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.

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 Fibroblast growth factor-21 serum concentrations are associated with metabolic and hepatic markers in humans

2012 ◽  
Vol 216 (2) ◽  
pp. 135-143 ◽  
Author(s):  
Susan Kralisch ◽  
Anke Tönjes ◽  
Kerstin Krause ◽  
Judit Richter ◽  
Ulrike Lossner ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Serum Concentrations ◽  
The Metabolic Syndrome ◽  
Glutamyl Transferase ◽  
Culture Supernatants

Rather than a traditional growth factor, fibroblast growth factor-21 (FGF21) is considered to be a metabolic hormone. In the current study, we investigated serum FGF21 levels in the self-contained population of Sorbs. Serum FGF21 concentrations were quantified by ELISA and correlated with IGF1 as well as metabolic, renal, hepatic, inflammatory, and cardiovascular parameters in 913 Sorbs from Germany. Moreover, human IGF1 protein secretion was investigated in FGF21-stimulated HepG2 cells. Median FGF21 serum concentrations were 2.1-fold higher in subjects with type 2 diabetes mellitus (141.8 ng/l) compared with controls (66.7 ng/l). Furthermore, nondiabetic subjects with FGF21 levels below the detection limit of the ELISA showed a more beneficial metabolic profile compared with subjects with measurable FGF21. Moreover, FGF21 was significantly lower in female compared with male subjects after adjustment for age and BMI. In multiple regression analyses, circulating FGF21 concentrations remained independently and positively associated with gender, systolic blood pressure, triglycerides, and γ glutamyl transferase whereas a negative association was observed with IGF1 in nondiabetic subjects. Notably, FGF21 significantly inhibited IGF1 secretion into HepG2 cell culture supernatants in preliminary in vitro experiments. FGF21 serum concentrations are associated with facets of the metabolic syndrome, hepatocellular function, as well as GH status.

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 Predicts the Metabolic Syndrome and Type 2 Diabetes in Caucasians

Diabetes Care ◽  
2012 ◽  
Vol 36 (1) ◽  
pp. 145-149 ◽  
Author(s):  
T. Bobbert ◽  
F. Schwarz ◽  
A. Fischer-Rosinsky ◽  
A. F. H. Pfeiffer ◽  
M. Mohlig ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
The Metabolic Syndrome

scholarly journals The Speed of Ingestion of a Sugary Beverage Has an Effect on the Acute Metabolic Response to Fructose

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1916
Author(s):  
Mehmet Kanbay ◽  
Begum Guler ◽  
Lale A. Ertuglu ◽  
Tuncay Dagel ◽  
Baris Afsar ◽  
...  
Keyword(s):  
Uric Acid ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Apple Juice ◽  
Metabolic Response ◽  
Serum Glucose ◽  
Metabolic Effects ◽  
Fibroblast Growth Factor 21 ◽  
Model Assessment ◽  
Fibroblast Growth

Background: The consumption of sweetened beverages is associated with increased risk of metabolic syndrome, cardiovascular disease, and type 2 diabetes mellitus. Objective: We hypothesized that the metabolic effects of fructose in sugary beverages might be modulated by the speed of ingestion in addition to the overall amount. Design: Thirty healthy subjects free of any disease and medication were recruited into two groups. After overnight fasting, subjects in group 1 drank 500 mL of apple juice over an hour by drinking 125 mL every 15 min, while subjects in group 2 drank 500 mL of apple juice over 5 min. Blood samples were collected at time zero and 15, 30, 60, and 120 min after ingestion to be analyzed for serum glucose, insulin, homeostatic model assessment (HOMA-IR) score, fibroblast growth factor 21, copeptin, osmolarity, sodium, blood urea nitrogen (BUN), lactate, uric acid, and phosphate levels. Results: Serum glucose, insulin, HOMA-IR, fibroblast growth factor 21, copeptin, osmolarity, sodium, BUN, and lactate levels increased following apple juice ingestion. The increases were greater in the fast-drinking group, which were more significant after 15 min and 30 min compared to baseline. The changes in uric acid were not statistically different between the groups. Phosphate levels significantly increased only in the fast-drinking group. Conclusion: Fast ingestion of 100% apple juice causes a significantly greater metabolic response, which may be associated with negative long-term outcomes. Our findings suggest that the rate of ingestion must be considered when evaluating the metabolic impacts of sweetened beverage consumption.

scholarly journals Fibroblast Growth Factor 21 and the Adaptive Response to Nutritional Challenges

2019 ◽  
Vol 20 (19) ◽  
pp. 4692 ◽  
Author(s):  
Úrsula Martínez-Garza ◽  
Daniel Torres-Oteros ◽  
Alex Yarritu-Gallego ◽  
Pedro F. Marrero ◽  
Diego Haro ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Metabolic Response ◽  
Therapeutic Potential ◽  
Metabolic Effects ◽  
Fibroblast Growth Factor 21 ◽  
Signal Pathways ◽  
Fibroblast Growth ◽  
The Impact

The Fibroblast Growth Factor 21 (FGF21) is considered an attractive therapeutic target for obesity and obesity-related disorders due to its beneficial effects in lipid and carbohydrate metabolism. FGF21 response is essential under stressful conditions and its metabolic effects depend on the inducer factor or stress condition. FGF21 seems to be the key signal which communicates and coordinates the metabolic response to reverse different nutritional stresses and restores the metabolic homeostasis. This review is focused on describing individually the FGF21-dependent metabolic response activated by some of the most common nutritional challenges, the signal pathways triggering this response, and the impact of this response on global homeostasis. We consider that this is essential knowledge to identify the potential role of FGF21 in the onset and progression of some of the most prevalent metabolic pathologies and to understand the potential of FGF21 as a target for these diseases. After this review, we conclude that more research is needed to understand the mechanisms underlying the role of FGF21 in macronutrient preference and food intake behavior, but also in β-klotho regulation and the activity of the fibroblast activation protein (FAP) to uncover its therapeutic potential as a way to increase the FGF21 signaling.

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