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β-Klotho (KLB) is a member of the Klotho protein family, which is mainly distributed in organs and tissues such as the liver, fat, pancreas, and brain. KLB is a single-pass transmembrane protein whose structural characteristics determine that KLB acts as a co-receptor for fibroblast growth factor (FGF) 19/21 targeting the activation of fibroblast growth factor receptor (FGFRs). KLB is involved in the regulation of blood glucose, lipids, body weight, bile acid circulation, and hepatocyte proliferation in the FGF21/19-KLB-FGFRs pathway. This paperwill review the structural characteristics and distribution of KLB, as well as the regulatory mechanism of material energy and its role in tumor formation in the FGF19/21-KLB-FGFRs pathways.
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Objective@#To examine the associations of fibroblast growth factor 19 (FGF19), its co-receptor KLB gene and its receptor FGFR4 with susceptibility to sarcopenia, so as to provide insights into elucidation of sarcopenia pathogenesis and formulation of precision interventions for sarcopenia.@*Methods@#A case-control study was conducted. Patients with sarcopenia at ages of 60 years and older included in the Zhejiang Provincial Elderly Health Surveillance Cohorts were selected as the sarcopenia group, and normal residents at ages of 60 years and older were served as controls. Subjects' demographics were collected using questionnaire surveys, and the height, body weight, appendicular skeletal muscle mass and grip strength were measured. Genomic DNA was extracted from blood samples for multiplex PCR targeted capture. The associations between the KLB gene single-nucleotide polymorphisms (SNPs) and susceptibility to sarcopenia were evaluated using multivariable logistic regression models. @*Results@#There were 200 cases in the sarcopenia group, including 91 men and 109 women, and 180 cases in the control group, including 70 men and 110 women. All SNPs satisfied the Hardy-Weinberg equilibrium, and the minor allele frequencies were all > 0.05. There were no significant differences in the distribution of SNPs between the sarcopenia and control groups (all P>0.05). Multivariable logistic regression analysis showed that the SNP rs2687968 locus in the KLB gene was significantly associated with the susceptibility to sarcopenia among the elderly men (superdominant model), and individuals carrying the AC allele had a 2.332-fold higher risk of sarcopenia than those carrying the AA/CC allele (95%CI: 1.882-3.313). @*Conclusions@#KLB gene may correlate with the susceptibility to sarcopenia among the elderly men.
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Objective:To investigate the significance of serum fibroblast growth factor 19 (FGF19), Klotho and fibroblast growth factor receptor 4 (FGFR4) protein expression in patients with primary biliary cirrhosis (PBC).Methods:Sixty-three patients with PBC who received treatment in Ningbo Huamei Hospital, University of Chinese Academy of Sciences between August 2017 and July 2020 were included in the PBC group. An additional 51 healthy patients who concurrently received physical examination in the same hospital were included in the control group. Serum FGF19, Klotho and FGFR4 protein expression were determined by enzyme linked immunosorbent assay.Results:Serum FGF19 and FGFR4 protein in PBC group were (178.86 ± 21.28) ng/L and (2.96 ± 0.47) ng/L, respectively, which were significantly higher than those in the control group [(69.93 ± 12.12) ng/L, (1.21 ± 0.35) ng/L, t = 32.51, 27.98, both P < 0.05]. Klotho protein expression in the PBC group was significantly lower than that in the control group [(3.25 ± 0.89) μg/L vs. (9.67 ± 1.53) μg/L, t = 22.08, P < 0.05]. Serum levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase in the PBC group were (84.25 ± 13.24) U/L, (71.82 ± 10.35) U/L, (278.93 ± 32.45) U/L, respectively, which were significantly higher than those in the control group [(23.76 ± 3.42) U/L, (23.10 ± 4.53) U/L, (76.81 ± 16.36) U/L, t = 31.75, 31.26, 40.48, all P < 0.05]. The receiver operating characteristic curve analysis showed that the sensitivity and specificity of FGF19 in the diagnosis of PBC were 76.67% and 61.90%, respectively, they were 58.82% and 66.67% for Klotho protein diagnosis, 54.55% and 76.67% for FGFR4 protein. Pearson analysis revealed that there was a positive linear relationship between FGF19 and FGFR4 protein ( r = 0.78, P < 0.05), while there was a negative linear relationship between Klotho protein and FGFR4 protein ( r = -0.72, P < 0.05). Conclusion:In patients with PBC, serum FGF19 and FGFR4 protein levels are increased, while Klotho protein level is decreased. There is a positive linear relationship between FGF19 and FGFR4 protein, and there is a negative linear relationship between Klotho protein and FGFR4 protein. This study is highly innovative and scientific.
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@#AIM: To explore the application value of serum pigment epithelial derived factors(PEDF), fibroblast growth factor 19(FGF19)and β-endorphin(β-EP)in the diagnosis and severity assessment of primary glaucoma. <p>METHODS: A total of 102 patients with primary glaucoma in the hospital were enrolled as study group between February 2018 and February 2020, while other 102 healthy controls during the same period were enrolled as control group. The levels of peripheral serum PEDF, FGF19 and β-EP were compared between the two groups. And their diagnostic value for primary glaucoma was analyzed. The study group was divided into severe and non-severe groups according to the diagnostic criteria for severe primary glaucoma. The levels of peripheral serum PEDF, FGF19 and β-EP were compared between severe group and non-severe group. And their evaluation value for disease severity was analyzed. The risk factors of disease severity were analyzed by multivariate Logistic regression analysis. <p>RESULTS: The level of serum PEDF in study group was significantly lower than that in control group, while levels of FGF19 and β-EP were significantly higher than those in control group(<i>P</i><0.001). AUC values of PEDF, FGF19 and β-EP levels in the diagnosis of primary glaucoma were 0.695, 0.754 and 0.768, respectively. The level of serum PEDF in severe group was significantly lower than that in non-severe group(<i>P</i><0.001), while levels of FGF19 and β-EP were significantly higher than those in non-severe group(<i>P</i><0.001). <i>AUC</i>values of PEDF, FGF19 and β-EP levels in assessing the severity of primary glaucoma were 0.731, 0.709 and 0.685, respectively. PEDF lower than 9.66pg/mL, FGF19 higher than 143.75ng/L and β-EP higher than 106.27ng/L were independent influencing factors of severe primary glaucoma(<i>OR</i>=2.280, 1.570, 1.413, all <i>P</i><0.05). <p>CONCLUSION: FGF19 and β-EP are of auxiliary diagnostic value in primary glaucoma, while PEDF and FGF19 are of evaluation value in disease severity. PEDF lower than 9.66pg/mL, FGF19 higher than 143.75ng/L and β-EP higher than 106.27ng/L are independent influencing factors of severe primary glaucoma.
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Fibroblast growth factor receptor (FGFR), as a member of the receptor tyrosine kinase family, participates in a variety of biological processes by binding to ligand fibroblast growth factors (FGFs) and activating downstream signaling pathways, such as cell proliferation, migration, anti-apoptosis, angiogenesis, etc. FGFR gene amplification, missense mutations, oncogenic fusion are related to the occurrence and development of many cancers. FGFR has become an important potential target in cancer treatment. At present most of these studies focus on FGFR1-3, however there is growing evidence implicating an important and unique role of FGFR4 in oncogenesis and resistance to anti-tumor therapy in multiple types of cancer. The abnormality of FGF19-FGFR4 signaling pathway has been proved to be a carcinogenic factor of liver cancer. Importantly, there are several novel FGFR4-specific inhibitors in clinical trials, FGFR4 is therefore a promising target for the treatment of hepatocellular carcinoma harboring aberrant FGF19-FGFR4 signaling. In this review, we focus on assessing the role of FGFR4 in liver cancer, including a summary of the structure and ligand of FGFR4, downstream signaling pathways, abnormal activation in liver cancer, and the research progress of small molecule FGFR4 inhibitors, FGFR4 monoclonal antibodies and combined immunotherapy.
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Fibroblast growth factor 19 (FGF19) is an endocrine hormone and it's primarily regulated by bile acids. FGF19 helps to reduce body weight, a variety of weight loss mechanism are achieved by increasing the level of FGF19. FGF19 can reverse mitochondrial dysfunction caused by obesity. The main pathogenesis of diabetes is insulin resistance and islet β cell defects, which can cause microangiopathy and cardiovascular diseases. FGF19 can fundamentally protect the function of islet β cells, improve insulin resistance, increase insulin sensitivity, and achieve the purpose of reducing blood glucose by insulin-independent manner. Diabetic patients have different degrees of complications. FGF19 can protect the diabetic cardiomyocytes by improving the energy metabolism of diabetic cardiomyocytes. It may play a protective role in the development of diabetic retinopathy and diabetic nephropathy. The results of this review paper show that FGF19 plays an important role in the treatment of obesity, diabetes and its complications, and regulating FGF19 is expected to become a new strategy for the treatment of obesity and diabetes.
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Objective: To assess the potential value of fibroblast growth factor 19 (FGF19) as predictors of gastrointestinal dysfunction in children with sepsis. Methods: A prospective study was conducted, and 101 pediatric patients diagnosed with sepsis and admitted to the pediatric intensive care unit (PICU) at Shanghai Children's Hospital, Shanghai Jiao Tong University were enrolled from January 2018 to December 2018. Eleven cases with missing serum FGF19 were excluded, and 90 cases were analyzed in this study. According to whether gastrointestinal dysfunction occurred in patients with sepsis during PICU hospitalization, patients were divided into two groups, including sepsis-associated ga-strointestinal dysfunction group (n=32) and sepsis without gastrointestinal dysfunction group (n=58). Serum FGF19 level was determined on PICU admission. The difference of serum FGF19 levels between the two groups were compared by using Mann-Whitney U test, and multivariate Logistic regression analysis was used to assess the association of FGF19 level with sepsis-associated ga-strointestinal dysfunction. Results: The total PICU mortality rate was 12.2% (11/90). There was a tendency for increased PICU mortality in patients with sepsis-associated gastrointestinal dysfunction compared with patients without gastrointestinal dysfunction, but without statistical significance (18.8% vs 8.6%, P=0.160). Serum FGF19 levels were significantly decreased in patients with sepsis-associated gastrointestinal dysfunction compared with patients without gastrointestinal dysfunction [48.4 (27.7, 95.6) μg/mL vs 77.6 (45.8, 151.2) μg/mL, P=0.046]. The results of receiver operating characteristic (ROC) curve analysis showed that the area under ROC curve (AUC) for FGF19 predicting gastrointestinal dysfunction in pediatric patients with sepsis was 0.636 (95%CI 0.515-0.757), which was similar to the predictive capacity of procalcitonin [AUC=0.683 (95%CI 0.562-0.804), P=0.597]. In addition, serum FGF19 levels lower than 60 μg/mL on PICU admission indicated an increased risk of gastrointestinal dysfunction in pediatric patients with sepsis. Conclusion: Serum FGF19 is a novel predictor of gastrointestinal dysfunction in pediatric patients with sepsis.
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Objective To observe the expression of FGF19 (fibroblast growth factor 19) and PEDF (pigment epithelium-derived factor) in the serum of type 2 diabetic retinopathy (DR) patients and discuss their significance.Methods Total 89 patients with type 2 diabetes were selected and divided into two groups according to whether they were combined with diabetic retinopathy:45 patients with type 2 diabetes alone (DM group) and 44 patients with type 2 diabetes mellitus combined with retinopathy (DR group).At the same time,40 healthy people were selected as the control group (NDM group).The serum levels of FGF19 and PEDF and their biochemical indexes were detected and compared in each group.The correlation between the indexes and the relationship between FGF19,PEDF and DR were analyzed.Results Compared with NDM group,serum FGF19 level in DM group and DR group decreased,while C-reactive protein (CRP) and PEDF level in DM group and DR group increased (P ＜ 0.05);serum FGF19 level in DR group was lower than that inDMgroup,while serum PEDF level was higher than that in DM group (P ＜0.05).The levels of fasting blood glucose (FBG),fasting insulin levels (FINS),glycosylated hemoglobin (HbA1c),total cholesterol (TC),high density lipoprotein (HDL) and low density lipoprotein (LDL) in DM and DR groups were higher than those in NDM group (P ＜ 0.05),but there was no significant difference between DM group and DR group (P ＞ 0.05);the levels of Hcy,triacylglycerol (TG) and CRP in DR group were higher than those in DM and NDM group (P ＜ 0.05),and the levels of VLDL were lower than those in DM and NDM group (P ＜ 0.05).The level of serum FGF19 was positively correlated with HDL and CRP in patients with DR (r =0.341,0.623,P ＜ 0.05),and negatively correlated with fasting blood glucose(r =-0.428,P ＜0.05);The level of serum PEDF in patients with DR were negatively correlated with FINS (r =-0.343,P ＜0.05).When the serum level of PEDF ＞ 12.76 mg/L,the sensitivity and specificity of PEDF dignosing DR were 80.9％ and 56.7％ respectively.Conclusions In patients with DR,serum FGF19 level decreased and serum PEDF levels increased.The level of both changes is closely related to DR and may be involved in the development of DR.
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Adipose tissue is not only an energy storage organ, but also an endocrine organ involved in metabolic processes. It has the function of secreting various adipokines, such as leptin, adiponectin, etc. Adipose tissue and adipokines are involved in the regulation of glucose and lipid metabolism, which show great value in the study of metabolic diseases such as diabetes and obesity. As a fibroblast growth factor (FGFs), the family of protein hormone-like factors 19 (FGF19) and FGF21 have roles in decreasing body weight, increasing insulin sensitivity, improving blood lipid spectrum, etc. FGF19 and FGF21 are promising target drugs for the treatment of metabolic diseases. The recent research progress on the glycolipid metabolism regulating of FGF19 and FGF21 in adipose tissue were summarized and the application prospects were reviewed.
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[Summary] Bile acid is a main component of bile ,which plays a key role in keeping cholesterol metabolism balance in vivo and promoting lipids digestion in intestine. Recently ,more and more researches focus on bile acid for its regulating effect on glucose ,lipid and energy metabolism as a signal molecule. The reabsorbed bile acid stimulates the secretion of fibroblast growth factor 19 (FGF19) and glucagon-like peptide-1(GLP-1) in the intestine by activating a nuclear receptor farnesoid X-activated receptor (FXR) and a membrane receptor TGR5. FGF19 and GLP-1 regulate hepatic glucose metabolism through different pathways. Here ,we briefly summarize the research progress and relationship between bile acid induced gut hormones and hepatic glucose metabolism.