Cynomolgus monkey gallbladder bile contains high concentrations of fibroblast growth factor 19


  • Potential conflict of interest: Nothing to report.

To the Editor:

Fibroblast growth factor 19 (FGF19) is a unique member of the FGF family. It is one of the three secreted FGFs (FGF19, FGF21, and FGF23) that are devoid of mitogenic activity and can be released into the circulation to fulfill an endocrine mode of action.[1-3] It is intriguing that Zweers et al.[4] reported that human bile contains FGF19. In fact, the levels of FGF19 in human gallbladder bile are 100-fold higher than the circulating FGF19 (21.9 ± 13.3 ng/mL versus 0.22 ± 0.14 ng/mL).[4] In addition, they showed that the FGF19 gene is expressed in the adult human gallbladder, and high levels of FGF19 can be secreted from gallbladder mucosal explants.[4] This indicates that a major source of FGF19 in the bile is from mucosal cells of the gallbladder. On the other hand, the messenger RNA (mRNA) of FGF15 (FGF19 ortholog) was virtually undetectable in murine gallbladder.[4] Thus far, the human species is the only species being reported to have a high concentration of FGF19 in the gallbladder bile. To address the skeptical view of an endocrine factor appearing in an exocrine space, we examined gallbladder bile from cynomolgus monkeys (Macaca fascicularis) for the presence of FGF19. In addition, circulating concentrations of FGF19 in monkeys and its responses to the presence and absence of bile acid was determined.

In normal male adult monkeys, the gallbladder bile FGF19 concentrations range from 3,827 to 23,961 pg/mL and average 10,533 pg/mL (Table 1). Interestingly, serum FGF19 concentrations in the monkeys range from 85 to 592 pg/mL and average 358 pg/mL (Table 1), which is similar to that in human (range 49 to 590 pg/mL)[5] and 30-fold lower than that in gallbladder bile. Furthermore, serum concentrations of FGF19 increased significantly after enteral bile acid (chenodeoxycholic acid [CDCA]) stimulation, while it decreased substantially after enteral bile acid sequestration (cholestyramine) (Fig. 1). This is also consistent with the observations in human.[5]

Table 1. Demographics and FGF19 Concentrations in Male Cynomolgus Monkeys
Animal No.Age (yrs)Body Weight (kg)FGF19 (pg/mL)
  1. Animals were cared for in accordance to the Guide for the Care and Use of Laboratory Animals (1996) and protocols were approved by the Kunming Biomed International IACUC. Gallbladder bile samples were taken from animals involved in studies not directly related to BA metabolism or FGF19 regulation during scheduled necropsy. Blood samples were taken from conscious animals being trained for the procedures after an overnight fast. Bile or serum FGF19 concentrations were determined using a human FGF19 ELISA kit purchased from BioVendor (Candler, NC).

Gallbladder Bile FGF19 Concentrations
Serum FGF19 Concentrations
Figure 1.

Serum FGF19 concentrations in response to CDCA or cholestyramine treatment in male cynomolgus monkeys. Procedures were carried out in conscious animals. Before experiments, animals were subjected to training (chair restraint, blood draw, and oral gastric intubation) and became collaborative on these procedures. Following overnight fasting, blood samples were drawn in the morning prior to (basal) and after a single dose of CDCA at 15 mg/kg (n = 4) or cholestyramine at 250 mg/kg (n = 4) by way of oral gastric intubation. *P < 0.05 (paired Student t test).

This is the first report to document high levels of FGF19 detected in the gallbladder bile in monkeys. The finding enhances our confidence in the observation that the presence of FGF19 in bile is valid and most likely physiological. The similar serum FGF19 profile of the two species furthers our interest in using monkeys as a model to understand the potential dual endocrine/exocrine roles of FGF19.

  • Luna Luo1*

  • Faustine Luo1*

  • Tony Wang, Ph.D.2

  • 1Albany High School, Albany, CA

  • 2Kunming Biomed International, Cheng-Gong District, Kunming, Yunan, China