Dietary oxidized lipids in redox biology: Oxidized olive oil disrupts lipid metabolism and induces intestinal and hepatic inflammation in C57BL/6J mice

Yifan Bao; Magdalena Osowiecka; Christiane Ott; Vasiliki Tziraki; Lukas Meusburger; Claudia Blaßnig; Daniela Krivda; Petra Pjevac; Joana Séneca Cardoso Da Silva; Matthias Strauß; Christina Steffen; Verena  Heck; Soner Aygün; Kalina Duszka; Kevin Doppelmayer; Tilman Grune; Marc Pignitter

doi:10.1016/j.redox.2025.103575

Dietary oxidized lipids in redox biology: Oxidized olive oil disrupts lipid metabolism and induces intestinal and hepatic inflammation in C57BL/6J mice

Yifan Bao
, Magdalena Osowiecka
, Christiane Ott
, Vasiliki Tziraki
, Lukas Meusburger
, Claudia Blaßnig
, Daniela Krivda
, Petra Pjevac
, Joana Séneca Cardoso Da Silva
, Matthias Strauß
, Christina Steffen
, Verena Heck
, Soner Aygün
, Kalina Duszka
, Kevin Doppelmayer
, Tilman Grune
, Marc Pignitter (Korresp. Autor*in)

Veröffentlichungen: Beitrag in Fachzeitschrift › Artikel › Peer Reviewed

Abstract

Olive oil, rich in oleic acid, is often regarded as a healthier alternative to animal fats high in saturated fatty acids and plant oils rich in oxidizable polyunsaturated fatty acids. However, the redox biological implications and health effects of oxidized olive oil (ox-OO) remain underexplored. Our study investigated its impact on lipid metabolism, intestinal and hepatic inflammation, and gut microbiota. Female C57BL/6J mice were fed either a standard normal (NFD), high-fat diet (HFD), an NFD-ox-OO or HFD-ox-OO, in which ox-OO (180 °C heating, 10 min) was the sole lipid source. Inflammation was assessed using macrophage marker F4/80 immunohistochemical (IHC) staining. Gene expression of inflammatory and lipid metabolism markers (IL-10, NF-kBp65, IL-1β, TNFα, TLR4, COX2, PPARα, PPARγ, CPT1a, SCAD, MCAD, LCAD) was analyzed by qRT-PCR. Soluble epoxide hydrolase (sEH) protein expression was measured using IHC. Oxylipin and carnitine profiles were determined by LC-MS/MS. Gut microbiota was analyzed by 16S rRNA sequencing. Ox-OO disrupted redox homeostasis, leading to lipid metabolic dysfunction in the intestines and liver. In the duodenum and proximal jejunum, ox-OO decreased the levels of anti-inflammatory oxylipins and increased pro-inflammatory mediators, leading to inflammation. In the ileum and colon, ox-OO caused lipid metabolic dysregulation and inflammation. Colon inflammation was linked to inhibited mitochondrial β-oxidation and decreased short-chain fatty acid-producing microbiomes. Notably, redox imbalances were further implicated by the identification of 9,10-epoxy-stearic acid, a novel inflammatory lipid mediator oxidized from dietary oleic acid, which upregulated sEH. Ox-OO affects lipid metabolism and may contribute to inflammation in the gut and liver, raising questions about the assumption that olive oil is always beneficial and suggesting possible risks linked to oxidized oleic acid.

Originalsprache	Englisch
Aufsatznummer	103575
Seitenumfang	17
Fachzeitschrift	Redox biology
Jahrgang	81
Frühes Online-Datum	1 März 2025
DOIs	https://doi.org/10.1016/j.redox.2025.103575
Publikationsstatus	Veröffentlicht - Apr. 2025

Fördermittel

Additionally, gene expression of PPAR\u03B1 in the liver was significantly suppressed, while COX2 gene expression was markedly elevated (Fig. 7D), further supporting the presence of an inflammatory trend and lipid metabolism dysfunction, especially in ARA metabolism. These effects on lipid metabolism also extended to other lipid-regulating sites, notably white adipose tissue, where COX2 expression was highest in the HFD-ox-OO group (Fig. S20A). In the NFD and NFD-ox-OO groups, adipocytes were normal in size and morphology, with minimal extracellular matrix deposition. However, the HFD-ox-OO group showed significant adipocyte hypertrophy, irregular distribution, increased inflammatory cell infiltration, and fibrosis, reflecting tissue damage and lipid metabolic dysfunction (Fig. S20B).This work was supported by the Austrian Academy of Sciences [DOC-Fellowship 26332], the Austrian Science Fund [FWF P34512] and International Communication of the Austrian Research Foundation [\u00D6FG 06/16321]. Research in immunhistologial microscopy was supported by the Imaging center Core Facilities, Medical University of Vienna. Additionally, we sincerely thank Stefanie Deubel and Alice Mika (Department of Molecular Toxicology and Max Rubner Laboratory, German Institute of Human Nutrition) for their support with the section of the animals and the preparation and staining of histological samples. This work was supported by the Austrian Academy of Sciences [DOC-Fellowship 26332], the Austrian Science Fund [FWF P34512] and International Communication of the Austrian Research Foundation [\u00D6FG 06/16321]. Research in immunhistologial microscopy was supported by the Imaging center Core Facilities, Medical University of Vienna. Additionally, we sincerely thank Stefanie Deubel and Alice Mika (Department of Molecular Toxicology and Max Rubner Laboratory, German Institute of Human Nutrition) for their support with the section of the animals and the preparation and staining of histological samples.

ÖFOS 2012

106026 Ökosystemforschung
106022 Mikrobiologie
104004 Chemische Biologie

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10.1016/j.redox.2025.103575Lizenz: CC BY 4.0

https://phaidra.univie.ac.at/o:2156950Lizenz: CC BY 4.0

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Bao, Y., Osowiecka, M., Ott, C., Tziraki, V., Meusburger, L., Blaßnig, C., Krivda, D., Pjevac, P., Séneca Cardoso Da Silva, J., Strauß, M., Steffen, C., Heck, V., Aygün, S., Duszka, K., Doppelmayer, K., Grune, T., & Pignitter, M. (2025). Dietary oxidized lipids in redox biology: Oxidized olive oil disrupts lipid metabolism and induces intestinal and hepatic inflammation in C57BL/6J mice. Redox biology, 81, Artikel 103575. https://doi.org/10.1016/j.redox.2025.103575

@article{432d169663dd4bcc86ad98e8b58a562a,

title = "Dietary oxidized lipids in redox biology: Oxidized olive oil disrupts lipid metabolism and induces intestinal and hepatic inflammation in C57BL/6J mice",

abstract = "Olive oil, rich in oleic acid, is often regarded as a healthier alternative to animal fats high in saturated fatty acids and plant oils rich in oxidizable polyunsaturated fatty acids. However, the redox biological implications and health effects of oxidized olive oil (ox-OO) remain underexplored. Our study investigated its impact on lipid metabolism, intestinal and hepatic inflammation, and gut microbiota. Female C57BL/6J mice were fed either a standard normal (NFD), high-fat diet (HFD), an NFD-ox-OO or HFD-ox-OO, in which ox-OO (180 °C heating, 10 min) was the sole lipid source. Inflammation was assessed using macrophage marker F4/80 immunohistochemical (IHC) staining. Gene expression of inflammatory and lipid metabolism markers (IL-10, NF-kBp65, IL-1β, TNFα, TLR4, COX2, PPARα, PPARγ, CPT1a, SCAD, MCAD, LCAD) was analyzed by qRT-PCR. Soluble epoxide hydrolase (sEH) protein expression was measured using IHC. Oxylipin and carnitine profiles were determined by LC-MS/MS. Gut microbiota was analyzed by 16S rRNA sequencing. Ox-OO disrupted redox homeostasis, leading to lipid metabolic dysfunction in the intestines and liver. In the duodenum and proximal jejunum, ox-OO decreased the levels of anti-inflammatory oxylipins and increased pro-inflammatory mediators, leading to inflammation. In the ileum and colon, ox-OO caused lipid metabolic dysregulation and inflammation. Colon inflammation was linked to inhibited mitochondrial β-oxidation and decreased short-chain fatty acid-producing microbiomes. Notably, redox imbalances were further implicated by the identification of 9,10-epoxy-stearic acid, a novel inflammatory lipid mediator oxidized from dietary oleic acid, which upregulated sEH. Ox-OO affects lipid metabolism and may contribute to inflammation in the gut and liver, raising questions about the assumption that olive oil is always beneficial and suggesting possible risks linked to oxidized oleic acid.",

keywords = "oxidized olive oil, inflammation, lipid metabolic dysfunction, gut microbiota, 9,10-Epoxy-stearic acid, Gut microbiota, Lipid metabolic dysfunction, Oxidized olive oil, Inflammation",

author = "Yifan Bao and Magdalena Osowiecka and Christiane Ott and Vasiliki Tziraki and Lukas Meusburger and Claudia Bla{\ss}nig and Daniela Krivda and Petra Pjevac and \{S{\'e}neca Cardoso Da Silva\}, Joana and Matthias Strau{\ss} and Christina Steffen and Verena Heck and Soner Ayg{\"u}n and Kalina Duszka and Kevin Doppelmayer and Tilman Grune and Marc Pignitter",

note = "Publisher Copyright: {\textcopyright} 2025 The Authors Accession Number WOS:001440431400001 PubMed ID 40043451 ",

year = "2025",

month = apr,

doi = "10.1016/j.redox.2025.103575",

language = "English",

volume = "81",

journal = "Redox biology",

issn = "2213-2317",

publisher = "Elsevier",

}

Bao, Y, Osowiecka, M, Ott, C, Tziraki, V, Meusburger, L, Blaßnig, C, Krivda, D, Pjevac, P , Séneca Cardoso Da Silva, J, Strauß, M, Steffen, C, Heck, V, Aygün, S, Duszka, K, Doppelmayer, K, Grune, T & Pignitter, M 2025, 'Dietary oxidized lipids in redox biology: Oxidized olive oil disrupts lipid metabolism and induces intestinal and hepatic inflammation in C57BL/6J mice', Redox biology, Jg. 81, 103575. https://doi.org/10.1016/j.redox.2025.103575

TY - JOUR

T1 - Dietary oxidized lipids in redox biology: Oxidized olive oil disrupts lipid metabolism and induces intestinal and hepatic inflammation in C57BL/6J mice

AU - Bao, Yifan

AU - Osowiecka, Magdalena

AU - Ott, Christiane

AU - Tziraki, Vasiliki

AU - Meusburger, Lukas

AU - Blaßnig, Claudia

AU - Krivda, Daniela

AU - Pjevac, Petra

AU - Séneca Cardoso Da Silva, Joana

AU - Strauß, Matthias

AU - Steffen, Christina

AU - Heck, Verena

AU - Aygün, Soner

AU - Duszka, Kalina

AU - Doppelmayer, Kevin

AU - Grune, Tilman

AU - Pignitter, Marc

PY - 2025/4

Y1 - 2025/4

N2 - Olive oil, rich in oleic acid, is often regarded as a healthier alternative to animal fats high in saturated fatty acids and plant oils rich in oxidizable polyunsaturated fatty acids. However, the redox biological implications and health effects of oxidized olive oil (ox-OO) remain underexplored. Our study investigated its impact on lipid metabolism, intestinal and hepatic inflammation, and gut microbiota. Female C57BL/6J mice were fed either a standard normal (NFD), high-fat diet (HFD), an NFD-ox-OO or HFD-ox-OO, in which ox-OO (180 °C heating, 10 min) was the sole lipid source. Inflammation was assessed using macrophage marker F4/80 immunohistochemical (IHC) staining. Gene expression of inflammatory and lipid metabolism markers (IL-10, NF-kBp65, IL-1β, TNFα, TLR4, COX2, PPARα, PPARγ, CPT1a, SCAD, MCAD, LCAD) was analyzed by qRT-PCR. Soluble epoxide hydrolase (sEH) protein expression was measured using IHC. Oxylipin and carnitine profiles were determined by LC-MS/MS. Gut microbiota was analyzed by 16S rRNA sequencing. Ox-OO disrupted redox homeostasis, leading to lipid metabolic dysfunction in the intestines and liver. In the duodenum and proximal jejunum, ox-OO decreased the levels of anti-inflammatory oxylipins and increased pro-inflammatory mediators, leading to inflammation. In the ileum and colon, ox-OO caused lipid metabolic dysregulation and inflammation. Colon inflammation was linked to inhibited mitochondrial β-oxidation and decreased short-chain fatty acid-producing microbiomes. Notably, redox imbalances were further implicated by the identification of 9,10-epoxy-stearic acid, a novel inflammatory lipid mediator oxidized from dietary oleic acid, which upregulated sEH. Ox-OO affects lipid metabolism and may contribute to inflammation in the gut and liver, raising questions about the assumption that olive oil is always beneficial and suggesting possible risks linked to oxidized oleic acid.

AB - Olive oil, rich in oleic acid, is often regarded as a healthier alternative to animal fats high in saturated fatty acids and plant oils rich in oxidizable polyunsaturated fatty acids. However, the redox biological implications and health effects of oxidized olive oil (ox-OO) remain underexplored. Our study investigated its impact on lipid metabolism, intestinal and hepatic inflammation, and gut microbiota. Female C57BL/6J mice were fed either a standard normal (NFD), high-fat diet (HFD), an NFD-ox-OO or HFD-ox-OO, in which ox-OO (180 °C heating, 10 min) was the sole lipid source. Inflammation was assessed using macrophage marker F4/80 immunohistochemical (IHC) staining. Gene expression of inflammatory and lipid metabolism markers (IL-10, NF-kBp65, IL-1β, TNFα, TLR4, COX2, PPARα, PPARγ, CPT1a, SCAD, MCAD, LCAD) was analyzed by qRT-PCR. Soluble epoxide hydrolase (sEH) protein expression was measured using IHC. Oxylipin and carnitine profiles were determined by LC-MS/MS. Gut microbiota was analyzed by 16S rRNA sequencing. Ox-OO disrupted redox homeostasis, leading to lipid metabolic dysfunction in the intestines and liver. In the duodenum and proximal jejunum, ox-OO decreased the levels of anti-inflammatory oxylipins and increased pro-inflammatory mediators, leading to inflammation. In the ileum and colon, ox-OO caused lipid metabolic dysregulation and inflammation. Colon inflammation was linked to inhibited mitochondrial β-oxidation and decreased short-chain fatty acid-producing microbiomes. Notably, redox imbalances were further implicated by the identification of 9,10-epoxy-stearic acid, a novel inflammatory lipid mediator oxidized from dietary oleic acid, which upregulated sEH. Ox-OO affects lipid metabolism and may contribute to inflammation in the gut and liver, raising questions about the assumption that olive oil is always beneficial and suggesting possible risks linked to oxidized oleic acid.

KW - oxidized olive oil

KW - inflammation

KW - lipid metabolic dysfunction

KW - gut microbiota

KW - 9,10-Epoxy-stearic acid

KW - Gut microbiota

KW - Lipid metabolic dysfunction

KW - Oxidized olive oil

KW - Inflammation

UR - https://www.scopus.com/pages/publications/85219115947

U2 - 10.1016/j.redox.2025.103575

DO - 10.1016/j.redox.2025.103575

M3 - Article

SN - 2213-2317

VL - 81

JO - Redox biology

JF - Redox biology

M1 - 103575

ER -

Dietary oxidized lipids in redox biology: Oxidized olive oil disrupts lipid metabolism and induces intestinal and hepatic inflammation in C57BL/6J mice

Abstract

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ÖFOS 2012

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