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

Overview

Authors: Ken-yu Hironao¹, Shoma Fujino¹, Yusei Johta¹, Kevin Odongo¹, Hitoshi Ashida¹, Yoko Yamashita¹

ORCID iDs: Hitoshi Ashida, Yoko Yamashita

Department of Agrobioscience, Graduate School of Agricultural Science, Kobe University, Nada-ku, Kobe‌‌, Japan

Institutions: Kobe University (Japan)

Journal: PloS one, volume 21, issue 6, article e0347055

Dates: received 21 November 2025; accepted 24 March 2026; published online 1 June 2026

Type: Research article · Language: English

License: CC BY

Identifiers: DOI 10.1371/journal.pone.0347055 · PMID 42224300 · PMCID PMC13225654 · OpenAlex W7163045003

Open access: gold, a free copy (OpenAlex)

Status: data only

Categories: mouse (organism), other condition (population), cellular / molecular (subfield)

Methods: Statistics, Smoothing, state filtering, decompositions

MeSH: Fatty Acids*, Hydroxybenzoates*, Inflammation*, Microglia*, NF-kappa B*, Obesity*, Signal Transduction*, Animals, Cytokines, Diet, High-Fat, I-kappa B Kinase, Male, Mice, Mice, Inbred C57BL (* major topic)

Journal subjects: Biology and Life Sciences, Immunology, Immune Response, Inflammation, Medicine and Health Sciences, Clinical Medicine, Signs and Symptoms, Cell Biology, Cellular Types, Animal Cells, Glial Cells, Microglial Cells, Physiology, Physiological Parameters, Body Weight, Obesity, Anatomy, Brain, Hypothalamus, Biochemistry, Lipids, Fatty Acids, Research and Analysis Methods, Mathematical and Statistical Techniques, Statistical Methods, Multivariate Analysis, Principal Component Analysis, Physical Sciences, Mathematics, Statistics, Nutrition, Diet, Cell Physiology, Cell Metabolism

Topic: Neuroinflammation and Neurodegeneration Mechanisms (Neurology, Neuroscience), according to OpenAlex

Funding: Japan Society for the Promotion of Science (KAKENHI20K05924, 21J20240); Mishima Kaiun Memorial Foundation (NA)

Citations: not cited yet (Europe PMC); 56 references in the paper

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.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

Datasets cited

zenodo:19610302 — at Zenodo; found in “Data Availability”

Data Availability

The data underlying the results presented in the study are available from (https://doi.org/10.5281/zenodo.19610302).

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

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Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 6 authors, 14 MeSH terms, 2 funders, 56 references.

Cite

This paper

Hironao, K.-y., Fujino, S., Johta, Y., Odongo, K., Ashida, H., & Yamashita, Y. (2026). Protocatechuic acid prevents obesity caused by long-chain saturated fatty acid-induced inflammation in mouse microglia via inhibition of the NF-κB pathway. PloS one, 21(6), e0347055. https://doi.org/10.1371/journal.pone.0347055

BibTeX

@article{hironao2026protocatechuic, author = {Hironao, Ken-yu and Fujino, Shoma and Johta, Yusei and Odongo, Kevin and Ashida, Hitoshi and Yamashita, Yoko}, title = {{Protocatechuic acid prevents obesity caused by long-chain saturated fatty acid-induced inflammation in mouse microglia via inhibition of the NF-κB pathway}}, journal = {PloS one}, year = {2026}, month = jun, volume = {21}, number = {6}, pages = {e0347055}, publisher = {PLOS}, issn = {1932-6203}, doi = {10.1371/journal.pone.0347055}, url = {https://doi.org/10.1371/journal.pone.0347055}, pmid = {42224300}, pmcid = {PMC13225654} }

RIS

TY - JOUR AU - Hironao, Ken-yu AU - Fujino, Shoma AU - Johta, Yusei AU - Odongo, Kevin AU - Ashida, Hitoshi AU - Yamashita, Yoko TI - Protocatechuic acid prevents obesity caused by long-chain saturated fatty acid-induced inflammation in mouse microglia via inhibition of the NF-κB pathway T2 - PloS one J2 - PLoS One PY - 2026 DA - 2026/06/01 VL - 21 IS - 6 SP - e0347055 SN - 1932-6203 PB - PLOS DO - 10.1371/journal.pone.0347055 UR - https://doi.org/10.1371/journal.pone.0347055 LA - en ER -

CSL-JSON

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