Lowered fasting chenodeoxycholic acid correlated with the decrease of fibroblast growth factor 19 in Chinese subjects with impaired fasting glucose

Jing Zhang,Qichen Fang,Han Yan,Weiping Jia,Hu Zhou,Yinan Zhang,Huating Li,Jingjing Xu,Li Fang,Qianqian Song,Aimin Xu,Shuqin Chen,Yang Ye

doi:10.1038/s41598-017-06252-6

Abstract

The gut-derived hormone Fibroblast growth factor 19 (FGF19) could regulate glucose metabolism and is induced by bile acids (BAs) through activating Farnesoid X Receptor (FXR). FGF19 was found to decrease in subjects with isolated-impaired fasting glucose (I-IFG) and type 2 diabetes mellitus (T2DM). However, the reason for the change of FGF19 in subjects with different glucometabolic status remained unclear. Here we measured six BAs including chenodeoxycholic acid (CDCA), cholic acid, deoxycholic acid, their glycine conjugates and FGF19 levels during oral glucose tolerance test (OGTT) in normal glucose tolerance (NGT), isolated-impaired glucose tolerance, I-IFG, combined glucose intolerance (CGI) and T2DM subjects. After OGTT, serum FGF19 peaked at 120 min in all subjects. Glycine conjugated BAs peaked at 30 min, while free BAs did not elevated significantly. Consistent with the decrease trend in FGF19 levels, fasting serum CDCA levels in subjects with I-IFG, CGI and T2DM were significantly lower than NGT subjects (P < 0.05). Fasting serum CDCA was independently associated with FGF19. CDCA strongly upregulated FGF19 mRNA levels in LS174T cells in a dose- and time-dependent manner. These results suggest that the decrease of FGF19 in subjects with I-IFG was at least partially due to their decrease of CDCA acting via FXR.

Highlights

Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder that has been recognized as a challenging contemporary threat to public health[1]
Fasting serum chenodeoxycholic acid (CDCA) levels decreased in impaired fasting glucose (I-IFG), combined glucose intolerance (CGI) and type 2 diabetes mellitus (T2DM) subjects, which was coincided with the decrease trend in Fibroblast growth factor 19 (FGF19) concentration
Our results suggested the possibility that the change of fasting FGF19 in subjects with different glucometabolic status might be related with bile acids (BAs)

Summary

Introduction

Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder that has been recognized as a challenging contemporary threat to public health[1]. Patients with pre-diabetes and T2DM showed an increase in serum FGF21 compared with the normal control[9]. IFG and IGT are two categories of pre-diabetes that have different pathophysiological characteristics of glucose metabolism[3]. IFG is due to increased hepatic glucose production, whereas IGT mainly results from peripheral insulin resistance[3]. These clinical data have provided support for the role of FGF19 as a potential mediator with effects on glucose metabolism in humans[6, 17, 18]. We investigated the physiological change of serum FGF19 and individual BAs following 75-g oral glucose tolerance test (OGTT) in Chinese subjects with different glucose tolerance categories, and explored the relationship between serum individual BAs and FGF19

Methods

Results

Conclusion