FGF 21 deficiency slows gastric emptying and reduces initial blood alcohol concentration in mice exposed to acute alcohol in fasting state

Abstract

Excess alcohol consumption can lead to alcoholic liver disease. Fibroblast growth factor 21 (FGF21) is a metabolic regulator with multiple physiologic functions. Previous study demonstrated that FGF21 deficiency exacerbated alcohol-induced liver injury and exogenous FGF21 administration protected liver from chronic alcohol-induced injury. In this study, we aimed to explore the role of FGF21 in alcohol metabolism in mice. FGF21 knockout (KO) mice and the wild type(WT) control mice were divided into two groups and fasted for 24 h followed by a bonus of alcohol treatment at a dose of 5 g/kg body weight via gavage. Serum alcohol concentration was measured after gavage at 0.5, 2, 3, 4 and 6 h, respectively. At the end, gastric and liver tissues were collected. Serum alcohol concentration of KO mice was significantly lower than that of WT at 0.5 h after alcohol expose. There were no significant differences in alcohol dehydrogenase (ADH) activity and aldehyde dehydrogenase 2 (ALDH2) activity in gastric and liver tissues between WT and the KO mice. However, gastric emptying time of KO mice was much longer than that of WT mice. In addition, the intestinal permeability and serum GLP-1 level of KO mice were significantly higher than that of WT mice. These results suggest that FGF21 deficiency slow gastric emptying rate and indirectly influence initial alcohol metabolism in mice exposed to acute alcohol. Our findings provide additional information for understanding the gastrointestinal mechanism of alcoholic liver disease and other alcohol use disorders.

Keywords: Alcohol; Fibroblast growth factor 21; Gastric emptying.

Fig. 1. FGF21 deficiency decreased initial blood alcohol concentration

Serum FGF21 levels markedly increased in fasting state in WT mice(A). Alcohol concentration of KO group was significantly lower than that of WT group at 0.5 hs after alcohol administration in fasting state (B) but not in fed state (C).

Fig. 2. No difference of ADH and ALDH2 activity between WT and FGF21KO mice in gastric and liver tissues

(A) ADH activity in liver tissue. (B)ADH activity in stomach tissue. (C) ALDH2 activity in liver tissue. (D) ALDH2 activity in stomach tissue.

Fig. 3. FGF21 deficiency delayed gastric emptying and increased serum GLP-1 level

The fluorescence image tracing of the WT (left) and FGF21KO (right) mice at different time points after acute alcohol administration. (A)20min after imaging agent gavage. (B)80min after imaging agent gavage. (C)170min after imaging agent gavage. (D)230min after imaging agent gavage. (E)Serum GLP-1 levels of WT and FGF21 KO mice in fed and fasting state.

Fig. 4

FGF21 deficiency increased the intestinal permeability. Relative Serum FD-4 concentration of mice treated with alcohol.