Relation between fibroblast growth factor–21, adiposity, metabolism, and weight reduction

Mai, Knut; Schwärz, F.; Bobbert, Thomas; Andres, Janin; Assmann, Anke; Pfeiffer, Andreas F. H.; Spranger, Joachim

doi:10.1016/j.metabol.2010.02.016

Cited by 53 publications

(37 citation statements)

References 26 publications

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“…Previously, lipid-heparin infusion to healthy men induced a threefold rise in FFA and eightfold rise in TG concentrations, but the FGF21 levels remained unchanged (15). The differences between these findings and ours include the route of fat administration (i.v.…”

Section: Discussioncontrasting

confidence: 72%

Decrease in circulating fibroblast growth factor 21 after an oral fat load is related to postprandial triglyceride-rich lipoproteins and liver fat

Matikainen

Taskinen²,

Stennabb

et al. 2012

European Journal of Endocrinology

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Background: Elevated levels of circulating fibroblast growth factor 21 (FGF21) are commonly encountered in type 2 diabetes, dyslipidemia, and non-alcoholic fatty liver disease, all of which share exaggerated postprandial lipemia as a common proatherogenic feature. How FGF21 responds to an oral fat load in man is unknown. Methods: We measured liver fat contents and subcutaneous and visceral fat volumes in 47 healthy subjects, who also underwent an oral fat load with measurements of plasma FGF21 and free fatty acid (FFA). Triglyceride (TG), apolipoprotein B-48 (apoB-48), and apoB-100 concentrations were measured in triglyceride-rich lipoprotein (TRL) fractions. Results: When compared with fasting levels, the concentration of FGF21 decreased significantly at 4 h (P!0.05) and tended to return to fasting levels at 8 h after an oral fat load. Fasting and postprandial FGF21 correlated significantly with liver fat as well as with TRLs in the chylomicron and especially in very low-density lipoprotein 1 (VLDL1) and VLDL2 fractions representing remnant particles, but not with FFA. Subjects with increased liver fat (O5%, nZ12) showed impaired suppression of FGF21 at 4 h (P!0.05) and at 8 h (PZ0.01) and demonstrated higher postprandial TG area under the curve in plasma and TRL fractions (P%0.032) compared with those with normal liver fat (%5%, nZ35). Conclusions: We observed a significant decrease of FGF21 concentration after an oral fat load. Fasting and postprandial FGF21 levels were closely related to large VLDL and remnants, but not to plasma FFA. Our pilot findings suggest that the postprandial accumulation of TRL remnants and liver fat may modulate postprandial FGF21 levels.

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Section: Discussioncontrasting

confidence: 72%

Decrease in circulating fibroblast growth factor 21 after an oral fat load is related to postprandial triglyceride-rich lipoproteins and liver fat

Matikainen

Taskinen²,

Stennabb

et al. 2012

European Journal of Endocrinology

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“…These results are in concordance with those obtained in mice after fasting, indicating a possible response of FGF21 to fasting after PPARa activation (37,45), suggesting that FGF21 might be related to the improvement in insulin sensitivity associated with weight loss induced by VLCD in obese patients (45). However, on the other hand, FGF21 levels were not modified by moderate weight reduction (w5 kg) after a 6-month weight loss program based on hypocaloric diet and physical activity in a group of 30 obese subjects (78). Moreover, significant weight loss associated with bariatric surgery in 23 nondiabetic morbidly obese patients did not modify serum FGF21 levels over time (79).…”

Section: Fgf21 and Obesitysupporting

confidence: 74%

MECHANISMS IN ENDOCRINOLOGY: Biological role, clinical significance, and therapeutic possibilities of the recently discovered metabolic hormone fibroblastic growth factor 21

Iglesias

Selgas

Romero

et al. 2012

European Journal of Endocrinology

101

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Fibroblast growth factor 21 (FGF21), a 181 amino acid circulating protein, is a member of the FGF superfamily, with relevant metabolic actions. It acts through the interaction with specific FGF receptors and a cofactor called β-Klotho, whose expression is predominantly detected in metabolically active organs. FGF21 stimulates glucose uptake in adipocytes via the induction of glucose transporter-1. This action is additive and independent of insulin. β-Cell function and survival are preserved, and glucagon secretion is reduced by this protein, thus decreasing hepatic glucose production and improving insulin sensitivity. Lipid profile has been shown to be improved by FGF21 in several animal models. FGF21 increases energy expenditure in rodents and induces weight loss in diabetic nonhuman primates. It also exerts favorable effects on hepatic steatosis and reduces tissue lipid content in rodents. Adaptive metabolic responses to fasting, including stimulation of ketogenesis and fatty acid oxidation, seem to be partially mediated by FGF21. In humans, serum FGF21 concentrations have been found elevated in insulin-resistant states, such as impaired glucose tolerance and type 2 diabetes. FGF21 levels are correlated with hepatic insulin resistance index, fasting blood glucose, HbA1c, and blood glucose after an oral glucose tolerance test. A relationship between FGF21 levels and long-term diabetic complications, such as nephropathy and carotid atheromatosis, has been reported. FGF21 levels decreased in diabetic patients after starting therapy with insulin or oral agents. Increased FGF21 serum levels have also been found to be associated with obesity. In children, it is correlated with BMI and leptin levels, whereas in adults, FGF21 levels are mainly related to several components of the metabolic syndrome. Serum FGF21 levels have been found to be elevated in patients with ischemic heart disease. In patients with renal disease, FGF21 levels exhibited a progressive increase as renal function deteriorates. Circulating FGF21 levels seem to be related to insulin resistance and inflammation in dialysis patients. In summary, FGF21 is a recently identified hormone with antihyperglycemic, antihyperlipidemic, and thermogenic properties. Direct or indirect potentiation of its effects might be a potential therapeutic target in insulin-resistant states.

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“…The FGF-21 level was indicated to be associated with several symptoms of metabolic syndrome (Zhang et al, 2008). However, other studies revealed that FGF-21 was positively associated with metabolic disorders, including dyslipidemia, obesity, high plasma glucose level and insulin resistance (Dostalova et al, 2008;Mai et al, 2011;Chavez et al, 2009). The cause of these discrepancies is still unclear.…”

Section: Discussionmentioning

confidence: 98%

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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Relation between fibroblast growth factor–21, adiposity, metabolism, and weight reduction

Cited by 53 publications

References 26 publications

Decrease in circulating fibroblast growth factor 21 after an oral fat load is related to postprandial triglyceride-rich lipoproteins and liver fat

Decrease in circulating fibroblast growth factor 21 after an oral fat load is related to postprandial triglyceride-rich lipoproteins and liver fat

MECHANISMS IN ENDOCRINOLOGY: Biological role, clinical significance, and therapeutic possibilities of the recently discovered metabolic hormone fibroblastic growth factor 21

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

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