Abstract
BackgroundRecent studies show that bile acids are involved in glucose and energy homeostasis through activation of G protein coupled membrane receptor (TGR5) and farnesoid X receptor (FXR). A few researches have explored changes of TGR5 and FXR in animals with impaired glucose regulation. This study aimed to observe changes of plasma total bile acids (TBA), glucagon-like-peptide 1 (GLP-1), fibroblast growth factor 15 (FGF15), intestinal expressions of TGR5 and FXR, and correlations between them in rats with glucose intolerance.MethodsBesides plasma fasting glucose, lipid, TBAs, alanine transaminase (ALT), active GLP-1(GLP-1A) and FGF15, a postprandial meal test was used to compare responses in glucose, insulin and GLP-1A among groups. The expressions of TGR5 and FXR in distal ileum and ascending colon were quantified by real-time PCR and western blot.ResultsTGR5 expression was significantly decreased in distal ileum in DM group compared to other groups, and TGR5 and FXR expressions in ascending colon were also decreased in DM group compared to other groups. Correlation analysis showed correlations between TBA and GLP-1A or FGF15. GLP-1A was correlated with TGR5 mRNA expression in colon, and FGF15 was correlated with FXR mRNA expression in colon.ConclusionsThese results indicates that bile acid-TGR5/FXR axis contributes to glucose homeostasis.
Highlights
Recent studies show that bile acids are involved in glucose and energy homeostasis through activation of G protein coupled membrane receptor (TGR5) and farnesoid X receptor (FXR)
Animal experiments Thirty-three four-week old male SD rats were purchased from Slaccas Laboratory Animal, Shanghai, China. They were divided into 3 groups: 1) Normal Control (NC) group, 10 rats were fed with regular chow; 2) Impaired glucose tolerance (IGT) group, 10 rats were fed with high-fat, high-sugar diet serving as insulin-resistant models; 3) Type 2 diabetes mellitus (DM) group, 13 rats were treated with a low dose of STZ after fourweek high-fat, high-sugar diet to induce type 2 diabetes
High-fat, high-sugar diet lead to liver injury As shown in Table 1(the plasma was collected on the day rats were sacrificed), high-fat, high-sugar diet resulted in significant increase of body weight in the imparied glucose tolerance (IGT) and DM groups compared to the normal control (NC) group
Summary
Recent studies show that bile acids are involved in glucose and energy homeostasis through activation of G protein coupled membrane receptor (TGR5) and farnesoid X receptor (FXR). This study aimed to observe changes of plasma total bile acids (TBA), glucagon-like-peptide 1 (GLP-1), fibroblast growth factor 15 (FGF15), intestinal expressions of TGR5 and FXR, and correlations between them in rats with glucose intolerance. In 1999, bile acids were discovered to be natural ligands of the nuclear receptor, FXR [2],which is highly expressed in liver, intestine, kidney, and adrenal glands. The FXR pathway is important in negative feedback regulation of bile acid synthesis. FXR in liver is activated by bile acids synthesized in the hepatocytes or from the enterohepatic circulation to inhibit expression of cholesterol 7ɑ-hydroxylase (CYP7A1), a rate-limiting enzyme in bile.
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