Autophagic control of cardiac steatosis through FGF21 in obesity-associated cardiomyopathy

Rupérez, Celia; Lerín, Carles; Ferrer-Curriu, Gemma; Cairó, Montserrat; Mas‐Stachurska, Aleksandra; Sitges, Marta; Villarroya, Joan; Giralt, Marta; Villarroya, Francesc; Planavila, Anna

doi:10.1016/j.ijcard.2018.02.109

Cited by 36 publications

(34 citation statements)

References 49 publications

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“…Immunoblotting analyses showed no significant changes in LC3B-I or LC3B-II or in p62 protein in hearts from WT animals as a consequence of alcohol consumption. However, in Fgf21-null mice, we found a reduction of LC3B-II and an accumulation of the autophagic substrate of degradation p62, consistent with a reduction in autophagy, as previously reported in other models of cardiac disease [30]. We found an increase in Parkin levels in alcoholic Fgf21-null mice (supplementary material, Figure S1B), consistent with a blockade of autophagy/mitophagy.…”

Section: Alcoholic Cardiomyopathy Promotes Mitochondrial Dysfunction supporting

confidence: 90%

The protective effect of fibroblast growth factor‐21 in alcoholic cardiomyopathy: a role in protecting cardiac mitochondrial function

Ferrer-Curriu

Guitart‐Mampel

Rupérez

et al. 2020

The Journal of Pathology

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Alcoholic cardiomyopathy (ACM) resulting from chronic alcohol misuse is one of the main contributors leading to heart failure and cardiovascular mortality. Fibroblast growth factor 21 (FGF21) is a well‐established cardioprotective factor. We aimed to study the role of FGF21 in experimentally induced models and clinical affected patients with cardiac damage due to chronic alcohol consumption. We found that circulating FGF21 levels and cardiac FGF21 and β‐klotho protein levels were increased in subjects with chronic alcohol consumption. As an experimental model of ACM, we fed wild‐type and Fgf21 knockout (Fgf21−/−) mice with a 4% alcohol liquid diet for 4 and 12 weeks. FGF21 circulating levels and FGF21 expression in the myocardium were also increased in wild‐type mice after chronic alcohol intake. Fgf21−/− mice develop a higher degree of cardiac hypertrophy, fibrosis, and cardiac dysfunction after chronic alcohol consumption than wild‐type mice. Moreover, the myocardium of Fgf21−/− mice showed signs of metabolic deregulation, oxidative stress, and mitochondrial dysfunction after alcohol intake. Finally, human cardiac biopsies from patients with chronic alcohol consumption developing ACM presented a higher degree of oxidative stress which positively correlated with the FGF21 protein levels in the myocardium. We conclude that plasma levels and cardiac myocyte FGF21 expression were induced in response to chronic alcohol consumption. The lack of FGF21 aggravated cardiac damage produced by ACM, in association with enhanced mitochondrial and oxidative stress, thus pointing to FGF21 as a protective agent against development of alcohol‐induced cardiomyopathy. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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Section: Alcoholic Cardiomyopathy Promotes Mitochondrial Dysfunction supporting

confidence: 90%

The protective effect of fibroblast growth factor‐21 in alcoholic cardiomyopathy: a role in protecting cardiac mitochondrial function

Ferrer-Curriu

Guitart‐Mampel

Rupérez

et al. 2020

The Journal of Pathology

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“…The higher degree of cardiac fibrosis in Fgf21 −/− mice following exposure to different stimuli has been extensively reported . However, whether the presence of this enhanced fibrosis is a direct cause of the lack of FGF21 or an indirect consequence of overt cardiac damage has not been studied.…”

Section: Resultsmentioning

confidence: 99%

Fibroblast growth factor‐21 protects against fibrosis in hypertensive heart disease

Ferrer-Curriu

Redondo-Angulo

Guitart‐Mampel

et al. 2019

The Journal of Pathology

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FGF21 is an endocrine factor that contributes to multiple pathophysiological processes, mainly via its action as a metabolic regulator and cardioprotective agent. Recent studies have shown increased circulating FGF21 levels in hypertensive patients and in mouse models of hypertension. However, the relevance of FGF21 in hypertensive heart disease has not been addressed. Hypertension was induced by treating 4‐month old WT and Fgf21−/− mice with angiotensin II (AngII) for 1 week, resulting in a similar increase in blood pressure in both genotypes. Plasma FGF21 levels and expression in heart and liver were significantly increased in hypertensive WT mice relative to controls, an effect that was associated with increased expression levels of β‐klotho specifically in the heart. Fgf21−/− mice developed a greater degree of hypertensive heart disease than WT mice, notably characterized by extensive cardiac dysfunction and fibrosis. In vitro and in vivo studies further showed that FGF21 exerted a marked protective effect against cardiac fibrosis. Finally, left ventricle biopsies from human hypertensive heart donors, especially those developing cardiomyopathy, showed a significant increase in FGF21expression compared with normotensive controls, a finding that was associated with significantly enhanced cardiac hypertrophy and fibrosis. We conclude that during hypertension, both systemic and cardiac‐produced FGF21 are induced and act on the heart, protecting it from hypertensive heart disease. Thus, FGF21 acts as key factor in the fibrogenesis associated with hypertensive heart disease. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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“…Moreover, in rodents, it has been reported that FGF21 expression protects against pathologic cardiac hypertrophy, oxidative stress, and myocardial infarction (Planavila et al, 2013, 2015; Joki et al, 2015). In the heart, FGF21 acts in the manner of an autocrine and controls autophagy in obesity-induced cardiomyopathy (Rupérez et al, 2018). In skeletal muscle, FGF21 expression was found undetectable or to be limitedly expressed in basal conditions (Izumiya et al, 2008; Hojman et al, 2009; Pereira et al, 2017; Tezze et al, 2017; Rodríguez-Nuevo et al, 2018).…”

Section: Fgf21 In Cardiac and Skeletal Musclementioning

confidence: 99%

FGF21 as Modulator of Metabolism in Health and Disease

2019

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Fibroblast growth factor 21 (FGF21) is a hormone that regulates important metabolic pathways. FGF21 is expressed in several metabolically active organs and interacts with different tissues. The FGF21 function is complicated and well debated due to its different sites of production and actions. Striated muscles are plastic tissues that undergo adaptive changes within their structural and functional properties in order to meet their different stresses, recently, they have been found to be an important source of FGF21. The FGF21 expression and secretion from skeletal muscles happen in both mouse and in humans during their different physiological and pathological conditions, including exercise and mitochondrial dysfunction. In this review, we will discuss the recent findings that identify FG21 as beneficial and/or detrimental cytokine interacting as an autocrine or endocrine in order to modulate cellular function, metabolism, and senescence.

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Autophagic control of cardiac steatosis through FGF21 in obesity-associated cardiomyopathy

Cited by 36 publications

References 49 publications

The protective effect of fibroblast growth factor‐21 in alcoholic cardiomyopathy: a role in protecting cardiac mitochondrial function

The protective effect of fibroblast growth factor‐21 in alcoholic cardiomyopathy: a role in protecting cardiac mitochondrial function

Fibroblast growth factor‐21 protects against fibrosis in hypertensive heart disease

FGF21 as Modulator of Metabolism in Health and Disease

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