Serum FGF23 Levels Research Articles

2255. Fibroblast Growth Factor 23, a Potential Risk Factor for Cardiovascular Diseases Is Associated with Abacavir/Lamivudine Use in HIV Patients

BackgroundThe fibroblast growth factor (FGF) 23 is a hormone-like molecule that secretes from osteoblasts and has the function of suppressing the reabsorption of phosphorus in the distal renal tubule and lowering serum phosphorus. It has been shown that renal dysfunction increases serum FGF23 levels. Although the mechanism remains to be determined, it is also reported that the elevation of serum FGF23 might increase the risk of coronary vascular diseases (CVD). Nevertheless, there are very few reports related to FGF23 in patients with HIV. The goal of the present study was to investigate the relationship between serum FGF23 levels and clinical factors HIV patients.MethodsMale HIV patients who visited the outpatient clinic of Teikyo University Hospital, Tokyo, Japan in 2015 and had been treated with anti-retroviral therapy for more than six months were enrolled. In addition to serum FGF23, clinical factors were also collected, including age, ART regimens, and laboratory data, and Framingham Coronary Heart Disease Risk Score (FHS). To study correlations with FGF23, spearman coefficients was used. To identify factors independently related with FGF23, multiple regression analysis was used.ResultsSixty-seven patients were enrolled. The median age was 43.7 years old. Median CD4 cell counts was 529/μL, and the median serum FGF 23 level was 36.0 pg/mL. According to spearman coefficients, serum FGF23 levels correlated with HIV RNA > 50 copies (r = 0.3911, P = 0.0011), serum cystatin C level (r = 0.3199, P = 0.0097), and some specific anti-HIV drugs; abacavir (ABC)/lamivudine (3TC) use (r = 0.3345, P = 0.0057). FHS was not correlated (P = 0.9655). According to multiple regression analysis, ABC/3TC use (P = 0.00990) and HIV RNA >50 copies (P = 0.00002) were significant factors related with the increase of serum FGF23 levels.ConclusionPoor virological control and ABC/3TC use were significant factors that elevated serum FGF23 levels. Considering that ABC/3TC is a well-known factor in the increase of the risk of CVD, FGF23 might be one of the factors that increases the risk of CVD in HIV patients receiving ABC/3TC, though FGF23 was not significantly related with FHS in our all study patients.Disclosures All authors: No reported disclosures.

Correlations between serum concentration of three bone-derived factors and obesity and visceral fat accumulation in a cohort of middle aged men and women

BackgroundThe aim of this study was to investigate the interrelationships between three bone-derived factors [serum osteocalcin (OCN), fibroblast growth factor (FGF) 23, and neutrophil gelatinase-associated lipocalin (NGAL) levels] and body fat content and distribution, in order to reveal the potential endocrine function of bone in the development of obesity.MethodsWe recruited 1179 people (aged 59.5 ± 6.2 years) from communities in Shanghai. Serum OCN levels were determined using an electrochemiluminescence immunoassay. Serum FGF23 and NGAL levels were determined using a sandwich enzyme-linked immunosorbent assay. The abdominal fat distribution, including visceral fat area (VFA), was assessed by magnetic resonance imaging. Visceral obesity was defined as a VFA ≥ 80 cm2.ResultsSerum OCN levels were inversely correlated with body fat parameters, while FGF23 and NGAL were positively correlated (P < 0.05). After adjusting for confounders, waist circumference (W) and VFA had a closer relationship with serum OCN, FGF23, and NGAL levels than body mass index (BMI) and body fat percentage (fat%, all P < 0.05). The risk of visceral obesity significantly increased with higher FGF23 and/or NGAL levels, as well as with reduced OCN levels (all P < 0.05). In addition, serum OCN, FGF23, and NGAL levels were independently associated with visceral obesity (all P < 0.01). The relationships persisted among subjects with normal glucose tolerance or subjects with hyperglycaemia (both P < 0.05).ConclusionsCompared to the indicators of overall adiposity such as BMI or fat%, visceral adiposity indicators (W or VFA) were more closely related to serum OCN, FGF23 and NGAL levels. There was no interaction among the relationship of three bone-derived factors with visceral obesity, which revealed the independent relationship of endocrine function of skeleton with body fat.

A1328 Effect of salt intervention on serum levels of FGF23 in Chinese adults

A1328 Effect of salt intervention on serum levels of FGF23 in Chinese adults

A3155 A2A Receptor Attenuates Hypertensive Cardiac Remodeling via Promoting Brown Adipose Tissue-Derived FGF21

Objectives: Recent studies demonstrate that adipose tissue-derived adipokines are involved in the regulation of hypertensive heart disease. However, the molecular mechanism underlying the endocrine role of BAT in pathological cardiac remodeling remains unknown. Methods: WT or adenosine A2A receptor (A2AR) KO mice were randomly assigned to sham group or deoxycorticosterone acetat (DOCA)-salt group. In order to determine whether the protective role of A2AR against hypertensive cardiac remodeling is BAT dependent, the interscapular BAT (iBAT) was surgically deleted and these mice were intraperitoneally injected with rFGF21 protein. For transplantation, 0.2 g iBAT obtained from donor WT or A2ARKO mice was immediately transplanted into the intrascapular region of recipient mice after iBAT depletion. iBAT CT imaging and 3D Reconstruction was obtained through X-Rays Acquire mode after intravenously injected with micellar SRFluor680 6–8 hours. The cardiac function of DOCA-salt mice was detected by echocardiography and the expressional diversity of related markers were detected by PCR and western blot. Results: We show that A2ARKO caused iBAT dysfunction, leading to accelerated cardiac fibrosis in hypertensive mice. A2AR activation promoted expression and secretion of FGF21 in brown adipocytes. More importantly, iBAT transplantation from A2ARKO mice to wild type mice reduced serum FGF21 level and aggravated hypertensive cardiac remodeling. Recombinant FGF21 administration rescued surgical iBAT depletion-induced dramatic hypertensive cardiac remodeling. Conclusion: The present study provides the first line of evidence for a direct crosstalk between BAT activity and cardiac protection in hypertension, which is largely dependent upon BATA2AR-mediated regulation of FGF21 and the endocrine function of FGF21 in the heart.

Increased serum FGF2 levels in first-episode, drug-free patients with schizophrenia

Preclinical and clinical studies suggest that brain-derived neurotrophic factor and nerve growth factor are involved in the pathogenesis of schizophrenia (SCZ). However, the roles of other neurotrophic factors in SCZ remain unclear. The aim of this study was to investigate the blood levels of FGF2 and ADNP in first-episode, drug-free SCZ patients compared with healthy control subjects. 20 SCZ patients, and 20 age and sex matched controls were recruited in this study. Serum FGF2 and ADNP protein levels were measured by ELISA assay, and the results showed that FGF2 levels were significantly increased in patients with SCZ when compared with controls, whereas ADNP protein levels did not significantly associated with SCZ. However, we found that blood ADNP mRNA levels were significantly increased in the patients with SCZ when compared with controls. In addition, subgroup analyses suggested that FGF2 levels were significantly increased in female patients of SCZ, but not in male patients of SCZ. Correlation analyses suggested that age and disease severity (PANSS score) did not have moderating effects on the serum FGF2 levels. Taken together, our results for the first time demonstrated that blood FGF2 was up-regulated in first-episode, drug free-SCZ patients, therefore enhancing the knowledge of neurotrophic factor profile in patients with SCZ.

Correlations between serum FGF21 and IRISIN levels and nutritional, biochemical, and anthropometric parameters in non-alcoholic fatty liver disease

Correlations between serum FGF21 and IRISIN levels and nutritional, biochemical, and anthropometric parameters in non-alcoholic fatty liver disease

Differential expression of serum biomarkers in hemodialysis patients with mild cognitive decline: A prospective single-center cohort study

Studies suggest that hemodialysis patients are at a higher risk for cognitive decline than healthy individuals; however, underlying mechanisms have not been fully elucidated. We aimed to investigate the roles of serum biomarkers, such as brain-derived neurotrophic factor (BDNF), inflammatory cytokines, fibroblast growth factor (FGF)-23 and its co-receptor α-klotho and platelet (PLT) count in mild cognitive decline (MCD) of patients undergoing hemodialysis in this prospective cohort study. Serum levels of BDNF, tumour necrosis factor (TNF)-α, interleukin (IL)-6 and the number of PLT were significantly altered in the MCD group compared with those in healthy controls (HCs) or those with normal cognitive function (NCF). Although serum α-klotho and FGF-23 levels were significantly altered in the MCD group, there were no statistical differences between the MCD and NCF groups. Serum BDNF levels and PLT counts were significantly correlated with cognitive test scores. Receiver operating characteristic (ROC) curves demonstrated that BDNF and PLT were potential biomarkers for improved MCD diagnosis in patients with hemodialysis. These findings suggest that hemodialysis-related MCD is associated with altered BDNF, TNF-α and IL-6 levels as well as PLT counts and that serum BDNF levels and PLT counts are potential biomarkers for hemodialysis-related MCD diagnosis.

Molecular analysis of enthesopathy in a mouse model of hypophosphatemic rickets.

The bone tendon attachment site known as the enthesis comprises a transitional zone between bone and tendon, and plays an important role in enabling movement at this site. X-linked hypophosphatemia (XLH) is characterized by impaired activation of vitamin D, elevated serum FGF23 levels and low serum phosphate levels, which impair bone mineralization. Paradoxically, an important complication of XLH is mineralization of the enthesis (enthesopathy). Studies were undertaken to identify the cellular and molecular pathways important for normal post-natal enthesis maturation and to examine their role during the development of enthesopathy in mice with XLH (Hyp). The Achilles tendon entheses of Hyp mice demonstrate an expansion of hypertrophic-appearing chondrogenic cells by P14. Post-natally, cells in wild-type and Hyp entheses similarly descend from scleraxis- and Sox9-expressing progenitors; however, Hyp entheses exhibit an expansion of Sox9-expressing cells, and enhanced BMP and IHH signaling. These results support a role for enhanced BMP and IHH signaling in the development of enthesopathy in XLH.

Relevance of serum angiogenic cytokines in adult patients with dermatomyositis

BackgroundUntil now, there are few studies evaluating serum levels of angiogenic cytokines in dermatomyositis (DM). Therefore, the aims of the present study were: (a) to analyze systematically and simultaneously serum levels of angiogenin (ANG), angiopoietin (ANGPT)-1, vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF)-1 and − 2, platelet derived growth factor (PDGF)-AA and -BB in DM; (b) to correlate the serum level of these cytokines with the DM clinical and laboratory features.MethodsThis is a cross sectional study, in which 48 patients with DM aged 18 to 45 years were gender-, age- and ethnicity-matched with 48 healthy individuals (control group). The serum levels of cytokines analyses were performed by multiplex immunoassay. The parameters of DM activity were based on the scores established by the International Myositis Assessment & Clinical Studies Group.ResultsThe mean ages, gender frequencies and ethnicities were comparable between the patients with DM and the control group. A significantly higher serum FGF-1 and FGF-2 levels (P < 0.001 and P < 0.001, respectively), lower VEGF and PDGF-AA levels (P = 0.009 and P = 0.022), and comparable ANG, ANGPT-1 and PDGF-BB levels were observed in DM patients compared to controls. There was a tendency for cytokines (with the exceptions of VEGF and PDGF-BB) to correlate positively with the DM activity parameters, whereas FGF-2 correlated inversely. Moreover, FGF-1 strongly correlated with DM cutaneous manifestations.ConclusionsThe present data provide the relevance of different serum angiogenic cytokines in patients with DM. Additional studies will be needed to validate the data obtained in this work.

Effect of Sucroferric Oxyhydroxide on Fibroblast Growth Factor 23 Levels in Hemodialysis Patients

Objective: This study investigated the effects of sucroferric oxyhydroxide on fibroblast growth factor (FGF)-23 and dose reduction of erythropoiesis-stimulating agents (ESA) and intravenous saccharated ferric oxide in hemodialysis patients. Methods: In this prospective, open-label, parallel-group, multicenter trial involving patients receiving lanthanum carbonate hydrate, eligible patients were randomized to a sucroferric oxyhydroxide group or a control group. Hemoglobin, serum phosphate, FGF-23, iron, and ferritin levels, as well as transferrin saturation, doses of intravenous saccharated ferric oxide and ESA administered, and the erythropoietin responsiveness index (ERI) were monitored for 24 weeks. Results: Sixty-eight eligible patients were allocated to receive sucroferric oxyhydroxide (n = 34) or serve as controls (n = 34). Data for 31 patients in the sucroferric oxyhydroxide group and 32 in the control group were analyzed. Serum phosphate was equally well controlled in both groups. In the sucroferric oxyhydroxide group, intact FGF-23 levels decreased significantly from baseline at the end of the study (p = 0.01) and there was a significant difference compared with the control group (p = 0.035). Required doses of ESA and ERI were significantly reduced in the sucroferric oxyhydroxide group decreased significantly. The dose of intravenous saccharated ferric oxide required in the sucroferric oxyhydroxide group was significantly lower than that at baseline (p = 0.006) and in the control group (p = 0.003). Conclusions: Treatment of hyperphosphatemia with sucroferric oxyhydroxide was effective in patients on hemodialysis, resulting in decreased serum FGF-23 levels and a reduction in the required dose of saccharated ferric oxide.

Serum FGF-21 Is Associated with Future Cardiovascular Events in Patients with Coronary Artery Disease—Results from a Median Follow-Up of 4.8 Years Study

Objectives: To investigate whether the serum fibroblast growth factor (FGF) 21 levels can be used to predict the future development of major adverse cardiovascular events (MACEs). Methods: 253 patients at baseline received subsequent follow-up, 234 of whom finished the data collection. Independent predictors of MACEs were identified using Cox proportional hazards regression analysis. The prognostic value of FGF-21 levels for MACEs was evaluated by Kaplan-Meier survival analysis. Results: Of 229 patients finally enrolled in the analysis, 27 of 60 without coronary artery disease (CAD) at baseline experienced a MACE, and 132 of 169 patients with CAD at baseline experienced a MACE. Among patients with CAD at baseline, serum FGF-21 levels were significantly higher in patients with MACEs (P&amp;lt;0.05) than in patients without MACEs. Kaplan-Meier survival analysis showed a significantly lower event-free survival (P=0.001) among patients with a higher serum FGF-21 level than in those with a lower serum FGF-21 level. Further Cox proportional hazards regression analysis, including the traditional risk factors for cardiovascular disease, showed that serum FGF-21 was one of the independent predictors of the occurrence of MACEs. Conclusions: In patients with CAD at baseline, an elevated serum FGF-21 level was associated with the development of a MACE in the future. Disclosure Y. Bao: None. Y. Shen: None. X. Zhang: None. Y. Xu: None. Q. Xiong: None. Z. Lu: None. X. Ma: None.

Effect of Reduced Intake of Branched-Chain Amino Acids (BCAA) on Insulin Secretion and Sensitivity in Type 2 Diabetes

Circulating BCAA (valine, leucine, isoleucine) are increased in insulin resistant states and predict type 2 diabetes (T2D) suggesting a role of BCAA in the development of insulin resistance. Thus, we hypothesized that a dietary decrease of BCAA improves insulin sensitivity (IS) and oxidative phosphorylation in T2D and increases the levels of the hepatic metabolic regulator fibroblast-growth factor (FGF-21). In a randomized, placebo-controlled, double-blinded study, 12 patients (8 male, 4 female; age 54±4 years, body mass index 30.8±2.8 kg/m2, HbA1c 6.6±0.9%, 49±10 mmol/mol) with known T2D duration of &amp;lt;5 years, received a 4-week isocaloric diet with constant protein intake of 1 g/kg body weight. In a cross-over design, their diet comprised either the complete amino acid set (BCAA+) or a 60% reduction in BCAA (BCAA-) for 1 week. Whole body IS was assessed by hyperinsulinemic-euglycemic clamps and beta-cell function by mixed-meal tolerance tests (MMT). Mitochondrial efficiency was assessed from the respiratory control ratio (RCR) measured by high-resolution respirometry in muscle and adipose tissue. FGF-21 serum levels were quantified by ELISA. IS was lower after BCAA- diet (3.1±1.7 mg*kg-1*min-1) compared to BCAA+ diet (3.5±1.8 mg*kg-1*min-1, p&amp;lt;0.01). However, this difference disappeared after normalization for prevalent insulin levels. MMT showed lower increases in insulin and C-peptide after BCAA- than BCCA+ diet (incremental insulin area under the curve: 21±11 vs. 29±19 mU*ml-1*4 h-1, p&amp;lt;0.01). RCR in adipose tissue was 1.7-fold higher after BCAA- diet (p&amp;lt;0.05), but unchanged in skeletal muscle. The BCAA- diet also increased FGF-21 levels (from 323±189 to 405±233 pg/ml, p&amp;lt;0.05) which likely contributes to the effect on energy metabolism. In conclusion, short-term dietary reduction of BCAA decreases meal-induced insulin and C-peptide secretion, increases FGF-21 levels and stimulates mitochondrial efficiency in adipose tissue, but fails to improve IS in T2D. Disclosure Y. Karusheva: None. T. van Gemert: None. M. Simon: None. D.F. Markgraf: None. K. Strassburger: None. D. Schmoll: Employee; Self; Sanofi-Aventis Deutschland GmbH. V. Burkart: None. K. Müssig: None. J. Szendroedi: None. M. Roden: Speaker's Bureau; Self; Boehringer Ingelheim GmbH. Research Support; Self; Boehringer Ingelheim GmbH. Consultant; Self; Poxel SA. Research Support; Self; Danone Nutricia Early Life Nutrition, GlaxoSmithKline plc., Nutricia Advanced Medical Nutrition, Sanofi.

Impact of Altered Mineral Metabolism on Pathological Cardiac Remodeling in Elevated Fibroblast Growth Factor 23.

Clinical and experimental studies indicate a possible link between high serum levels of fibroblast growth factor 23 (FGF23), phosphate, and parathyroid hormone (PTH), deficiency of active vitamin D (1,25D) and klotho with the development of pathological cardiac remodeling, i.e., left ventricular hypertrophy and myocardial fibrosis, but a causal link has not been established so far. Here, we investigated the cardiac phenotype in klotho hypomorphic (kl/kl) mice and Hyp mice, two mouse models of elevated FGF23 levels and klotho deficiency, but differing in parameters of mineral metabolism, by using histology, quantitative real-time PCR, immunoblot analysis, and serum and urine biochemistry. Additionally, the specific impact of calcium, phosphate, PTH, and 1,25D on hypertrophic growth of isolated neonatal rat cardiac myocytes was investigated in vitro. Kl/kl mice displayed high serum Fgf23 levels, increased relative heart weight, enhanced cross-sectional area of individual cardiac myocytes, activated cardiac Fgf23/Fgf receptor (Fgfr) 4/calcineurin/nuclear factor of activated T cell (NFAT) signaling, and induction of pro-hypertrophic NFAT target genes including Rcan1, bMHC, brain natriuretic peptide (BNP), and atrial natriuretic peptide (ANP) as compared to corresponding wild-type (WT) mice. Investigation of fibrosis-related molecules characteristic for pathological cardiac remodeling processes demonstrated ERK1/2 activation and enhanced expression of Tgf-β1, collagen I, and Mmp2 in kl/kl mice than in WT mice. In contrast, despite significantly elevation of serum and cardiac Fgf23, and reduced renal klotho expression, Hyp mice showed no signs of pathological cardiac remodeling. Kl/kl mice showed enhanced serum calcium and phosphate levels, while Hyp mice showed unchanged serum calcium levels, lower serum phosphate, and elevated serum iPTH concentrations compared to corresponding WT mice. In cultured cardiac myocytes, treatment with both calcium or phosphate significantly upregulated endogenous Fgf23 mRNA expression and stimulated hypertrophic cell growth and expression of pro-hypertrophic genes. The treatment with PTH induced hypertrophic cell growth only, and stimulation with 1,25D had no significant effects. In conclusion, our data indicate that Hyp mice, in contrast to kl/kl mice appear to be protected from pathological cardiac remodeling during conditions of high FGF23 levels and klotho deficiency, which may be due, at least in part, to differences in mineral metabolism alterations, i.e., hypophosphatemia and lack of hypercalcemia.

FGF21 regulates insulin sensitivity following long-term chronic stress

ObjectivePost-traumatic stress disorder (PTSD) increases type 2 diabetes risk, yet the underlying mechanisms are unclear. We investigated how early-life exposure to chronic stress affects long-term insulin sensitivity. MethodsC57Bl/6J mice were exposed to chronic variable stress for 15 days (Cvs) and then recovered for three months without stress (Cvs3m). ResultsCvs mice showed markedly increased plasma corticosterone and hepatic insulin resistance. Cvs3m mice exhibited improved whole-body insulin sensitivity along with enhanced adipose glucose uptake and skeletal muscle mitochondrial function and fatty acid oxidation. Plasma FGF21 levels were substantially increased and associated with expression of genes involved in fatty acid oxidation and formation of brown-like adipocytes. In humans, serum FGF21 levels were associated with stress coping long time after the exposure. ConclusionsEarly-life exposure to chronic stress leads to long term improvements in insulin sensitivity, oxidative metabolism and adipose tissue remodeling. FGF21 contributes to a physiological memory mechanism to maintain metabolic homeostasis.

Serum and urine FGF23 and IGFBP-7 for the prediction of acute kidney injury in critically ill children

BackgroundFibroblast growth factor 23 (FGF23) and insulin-like growth factor binding protein 7 (IGFBP-7) are suggested to be biomarkers for predicting acute kidney injury (AKI). We compared them with proposed AKI biomarker of cystatin C (CysC), and aimed (1) to examine whether concentrations of these biomarkers vary with age, body weight, illness severity assessed by pediatric risk of mortality III score, and kidney function assessed by estimated glomerular filtration rate (eGFR), (2) to determine the association between these biomarkers and AKI, and (3) to evaluate whether these biomarkers could serve as early independent predictors of AKI in critically ill children.MethodsThis prospective single center study included 144 critically ill patients admitted to the pediatric intensive care unit (PICU) regardless of diagnosis. Serum and spot urine samples were collected during the first 24 h after PICU admission. AKI was diagnosed based on the AKI network (AKIN) criteria.ResultsTwenty-one patients developed AKI within 120 h of sample collection, including 11 with severe AKI defined as AKIN stages 2 and 3. Serum FGF23 levels were independently associated with eGFR after adjustment in a multivariate linear analysis (P < 0.001). Urinary IGFBP-7 (Adjusted OR = 2.94 per 1000 ng/mg increase, P = 0.035), serum CysC (Adjusted OR = 5.28, P = 0.005), and urinary CysC (Adjusted OR = 1.13 per 1000 ng/mg increase, P = 0.022) remained significantly associated with severe AKI after adjustment for body weight and illness severity, respectively. Urinary IGFBP-7 level was predictive of severe AKI and achieved the AUC of 0.79 (P = 0.001), but was not better than serum (AUC = 0.89, P < 0.001) and urinary (AUC = 0.88, P < 0.001) CysC in predicting severe AKI.ConclusionsSerum FGF23 levels were inversely related to measures of eGFR. In contrast to serum and urinary FGF23 which are not associated with AKI in a general and heterogeneous PICU population, an increased urinary IGFBP-7 level was independently associated with the increased risk of severe AKI diagnosed within the next 5 days after sampling, but not superior to serum or urinary CysC in predicting severe AKI in critically ill children.

Fibroblast growth factor-21 is a potential diagnostic factor for patients with gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is a metabolic disease with symptoms of hyperglycemia, insulin resistance and fetal maldevelopment. Evidence has indicated that fibroblast growth factor (FGF)-21 is a multifunctional protein and exhibits potential therapeutic value for metabolic diseases. The present study investigated the diagnostic value of FGF-21 serum levels in patients with GDM (n=50) and age-matched healthy individuals (n=50). It was demonstrated that the gene and protein expression levels of FGF-21 were downregulated in adipose cells in patients with GDM compared with those in healthy individuals. The results also indicated that the serum levels of FGF-21 were downregulated in patients with GDM compared with those in healthy individuals. In addition, it was demonstrated that blood glucose and blood pressure were higher in patients with GDM compared with those in healthy individuals. GDM patients had a markedly higher insulin resistance and glucose tolerance than healthy individuals. However, GDM patients had significantly lower serum levels of insulin than healthy individuals. It was observed that the serum levels of FGF-21 were positively correlated with those of glucose in GDM patients. In conclusion, these results indicate that decreased FGF-21 levels are associated with the risk of GDM, suggesting that FGF-21 may be a potential diagnostic factor for GDM.

An Overview of FGF19 and FGF21: The Therapeutic Role in the Treatment of the Metabolic Disorders and Obesity.

Fibroblast growth factors (FGFs) are responsible for the regulation of a wide range of biological functions, among which cellular proliferation, survival, migration, and differentiation could be pointed out. FGF19 controls the enterohepatic bile acid/cholesterol system, and FGF21 modulates fatty acid/glucose metabolism. Obesity, type 2 diabetes, coronary artery disease, and cancer, all can alter FGF21 circulating concentrations. In contrast to FGF21, metabolic diseases exhibit reduced serum FGF19 levels. Accordingly, FGF19 and FGF21 play important roles in regulating glucose and lipid metabolism. Hence, we present here a timely review on the relationship between FGF19/21 and metabolic diseases, especially obesity, and their probable role in development and treatment of obesity seems necessary.

Association between Serum FGF21 levels and bone mineral density in healthy postmenopausal Korean women

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Expression of Fibroblast Growth Factor 21 and β-Klotho Regulates Hepatic Fibrosis through the Nuclear Factor-κB and c-Jun N-Terminal Kinase Pathways.

Background/AimsFibroblast growth factor (FGF) 21 is associated with hepatic inflammation and fibrosis. However, little is known regarding the effects of inflammation and fibrosis on the β-Klotho and FGF21 pathway in the liver.MethodsEnrolled patients had biopsy-confirmed viral or alcoholic hepatitis. FGF19, FGF21 and β-Klotho levels were evaluated using enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and Western blotting. Furthermore, we explored the underlying mechanisms for this process by evaluating nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK) pathway involvement in Huh-7 cells.ResultsWe observed that the FGF19 and FGF21 serum and mRNA levels in the biopsied liver tissue gradually increased and were correlated with fibrosis stage. Inflammatory markers (interleukin 1β [IL-1β], IL-6, and tumor necrosis factor-α) were positively correlated, while β-Klotho expression was negatively correlated with the degree of fibrosis. In Huh-7 cells, IL-1β increased FGF21 levels and decreased β-Klotho levels. NF-κB and JNK inhibitors abolished the effect of IL-1β on both FGF21 and β-Klotho expression. FGF21 protected IL-1β-induced growth retardation in Huh-7 cells.ConclusionsThese results indicate that the inflammatory response during fibrogenesis increases FGF21 levels and suppresses β-Klotho via the NF-κB and JNK pathway. In addition, FGF21 likely protects hepatocytes from hepatic inflammation and fibrosis.

The association of serum FGF23 and non-alcoholic fatty liver disease is independent of vitamin D in type 2 diabetes patients.

Recent studies have shown that circulating fibroblast growth factor (FGF) 23 and vitamin D levels are closely correlated with insulin resistance. The aim of this study was to investigate the relationship among serum FGF 23 levels, serum 25-hydroxyvitamin D [25(OH)D] levels, and non-alcoholic fatty liver disease (NAFLD) in Chinese patients with type 2 diabetes mellitus (T2DM). This study enrolled 331 hospitalized T2DM patients (209 patients with NAFLD and 122 patients without NAFLD). Serum FGF23 levels were measured using a sandwich enzyme-linked immunosorbent assay. Serum 25(OH)D levels were determined by an electrochemiluminescence immunoassay. NAFLD was diagnosed by hepatic ultrasound, and the fatty liver index (FLI) was calculated to quantify hepatic steatosis. Results showed that T2DM patients with NAFLD had significantly higher serum FGF23 levels (44.17 [37.92-51.30] pg/mL vs 40.21 [34.07-48.33] pg/mL, P=.002), but lower serum 25(OH)D levels (16.43 [12.70-21.37] ng/mL vs 19.59 [13.78-26.26] ng/mL, P=.002) than those without NAFLD. Moreover, the incidence rate of NAFLD increased with increasing serum FGF23 levels and decreased with increasing 25(OH)D levels (both P<.05). Logistic regression analysis showed that both serum FGF23 and 25(OH)D levels were independent factors for NAFLD (both P<.05). Furthermore, a multiple stepwise regression analysis also revealed that both serum FGF23 and 25(OH)D levels were independently correlated with FLI (both P<.01). In conclusion, both high FGF23 and low vitamin D levels showed an independent relationship with NAFLD in Chinese T2DM patients, indicating that FGF23 and vitamin D function via different regulatory pathways in the liver.