ArticleNPJ science of food2026
Integration of transcriptomics and gut microbiomics reveals walnut septum polyphenols alleviate HFD-induced lipid disorders.
Article in NPJ science of food, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
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.
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