scholarly journals Fibroblast Growth Factor 21, Adiponectin, and Irisin as Markers of Unfavorable Metabolic Features in 12-Year-Old Children

2019 ◽  
Vol 3 (4) ◽  
pp. 825-837 ◽  
Author(s):  
Satu Seppä ◽  
Sirpa Tenhola ◽  
Raimo Voutilainen

Abstract Context Among cytokines, fibroblast growth factor 21 (FGF21), adiponectin (Adn), and irisin have been considered potential biomarkers for insulin sensitivity (IS). Objective We evaluated whether serum FGF21, Adn, and irisin associate with markers of IS and serum lipids in 12-year-old children. Design, Participants, and Main Outcome Measures This cohort study included 192 12-year-old children (109 girls). Seventy-eight of them had been born appropriate for gestational age (AGA), 70 small for gestational age (SGA), and 44 from preeclamptic pregnancies (PREs) as AGA. Fasting serum FGF21, Adn, irisin, lipids, inflammatory markers, and IS markers were measured. Quantitative insulin sensitivity check index (QUICKI) was calculated. Results The means of serum FGF21, high molecular weight (HMW) Adn, and irisin did not differ between the sexes or between the SGA, AGA, and PRE children. In the whole study population, FGF21 associated positively with irisin and uric acid and negatively with leptin and high-density lipoprotein cholesterol (HDL-C). HMW Adn associated positively with total Adn, HDL-C, leptin, and SHBG. Apart from FGF21, irisin associated positively with insulin, high-sensitivity C-reactive protein, γ-glutamyltransferase, and triglycerides, and negatively with QUICKI, SHBG, and IGF binding protein-1. In multivariate regression analyses, irisin predicted lower IS and HMW Adn predicted higher HDL-C body mass index-independently, whereas FGF21 had no independent contribution to IS or lipid variables. Conclusion In 12-year-old children, serum irisin was associated with markers reflecting reduced IS. HMW Adn predicted HDL-C, whereas FGF21 did not contribute to IS or lipid parameters in multivariate regression analyses.

2017 ◽  
Author(s):  
◽  
Gabriela V. Tamassia

Obesity and diabetes play a major role in many diseases prevalent in our current society. Fibroblast Growth Factor 21 (FGF21) is a recently discovered hormone that has potential for therapeutic treatment of obesity and diabetes. It acts as a hormone in times of metabolic stress and is shown to stimulate hepatic fatty acid oxidation, ketogenesis, induce weight loss, allow for sustained decrease in plasma glucose and triglycrides, and decrease the growth hormone response. Obese or diabetic individuals often have higher than normal amounts of circulating FGF21; consequently, they may be considered FGF21 resistant. It is then advantageous to have an assay to measure FGF21 that will allow us to study FGF21 further. It is also important to study FGF21 in various livestock species for potential biomarkers, or as indicators of carcass quality that could prove to advance further research. We have developed a working FGF21 assay using an amplified luminescent proximity homogeneous assay (AlphaLISA). It is a homogeneous, no-wash immunoassay with high sensitivity and wide dynamic range. It is a bead based technology that brings two antibodies near each other allowing for an unstable singlet oxygen to trigger a downstream cascade of chemical events leading to a sharp intense chemiluminescent emission that can be read on an EnVision machine. The assay was set up using a 'sandwich' design with guinea pig or rabbit anti-bovine FGF21 antibodies attached to the acceptor beads and biotinylated rabbit anti-bovine FGF21 antibodies x attached to a streptavidin coated donor bead. The assay has a working range from 0.2-200 ng/ml. Standard curves in serum from bovine, porcine, rabbit, rat, ewe, fetal bovine has been conducted and assay conditions were optimized for each. Manipulations of the sera were necessary in order to get functional curves. These included diluting it 2 fold or more, depending on the species, and increasing incubation temperatures. The assay can function using both serum and plasma.


2014 ◽  
Vol 92 (11) ◽  
pp. 927-935 ◽  
Author(s):  
Wenhe Zhu ◽  
Changwen Wang ◽  
Lei Liu ◽  
Yan Li ◽  
Xiaokun Li ◽  
...  

Fibroblast growth factor 21 (FGF-21), which is a modulator of glucose and lipid homeostasis, acts as a novel therapeutic reagent for many metabolic perturbations. However, its potential as a treatment for cardiovascular disease, especially atherosclerosis (AS) has not been fully explored. Here, we report that recombinant FGF-21 improves resistance to cell damage from oxidative stress in vitro, and from atherosclerosis in vivo. Human umbilical vein endothelial cells (HUVECs) were induced with H2O2, followed by treatment with high purity recombinant FGF-21. The results indicated that FGF-21 significantly enhanced cell viability and decreased the degree of DNA fragmentation in HUVECs, as caused by H2O2 stress induction. Further studies revealed that FGF-21 inhibited H2O2-induced cell apoptosis by preventing the activation of mitogen-activated protein kinase (MAPK) signaling pathways. In an established rat model, FGF-21 dramatically improved the condition of atherosclerotic rats by decreasing serum levels of total triglyceride (TG), low density lipoprotein cholesterol (LDL-C), and total cholesterol (TC), and by increasing the serum levels of high density lipoprotein cholesterol (HDL-C). FGF-21 also has antioxidant effects in the atherosclerotic rat, such that increased levels of superoxide dismutase, reduced glutathione, and reduced malondialdehyde were observed. These data provide novel insight into the potential use of FGF-21 in the prevention and treatment of human cardiovascular diseases.


2016 ◽  
Vol 35 (2) ◽  
pp. 142-149 ◽  
Author(s):  
Narattaphol Charoenphandhu ◽  
Panan Suntornsaratoon ◽  
Nateetip Krishnamra ◽  
Piangkwan Sa-nguanmoo ◽  
Pongpun Tanajak ◽  
...  

2009 ◽  
Vol 1 (3) ◽  
pp. 76 ◽  
Author(s):  
Yani Lina ◽  
Gatot Susilo Lawrence ◽  
Andi Wijaya ◽  
Suryani As'ad

BACKGROUND: Fibroblast growth factor-21 (FGF21) is known as an important endocrine and paracrine regulator of metabolic homeostasis. Recent studies have shown that FGF21 attenuates lipolysis in human adipocytes, which is suggested as a FGF21's mechanism as anti-hyperlipidemia, anti-hyperglycemia and anti-obesity. The aim of this study was to measure the correlation between FGF21, FFA, hsCRP and HOMA-IR among Indonesian obese non diabetic males.METHOD: The study was observational with cross sectional design. The analysis was done in 137 subjects aged 30-60 years with non diabetic abdominal obesity. We measured the biochemical markers FGF21, FFA, hsCRP, fasting insulin and fasting glucose. We also measured weight, height, waist circumrefence (WC), creatinine, serum glutamin oxaloacetic transaminase (SGOT), and serum glutamic pyruvic transaminase (SGPT), systolic blood pressure (SBP) and diastolic blood pressure (DBP). Correlation between markers was measured using Pearson and Spearman's analysis.  RESULT: There were significant positive correlations between FGF21-HOMA-IR (r=0.314, p=0.000); FGF21-WC (r=0.173, p=0.043); FFA=hsCRP (r=0.270, p=0.001); and WC-HOMA-IR (r=0.279, p=0.001). There was significant negative correlation between FGF21-FFA (r=-0.038, p=0.657) and FGF21-hsCRP (r=-0.061, p=0.482). CONCLUSION: In this study we found that although there was no significant correlation, FGF21 might act as an anti-lipolytic and anti-inflammation agent among Indonesian obese non-diabetic males. Our findings agree with results of previous studies that the positive correlation between FGF21-WC and FGF21-HOMA-IR moght occur as a compensatory mechanism or resistance to FGF21 in obesity.KEYWORDS: Obesity, FGF21, FFA, hsCRP, HOMA-IR


2021 ◽  
Vol 8 ◽  
Author(s):  
Yingjie Chee ◽  
Grace Lx Toh ◽  
Chien Joo Lim ◽  
Liuh Ling Goh ◽  
Rinkoo Dalan

Background and Aims: Fibroblast growth factor 21 (FGF21), an emerging metabolic hepatokine, is associated with atherosclerosis. An interaction with sex has been described in various populations. We aimed to study whether sex modulates the relationship between FGF21 and subclinical carotid atherosclerosis in a diabetes-enriched multiethnic population of Singapore. We explore differences in intermediary mechanisms, in terms of hypertension, lipids, and inflammation, between FGF21 and atherosclerosis.Methods: We recruited 425 individuals from a single diabetes center in Singapore, and demographics, anthropometry, metabolic profile, FGF21, and carotid ultrasonography were performed. Multivariable logistic regression models were used to study the association between subclinical atherosclerosis and FGF21 adjusting for age, ethnicity, body mass index (BMI), hemoglobin A1c (HbA1c), systolic and diastolic blood pressures, and low-density lipoprotein (LDL)-cholesterol separately for males and females as two groups after an interaction test.Results: An interaction test assessing interaction by sex on the relationship between subclinical atherosclerosis and FGF21 showed a significant interaction with sex (Pinteraction = 0.033). In the female subgroup, significant independent associations of standardized lnFGF21 with subclinical atherosclerosis were seen, with 1 SD increment in lnFGF21 being associated with 1.48-fold (95% CI: 1.03, 2.12; p = 0.036) increase in risk. In the male subgroup, the association of subclinical atherosclerosis with standardized lnFGF21 was not significant [odds ratio (OR) (95% CI): 0.90 (0.63, 1.28); p = 0.553]. We found sex interactions with pulse pressure being significantly associated in females only and triglycerides and C-reactive protein being associated with males only.Conclusion: FGF21 is positively associated with subclinical carotid atherosclerosis in women, but not in men. The sex–racial patterns in the mechanisms by which FGF21 causes subclinical atherosclerosis needs to be explored in larger population-based studies and mechanistically studied in greater detail.


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