Gut microbial metabolites of linoleic acid are metabolized by accelerated peroxisomal β-oxidation in mammalian cells

Morito, Katsuya; Shimizu, Ryota; Kitamura, Nahoko; Park, Si‐Bum; Kishino, Shigenobu; Ogawa, Jun; Fukuta, Tatsuya; Kogure, Kentaro; Tanaka, Tamotsu

doi:10.1016/j.bbalip.2019.07.010

Cited by 13 publications

(6 citation statements)

References 32 publications

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“…Morita et al. ( Morito et al., 2019 ) report that h 18:1 is degraded by cultured mammalian cells and that degradation is significantly reduced in Chinese hamster ovary cells that lack peroxisomes consistent with hydroxy fatty acid activation of PPARα. Immunological targets that modulate the innate immune response have been identified for two of the hydroxy fatty acid molecular species that are synthesized by S. aureus ( h 18:0 and h 18:1) ( Figure 6 ), but not the h 16:0 lipid product.…”

Section: Discussionmentioning

confidence: 99%

“…The hydroxylated derivatives of linoleic acid, 9- and 13-hydroxyoctadecadienoic acids (9-HODE, 13-HODE), arising from either enzymatic synthesis ( Shureiqi et al., 2003 ; Wedel et al., 2022 ) or oxidative damage ( Upston et al., 1997 ) are activating ligands for PPARγ ( Itoh et al., 2008 ; Umeno et al., 2020 ) and PPARα ( Lucarelli et al., 2022 ; Delerive et al., 2000 ). PPAR activation leads to enhanced peroxisomal β-oxidation and OhyA products stimulate peroxisome proliferation in cultured cells ( Morito et al., 2019 ). The HODEs attenuate inflammatory processes including leukocyte chemotaxis ( Henricks et al., 1991 ), degranulation of polymorphonuclear leukocytes ( van de Velde et al., 1995 ) and suppress the innate immune response and inflammation in gut epithelia and macrophages ( Dubrac and Schmuth, 2011 ; Delerive et al., 1999 ).…”

Section: Introductionmentioning

confidence: 99%

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Staphylococcus aureus oleate hydratase produces ligands that activate host PPARα

Radka,

Frank,

Simmons

et al. 2024

Front. Cell. Infect. Microbiol.

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Commensal gut bacteria use oleate hydratase to release a spectrum of hydroxylated fatty acids using host-derived unsaturated fatty acids. These compounds are thought to attenuate the immune response, but the underlying signaling mechanism(s) remain to be established. The pathogen Staphylococcus aureus also expresses an oleate hydratase and 10-hydroxyoctadecanoic acid (h18:0) is the most abundant oleate hydratase metabolite found at Staphylococcal skin infection sites. Here, we show h18:0 stimulates the transcription of a set of lipid metabolism genes associated with the activation of peroxisome proliferator activated receptor (PPAR) in the RAW 264.7 macrophage cell line and mouse primary bone marrow-derived macrophages. Cell-based transcriptional reporter assays show h18:0 selectively activates PPARα. Radiolabeling experiments with bone marrow-derived macrophages show [1-14C]h18:0 is not incorporated into cellular lipids, but is degraded by β-oxidation, and mass spectrometry detected shortened fragments of h18:0 released into the media. The catabolism of h18:0 was >10-fold lower in bone marrow-derived macrophages isolated from Ppara−/− knockout mice, and we recover 74-fold fewer S. aureus cells from the skin infection site of Ppara−/− knockout mice compared to wildtype mice. These data identify PPARα as a target for oleate hydratase-derived hydroxy fatty acids and support the existence of an oleate hydratase-PPARα signaling axis that functions to suppress the innate immune response to S. aureus.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Staphylococcus aureus oleate hydratase produces ligands that activate host PPARα

Radka,

Frank,

Simmons

et al. 2024

Front. Cell. Infect. Microbiol.

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“…However, it was shown that elevated dietary linoleic acid increased gastric carcinoma cell invasion and metastasis in mice ( 59 , 60 ). Considering that gut microbes can convert linoleic acid into other compounds ( 61 , 62 ), different ways of supplementing linoleic acid (e.g., orally and intraperitoneally) might explain the variation in results across studies. Linoleic acid has been widely studied clinically as a nutritional supplement ( 63 , 64 ), higher linoleic acid intake, as assessed by dietary surveys or biomarkers, was associated with a lower risk of death from all causes, especially cardiovascular diseases and cancers ( 63 , 65 ).…”

Section: Discussionmentioning

confidence: 99%

Multi-omics analysis reveals that linoleic acid metabolism is associated with variations of trained immunity induced by distinct BCG strains

Xu,

Chen,

Huang

et al. 2024

Sci. Adv.

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Trained immunity is one of the mechanisms by which BCG vaccination confers persistent nonspecific protection against diverse diseases. Genomic differences between the different BCG vaccine strains that are in global use could result in variable protection against tuberculosis and therapeutic effects on bladder cancer. In this study, we found that four representative BCG strains (BCG-Russia, BCG-Sweden, BCG-China, and BCG-Pasteur) covering all four genetic clusters differed in their ability to induce trained immunity and nonspecific protection. The trained immunity induced by BCG was associated with the Akt-mTOR-HIF1α axis, glycolysis, and NOD-like receptor signaling pathway. Multi-omics analysis (epigenomics, transcriptomics, and metabolomics) showed that linoleic acid metabolism was correlated with the trained immunity–inducing capacity of different BCG strains. Linoleic acid participated in the induction of trained immunity and could act as adjuvants to enhance BCG-induced trained immunity, revealing a trained immunity–inducing signaling pathway that could be used in the adjuvant development.

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“…The ionization energy was 70 eV. The FA methylesters from SM of skin were also analyzed by gas chromatography (GC) (Shimadzu GC‐15A; Shimadzu, Kyoto, Japan) equipped with a capillary column (DB‐225, 0.25 μm film thickness, 30 m length, 0.25 mm ID; Agilent Technologies, Santa Clara, CA, USA) (Morito et al, 2019). In this analysis, isolated SM and hSM were combined, and synthetic 17:0/17:0 phosphatidylcholine was added to the sample as an internal standard before methylesterification.…”

Section: Methodsmentioning

confidence: 99%

Mass Spectrometric Analysis of Sphingomyelin with N‐α‐Hydroxy Fatty Acyl Residue in Mouse Tissues

Ali

Yamashita

Morishige

et al. 2020

Lipids

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Sphingomyelin (SM) with N‐α‐hydroxy fatty acyl residues (hSM) has been shown to occur in mammalian skin and digestive epithelia. However, the metabolism and physiological relevance of this characteristic SM species have not been fully elucidated yet. Here, we show methods for mass spectrometric characterization and quantification of hSM. The hSM in mouse skin was isolated by TLC. The hydroxy hexadecanoyl residue was confirmed by electron impact ionization‐induced fragmentation in gas chromatography–mass spectrometry. Mass shift analysis of acetylated hSM by time of flight mass spectrometry revealed the number of hydroxyl groups in the molecule. After correcting the difference in detection efficacy, hSM in mouse skin and intestinal mucosa were quantified by liquid chromatography–tandem mass spectrometry, and found to be 16.5 ± 2.0 and 0.8 ± 0.4 nmol/μmol phospholipid, respectively. The methods described here are applicable to biological experiments on hSM in epithelia of the body surface and digestive tract.

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Gut microbial metabolites of linoleic acid are metabolized by accelerated peroxisomal β-oxidation in mammalian cells

Cited by 13 publications

References 32 publications

Staphylococcus aureus oleate hydratase produces ligands that activate host PPARα

Staphylococcus aureus oleate hydratase produces ligands that activate host PPARα

Multi-omics analysis reveals that linoleic acid metabolism is associated with variations of trained immunity induced by distinct BCG strains

Mass Spectrometric Analysis of Sphingomyelin with N‐α‐Hydroxy Fatty Acyl Residue in Mouse Tissues

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