Serum fibroblast growth factor 19 (FGF19) levels are associated with atherogenic dyslipidemia in patients with type 2 diabetes.
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ABSTRACT:
SUBMITTER: Hu JY
PROVIDER: S-EPMC8478367 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Prostate cancer is the most common visceral malignancy and the second leading cause of cancer deaths in US men. There is broad evidence that fibroblast growth factor (FGF) receptors are important in prostate cancer initiation and progression, but the contribution of particular FGFs in this disease is not fully understood. The FGF family members FGF19, FGF21, and FGF23 comprise a distinct subfamily that circulate in serum and act in an endocrine manner. These endocrine FGFs require α-Klotho (KL) and/or β-Klotho (KLB), two related single-pass transmembrane proteins restricted in their tissue distribution, to act as coreceptors along with classic FGF receptors (FGFR) to mediate potent biologic activity. Here we show that FGF19 is expressed in primary and metastatic prostate cancer tissues, where it functions as an autocrine growth factor. Exogenous FGF19 promoted the growth, invasion, adhesion, and colony formation of prostate cancer cells at low ligand concentrations. FGF19 silencing in prostate cancer cells expressing autocrine FGF19 decreased invasion and proliferation in vitro and tumor growth in vivo. Consistent with these observations, KL and/or KLB were expressed in prostate cancer cells in vitro and in vivo, raising the possibility that additional endocrine FGFs may also exert biologic effects in prostate cancer. Our findings support the concept that therapies targeting FGFR signaling may have efficacy in prostate cancer and highlight FGF19 as a relevant endocrine FGF in this setting.
| S-EPMC3630260 | biostudies-literature
Project description:BackgroundIncreasing evidence suggests that fibroblast growth factor 19 (FGF19) is a regulator of glucose metabolism and may provide a new therapeutic target for type 1 diabetes (T1D). However, the clinical relevance of FGF19 in T1D remains unclear. In this study, we examined the relationship between the serum FGF19 concentration and T1D.MethodsThis study included 81 newly diagnosed T1D patients and 80 sex- and age-matched healthy controls. The correlation between the FGF19 concentration and clinical characteristics of T1D patients and healthy controls was investigated. Logistic regression analysis was performed to determine whether levels of FGF19 were independently associated with T1D.ResultsThe fasting serum FGF19 levels in the T1D group were significantly lower than those in the control group [159.9 (100.0-272.7) vs. 205.0 (126.9-307.9) pg/mL, P=0.008]. In all subjects, serum FGF19 levels were negatively correlated with fasting blood glucose (FBG) (r=-0.192, P=0.015). In the control group, serum FGF19 levels were positively correlated with total cholesterol (TC) (r=0.338, P=0.002) and low-density lipoprotein cholesterol (LDL-c) (r=0.300, P=0.007). In addition to sex and body mass index (BMI), FGF19 was an independent impact factor for T1D [odds ratio (OR) =0.541, P=0.023; adjusted for sex, age, BMI, presence of hypertension, and presence of dyslipidemia].ConclusionsLow serum FGF19 level is associated with T1D, which could serve as a risk factor for T1D.
| S-EPMC8033349 | biostudies-literature
Project description:BackgroundFibroblast growth factor 21 (FGF21) increases glucose uptake. It is unknown if FGF21 serum levels are affected by exercise.Methodology/principal findingsThis was a comparative longitudinal study. Anthropometric and biochemical evaluation were carried out before and after a bout of exercise and repeated after two weeks of daily supervised exercise. The study sample was composed of 60 sedentary young healthy women. The mean age was 24±3.7 years old, and the mean BMI was 21.4±7.0 kg/m². The anthropometric characteristics did not change after two weeks of exercise. FGF21 levels significantly increased after two weeks of exercise (276.8 ng/l (142.8-568.6) vs. (460.8 (298.2-742.1), p<0.0001)). The delta (final-basal) log of serum FGF21, adjusted for BMI, showed a significant positive correlation with basal glucose (r = 0.23, p = 0.04), mean maximal heart rate (MHR) (r = 0.54, p<0.0001), mean METs (r = 0.40, p = 0.002), delta plasma epinephrine (r = 0.53, p<0.0001) and delta plasma FFAs (r = 0.35, p = 0.006). A stepwise linear regression model showed that glucose, MHR, METs, FFAs, and epinephrine, were factors independently associated with the increment in FGF21 after the exercise program (F = 4.32; r² = 0.64, p<0.0001).ConclusionsSerum FGF21 levels significantly increased after two weeks of physical activity. This increment correlated positively with clinical parameters related to the adrenergic and lipolytic response to exercise.Trial registrationClinicalTrials.gov NCT01512368.
| S-EPMC3365112 | biostudies-literature
Project description:Basal-like breast cancer is an aggressive tumor subtype with poor prognosis. The discovery of underlying mechanisms mediating tumor cell survival, and the development of novel agents to target these pathways, is a priority for patients with basal-like breast cancer. From a functional screen to identify key drivers of basal-like breast cancer cell growth, we identified fibroblast growth factor receptor 4 (FGFR4) as a potential mediator of cell survival. We found that FGFR4 mediates cancer cell survival predominantly via activation of PI3K/AKT. Importantly, a subset of basal-like breast cancer cells also secrete fibroblast growth factor 19 (FGF19), a canonical ligand specific for FGFR4. siRNA-mediated silencing of FGF19 or neutralization of extracellular FGF19 by anti-FGF19 antibody (1A6) decreases AKT phosphorylation, suppresses cancer cell growth and enhances doxorubicin sensitivity only in the FGFR4+/FGF19+ breast cancer cells. Consistently, FGFR4/FGF19 co-expression was also observed in 82 out of 287 (28.6%) primary breast tumors, and their expression is strongly associated with AKT phosphorylation, Ki-67 staining, higher tumor stage and basal-like phenotype. In summary, our results demonstrated the presence of an FGFR4/FGF19 autocrine signaling that mediates the survival of a subset of basal-like breast cancer cells and suggest that inactivation of this autocrine loop may potentially serve as a novel therapeutic intervention for future treatment of breast cancers.
| S-EPMC5295378 | biostudies-literature
Project description:Objective: Fibroblast growth factor 19 (FGF19) plays an indispensable role in regulating bile acid, glucose, and lipid metabolism, and alterations of its circulating concentration is associated with the development of type 2 diabetes (T2D). Atherosclerosis is directly related to the death-deriving diabetic macroangiopathy in T2D, yet relationships between FGF19 and atherosclerosis in T2D remain unclear. The aim of this study was to investigate the association of circulating FGF19 levels with the development of subclinical atherosclerosis (subAS) in patients with T2D in a 3-year prospective study. Methods: In the present study, 153 newly diagnosed T2D patients without subAS were recruited at baseline, and 137 of them completed a 3-year follow-up. FGF19 levels were measured in fasting serum samples collected at baseline and the third-year visits. Carotid, femoral, and iliac intima-media thickness (IMT) were detected by high-resolution B-mode ultrasound to determine the presence of subAS. Logistic regression analysis was applied to assess the relationship between serum FGF19 and subAS in patients with T2D. Results: At baseline, serum FGF19 levels were positively correlated with carotid IMT and iliac IMT in men (r = 0.239, P = 0.036; r = 0.309, P = 0.006). At the 3-year follow-up, 25 out of 153 patients developed subAS, and FGF19 levels in men were higher in the subAS group than in the non-subAS group [202.7 (177.9-373.6) vs. 133.4 (85.6-171.3) pg/ml, P = 0.028]. Furthermore, in men, higher baseline levels of FGF19 were independently associated with a greater risk of subAS at year 3 in patients with T2D with an odds ratio (OR) of 4.798 per 1 standard deviation (SD) of the FGF19 concentration [OR = 4.798 (95% CI, 1.680-13.706), P = 0.003]. Baseline FGF19 levels yielded an area under the receiver operating characteristic curve of 0.769 to predict the development of subAS at year 3 in men with T2D. Conclusions: Serum FGF19 levels could help in predicting the development of atherosclerosis in men with T2D.
| S-EPMC7258879 | biostudies-literature
Project description:FGF19 and FGF21 are distinctive members of the FGF family that function as endocrine hormones. Their potent effects on normalizing glucose, lipid, and energy homeostasis in disease models have made them an interesting focus of research for combating the growing epidemics of diabetes and obesity. Despite overlapping functions, FGF19 and FGF21 have many discrete effects, the most important being that FGF19 has both metabolic and proliferative effects, whereas FGF21 has only metabolic effects. Here we identify the structural determinants dictating differential receptor interactions that explain and distinguish these two physiological functions. We also have generated FGF19 variants that have lost the ability to induce hepatocyte proliferation but that still are effective in lowering plasma glucose levels and improving insulin sensitivity in mice. Our results add valuable insight into the structure-function relationship of FGF19/FGF21 and identify the structural basis underpinning the distinct proliferative feature of FGF19 compared with FGF21. In addition, these studies provide a road map for engineering FGF19 as a potential therapeutic candidate for treating diabetes and obesity.
| S-EPMC2922594 | biostudies-literature
Project description:Fibroblast growth factor 21 (FGF21) is a major metabolic regulator that has been shown to be elevated in a number of metabolic disturbances including type 2 diabetes mellitus (T2DM) and the metabolic syndrome, but few studies about the relationship between serum FGF21 and the complications of diabetes have been done. Since the association between FGF21 and diabetic retinopathy is not clear, this study was conducted to investigate this relationship. In this cross-sectional study, 61 subjects (14 healthy controls, 22 diabetic patients without retinopathy, and 25 patients with diabetic retinopathy) were evaluated. All patients in the study were examined for the presence of diabetic retinopathy. Various clinical and biochemical parameters including FGF21 were evaluated and analyzed and compared between the study groups. Serum levels of FGF21 showed a significant difference between the three groups (P=0.003) but the difference between diabetic patients with and without retinopathy was not significant (P=0.122). Regression model was used to evaluate the role of FGF21 in predicting diabetic retinopathy. In the multivariate logistic regression model after adjustment of systolic blood pressure and fasting blood glucose, the level of FGF21 was not associated with diabetic retinopathy. In the multivariate model, only fasting blood glucose was associated with diabetic retinopathy (P=0.009). According to the results of this study, serum levels of FGF21 in diabetic patients was higher than the control group but these raised levels could not predict the presence of diabetic retinopathy.
| S-EPMC5735335 | biostudies-literature
Project description:BackgroundEarly diagnosis of atrial fibrillation is important as it is crucial for improving patient outcomes. Fibroblast growth factor-2 (FGF2) may serve as a diagnostic biomarker for heart failure due to its ability to promote cardiac fibrosis and hypertrophy; however, the relationship between FGF2 concentration and heart failure is unclear. Therefore, this study aimed to explore whether FGF2 could aid in distinguishing patients with heart failure from healthy controls and those with dyspnea without heart failure. Additionally, to evaluate the possible correlation between serum FGF2 levels and its diagnostic parameters in patients with heart failure.MethodsPlasma FGF2 concentration was measured in 114 patients with a complaint of dyspnea (enrolled in the study between January 2022 and August 2022). Based on heart failure diagnosis, the patients were assigned to three groups, as follows: heart failure (n = 80), non-heart-failure dyspnea (n = 34), and healthy controls (n = 36), following physical examination. Possible correlations between serum FGF2 levels and other prognostic parameters in patients with heart failure were analyzed.ResultsSerum FGF2 levels were higher in patients with heart failure (125.60 [88.95, 183.40] pg/mL) than in those with non-heart-failure dyspnea (65.30 [28.85, 78.95] pg/mL) and healthy controls (78.90 [60.80, 87.20] pg/mL) (p < 0.001). Receiver operating characteristic curve analysis identified FGF2 concentration as a significant predictor in heart failure diagnosis, with an area under the curve of 0.8693 (p < 0.0001). Importantly, in the heart failure group, serum FGF2 concentrations correlated with key prognostic parameters for heart failure, such as reduced left ventricular ejection fraction and elevated serum levels of N-terminal pro-B-type natriuretic peptide.ConclusionsElevated serum FGF2 level is strongly associated with an increased risk of heart failure and could serve as a useful biomarker to complement vital diagnostic parameters for heart failure.
| S-EPMC10868019 | biostudies-literature
Project description:High levels of fibroblast growth factor 23 are associated with accelerated progression of CKD. Whether high fibroblast growth factor 23 levels also predict incident CKD is uncertain.A prospective case-cohort study was conducted within the Action to Control Cardiovascular Risk in Diabetes Trial. The analytic sample consisted of a random subcohort of 590 patients with type 2 diabetes without prevalent CKD at baseline, 124 of whom developed incident CKD during follow-up, and 520 additional patients with incident CKD outside the random subcohort. The association between serum intact fibroblast growth factor 23 and incident CKD, defined as the new onset of eGFR<60 ml/min per 1.73 m(2) that represented a ?25% decrease from baseline in an individual with eGFR?60 ml/min per 1.73 m(2) and no microalbuminuria (<30 mg/g creatinine) at baseline, was tested.The mean baseline eGFR in the random subcohort was 90.9±22.7 ml/min per 1.73 m(2). During a median follow-up of 4.7 years, there was a total of 644 patients with incident CKD. The median baseline fibroblast growth factor 23 level was modestly higher among patients with incident CKD versus controls (43.5, interquartile range=34.7-55.1 versus 39.8, interquartile range=31.9-49.5 pg/ml; P<0.001). Higher baseline fibroblast growth factor 23 levels were associated with higher risk of incident CKD in unadjusted and demographics-adjusted models, but the effect was attenuated after additional adjustment for clinical risk factors and baseline eGFR (hazard ratio per SD of natural log fibroblast growth factor 23, 1.09; 95% confidence interval, 0.94 to 1.27), which was the strongest predictor of incident CKD. Consistent with the results of primary analyses, baseline fibroblast growth factor 23 was not associated with eGFR slope.Higher fibroblast growth factor 23 levels are not independently associated with higher risk of incident CKD in patients with type 2 diabetes.
| S-EPMC4284418 | biostudies-literature
Project description:BackgroundWhether microalbuminuria predicts renal outcomes in patients with type 2 diabetes mellitus (T2DM) is argued. Fibroblast growth factor 21 (FGF-21) levels were elevated by the pathogenic process of diabetic kidney disease. The purpose of the study was to evaluate the associations of FGF-21 and renal outcomes in subjects with T2DM.MethodsChinese patients with T2DM were enrolled and then observed prospectively, and FGF-21 levels at baseline were measured. The associations of FGF-21 levels and renal composite events, defined by a drop > 30% of eGFR or worsening category of albuminuria, were evaluated using Cox analysis. The appropriate cut-off value of FGF-21 was mapped by the receiver operating characteristic (ROC) curve.ResultsAmong 312 subjects, higher FGF-21 levels were associated with higher risks of renal events in Cox analysis. The area under the curve of FGF-21 levels in the ROC curve was optimal (0.67, p < 0.001), and the cut-off value of 1.40 pg/dl exhibited the best sensitivity (76.2%) and specificity (53.5%). The frequency of renal composite events was higher in subjects with FGF-21 ≥ 1.40 pg/dl than in others (30% vs. 10%, p<0.001 by the log-rank test). The worse renal outcomes predicted by FGF-21 ≥ 1.40 pg/dl were confirmed using the adjustments of Cox sequential models (hazard ratio 2.28, 95% confidence interval 1.23-4.24, p=0.009) and consistent across subjects with different status of baseline characteristics and renal risks.ConclusionFGF-21 levels were proportional to the risks of renal events in broad- spectrum Chinese T2DM subjects, making it a potential biomarker to predict the renal outcomes of T2DM.
| S-EPMC9069677 | biostudies-literature