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

The British Journal of Nutrition
Yori OzakiA Takenaka

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 h...Continue Reading

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Citations

Nov 24, 2016·Journal of Internal Medicine·A Kharitonenkov, R DiMarchi
Dec 7, 2018·Current Opinion in Endocrinology, Diabetes, and Obesity·Jasreena K Nijjar, Diane Stafford
Mar 29, 2019·The Journal of Physiology·Stephanie von Holstein-Rathlou, Matthew P Gillum
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Feb 13, 2020·Endocrinology·Cristal M HillChristopher D Morrison
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Mar 25, 2017·Scientific Reports·Yoshiaki NakayamaMorichika Konishi
Jul 1, 2020·Clinical Nutrition : Official Journal of the European Society of Parenteral and Enteral Nutrition·Daniela FangmannMatthias Laudes
Mar 23, 2021·Bioscience, Biotechnology, and Biochemistry·Yori Ozaki-MasuzawaTaiichiro Seki
Sep 4, 2021·Proceedings of the National Academy of Sciences of the United States of America·Jason F CooperMonica Driscoll

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