ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
[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.