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Background <p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a global health concern characterized by hepatic steatosis and metabolic dysregulation. Metyrapone (MTR), an 11β-hydroxylase inhibitor, is widely used clinically to modulate cortisol levels; however, its potential hepatotoxicity during early zebrafish development remains poorly understood.</p> Objectives <p>This study investigated the hepatotoxic effects and underlying mechanisms of MTR exposure in the early developmental stages of zebrafish.</p> Results <p>Survival rates and morphology, including body length, were largely unaffected at the tested concentrations. However, MTR treatment induced fatty liver, as evidenced by Oil Red O staining and dose-dependent increases in total triglyceride and cholesterol levels. This lipid accumulation was accompanied by the upregulation of key lipid metabolism-related genes, including <i>ppar</i>γ, <i>acsl1b</i>, <i>srebp1</i>, and <i>fasn</i>. Although biochemical changes were observed, no significant alterations in liver area were observed in Tg[<i>fabp10a</i>:DsRed] larvae. MTR exposure triggered oxidative stress, characterized by the increased production of reactive oxygen species, upregulation of <i>gpx1a</i>, and downregulation of <i>cat</i>. MTR exposure increased the expression of endoplasmic reticulum (ER) stress markers (<i>ern1</i>, <i>atf4</i>, <i>atf6</i>, and <i>ddit3</i>).</p> Conclusion <p>MTR induces hepatic steatosis and cellular stress in zebrafish larvae, reflecting key features associated with early hepatic lipid dysregulation, oxidative stress, and ER stress that are relevant to MASLD.</p>

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Metyrapone induces oxidative and ER stresses via fatty liver in zebrafish larvae

  • 期刊论文

  • 发表日期：

    2026年6月23日

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  • Soon Seok Kim,
  • Donggon Yoo,
  • Hang-Suk Chun,
  • Woo-Keun Kim

摘要

Background

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a global health concern characterized by hepatic steatosis and metabolic dysregulation. Metyrapone (MTR), an 11β-hydroxylase inhibitor, is widely used clinically to modulate cortisol levels; however, its potential hepatotoxicity during early zebrafish development remains poorly understood.

Objectives

This study investigated the hepatotoxic effects and underlying mechanisms of MTR exposure in the early developmental stages of zebrafish.

Results

Survival rates and morphology, including body length, were largely unaffected at the tested concentrations. However, MTR treatment induced fatty liver, as evidenced by Oil Red O staining and dose-dependent increases in total triglyceride and cholesterol levels. This lipid accumulation was accompanied by the upregulation of key lipid metabolism-related genes, including pparγ, acsl1b, srebp1, and fasn. Although biochemical changes were observed, no significant alterations in liver area were observed in Tg[fabp10a:DsRed] larvae. MTR exposure triggered oxidative stress, characterized by the increased production of reactive oxygen species, upregulation of gpx1a, and downregulation of cat. MTR exposure increased the expression of endoplasmic reticulum (ER) stress markers (ern1, atf4, atf6, and ddit3).

Conclusion

MTR induces hepatic steatosis and cellular stress in zebrafish larvae, reflecting key features associated with early hepatic lipid dysregulation, oxidative stress, and ER stress that are relevant to MASLD.