scholarly journals Dietary Essential Amino Acid Restriction Promotes Hyperdipsia via Hepatic FGF21

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1469
Author(s):  
Patricia M. Rusu ◽  
Andrea Y. Chan ◽  
Mathias Heikenwalder ◽  
Oliver J. Müller ◽  
Adam J. Rose
Keyword(s):  
Amino Acid ◽  
Growth Factor ◽  
Dietary Protein ◽  
Essential Amino Acid ◽  
De Novo ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
De Novo Biosynthesis ◽  
Dietary Requirements ◽  
Dietary Amino Acid

Prior studies have reported that dietary protein dilution (DPD) or amino acid dilution promotes heightened water intake (i.e., hyperdipsia) however, the exact dietary requirements and the mechanism responsible for this effect are still unknown. Here, we show that dietary amino acid (AA) restriction is sufficient and required to drive hyperdipsia during DPD. Our studies demonstrate that particularly dietary essential AA (EAA) restriction, but not non-EAA, is responsible for the hyperdipsic effect of total dietary AA restriction (DAR). Additionally, by using diets with varying amounts of individual EAA under constant total AA supply, we demonstrate that restriction of threonine (Thr) or tryptophan (Trp) is mandatory and sufficient for the effects of DAR on hyperdipsia and that liver-derived fibroblast growth factor 21 (FGF21) is required for this hyperdipsic effect. Strikingly, artificially introducing Thr de novo biosynthesis in hepatocytes reversed hyperdipsia during DAR. In summary, our results show that the DPD effects on hyperdipsia are induced by the deprivation of Thr and Trp, and in turn, via liver/hepatocyte-derived FGF21.

scholarly journals Fibroblast Growth Factor 21 Corrects Obesity in Mice

Endocrinology ◽  
2008 ◽  
Vol 149 (12) ◽  
pp. 6018-6027 ◽  
Author(s):  
Tamer Coskun ◽  
Holly A. Bina ◽  
Michael A. Schneider ◽  
James D. Dunbar ◽  
Charlie C. Hu ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
De Novo ◽  
Caloric Intake ◽  
De Novo Lipogenesis ◽  
Leptin Resistance ◽  
Health Concern ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Lipid Control

Fibroblast growth factor 21 (FGF21) is a metabolic regulator that provides efficient and durable glycemic and lipid control in various animal models. However, its potential to treat obesity, a major health concern affecting over 30% of the population, has not been fully explored. Here we report that systemic administration of FGF21 for 2 wk in diet-induced obese and ob/ob mice lowered their mean body weight by 20% predominantly via a reduction in adiposity. Although no decrease in total caloric intake or effect on physical activity was observed, FGF21-treated animals exhibited increased energy expenditure, fat utilization, and lipid excretion, reduced hepatosteatosis, and ameliorated glycemia. Transcriptional and blood cytokine profiling studies revealed effects consistent with the ability of FGF21 to ameliorate insulin and leptin resistance, enhance fat oxidation and suppress de novo lipogenesis in liver as well as to activate futile cycling in adipose. Overall, these data suggest that FGF21 exhibits the therapeutic characteristics necessary for an effective treatment of obesity and fatty liver disease and provides novel insights into the metabolic determinants of these activities.

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

2015 ◽  
Vol 114 (9) ◽  
pp. 1410-1418 ◽  
Author(s):  
Yori Ozaki ◽  
Kenji Saito ◽  
Kyoko Nakazawa ◽  
Morichika Konishi ◽  
Nobuyuki Itoh ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Amino Acid ◽  
Growth Factor ◽  
Hepatic Steatosis ◽  
Growth Retardation ◽  
Protein Malnutrition ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Low Protein ◽  
Igf I

AbstractProtein 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.

scholarly journals Fibroblast Growth Factor-21 Controls Dietary Protein Intake in Male Mice

Endocrinology ◽  
2019 ◽  
Vol 160 (5) ◽  
pp. 1069-1080 ◽  
Author(s):  
Karlton R Larson ◽  
Aki T-B Chaffin ◽  
Michael L Goodson ◽  
Yanbin Fang ◽  
Karen K Ryan
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Dietary Protein ◽  
Protein Intake ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Dietary Protein Intake ◽  
Male Mice

scholarly journals Identification of a Domain within Peroxisome Proliferator-Activated Receptor γ Regulating Expression of a Group of Genes Containing Fibroblast Growth Factor 21 That Are Selectively Repressed by SIRT1 in Adipocytes

2007 ◽  
Vol 28 (1) ◽  
pp. 188-200 ◽  
Author(s):  
Hong Wang ◽  
Li Qiang ◽  
Stephen R. Farmer
Keyword(s):  
Amino Acid ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Constitutive Expression ◽  
Fibroblast Growth Factor 21 ◽  
Peroxisome Proliferator ◽  
Fibroblast Growth ◽  
Peroxisome Proliferator Activated Receptor ◽  
Group 2 ◽  
Pparγ Expression

ABSTRACT Peroxisome proliferator-activated receptor γ (PPARγ) activity is regulated through association with ligands that include the thiazolidinedione class of antidiabetic drugs, as well as derivatives of polyunsaturated fatty acids. Induction of PPARγ target gene expression involves ligand-dependent reconfiguration of the ligand-binding domain (LBD), followed by recruitment of specific transcriptional coactivators. In this study, we have identified an amino acid (F372) within helix 7 of the LBD that is required for the response of PPARγ to endogenous ligands. Additionally, the data show that this amino acid is also required for expression of a novel subset of adipocyte genes (group 2), including fibroblast growth factor 21 (FGF21), and that the FGF21 gene is a direct target of PPARγ. Expression of the group 2 genes is selectively repressed by the NAD-dependent deacetylase SIRT1 in mature 3T3-L1 adipocytes, since knockdown of SIRT1 through the constitutive expression of a corresponding RNA interference enhances their expression without affecting the expression of classic adipogenic genes, such as adiponectin and FABP4/aP2. It appears that many of the group 2 genes repressed by SIRT1 in mature adipocytes correspond to the same set of genes that are selectively activated by treatment of fat cells with the PPARγ ligand, troglitazone. These data support a role for helix 7 of the LBD of PPARγ in regulating adipocyte function and suggest that inhibition of SIRT1 in adipocytes induces the same insulin-sensitizing action as PPARγ ligands.

Fibroblast growth factor-21 predicts adverse outcome in community-acquired pneumonia

2018 ◽  
Author(s):  
Fahim Ebrahimi ◽  
Carole Wolffenbuttel ◽  
Claudine A Blum ◽  
Beat Muller ◽  
Philipp Schuetz ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Adverse Outcome ◽  
Community Acquired Pneumonia ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth

Effects of anti-inflammatory treatment on fibroblast growth factor-21 in obesity and metabolic syndrome

2019 ◽  
Author(s):  
Fahim Ebrahimi ◽  
Sandrine Urwyler ◽  
Matthias Betz ◽  
Emanuel Christ ◽  
Philipp Schuetz ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Anti Inflammatory

Fibroblast growth factor 21 (FGF21) in hyper- and hypothyroidism, association with metabolic disturbances

2020 ◽  
Author(s):  
Ewa Szczepańska ◽  
Małgorzata Gietka-Czernel ◽  
Piotr Glinicki ◽  
Helena Jastrzębska ◽  
Jadwiga Słowińska-Srzednicka ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Metabolic Disturbances
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