[High-intensity interval training (HIIT) induces hepatic ketone body production possibly through altering expression of mTORC1, PPARα and FGF21 in mice].

The present study aims to investigate the production of ketone body in the liver of mice after 6 weeks of high-intensity interval training (HIIT) intervention and explore the possible mechanisms. Male C57BL/6J mice (7-week-old) were randomly divided into control and HIIT groups. The control group did not engage in exercise, while the HIIT group underwent a 6-week HIIT (10° slope treadmill exercise). Changes in weight and body composition were recorded, and blood ketone body levels were measured before, immediately after, and 1 h after each HIIT exercise. After 6-week HIIT, the levels of free fatty acids in the liver and serum were detected using reagent kits, and expression levels of regulatory factors and key enzymes of ketone body production in the mouse liver were detected by Western blot and qPCR. The results showed that, the blood ketone body levels in the HIIT group significantly increased immediately after a single HIIT and 1 h after HIIT, compared with that before HIIT. The body weight of the control group gradually increased within 6 weeks, while the HIIT group mice did not show significant weight gain. After 6-week HIIT, compared with the control group, the HIIT group showed decreased body fat ratio, increased lean body weight ratio, and increased free fatty acid levels in liver and serum. Liver carnitine palmitoyl transferase-I (CPT-I), peroxisome proliferator activated receptor α (PPARα), and fibroblast growth factor 21 (FGF21) protein expression levels were up-regulated, whereas mammalian target of rapamycin complex 1 (mTORC1) protein expression level was significantly down-regulated in the HIIT group, compared with those in the control group. These results suggest that HIIT induces hepatic ketone body production through altering mTORC1, PPARα and FGF21 expression in mice.

Elevated serum FGF21 is an independent predictor for adverse events in hemodialysis patients from two large centers: a prospective cohort study.

Introduction: We explored the relationship and the predictive value of serum fibroblast growth factor 21 (FGF21) with all-cause mortality, major adverse cardiovascular events (MACEs) and pneumonia in hemodialysis (HD) patients.Methods: A total of 388 Chinese HD patients from two HD centers were finally enrolled in this prospective cohort study (registration number: ChiCTR 1900028249) between January 2018 and December 2018. Serum FGF21 was detected. Patients were followed up with a median period of 47 months to record the MACEs and pneumonia until death or 31 December 2022.Results: The incidence of all-cause mortality, MACEs and pneumonia in HD patients were 20.6%, 29.6%, and 34.8%, respectively. The optimal cutoffs for FGF21 to predict all-cause mortality, MACEs and pneumonia were 437.57 pg/mL, 216.99 pg/mL and 112.79 pg/mL. Multivariate Cox regression analyses showed that FGF21, as a categorical variable, was an independent predictor for all-cause mortality, MACEs and pneumonia (HR, 3.357, 95% CI, 2.128-5.295, p < 0.001; HR, 1.575, 95% CI, 1.046-2.371, p = 0.029; HR, 1.784; 95% CI, 1.124-2.830; p = 0.014, respectively). The survival nomogram, MACEs-free survival nomogram and pneumonia-free survival nomogram based on FGF21 constructed for individualized assessment of HD patients had a high C-index with 0.841, 0.706 and 0.734.Conclusion: Higher serum FGF21 is an independent predictor of all-cause mortality, MACEs and pneumonia in HD patients.

Exploring the correlation between serum fibroblast growth factor-21 levels and Sarcopenia: a systematic review and meta-analysis.

BACKGROUND: Fibroblast growth factor 21 (FGF-21) plays an important role in the growth and metabolism of skeletal muscle cells. This study aims to systemically review the evidence regarding the relationship between FGF-21 levels and Sarcopenia, as well as the related influential factors. METHODS: This review was conducted according to the PRISMA guidelines. We comprehensively searched PubMed, EMBASE, the Web of Science, Scopus, and Chinese Databases (CNKI, Wan Fang, VIP, and CBM) up to 1 May 2023. 3 investigators performed independent literature screening and data extraction of the included literature, and two investigators performed an independent quality assessment of case-control studies using the Joanna Briggs Institute (JBI) tool. Data analysis was performed using Review Manager 5.4 software. For continuous various outcomes, mean difference (MD) or standard mean difference (SMD) with 95% confidence intervals (CIs) was applied for assessment by fixed-effect or random-effect model analysis. The heterogeneity test was performed by the Q-statistic and quantified using I2, and publication bias was evaluated using a funnel plot. RESULTS: Five studies with a total of 625 cases were included in the review. Meta-analysis showed lower BMI in the sarcopenia group [MD= -2.88 (95% CI, -3. 49, -2.27); P < 0.00001; I2 = 0%], significantly reduced grip strength in the sarcopenia group compared to the non-sarcopenia group [MD = -7.32(95% CI, -10.42,-4.23); P < 0.00001; I2 = 93%]. No statistically significant differences in serum FGF21 levels were found when comparing the two groups of subjects [SMD = 0.31(95% CI, -0.42, 1.04); P = 0.41; I2 = 94%], and no strong correlation was found between the onset of sarcopenia and serum FGF21 levels. CONCLUSION: The diagnosis of sarcopenia is followed by a more significant decrease in muscle mass and strength, but there is a lack of strong evidence to support a direct relationship between elevated organismal FGF21 and sarcopenia, and it is not convincing to use FGF21 as a biological or diagnostic marker for sarcopenia. The currently used diagnostic criteria for sarcopenia and setting of cut-off values for each evaluation parameter no longer seem to match clinical practice.

High circulating fibroblast growth factor-21 levels as a screening marker in fatty pancreas patients.

Background: The study aimed to detect the serum levels of fibroblast growth factor-21 (FGF-21) in fatty pancreas (FP) patients and to investigate their potential clinical value. Methods: We screened patients with FP using transabdominal ultrasound. The anthropometric, biochemical and serum levels of FGF-21 were compared between the FP group and the normal control (NC) group. A receiver operating characteristic (ROC) curve was used to evaluate the predictive value of serum FGF-21 for FP patients. Results: Compared with the NC group, body mass index, fasting blood glucose levels, uric acid levels and cholesterol levels of the FP group were significantly higher, while the high-density lipoprotein level was lower. In addition, levels of serum FGF-21, resistin, leptin and tumor necrosis factor-α were significantly higher than those in the NC group, while the serum adiponectin level was lower. Pearson analysis showed serum FGF-21 levels in FP patients were negatively correlated with leptin. The ROC curve showed the best critical value of the serum FGF-21 level in FP patients was 171 pg/mL (AUC 0.744, P = 0.002, 95% confidence intervals 0.636-0.852). Conclusion: Serum FGF-21 was closely related to fatty pancreas. Detecting serum FGF-21 levels may help identify the population susceptible to FP.

Determination of FGF23 Levels for the Diagnosis of FGF23-Mediated Hypophosphatemia.

Fibroblast growth factor-23 (FGF23) measurement is a critical tool in the evaluation of patients with disordered phosphate homeostasis. Available laboratory reference ranges for blood FGF23 were developed using samples from normophosphatemic individuals. Reliance on such values can lead to misdiagnosis in patients with FGF23-mediated hypophosphatemia, such as X-linked hypophosphatemia (XLH) and tumor-induced osteomalacia (TIO), in whom pathology-driving FGF23 levels can be in the "normal range." To determine FGF23 levels that are diagnostic for the identification of patients with FGF23-mediated hypophosphatemic disorders, we studied 149 patients with various disorders of FGF23-mediated and FGF23-independent hypophosphatemia and defined cut-off levels for both intact FGF23 (iFGF23) and C-terminal FGF23 (cFGF23) that can accurately distinguish between FGF23-mediated and FGF23-independent hypophosphatemia. In addition, to demonstrate the relationship between FGF23 and phosphate across the spectrum of human physiology, we assessed blood levels of FGF23 and phosphate in 434 patients with various forms of hypophosphatemia, hyperphosphatemia, and normophosphatemia. An intact FGF23 cut point of 27 pg/mL was 100% sensitive and specific in distinguishing FGF23-mediated from FGF23-independent hypophosphatemia, and a cFGF23 cut point of 90 RU/mL was 100% sensitive and specific in distinguishing specifically TIO from FGF23-independent hypophosphatemia. There was overlap in the cFGF23 range of 45-90 RU/mL between genetic forms of FGF23 excess and FGF23-independent hypophosphatemia, substantiating the superiority of iFGF23 over cFGF23 in making the diagnosis of FGF23-mediated hypophosphatemia. In this cohort, using the laboratory upper limit of normal for cFGF23 (180 RU/mL) would result in a misdiagnosis in more than half of patients with FGF23-mediated hypophosphatemia. In this, the largest study of FGF23 in chronic hypophosphatemia to date, we established iFGF23 and cFGF23 cut-off values to assist in the evaluation and diagnosis of hypophosphatemic conditions. © 2022 American Society for Bone and Mineral Research (ASBMR). This article has been contributed to by US Government employees and their work is in the public domain in the USA.

Fibroblast Growth Factor 21 Levels and Bone Mineral Density in Metabolically Healthy and Metabolically Unhealthy Obese Children

Objective: The harmful or beneficial effect of obesity on bone mineral density (BMD) remains controversial in children and adolescents. Fibroblast growth factor 21 (FGF21) is a metabolic factor that plays a specific role in the regulation of carbohydrate and lipid metabolism. However, the role of FGF21 in bone metabolism appears paradoxical and is complex. To determine whether serum FGF21 level was associated with BMD in obese children and adolescents. Methods: The study was conducted with the participation of children and adolescents aged 8-18 years. Ninety-eight obese children were included in the study group and 44 children were included in the control group. BMD, in addition to the routine obesity workup, which includes fasting blood glucose, fasting insulin levels, lipid profile, and liver enzymes; serum FGF21 levels have been analyzed. Results: The mean age of the obese group (n=98) was 13.34±2.24 years and the mean age of controls (n=44) was 13.48±2.87 years. Based on International Diabetes Federation criteria, 15 of 98 (15.3%) patients were metabolically unhealthy. FGF21 levels were 193.54±139.62 mg/dL in the obese group and 158.69±151.81 mg/dL in the control group (p=0.06). There was no difference between the FGF21 and BMD z-score values of girls and boys in the obese and control groups (p>0.05). Conclusion: BMD-z-score was increased in obese children compared to healthy control. Moreover, BMD-z-score tended to be higher when more metabolic risk factors were present. However, there was no significant relationship between FGF21 levels and BMD z-score values in obese children.

Effect of Aerobic Exercise Training on Circulating Fibroblast Growth Factor-21 Response to Glucose Challenge in Overweight and Obese Men: A Pilot Study.

BACKGROUND AND STUDY PURPOSE: Fibroblast growth factor-21 (FGF21) is a liver-derived hormone that lowers blood glucose. Although aerobic exercise training also lowers blood glucose, its effect on circulating FGF21levels remains obscure. This study aimed to examine the effect of aerobic exercise training on serum FGF21 levels in overweight and obese men. METHODS: A total of 14 overweight/obese men were included in the analyses. Participants attended supervised aerobic exercise training for 12 weeks (three times per week) and completed the standard oral glucose tolerance test pre- and post-exercise training. Plasma glucose, serum insulin, and serum FGF21 levels were measured at fasting and 60 and 120 min after glucose loading. RESULTS: The exercise training reduced plasma glucose and serum FGF21 levels during glucose loading (p<0.05). The change in the area under the curve of plasma glucose was positively correlated with that in the area under the curve of serum FGF21 (r s =0.569, p=0.034). CONCLUSION: Lowering postprandial circulating FGF21 levels may be associated with the improved glucose tolerance induced by habitual aerobic exercise in overweight and obese men.

FGF21 response to sucrose is associated with BMI and dorsal striatal signaling in humans.

OBJECTIVE: This study examined associations between BMI and dietary sugar intake with sucrose-induced fibroblast growth factor 21 (FGF21) and whether circulating FGF21 is associated with brain signaling following sucrose ingestion in humans. METHODS: A total of 68 adults (29 male; mean [SD), age 23.2 [3.8] years; BMI 27.1 [4.9] kg/m2 ) attended visits after a 12-hour fast. Plasma FGF21 was measured at baseline and at 15, 30, and 120 minutes after sucrose ingestion (75 g in 300 mL of water). Brain cerebral blood flow responses to sucrose were measured using arterial spin labeling magnetic resonance imaging. RESULTS: Higher circulating FGF21 levels were associated with reduced blood flow in the striatum in response to sucrose (ß = -7.63, p = 0.03). This association was greatest among persons with healthy weight (ß = -15.70, p = 0.007) and was attenuated in people with overweight (ß = -4.00, p = 0.63) and obesity (ß = -12.45, p = 0.13). BMI was positively associated with FGF21 levels in response to sucrose (ß = 0.53, p = 0.02). High versus low dietary sugar intake was associated with greater FGF21 responses to acute sucrose ingestion in individuals with healthy weight (ß = 8.51, p = 0.04) but not in individuals with overweight or obesity (p > 0.05). CONCLUSIONS: These correlative findings support evidence in animals showing that FGF21 acts on the brain to regulate sugar consumption through a negative feedback loop.

Non-Alcoholic Fatty Liver Disease in Long-Term Type 2 Diabetes: Role of rs738409 PNPLA3 and rs499765 FGF21 Polymorphisms and Serum Biomarkers.

Fibroblast growth factor 21 (FGF21) signaling and genetic factors are involved in non-alcoholic fatty liver disease (NAFLD) pathogenesis. However, these factors have rarely been studied in type 2 diabetes mellitus (T2D) patients from admixed populations such as in those of Brazil. Therefore, we aimed to evaluate rs738409 patanin-like phospholipase domain-containing protein (PNPLA3) and rs499765 FGF21 polymorphisms in T2D, and their association with NAFLD, liver fibrosis, and serum biomarkers (FGF21 and cytokeratin 18 levels). A total of 158 patients were included, and the frequency of NAFLD was 88.6%, which was independently associated with elevated body mass index. Significant liver fibrosis (≥F2) was detected by transient elastography (TE) in 26.8% of NAFLD patients, and was independently associated with obesity, low density lipoprotein, and gamma-glutamyl transferase (GGT). PNPLA3 GG genotype and GGT were independently associated with cirrhosis. PNPLA3 GG genotype patients had higher GGT and AST levels; PNPLA3 GG carriers had higher TE values than CG patients, and FGF21 CG genotype patients showed lower gamma-GT values than CC patients. No differences were found in serum values of FGF21 and CK18 in relation to the presence of NAFLD or liver fibrosis. The proportion of NAFLD patients with liver fibrosis was relevant in the present admixed T2D population, and was associated with PNPLA3 polymorphisms.

The fibroblast growth factor 21 concentration in children with mitochondrial disease does not depend on the disease stage, but rather on the disease genotype.

ABSTRACT: The fibroblast growth factor 21 (FGF21) is a new biomarker of mitochondrial diseases (MD). FGF21 concentration may be used to define the severity of mitochondrial disease. AIM OF THE STUDY: The study objective was to verify if the FGF21 concentration in paediatric patients with MD was correlated with the disease severity and stage and to assess the correlation between FGF21 levels and the genetic background of MD. MATERIAL AND METHODS: The disease stage in MD subjects was determined on the basis of the International Paediatric Mitochondrial Disease Scale (IPMDS) and the concentrations of FGF21, lactic and pyruvic acids, alanine and creatine kinase in serum were assessed in those patients. RESULTS: The median age of children with MD (n = 32) was 33 months (range: 2-213), in the control group (n = 21) the median age was 42 months (range: 8-202). The concentrations of FGF21, lactic acid and pyruvic acid were higher in MD patients than in the control group. No correlation between the disease severity (IPMDS) and serum FGF21 concentration was found. The FGF21 concentration was higher in patients whose MD resulted from nuclear gene damage (nDNA), median FGF21 = 1022 (84-8873) pg/ml, than in patients with MD resulting from mitochondrial damage (mtDNA), median FGF21 = 736 (188-2906) pg/ml, or with an abnormal variant in the PDHA1 gene, median FGF21 = 58 (25-637) pg/ml. CONCLUSIONS: There is no correlation between the stage of MD and FGF21 level. Higher FGF21 values are seen in patients whose MD results from an abnormal nDNA variant rather than mtDNA damage.

Fibroblast Growth Factor 21 as a Marker of Prediabetes in Patients with Non-alcoholic Fatty Liver Disease.

BACKGROUND: Fibroblast growth factor 21 is a peptide primarily secreted by the liver in response to peroxisome proliferator-activated receptor-α activation which plays an important role in regulating carbohydrate and lipid metabolism. This study investigated the association between fibroblast growth factor 21 and prediabetes in obese patients with non-alcoholic fatty liver disease in adult population. METHODS: A total of 85 obese non-alcoholic fatty liver disease patients without (n = 49) and with prediabetes (n = 36) were included. Serum fibroblast growth factor 21 levels were determined by enzyme-linked immunosorbent assay. RESULTS: Higher fibroblast growth factor 21 serum levels were observed in patients with prediabetes, metabolic syndrome, dyslipidemia, and insulin resistance. There were significant correlations between fibroblast growth factor 21 and waist-to-stature ratio, visceral adiposity index, triglycerides, very low-density lipoproteins, alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), Quantitative Insulin Sensitivity Check Index, and Stumvoll index of insulin sensitivity. Fibroblast growth factor 21 level ≥320 pg/mL was associated with a 4.2-fold higher risk of prediabetes and ≥270 pg/mL for metabolic syndrome approximately 4 times. CONCLUSION: Fibroblast growth factor 21 is associated with increased risk for prediabetes, metabolic syndrome, and insulin resistance in obese patients with non-alcoholic fatty liver disease.

Novel Adipokines CTRP1, CTRP9, and FGF21 in Pediatric Type 1 and Type 2 Diabetes: A Cross-Sectional Analysis.

INTRODUCTION: Pediatric obesity and diabetes has increased over the last several decades. While the role of common adipokines on metabolic parameters has been well studied in adults, the relationship of novel adipokines and hepatokines in pediatric type 1 (T1D) and type 2 diabetes (T2D) is not well understood. This study assessed novel adipokines C1q/TNF-related proteins (CTRP1 and CTRP9), and hepatokine fibroblast growth factor 21 (FGF21) in youth with T1D and T2D diabetes. METHODS: Participants (n = 80) with T1D (n = 40) enrolled in the Pediatric Diabetes Consortium (PDC) T1D NeOn registry, and T2D (n = 40) from the PDC T2D registry. Cross-sectional analysis compared adipokines (CTRP1, CTRP9, FGF21) between T1D and T2D, and regression models assessed adipokine relationship with clinical characteristics. RESULTS: The mean age of the participants was 14.9 ± 2 years, and 50% were female. T2D participants had a shorter diabetes duration (p = 0.0009), higher weight (p < 0.0001), and BMI (p < 0.0001) than T1D participants. CTRP9 levels were higher in T1D (13,903.6 vs. 3,608.5 pg/mL, p = 0.04) than T2D, and FGF21 levels were higher in T2D (113.1 vs. 70.6 pg/mL, p = 0.03) than T1D, with no differences in CTRP1. In regression analysis of T1D, CTRP9 was positively associated with C-peptide (p = 0.006), and FGF21 was positively associated with hemoglobin A1c (p = 0.04). In T2D, CTRP1 was positively associated with HbA1c (p < 0.001) and glucose (p = 0.004), even after controlling for age, sex, and BMI. CONCLUSIONS: CTRP9 levels are higher in youth with T1D compared to T2D, and FGF21 levels are higher in youth with T2D than T1D. Novel adipokines are related to metabolic homeostasis in the inflammatory milieu of pediatric diabetes.

The Regulatory Role of the Central and Peripheral Serotonin Network on Feeding Signals in Metabolic Diseases.

Central and peripheral serotonin (5-hydroxytryptamine, 5-HT) regulate feeding signals for energy metabolism. Disruption of central 5-HT signaling via 5-HT2C receptors (5-HT2CRs) induces leptin-independent hyperphagia in mice, leading to late-onset obesity, insulin resistance, and impaired glucose tolerance. 5-HT2CR mutant mice are more responsive than wild-type mice to a high-fat diet, exhibiting earlier-onset obesity and type 2 diabetes. High-fat and high-carbohydrate diets increase plasma 5-HT and fibroblast growth factor-21 (FGF21) levels. Plasma 5-HT and FGF21 levels are increased in rodents and humans with obesity, type 2 diabetes, and non-alcohol fatty liver diseases (NAFLD). The increases in plasma FGF21 and hepatic FGF21 expression precede hyperinsulinemia, insulin resistance, hyperglycemia, and weight gain in mice fed a high-fat diet. Nutritional, pharmacologic, or genetic inhibition of peripheral 5-HT synthesis via tryptophan hydroxylase 1 (Tph1) decreases hepatic FGF21 expression and plasma FGF21 levels in mice. Thus, perturbing central 5-HT signaling via 5-HT2CRs alters feeding behavior. Increased energy intake via a high-fat diet and/or high-carbohydrate diet can upregulate gut-derived 5-HT synthesis via Tph1. Peripheral 5-HT upregulates hepatic FGF21 expression and plasma FGF21 levels, leading to metabolic diseases such as obesity, insulin resistance, type 2 diabetes, and NAFLD. The 5-HT network in the brain-gut-liver axis regulates feeding signals and may be involved in the development and/or prevention of metabolic diseases.

The effectiveness of small heterodimer partner and FGF 19 levels in prediction of perinatal morbidity in intrahepatic cholestasis of pregnancy.

Fibroblast growth factor 19 (FGF19) and small heterodimer partner (SHP) are molecules responsible for controlling serum bile acid levels. We designed this study for evaluating the effects of FGF 19 and SHP in intrahepatic cholestasis of pregnancy (ICP). Fifty-six pregnant women having ICP and 20 healthy pregnant women were included in the study. The patients were followed up until delivery in terms of pregnancy-related morbidity/mortality. Serum FGF 19 and SHP levels were determined by enzyme-linked immunosorbent assay (ELISA). Serum FGF 19 and SHP levels were significantly higher in the patient group compared to the control group (p: .04, p: .003, respectively). In ROC analysis, SHP level above 1995 ng/L was found effective in predicting the need for neonatal intensive care unit (ICU) follow-up with 53.8% sensitivity and 77.8% specificity. High SHP levels were correlated with perinatal morbidity, mortality and neonatal ICU hospitalisation.Impact StatementWhat is already known on this subject? Itching, elevated serum transaminase and serum total bile acid (TBA) levels are the most important clinical and biochemical findings of intrahepatic cholestasis of pregnancy (ICP). Fibroblast growth factor 19 (FGF19) and small heterodimer partner (SHP) are molecules - responsible for controlling serum bile acid levels. ICP is associated with preterm labour, asphyxia, foetal distress, stillbirth and preeclampsia.What do the results of this study add? Serum FGF 19 and SHP levels were significantly higher in the patient group compared to the control group. High SHP level was found effective in predicting the need for neonatal intensive care unit and showed a negative correlation with birth week and birth weight.What are the implications of these findings for clinical practice and/or further research? Checking SHP levels can help to predict perinatal mortality and morbidity. Treatments to be developed through the mechanism of action of FGF 19 and SHP can be promising in the treatment of ICP and other cholestatic liver diseases.

Association of serum fibroblast growth factor 21 with diabetic complications and insulin dose in patients with type 1 diabetes mellitus.

INTRODUCTION: Fibroblast growth factor (FGF) 21 is an important regulator of glycemic control, but the association between circulating FGF21 and diabetic complications is poorly understood. Moreover, basal FGF21 secretion, especially in response to insulin dose, in patients with type 1 diabetes mellitus (T1DM), has not been well examined. Therefore, this study aimed to determine the association of circulating FGF21 levels with diabetic complications and insulin dosage in middle-aged and elderly patients with T1DM. MATERIALS AND METHODS: A total of 127 middle-aged and elderly patients with T1DM, including 68 patients with diabetic complications, and 106 non-diabetic individuals were analyzed in this cross-sectional study. Information on demographic characteristics and T1DM was extracted from their electronic medical records. Serum FGF21 levels were determined using ELISA. RESULTS: Serum FGF21 levels were significantly lower in T1DM patients (75.2 [37.4-135.1] pg/mL) than in non-diabetic participants (151.6 [92.0-224.6] pg/mL; P < 0.001). No diabetic complications were associated with serum FGF21 concentrations. Both basal and bolus insulin doses were significantly and positively correlated with serum FGF21 levels (P < 0.05). Stepwise multiple regression analysis showed that FGF21 level was associated with age and body mass index (P < 0.05), while the basal insulin dose was an independent positive predictor of serum FGF21 levels (ß = 0.197, P = 0.032). CONCLUSIONS: Circulating FGF21 levels are reduced in patients with T1DM; however, they are not associated with diabetic complications. In addition, aging, obesity, and insulin dosage are positive determinants of circulating FGF21.

Phosphaturic mesenchymal tumor: An underdiagnosed rare entity.

Tumor-induced osteomalacia is a paraneoplastic syndrome resulting in renal phosphate wasting and decreased bone mineralization. Phosphaturic mesenchymal tumors represent a rare etiology of tumor-induced osteomalacia. They are exceptionally rare, probably accounting for < 0.01% of all soft tissue tumors. Most PMTs present as small inapparent lesions that require very careful clinical examination and radionucleotide scan for localization. Here we describe a case in a 65 years old woman with recurrent multiple bone fractures and subsequent detection of a tumor involving right femur and adjacent soft tissue, low phosphate level and elevated serum Fibroblast growth factor-23 (FGF-23).

Elevated Serum Fibroblast Growth Factor 21 Is Relevant to Heart Failure Patients with Reduced Ejection Fraction.

OBJECTIVE: The aim of this study was to evaluate the roles of fibroblast growth factor 21 (FGF21) in heart failure patients with reduced ejection fraction and its association with Heart Failure with reduced Ejection Fraction (HFrEF). METHODS: The level of FGF21 was measured by enzyme-linked immunosorbent assay (ELISA) in 199 subjects enrolled in this study, including 128 subjects with HFrEF and 71 control subjects. The mean follow-up time was 13.36 months. The left ventricular end-diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF) percentage were evaluated by the 2D echocardiography. Serum brain natriuretic peptide (BNP) was measured in the routine clinical laboratory. RESULTS: The serum FGF21 level was evidently higher in patients with HFrEF than in the control group (228.72 ± 24.04 vs. 171.60 ± 12.98, p < 0.001). After 1 year of follow-up, 61 patients (47.66%) with heart failure were readmitted to the hospital, including 8 deaths (13.11%). The AUC of the receiver operating characteristic (ROC) curve for the predictive value of FGF21 for prognosis was 0.964. Kaplan-Meier analysis results showed that there were significant differences in the 1-year mortality and heart failure readmission events between the grouped subjects. A poor prognosis was correlated with the serum level of FGF21, BNP, LVEDD, and LVEF, which was confirmed by the univariate Cox analysis. CONCLUSION: FGF21 was independently associated with an increased risk of mortality and readmission HFrEF patients. Therefore, FGF21 has the potential to be a biomarker for the progression of HFrEF in patients.

Plasma FGF21 concentrations and spontaneous self-selection of protein suggest that 15% protein in the diet may not be enough for male adult rats.

Protein requirement has been determined at 10%-15% energy. Under dietary self-selection, rats ingest 25%-30% energy as protein and regulate FGF21 (a hormone signaling protein deficiency) to levels lower than those measured with a 15% protein (15P) diet. Our hypothesis is that if a 15P diet was indeed sufficient to ensure protein homeostasis, it is probably a too low protein level to ensure optimal energy homeostasis. Adult male Wistar rats were used in this study. The first objective was to determine the changes in food intake, body composition, and plasma FGF21, IGF-1, and PYY concentrations in rats fed 8P, 15P, 30P, 40P, or 50P diets. The second was to determine whether the FGF21 levels measured in the rats were related to spontaneous protein intake. Rats were fed a 15P diet and then allowed to choose between a protein diet and a protein-free diet. Food intake and body weight were measured throughout the experiments. Body composition was determined at different experimental stages. Plasma samples were collected to measure FGF21, IGF-1, and PYY concentrations. A 15P diet appears to result in higher growth than that observed with the 30P, 40P, and 50P diets. However, the 15P diet probably does not provide optimal progression of body composition owing to a tendency of 15P rats to fix more fat and energy in the body. The variable and higher concentrations of FGF21 in the 15P diet suggest a deficit in protein intake, but this does not appear to be a parameter reflecting the adequacy of protein intake relative to individual protein requirements.NEW & NOTEWORTHY Under dietary self-selection, rats choose to ingest 25%-30% of energy as protein, a value higher than the protein requirement (10%-15%). According to our results, this higher spontaneous intake reflects the fact that rats fed a 15% protein diet, compared with high-protein diets, tend to bind more fat and have higher concentrations of FGF21, a hormone signaling protein deficiency. A 15% protein diet appears to be sufficient for protein homeostasis but not for optimal energy homeostasis.

Circulating fibroblast growth factor 21 links hemodynamics with kidney function in middle-aged and older adults: A mediation analysis.

Altered hemodynamics are commonly observed in individuals with declining renal function; however, the pathophysiological mechanisms linking renal dysfunction and hemodynamics have not been fully elucidated. Fibroblast growth factor 21 (FGF21), which upregulates sympathetic nerve activity, can alter systemic hemodynamics, and its level can increase as renal function declines. This study aimed to determine the associations among circulating FGF21 levels, hemodynamics, and renal function in middle-aged and older adults. In a total of 272 middle-aged and older adults (age range: 46-83 years), estimated glomerular filtration rate (eGFR), hemodynamics (brachial and aortic blood pressure and aortic pulse wave velocity [PWV]), and serum FGF21 levels were measured. For mediation analysis, hemodynamic parameters were entered as outcomes. eGFR or log-transformed urinary albumin and creatinine ratio (UACR) and log-transformed serum FGF21 levels were set as the predictors and mediator, respectively. According to multivariable regression models after adjusting for potential covariates, serum FGF21 levels were significantly associated with brachial systolic blood pressure (ß = 0.140), pulse pressure (ß = 0.136), and aortic PWV (ß = 0.144). Mediation analyses showed that serum FGF21 levels significantly mediated the relationship of eGFR with brachial systolic blood pressure (indirect effect [95% confidence interval]: -0.032 [-0.071, -0.002]), pulse pressure (-0.019 [-0.041, -0.001]), and aortic PWV (-0.457 [-1.053, -0.021]) and the relationship of UACR with aortic PWV (7.600 [0.011, 21.148]). These findings suggest that elevated circulating FGF21 levels partially mediate the association of elevated blood pressure and/or aortic stiffness with renal dysfunction in middle-aged and older adults.

Mice with high FGF21 serum levels had a reduced preference for morphine and an attenuated development of acute antinociceptive tolerance and physical dependence.

Because of increased opioid misuse, there is a need to identify new targets for minimizing opioid tolerance, and physical and psychological dependence. Previous studies showed that fibroblast growth factor 21 (FGF21) decreased alcohol and sweet preference in mice. In this study, FGF21-transgenic (FGF21-Tg) mice, expressing high FGF21 serum levels, and wildtype (WT) C57BL/6J littermates were treated with morphine and saline to determine if differences exist in their physiological and behavioral responses to opioids. FGF21-Tg mice displayed reduced preference for morphine in the conditioned place preference assay compared to WT littermates. Similarly, FGF21-Tg mice had an attenuation of the magnitude and rate of acute morphine antinociceptive tolerance development, and acute and chronic morphine physical dependence, but exhibited no change in chronic morphine antinociceptive tolerance. The ED50 values for morphine-induced antinociception in the 55 °C hot plate and the 55 °C warm-water tail withdrawal assays were similar in both strains of mice. Likewise, FGF21-Tg and WT littermates had comparable responses to morphine-induced respiratory depression. Overall, FGF21-Tg mice had a decrease in the development of acute analgesic tolerance, and the development of physical dependence, and morphine preference. FGF21 and its receptor have therapeutic potential for reducing opioid withdrawal symptoms and craving, and augmenting opioid therapeutics for acute pain patients to minimize tolerance development.