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. 2024 Jan 3:102:skae338.
doi: 10.1093/jas/skae338.

Dietary bile acids alleviate corticosterone-induced fatty liver and hepatic glucocorticoid receptor suppression in broiler chickens

Jie Liu  1 , Ke Zhang  1 , Mindie Zhao  1 , Liang Chen  1 , Huimin Chen  1 , Yulan Zhao  1 , Ruqian Zhao  1   2
Affiliations

Dietary bile acids alleviate corticosterone-induced fatty liver and hepatic glucocorticoid receptor suppression in broiler chickens

Jie Liu et al. J Anim Sci. .

Abstract

The aim of this study was to investigate the alleviating effects and mechanisms of bile acids (BA) on corticosterone-induced fatty liver in broiler chickens. Male Arbor Acres chickens were randomly divided into 3 groups: control group (CON), stress model group (CORT), and BA-treated group (CORT-BA). The CORT-BA group received a diet with 250 mg/kg BA from 21 d of age. From days 36 to 43, both the CORT and CORT-BA groups received subcutaneous injections of corticosterone to simulate chronic stress. The results indicated that BA significantly mitigated the body weight loss, liver enlargement, and hepatic lipid deposition caused by corticosterone (P < 0.05). Liver RNA-seq analysis showed that BA alleviated corticosterone-induced fatty liver by inhibiting lipid metabolism pathways, including fatty acid biosynthesis, triglyceride biosynthesis, and fatty acid transport. Additionally, BA improved corticosterone-induced downregulation of glucocorticoid receptor (GR) expression (P < 0.05). Molecular docking and cellular thermal shift assays revealed that hyodeoxycholic acid (HDCA), a major component of compound BA, could bind to GR and enhance its stability. In conclusion, BA alleviated corticosterone-induced fatty liver in broilers by inhibiting lipid synthesis pathways and mitigating the suppression of hepatic GR expression.

Keywords: bile acid; broiler; fatty liver; glucocorticoid receptor; stress.

Plain language summary

Chronic stress leads to a sustained increase in glucocorticoids, which can impair the health of broiler chickens. In this study, chronic stress was simulated by corticosterone treatment, and a complex bile acid (BA) supplement, primarily composed of hyodeoxycholic acid (HDCA), was added to the diet to explore the anti-stress effects of bile acids in broiler chickens. The results showed that BA alleviated the growth suppression caused by prolonged corticosterone exposure. Transcriptome analysis of liver tissue revealed that BA mitigated corticosterone-induced fatty liver primarily by reducing lipid synthesis. Additionally, BA reversed the corticosterone-induced downregulation of hepatic glucocorticoid receptor (GR) expression, though the underlying mechanism remains unclear. Therefore, molecular docking and cellular thermal shift assays were conducted, which revealed that HDCA binds to GR, enhancing the stability of the GR protein. These findings suggest that BA may regulate lipid metabolism and stress responses, offering a promising strategy to mitigate stress-induced liver damage in poultry.

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Conflict of interest statement

The authors declare no real or perceived conflicts of interest.

Figures

Figure 1.
Figure 1.
Bile acids alleviated corticosterone-induced growth inhibition and hepatic lipid deposition. (A) Body weight at 43 d of age (n = 15). (B) Body weight gain from 36 to 43 d of age (n = 15). (C) Liver index (n = 15). (D) Representative images of liver general appearance. (E) Oil Red O staining and HE staining of liver. (F) Liver TG content (n = 10). (G) Liver TCH content (n = 10). Data shown are the means ± SD. *P < 0.05, **P < 0.01, ***P < 0.001.
Figure 2.
Figure 2.
Enrichment analysis of DEGs in the liver. (A) Principal component analysis. (B) Differential gene volcano plots. (C) KEGG pathway enrichment.
Figure 3.
Figure 3.
GSEA enrichment analysis of DEGs in the liver. (A) GSEA pathway enrichment. (B) Heatmap for fatty acid biosynthesis process related genes. (C) Heatmap for triglyceride biosynthesis process related genes. (D) Heatmap for fatty acid transporters related genes. Five samples per group (n = 5).
Figure 4.
Figure 4.
Effect of bile acids on the expression of lipid metabolism genes and GR in the liver. (A) SCD mRNA expression. (B) FASN mRNA expression. (C) ACACA mRNA expression. (D) THRSP mRNA expression. (E) PNPLA3 mRNA expression. (F) FABP4 mRNA expression. (G) GR mRNA expression. (H) GR protein expression. Data shown are the means ± SD. Ten samples per group (n = 10). ***P < 0.001.
Figure 5.
Figure 5.
Biophysical binding of HDCA with GR. (A) Chemical structure of HDCA. (B) Alignment of the LBD protein sequences of human and chicken GR. (C) Molecular docking analysis of GR-LBD and HDCA or dexamethasone. (D) The stabilizing effect of HDCA for GR in AML12 cells. Data shown are the means ± SD. *P < 0.05, **P < 0.01, ***P < 0.001.
See this image and copyright information in PMC

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