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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.

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