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1.
Increased serum levels of fibroblast growth factor 23 after an ultradistance run.
Kerschan-Schindl, K, Skenderi, K, Wahl-Figlash, K, Gelles, K, Föger-Samwald, U, Thalmann, M, Tsironi, M, Szekeres, T, Pietschmann, P
Journal of science and medicine in sport. 2021;(3):297-300
Abstract
OBJECTIVES Healthy bones need to be loaded on a regular basis. However, overstrenuous exercise causes uncoupling of bone metabolism. Thus, it is important to be aware of exercise-induced alterations in bone metabolism. The aim of this observational study was to determine whether participation in an ultradistance run has an impact on the phosphaturic hormone fibroblast growth factor 23 (FGF23), which is produced by osteocytes and suppresses osteoblast differentiation as well as matix mineralization. DESIGN Observational study. METHODS Nine participants of the Spartathlon (246km) had venous blood samples taken before and within 15min after finishing the race as well as during recovery. Serum levels of FGF23, phosphate, and blood urea nitrogen were determined. RESULTS FGF23 increased 6.5-fold from pre-race to post-race (2.2pmol/L [IQR: 0.4; 3.2pmol/L] to 14.4pmol/L [IQR: 4.7; 20.0pmol/L]; p=0.001). Thereafter, serum levels of FGF23 fell to 1.4pmol/L [IQR: 0.5; 1.7pmol/L] (p<0.0001). The differences in FGF23 levels between pre-race and recovery (3 days after the start) did not achieve statistical significance (p=0.614). Serum levels of phosphate and blood urea nitrogen also did not change significantly. CONCLUSIONS Since FGF23 plays a central role in mineral homeostasis, the transient overexpression of FGF23 may be an important contributor to the short-term uncoupling of bone metabolism induced by overstrenuous exercise.
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The Effect of a Life-Style Intervention Program of Diet and Exercise on Irisin and FGF-21 Concentrations in Children and Adolescents with Overweight and Obesity.
Karampatsou, SI, Genitsaridi, SM, Michos, A, Kourkouni, E, Kourlaba, G, Kassari, P, Manios, Y, Charmandari, E
Nutrients. 2021;(4)
Abstract
Overweight and obesity in childhood and adolescence represent major public health problems of our century, and account for increased morbidity and mortality in adult life. Irisin and Fibroblast Growth Factor 21 (FGF-21) have been proposed as prognostic and/or diagnostic biomarkers in subjects with obesity and metabolic syndrome, because they increase earlier than other traditional biomarkers. We determined the concentrations of Irisin and FGF-21 in children and adolescents with overweight and obesity before and after one year of a life-style intervention program of diet and physical exercise and explored the impact of body mass index (BMI) reduction on the concentrations of Irisin, FGF-21 and other cardiometabolic risk factors. Three hundred and ten (n = 310) children and adolescents (mean age ± SD: 10.5 ± 2.9 years) were studied prospectively. Following one year of the life-style intervention program, there was a significant decrease in BMI (p = 0.001), waist-to-hip ratio (p = 0.024), waist-to-height ratio (p = 0.024), and Irisin concentrations (p = 0.001), and an improvement in cardiometabolic risk factors. There was no alteration in FGF-21 concentrations. These findings indicate that Irisin concentrations decreased significantly as a result of BMI reduction in children and adolescents with overweight and obesity. Further studies are required to investigate the potential role of Irisin as a biomarker for monitoring the response to lifestyle interventions and for predicting the development of cardiometabolic risk factors.
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Two-year retrospective study of the effect of preemptive kidney transplantation and pretransplant mineral bone factors on calcium in post-kidney transplant recipients.
Tsujita, M, Goto, N, Futamura, K, Okada, M, Hiramitsu, T, Narumi, S, Uchida, K, Morozumi, K, Watarai, Y
Clinical and experimental nephrology. 2020;(9):836-841
Abstract
BACKGROUND Preemptive kidney transplantation (PEKT) incidence has recently increased in Japan. The effect of PEKT and mineral bone factors before kidney transplantation (KTx) on long-term calcium (Ca) levels remains unknown. METHODS Eighty-one consecutive patients at Nagoya Daini Red Cross Hospital were included in this study (PEKT group with 41 patients and non PEKT group with 40 patients). Ca metabolism, including intact fibroblast growth factor 23 (iFGF23), were measured before KTx and intact parathyroid hormone (iPTH), and corrected Ca (cCa) were measured before KTx and 6 months (M), 12 M, and 24 M after KTx. RESULTS In PEKT group, cCa levels at 24 M were higher from the baseline level. At baseline, cCa levels had a positive correlation with iFGF23 levels (r = 0.51; p < 0.001) and a negative correlation with iPTH levels (r = 0.51; p < 0.001). The cCa difference between baseline and 24 M was 0.8 ± 0.6 mg/dL in PEKT group and 0.3 ± 0.7 mg/dL in non-PEKT group (p = 0.001). A multivariate linear regression analysis showed iFGF23 and iPTH at baseline in entire groups were useful markers on calcium levels at 24 M. However, in PEKT group, both markers were found to be not associated with Ca at 24 M, whereas in non PEKT group, iPTH was the only effective marker. CONCLUSIONS This study suggested that iFGF23 and iPTH may be useful markers of the calcium status after KTx. However, no correlation was noted in PEKT group.
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Fibroblast growth factor 23 and cognitive impairment: The health, aging, and body composition study.
Drew, DA, Katz, R, Kritchevsky, S, Ix, JH, Shlipak, M, Newman, AB, Hoofnagle, A, Fried, L, Gutiérrez, OM, Sarnak, M
PloS one. 2020;(12):e0243872
Abstract
BACKGROUND Concentrations of fibroblast growth factor 23 (FGF-23), a hormone that regulates phosphorus and vitamin D metabolism, increase as kidney function declines. Excess fibroblast growth factor 23 may impact brain function through promotion of vascular disease or through direct effects on neuronal tissue. METHODS In the Healthy Aging and Body Composition Study, a longitudinal observational cohort of well-functioning older adults, intact serum FGF-23 was assayed in 2,738 individuals. Cognitive function was assessed at baseline and longitudinally at years 3, 5, and 8 by administration of the Modified Mini Mental State Examination (3MSE), a test of global cognitive function, and the Digit Symbol Substitution Test (DSST), a test primarily of executive function. The associations between FGF-23 and baseline cognitive function and incident cognitive impairment were evaluated using logistic and Poisson regression respectively, and were adjusted for demographics, baseline estimated glomerular filtration rate (eGFR), urine albumin/creatinine ratio, comorbidity, and other measures of mineral metabolism including soluble klotho. RESULTS The mean (SD) age was 74(3) years, with 51% female, and 39% black. The median (25th, 75th) FGF-23 concentration was 47 pg/mL (37, 60). Three hundred ninety-two individuals had prevalent cognitive impairment by the 3MSE and 461 by the DSST. There was no observed association between FGF-23 and baseline cognitive function for either cognitive test. There were 277 persons with incident cognitive impairment by 3MSE, and 333 persons with incident cognitive impairment by DSST. In fully adjusted models, each two-fold higher concentration of baseline FGF-23 was not associated with incident cognitive impairment by the 3MSE (IRR = 1.02[0.88, 1.19] fully adjusted model) or by the DSST (IRR = 0.98 [0.84, 1.15]. We saw no difference when analyses were stratified by eGFR greater than or less than 60 ml/min/1.73m2. CONCLUSION Intact FGF-23 was not associated with baseline cognitive function or incident cognitive impairment in this cohort well-functioning older adults.
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FGF21 and its Relationship with Inflammatory and Metabolic Parameters in HIV Patients after Antiretroviral Treatment.
Ruiz-Padilla, AJ, Ruiz-Noa, Y, Del Rocio Ibarra-Reynoso, L, Lazo-de-la-Vega-Monroy, ML, Alonso-Castro, AJ, Sánchez-Barajas, M, Alvarez-Alvarez, RM, Del Carmen Preciado-Puga, M
Current HIV research. 2020;(5):308-314
Abstract
BACKGROUND Fibroblast Growth Factor 21 (FGF21) serum levels are associated with insulin resistance and metabolic syndrome in HIV patients. OBJECTIVE To quantify FGF21 levels in HIV patients using antiretroviral therapy (ART) and to analyze a possible association between serum FGF21 levels and lipid profile, levels of proinflammatory cytokines, and atherogenic risk factors. MATERIALS AND METHODS Twenty patients with HIV infection, who received ART in a scheme consisting of Tenofovir/Emtricitabine+Lopinavir/Ritonavir, were enrolled in this study. The serum levels of FGF21, inflammatory parameters (IL-6 and IL-1β), glucose, cholesterol, triglycerides, and insulin were determined at baseline and after 36 weeks of treatment. The homeostatic model assessment for insulin resistance (HOMA-IR) and the atherogenic risk factor were also calculated. RESULTS After 36 weeks, serum FGF21 levels decreased significantly (p=0.011), whereas IL-6 levels (r=0.821, p=0.0001) and the CD4+ T cell count (r=0.446, p=0.048), showed a positive correlation with the decrease in FGF21 levels. There was an increase in total cholesterol (r=-0.483, p=0.031), LDL (r=-0.496, p=0.026), VLDL (r=-0.320, p=0.045), and the atherogenic index factor (r=-0.539, p=0.014), these values showed a negative correlation with FGF21 levels. CONCLUSION The decrease of serum FGF21 levels due to ART is associated with the alteration in lipid profile and an increased risk for cardiovascular diseases. These variations are predictors of inflammatory status in HIV patients using antiretroviral therapy.
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FGF23-klotho axis as predictive factors of fractures in type 2 diabetics with early chronic kidney disease.
Ribeiro, AL, Mendes, F, Carias, E, Rato, F, Santos, N, Neves, PL, Silva, AP
Journal of diabetes and its complications. 2020;(1):107476
Abstract
BACKGROUND The aim of our study was to evaluate the relevance of FGF23-klotho axis in the predisposition for bone fractures in type 2 diabetic patients with early chronic kidney disease. METHODS In a prospective study we included 126 type 2 diabetic patients with CKD stages 2-3 (from 2010 to 2017). We used descriptive statistics, ANOVA and chi-square test. Our population was divided into two groups according to the occurrence of a bone fracture event or not, and the groups were compared considering several biological and laboratorial parameters. We employed a multiple regression model to identify risk factors for bone fracture events and hazard ratios (HR) were calculated using a backward stepwise likelihood ratio (LR) Cox regression. RESULTS Patients with a fracture event displayed higher levels of FGF-23, Phosphorus, PTH, TNF-α, OxLDL, HOMA-IR, calcium × phosphorus product and ACR and lower levels of Osteocalcin, α-Klotho, 25(OH)D3 and eGFR compared with patients without a fracture event (p < 0.001). The number of patients with a fracture event was higher than expected within inclining CKD stages (χ2, p = 0.06). The occurrence of fracture and the levels of TNF- α, klotho, 25(OH)D3 and OxLDL were found to predict patient entry into RRT (p < 0.05). Age, osteocalcin, α-Klotho and FGF-23 independently influenced the occurrence of bone fracture (p < 0.05). CONCLUSIONS α-Klotho and FGF-23 levels may have a good clinical use as biomarkers to predict the occurrence of fracture events.
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Gallbladder Dyskinesia Is Associated With an Impaired Postprandial Fibroblast Growth Factor 19 Response in Critically Ill Patients.
Koelfat, KVK, Plummer, MP, Schaap, FG, Lenicek, M, Jansen, PLM, Deane, AM, Olde Damink, SWM
Hepatology (Baltimore, Md.). 2019;(1):308-318
Abstract
Critical illness is associated with a disturbed regulation of gastrointestinal hormones resulting in functional and metabolic anomalies. Fibroblast growth factor 19 (FGF19) is an ileum-derived metabolic hormone induced by bile salts upon gallbladder emptying after enteral nutrient stimulation. Our aim was to study the nutrient-stimulated FGF19 response in 24 patients admitted to the intensive care unit (ICU) compared with 12 healthy controls. All subjects received intraduodenal high-lipid nutrient infusion for 120 minutes. Blood was collected every 30 minutes until 1 hour after infusion, and gallbladder emptying was studied by ultrasound. Serum levels of bile salts and FGF19 were assessed. ICU patients had significantly higher fasting bile salt serum levels compared with controls, whereas FGF19 serum levels were similar. In both groups, nutrient infusion elicited substantial bile salt elevations (P < 0.001), peaking at 90 minutes, albeit with a significantly lower peak in the ICU patients (P = 0.029). In controls, FGF19 was significantly elevated relative to baseline from 120 minutes onward (P < 0.001). In ICU patients, the FGF19 response was blunted, as reflected by significantly lower FGF19 elevations at 120, 150, and 180 minutes (P < 0.05) and significantly lower area under the curve (AUC) values compared with controls (P < 0.001). Gallbladder dysmotility was associated with the impaired FGF19 response in critical illness. The gallbladder ejection fraction correlated positively with FGF19 AUC values (ρ = +0.34, P = 0.045). In 10 of 24 ICU patients, gallbladder emptying was disturbed. These patients had significantly lower FGF19 AUC values (P < 0.001). Gallbladder emptying and the FGF19 response were respectively disturbed or absent in patients receiving norepinephrine. Conclusion: The nutrient-stimulated FGF19 response is impaired in ICU patients, which is mechanistically linked to gallbladder dysmotility in critical illness. This may contribute to disturbed liver metabolism in these patients and has potential as a nutritional biomarker.
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Effects of sodium-glucose cotransporter 2 inhibitor (dapagliflozin) on food intake and plasma fibroblast growth factor 21 levels in type 2 diabetes patients.
Kosugi, R, Nakatani, E, Okamoto, K, Aoshima, S, Arai, H, Inoue, T
Endocrine journal. 2019;(8):677-682
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Abstract
The objective of this study was to investigate whether sodium-glucose cotransporter 2 inhibitors (SGLT2i) treatment in patients with type 2 diabetes induced compensatory hyperphagia by reducing fibroblast growth factor 21 (FGF21) secretion. This prospective study was performed in 26 type 2 diabetes patients treated with dapagliflozin (5 mg/day). Hormonal factors associated with glucose metabolism, dietary intakes estimated by brief self-administered diet-history questionnaire (BDHQ), body weight (BW), and body composition were measured at baseline, and 4 and 12 weeks after dapagliflozin. At 12 weeks, HbA1c levels and BW decreased significantly (both p < 0.0001). BMI at baseline was predictive to baseline log10 (FGF21) (p = 0.037). This study showed no change in FGF21, but insulin and glucagon levels decreased significantly (both p < 0.05). Although hyperphagia was found in 10 patients (38.5%), defining hyperphagia as >20% increase in carbohydrate intake, dapagliflozin treatment induced no hyperphagia, when analyzed by all subjects, and there was no significant association between changes in FGF21 levels and carbohydrate intake. On the other hand, a positive correlation between changes in FGF21 levels or carbohydrate intake and BW was observed (both p < 0.005). Taken together, this study demonstrates that the intervention to maintain the reduced levels in FGF21 is beneficial for BW reduction in type 2 diabetes patients treated with SGLT2i.
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IVACAFTOR restores FGF19 regulated bile acid homeostasis in cystic fibrosis patients with an S1251N or a G551D gating mutation.
van de Peppel, IP, Doktorova, M, Berkers, G, de Jonge, HR, Houwen, RHJ, Verkade, HJ, Jonker, JW, Bodewes, FAJA
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society. 2019;(2):286-293
Abstract
OBJECTIVE Disruption of the enterohepatic circulation of bile acids (BAs) is part of the gastrointestinal phenotype of cystic fibrosis (CF). Ivacaftor (VX-770), a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator, improves pulmonary function in CF patients with class III gating mutations. We studied the effect of ivacaftor on the enterohepatic circulation by assessing markers of BA homeostasis and their changes in CF patients. METHODS In CF patients with an S1251N mutation (N = 16; age 9-35 years S125N study/NTR4873) or a G551D mutation (N = 101; age 10-24 years; GOAL study/ NCT01521338) we analyzed plasma fibroblast growth factor 19 (FGF19) and 7α-hydroxy-4-cholesten-3-one (C4) levels, surrogate markers for intestinal BA absorption and hepatic synthesis, respectively, before and after treatment with ivacaftor. RESULTS At baseline, median FGF19 was lower (52% and 53%, P < .001) and median C4 higher (350% and 364%, P < .001), respectively, for the S1251 N and G551D mutation patient groups compared to healthy controls. Treatment with ivacaftor significantly increased FGF19 and reduced C4 levels towards normalization in both cohorts but this did not correlate with CFTR function in other organs, as measured by sweat chloride levels or pulmonary function. CONCLUSIONS We demonstrate that patients with CFTR gating mutations display interruption of the enterohepatic circulation of BAs reflected by lower FGF19 and elevated C4 levels. Treatment with ivacaftor partially restored this disruption of BA homeostasis. The improvement did not correlate with established outcome measures of CF, suggesting involvement of modulating factors of CFTR correction in different organs.
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Relationship between cFGF23/Klotho ratio and phosphate levels in patients with chronic kidney disease.
Liu, Z, Zhou, H, Chen, X, Chen, H, Wang, Y, Wang, T, Cai, L, Hong, Y, Ke, H, Zheng, J
International urology and nephrology. 2019;(3):503-507
Abstract
PURPOSE To characterize the relationship between the cFGF23/Klotho ratio and phosphate level in patients with chronic kidney disease (CKD). METHODS A total of 152 patients with CKD stage 3-5 (CKD stage 3: n = 74; CKD stage 4: n = 60; CKD stage 5: n = 18) were included in the study. Thirty healthy volunteers served as controls. Intact-FGF23, cFGF23, Klotho, serum calcium, serum phosphate, and serum creatinine were measured, and estimated glomerular filtration rate (eGFR) was calculated. The Kruskal-Wallis H test was used for comparison between groups, and the Spearman test was used for correlation analysis. RESULTS In CKD stage 3-5, creatinine and iFGF23 levels, as well as the cFGF23/Klotho ratio, were higher (P < 0.01), phosphate levels were higher (P < 0.05), and Klotho levels were lower (P < 0.01), compared with controls. C-terminal-FGF23 levels were higher in CKD phase 4-5 (P < 0.05). In CKD stage 4-5, creatinine, iFGF23, and phosphate levels, as well as the cFGF23/Klotho ratio, were higher (P < 0.01), cFGF23 levels were higher (P < 0.05), and Klotho levels were lower (P < 0.05), compared with CKD stage 3. In CKD stage 5, creatinine and cFGF23 levels, as well as the cFGF23/Klotho ratio, were higher (P < 0.01), phosphate and iFGF23 levels were higher (P < 0.05), and Klotho levels were lower (P < 0.01), compared with CKD stage 4. Phosphate was positively correlated with the cFGF23/Klotho ratio (r = 0.235, P < 0.01). CONCLUSIONS EGFR reduction was associated with an increased cFGF23/Klotho ratio, and the cFGF23/Klotho ratio was positively correlated with phosphate. This suggests that the phosphate level can be controlled by modifying the cFGF23/Klotho ratio.