ORIGINAL RESEARCH article
Front. Vet. Sci.
Sec. Animal Nutrition and Metabolism
Volume 12 - 2025 | doi: 10.3389/fvets.2025.1646921
Chronic Stress-Induced Downregulation of MFN1 Contributes to Fatty Liver in Chickens
Provisionally accepted
- Key Laboratory of Animal Physiology and Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China
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Background Chronic stress is a major contributor to Fatty Liver Syndrome (FLS) in fast-growing broilers, leading to physiological dysfunctions that compromise growth and immune response. This study aimed to investigate the effects of chronic stress on hepatic lipid metabolism and mitochondrial dynamics in broilers. Method Forty 1-day-old male AA broilers were randomly allocated into two groups (n = 20): control (CON) and corticosterone-treated (CORT). From day 38, the CORT group received twice-daily subcutaneous injections of CORT (4 mg/kg/day) for 7 days to simulate in vivo chronic stress model. The loss-of-function approaches in cell culture models were also applied to investigate the role of MFN1 in CORT-induced mitochondrial dysfunction. Results Chronic CORT treatment induced significant hepatic steatosis and liver injury in broilers. Furthermore, CORT disrupted mitochondrial function, as indicated by excessive mitochondrial fragmentation, a pronounced decrease in mitochondrial membrane potential (MMP), and aberrant oxidative stress responses in both in vivo and in vitro models. Studies showed that glucocorticoid receptor (GR)-mediated downregulation of MFN1 plays a critical role in CORT-induced disruption of lipid metabolism. Importantly, restoration of MFN1 expression effectively rescued mitochondrial morphology and function and attenuated lipid accumulation in hepatocytes. Conclusion This study reveals a key mechanism by which chronic stress impairs mitochondrial fusion via GR-mediated suppression of MFN1, driving fatty liver development in broilers. These findings underscore the critical role of MFN1 in mitochondrial dynamics and lipid metabolism, offering novel insights for potential therapeutic strategies against fatty liver disease in poultry.
Keywords: chronic stress, glucocorticoid, mitochondrial fusion, mfn1, GR
Received: 14 Jun 2025; Accepted: 11 Sep 2025.
Copyright: © 2025 Zhang, Yu, Chen, Guan, Wang, Liu, Zhao, Zhao and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Lei Wu, leiwu@njau.edu.cn
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