Fasting plasma chenodeoxycholic acid and cholic acid concentrations are inversely correlated with insulin sensitivity in adults

Bertrand Cariou,Martine Laville,Maud Chetiveaux,Yassine Zaïr,Etienne Pouteau,Béatrice Guyomarc'H-Delasalle,Michel Krempf,Emmanuel Disse

doi:10.1186/1743-7075-8-48

Abstract

BackgroundAccumulating data suggest a novel role for bile acids (BAs) in modulating metabolic homeostasis. BA treatment has been shown to improve glucose tolerance and to increase energy expenditure in mice. Here, we investigated the relationship between fasting plasma BAs concentrations and metabolic parameters in humans.FindingsFasting plasma glucose, insulin and lipid profile were measured in 14 healthy volunteers, 20 patients with type 2 diabetes (T2D), and 22 non-diabetic abdominally obese subjects. Insulin sensitivity was also assessed by the determination of the glucose infusion rate (GIR) during a hyperinsulinemic-euglycemic clamp in a subgroup of patients (9 healthy and 16 T2D subjects). Energy expenditure was measured by indirect calorimetry. Plasma cholic acid (CA), chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA) concentrations were analyzed by gas chromatograph-mass spectrometry. In univariable analysis, a positive association was found between HOMA-IR and plasma CDCA (β = 0.09, p = 0.001), CA (β = 0.03, p = 0.09) and DCA concentrations (β = 0.07, p < 0.0001). Spearman analysis retrieved an inverse relationship between plasma CDCA (r = -0.44, p = 0.03), CA (r = -0.65, p = 0.001) and the GIR. HOMA-IR remained positively associated with CDCA (β = 0.11, p = 0.01), CA (β = 0.04, p = 0.01) and DCA (β = 0.06, p = 0.007) in multivariable analysis, after adjustment for age, gender, BMI, HbA1C and plasma lipid parameters. In contrast, HbA1c, energy expenditure and plasma lipid concentrations were not correlated with plasma BAs levels in multivariable analysis.ConclusionsBoth plasma CDCA, CA and DCA concentrations were negatively associated with insulin sensitivity in a wide range of subjects.

Highlights

Accumulating data suggest a novel role for bile acids (BAs) in modulating metabolic homeostasis
Both plasma chenodeoxycholic acid (CDCA), cholic acid (CA) and deoxycholic acid (DCA) concentrations were negatively associated with insulin sensitivity in a wide range of subjects
Circulating bile acids and glucose homeostasis Total plasma BAs concentrations were higher in both obese and type 2 diabetes (T2D) in comparison with the healthy controls, but the difference reached statistical significance only for the obese subjects compared to controls (Table 1)

Summary

Introduction

Accumulating data suggest a novel role for bile acids (BAs) in modulating metabolic homeostasis. BA treatment has been shown to improve glucose tolerance and to increase energy expenditure in mice. Bile acids (BAs) and BA receptors emerge as new modulators of glucose homeostasis [1]. The addition of cholic acid (CA) to the diet increases energy expenditure and prevents the development of high fat-induced obesity and insulin resistance in mice [10]. This metabolic effect of CA is mediated by the binding to the G-protein-coupled receptor TGR5 [11,12], leading to the induction of the cAMP-dependent thyroid hormone activation enzyme DIO2 (type 2 iodothyronine deiodinase) in brown adipose tissue [10]. Human TGR5 is activated by several BAs, with lithocholic acid (LCA)

Objectives

Methods

Results

Conclusion