Serum concentrations and tissue expression of a novel endocrine regulator fibroblast growth factor‐21 in patients with type 2 diabetes and obesity

Mráz, Miloš; Bartlova, Marketa; Lacinová, Z; Michalský, David; Kasalický, M; Haluzíková, D; Matoulek, Martin; Dostálová, I; Humenanska, Viera; Haluzı́k, Martin

doi:10.1111/j.1365-2265.2008.03502.x

Cited by 255 publications

(234 citation statements)

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“…Furthermore, our results indicate that adipose tissue is the main source of circulating FGF21 in obese women. This hypothesis is confirmed by the observation of an increase in FGF21 expression in visceral fat in obese subjects (20). It should be emphasised that the stronger association between FGF21 and HOMA-IR values than fat mass and waist circumference implies that higher FGF21 production and secretion may be an inefficient contraregulatory mechanism preventing insulin resistance development in obese subjects.…”

Section: Discussionsupporting

confidence: 71%

“…Results including decrease (18), no change (19) and increase (20) were all described. However, it should be noted that an increase in FGF21 levels was observed in patients when combined with very-low-calorie diet (VLCD) and fenofibrate therapy (20). The results of study in monozygotic and dizygotic young adult twins revealed that genetic factors moderately contributed to circulating FGF21 variability (21).…”

Section: Introductionmentioning

confidence: 99%

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Circulating FGF21 levels are related to nutritional status and metabolic but not hormonal disturbances in polycystic ovary syndrome

Olszanecka-Glinianowicz¹,

Madej²,

Wdowczyk³

et al. 2015

European Journal of Endocrinology

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Objective: The aim of this study was to analyse relationships between plasma fibroblast growth factor 21 (FGF21) levels and nutritional status, and metabolic and hormonal disturbances in polycystic ovary syndrome (PCOS) women. Design and setting: A cross-sectional study involving 85 PCOS (48 obese) and 72 non-PCOS women (41 obese) was conducted to evaluate the relationship between FGF21 levels and PCOS. Methods: Anthropometric parameters and body composition were determined. In the fasting state; serum concentrations of glucose, androgens, FSH, LH, SHBG, insulin and FGF21 were measured. Results: Plasma FGF21 levels were significantly higher in obese women compared with normal-weight women in both PCOS and non-PCOS subgroups (120.3 (18.2-698) vs 62.3 (16.4-323.6) pg/ml, P!0.05 and 87.2 (12.9-748.4) vs 62.9 (18.0-378.8) pg/ml, P!0.05 respectively). Additionally, circulating FGF21 levels were significantly higher in the obese PCOS subgroup compared with the non-PCOS subgroup (120.3 (18.2-698.0) vs 87.2 (12.9-748.4) pg/ml, P!0.05). Circulating FGF21 levels were proportional to BMI (RZ0.27; P!0.001), body fat mass (RZ0.24; P!0.01) and percentage (RZ0.24; P!0.01), as well as waist circumference (RZ0.26; P!0.01). Additionally, plasma insulin and homeostasis model assessment of insulin resistance (HOMA-IR) values were related to FGF21 levels (RZ0.44; P!0.001 and RZ0.19; P!0.05 respectively). In multiple regression analysis, circulating FGF21 level variability was explained by HOMA-IR values and fat percentage, as well as waist circumference, but not correlated with oestradiol levels and free androgen index values. Conclusions: Higher circulating FGF21 levels are related to nutritional status and insulin resistance independent of PCOS. Increased FGF21 is associated with metabolic but not hormonal disturbances.

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Section: Discussionsupporting

confidence: 71%

Section: Introductionmentioning

confidence: 99%

Circulating FGF21 levels are related to nutritional status and metabolic but not hormonal disturbances in polycystic ovary syndrome

Olszanecka-Glinianowicz¹,

Madej²,

Wdowczyk³

et al. 2015

European Journal of Endocrinology

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“…Some studies have shown that fasting and feeding may regulate FGF21 expression (Uebanso et al, 2011). This factor may be a risk factor for some diseases like insulin resistance, type 2 diabetes mellitus and metabolic syndrome (Mraz et al, 2009;Bobbert et al, 2013). Some studies have revealed that serum FGF21 influenced by high blood glucose, increased body mass index, uric acid level and low physical activity (Cuevas-Ramos et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Serum Level of Fibroblast Growth Factor 21 in Type 2 Diabetic Patients with and without Metabolic Syndrome

Shafaei¹,

Khoshnia²,

Marjani³

2015

J. of Medical Sciences

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Effect of FGF21 on metabolic syndrome patients is not exactly clear. In the present study, we assessed serum level of fibroblast growth factor 21 in type 2 diabetic patients with and without metabolic syndrome in Gorgan. The study groups consisted of 120 patients with type 2 diabetes and 60 healthy subjects. Diabetic patients divided into two groups. All subjects were matched according to age and sex. The mean waist circumference, systolic and diastolic blood pressure, triglyceride and fasting blood glucose levels and body mass index were significantly higher in the subjects with metabolic syndrome than control group, but the mean HDL-cholesterol was significantly lower (p = 0.0001). Mean serum level of FGF21 was higher in type 2 diabetic subjects with and without metabolic syndrome than that of control subject (p = 0.0001). There were significant negative correlation between FGF21 and BMI, diastolic blood pressure and HDL-cholesterol in subjects with metabolic syndrome (p<0.05). There were also significant negative correlation between FGF21 and cholesterol and HDL-cholesterol in control group (p<0.05). The findings of this study suggest that serum FGF21 are higher in patients with type 2 diabetes with and without metabolic syndrome than in age and sex matched control group. Our study shows that some of metabolic syndrome components (especially HDL-cholesterol) are associated with high serum FGF21 levels. Because of different effects of FGF21 in rodents, primates and in humans, it may require more investigating on metabolic effects of FGF21 in human's samples.

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“…It has been predominantly investigated in the liver and adipose tissue [10]. However, FGF21 is also expressed in other tissues such as the myocardium [11].…”

Section: Introductionmentioning

confidence: 99%

Fibroblast growth factor 21 protects the heart from apoptosis in a diabetic mouse model via extracellular signal-regulated kinase 1/2-dependent signalling pathway

et al. 2015

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Aims/hypothesis This study investigated fibroblast growth factor 21 (FGF21)-mediated cardiac protection against apoptosis caused by diabetic lipotoxicity and explored the protective mechanisms involved. Methods Cardiac Fgf21 mRNA expression was examined in a diabetic mouse model using real-time PCR. After preincubation of palmitate-treated cardiac H9c2 cells and primary cardiomyocytes with FGF21 for 15 h, apoptosis and Fgf21-induced cell-survival signalling were investigated using small interfering (si)RNA and/or pharmacological inhibitors. We also examined the cardiac apoptotic signalling and structural and functional indices in wild-type and Fgf21-knockout (Fgf21-KO) diabetic mice.Results In a mouse model of type 1 diabetes, cardiac Fgf21 expression was upregulated about 40-fold at 2 months and 3-1.5-fold at 4 and 6 months after diabetes. FGF21 significantly reduced palmitate-induced cardiac apoptosis. Mechanistically, palmitate downregulated, but FGF21 upregulated, phosphorylation levels of extracellular signal-regulated kinase (ERK)1/ 2, mitogen-activated protein kinase 14 (p38 MAPK) and AMP-activated protein kinase (AMPK). Inhibition of each kinase with its inhibitor and/or siRNA revealed that FGF21 prevents palmitate-induced cardiac apoptosis via upregulating the ERK1/2-dependent p38 MAPK-AMPK signalling pathway. In vivo administration of FGF21, but not FGF21 plus ERK1/2 inhibitor, to diabetic or fatty-acid-infused mice significantly prevented cardiac apoptosis and reduced inactivation of ERK1/2, p38 MAPK and AMPK and prevented cardiac remodelling and dysfunction. The Fgf21-KO mice were more susceptible to diabetes-induced cardiac apoptosis, and this could be prevented by administration of FGF21. Deletion of Fgf21 did not further exacerbate cardiac dysfunction. Conclusions/interpretation These results demonstrate that FGF21 prevents lipid-or diabetes-induced cardiac apoptosis by activating the ERK1/2-p38 MAPK-AMPK pathway. FGF21 may be a therapeutic target for the treatment of diabetes-related cardiac damage.Electronic supplementary material The online version of this article

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Serum concentrations and tissue expression of a novel endocrine regulator fibroblast growth factor‐21 in patients with type 2 diabetes and obesity

Abstract: An increase in FGF21 levels after VLCD and fenofibrate treatment may contribute to positive metabolic effect of these interventions and suggests the possibility of direct positive metabolic effects of FGF21 in humans.

Cited by 255 publications

References 28 publications

Circulating FGF21 levels are related to nutritional status and metabolic but not hormonal disturbances in polycystic ovary syndrome

Circulating FGF21 levels are related to nutritional status and metabolic but not hormonal disturbances in polycystic ovary syndrome

Serum Level of Fibroblast Growth Factor 21 in Type 2 Diabetic Patients with and without Metabolic Syndrome

Fibroblast growth factor 21 protects the heart from apoptosis in a diabetic mouse model via extracellular signal-regulated kinase 1/2-dependent signalling pathway

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