Rapid increase in fibroblast growth factor 21 in protein malnutrition and its impact on growth and lipid metabolism
Open accessAbstract
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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Liver FGF21 expression and circulating FGF21 protein levels are increased by the restriction of protein intake in mice, rats, and humans.
“liver FGF21 expression and circulating FGF21 protein levels are increased by the restriction of protein intake in mice, rats, and humans”
From FGF21 and the physiological regulation of macronutrient preference (2020) · cites this paper as [147]
Reductions in dietary protein intake-or the intake of specific amino acids-increase liver FGF21 mRNA expression and circulating FGF21 protein levels.
“reductions in dietary protein intake—or the intake of specific amino acids—increase liver FGF21 mRNA expression and circulating FGF21 protein levels”
From FGF21 and the physiological regulation of macronutrient preference (2020) · cites this paper as [147]
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- Authors
- Ozaki, Y., Saito, K., Nakazawa, K., Konishi, M., Itoh, N., Hakuno, F., Takahashi, S.-I., Kato, H., & Takenaka, A.
- Affiliations
- Meiji University (JP)
- The University of Tokyo (JP)
- Kobe Pharmaceutical University (JP)
- Kyoto University (JP)
- Corresponding author
- Takenaka, Asako
- ORCID
- Venue
- British Journal Of Nutrition
- Publisher
- Cambridge University Press (CUP)
- Published
- 2015-09-02
- Volume
- 114
- Issue
- 9
- Pages
- 1410-1418
- ISSN
- 0007-1145 (ISSN-L)
- 1475-2662
- OpenAlex
- W2213273134
- Cited by
- 51
- References
- 42
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 1 · 2023: 4 · 2022: 1 · 2021: 7 · 2020: 6 · 2019: 8 · 2018: 5 · 2017: 7 · 2016: 5 · 2015: 2
- FWCI
- 2.75
- Type
- journal article
- Language
- en
- Update notices
- correction (2015-09-24)
- Open access
- bronze
- doi.org
- Locations
- British Journal Of Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Meiji University
- University of North Carolina at Chapel Hill
- Japan Society for the Promotion of Science (25221204, 15K07444, 15H04583)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Keywords
- FGF21, protein malnutrition, hepatic steatosis, insulin-like growth factor I, growth retardation, amino acid starvation, lipid metabolism, obesity, FGF21 knockout mice, low-protein diet, hepatic gene expression
- MeSH terms
- Animals, Cholesterol, Fatty Liver, Fibroblast Growth Factors, Insulin-Like Growth Factor I, Liver, Male, Obesity, Protein-Energy Malnutrition, RNA, Messenger, Growth Hormone, Triglycerides, Up-Regulation, Rats, Wistar, Mice, Knockout, Diet, Protein-Restricted, Oligonucleotide Array Sequence Analysis, Lipid Metabolism, Mice, Rats, Adipose Tissue, White
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