Protocatechuic acid prevents obesity caused by long-chain saturated fatty acid-induced inflammation in mouse microglia via inhibition of the NF-κB pathway

Ken-yu Hironao, Shoma Fujino, Yusei Johta, Kevin Odongo, Hitoshi Ashida and Yoko Yamashita

PLOS ONE, 2026, vol. 21, issue 6, 1-22

Abstract: Long-chain saturated fatty acids (LCSFAs), abundant in animal fats, can directly activate microglia and elicit inflammatory responses. Excessive intake of LCSFA-rich high-fat diets (HFDs) has been linked to microglial activation in the brain (particularly within the hypothalamus, a central regulator of energy metabolism) and to metabolic disorders, including obesity. Here, we report that protocatechuic acid (PCA) suppressed the inflammatory response in murine microglia induced by LCSFAs. PCA inhibited the ubiquitin-proteasome degradation of IκBα induced by LCSFAs, suppressing the nuclear translocation of NF-κB and the expression of pro-inflammatory cytokine genes, which was indicated to be attributed to the suppression of I kappa B kinase. In addition, PCA prevented obesity by inhibiting the accumulation of activated microglia in the ARC of HFD-fed mice. This study is the first to demonstrate that PCA suppresses the inflammatory response of microglia induced by LCSFAs and ARC inflammation in HFD-fed mice. These findings provide new evidence and insights into the mechanisms by which polyphenols, including PCA and its analogs, ameliorate diet-induced obesity.

Date: 2026
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0347055

DOI: 10.1371/journal.pone.0347055

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