Fibroblast Growth Factor 21 in Patients with Acromegaly

2017 ◽  
Vol 125 (10) ◽  
pp. 649-654 ◽  
Author(s):  
Jowita Halupczok-Żyła ◽  
Aleksandra Jawiarczyk-Przybyłowska ◽  
Marek Skrzypski ◽  
Mathias Strowski ◽  
Marek Bolanowski
Keyword(s):  
Growth Factor ◽  
Disease Activity ◽  
Fibroblast Growth Factor ◽  
Body Mass ◽  
Hdl Cholesterol ◽  
Fibroblast Growth Factor 21 ◽  
Control Group ◽  
Fibroblast Growth ◽  
Anthropometric Parameters ◽  
Cholesterol Levels

Abstract Introduction The goal of the study was to investigate fibroblast growth factor-21 (FGF-21) levels in acromegalic patients in relation to the disease activity and to compare them with controls. Further, we aimed to evaluate the associations between FGF-21 and random growth hormone (GH), insulin-like growth factor-1 (IGF-1), metabolic and anthropometric parameters. Materials and methods The study group consisted of 50 acromegalic patients divided into 3 subgroups on the basis of disease activity (AA – active acromegaly, CD – controlled disease, CA – cured acromegaly). 27 subjects were assigned to the control group (CG). Blood samples were obtained from all participants to assess FGF-21, GH, IGF-1, lipids, glucose and insulin levels. Body mass, body mass index and body composition were also evaluated. Results There were no statistically significant differences in FGF-21 concentrations across all groups despite of subjects classification. FGF-21 correlated positively with random GH in the groups: CA, CD+CA, AA+CD+CA (r=0.48, p=0.049; r=0.39, p=0.023; r=0.33, p=0.02; respectively); with IGF-1 in the AA+CD+CA group (r=0.29, p=0.041); with triglycerides in the following groups: CD, CD+CA, AA+CD+CA (r=0.63, p=0.08; r=0.44, p=0.01; r=0.37, p=0.007; respectively) and with age in the CG and CD+CA groups (r=0.41, p=0.029; r=0.42, p=0.029; respectively). There were statistically significant negative correlations between FGF-21 and HDL-cholesterol levels in the groups: CD, CD+CA, AA+CD+CA (r=-0.53, p=0.03; r=-0.37, p=0.032; r=-0.29, p=0.036, respectively). Conclusions FGF-21 levels were similar in patients with acromegaly compared to controls. However, our results indicate that FGF-21 may have a potential role in the development of acromegaly complications.

scholarly journals Effect of Fibroblast Growth Factor 21 on the Expression of TLR4 and BAMBI Genes in Cholesterol-Treated Human Hepatic Stellate Cells

2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Elham Shakerian ◽  
Narges Mohammad Taghvaei ◽  
Zohre Askari ◽  
Reza Afarin
Keyword(s):  
Growth Factor ◽  
Mrna Expression ◽  
Fibroblast Growth Factor ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Fibroblast Growth Factor 21 ◽  
Control Group ◽  
Type I ◽  
Fibroblast Growth ◽  
Human Hscs

Background: Activated hepatic stellate cells (HSCs) are the primary mediators in the progression of hepatic fibrosis. The activation of toll-like receptor 4 (TLR4) signaling leads to the downregulation of the transmembrane inhibitory transforming growth factor-beta (TGF-β) pseudoreceptor BMP and activin membrane-bound inhibitor (BAMBI) on HSCs. Fibroblast growth factor 21 (FGF21) is a natural secretory protein in the body with effects, such as the reduction of fat accumulation and oxidation of lipids; however; no study has investigated FGF21 ability to prevent the progression of liver fibrosis. Objectives: This study aimed to examine the beneficial effects of FGF21 to reduce cholesterol-activated human HSCs. Methods: The human HSCs were incubated in media containing different concentrations of cholesterol, including 25, 50, 75, 100, 125, and 150 μM, for 24 h and then incubated with FGF21 for 24 h. Total ribonucleic acids were extracted and reversely transcribed into complementary deoxyribonucleic acid. A quantitative real-time polymerase chain reaction was performed in this study. Results: The results showed that the messenger ribonucleic acid (mRNA) expression of TGF-β, collagen, type I, alpha 1 (collagen1α), and TLR4 genes increased significantly in the presence of cholesterol (75 and 100 μM), compared to that of the control group (* P < 0.05, ** P < 0.01, and *** P < 0.001); nevertheless, the mRNA expression of the BAMBI gene significantly reduced, compared to that of the control group (* P < 0.05). The FGF21 significantly reduced the mRNA expression of TGF-β, collagen1α, and TLR4 genes (# P < 0.05). The mRNA expression of the BAMBI gene significantly increased with FGF21 (# P < 0.05). Conclusions: It was concluded that the treatment with FGF21 reduces the cholesterol-activated HSCs by decreasing the mRNA expression of the TLR4, TGF-β, and collagen1α genes and increasing the mRNA expression of the BAMBI gene.

scholarly journals SAT-046 Insulin-Like Growth Factor and Fibroblast Growth Factor 21 in Men with Klinefelter Syndrome

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Simon Chang ◽  
Rikke Hjortebjerg ◽  
Anders Bojesen ◽  
Mette Bjerre ◽  
Claus Hojbjerg Gravholt
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Klinefelter Syndrome ◽  
Protein A ◽  
Serum Levels ◽  
Fibroblast Growth Factor 21 ◽  
Control Group ◽  
Insulin Like Growth Factor ◽  
Fibroblast Growth ◽  
Igf System

Abstract Background: Men with 47, XXY Klinefelter syndrome (KS) commonly present with obesity, metabolic disorders, and insulin insensitivity. The insulin-like growth factor (IGF) system has pleiotropic effects including regulation of glucose metabolism. Fibroblast growth factor 21 (FGF21) is associated with weight loss and favourable metabolic changes, but patients with obesity or type 2 diabetes might be resistant to this effect despite presenting with increased levels. Aim: To describe levels of components in the IGF system and FGF21 among men with KS, either treated or not treated with testosterone supplementation therapy (TT), in comparison with control males. Methods: A total of 66 men with KS were included, 33 without current TT and 33 with current TT. A control group of 70 healthy age-matched males were included. Serum levels of insulin-like growth factor 1 (IGF-1), insulin-like growth factor-binding protein 3 (IGFBP3), pregnancy-associated plasma protein A (PAPP-A), FGF21, and fibroblast activation protein (FAP) were compared between the three groups applying the Kruskal-Wallis test. Results: Levels of (IGF-1 µg/L) were not different between the groups (median (25-75 %), untreated KS 162 (140-201.5), treated KS 165 (128.5-215), controls 176.5 (150.8-214.5), p=0.5). Similarly, FGF21 levels (ng/L) were comparable between the groups (median (25-75 %), untreated KS 84.7 (53.3-217.6), treated KS 97.2 (56.4-224.8), controls 100.3 (66.0-191.0), p=0.9). Levels of IGFBP3, PAPP-A and FAP were also found to be comparable between the groups (p≥0.2). Conclusion: This was the first study investigating FGF21 in men with KS. Our results indicate that regulation of the IGF-1 system and levels of FGF21 are not altered in men with KS compared with age-matched controls, and that TT in men with KS does not affect these systems.

scholarly journals Thioredoxin-1 and Correlations of the Plasma Cytokines Regarding Aortic Valve Stenosis Severity

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 1041
Author(s):  
Peteris Tretjakovs ◽  
Juris Lurins ◽  
Simons Svirskis ◽  
Gita Gersone ◽  
Dace Lurina ◽  
...  
Keyword(s):  
Growth Factor ◽  
Aortic Valve ◽  
Fibroblast Growth Factor ◽  
Aortic Valve Stenosis ◽  
Plasma Levels ◽  
Fibroblast Growth Factor 21 ◽  
Control Group ◽  
Fibroblast Growth ◽  
Local Inflammatory Response ◽  
Thioredoxin 1

Aortic valve stenosis (AS) develops not only with a pronounced local inflammatory response, but also oxidative stress is involved. The aim of this study was to evaluate the plasma levels of thioredoxin-1 (TRX1), myeloperoxidase (MPO), chemerin, growth differentiation factor 15 (GDF-15), angiopoietin-2 (Ang-2), vascular endothelial growth factor A (VEGF-A), fibroblast growth factor 2 (FGF-2), fibroblast growth factor 21 (FGF-21), and metalloproteinase (MMP)-1, -3, and -9 in acquired AS patients as well as to clarify the correlations of TXR1 and the plasma inflammatory biomarkers regarding AS severity. AS patients were classified into three groups: 16 patients with mild AS stenosis, 19 with moderate and 11 with severe AS, and 30 subjects without AS were selected as a control group. AS patients had significantly higher plasma levels of TRX1 compared to controls, but the highest difference was found in mild AS patients compared to the controls. We conclude that AS is associated with significantly increased plasma TRX1 levels, and TRX1 might serve as a specific and sensitive biomarker of AS. TRX1 and also chemerin, GDF-15, VEGF-A, FGF-2 and FGF-21 significantly correlate with AS severity degrees. TRX1 also showed positive association with FGF-2, VEGF-A, and MMP-3 in all AS patients.

scholarly journals Novel Adipokine Fibroblast Growth Factor 21 Is Increased in Rheumatoid Arthritis

2012 ◽  
pp. 489-494 ◽  
Author(s):  
H. HULEJOVÁ ◽  
L. ANDRÉS CEREZO ◽  
M. KUKLOVÁ ◽  
O. PECHA ◽  
T. VONDRÁČEK ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Growth Factor ◽  
Synovial Fluid ◽  
Disease Activity ◽  
Fibroblast Growth Factor ◽  
Serum Glucose ◽  
Lipid Profiles ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Reactive Protein

Fibroblast growth factor-21 (FGF-21) has been recently characterized as a new adipokine. The aim of this study was to assess FGF-21 levels in patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and to study the relationship between FGF-21, disease activity and metabolic status. The levels of FGF-21 in serum and synovial fluid samples from 38 patients with RA and 42 control individuals with OA were determined by ELISA. Patients were assessed for disease activity using the disease activity score (DAS28), a serum glucose and lipid profile. Age, sex and BMI-adjusted FGF-21 levels in the serum (p=0.024) and synovial fluid (p=0.010) samples were significantly higher in patients with RA when compared with OA. The levels of FGF-21 in the serum significantly correlated with the levels in the synovial fluid. Serum and synovial fluid FGF-21 levels adjusted for confounders correlated positively with C-reactive protein. The levels of FGF-21 were positively correlated with BMI in patients with RA; however, the levels were not associated with disease activity or lipid profiles. Furthermore, serum FGF-21 levels were significantly higher in seropositive compared with seronegative RA patients. This work shows that patients with seropositive RA have increased levels of FGF-21. The results suggest that FGF-21 is related to BMI but not disease activity or lipid profiles in patients with RA.

scholarly journals Transient postprandial increase in intact circulating fibroblast growth factor-21 levels after Roux-en-Y gastric bypass: a randomized controlled clinical trial

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11174
Author(s):  
Mette S. Nielsen ◽  
Susanna Søberg ◽  
Julie B. Schmidt ◽  
Anne Chenchar ◽  
Anders Sjödin ◽  
...  
Keyword(s):  
Weight Loss ◽  
Gastric Bypass ◽  
Growth Factor ◽  
Energy Balance ◽  
Fibroblast Growth Factor ◽  
Negative Energy ◽  
Negative Energy Balance ◽  
Fibroblast Growth Factor 21 ◽  
Control Group ◽  
Fibroblast Growth

Background Despite a consistent link between obesity and increased circulating levels of fibroblast growth factor-21 (FGF21), the effect of weight-loss interventions on FGF21 is not clear. We aimed to determine the short- and long-term effects of Roux-en-Y gastric bypass (RYGB) on intact plasma FGF21 levels and to test the hypothesis that RYGB, but not diet-induced weight loss, increases fasting and postprandial responses of FGF21. Method Twenty-eight participants with obesity followed a low-calorie diet for 11 weeks. The 28 participants were randomized to undergo RYGB surgery at week 8 (RYGB group, n = 14), or to a control group scheduled for surgery at week 12 (n = 14). Fasting levels of intact, biologically active FGF21 (amino acids 1-181) and its postprandial responses to a mixed meal were assessed at week 7 and 11, and 78 weeks (18 months) after RYGB. Results At week 11 (3 weeks after RYGB), postprandial responses of intact FGF21 were enhanced in participants undergoing surgery at week 8 (change from week 7 to 11: P = 0.02), whereas no change was found in non-operated control participants in similar negative energy balance (change from week 7 to 11: P = 0.81). However, no between-group difference was found (P = 0.27 for the group-week-time interaction). Fasting, as well as postprandial responses in intact FGF21, were unchanged 18 months after RYGB when both the RYGB and control group were collapsed together (change from week 7 to 78 weeks after RYGB: P = 0.17). Conclusion Postprandial intact FGF21 levels were enhanced acutely after RYGB whereas no signs of sustained changes were found 18 months after surgery. When comparing the acute effect of RYGB with controls in similar negative energy balance, we failed to detect any significant differences between groups, probably due to the small sample size and large inter-individual variations, especially in response to surgery.

scholarly journals Fibroblast Growth Factor 23 to Alpha-Klotho Index Correlates with Systemic Sclerosis Activity: A Proposal for Novel Disease Activity Marker

2018 ◽  
Vol 7 (12) ◽  
pp. 558 ◽  
Author(s):  
Przemyslaw Kotyla ◽  
Aneta Kruszec-Zytniewska ◽  
Aleksander Owczarek ◽  
Magdalena Olszanecka-Glinianowicz ◽  
Jerzy Chudek
Keyword(s):  
Systemic Sclerosis ◽  
Growth Factor ◽  
Disease Activity ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Control Group ◽  
Fibroblast Growth ◽  
Potential Marker ◽  
System Functioning ◽  
Modified Rodnan Skin Score

Systemic sclerosis, a connective tissue disease, is characterized by thickening of the skin, massive fibrosis of internal organs, vasculopathy, and immune system functioning aberration. Recently, vitamin D (VD) deficit, seen almost universally in patients with systemic sclerosis (SSc), has gained much attention. VD metabolism is precisely orchestrated at the level of the kidney by regulators: parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) and their receptors with a FGF23 co-receptor—α-Klotho. The aim of this study was to assess the levels of VD, α-Klotho, FGF23 in SSc patients and to find the relationship between those parameters and disease activity. We enrolled 48 SSc patients with a diffuse variant of SSc and 23 sex- and age-matched healthy volunteers that served as the control group (CG). Patients were characterized by lower level of VD in comparison to CG (19.8 (12.6–28.9) vs. 24.5 (21.3–31.5) ng/mL; p < 0.01), significantly reduced levels of iFGF23 (19.3 (12.1–30.5) vs. 73.9 (59.7–110.2) pg/mL p < 0.001), and similar α-Klotho concentrations (1415 ± 557 vs. 1526 ± 397 pg/mL), respective. None of these parameters correlated with the extent of skin involvement (modified Rodnan Skin Score) and disease activity according to Eustar 2017 guidelines. The FGF23/α-Klotho index was significantly reduced in SSc patients (0.013 (0.0081–0.025) vs. 0.055 (0.038–0.095); p < 0.001), and its log10 correlated (r = 0.35; p < 0.001) with disease activity score (Eular2017). Our data showed that the FGF23/α-Klotho index may be considered as a novel, potential marker of systemic sclerosis activity.

scholarly journals Serum Fibroblast Growth Factor 21 Levels in Children and Adolescents with Hashimoto’s Thyroiditis before and after l-Thyroxin Medication: A Prospective Study

Medicina ◽  
2021 ◽  
Vol 57 (12) ◽  
pp. 1374
Author(s):  
Pavlos Drongitis ◽  
Eleni P. Kotanidou ◽  
Anastasios Serbis ◽  
Vasiliki Rengina Tsinopoulou ◽  
Spyridon Gerou ◽  
...  
Keyword(s):  
Growth Factor ◽  
Children And Adolescents ◽  
Fibroblast Growth Factor ◽  
Subclinical Hypothyroidism ◽  
Hashimoto’S Thyroiditis ◽  
Hashimoto's Thyroiditis ◽  
Fibroblast Growth Factor 21 ◽  
Control Group ◽  
Fibroblast Growth ◽  
Sites Of Action

Backgrounds and Objectives: Fibroblast growth factor 21 (FGF-21) is a complex hormone, sharing common sites of action with thyroid hormones. We investigated the association among FGF-21 levels, resting metabolic rate (RMR), and l-thyroxin (LT4) treatment in children and adolescents with Hashimoto’s thyroiditis. Materials and Methods: A total of 60 youngsters with chronic autoimmune thyroiditis (AIT) (30 with subclinical hypothyroidism, 30 with euthyroidism) and 30 age and sex-matched healthy participants (5–18 years old) were enrolled in the study. Anthropometric, biochemical parameters, and RMR levels were assessed in all participants; serum FGF-21 levels were measured in the control group and the group with subclinical hypothyroidism before and six months after medication with LT4. Results: FGF-21 levels were lower in the treatment group compared with the healthy ones, but this difference was not statistically significant (p > 0.05); despite the increase in FGF-21 levels after six months of LT4 treatment, this difference was not statistically significant (p > 0.05). Free thyroxin (FT4) levels correlated well with FGF-21 levels (r = 0.399, p < 0.01), but further analysis revealed no interaction between these two variables. Both patient groups presented elevated triglyceride (TG) levels compared to controls (p < 0.05). LT4 treatment had no impact on RMR and lipid or liver or glycaemic parameters. An increase in fat mass and fat-free mass were reported, independently of FGF-21 levels. Conclusions: In youngsters with subclinical hypothyroidism due to Hashimoto’s thyroiditis, the serum FGF-21 levels are not significantly lower than in healthy individuals and increase after treatment with LT4 without a statistical significance. Further studies with a large number of young patients and severe hypothyroidism are recommended to confirm our results.

scholarly journals Lower Serum Fibroblast Growth Factor 21 Levels are Associated with Normal Lumbar Spine Bone Mineral Density in Hemodialysis Patients

2020 ◽  
Vol 17 (6) ◽  
pp. 1938
Author(s):  
Yin-Ting Wu ◽  
Bang-Gee Hsu ◽  
Chih-Hsien Wang ◽  
Yu-Li Lin ◽  
Yu-Hsien Lai ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Body Mass Index ◽  
Body Weight ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Body Mass ◽  
Bone Mineral ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Mineral Density

Recent evidence has indicated that fibroblast growth factor 21 (FGF21) regulates longitudinal bone growth, with increased FGF21 levels leading to bone loss. The present study evaluated the relationship between bone mineral density (BMD) and serum FGF21 levels in patients undergoing hemodialysis (HD). We analyzed blood samples from 95 patients undergoing HD and measured BMD using dual-energy X-ray absorptiometry of the lumbar vertebrae (L2–L4). Serum FGF21 concentrations were determined using a commercially available enzyme-linked immunosorbent assay kit. Thirteen (11.6%) patients were found to have osteoporosis, 27 (28.4%) osteopenia, and 57 patients had normal BMD. Advanced age and decreased body mass index, height, body weight, waist circumference, and triglyceride level were associated with lower lumbar T-scores, as were increased alkaline phosphatase, urea reduction rate, fractional clearance index for urea, and FGF21 levels. Low log-FGF21, increased body mass index, increased pre-HD body weight, and increased logarithmically transformed triglycerides (log-TG) were found to be significantly and independently associated with lumbar BMD by multivariate forward stepwise linear regression analysis with adjustment for significant confounders. We conclude that high serum FGF21 level is negatively associated with BMD in patients undergoing HD.

scholarly journals Fibroblast Growth Factor 21 Reduces Cholesterol-Induced Hepatic Fibrogenesis by Inhibiting TGF-β/Smad3C Signaling Pathway in LX2 Cells

2021 ◽  
Vol 21 (4) ◽  
Author(s):  
Reza Afarin ◽  
Hossein Babaahmadi Rezaei ◽  
Seyed Hamid Yaghouti ◽  
Narges Mohammad Taghvaei
Keyword(s):  
Growth Factor ◽  
Liver Fibrosis ◽  
Fibroblast Growth Factor ◽  
Cell Line ◽  
Signaling Pathway ◽  
Group Treatment ◽  
Fibroblast Growth Factor 21 ◽  
Control Group ◽  
Fibroblast Growth ◽  
Hepatic Fibrogenesis

Background: Liver fibrosis is often attributed to the activation of hepatic stellate cells (HSCs) and excessive scar formation in the liver. Advanced stages of the disease often lead to liver cirrhosis and hepatocellular carcinoma (HCC). Fibroblast growth factor 21 (FGF21) is a secreted protein, which has anti-diabetic and lipocaic effects. Objectives: In this study, we investigated the ability of FGF21 to reduce hepatic fibrogenesis due to the accumulation of free cholesterol in the LX2 cell line (a type of HSC-derived cell line) and its mechanism of action. Methods: Cells were treated with 25, 50, 75, and 100 μM concentrations of cholesterol for 24 and 48 h. The mRNA expression of genes of TGF-β, αSMA, and collagen1α and the level of Smad3C protein were measured to assess liver fibrosis. Next, the cells were treated with FGF21 for 24 h, and the expression levels of TGF-β, αSMA, collagen 1α, and Smad3C protein were measured. Results: The results showed that the expression of TGF-β, αSMA, collagen 1α genes, and also the level of Smad3C protein in the presence of cholesterol increased significantly compared to the control group. Treatment with FGF-21 also significantly reduced the expression of TGF-β, αSMA, and collagen 1α genes. Conclusions: Cholesterol by increasing the level of Smad3C protein and activating the TGF-β signaling pathway increases major proteins involved in the production of extracellular matrix, including collagen 1α. Besides, FGF21 inhibits the further activation of HSCs by inhibiting the TGF-β/Smad3C signaling pathway and thus can prevent the progression of liver fibrosis.

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