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<p>Cellular senescence in adipocytes is a key driver of age-related inflammation and metabolic impairment. The present study explored the crosstalk between lipid metabolism and the RAGE network in adipocytes through an integrated bioinformatic and in vitro approach. Analysis of differentially expressed genes (DEGs) derived from GEO datasets identified a putative regulatory association involving PPAR-α, RAGE, and c-JUN (AP-1). Molecular docking and molecular dynamics were performed on Naringenin and Doramapimod to assess anti-inflammatory and p38 MAPK inhibitory functions. Doramapimod showed a comparatively stronger binding to PPAR-α than Naringenin, which has moderate binding affinity. Rapamycin was excluded due to its macrolide structure. Exposure to H<sub>2</sub>O<sub>2</sub> induced senescence-like changes in differentiated 3T3-L1 adipocytes, driving SASP biomarker dysregulation and PPAR-α downregulation. Interestingly, Doramapimod effectively suppressed the expression of inflammatory marker genes, while Naringenin promoted the partial recovery of PPAR-α and PIK3CA mRNA expression. These findings suggest a putative link between lipid metabolism and the RAGE signalling pathway at the transcriptional level. Future studies involving siRNA knockdown, protein expression profiling, and in vivo models are required to define the functional co-dependence of these network components.</p>

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Integrative bioinformatic and in vitro analysis identifies putative lipid metabolism-associated RAGE network components in murine adipocyte senescence

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月27日

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  • Ashish Kumar,
  • Kavitha Thirumurugan

摘要

Cellular senescence in adipocytes is a key driver of age-related inflammation and metabolic impairment. The present study explored the crosstalk between lipid metabolism and the RAGE network in adipocytes through an integrated bioinformatic and in vitro approach. Analysis of differentially expressed genes (DEGs) derived from GEO datasets identified a putative regulatory association involving PPAR-α, RAGE, and c-JUN (AP-1). Molecular docking and molecular dynamics were performed on Naringenin and Doramapimod to assess anti-inflammatory and p38 MAPK inhibitory functions. Doramapimod showed a comparatively stronger binding to PPAR-α than Naringenin, which has moderate binding affinity. Rapamycin was excluded due to its macrolide structure. Exposure to H2O2 induced senescence-like changes in differentiated 3T3-L1 adipocytes, driving SASP biomarker dysregulation and PPAR-α downregulation. Interestingly, Doramapimod effectively suppressed the expression of inflammatory marker genes, while Naringenin promoted the partial recovery of PPAR-α and PIK3CA mRNA expression. These findings suggest a putative link between lipid metabolism and the RAGE signalling pathway at the transcriptional level. Future studies involving siRNA knockdown, protein expression profiling, and in vivo models are required to define the functional co-dependence of these network components.