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<p>Walnut septum, an underutilized agricultural by-product, exhibits anti-obesity potential. However, the in vivo hypolipidemic mechanisms of walnut septum polyphenols (WSP) remain unexplored. We investigated the effects of WSP on lipid metabolism in high-fat diet (HFD)-fed mice using integrated transcriptomic and gut microbiomic analyses. The results indicated that WSP inhibited lipid accumulation in HFD mice and ameliorated HFD-induced oxidative stress, inflammation, and gut barrier impairment. Further studies revealed that WSP positively regulated FoxO1 expression by suppressing the PI3K/AKT signaling pathway, which in turn inhibited hepatic lipid synthesis in HFD mice. Furthermore, WSP concurrently remodeled gut microbiota <i>via</i> selective enrichment of beneficial <i>Akkermansia</i> and depletion of inflammation-associated <i>norank_f__Desulfovibrionaceae</i>. This microbial shift correlated with enhanced intestinal barrier integrity, reduced endotoxemia, and a predicted upregulation of propanoate metabolism. This study provides the first evidence of the synergistic regulation of the PI3K/AKT/FoxO1 pathway and gut microbiota restructuring by WSP, establishing a scientific foundation for valorizing walnut-processing waste into nutraceuticals against obesity.</p><p></p>

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Integration of transcriptomics and gut microbiomics reveals walnut septum polyphenols alleviate HFD-induced lipid disorders

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月26日

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  • Yue-Xiu Pan,
  • Lei Peng,
  • Xia Hu,
  • Jin-lian Chen,
  • Min Su,
  • Jing-jing Dai,
  • Jun Sheng,
  • Zi-Shan Hong,
  • Jing Xie,
  • Yang Tian

摘要

Walnut septum, an underutilized agricultural by-product, exhibits anti-obesity potential. However, the in vivo hypolipidemic mechanisms of walnut septum polyphenols (WSP) remain unexplored. We investigated the effects of WSP on lipid metabolism in high-fat diet (HFD)-fed mice using integrated transcriptomic and gut microbiomic analyses. The results indicated that WSP inhibited lipid accumulation in HFD mice and ameliorated HFD-induced oxidative stress, inflammation, and gut barrier impairment. Further studies revealed that WSP positively regulated FoxO1 expression by suppressing the PI3K/AKT signaling pathway, which in turn inhibited hepatic lipid synthesis in HFD mice. Furthermore, WSP concurrently remodeled gut microbiota via selective enrichment of beneficial Akkermansia and depletion of inflammation-associated norank_f__Desulfovibrionaceae. This microbial shift correlated with enhanced intestinal barrier integrity, reduced endotoxemia, and a predicted upregulation of propanoate metabolism. This study provides the first evidence of the synergistic regulation of the PI3K/AKT/FoxO1 pathway and gut microbiota restructuring by WSP, establishing a scientific foundation for valorizing walnut-processing waste into nutraceuticals against obesity.