scholarly journals Purinergic Signaling Controls Fibroblast Growth Factor‐21 Expression in Skeletal Muscle through Akt/mTOR Pathway.

2018 ◽  
Vol 32 (S1) ◽  
Author(s):  
Manuel Arias‐Calderón ◽  
Camilo Morales ◽  
Walter Vasquez ◽  
Nadia Hernández ◽  
Enrique Jaimovich ◽  
...  
Diabetes ◽  
2018 ◽  
Vol 67 (4) ◽  
pp. 594-606 ◽  
Author(s):  
Magdalene K. Montgomery ◽  
Ruzaidi Mokhtar ◽  
Jacqueline Bayliss ◽  
Helena C. Parkington ◽  
Victor M. Suturin ◽  
...  

2011 ◽  
pp. 757-767 ◽  
Author(s):  
T. KOTULÁK ◽  
J. DRÁPALOVÁ ◽  
P. KOPECKÝ ◽  
Z. LACINOVÁ ◽  
P. KRAMÁŘ ◽  
...  

We studied the changes in serum fibroblast growth factor-21 (FGF-21) concentrations, its mRNA, and protein expression in skeletal muscle and adipose tissue of 15 patients undergoing cardiac surgery. Blood samples were obtained: prior to initiation of anesthesia, prior to the start of extracorporeal circulation, upon completion of the surgery, and 6, 24, 48, and 96 hours after the end of the surgery. Tissue sampling was performed at the start and end of surgery. The mean baseline serum FGF-21 concentration was 63.1 (43.03-113.95) pg/ml and it increased during surgery with peak 6 hours after its end [385.5 (274.55-761.65) pg/ml, p<0.001], and returned to baseline value [41.4 (29.15-142.83) pg/ml] 96 hours after the end of the surgery. Serum glucose, insulin, CRP, IL-6, IL-8, MCP-1, and TNF-alpha concentrations significantly increased during the surgery. Baseline FGF-21 mRNA expression in skeletal muscle was higher than in both adipose tissue depots and it was not affected by the surgery. Epicardial fat FGF-21 mRNA increased after surgery. Muscle FGF-21 mRNA positively correlated with blood glucose levels at the end of the surgery. Our data suggest a possible role of FGF-21 in the regulation of glucose metabolism and insulin sensitivity in surgery-related stress.


2021 ◽  
Vol 12 ◽  
Author(s):  
Hui Sun ◽  
Matthew Sherrier ◽  
Hongshuai Li

Fibroblast growth factor 21 (FGF21) is an atypical member of the FGF family, which functions as a powerful endocrine and paracrine regulator of glucose and lipid metabolism. In addition to liver and adipose tissue, recent studies have shown that FGF21 can also be produced in skeletal muscle. As the most abundant tissue in the human body, skeletal muscle has become increasingly recognized as a major site of metabolic activity and an important modulator of systemic metabolic homeostasis. The function and mechanism of action of muscle-derived FGF21 have recently gained attention due to the findings of considerably increased expression and secretion of FGF21 from skeletal muscle under certain pathological conditions. Recent reports regarding the ectopic expression of FGF21 from skeletal muscle and its potential effects on the musculoskeletal system unfolds a new chapter in the story of FGF21. In this review, we summarize the current knowledge base of muscle-derived FGF21 and the possible functions of FGF21 on homeostasis of the musculoskeletal system with a focus on skeletal muscle and bone.


2020 ◽  
Vol 65 (3) ◽  
pp. 85-95
Author(s):  
G Rosales-Soto ◽  
A Diaz-Vegas ◽  
M Casas ◽  
A Contreras-Ferrat ◽  
E Jaimovich

Fibroblast growth factor 21 (FGF21) is a pleiotropic peptide hormone that is considered a myokine playing a role in a variety of endocrine functions, including regulation of glucose transport and lipid metabolism. Although FGF21 has been associated with glucose metabolism in skeletal muscle cells, its cellular mechanism in adult skeletal muscle fibers glucose uptake is poorly understood. In the present study, we found that FGF21 induced a dose−response effect, increasing glucose uptake in skeletal muscle fibers from the flexor digitorum brevis muscle of mice, evaluated using the fluorescent glucose analog 2-NBDG (300 µM) in single living fibers. This effect was prevented by the use of either cytochalasin B (5 µM) or indinavir (100 µM), both antagonists of GLUT4 activity. The use of PI3K inhibitors such as LY294002 (50 µM) completely prevented the FGF21-dependent glucose uptake. In fibers electroporated with the construct encoding GLUT4myc-eGFP chimera and stimulated with FGF21 (100 ng/mL), a strong sarcolemmal GLUT4 label was detected. This effect promoted by FGF21 was demonstrated to be dependent on atypical PKC-ζ, by using selective PKC inhibitors. FGF21 at low concentrations potentiated the effect of insulin on glucose uptake but at high concentrations, completely inhibited the uptake in the presence of insulin. These results suggest that FGF21 regulates glucose uptake by a mechanism mediated by GLUT4 and dependent on atypical PKC-ζ in skeletal muscle.


Diabetes ◽  
2015 ◽  
Vol 64 (8) ◽  
pp. 2757-2768 ◽  
Author(s):  
Lydia-Ann L.S. Harris ◽  
James R. Skinner ◽  
Trevor M. Shew ◽  
Terri A. Pietka ◽  
Nada A. Abumrad ◽  
...  

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Chu-Sook Kim ◽  
Yeonsoo Joe ◽  
Hye-Seon Choi ◽  
Sung Hoon Back ◽  
Jeong Woo Park ◽  
...  

Author(s):  
Albert Pérez-Martí ◽  
Viviana Sandoval ◽  
Pedro F. Marrero ◽  
Diego Haro ◽  
Joana Relat

AbstractObesity is a worldwide health problem mainly due to its associated comorbidities. Fibroblast growth factor 21 (FGF21) is a peptide hormone involved in metabolic homeostasis in healthy individuals and considered a promising therapeutic candidate for the treatment of obesity. FGF21 is predominantly produced by the liver but also by other tissues, such as white adipose tissue (WAT), brown adipose tissue (BAT), skeletal muscle, and pancreas in response to different stimuli such as cold and different nutritional challenges that include fasting, high-fat diets (HFDs), ketogenic diets, some amino acid-deficient diets, low protein diets, high carbohydrate diets or specific dietary bioactive compounds. Its target tissues are essentially WAT, BAT, skeletal muscle, heart and brain. The effects of FGF21 in extra hepatic tissues occur through the fibroblast growth factor receptor (FGFR)-1c together with the co-receptor β-klotho (KLB). Mechanistically, FGF21 interacts directly with the extracellular domain of the membrane bound cofactor KLB in the FGF21- KLB-FGFR complex to activate FGFR substrate 2α and ERK1/2 phosphorylation. Mice lacking KLB are resistant to both acute and chronic effects of FGF21. Moreover, the acute insulin sensitizing effects of FGF21 are also absent in mice with specific deletion of adipose KLB or FGFR1. Most of the data show that pharmacological administration of FGF21 has metabolic beneficial effects. The objective of this review is to compile existing information about the mechanisms that could allow the control of endogenous FGF21 levels in order to obtain the beneficial metabolic effects of FGF21 by inducing its production instead of doing it by pharmacological administration.


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