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Background <p>Chronic hearing impairment represents a major global health burden, profoundly diminishing quality of life due to its association with depression and cognitive decline. Recent studies have identified metabolic-dysfunction-associated steatohepatitis (MASH) as an independent systemic risk factor for accelerated hearing loss, implicating a functional liver–inner ear axis. However, the molecular and vascular mechanisms through which MASH-induced systemic inflammation compromises cochlear integrity remain uncertain.</p> Methods <p>We investigated the impact of MASH on cochlear pathology and auditory function. MASH was induced in 8-week-old male BALB/c mice by feeding a methionine–choline-deficient (MCD) diet for 4 weeks. After this induction period, the mice were exposed to acoustic trauma and maintained on the same diet for an additional 2 weeks. Systemic and cochlear evaluations were performed to assess the impact of MASH on auditory function and related physiological alterations.</p> Results <p>The MCD diet induced severe hepatic steatosis and lobular inflammation, accompanied by cochlear stria vascularis (SV) hyperpermeability and inflammation characterized by elevated interleukin (IL)-1β and lipocalin-2 (LCN2), without overt hearing loss or hair cell damage. Following noise exposure, MCD-fed mice demonstrated significantly delayed auditory recovery compared to chow-fed controls. This delay was associated with cochlear synaptopathy (CtBP2 degeneration), exacerbated BLB dysfunction, and ultrastructural alterations in endothelial cells, pericytes, and perivascular macrophages within the stria vascularis. PDGFRβ expression was significantly reduced, while proinflammatory mediators (IL-6, IL-1β, and LCN2) were upregulated, suggesting concurrent vascular injury and inflammatory activation.</p> Conclusion <p>These findings demonstrate that MASH sensitizes the cochlea to noise-induced injury through disruption of the BLB and sustained inflammation, providing a preclinical model and mechanistic insight into the link between MASH and hearing loss.</p>

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Metabolic-dysfunction-associated steatohepatitis impairs cochlear integrity and delays auditory recovery after noise trauma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月6日

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  • Sheng Jin,
  • Soo Jeong Kim,
  • Ah-Ra Lyu,
  • Sun-Ae Shin,
  • Tae Hwan Kim,
  • Long Jin,
  • Jun Young Heo,
  • Min Jung Park,
  • Yong-Ho Park

摘要

Background

Chronic hearing impairment represents a major global health burden, profoundly diminishing quality of life due to its association with depression and cognitive decline. Recent studies have identified metabolic-dysfunction-associated steatohepatitis (MASH) as an independent systemic risk factor for accelerated hearing loss, implicating a functional liver–inner ear axis. However, the molecular and vascular mechanisms through which MASH-induced systemic inflammation compromises cochlear integrity remain uncertain.

Methods

We investigated the impact of MASH on cochlear pathology and auditory function. MASH was induced in 8-week-old male BALB/c mice by feeding a methionine–choline-deficient (MCD) diet for 4 weeks. After this induction period, the mice were exposed to acoustic trauma and maintained on the same diet for an additional 2 weeks. Systemic and cochlear evaluations were performed to assess the impact of MASH on auditory function and related physiological alterations.

Results

The MCD diet induced severe hepatic steatosis and lobular inflammation, accompanied by cochlear stria vascularis (SV) hyperpermeability and inflammation characterized by elevated interleukin (IL)-1β and lipocalin-2 (LCN2), without overt hearing loss or hair cell damage. Following noise exposure, MCD-fed mice demonstrated significantly delayed auditory recovery compared to chow-fed controls. This delay was associated with cochlear synaptopathy (CtBP2 degeneration), exacerbated BLB dysfunction, and ultrastructural alterations in endothelial cells, pericytes, and perivascular macrophages within the stria vascularis. PDGFRβ expression was significantly reduced, while proinflammatory mediators (IL-6, IL-1β, and LCN2) were upregulated, suggesting concurrent vascular injury and inflammatory activation.

Conclusion

These findings demonstrate that MASH sensitizes the cochlea to noise-induced injury through disruption of the BLB and sustained inflammation, providing a preclinical model and mechanistic insight into the link between MASH and hearing loss.