Fibroblast growth factor 21 in metabolic syndrome

Yang, Ming; Liu, Chongbin; Jiang, Na; Liu, Yan; Luo, Shilu; Li, Chenrui; Zhao, Hao; Han, Yachun; Chen, Wei; Li, Li; Xiao, Li; Sun, Lin

doi:10.3389/fendo.2023.1220426

Cited by 11 publications

(10 citation statements)

References 120 publications

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“…There is evidence to indicate the promising potential of FGF21 administration in addressing cardiometabolic disorders, such as obesity, diabetes and ageing ( 5 , 6 , 8 , 31 ). Herein, significantly elevated serum levels of FGF21 were observed in rats post-infarction, consistent with previous reports that serum FGF21 levels paradoxically increase in diabetes and its cardiovascular complications ( 9 , 32 ). Hence, the increased serum levels of FGF21 and the decreased expression of KLB following MI may reflect a compensatory response to FGF21 resistance ( 5 ).…”

Section: Discussionsupporting

confidence: 92%

Ultrasound‑targeted microbubble destruction technology delivering β‑klotho to the heart enhances FGF21 sensitivity and attenuates heart remodeling post‑myocardial infarction

Yue,

Li,

et al. 2024

Int J Mol Med

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Fibroblast growth factor (FGF)21 is a peptide hormone that improves mitochondrial function and energy metabolism, and the deficiency of its co-receptor β-klotho (KLB) causes decreased FGF21 sensitivity. The present study examined whether the cardiac delivery of plasmids containing the KLB gene via ultrasound-targeted microbubble destruction (UTMD) enhances the efficacy of FGF21 against heart failure post-acute myocardial infarction (AMI). For this purpose, the levels of FGF21 in patients and rats with heart dysfunction post-infarction were determined using ELISA. Sprague-Dawley rats received the 3X UTMD-mediated delivery of KLB@cationic microbubbles (KLB@CMBs) 1 week following the induction of AMI. Echocardiography, histopathology and biochemical analysis were performed at 4 weeks following the induction of AMI. The results revealed that patients with heart failure post-infarction had higher serum FGF21 levels than the healthy controls. However, the downstream signal, KLB, but not α-klotho, was reduced in the heart tissues of rats with AMI. As was expected, treatment with FGF21 did not substantially attenuate heart remodeling post-infarction. It was found that decreased receptors KLB in the heart may result in the insensitivity to FGF21 treatment. In vivo , the UTMD technology-mediated delivery of KLB@ CMBs to the heart significantly enhanced the effects of FGF21 administration on cardiac remodeling and mitochondrial dysfunction in the rats following infarction. The delivery of KLB to the heart by UTMD and the administration of FGF21 attenuated mitochondrial impairment and oxidative stress by activating nuclear factor erythroid 2-related factor 2 signals. On the whole, the present study demonstrates that the cardiac delivery of KLB significantly optimizes the cardioprotective effects of FGF21 therapy on adverse heart remodeling. UTMD appears a promising interdisciplinary approach with which to improve heart failure post-myocardial infarction.

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Section: Discussionsupporting

confidence: 92%

Ultrasound‑targeted microbubble destruction technology delivering β‑klotho to the heart enhances FGF21 sensitivity and attenuates heart remodeling post‑myocardial infarction

Yue,

Li,

et al. 2024

Int J Mol Med

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“…High levels of circulating FGF21 are often linked to different dysfunctional metabolic processes, such as obesity [ 36 ]. In accordance with these studies, we found an upregulation of this hormone in the serum of the obese group, suggesting that serum FGF21 levels are indicative of a lipid dysregulation that occurs in obese patients with MAFLD.…”

Section: Discussionmentioning

confidence: 99%

Significant Increase in Oxidative Stress Indices in Erythrocyte Membranes of Obese Patients with Metabolically-Associated Fatty Liver Disease

Tutino,

De Nunzio,

Donghia

et al. 2024

JPM

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Metabolic dysfunction-associated hepatic steatosis (MAFLD) indicates the metabolic risk associated with hepatic steatosis, overweight and obesity, and clinical evidence of metabolic dysregulation. Since MAFLD is one of the diseases that show a high frequency of alterations in the lipid content of cell membranes, the aim of this study was to evaluate the indices of oxidative damage of erythrocyte membranes in overweight and obese MAFLD subjects. The study was conducted on serum samples and red blood cell membranes of overweight and obese MAFLD subjects. For each patient, biochemical measurements and lipidomic analyses of erythrocytes membranes were performed. Significant differences in fatty acid profiles of RBC membranes were found between overweight and obese patients. In particular, the Peroxidation Index (PI) was higher in the erythrocyte membranes of obese subjects than in overweight subjects. The same behavior was observed for Unsaturation Index (UI) and Free Radical Stress Index (Free RSI), supporting the fact that the systemic increase in oxidative stress was associated with obesity. The study shows that there is a different susceptibility to erythrocyte membrane peroxidation for overweight and obese subjects, and the increased values of oxidative stress indices observed in the erythrocyte membranes of obese patients with MAFLD may be a possible indicator of pro-oxidative events occurring in obesity-related diseases.

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“…Elevated levels of circulating FGF21 are observed in various metabolic disorders, including DM, obesity, and cardiovascular disease. This seemingly paradoxical occurrence is commonly characterized as a state of "FGF21 resistance" or viewed as a compensatory protective response to metabolic stress (36,37). A clinical investigation assessed circulating FGF21 levels in 2066 hospitalized patients with DM, revealing that individuals in the low urinary glucose excretion group exhibited higher body mass index (BMI) and serum FGF21 levels.…”

Section: Energy Metabolism and Innate Immunity In Dkdmentioning

confidence: 99%

Critical role of FGF21 in diabetic kidney disease: from energy metabolism to innate immunity

Liang,

Chen,

Chang

et al. 2024

Front. Immunol.

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Diabetic kidney disease (DKD) stands as the predominant cause of chronic kidney disease (CKD) on a global scale, with its incidence witnessing a consistent annual rise, thereby imposing a substantial burden on public health. The pathogenesis of DKD is primarily rooted in metabolic disorders and inflammation. Recent years have seen a surge in studies highlighting the regulatory impact of energy metabolism on innate immunity, forging a significant area of research interest. Within this context, fibroblast growth factor 21 (FGF21), recognized as an energy metabolism regulator, assumes a pivotal role. Beyond its role in maintaining glucose and lipid metabolism homeostasis, FGF21 exerts regulatory influence on innate immunity, concurrently inhibiting inflammation and fibrosis. Serving as a nexus between energy metabolism and innate immunity, FGF21 has evolved into a therapeutic target for diabetes, nonalcoholic steatohepatitis, and cardiovascular diseases. While the relationship between FGF21 and DKD has garnered increased attention in recent studies, a comprehensive exploration of this association has yet to be systematically addressed. This paper seeks to fill this gap by summarizing the mechanisms through which FGF21 operates in DKD, encompassing facets of energy metabolism and innate immunity. Additionally, we aim to assess the diagnostic and prognostic value of FGF21 in DKD and explore its potential role as a treatment modality for the condition.

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Fibroblast growth factor 21 in metabolic syndrome

Cited by 11 publications

References 120 publications

Ultrasound‑targeted microbubble destruction technology delivering β‑klotho to the heart enhances FGF21 sensitivity and attenuates heart remodeling post‑myocardial infarction

Ultrasound‑targeted microbubble destruction technology delivering β‑klotho to the heart enhances FGF21 sensitivity and attenuates heart remodeling post‑myocardial infarction

Significant Increase in Oxidative Stress Indices in Erythrocyte Membranes of Obese Patients with Metabolically-Associated Fatty Liver Disease

Critical role of FGF21 in diabetic kidney disease: from energy metabolism to innate immunity

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