In:
British Journal of Nutrition, Cambridge University Press (CUP), Vol. 114, No. 9 ( 2015-11-14), p. 1410-1418
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.
Type of Medium:
Online Resource
ISSN:
0007-1145
,
1475-2662
DOI:
10.1017/S0007114515002846
Language:
English
Publisher:
Cambridge University Press (CUP)
Publication Date:
2015
detail.hit.zdb_id:
2016047-1
SSG:
12
SSG:
21
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