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
N1 - Publisher Copyright:
© 2025 The Authors
PY - 2025/3/1
Y1 - 2025/3/1
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 - http://www.scopus.com/inward/record.url?scp=85219115947&partnerID=8YFLogxK
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 -