Changes In Fibroblast Growth Factor Research Articles

Dynamic changes of fibroblast growth factor 21 levels in response to acute and chronic alcohol consumption

Dynamic changes of fibroblast growth factor 21 levels in response to acute and chronic alcohol consumption

Systemic Parameters of the Renin-Angiotensin-Aldosterone System Remain Unaffected by Changes in Fibroblast Growth Factor 23 Levels in Hemodialysis Patients

Systemic Parameters of the Renin-Angiotensin-Aldosterone System Remain Unaffected by Changes in Fibroblast Growth Factor 23 Levels in Hemodialysis Patients

Hypophosphataemia, fibroblast growth factor 23 and third-generation intravenous iron compounds: a narrative review.

Third-generation intravenous (i.v.) iron preparations are safe and efficacious and are increasingly used in the treatment of iron-deficiency anaemia. Hypophosphataemia is emerging as an established side-effect following the administration of certain compounds. Symptoms of hypophosphataemia can be masked by their similarity to those of iron-deficiency anaemia and both acute and chronic hypophosphataemia can be detrimental. Hypophosphataemia appears to be linked to imbalances in the metabolism of the phosphatonin fibroblast growth factor 23. In this narrative review, we discuss the possible pathophysiology behind this phenomenon, the studies comparing third-generation i.v. iron compounds, and the potential implications of the changes in fibroblast growth factor 23 and hypophosphataemia. We also present an algorithm of how to approach such patients requiring i.v. iron in anticipation of hypophosphataemia and how the impact related to it can be minimized.

Effect of High Intensity Interval Training on the Level of Atrial Fibrillation, Fibroblast Growth Factor 23 and Klotho Protein in Male Rats with Renal Failure

Introduction: Cardiovascular problems and atrial fibrillation is one of the most prevalent secondary consequences in hemodialysis patients. This study aimed to examine the effect of high intensity interval training on the level of atrial fibrillation, fibroblast growth factor 23 and Klotho in male rats with chronic kidney disease. Methods: In this study, 30 male rats Wistar (7-8 weeks) were randomly assigned into three groups of exercise, control and sham. Rats in the exercise and control groups were entered to the study by using nephrectomy 5/6Nx, which made renal failure. Exercise protocol included training protocol as high intensity interval training (85% Maximum oxygen consumption) on treadmill for 8 weeks and three sessions in each week. Atrial fibrillation, fibroblast growth factor 23, Klotho, and other parameters were examined at the post intervention in all three groups. Data analysis was performed by one-way ANOVA and to examine the difference between groups, followed post-hoc Bonferroni analysis test at P <0.05. Results: Interval training was able to make a significant difference between the exercise and control groups in the level of atrial fibrillation (P<0/05). Klotho protein also had a considerable increase in the exercise group compared to the control group. However, the fibroblast growth factor 23 did not differ significantly between the exercise and control groups (P>0/05). Conclusion: High intensity interval training can cause a significant decrease in the level of atrial fibrillation in chronic kidney patients; however, in the process of this improvement, the changes in fibroblast growth factor 23 and related factors are less and the role of Klotho protein has an important effect.

Changes in Fibroblast Growth Factor 23 and Soluble Klotho Levels After Hemodialysis Initiation

Rationale & ObjectivePatients with chronic kidney failure have markedly elevated fibroblast growth factor 23 (FGF-23) levels and decreased soluble Klotho levels. However, no studies have examined the effects of hemodialysis initiation on the levels of these hormones and other parameters of mineral metabolism.Study DesignProspective single-arm study.Setting & Participants20 individuals with incident kidney failure initiating hemodialysis.ExposureInitiation of hemodialysis. Dose adjustments of phosphate binders and vitamin D receptor activators and use of calcimimetics, erythropoiesis-stimulating agents, and intravenous iron were prohibited.OutcomesChanges in serum levels of FGF-23, soluble Klotho, and other biochemical parameters of mineral metabolism, measured before and after each hemodialysis session, for a total of 4 sessions over 5 days.Analytical ApproachRepeated-measures analysis of variance.ResultsAt baseline, participants had 18-fold higher median FGF-23 levels and 1.6-fold lower mean soluble Klotho levels compared with age- and sex-matched healthy individuals. Initiation of hemodialysis led to progressive reductions in serum phosphorus, intact parathyroid hormone, and FGF-23 levels, with dialysis-related fluctuations. No reductions were observed in levels of α1-microglobulin, which has molecular weight comparable to FGF-23. The magnitude of the FGF-23 level reductions was strongly associated with concomitant changes in serum phosphorus levels but not with the changes in intact parathyroid hormone levels. Soluble Klotho levels did not change after the initiation of hemodialysis.LimitationsSingle-arm design, small sample size, short follow-up period.ConclusionsInitiation of hemodialysis in patients with chronic kidney failure led to progressive reductions in FGF-23 levels in association with reductions in serum phosphorus levels. These results suggest that phosphorus is a strong inducer of FGF-23 production and that regulation of FGF-23 production is a rapid process.

ВПЛИВ ФАКТОРУ РОСТУ ФІБРОБЛАСТІВ 19 НА СТАН ВУГЛЕВОДНОГО ОБМІНУ У ХВОРИХ НА ЦУКРОВИЙ ДІАБЕТ 2 ТИПУ З СУПУТНЬОЮ БІЛІАРНОЮ ПАТОЛОГІЄЮ


 
 
 This article analyzes the changes of fibroblast growth factor 19 (FRF-19) in serum content and presence of the connections between this marker and carbohydrate metabolism in patients with diabetes mellitus type 2 and chronic cholecystitis, as well as in patients with isolated chronic cholecystitis. 34 patients with type 2 diabetes mellitus and concomitant chronic cholecystitis and 31 patients with isolated chronic cholecystitis were examined in the gastroenterologic and endocrinological departments of «Regional Clinical Hospital» (Kharkiv, Ukraine). Determination of FRF-19 level was carried out by enzyme immunoassay. In patients with combined course of type 2 diabetes mellitus and concomitant chronic cholecystitis, there is a significant decrease in serum FRF-19 concentration, an increase in glycemia, insulinemia and insulin resistance, determined by the HOMA index, compared with patients with isolated chronic cholecystitis, in whom high concentrations of FRF-19 were accompanied by no disturbance of carbohydrate metabolism.
 
 

Changes in FGF-23, Neutrophil/Platelet Activation Markers, and Angiogenin in Advanced Chronic Kidney Disease and Their Effect on Arterial Stiffness

Aims: The aims of this study were to measure changes in fibroblast growth factor 23 (FGF-23), neutrophil (elastase, lactoferrin)/platelet activation marker (mean platelet volume-to-platelet count ratio [MPR]), and angiogenin according to the stage of chronic kidney disease (CKD), and to evaluate the association of FGF-23, elastase, lactoferrin, MPR, and angiogenin with arterial stiffness using brachial-ankle pulse wave velocity (ba-PWV) in CKD patients. Methods: According to the estimated glomerular filtration rate (eGFR) calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, the patients were allocated to five groups: (1) normal controls (eGFR ≥90 mL/min/1.73 m2 without pathologic, urine [proteinuria], blood [electrolyte], and imaging abnormalities; n = 22); (2) CKD stage 2 (eGFR 60–89 mL/min/1.73 m2; n = 17); (3) CKD stage 3 (eGFR 30–59 mL/min/1.73 m2; n = 22); (4) CKD stage 4 (eGFR 15–30 mL/min/1.73 m2; n = 17); and (5) CKD stage 5-hemodialysis (HD) (n = 30). All the patients were free of clinically apparent cardiovascular disease. Serum FGF-23, elastase, lactoferrin, and angiogenin concentrations and the MPR were measured to study the association of the above parameters with the clinical (age, sex, presence of diabetes mellitus, and blood pressure), biochemical (calcium, phosphorus, uric acid, intact parathyroid hormone [PTH], low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein), and ba-PWV values of the CKD patients. Results: (1) The mean ba-PWV values were 1,497.2 ± 206.4 cm/s in the controls, 1,649.0 ± 247.9 cm/s in the CKD stage 2 group (p < 0.05 vs. controls), 1,655.8 ± 260.3 cm/s in the CKD stage 3 group (p < 0.05 vs. controls), 1,823.0 ± 402.4 cm/s in the CKD stage 4 group (p < 0.05 vs. controls and CKD stages 2 and 3), and 1,905.2 ± 374.1 cm/s in the CKD stage 5-HD group (p < 0.05 vs. controls and CKD stage 2). (2) The mean log10(FGF-23) concentration values were 0.77 ± 0.27, 0.97 ± 0.48, 1.10 ± 0.35 (p < 0.05 vs. controls and CKD stage 2), 1.35 ± 0.48 (p < 0.05 vs. controls and CKD stages 2 and 3), and 2.12 ± 0.82 (p < 0.05 vs. controls and CKD stages 2–4); the mean angiogenin levels were 230.6 ± 70.5 pg/mL, 283.0 ± 53.5 pg/mL (p < 0.05 vs. controls), 347.3 ± 76.9 pg/mL (p < 0.05 vs. controls and CKD stage 2), 445.9 ± 90.6 pg/mL (p < 0.05 vs. controls and CKD stages 2 and 3), and 370.9 ± 142.4 pg/mL (p < 0.05 vs. controls and CKD stages 2 and 3). (3) In the stage 3–4 CKD/HD patients, the mean elastase-to-neutrophil and lactoferrin-to-neutrophil ratios were significantly lower than in the controls and the stage 2 CKD patients. (4) Our multivariate linear regression analyses showed that age, pulse pressure, mean arterial pressure, PTH, and FGF-23 were independently associated with ba-PWV values. Conclusions: Circulating FGF-23 and angiogenin concentrations gradually increased as CKD advanced, whereas neutrophil activation markers were significantly lower in the stage 3–4 CKD/HD patients than in the controls and stage 2 CKD patients. FGF-23 was weakly associated with ba-PWV values in patients with CKD/HD and no previous cardiovascular disease.

Role of fibroblast growth factor 23 in the development of cardiovascular diseases in patients with end-stage renal failure on programmed hemodialysis

To determine the nature of changes in fibroblast growth factor 23 (FGF-23) and other bone mineral metabolism parameters detectable in the blood of patients with end-stage chronic renal failure (CRF) and to analyze their links to the development of cardiovascular events in uremic intoxication. A total of 75 patients (45 men and 30 women) aged 23 to 66 years (mean age, 53±2.1 years) with Stage VD CKF were examined. The levels of parathyroid hormone (PTH), calcium, phosphorus, the morphogenetic protein FGF-23, and the cardiospecific protein troponin I were investigated. Doppler echocardiography was performed on an Aloka 4000 machine. Left ventricular (LV) mass index (LVMI), LV systolic and diastolic function, and peak systolic blood flow velocity in the aortic arch (Vps) were estimated. As LVMI became higher, there were increases in the level of PTH and that of FGF-23 that plays a significant role in the processes of bone remodeling and vascular calcification. Analysis of correlations between a change in FGF-23 concentrations depending on the morphological and functional parameters of the cardiovascular system (CVS) revealed a strong direct correlation between FGF-23 levels and LVMI (r=0.746; p<0.01), a significant inverse correlation between FGF-23 and ejection fraction (r=-0.901; p<0.05), and a direct correlation of FGF-23 and troponin I (r=0.544; p<0.05). FGF-2 increasing from moderate to very high levels indicates that there is a high risk for remodeling processes in the CVS even in the absence of baseline echocardiographic signs of myocardial hypertrophy, normal aortic pulse wave velocity, and compensation of other risk factors, such as hypertension, uremia, hyperparathyroidism, even without increasing the markers of cardiovascular events, such as hyperphosphatemia. The elevated level of FGF-23 suggests that there is a need for cardioprotective therapy, the goal of which is to correct of the level of this factor.

Changes in fibroblast growth factor 9 mRNA in granulosa and theca cells during ovarian follicular growth in dairy cattle.

Fibroblast growth factor 9 (FGF9) has been suggested to act as an antidifferentiation factor in cattle by reducing steroidogenesis and increasing cell proliferation in granulosa (GC) and theca (TC) cells. The objective of this study was to characterize FGF9 mRNA abundance in GC and TC during development of dominant follicles in dairy cattle. Estrous cycles of nonlactating dairy cattle were synchronized, and ovaries were collected on either d 3 to 4 (n=8) or 5 to 6 (n=8) postovulation for GC and TC RNA extraction from small (1-5mm), medium (5.1-8mm), and large (8.1-18mm) follicles for PCR analysis. The FGF9 mRNA abundance was greater in GC than in TC. In GC, FGF9 mRNA abundance was greater in small, medium, and large estrogen-inactive [i.e., concentrations of estradiol (E2)<progesterone (P4)] follicles than in large E2-active (i.e., concentrations of E2>P4) follicles at both early (d 3-4) and late (d 5-6) growing phases of first dominant follicle. Abundance of FGF9 mRNA increased in medium-sized follicles from early to late growing phase of the dominant follicle. In TC, FGF9 mRNA abundance was greater in large E2-inactive follicles than in large E2-active follicles on d 3 to 4 postovulation; no significant differences in TC FGF9 mRNA existed among follicle types on d 5 to 6 postovulation. Correlations among levels of follicular fluid hormones and FGF9 mRNA levels revealed significant negative correlations between GC FGF9 mRNA abundance and follicular fluid E2 (r=-0.68), free IGF-1 (r=-0.63), and E2-to-P4 ratio (r=-0.58). In summary, abundance of FGF9 mRNA in GC and TC increases in medium-sized follicles during development of dominant follicles and is less in dominant E2-active than subordinate E2-inactive follicles, suggesting that FGF9 signaling could contribute to normal follicle development and steroidogenesis in dairy cattle.

Significantly higher peripheral fibroblast growth factor-2 levels in patients with major depressive disorder: A preliminary meta-analysis under MOOSE guidelines.

In vivo and in vitro studies demonstrate the important roles of fibroblast growth factor (FGF) and FGF receptors (FGFRs) in neural survival, neurogenesis, oxidative stress, and emotional behavior. However, evidence on the role of FGF and FGFR in the pathophysiology of major depressive disorder (MDD) remains limited and inconclusive. This preliminary meta-analysis aimed to examine changes in peripheral or central FGF and FGFR levels in patients with MDD. Electronic research through platform of PubMed and ClinicalTrials.gov. We used the inclusion criteria: articles discussing the comparisons of FGF levels, either in peripheral or central environment, in patients with MDD and in healthy controls (HC); articles on clinical trials in humans; and case-control trials. Case reports or series and nonclinical trials were excluded. Using a thorough literature search, the FGF/FGFR levels in patients with MDD and HC were compared. Four studies on peripheral FGF-2 and 3 on central FGF-2 and FGFR1 levels were included. The findings reveal significantly higher peripheral FGF-2 protein and central FGFR1 RNA levels in patients with MDD than in HC (P = 0.005 and 0.006, separately), but no significant association with clinical variables. There was also no significant difference in the central FGF-2 levels in patients with MDD and in HC (P = 0.180). The study has limitations of a small number of included studies, lack of meta-analysis of the FGF changes along with treatment, and lack of direct evidence on correlation of peripheral FGF-2 with central FGF-2 levels. This preliminary meta-analysis points out a new direction for future studies investigating the relationship among MDD, oxidative stress, and the FGF family.

FGF 19 and Bile Acids Increase Following Roux-en-Y Gastric Bypass but Not After Medical Management in Patients with Type 2 Diabetes

This study aims to quantify changes in fibroblast growth factor 19 (FGF19) and bile acids (BAs) in patients with uncontrolled type 2 diabetes randomized to Roux-en-Y gastric bypass (RYGB) vs intensive medical management (IMM) and matched for similar reduction in HbA1c after 1 year of treatment. Blood samples were drawn from patients who underwent a test meal challenge before and 1 year after IMM (n = 15) or RYGB (n = 15). Mean HbA1c decreased from 9.7 to 6.4% after RYGB and from 9.1 to 6.1% in the IMM group. At 12 months, the number of diabetes medications used per subject in the RYGB group (2.5 ± 0.5) was less than in the IMM group (4.6 ± 0.3). After RYGB, FGF19 increased in the fasted (93 ± 15 to 152 ± 19 pg/ml; P = 0.008) and postprandial states (area under the curve (AUC), 10.8 ± 1.9 to 23.4 ± 4.1 pg × h/ml × 10(3); P = 0.006) but remained unchanged following IMM. BAs increased after RYGB (AUC ×10(3), 6.63 ± 1.3 to 15.16 ± 2.56 μM × h; P = 0.003) and decreased after IMM (AUC ×10(3), 8.22 ± 1.24 to 5.70 ± 0.70; P = 0.01). No changes were observed in the ratio of 12α-hydroxylated/non-12α-hyroxylated BAs. Following RYGB, FGF19 AUC correlated with BAs (r = 0.54, P = 0.04) and trended negatively with HbA1c (r = -0.44; P = 0.09); these associations were not observed after IMM. BA and FGF19 levels increased after RYGB but not after IMM in subjects who achieved similar improvement in glycemic control. Further studies are necessary to determine whether these hormonal changes facilitate improved glucose homeostasis.

Igfbp2 Deletion in Ovariectomized Mice Enhances Energy Expenditure but Accelerates Bone Loss.

Previously, we reported sexually dimorphic bone mass and body composition phenotypes in Igfbp2(-/-) mice (-/-), where male mice exhibited decreased bone and increased fat mass, whereas female mice displayed increased bone but no changes in fat mass. To investigate the interaction between IGF-binding protein (IGFBP)-2 and estrogen, we subjected Igfbp2 -/- and +/+ female mice to ovariectomy (OVX) or sham surgery at 8 weeks of age. At 20 weeks of age, mice underwent metabolic cage analysis and insulin tolerance tests before killing. At harvest, femurs were collected for microcomputed tomography, serum for protein levels, brown adipose tissue (BAT) and inguinal white adipose tissue (IWAT) adipose depots for histology, gene expression, and mitochondrial respiration analysis of whole tissue. In +/+ mice, serum IGFBP-2 dropped 30% with OVX. In the absence of IGFBP-2, OVX had no effect on preformed BAT; however, there was significant "browning" of the IWAT depot coinciding with less weight gain, increased insulin sensitivity, lower intraabdominal fat, and increased bone loss due to higher resorption and lower formation. Likewise, after OVX, energy expenditure, physical activity and BAT mitochondrial respiration were decreased less in the OVX-/- compared with OVX+/+. Mitochondrial respiration of IWAT was reduced in OVX+/+ yet remained unchanged in OVX-/- mice. These changes were associated with significant increases in Fgf21 and Foxc2 expression, 2 proteins known for their insulin sensitizing and browning of WAT effects. We conclude that estrogen deficiency has a profound effect on body and bone composition in the absence of IGFBP-2 and may be related to changes in fibroblast growth factor 21.

Fibroblast growth factor 23 in acute kidney injury.

To review the emerging literature on changes in fibroblast growth factor 23 (FGF23) levels in the setting of acute kidney injury (AKI). Studies suggest that FGF23 levels are elevated in patients with AKI and correlate with increased risk of death or need for dialysis in adults, or prolonged ventilation time and higher fluid gain in children. Animal studies have shown that the cause behind this FGF23 increase is multifactorial and includes increased production in bone and decreased clearance, but not vitamin D or parathyroid hormone (PTH) activated pathways. Interestingly, FGF23 levels are found to be mildly elevated even in hospitalized patients without kidney injury, although this observation may be limited to only c-terminal FGF23 fragments. The prognostic implications of an elevated FGF23 value in patients with AKI need to be confirmed in larger cohorts and evaluated for long-term outcomes such as the development of new chronic kidney disease (CKD) or CKD progression, as well as cardiovascular disease, similar to the studies of FGF23 in the prevalent CKD population. FGF23 levels are elevated in patients with AKI and are associated with morbidity and mortality in small human studies. Mechanistic work in animals suggests that the elevation is independent of PTH or vitamin D signaling pathways. Much work remains to understand the physiology behind FGF23 elevation and the long-term effects of FGF23 in AKI.

Correlations and time course of FGF23 and markers of bone metabolism in maintenance hemodialysis patients

ObjectiveParathyroid hormone (iPTH) and fibroblast growth factor 23 (FGF23) are elevated in secondary hyperparathyroidism. In hemodialysis, higher dialysate calcium (1.5mmol/L) induces intradialytic suppression of iPTH, whereas its impact on FGF23 and markers of bone metabolism is unknown. We assessed the time course of FGF23 and markers of bone metabolism in relationship to dialysate calcium. Design and methodsIn this prospective cohort study of 19 patients on maintenance hemodialysis, we measured serum calcium (sCa), inorganic phosphate (iP), blood urea nitrogen (BUN), β2-microglobulin (ßMG), iPTH, FGF23, aminoterminal propeptide type 1 procollagen (P1NP), C-telopeptide of type I collagen for bone degradation (CTX-I), osteocalcin (OC), bone specific alkaline phosphatase (BALP), and tartrate-resistant acid phosphatase (TRAP5b) during a single hemodialysis session at baseline, 1, 2, and 3h of dialysis. The time course of measured parameters was compared according to groups of prescribed dialysate calcium of 1.25mmol/L and 1.5mmol/L. ResultsiPTH declined in the 1.5mmol/L dialysis group as serum calcium increased whereas it tended to increase in the 1.25mmol/L group without significant changes in serum calcium. Patients on long-term dialysate calcium of 1.5mmol/L had significantly lower CTX-I levels and tended to lower levels of iPTH, FGF23, OC, P1NP and TRAP5b at the start of dialysis compared to those on 1.25mmol/L. CTX-I, FGF23 and OC but not BALP, P1NP and TRAP5b decreased during dialysis independent of dialysate calcium. ConclusionsIn spite of immediate effects on iPTH, dialysate calcium does not acutely affect other parameters of bone and mineral metabolism. Short summaryDialysate calcium concentration is known to have both immediate and longer-term impact on parathyroid hormone levels in hemodialysis patients. Little is known about the acute impact of dialysate calcium on bone metabolism. In this cross-sectional study of prevalent hemodialysis patients, we found no evidence of immediate short-term dialysate calcium-induced changes of fibroblast growth factor 23 or anabolic and catabolic markers of bone turnover during hemodialysis. However, differences in CTX-I and to a lesser extent other parameters between groups of higher and lower dialysate calcium suggest a longer-term effect that remains to be validated.

The Changes of Muscle FGF-6 Expression at Different Time Points after Exercise-induced Muscle Damage.

To investigate the changes of fibroblast growth factor (FGF)-6 expression in the regeneration and repair process after exercise-induced muscle damage (EIMD) and the relationship with skeletal muscle regeneration and repair. The expression of FGF-6 at different time points was examined by reverse transcription-polymerase chain reaction (PCR) and immunohistochemistry staining after a downhill treadmill exercise. Skeletal muscle injury and regeneration at different times after EIMD was assessed by haematoxylin and eosin (H and E) staining. The FGF-6 protein expression was initially elevated and followed by a gradual reduction, while the changes of FGF-6 mRNA were almost all raised after the treadmill exercise. The results point out that FGF-6 is closely related to skeletal muscle regeneration and repair, probably implying a dual function in muscle regeneration.

How does the motor relearning program improve neurological function of brain ischemia monkeys?

The motor relearning program can significantly improve various functional disturbance induced by ischemic cerebrovascular diseases. However, its mechanism of action remains poorly understood. In injured brain tissues, glial fibrillary acidic protein and neurofilament protein changes can reflect the condition of injured neurons and astrocytes, while vascular endothelial growth factor and basic fibroblast growth factor changes can indicate angiogenesis. In the present study, we induced ischemic brain injury in the rhesus macaque by electrocoagulation of the M1 segment of the right middle cerebral artery. The motor relearning program was conducted for 60 days from the third day after model establishment. Immunohistochemistry and single-photon emission CT showed that the numbers of glial fibrillary acidic protein-, neurofilament protein-, vascular endothelial growth factor- and basic fibroblast growth factor-positive cells were significantly increased in the infarcted side compared with the contralateral hemisphere following the motor relearning program. Moreover, cerebral blood flow in the infarcted side was significantly improved. The clinical rating scale for stroke was used to assess neurological function changes in the rhesus macaque following the motor relearning program. Results showed that motor function was improved, and problems with consciousness, self-care ability and balance function were significantly ameliorated. These findings indicate that the motor relearning program significantly promoted neuronal regeneration, repair and angiogenesis in the surroundings of the infarcted hemisphere, and improve neurological function in the rhesus macaque following brain ischemia.

Randomized Trial Assessing the Effects of Ergocalciferol Administration on Circulating FGF23

Fibroblast growth factor 23 is a phosphate- and vitamin D-regulating hormone. The objective of this study was to determine the effect of ergocalciferol administration on fibroblast growth factor 23 levels in healthy vitamin D-deficient subjects. In this 12-week trial conducted in a clinical research center, 18- to 45-year-old subjects (n=90) with 25-hydroxyvitamin D levels ≤20 ng/ml (by chemiluminescent immunoassay) were randomized to weekly ergocalciferol treatment of 50,000 international units or placebo, while consuming a self-selected diet. Changes in fibroblast growth factor 23, 25-hydroxyvitamin D (by liquid chromatography/tandem mass spectroscopy), 1,25-dihydroxyvitamin D, parathyroid hormone, and serum phosphate were measured. Mean 25-hydroxyvitamin D (P<0.0001), 1,25-dihydroxyvitamin D (P=0.01), and fibroblast growth factor 23 (P=0.003) increased in the treatment versus placebo group. In the treatment group, 25-hydroxyvitamin D increased from 18 ± 7 to 40 ± 12 ng/ml at week 4 (P<0.0001) and remained stable at 43 ± 12 ng/ml at week 12 (P<0.0001); 1,25-dihydroxyvitamin D increased from 42 ± 17 to 52 ± 18 pg/ml at week 4 (P<0.001) and then remained stable, and fibroblast growth factor 23 increased from 43 ± 17 to 60 ± 33 pg/ml at week 8 (P=0.001) and 74 ± 42 pg/ml at week 12 (P<0.0001). Urinary phosphate excretion increased within the treatment group, but parathyroid hormone and serum phosphate were unchanged. Ergocalciferol administration increases circulating fibroblast growth factor 23. When measuring fibroblast growth factor 23, concurrent 25-hydroxyvitamin D measurements should be obtained, because vitamin D deficiency may lower circulating fibroblast growth factor 23 levels.

Changes in fibroblast growth factor 23 during treatment of secondary hyperparathyroidism with alfacalcidol or paricalcitol

Fibroblast growth factor 23 (FGF23) increases renal phosphate excretion and decreases the formation of 1,25 dihydroxyvitamin D. In patients with chronic kidney disease, plasma FGF23 levels are markedly elevated by unknown mechanisms. We explored the changes in FGF23 during treatment of secondary hyperparathyroidism (SHPT) with alfacalcidol or paricalcitol in haemodialysis patients. Intravenous alfacalcidol and paricalcitol were compared in haemodialysis patients with SHPT in a randomized 2 × 16-week cross-over study, with 6 weeks washout period preceding treatment and between treatment periods. In 57 of the enrolled patients, blood samples were frozen before and after each treatment period and available for measurement of FGF23. Treatment with both analogues increased FGF23 (P < 0.05 in all treatment periods). The magnitude of increase was similar for alfacalcidol and paricalcitol (Period 1: 223 versus 314%; P = 0.384 and Period 2: 174 versus 227%; P = 0.510) and the levels returned to pre-treatment levels during the washout period. Independent predictors of rise in FGF23 were baseline levels of FGF23 (P < 0.01), changes in ionized calcium (P < 0.01) and phosphate (P < 0.01) and cumulative dose of vitamin D analogues (P = 0.024). Alfacalcidol and paricalcitol increase the plasma levels of FGF23 equally and substantially in haemodialysis patients.

Changes in Fibroblast Growth Factor 21 with Modest Weight Loss

Fibroblast growth factor 21 (FGF21) - one of several atypical fibroblast growth factors with endocrine hormone functions - has been shown to stimulate insulin-mediated glucose uptake in adipocytes and to increase fat utilization and energy expenditure. FGF21 concentrations appear to be greater in obese and insulin resistant individuals; however, information on the FGF21 response to modest weight loss is scant. PURPOSE: The objectives of this investigation were to characterize the effects of modest weight loss on circulating concentrations of FGF21 and to determine relationships between FGF21 and changes in body composition and insulin sensitivity in obese men. METHODS: Nine obese men (age = 41.5 +/- 7.1; weight = 101.7 +/- 21.0 kg; BMI = 32.8 +/- 3.6 kg/m2; body fat = 35 +/- 4%) were assigned to exercise and dietary restriction in order to reach a targeted weight loss of 8 to 10% of initial body weight over a 6 to 10-month period. Blood samples were analyzed for glucose, insulin and clinical markers of insulin sensitivity; FGF21, non-esterified fatty acids, adiponectin, interleukin-6 and tumor necrosis factor-alpha concentrations; and myeloperoxidase activity (MPOa) at regular weight loss intervals (2-4%, 4-6%, 6-8% and target weight loss). RESULTS: Body fat decreased by 4% (p < 0.0001) and lean mass decreased by 3% (p < 0.0001) with the targeted weight loss. Markers of insulin sensitivity (HOMA = -28.6%; glucose/insulin ratio = +17.9%) were improved with as little as 4-6% weight-loss (p < 0.0006). FGF21 was significantly reduced with 2-4% weight loss and decreased by 57.3% with target weight loss (p = 0.0051). Changes in total lean mass and fat mass were not correlated, but together accounted for 36% of the variation in FGF21 (p < 0.0001). The improved insulin sensitivity with weight loss was not correlated with changes in FGF21 or to changes in lean and fat mass. CONCLUSIONS: Modest weight loss resulted in improved insulin sensitivity and a decrease in FGF21 concentrations. Measurable changes in lean and fat mass, FGF21, and insulin sensitivity do not appear to occur simultaneously with weight loss. Funded by an Alabama Agriculture Experiment Station Foundation Grant

Pancreatic Development and Disease

Pancreatic Development and Disease