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<p>Obesity promotes a range of associated conditions, including hearing impairment; however, mechanisms are lacking. Self-evidently, an insult on any cellular constituent of the auditory organ can disrupt hearing. Here, using the mouse auditory cell line, HEI-OC1, we provide insights into adipose-associated ototoxicity. Adipose extracts from mice with obesity, diet- or genetically induced, suppress HEI-OC1’s survival and ATP generation. Proteomic profiling shows an upregulation of the inflammatory response pathway and proteins such as Podoplanin and Low-density lipoprotein receptor. Likewise, the Programmed cell death 4 (PDCD4) protein was induced. These results correspond to a downregulation of glycolysis and oxidative phosphorylation but an upregulation of the G2/M checkpoint. Additionally, pathways such as IL6-JAK-STAT3, IL2-STAT5, interferon gamma response, cholesterol response, bile acid metabolism, RAS, Apoptosis, and TGF-β were upregulated. Furthermore, the adipose extracts cause cellular morphological changes consistent with cells under stress. Functional assays point to alterations in levels of proteins related to calcium and ER homeostasis/stress. The ER-resident protein SARAF, an inhibitor of calcium overfilling, is among the proteins markedly downregulated. GRP78 protein levels increased, suggesting ER/calcium stress. Finally, Thapsigargin impairs HEI-OC1 survival, reminiscent of the effect of the adipose tissue extracts. Our analyses warrant further exploration of inflammation and ER/calcium stress in connection to obesity-associated ototoxicity.</p>

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Ototoxic impacts of adipose-derived extracts on a murine auditory cell line: molecular insights from proteomic analyses

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月24日

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  • Appolinaire A. Olou,
  • Wesley Tom,
  • Gary Krzyzanowski,
  • Chao Jiang,
  • Dinesh Chandel,
  • Nirmalee Fernando,
  • Rama Thelagathoti,
  • Dominic Cosgrove,
  • M. Rohan Fernando

摘要

Obesity promotes a range of associated conditions, including hearing impairment; however, mechanisms are lacking. Self-evidently, an insult on any cellular constituent of the auditory organ can disrupt hearing. Here, using the mouse auditory cell line, HEI-OC1, we provide insights into adipose-associated ototoxicity. Adipose extracts from mice with obesity, diet- or genetically induced, suppress HEI-OC1’s survival and ATP generation. Proteomic profiling shows an upregulation of the inflammatory response pathway and proteins such as Podoplanin and Low-density lipoprotein receptor. Likewise, the Programmed cell death 4 (PDCD4) protein was induced. These results correspond to a downregulation of glycolysis and oxidative phosphorylation but an upregulation of the G2/M checkpoint. Additionally, pathways such as IL6-JAK-STAT3, IL2-STAT5, interferon gamma response, cholesterol response, bile acid metabolism, RAS, Apoptosis, and TGF-β were upregulated. Furthermore, the adipose extracts cause cellular morphological changes consistent with cells under stress. Functional assays point to alterations in levels of proteins related to calcium and ER homeostasis/stress. The ER-resident protein SARAF, an inhibitor of calcium overfilling, is among the proteins markedly downregulated. GRP78 protein levels increased, suggesting ER/calcium stress. Finally, Thapsigargin impairs HEI-OC1 survival, reminiscent of the effect of the adipose tissue extracts. Our analyses warrant further exploration of inflammation and ER/calcium stress in connection to obesity-associated ototoxicity.