FGF21: a promising therapeutic agent for alcoholic cardiomyopathy?^†

Abstract

The metabolic regulator fibroblast growth factor 21 (FGF21) has been reported as a cardioprotective factor regulating cardiac remodeling in several cardiac diseases. In a recent issue of The Journal of Pathology, Ferrer‐Curriu, Guitart‐Mampel et al investigated FGF21 in alcoholic cardiomyopathy (ACM). They showed that FGF21 deficiency aggravates alcohol‐induced cardiac damage and dysfunction by exacerbating mitochondrial alterations, oxidative stress, and lipid metabolic dysregulation, suggesting FGF21 as a promising therapeutic agent in ACM. Paradoxically, FGF21 cardiac and circulating levels correlate with cardiac damage and oxidative stress in patients with ACM, pointing to FGF21 as a potential biomarker of alcohol‐induced cardiac damage. Further studies are needed to address when FGF21 can be used as a diagnostic biomarker and when it can be used as a therapeutic agent to treat ACM. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

The role of FGF21 in the pathogenesis of cardiovascular disease

“…Animal experiments further confirmed that FGF21 treatment could significantly reduce cardiac hypertrophy and dysfunction induced by Ang II [118] . Researchers recently proposed that FGF21 might be a promising diagnostic marker and therapeutic target for alcoholic cardiomyopathy (ACM) [119] . Studies have found that chronic alcohol consumption induces FGF21 levels in the plasma and cardiomyocytes [120] .…”

“…[ 118 ] Researchers recently proposed that FGF21 might be a promising diagnostic marker and therapeutic target for alcoholic cardiomyopathy (ACM). [ 119 ] Studies have found that chronic alcohol consumption induces FGF21 levels in the plasma and cardiomyocytes. [ 120 ] The deficiency of FGF21 exacerbated cardiac mitochondrial dysfunction and oxidative stress in response to alcohol exposure, suggesting that FGF21 may protect the heart from ACM by activating the antioxidant defense system in the myocardium.…”

Aortic Injury Induced by Benzo(a)pyrene and Atherogenic Diet Increased Hepatic FGF21 Expression in C57BL/6J Mice

“…Since FGF21 expression levels correlate with serum concentrations of LDL and TC and lesion size and intensity, we can assume that FGF21 expression increases in response to high lipid concentration and atherogenic lesions. Recent studies have shown that FGF21 expression in the heart increases during cardiac stress to mediate compensatory stress responses (30,31). Furthermore, the expression of endogenous FGF21 increases in vascular calcification, and exogenous FGF21 has been shown to ameliorate aortic calcification (32).…”

Mechanism of fibroblast growth factor 21 in cardiac remodeling

“…By improving FGFR1 phosphorylation, long-term FGF21 administration helped to alleviate high-fat-diet-induced left heart dysfunction and restored FGF21 sensitivity ( 116 ). In alcoholic cardiomyopathy, FGF21 improved adverse effects related to dysfunctional mitochondria by mediating autophagic pathways ( 117 ). However, a recent study reported that FGF21-FGFR4 signaling upregulated the activity of ERK1/2, enhancing diabetes mouse concentric cardiac hypertrophy and adverse cardiac remodeling ( 11 ).…”