期刊
BRITISH JOURNAL OF NUTRITION
卷 114, 期 9, 页码 1410-1418出版社
CAMBRIDGE UNIV PRESS
DOI: 10.1017/S0007114515002846
关键词
DNA microarray analysis; Fibroblast growth factor 21; Low-protein diets; Protein malnutrition; Fgf21
资金
- Programme for Promotion of Basic and Applied Researches for Innovations in Bio-oriented Industry and Science and Technology Research Promotion Program for Agriculture, Forestry, Fisheries and Food Industry [25006A]
- Grants-in-Aid for Scientific Research [15H04583, 15K07444] Funding Source: KAKEN
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 liverderived 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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