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FGF-21, a newcomer in the field of hypertension research

Journal of Human Hypertension volume 27, pages 343–344 (2013)Cite this article

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Fibroblast growth factor (FGF)-21 was isolated as an atypical member of FGF family and in a relatively short period has surged with growing interest as a hormone/cytokine that has a crucial role in the regulation of glucose and lipid metabolism.1 FGF-21 is produced mainly from liver and this organ is supposed to supply most of the circulating FGF-21. However, adipocytes and skeletal muscle are also important sources of FGF-21, where it may act as a cytokine through autocrine or paracrine signaling.1, 2 The tissue specificity of FGF-21 actions is determined by the expression of βKlotho composing a cell-surface receptor complex with conventional FGF receptors. In animal models of diabetes,3 a pharmacological administration or overexpression of FGF-21 caused liver fat content and body weight reduction, amelioration of insulin resistance and lowering of blood glucose and lipid concentrations. This and subsequent studies have prompted researches on potential therapeutic applications of FGF-21 for metabolic diseases. For example,4 a polyethylene glycol-based polymerization of FGF-21 to overcome its short circulating half-life conferred enhanced antidiabetic pharmacology. In human,5 higher serum concentrations of FGF-21 were associated with various metabolic conditions including obesity, metabolic syndrome, glucose intolerance or type 2 diabetes, dyslipidemia and non-alcoholic fatty liver disease (NAFLD). Mechanisms for elevated FGF-21 concentrations under those conditions, which is discrepant from the generalized metabolic amelioration by the administration of FGF-21 in diabetes models, might include compensatory oversecretion against FGF-21 resistant state or common pathophysiological bases that enhance FGF-21 levels (for example, serum-free fatty acids). Fibrates, antihyperlipidemic agents and agonists for the transcription factor peroxisome proliferator-activated receptor (PPAR)-α, are known to upregulate the expression and serum concentration of FGF-21. Higher FGF-21 concentrations under chronic kidney diseases can be attributed to impaired excretion of it by the kidney. Reduced serum FGF-21 concentrations are known under conditions like anorexia nervosa, type 1 diabetes and latent autoimmune diabetes in adult.5 Under these conditions, reduced insulin concentrations may be a factor involved in the observed associations.

Reports that investigated a role of FGF-21 in development of cardiovascular diseases are limited. Higher levels of FGF-21 were recognized in patients with coronary heart diseases and were associated with adverse lipid profiles like increased triglyceride and decreased apolipoprotein A1 levels.6 An incubation of cardiac endothelial cells with oxidized-low density lipoprotein induced upregulation of FGF-21 expression, and experimental manipulations to increase or decrease FGF-21 expression levels led to reduction or induction, respectively, of endothelial cell apoptosis.7 Surprisingly, a relationship between the circulating FGF-21 levels and blood pressure has been paid no attention so far. In the present issue of the Journal of Human Hypertension, Semba et al.8 report for the first time that elevated serum FGF-21 levels were associated with hypertension after adjustments with multiple explanatory variables in a community cohort. It is worth mentioning that an inclusion of triglyceride levels as an explanatory variable substantially weakened the strength of association between the FGF-21 levels and hypertension. In a previous report,9 elevated FGF-21 levels were also associated with higher systolic blood pressure in type 2 diabetic patients in a univariable analysis. In this case, adjustments with use of fibrates, triglyceride levels and renal function failed to reproduce the association between them, which shows a similarity to the results by Semba et al.8

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  1. Department of Internal Medicine, Teikyo University School of Medicine, Itabashi, Tokyo, Japan

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Eto, K. FGF-21, a newcomer in the field of hypertension research. J Hum Hypertens 27, 343–344 (2013). https://doi.org/10.1038/jhh.2012.68

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