Low-protein diet induces, whereas high-protein diet reduces hepatic FGF21 production in mice, but glucose and not amino acids up-regulate FGF21 in cultured hepatocytes
Abstract
Fibroblast growth factor 21 (FGF21) is a polypeptide secreted by the liver and involved in several metabolic processes such as thermogenesis and lipid oxidation. The nutritional mechanisms controlling FGF21 production are poorly understood. This study aimed to investigate how dietary carbohydrates and proteins impact FGF21 production and how in turn, FGF21 is involved in the metabolic adaptation to changes in the carbohydrate and protein contents of the diet. For that purpose, we fed 25 male C57BL/6 mice diets composed of different protein and carbohydrate contents (normal-protein and carbohydrate diet (N=9, NPNC), low-protein high-carbohydrate diet (N=8, LPHC), high-protein low-carbohydrate diet (N=8, HPLC) for 3 weeks. We measured liver Fgf21 gene expression, synthesis and secretion as well as different parameters related to energy and glucose metabolism. We also investigated the direct role of amino acids and glucose in the control of Fgf21 gene expression in hepatocyte primary cultures (n=6). In vivo, FGF21 responds acutely to LPHC intake whereas under an HPLC diet, plasma FGF21 circulating levels are low in the fasted and refed states. In hepatocytes, Fgf21 expression was controlled by glucose but not amino acids. Both diets increased the thermic effect of feeding (TEF) and ketogenesis was increased in fasted HPLC mice. The results presented suggest that dietary glucose, rather than amino acids, directly controls FGF21 secretion, and that FGF21 may be involved in the increased TEF response to LPHC. The effects of the HPLC diet on ketogenesis and TEF are probably controlled by other metabolic pathways.
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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 [151]
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 [151]
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- Authors
- Chalvon-Demersay, T., Even, P. C., Tomé, D., Chaumontet, C., Piedcoq, J., Gaudichon, C., & Azzout-Marniche, D.
- Affiliations
- AgroParisTech (FR)
- Venue
- The Journal of Nutritional Biochemistry
- Publisher
- Elsevier BV
- Published
- 2016-10
- Volume
- 36
- Pages
- 60-67
- ISSN
- 0955-2863 (ISSN-L)
- OpenAlex
- W2501508167
- Cited by
- 37
- References
- 43
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 4 · 2023: 1 · 2022: 3 · 2021: 8 · 2020: 4 · 2019: 6 · 2018: 3 · 2017: 5
- FWCI
- 2.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Nutritional Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Nutrition, Genetics, and Disease
- Keywords
- FGF21, dietary protein, dietary carbohydrates, low-protein high-carbohydrate diet, high-protein low-carbohydrate diet, amino acids, hepatocytes, thermic effect of feeding, ketogenesis, energy metabolism
- MeSH terms
- Amino Acids, Animals, Adipose Tissue, Brown, Cells, Cultured, Dietary Proteins, Energy Metabolism, Fibroblast Growth Factors, Glucose, Liver, Male, Mice, Inbred C57BL, RNA, Messenger, Weaning, Gene Expression Regulation, Developmental, Diet, Protein-Restricted, Postprandial Period, Hepatocytes, Diet, Carbohydrate-Restricted, Rats, Adipose Tissue, White
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