Fibroblast Growth Factor 21 Levels Research Articles

Fibroblast Growth Factor 21 Correlates with the Prognosis of Dilated Cardiomyopathy

Objectives: The goal of this study was to evaluate whether serum fibroblast growth factor 21 (FGF21) levels can be used to predict the prognosis of dilated cardiomyopathy (DCM). Methods: 241 patients with DCM and 80 control subjects were recruited and followed up for an average of 16.12 months. A 2-dimensional (2-D) echocardiography technique was performed to calculate the left ventricular end-diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF) percentages. The levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and creatinine were measured in routine clinical laboratory tests. Serum FGF21 levels were measured by enzyme-linked immunosorbent assay (ELISA). Results: The levels of serum FGF21 were significantly higher in the DCM groups than in the control groups (225.85 ± 32.57 vs. 145.36 ± 30.57, p < 0.001). Serum FGF21 levels were positively correlated with the NYHA functional classification of heart failure (HF) (r = 0.610, p < 0.001) and NT-proBNP levels (r = 0.741, p < 0.001). Moreover, a negative correlation was observed between the serum FGF21 levels and the LVEF (r = –0.402, p < 0.001). FGF21, NT-proBNP, the LVEF and a history of atrial fibrillation (AF) correlated significantly with NYHA class IV (p < 0.05). The AUC of NT-proBNP for predicting NYHA class IV in DCM patients was greater than that of FGF21 (0.830 vs. 0.772, p < 0.001). Overall, 133 patients with DCM were recorded at the end point. Kaplan-Meier analysis results showed that the survival probability of those individuals with high levels of FGF21 and NT-proBNP was significantly lower than of those with low levels of these factors (p < 0.001). In the multivariate Cox analysis, FGF21 (HR 2.561; 95% CI 1.705–3.849) and NT-proBNP (HR 4.458; 95% CI 2.645–7.513) were independent predictors of a poor prognosis in DCM patients. Conclusions: Serum FGF21 levels were associated with the risk factors, severity, and prognosis of DCM. Therefore, FGF21 may serve as a novel biomarker for the prognosis of DCM.

Pharmacologic inhibition of serotonin htr2b ameliorates hyperglycemia and the altered expression of hepatic FGF21, Sdf2l1, and htr2a in db/db mice and KKAy mice

Plasma fibroblast growth factor 21 (FGF21) levels and hepatic FGF21, serotonin 2a receptor (htr2a), and stromal cell-derived factor 2 like 1 (Sdf2l1) expression are increased in insulin-resistant C57BL6J mice fed a high-fat diet. Here we show that plasma FGF21 levels and hepatic FGF21, Sdf2l1, and htr2a expression were decreased in 6-week-old db/db mice compared with C57BL6J mice, whereas they were increased in 6-week-old KKAy mice compared with KK mice. Expression of hepatic htr2b was increased in db/db mice and KKAy mice compared with controls. Treatment with the selective htr2b antagonist SB204741 suppressed the hyperglycemia in either db/db mice or KKAy mice. Treatment with SB20471 reversed the decreases in plasma FGF21 levels and hepatic FGF21, Sdf2l1, and htr2a expression in db/db mice, whereas it suppressed the increases in plasma FGF21 levels and hepatic FGF21, Sdf2l1, and htr2a expression in KKAy mice. Moreover, treatment with SB204741 increased plasma FGF21 levels and expression of hepatic FGF21, htr2a, and Sdf2l1 in C57BL6J mice, whereas it decreased plasma FGF21 levels and hepatic FGF21 expression in KK mice. These findings suggest that pharmacologic inhibition of htr2b ameliorates the hyperglycemia and altered expression of hepatic FGF21, Sdf2l1 and htr2a in obese and diabetic db/db and KKAy mice.

Small hepatitis B virus surface antigen promotes malignant progression of hepatocellular carcinoma via endoplasmic reticulum stress-induced FGF19/JAK2/STAT3 signaling.

Chronic hepatitis B virus (HBV) infection is one of the major global health problems. Although the small protein of hepatitis B virus surface antigen (HBsAg), SHBs, is the most abundant HBV viral protein, its pathogenic role and molecular mechanism in malignant progression of HBV-related hepatocellular carcinoma (HCC) remain largely unknown. Here we reported that SHBs expression induced epithelial-mesenchymal transition (EMT) process in HCC cells and significantly increased their migratory and invasive ability as well as metastatic potential. Mechanistically, SHBs expression in HCC cells induced endoplasmic reticulum (ER) stress that activated the activating transcription factor 4 (ATF4) to increase the expression and secretion of fibroblast growth factor 19 (FGF19). The autocrine released FGF19 in turn activated JAK2/STAT3 signaling for induction of EMT process in HCC. Notably, SHBs was positively correlated with the expression of mesenchymal markers, the phosphorylation status of JAK2 and STAT3 as well as FGF19 levels in human HCC samples. HCC patients with SHBs positive had a more advanced clinical stage and worse prognosis. These results suggest an important role of SHBs in the metastasis and progression of HCC and may highlight a potential target for preventive and therapeutic intervention of HBV-related HCC and its malignant progression.

The protective effect of fibroblast growth factor‐21 in alcoholic cardiomyopathy: a role in protecting cardiac mitochondrial function

Alcoholic cardiomyopathy (ACM) resulting from chronic alcohol misuse is one of the main contributors leading to heart failure and cardiovascular mortality. Fibroblast growth factor 21 (FGF21) is a well-established cardioprotective factor. We aimed to study the role of FGF21 in experimentally induced models and clinical affected patients with cardiac damage due to chronic alcohol consumption. We found that circulating FGF21 levels and cardiac FGF21 and β-klotho protein levels were increased in subjects with chronic alcohol consumption. As an experimental model of ACM, we fed wild-type and Fgf21 knockout (Fgf21-/- ) mice with a 4% alcohol liquid diet for 4 and 12 weeks. FGF21 circulating levels and FGF21 expression in the myocardium were also increased in wild-type mice after chronic alcohol intake. Fgf21-/- mice develop a higher degree of cardiac hypertrophy, fibrosis, and cardiac dysfunction after chronic alcohol consumption than wild-type mice. Moreover, the myocardium of Fgf21-/- mice showed signs of metabolic deregulation, oxidative stress, and mitochondrial dysfunction after alcohol intake. Finally, human cardiac biopsies from patients with chronic alcohol consumption developing ACM presented a higher degree of oxidative stress which positively correlated with the FGF21 protein levels in the myocardium. We conclude that plasma levels and cardiac myocyte FGF21 expression were induced in response to chronic alcohol consumption. The lack of FGF21 aggravated cardiac damage produced by ACM, in association with enhanced mitochondrial and oxidative stress, thus pointing to FGF21 as a protective agent against development of alcohol-induced cardiomyopathy. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Short-term protein restriction at advanced age stimulates FGF21 signalling, energy expenditure and browning of white adipose tissue.

Dietary protein restriction has been demonstrated to improve metabolic health under various conditions. However, the relevance of ageing and age-related decline in metabolic flexibility on the effects of dietary protein restriction has not been addressed. Therefore, we investigated the effect of short-term dietary protein restriction on metabolic health in young and aged mice. Young adult (3months old) and aged (18months old) C57Bl/6J mice were subjected to a 3-month dietary protein restriction. Outcome parameters included fibroblast growth factor 21 (FGF21) levels, muscle strength, glucose tolerance, energy expenditure (EE) and transcriptomics of brown and white adipose tissue (WAT). Here, we report that a low-protein diet had beneficial effects in aged mice by reducing some aspects of age-related metabolic decline. These effects were characterized by increased plasma levels of FGF21, browning of subcutaneous WAT, increased body temperature and EE, while no changes were observed in glucose homeostasis and insulin sensitivity. Moreover, the low-protein diet used in this study was well-tolerated in aged mice indicated by the absence of adverse effects on body weight, locomotor activity and muscle performance. In conclusion, our study demonstrates that a short-term reduction in dietary protein intake can impact age-related metabolic health alongside increased FGF21 signalling, without negatively affecting muscle function. These findings highlight the potential of protein restriction as a strategy to induce EE and browning of WAT in aged individuals.

Circulating levels of fibroblast growth factor 21 in gestational diabetes mellitus: a meta-analysis.

In recent times, the role of fibroblast growth factor 21 (FGF21) in patients with gestational diabetes mellitus (GDM) has been increasingly investigated. However, to our knowledge, no systematic analysis has been conducted yet to evaluate the relationship between FGF21 levels and GDM. Confirmed studies related to circulating FGF21 levels and GDM were searched from the databases of PubMed, ISI Web of Science, MEDLINE and EMBASE. Data were reported as standard mean difference (SMD) and associated 95% confidence intervals (CIs). Analysis were performed with Review Manager 5.2 and Stata version 11.0. A total of 392 cases and 435 controls in nine articles were included in this meta-analysis. The circulating FGF21 levels in pregnant women with GDM was higher than that in controls (random effects MD [95% CI] = 0.46, [0.07-0.86], p = 0.02). The result of multivariate meta-regression showed that sample size and point of sample collection contributed to heterogeneity (p = 0.033 and p = 0.047, respectively). Additionally, the results showed that there was no publication bias in this meta-analysis (Z = 1.36, p = 0.175; t = 1.24, p = 0.256, respectively). To conclude, this meta-analysis provides evidence that circulating FGF21 levels are higher in GDM subjects than controls, and it is important to clarify the relationship between circulating FGF21 levels and pregnant women with GDM in accurate prediction of GDM.

Circulating Fibroblast Growth Factor-21 Levels in Rheumatoid Arthritis: Associations With Disease Characteristics, Body Composition, and Physical Functioning

This study evaluated associations between fibroblast growth factor (FGF)-21, an adipokine associated with metabolic stress, and adverse longitudinal changes in body composition and physical functioning in patients with rheumatoid arthritis (RA). At baseline and follow-up, patients with RA aged 18-70 years completed whole-body dual-energy X-ray absorptiometry and peripheral quantitative computed tomography to quantify lean mass, fat mass, and muscle density. Dynamometry assessed muscle strength at the hand and knee, and physical functioning was measured with the Health Assessment Questionnaire (HAQ) and the Short Physical Performance Battery (SPPB). FGF-21 and inflammatory cytokines were measured at baseline. Linear and logistic regression analyses assessed associations between FGF-21 levels and both body composition and physical functioning over time. There were 113 patients with RA enrolled, and 84 (74%) returned for follow-up at a median of 2.68 years. At baseline, FGF-21 was associated with age, smoking, methotrexate use, adiposity, and inflammatory cytokines: tumor necrosis factor receptor type I, YKL-40, vascular endothelial growth factor (VEGF), and resistin. The highest FGF-21 quartile was associated with worse SPPB and HAQ. Higher baseline FGF-21 levels (per 1 SD) were associated with worsening in muscle density and area Z-scores (β -0.06, 95% CI -0.12 to 0.008, P = 0.08; and β -0.05, 95% CI -0.10 to 0.006, P = 0.08, respectively) and a greater probability of a clinically meaningful worsening of HAQ (OR 2.37, 95% CI 1.21-4.64, P = 0.01). The fourth FGF-21 quartile was associated with worsening of SPPB (β -0.57, 95% CI -1.04 to -0.09, P = 0.02). FGF-21 levels are associated with obesity and inflammatory cytokines, and with worsening in physical functioning in RA. These data support the hypothesis that FGF-21 can identify patients at risk of functional decline.

Disease-specific plasma levels of mitokines FGF21, GDF15, and Humanin in type II diabetes and Alzheimer\u2019s disease in comparison with healthy aging

Fibroblast Growth Factor 21 (FGF21), Growth Differentiation Factor 15 (GDF15), and Humanin (HN) are mitochondrial stress-related mitokines, whose role in health and disease is still debated. In this study, we confirmed that their plasma levels are positively correlated with age in healthy subjects. However, when looking at patients with type 2 diabetes (T2D) or Alzheimer’s disease (AD), two age-related diseases sharing a mitochondrial impairment, we found that GDF15 is elevated in T2D but not in AD and represents a risk factor for T2D complications, while FGF21 and HN are lower in AD but not in T2D. Moreover, FGF21 reaches the highest levels in centenarian’ offspring, a model of successful aging. As a whole, these data indicate that (i) the adaptive mitokine response observed in healthy aging is lost in age-related diseases, (ii) a common expression pattern of mitokines does not emerge in T2D and AD, suggesting an unpredicted complexity and disease-specificity, and (iii) FGF21 emerges as a candidate marker of healthy aging.

FGF21 and its Relationship with Inflammatory and Metabolic Parameters in HIV Patients after Antiretroviral Treatment.

Fibroblast Growth Factor 21 (FGF21) serum levels are associated with insulin resistance and metabolic syndrome in HIV patients. To quantify FGF21 levels in HIV patients using antiretroviral therapy (ART) and to analyze a possible association between serum FGF21 levels and lipid profile, levels of proinflammatory cytokines, and atherogenic risk factors. Twenty patients with HIV infection, who received ART in a scheme consisting of Tenofovir/Emtricitabine+Lopinavir/Ritonavir, were enrolled in this study. The serum levels of FGF21, inflammatory parameters (IL-6 and IL-1β), glucose, cholesterol, triglycerides, and insulin were determined at baseline and after 36 weeks of treatment. The homeostatic model assessment for insulin resistance (HOMA-IR) and the atherogenic risk factor were also calculated. After 36 weeks, serum FGF21 levels decreased significantly (p=0.011), whereas IL-6 levels (r=0.821, p=0.0001) and the CD4+ T cell count (r=0.446, p=0.048), showed a positive correlation with the decrease in FGF21 levels. There was an increase in total cholesterol (r=-0.483, p=0.031), LDL (r=-0.496, p=0.026), VLDL (r=-0.320, p=0.045), and the atherogenic index factor (r=-0.539, p=0.014), these values showed a negative correlation with FGF21 levels. The decrease of serum FGF21 levels due to ART is associated with the alteration in lipid profile and an increased risk for cardiovascular diseases. These variations are predictors of inflammatory status in HIV patients using antiretroviral therapy.

The role of chemerin in the pathogenesis of cholelithiasis in children and adolescents.

Adipokines and hepatokines are proteins secreted by adipose tissue and the liver. To date, the levels of adipokines and hepatokines in cholelithiasis have only been evaluated in studies in adult patients. The purpose of our research was to assess the levels of circulating adipokines: chemerin, vaspin, progranulin, retinol-binding protein 4 (RBP-4) and hepatokine: fibroblast growth factor 21 (FGF-21) and to compare their concentrations in paediatric patients with and without cholelithiasis. The prospective study included 54 children and adolescents diagnosed with gallstones and 26 controls. Fasting serum levels of adipokines and hepatokine were determined by enzyme-linked immunosorbent assays. The serum levels of chemerin, FGF-21 and RBP-4 were significantly higher in children and adolescents with gallstones compared to the control group. Elevated levels of triglycerides, RBP-4, and a homeostatic model for assessing insulin resistance (HOMA-IR) were observed in overweight or obese patients compared to patients with normal weight and cholelithiasis. Chemerin concentrations were increased in the normal-weight children and adolescents with cholelithiasis compared to the control group. Children and adolescents with gallstones and abnormal weight had significantly higher levels of chemerin, FGF-21 and RBP-4 than healthy controls. Elevated serum chemerin levels were significantly higher in non-obese patients with cholelithiasis than in non-obese controls, suggesting a potential role of chemerin in the development of cholelithiasis in children and adolescents.

Association of serum fibroblast growth factor 21 and urinary glucose excretion in hospitalized patients with type 2 diabetes.

Urinary glucose excretion (UGE) is mainly regulated by the sodium glucose cotransporter (SGLT)-2 in the proximal tubule of kidney. Lower UGE was associated with higher extent of insulin resistance in patients with type 2 diabetes. Animal studies suggested the relation of Fibroblast growth factor 21 (FGF21) and UGE. However, little was known about the association of FGF21 and UGE in human. We conducted a study to investigate the association of serum FGF21 and low UGE in patients with type 2 diabetes. A cohort of 2066 hospitalized patients with type 2 diabetes was screened for the fasting urinary glucose concentration and fasting blood glucose in the medical records. 70 patients with high UGE and 61 patients with Low UGE were analyzed. Frozen serum samples were used for the test of FGF21 levels. The body mass index (BMI) and serum FGF21 levels were higher in low UGE group. Multivariable logistic regression indicated the association of FGF21 and low UGE after adjusting for age, sex, renal function, fasting plasma glucose, the treatment of insulin, and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) index. Higher serum FGF21 levels were independently associated with low UGE in patients with type 2 diabetes.

Whey protein isolate inhibits hepatic FGF21 production, which precedes weight gain, hyperinsulinemia and hyperglycemia in mice fed a high-fat diet

Insufficient expression of hepatic fibroblast growth factor 21 (FGF21) and stromal cell-derived factor 2 like 1 (Sdf2l1) reportedly leads to insulin resistance and hepatosteatosis in obesity and type 2 diabetes. On the other hand, increased expression of hepatic serotonin receptor 2a (htr2a) in diet-induced obesity contributes to hepatosteatosis. Here we show that increases in circulating FGF21 levels and expression of hepatic FGF21 preceded weight gain, hyperinsulinemia, and hyperglycemia in C57BLJ6 mice fed a high-fat diet. Expression of hepatic htr2a and Sdf2l1 increased in insulin-resistant mice fed a high-fat diet. Intake of whey protein isolate decreased plasma FGF21 levels and expression of hepatic FGF21 in mice fed either a high-fat diet or a chow diet, whereas it only suppressed the overexpression of hepatic Sdf2 and htr2a in insulin-resistant mice fed a high-fat diet. Moreover, intake of whey protein isolate decreased plasma serotonin levels in mice fed either a high-fat diet or a chow diet. Genetic inhibition of tryptophan hydroxylase 1 decreased hepatic FGF21 expression and plasma FGF21 levels in mice. These findings suggest that increased hepatic FGF21 production precedes diet-induced weight gain, hyperinsulinemia, and hyperglycemia, and that intake of whey protein isolate could inhibit hepatic FGF21 production by suppressing peripheral serotonin synthesis.

Circulating Fibroblast Growth Factor-21 and Risk of Metachronous Colorectal Adenoma.

Prior work has shown that higher circulating concentrations of fibroblast growth factor-21 (FGF-21) are associated with an increased likelihood of developing colorectal cancer. We conducted a prospective study to assess the relationship between circulating FGF-21 and odds of developing early neoplastic lesions in the colorectum. A total of 94 study participants were included from the ursodeoxycholic acid (UDCA) trial, a phase III, randomized, double-blind, placebo-controlled clinical trial of the effect of 8-10mg/kg of body weight UDCA vs. placebo. Logistic regression analyses were conducted to evaluate the association between baseline FGF-21 concentrations and odds of developing a metachronous adenoma. Of the characteristics compared across tertiles of FGF-21 concentrations, including age, race, sex, BMI, and other variables, only a previous personal history of colorectal polyps prior to entry into the UDCA trial was statistically significantly related to FGF-21 levels, with a proportion of 26.7%, 56.7%, and 50.0% across the first, second, and third tertiles, respectively (p < 0.05). Higher circulating concentrations of FGF-21 were statistically significantly associated with greater odds of developing a metachronous colorectal adenoma. After adjusting for potential confounders and when compared with the lowest tertile of FGF-21, the adjusted ORs (95% CIs) for metachronous colorectal adenoma in the second and third tertiles were 4.72 (95% CI, 1.42-15.72) and 3.82 (95% CI, 1.15-12.68), respectively (p trend < 0.05). Our results reveal for the first time that, in addition to a recently discovered association with colorectal cancer, circulating FGF-21 concentrations are significantly and directly associated with odds of developing metachronous colorectal adenoma.

Relationship between physical activity and circulating fibroblast growth factor 21 in middle-aged and older adults.

Circulating levels of fibroblast growth factor 21 (FGF21) increase with advancing age and may lead to the development of cardiometabolic diseases via impaired lipid and glucose metabolism. While physical activity can reduce these risks of cardiometabolic dysfunction, it remains obscure whether circulation FGF21 levels are influenced by physical activity. The purpose of this study was to investigate the relations between daily physical activities and circulating FGF21 levels in middle-aged and older adults. In this cross-sectional study with 110 middle-aged and 102 older adults, circulating (serum) FGF21 levels were evaluated by enzyme-linked immunosorbent assay, and the time spent in light-intensity physical activity (LPA) and moderate-to-vigorous-intensity physical activity (MVPA) was assessed using a uniaxial accelerometer. Serum FGF21 levels in the older group (158pg/mL) were significantly higher than those in the middle-aged group (117pg/mL). When we examined the joint association of age (middle-aged or older) and MVPA (lower or higher than the median) groups, serum FGF21 levels in the older and higher MVPA group (116pg/mL) were significantly lower than those in the older and lower MVPA group (176pg/mL). However, there was no difference in serum FGF21 levels between the lower and higher MVPA groups in the middle-aged group. In multivariable liner regression analysis, serum FGF21 levels were independently determined by MVPA time after adjusting for potential covariates in older adults (β=-0.209). These cross-sectional study findings indicate that the time spent in MVPA is an independent determinant of circulating FGF21 levels, and that an age-related increase in serum FGF21 levels may be attenuated by habitually performing MVPA. (250/250 words).

Pemafibrate Protects Against Retinal Dysfunction in a Murine Model of Diabetic Retinopathy.

Diabetic retinopathy (DR) is one of the leading causes of blindness globally. Retinal neuronal abnormalities occur in the early stage in DR. Therefore, maintaining retinal neuronal activity in DR may prevent vision loss. Previously, pemafibrate, a novel selective peroxisome proliferator-activated receptor alpha modulator, was suggested as a promising drug in hypertriglyceridemia. However, the role of pemafibrate remains obscure in DR. Therefore, we aimed to unravel systemic and retinal changes by pemafibrate in diabetes. Adult mice were intraperitoneally injected with streptozotocin (STZ) to induce diabetes. After STZ injection, diet supplemented with pemafibrate was given to STZ-induced diabetic mice for 12 weeks. During the experiment period, body weight and blood glucose levels were examined. Electroretinography was performed to check the retinal neural function. After sacrifice, the retina, liver, and blood samples were subjected to molecular analyses. We found pemafibrate mildly improved blood glucose level as well as lipid metabolism, boosted liver function, increased serum fibroblast growth factor21 level, restored retinal functional deficits, and increased retinal synaptophysin protein expression in STZ-induced diabetic mice. Our present data suggest a promising pemafibrate therapy for the prevention of early DR by improving systemic metabolism and protecting retinal function.

Moderate-Intensity Continuous Training Improves FGF21 and KLB Expression in Obese Mice.

Fibroblast growth factor 21 (FGF21) and β-Klotho (KLB) play an important role in preventing and treating overweight and obesity. However, it is unclear what conditions promote FGF21 and KLB expression in different tissues. Therefore, we studied expression of FGF21 and KLB with respect to two exercise regimes: moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) (two popular strategies in weight loss). Mice were randomly divided into three groups (n = 8 per group): MICT, HIIT, and sedentary lifestyle (SED). All mice were fed a high-fat diet (HFD) for 12 weeks to induce obesity. The exercise was performed on a motorized treadmill for another eight weeks and the diet continued in each group. We found that both MICT and HIIT had positive effects on the loss of HFD-induced body weight increase and serum FGF21 levels. HIIT promoted decrease of the body weight and serum triglyceride (TG) levels, while MICT was more effective at enhancing FGF21 and KLB expression in the liver, brown adipose tissue (BAT), and muscle at the mRNA and protein levels.

Effects of beta-conglycinin intake on circulating FGF21 levels and brown adipose tissue activity in Japanese young men: a single intake study and a randomized controlled trial

BackgroundHuman brown adipose tissue (BAT) activity has beneficial effects on body composition and glucose metabolism. A previous study reported that beta-conglycinin intake induced postprandial fibroblast growth factor 21 (FGF21) secretion, thereby promoting adipose tissue thermogenesis in mice. Since it has not been evaluated whether beta-conglycinin intake is associated with induced FGF21 secretion and BAT thermogenesis in humans, the current study examined the effects of beta-conglycinin intake on circulating FGF21 level and BAT activity.MethodsTwenty-two healthy young male subjects participated. This study consisted of 2 interventional studies. In one of them, the effects of single beta-conglycinin intake at thermoneutral temperature on circulating FGF21 levels were examined (n = 7). The other study was a single-blinded randomized crossover trial of 2 weeks (n = 14). The subjects were exposed to mild cold conditions using a climatic chamber, and BAT activity was analyzed using thermography. Serum FGF21 level was determined by ELISA in these studies.ResultsIn the single intake study, serum FGF21 level was the highest before beta-conglycinin intake and gradually and significantly decreased throughout the 2-h experimental period (P < 0.05). The randomized crossover trial showed that 2-week beta-conglycinin intake did not affect serum FGF21 level and BAT activity, whereas changes (Δ) in baseline levels of serum FGF21 were positively correlated with Δ BAT activity (P < 0.05). In addition, analysis of each group revealed that there was significant correlation between the Δ serum FGF21 level and Δ BAT activity in the beta-conglycinin group (P < 0.05), but not in the placebo group.ConclusionsThis study reveals that although serum FGF21 levels are not increased by a single or short-term intake of beta-conglycinin, the Δ basal FGF21 level is associated with Δ BAT activity. These results suggest that human FGF21 responsiveness is different from that of rodents and support the importance of FGF21 in human BAT thermogenesis.Trial registrationThis study is registered with University Hospital Medical Information Network in Japan (number 000038723, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000043942).

High-protein diet more effectively reduces hepatic fat than low-protein diet despite lower autophagy and FGF21 levels.

Non-alcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent and nutrition intervention remains the most important therapeutic approach for NAFLD. Our aim was to investigate whether low- (LP) or high-protein (HP) diets are more effective in reducing liver fat and reversing NAFLD and which mechanisms are involved. 19 participants with morbid obesity undergoing bariatric surgery were randomized into two hypocaloric (1500-1600kcal/day) diet groups, a low protein (10E% protein) and a high protein (30E% protein), for three weeks prior to surgery. Intrahepatic lipid levels (IHL) and serum fibroblast growth factor 21 (FGF21) were measured before and after the dietary intervention. Autophagy flux, histology, mitochondrial activity and gene expression analyses were performed in liver samples collected during surgery. IHL levels decreased by 42.6% in the HP group, but were not significantly changed in the LP group despite similar weight loss. Hepatic autophagy flux and serum FGF21 increased by 66.7% and 42.2%, respectively, after 3weeks in the LP group only. Expression levels of fat uptake and lipid biosynthesis genes were lower in the HP group compared with those in the LP group. RNA-seq analysis revealed lower activity of inflammatory pathways upon HP diet. Hepatic mitochondrial activity and expression of β-oxidation genes did not increase in the HP group. HP diet more effectively reduces hepatic fat than LP diet despite of lower autophagy and FGF21. Our data suggest that liver fat reduction upon HP diets result primarily from suppression of fat uptake and lipid biosynthesis.

Association Between Circulating FGF21 Levels And Physical Activity In Abdominal Obese Adults

PURPOSE: Circulating fibroblast growth factor 21 (FGF21) is increased with abdominal obesity and may lead to the development of several chronic diseases such as diabetes and cardiovascular disease. Currently, the effect of daily physical activity on circulating FGF21 levels in abdominal obese adults is unclear. This study aimed to examine the cross-sectional association between circulating FGF21 levels and physical activity in abdominal obese adults. METHODS: This study recruited 207 middle-aged and older adults and classified them as 160 non-obese and 47 abdominal obese adults according to their abdominal circumference (men: ≥ 85 cm, women: ≥ 90 cm). Circulating serum FGF21 levels were evaluated using the ELIZA methods. Daily physical activity levels were objectively assessed using a uniaxial accelerometer and categorized into light-intensity physical activity (LPA) and moderate- to vigorous-intensity physical activity (MVPA). RESULTS: Abdominal obese adults had a higher median value of serum FGF21 levels when compared with non-obese adults (102 pg/mL vs. 139 pg/mL, P = 0.006). Serum FGF21 levels were correlated negatively with the time spent in LPA (rs = −0.326, P = 0.025) and MVPA (rs = −0.349, P = 0.016) in abdominal obese adults, but not in non-obese adults. When the participants were divided into four groups according to abdominal obesity and physical activity status, the significant interaction was indicated between abdominal obesity and MVPA (F = 7.386, P = 0.007), but not LPA. Additionally, abdominal obese adults with higher MVPA levels had lower serum FGF21 levels (P = 0.004). Furthermore, the association between abdominal obesity, MVPA status and FGF21 levels remained significant after adjusting for age, sex, peak oxygen consumption, blood lipid and glucose, current smoking status, and using medications (F = 6.229, P = 0.013). CONCLUSIONS: Lower serum FGF21 concentration was inversely related to higher physical activity levels, particularly in abdominal obese adults. These findings suggest that daily MVPA is effective for decreasing serum FGF21 levels in middle-aged and older adults with abdominal obesity.

Fibroblast growth factor 21 (FGF21) in children and adolescents with chronic kidney disease.

Fibroblast growth factor 21 (FGF21) is one of the members of endocrine arm of FGF family. Its actions as a glucose and lipids metabolism regulator are widely known. Although the mechanism of FGF21 action in kidneys is still under investigation, FGF21 was considered as a marker of early kidney function decline. While many researchers focused on adult subjects in this matter, there are no data regarding children. Therefore, we have investigated the relationship between plasma or urine FGF21 levels and kidney function in a group of 42 pediatric patients with chronic kidney disease (CKD). Anthropometrical parameters and blood pressure were taken, routine biochemical tests were performed. The concentration of FGF21 in serum and urine was determined by enzyme immunoassay. The results revealed significantly higher serum FGF21 concentration among children from CKD group. However, serum FGF21 level was not related to gender, proteinuria, eGFR or renal replacement therapy. Urine FGF21 concentration correlated negatively with albuminuria and positively with eGFR. Documented negative correlation of FGF21 fractional excretion and eGFR is not enough to support the role of FGF21 as a biomarker for predicting kidney disease progression in children and adolescents. Other mechanisms including local kidney FGF21 production or enhanced excretion due to higher extrarenal production may result in higher urine FGF21 concentrations.