scholarly journals Fibroblast Growth Factor 21 (Fgf21) Gene Expression Is Elevated in the Liver of Mice Fed a High-Carbohydrate Liquid Diet and Attenuated by a Lipid Emulsion but Is Not Upregulated in the Liver of Mice Fed a High-Fat Obesogenic Diet

2016 ◽  
Vol 146 (2) ◽  
pp. 184-190 ◽  
Author(s):  
Lei Hao ◽  
Kuan-Hsun Huang ◽  
Kyoko Ito ◽  
Sudathip Sae-tan ◽  
Joshua D Lambert ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Lipid Emulsion ◽  
Liquid Diet ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
High Fat ◽  
High Carbohydrate ◽  
Obesogenic Diet

scholarly journals The Orphan Nuclear Receptor ERRγ Regulates Hepatic CB1 Receptor-Mediated Fibroblast Growth Factor 21 Gene Expression

PLoS ONE ◽  
2016 ◽  
Vol 11 (7) ◽  
pp. e0159425 ◽  
Author(s):  
Yoon Seok Jung ◽  
Ji-Min Lee ◽  
Don-Kyu Kim ◽  
Yong-Soo Lee ◽  
Ki-Sun Kim ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Nuclear Receptor ◽  
Cb1 Receptor ◽  
Fibroblast Growth Factor 21 ◽  
Orphan Nuclear Receptor ◽  
Fibroblast Growth

Effect of vanillic acid and exercise training on fatty liver and insulin resistance in rats: Possible role of fibroblast growth factor 21 and autophagy

2021 ◽  
Keyword(s):  
Growth Factor ◽  
Fatty Liver ◽  
Fibroblast Growth Factor ◽  
Vanillic Acid ◽  
High Fat Diet ◽  
Male Rats ◽  
Swimming Exercise ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
High Fat

Abstract Background and aims The prevalence of non-alcoholic fatty liver disease has been alarmingly increased with no lines of effective treatment. Vanillic acid is a naturally occurring polyphenol with promising therapeutic effects. Exercise is well known to be an effective tool against obesity and its consequences. Thus, we aim to study the effect of vanillic acid alone and along with exercise on fatty liver induced by a high-fat diet in a rat model and to investigate possible novel mechanisms involved in their action. Methods In this study, 40 male rats were divided equally into five groups: control (standard chow diet), HFD (high-fat diet), HFD+VA (HFD+ vanillic acid (50 mg/kg/day orally), HFD+EX (HFD+ swimming exercise 5 days/week), HFD+VA+EX (HFD+ vanillic acid+ swimming exercise) for eight weeks. Results Body mass, liver weight, liver enzymes, cholesterol, and triglycerides were significantly decreased in the combined VA+EX group, with marked improvement in hyperglycemia, hyperinsulinemia, and consequently HOMA-IR index compared to the HFD group. These improvements were also reflected in the pathological view. VA and swimming, either solely or in combination, markedly increased hepatic and circulating fibroblast growth factor 21. Additionally, VA and swimming increased the immunohistochemical expression of the autophagosomal marker LC3 and decreased the expression of P62, which is selectively degraded during autophagy. Conclusions These results suggest the hepatoprotective effect of VA and swimming exercise against fatty liver and the involvement of FGF21 and autophagy in their effect.

scholarly journals Fasting decreases plasma FGF21 in obese subjects and the expression of FGF21 receptors in adipose tissue in both lean and obese subjects

2018 ◽  
Vol 239 (1) ◽  
pp. 73-80 ◽  
Author(s):  
Eva B Nygaard ◽  
Cathrine Ørskov ◽  
Thomas Almdal ◽  
Henrik Vestergaard ◽  
Birgitte Andersen
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Lipid Metabolism ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Adipose Tissues ◽  
Blood Samples ◽  
Obese Subjects

Fibroblast growth factor 21 (FGF21) is a metabolic regulator of energy and lipid metabolism. FGF21 is highly expressed in liver while FGF21 receptors (beta-klotho (KLB) and FGFR1c) are highly expressed in white adipose tissues (WATs). Plasma FGF21 has been shown to be increased after 7–10 days of fasting but oppositely plasma FGF21 is also increased in obesity. The aim of this study was to measure the effect of 60 h of fasting on plasma FGF21 levels in obese and lean subjects and to determine the gene expression of KLB and FGFR1c in the subcutaneous WAT before, during and after 60 h of fasting. Eight obese (BMI >30 kg/m2) and seven lean subjects (BMI <25 kg/m2) were fasted for 60 h and blood samples were taken at time 0 and after 12, 36 and 60 h of fasting. A biopsy from the subcutaneous WAT was taken at time 0, 12 and 60 h of fasting. FGF21 was measured in plasma by an ELISA and mRNA expression of KLB and FGFR1c was measured in WAT by quantitative PCR (qPCR). The fast significantly decreased plasma FGF21 in obese subjects while no change in plasma FGF21 was observed in lean subjects. Interestingly, KLB was significantly decreased in WAT in response to fasting in both lean and obese subjects indicating a potential important adaptive regulation of KLB in response to fasting.

FGF21 (Fibroblast Growth Factor 21) Defines a Potential Cardiohepatic Signaling Circuit in End-Stage Heart Failure

2021 ◽  
Author(s):  
Salah Sommakia ◽  
Naredos H. Almaw ◽  
Sandra H. Lee ◽  
Dinesh K.A. Ramadurai ◽  
Iosif Taleb ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Growth Factor ◽  
Ejection Fraction ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Reduced Ejection Fraction ◽  
End Stage ◽  
Signaling Circuit

Background: Extrinsic control of cardiomyocyte metabolism is poorly understood in heart failure (HF). FGF21 (Fibroblast growth factor 21), a hormonal regulator of metabolism produced mainly in the liver and adipose tissue, is a prime candidate for such signaling. Methods: To investigate this further, we examined blood and tissue obtained from human subjects with end-stage HF with reduced ejection fraction at the time of left ventricular assist device implantation and correlated serum FGF21 levels with cardiac gene expression, immunohistochemistry, and clinical parameters. Results: Circulating FGF21 levels were substantially elevated in HF with reduced ejection fraction, compared with healthy subjects (HF with reduced ejection fraction: 834.4 [95% CI, 628.4–1040.3] pg/mL, n=40; controls: 146.0 [86.3–205.7] pg/mL, n=20, P =1.9×10 −5 ). There was clear FGF21 staining in diseased cardiomyocytes, and circulating FGF21 levels negatively correlated with the expression of cardiac genes involved in ketone metabolism, consistent with cardiac FGF21 signaling. FGF21 gene expression was very low in failing and nonfailing hearts, suggesting extracardiac production of the circulating hormone. Circulating FGF21 levels were correlated with BNP (B-type natriuretic peptide) and total bilirubin, markers of chronic cardiac and hepatic congestion. Conclusions: Circulating FGF21 levels are elevated in HF with reduced ejection fraction and appear to bind to the heart. The liver is likely the main extracardiac source. This supports a model of hepatic FGF21 communication to diseased cardiomyocytes, defining a potential cardiohepatic signaling circuit in human HF.

scholarly journals Fibroblast Growth Factor 21 (FGF21) Protects against High Fat Diet Induced Inflammation and Islet Hyperplasia in Pancreas

PLoS ONE ◽  
2016 ◽  
Vol 11 (2) ◽  
pp. e0148252 ◽  
Author(s):  
Garima Singhal ◽  
ffolliott Martin Fisher ◽  
Melissa J. Chee ◽  
Tze Guan Tan ◽  
Abdelfattah El Ouaamari ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
High Fat Diet ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
High Fat ◽  
Islet Hyperplasia

scholarly journals Fibroblast growth factor 21 is required for beneficial effects of exercise during chronic high-fat feeding

2016 ◽  
Vol 121 (3) ◽  
pp. 687-698 ◽  
Author(s):  
Christine Loyd ◽  
I. Jack Magrisso ◽  
Michael Haas ◽  
Sowmya Balusu ◽  
Radha Krishna ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Metabolic Effects ◽  
Fibroblast Growth Factor 21 ◽  
Protein Kinase Activity ◽  
Fibroblast Growth ◽  
High Fat ◽  
Glucagon Receptor ◽  
The Metabolic Syndrome ◽  
Physiological Tests

Exercise is an effective therapy against the metabolic syndrome. However, the molecular pathways underlying the advantageous effects of exercise are elusive. Glucagon receptor signaling is essential for exercise benefits, and recent evidence indicates that a downstream effector of glucagon, fibroblast growth factor 21 (FGF21), is implicated in this response. Therefore, we tested the hypothesis that FGF21 action is necessary in mediating metabolic effects of exercise. We utilized acute exhaustive treadmill exercise in Wistar rats to identify a putative, concomitant increase in plasma glucagon and FGF21 with the increase in glucose and lactate following exercise. To test the necessity of FGF21 action in the exercise response, we exposed FGF21 congenitally deficient mice ( Fgf21 −/−) and their wild-type (Wt) littermates to chronic high-fat (HF) feeding and inoperable (sedentary) or operable (exercise) voluntary running wheels. Physiological tests were performed to assess the role of FGF21 in the beneficial effect of exercise on glucose metabolism. Wt and Fgf21 −/− littermates exhibited similar running behavior, and exercise was effective in suppressing weight and fat mass gain and dyslipidemia independently of genotype. However, exercise failed to positively affect hepatic triglyceride content and glucose tolerance in HF diet-fed Fgf21 −/− mice. Furthermore, Fgf21 −/− mice exhibited an impaired adaptation to exercise training, including reduced AMP-activated protein kinase activity in skeletal muscle. This study demonstrates that FGF21 action is necessary to achieve the full metabolic benefits of exercise during chronic HF feeding.

scholarly journals Th2 Cytokines Increase the Expression of Fibroblast Growth Factor 21 in the Liver

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1298
Author(s):  
Seul-Gi Kang ◽  
Seong-Eun Lee ◽  
Min-Jeong Choi ◽  
Joon-Young Chang ◽  
Jung-Tae Kim ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Intraperitoneal Administration ◽  
Janus Kinase ◽  
Fibroblast Growth Factor 21 ◽  
Dependent Manner ◽  
Th2 Cytokines ◽  
Fibroblast Growth

Interleukin-4 (IL-4) and IL-13 are the major T helper 2 (Th2) cytokines, and they are involved in the regulation of metabolism in the adipose tissue. The liver contains diverse innate and adaptive immune cells, but it remains to be determined whether Th2 cytokines modulate energy metabolism in the liver. Here, using gene expression data from the Gene Expression Omnibus (GEO) and the BXD mouse reference population, we determined that the Th2 cytokines IL-4 and IL-13 increase the secretion of fibroblast growth factor 21 (FGF21) in the liver. In vitro experiments confirmed that FGF21 was highly expressed in response to IL-4 and IL-13, and this response was abolished by the Janus kinase (JAK)-signal transducer and activator of transcription 6 (STAT6) blockade. Moreover, FGF21 expression in response to Th2 cytokines was augmented by selective peroxisome proliferator-activated receptor α (PPARα) inhibition. In vivo administration of IL-4 increased FGF21 protein levels in the liver in a STAT6-dependent manner, but FGF21 secretion in response to IL-4 was not observed in the epididymal white adipose tissue (eWAT) despite the activation of STAT6. Intraperitoneal administration of IL-33, an activator of type 2 immune responses, significantly increased the level of FGF21 in the serum and liver after 24 h, but repeated administration of IL-33 attenuated this effect. Taken together, these data demonstrate that the IL-4/IL-13–STAT6 axis regulates metabolic homeostasis through the induction of FGF21 in the liver.

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