Ask about this productRelated genes to: FGF21 antibody
- Gene:
- FGF21 NIH gene
- Name:
- fibroblast growth factor 21
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 19q13.33
- Locus Type:
- gene with protein product
- Date approved:
- 1999-11-26
- Date modifiied:
- 2014-11-18
Related products to: FGF21 antibody
Related articles to: FGF21 antibody
- Mammals rely on the integrated stress response (ISR) to maintain essential amino acid (EAA) homeostasis. The kinase GCN2 is a key ISR sensor that is rapidly activated by uncharged tRNAs during EAA deprivation, leading to eIF2α phosphorylation and selective translation of ATF4. ATF4 subsequently orchestrates a transcriptional program regulating amino acid metabolism, redox balance, and autophagy. In this study, we investigated the role of GCN2 in the early hepatic transcriptional response to dietary sulfur amino acids (SAA; methionine and cysteine) deprivation. Using ATF4-luciferase reporter mice, we demonstrate that short-term SAA deprivation rapidly activates the eIF2α-ATF4 pathway within 3 hours, with activation primarily localized to the liver. Complementary in vivo and ex vivo approaches revealed that genetic deletion or pharmacological inhibition of GCN2 abolishes early eIF2α phosphorylation and induction of ATF4 target gene, while PERK is dispensable for this response. Furthermore, GCN2 controls the induction of multiple adaptive transcriptional programs involved in amino acid transport, aminoacyl-tRNA synthesis, autophagy, serine biosynthesis, one-carbon metabolism and glutathione degradation highlighting a coordinated adaptive response to acute SAA deprivation. These findings establish GCN2 as a major sensor mediating the early hepatic response to SAA deprivation, and define a transcriptional program essential for maintaining amino acid homeostasis. In contrast, Fgf21 induction occurs independently of GCN2, indicating the existence of parallel adaptive mechanisms. Collectively, this work provides new insight into the early dynamics and molecular specificity of ISR activation in response to acute dietary SAA deprivation. - Source: PubMed
Publication date: 2026/08/13
Carraro ValérieCherpaz MaëlleLongechamp LucieCoudy-Gandilhon CécileParry LaurentVoyard GuillaumeMaurin Anne-CatherineJousse CélineAverous JulienCombaret LydiePapet IsabelleBruhat Alain - Studies have found that obesity and insulin resistance are linked to central precocious puberty (CPP) in girls, while serum fibroblast growth factor 21 (FGF21) levels are associated with obesity and insulin resistance and related to ovarian development, reproductive function, and gonadotropin-releasing hormone (GnRH) neuron development. The aim of this study was to investigate the levels of serum FGF21 in CPP in girls. - Source: PubMed
Publication date: 2026/08/13
Hao XiaojingWang JiangyaZhou RanSun MengCheng Yaying - Ultra-processed food (UPF) intake is a risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD) development, and fibroblast growth factor 21 (FGF21) is a key regulator of hepatic lipid metabolism, but its role in this association remains unclear. We aimed to investigate whether FGF21 mediates the UPF-MASLD relationship in a population-based cohort and whether berry extract (BE) protects against UPF-related liver injury through FGF21 signaling. This study included 29,386 participants with magnetic resonance imaging (MRI)-derived proton density fat fraction (PDFF) and iron-corrected T1 (cT1) from the UK Biobank. UPF intake was classified according to the NOVA system. Log-binomial and generalized linear regression models were used to estimate the associations of UPF with MASLD, PDFF, and cT1, respectively. In vivo, nine-month-old male C57BL/6J mice were fed a baked Western diet (BWD) with bilberry extract (BE, 200 mg/kg/day) or vehicle for 16 weeks. In vitro, the role of FGF21 was examined by knockdown experiments in AML12 hepatocytes. UPF consumption was linearly associated with a higher risk of MASLD, with per 10% increment associated with 9% higher risk of MASLD (RR 1.09 [95% CI 1.07-1.10]), as well as dose-dependent increases in PDFF and cT1. Among the 283 plasma proteins associated with PDFF, FGF21 showed the strongest association with UPF intake and accounted for the largest proportion of mediation in the UPF-PDFF association. A significant interaction between UPF and berry intake was observed in MASLD risk ( for interaction = 0.018). In the animal model, BE supplementation for 16 weeks alleviated BWD-induced hepatic steatosis, inflammation, and glucose intolerance, while upregulating hepatic FGF21, FGFR1c, and β-Klotho expression and improving mitochondrial function. FGF21 knockdown abrogated BE's protective effect against lipid accumulation in vitro. FGF21 emerged as a potential mediator of the association between UPF consumption and liver fat accumulation. Anthocyanin-rich dietary interventions may offer a promising strategy to prevent MASLD progression. - Source: PubMed
Publication date: 2026/07/25
Lv YanlingZhao FeiyangZhang YaqiZheng ZekunHou CunpengJiang GuanhuaLin ShanLiu LiegangChen Liangkai - Metabolic dysfunction-associated steatotic liver disease (MASLD) is clinically heterogeneous. Patients with similar body mass index, waist circumference, or noninvasive fibrosis stratum may differ markedly in histologic activity, fibrosis trajectory, and progression risk. Adipose tissue dysfunction helps explain this variation. Adipose dysfunction has been characterized by direct depot quantification, measurement of subcutaneous adipose tissue fibrogenesis, adipose tissue insulin resistance, and circulating adipokine profiles. These measures capture different features of adipose biology and have each been linked to liver injury or fibrosis severity. Clinically recognizable body-composition phenotypes-lean MASLD, sarcopenic visceral obesity, myosteatosis, and the hypertriglyceridemic waist-differ in accessibility, mechanistic specificity, and prognostic value. Recent therapeutic developments in metabolic dysfunction-associated steatohepatitis (MASH), including resmetirom, semaglutide, tirzepatide, fibroblast growth factor 21 (FGF21) analogs, and older adipose-directed agents such as pioglitazone, illustrate the importance of distinguishing adipose-mediated, weight-mediated, and liver-directed mechanisms. This review summarizes the literature on adipose tissue dysfunction in MASLD, the body-composition phenotypes associated with it, and recent therapeutic data in the context of adipose-liver-muscle biology. - Source: PubMed
Publication date: 2026/07/30
Cruz Andrew John LegaspiYuan Liyun - Idiopathic pulmonary fibrosis (IPF) remains a progressive and irreversible interstitial lung disease in which currently available antifibrotic therapies slow lung function decline but rarely alter the overall disease course. Increasing evidence suggests that IPF progression is driven not only by local epithelial injury and aberrant repair, but also by broader disturbances in systemic metabolism and redox homeostasis. Within this framework, fibroblast growth factor 21 (FGF21), a liver-derived endocrine hormone that signals through fibroblast growth factor receptors (FGFRs) in the presence of the β-Klotho (KLB) coreceptor, has emerged as a potentially relevant mediator. Recent studies have reported elevated circulating FGF21 together with reduced pulmonary KLB expression in patients with IPF, more severe bleomycin-induced fibrosis in Fgf21-deficient mice, and attenuation of fibrotic injury with preservation of alveolar type II epithelial cell (AEC2) survival after treatment with long-acting polyethylene glycol-conjugated FGF21 (PEG-FGF21). These findings suggest that FGF21 may be more than a metabolic stress marker in IPF. It may contribute to antifibrotic defense by enhancing nuclear factor erythroid 2-related factor 2 (Nrf2)-associated antioxidant responses, preserving epithelial integrity through reduced apoptosis and regulated autophagy, and promoting broader metabolic adaptation. Several translational questions remain unresolved. These include whether elevated circulating FGF21 reflects effective compensation or inadequate adaptation, whether reduced pulmonary KLB causes relative endocrine unresponsiveness, and which mechanism is most relevant to therapeutic translation. Overall, FGF21 represents a promising but still incompletely defined mechanistic and translational candidate in IPF. - Source: PubMed
Publication date: 2026/06/23
Li ShirongBao Hairong