A list of puns related to "FGF21"
For those who are interested in increasing lifespan by tracking and optimizing biological data, relatively high levels of FGF21 in the presence of low insulin and glucose may be a good strategy:
Video link: https://www.youtube.com/watch?v=NreBsyaj0l0
Watanabe M, Risi R, Camajani E, et al. Baseline HOMA IR and Circulating FGF21 Levels Predict NAFLD Improvement in Patients Undergoing a Low Carbohydrate Dietary Intervention for Weight Loss: A Prospective Observational Pilot Study. Nutrients. 2020;12(7):E2141. Published 2020 Jul 18. doi:10.3390/nu12072141
https://doi.org/10.3390/nu12072141
Background: Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver disease. Very low-calorie ketogenic diets (VLCKD) represent a feasible treatment as they induce profound weight loss and insulin resistance (IR) improvement. Despite the recognized benefits on NAFLD deriving from pharmacological administration of fibroblast growth factor 21 (FGF21), whose endogenous counterpart is a marker of liver injury, little is known about its physiology in humans.
Aim: To identify predictors of NAFLD improvement as reflected by the reduction of the non-invasive screening tool hepatic steatosis index (HSI) in obese patients undergoing a weight loss program.
Methods: Sixty-five obese patients underwent a 90-day dietary program consisting of a VLCKD followed by a hypocaloric low carbohydrate diet (LCD). Anthropometric parameters, body composition, and blood and urine chemistry were assessed.
Results: Unlike most parameters improving mainly during the VLCKD, the deepest HSI change was observed after the LCD (p = 0.02 and p < 0.0001, respectively). Baseline HOMA-IR and serum FGF21 were found to be positive (R = 0.414, p = 0009) and negative (R = 0.364, p = 0.04) independent predictors of HSI reduction, respectively.
Conclusions: We suggest that patients with IR and NAFLD derive greater benefit from a VLCKD, and we propose a possible role of human FGF21 in mediating NAFLD amelioration following nutritional manipulation.
am considering a ketogenic diet but am concerned since I have this snp with homozygous T alleles. Anyone have more information on this snp?
Zhang H, Zhang W, Yun D, et al. Alternate-day fasting alleviates diabetes-induced glycolipid metabolism disorders: roles of FGF21 and bile acids [published online ahead of print, 2020 Apr 30]. J Nutr Biochem. 2020;83:108403. doi:10.1016/j.jnutbio.2020.108403
https://doi.org/10.1016/j.jnutbio.2020.108403
Glycolipid metabolism disorder is one of the causes of type 2 diabetes (T2D). Alternate-day fasting (ADF) is an effective dietary intervention to counteract T2D. The present study is aimed to determine the underlying mechanisms of the benefits of ADF metabolic on diabetes-induced glycolipid metabolism disorders in db/db mice. Here, leptin receptor knock-out diabetic mice were subjected to 28 days of isocaloric ADF. We found that ADF prevented insulin resistance and bodyweight gain in diabetic mice. ADF promoted glycogen synthesis in both liver and muscle. ADF also activated recombinant insulin receptor substrate-1 (IRS-1)/protein kinase B (AKT/PKB) signalingοΌinactivated inflammation related AMP-activated protein kinase (AMPK) and the inflammation-regulating nuclear factor kappa-B (NF-ΞΊB) signaling in the liver. ADF also suppressed lipid accumulation by inactivating the expression of peroxisome proliferator-activated receptor gamma (PPAR-Ξ³) and sterol regulatory element-binding protein-1c (SREBP-1c). Furthermore, ADF elevated the expression of fibroblast growth factor 21 (FGF21) and down-stream signaling AMPK/silent mating type information regulation 2 homolog 1 (SIRT1)/peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1Ξ±) in the liver of diabetic mice. The mitochondrial biogenesis and autophagy were also stimulated by ADF. Interestingly, ADF also enhanced the bile acids (BAs) metabolism by generating more cholic acid (CA), deoxycholic acid (DCA) and tauroursodeoxycholic acid (TUDCA) in db/db mice. In conclusion, ADF could significantly inhibit T2D induced insulin resistance and obesity, promote insulin signalingοΌreduce inflammation, as well as promote glycogen synthesis and lipid metabolism. It possibly depends on FGF21 and BA metabolism to enhance mitochondrial biosynthesis and energy metabolism.
https://www.ncbi.nlm.nih.gov/pubmed/32421369
Welles JE1, Dennis MD1, Jefferson LS1, Kimball SR1.
Fibroblast growth factor 21 (FGF21) is a peptide hormone that acts to enhance insulin sensitivity and reverse many of the metabolic defects associated with consumption of a high-fat diet. Recent studies show that the liver is the primary source of FGF21 in the blood, and that hepatic FGF21 expression is upregulated by glucagon. Interestingly, glucagon acts to upregulate FGF21 production by primary cultures of rat hepatocytes and H4IIE and HepG2 hepatocarcinoma cells independent of changes in FGF21 mRNA abundance, suggesting that FGF21 protein expression is regulated post-transcriptionally. Based on these observations, the goal of the present study was to assess whether or not FGF21 mRNA is translationally regulated. The results show that FGF21 mRNA translation and secretion of the hormone are significantly upregulated in H4IIE cells exposed to 25 nM glucagon, independent of changes in FGF21 mRNA abundance. Furthermore, the glucagon-induced upregulation of FGF21 mRNA translation is associated with suppressed activity of the mechanistic target of rapamycin in complex 1 (mTORC1). Similarly, the results show that rapamycin-induced suppression of mTORC1 leads to upregulation of FGF21 mRNA translation with no change in FGF21 mRNA abundance. In contrast, activation of mTORC1 by refreshing the culture medium leads to downregulation of FGF21 mRNA translation. Notably, re-feeding fasted rats also leads to downregulation of FGF21 mRNA translation concomitantly with activation of mTORC1 in the liver. Overall, the findings support a model in which glucagon acts to upregulate FGF21 production by hepatocytes through suppression of mTORC1 and subsequent upregulation of FGF21 mRNA translation.
https://europepmc.org/articles/PMC6483847/figure/F4/
https://europepmc.org/articles/PMC6483847/
The pathophysiological significance of increased serum FGF21 concentrations in ESRD remains undefined. It is also not known whether the very high levels of FGF21 in ESRD patients represent an adaptation or maladaptation, i.e. whether it is protective or deleterious to the patient.
>Background/Hypothesis
>Beside its beneficial effects on weight loss, ketogenic diet (KD) causes dyslipidemia, a pro-inflammatory state involved in the development of hepatic steatosis, glucose intolerance and insulin resistance, although the latter is still being debated. Additionally, KD is known to increase fibroblast growth factor 21 (FGF21) plasma levels. However, FGF21 cannot initiate its beneficial actions on metabolism in these conditions. We therefore hypothesized and tested in the present study that KD may impair FGF21 signaling.
>Methods/Results
>Using indirect calorimetry, we found that KD-fed mice exhibited higher energy expenditure than regular chow (RC)-fed mice associated with increased Ucp1 levels in white adipose tissue (WAT), along with increased plasma FGF21 levels. We then assessed the effect of KD on FGF21 signaling in both the liver and WAT. We found that Fgfr4 and Klb (Ξ²-klotho) were downregulated in the liver, while Fgfr1 was downregulated in WAT of KD-fed mice. Because inflammation could be one of the mechanisms linking KD to impaired FGF21 signaling, we measured the expression levels of inflammatory markers and macrophage accumulation in WAT and liver and found an increased inflammation and macrophage accumulation in the liver, but surprisingly, a reduction of inflammation in WAT.We also showed that KD enhances lipid accumulation in the liver, which may explain hepatic inflammation and impaired Fgfr4 and Klb expression. In contrast, import of lipids from the circulation was significantly reduced in WAT of KD-fed mice, as suggested by a downregulation of Lpl and Cd36. This was further associated with reduced inflammation in WAT.
> Conclusion
> Altogether, these results indicate that KD could be beneficial for a given tissue but deleterious for another.
PLoS One. 2015; 10(5): e0126364. Published online 2015 May 14.
PMCID: PMC4431718
Ketogenic Diet Impairs FGF21 Signaling and Promotes Differential Inflammatory Responses in the Liver and White Adipose Tissue
Mohamed Asrih, et al
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4431718/
This is what the KD mice were getting, and this is what the regular chow mice were getting.
I find it quite shocking that nowhere in the paper do the authors question the validity of their findings for humans, in fact quite the opposite.
OTOH, I find the evidence of FGF21 resistance i
... keep reading on reddit β‘For those who are interested in increasing lifespan by tracking biological data, relatively high levels of FGF21 in the presence of low insulin and glucose may be a good strategy:
Video link: https://www.youtube.com/watch?v=NreBsyaj0l0
Please note that this site uses cookies to personalise content and adverts, to provide social media features, and to analyse web traffic. Click here for more information.