scholarly journals Development of a fibroblast growth factor 21 assay

2017 ◽  
Author(s):  
◽  
Gabriela V. Tamassia
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Dynamic Range ◽  
Metabolic Stress ◽  
High Sensitivity ◽  
Fibroblast Growth Factor 21 ◽  
Acid Oxidation ◽  
Fibroblast Growth ◽  
Obesity And Diabetes ◽  
Hepatic Fatty Acid Oxidation

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.

scholarly journals The starvation hormone, fibroblast growth factor-21, extends lifespan in mice

eLife ◽  
2012 ◽  
Vol 1 ◽  
Author(s):  
Yuan Zhang ◽  
Yang Xie ◽  
Eric D Berglund ◽  
Katie Colbert Coate ◽  
Tian Teng He ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Somatic Growth ◽  
Fibroblast Growth Factor 21 ◽  
Acid Oxidation ◽  
Fibroblast Growth ◽  
Amp Kinase ◽  
Starvation Response ◽  
Nad Metabolism ◽  
Hepatic Fatty Acid Oxidation

Fibroblast growth factor-21 (FGF21) is a hormone secreted by the liver during fasting that elicits diverse aspects of the adaptive starvation response. Among its effects, FGF21 induces hepatic fatty acid oxidation and ketogenesis, increases insulin sensitivity, blocks somatic growth and causes bone loss. Here we show that transgenic overexpression of FGF21 markedly extends lifespan in mice without reducing food intake or affecting markers of NAD+ metabolism or AMP kinase and mTOR signaling. Transcriptomic analysis suggests that FGF21 acts primarily by blunting the growth hormone/insulin-like growth factor-1 signaling pathway in liver. These findings raise the possibility that FGF21 can be used to extend lifespan in other species.

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
Keyword(s):  
Insulin Sensitivity ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Gestational Age ◽  
Multivariate Regression ◽  
Density Lipoprotein ◽  
High Sensitivity ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Regression Analyses

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.

scholarly journals Fibroblast Growth Factor 21 (FGF21), Free Fatty Acid (FFA), High Sensitivity C-reactive Protein (hsCRP) and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) Among Indonesian Obese Non-Diabetic Males

2009 ◽  
Vol 1 (3) ◽  
pp. 76 ◽  
Author(s):  
Yani Lina ◽  
Gatot Susilo Lawrence ◽  
Andi Wijaya ◽  
Suryani As'ad
Keyword(s):  
Blood Pressure ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
High Sensitivity ◽  
Significant Negative Correlation ◽  
Fibroblast Growth Factor 21 ◽  
Compensatory Mechanism ◽  
Model Assessment ◽  
Fibroblast Growth ◽  
Cross Sectional

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

A combined docosahexaenoic acid–thyroid hormone protocol upregulates rat liver β-Klotho expression and downstream components of FGF21 signaling as a potential novel approach to metabolic stress conditions

2017 ◽  
Vol 8 (11) ◽  
pp. 3980-3988 ◽  
Author(s):  
R. Vargas ◽  
B. Riquelme ◽  
J. Fernández ◽  
L. A. Videla
Keyword(s):  
Growth Factor ◽  
Thyroid Hormone ◽  
Docosahexaenoic Acid ◽  
Fibroblast Growth Factor ◽  
Metabolic Stress ◽  
Fibroblast Growth Factor 21 ◽  
Peroxisome Proliferator ◽  
Fibroblast Growth ◽  
Peroxisome Proliferator Activated Receptor ◽  
Novel Approach

We study the mechanism of how liver preconditioning by a DHA and triiodothyronine combined protocol underlies peroxisome-proliferator activated receptor α (PPARα)-fibroblast growth factor 21 (FGF21) upregulation.

scholarly journals Hepatic CREB3L3 Controls Whole-Body Energy Homeostasis and Improves Obesity and Diabetes

Endocrinology ◽  
2014 ◽  
Vol 155 (12) ◽  
pp. 4706-4719 ◽  
Author(s):  
Yoshimi Nakagawa ◽  
Aoi Satoh ◽  
Sachiko Yabe ◽  
Mika Furusawa ◽  
Naoko Tokushige ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Energy Homeostasis ◽  
Binding Protein ◽  
Whole Body ◽  
Fibroblast Growth Factor 21 ◽  
Peroxisome Proliferator ◽  
Fibroblast Growth ◽  
Peroxisome Proliferator Activated Receptor ◽  
Obesity And Diabetes

Transcriptional regulation of metabolic genes in the liver is the key to maintaining systemic energy homeostasis during starvation. The membrane-bound transcription factor cAMP-responsive element-binding protein 3-like 3 (CREB3L3) has been reported to be activated during fasting and to regulate triglyceride metabolism. Here, we show that CREB3L3 confers a wide spectrum of metabolic responses to starvation in vivo. Adenoviral and transgenic overexpression of nuclear CREB3L3 induced systemic lipolysis, hepatic ketogenesis, and insulin sensitivity with increased energy expenditure, leading to marked reduction in body weight, plasma lipid levels, and glucose levels. CREB3L3 overexpression activated gene expression levels and plasma levels of antidiabetic hormones, including fibroblast growth factor 21 and IGF-binding protein 2. Amelioration of diabetes by hepatic activation of CREB3L3 was also observed in several types of diabetic obese mice. Nuclear CREB3L3 mutually activates the peroxisome proliferator-activated receptor (PPAR) α promoter in an autoloop fashion and is crucial for the ligand transactivation of PPARα by interacting with its transcriptional regulator, peroxisome proliferator-activated receptor gamma coactivator-1α. CREB3L3 directly and indirectly controls fibroblast growth factor 21 expression and its plasma level, which contributes at least partially to the catabolic effects of CREB3L3 on systemic energy homeostasis in the entire body. Therefore, CREB3L3 is a therapeutic target for obesity and diabetes.

Fibroblast growth factor-21 predicts adverse outcome in community-acquired pneumonia

2018 ◽  
Author(s):  
Fahim Ebrahimi ◽  
Carole Wolffenbuttel ◽  
Claudine A Blum ◽  
Beat Muller ◽  
Philipp Schuetz ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Adverse Outcome ◽  
Community Acquired Pneumonia ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth

Effects of anti-inflammatory treatment on fibroblast growth factor-21 in obesity and metabolic syndrome

2019 ◽  
Author(s):  
Fahim Ebrahimi ◽  
Sandrine Urwyler ◽  
Matthias Betz ◽  
Emanuel Christ ◽  
Philipp Schuetz ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Anti Inflammatory
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