H.A. Bina, S.E. Lynes, M.D. Michael, A.B. Shanafelt et al., Fibroblast growth factor 21 controls glycemia via regulation of hepatic glucose flux and insulin sensitivity. Endocrinology 150, 4084–4093 (2009)CrossRefPubMedCentralPubMedGoogle Scholar
  25. 25.
    F.M. Fisher, P.C. Chui, P.J. Antonellis, H.A. Bina, A. Kharitonenkov, J.S. Flier et al., Obesity is an FGF21 resistant state. Diabetes 59, 2781–2789 (2010)CrossRefPubMedCentralPubMedGoogle Scholar
  26. 26.
    T. Lundåsen, M.C. Hunt, L.M. Nilsson, S. Sanyal, B. Angelin, S.E. Alexson et al., PPARalpha is a key regulator of hepatic FGF21. Biochem Biophys Res Commun. 360, 437–440 (2007)CrossRefPubMedGoogle Scholar
  27. 27.
    Y.L. Zhang, A. Hernandez-Ono, P. Siri, S. Weisberg, D. Conlon, M.J. Graham et al., Aberrant hepatic expression of PPARgamma2 stimulates hepatic lipogenesis in a mouse model of obesity, insulin resistance, dyslipidemia, and hepatic steatosis. J. Biol. Chem. 281, 37603–37615 (2006)CrossRefPubMedGoogle Scholar
  28. 28.
    J.S. Moyers, T.L. Shiyanova, F. Mehrbod, J.D. Dunbar, T.W. Noblitt, K.A. Otto et al., Molecular determinants of FGF-21 activity - synergy and cross-talk with PPARγ signaling. J. Cell. Physiol. 210, 1–6 (2007)CrossRefPubMedGoogle Scholar
  29. 29.
    H. Wang, L. Qiang, S.R. Farmer, Identification of a domain within peroxisome proliferator-activated receptor gamma regulating expression of a group of genes containing fibroblast growth factor 21 that are selectively repressed by SIRT1 in adipocytes. Mol. Cell. Biol. 28, 188–200 (2008)CrossRefPubMedCentralPubMedGoogle Scholar
  30. 30.
    Z. Wang, T. Nakayama, Inflammation, a link between obesity and cardiovascular disease. Mediators Inflamm. 2010, 535918 (2010)CrossRefPubMedCentralPubMedGoogle Scholar
  31. 31.
    Tamer Coskn, Holly au Bina, Michael a Schneider, James D Dunbar, Charlie C Hu, Yanyun Chen, David E Moller, and Alexei Kharitonenkov. “Fibroblast Growth Factor 21 Corrects Obesity in Mice”. Endocrinology 149, 6018–6027 (2008)CrossRefGoogle Scholar
  32. 32.
    M.J. Potthoff, T. Inagaki, S. Satapati, X. Ding, T. He, R. Goetz et al., FGF21 induces PGC-1alpha and regulates carbohydrate and fatty acid metabolism during the adaptive starvation response. Proc Natl Acad Sci U S A. 106, 10853–10858 (2009)CrossRefPubMedCentralPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.College of Life ScienceNortheast Agricultural UniversityHarbinChina
  2. 2.Harbin University of CommerceHarbinChina
  3. 3.College of Life SciencesUniversity of Chinese Academy of SciencesBeijingChina
  4. 4.Department of Endocrinology, The First Affiliated HospitalHarbin Medical UniversityHarbinChina
  5. 5.Department of Biostatistics, School of Public HealthHarbin Medical UniversityHarbinChina

Personalised recommendations