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Rapid increase in fibroblast growth factor 21 in protein malnutrition and its impact on growth and lipid metabolism

  • Yori Ozaki (a1), Kenji Saito (a2), Kyoko Nakazawa (a2), Morichika Konishi (a3), Nobuyuki Itoh (a4), Fumihiko Hakuno (a5), Shin-Ichiro Takahashi (a5), Hisanori Kato (a2) and Asako Takenaka (a1)...
  • Please note a correction has been issued for this article.

Abstract

Protein malnutrition promotes hepatic steatosis, decreases insulin-like growth factor (IGF)-I production and retards growth. To identify new molecules involved in such changes, we conducted DNA microarray analysis on liver samples from rats fed an isoenergetic low-protein diet for 8 h. We identified the fibroblast growth factor 21 gene (Fgf21) as one of the most strongly up-regulated genes under conditions of acute protein malnutrition (P<0·05, false-discovery rate<0·001). In addition, amino acid deprivation increased Fgf21 mRNA levels in rat liver-derived RL-34 cells (P<0·01). These results suggested that amino acid limitation directly increases Fgf21 expression. FGF21 is a polypeptide hormone that regulates glucose and lipid metabolism. FGF21 also promotes a growth hormone-resistance state and suppresses IGF-I in transgenic mice. Therefore, to determine further whether Fgf21 up-regulation causes hepatic steatosis and growth retardation after IGF-I decrease in protein malnutrition, we fed an isoenergetic low-protein diet to Fgf21-knockout (KO) mice. Fgf21-KO did not rescue growth retardation and reduced plasma IGF-I concentration in these mice. Fgf21-KO mice showed greater epididymal white adipose tissue weight and increased hepatic TAG and cholesterol levels under protein malnutrition conditions (P<0·05). Overall, the results showed that protein deprivation directly increased Fgf21 expression. However, growth retardation and decreased IGF-I were not mediated by increased FGF21 expression in protein malnutrition. Furthermore, FGF21 up-regulation rather appears to have a protective effect against obesity and hepatic steatosis in protein-malnourished animals.

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Corresponding author

* Corresponding author: A. Takenaka, fax +81 44 934 7902, email takenaka@meiji.ac.jp

References

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Rapid increase in fibroblast growth factor 21 in protein malnutrition and its impact on growth and lipid metabolism

  • Yori Ozaki (a1), Kenji Saito (a2), Kyoko Nakazawa (a2), Morichika Konishi (a3), Nobuyuki Itoh (a4), Fumihiko Hakuno (a5), Shin-Ichiro Takahashi (a5), Hisanori Kato (a2) and Asako Takenaka (a1)...
  • Please note a correction has been issued for this article.

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