scholarly journals Glucagon Receptor Signaling Regulates Energy Metabolism via Hepatic Farnesoid X Receptor and Fibroblast Growth Factor 21

Diabetes ◽  
2018 ◽  
Vol 67 (9) ◽  
pp. 1773-1782 ◽  
Author(s):  
Teayoun Kim ◽  
Shelly Nason ◽  
Cassie Holleman ◽  
Mark Pepin ◽  
Landon Wilson ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Farnesoid X Receptor ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Receptor Signaling ◽  
Glucagon Receptor

scholarly journals Activation of the Farnesoid X Receptor Induces Hepatic Expression and Secretion of Fibroblast Growth Factor 21

2012 ◽  
Vol 287 (30) ◽  
pp. 25123-25138 ◽  
Author(s):  
Holly A. Cyphert ◽  
Xuemei Ge ◽  
Alison B. Kohan ◽  
Lisa M. Salati ◽  
Yanqiao Zhang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Farnesoid X Receptor ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Hepatic Expression

scholarly journals Dual effects of fibroblast growth factor 21 on hepatic energy metabolism

2015 ◽  
Vol 227 (1) ◽  
pp. 37-47 ◽  
Author(s):  
Ricardo J Samms ◽  
Michelle Murphy ◽  
Maxine J Fowler ◽  
Scott Cooper ◽  
Paul Emmerson ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Lipid Content ◽  
Negative Regulator ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Hepatic Lipid ◽  
Siberian Hamsters ◽  
Hepatic Lipid Content

The aim of this study was to investigate the mechanisms by which fibroblast growth factor 21 (FGF21) affects hepatic integration of carbohydrate and fat metabolism in Siberian hamsters, a natural model of adiposity. Twelve aged matched adult male Siberian hamsters maintained in their long-day fat state since birth were randomly assigned to one of two treatment groups and were continuously infused with either vehicle (saline;n=6) or recombinant human FGF21 protein (1 mg/kg per day;n=6) for 14 days. FGF21 administration caused a 40% suppression (P<0.05) of hepatic pyruvate dehydrogenase complex (PDC), the rate-limiting step in glucose oxidation, a 34% decrease (P<0.05) in hepatic acetylcarnitine accumulation, an index of reduced PDC flux, a 35% increase (P<0.05) in long-chain acylcarnitine content (an index of flux through β-oxidation) and a 47% reduction (P<0.05) in hepatic lipid content. These effects were underpinned by increased protein abundance of PD kinase-4 (PDK4, a negative regulator of PDC), the phosphorylated (inhibited) form of acetyl-CoA carboxylase (ACC, a negative regulator of delivery of fatty acids into the mitochondria) and the transcriptional co-regulators of energy metabolism peroxisome proliferator activated receptor gamma co-activator alpha (PGC1α) and sirtuin-1. These findings provide novel mechanistic basis to support the notion that FGF21 exerts profound metabolic benefits in the liver by modulating nutrient flux through both carbohydrate (mediated by a PDK4-mediated suppression of PDC activity) and fat (mediated by deactivation of ACC) metabolism, and therefore may be an attractive target for protection from increased hepatic lipid content and insulin resistance that frequently accompany obesity and diabetes.

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 PSXIII-41 Fibroblast growth factor 21 promotes lipid oxidation and transportation while inhibits lipogenesis via AMP-activated protein kinase signaling pathway in bovine hepatocytes

2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 368-368
Author(s):  
Jianguo Wang ◽  
Xiaoyan Zhu ◽  
Baoyu Zhao
Keyword(s):  
Energy Metabolism ◽  
Growth Factor ◽  
Lipid Oxidation ◽  
Dairy Cows ◽  
Fibroblast Growth Factor ◽  
Signaling Pathway ◽  
Whole Body ◽  
Optimal Time ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth

Abstract Background: Fibroblast growth factor 21 (FGF21) plays essential roles in the regulation of whole body energy metabolism. However, it is not entirely clear for dairy cows whether FGF21 activates AMPK signaling pathway and what will be affected for lipid metabolism in bovine hepatocytes. Methods: Bovine hepatocytes were isolated from caudate lobes by using three-step of perfusion and collagenase digestion method. The accumulation of TG and the secretion of VLDL were examined in hepatocytes and supernatant, respectively. The expressions of the metabolic key factors were detected by Real-time PCR and Western Blot.Results: The 4th hour is the optimal time that FGF21 activates AMPK. FGF21 has significant dose-dependent inhibition of TG in bovine hepatocytes; and high concentration (1800 pg/mL) significantly promoted VLDL secretion at 4 h. The protein expression of APOB 100, APOE and MTTP, which are components of VLDL, were stimulated by FGF21, and all the mRNA expression reached the peak point (P &lt; 0.01) at medium concentration (900 pg/mL). Interestingly, the proteins associated with lipid transportation were promoted too, such as LDLR, CD36, L-FABP. To some extent, meanwhile, it could be observed that some genes regulating lipid oxidation were strengthened following FGF21 treatment. In detail, ACOX1 and SIRT1 were very sensitive to the concentration of FGF21, showing remarkable difference at low concentration (P &lt; 0.01); PGC-α, PPAR-α and CPT-1 showed significant changes at 900 pg/mL (P &lt; 0.01); CPT-2 required a higher concentration to achieve significant enhancement. However, the results had a negative impact on lipogenesis. SREBP1c, ACC, FASN and ACLY were inhibited after treatment with low or medium doses of FGF21 (P &lt; 0.01). Conclusion: FGF21 can promote lipid oxidation and transport, while inhibit lipid synthesis via activating AMPK signalling pathway in primary hepatocytes of dairy cows, thereby participation in the adaptive regulation of energy metabolism.

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