Intestinal and hepatic uptake of dietary peroxidized lipids and their decomposition products, and their subsequent effects on apolipoprotein a1 and paraoxonase1

Xueting Jiang, Pragney Deme, Rajat Gupta, Dmitry Litvinov, Kathryn Burge, Sampath Parthasarathy, Chandrakala Aluganti Narasimhulu

Research output: Contribution to journalArticlepeer-review


Both pro-and antiatherosclerotic effects have been ascribed to dietary peroxidized lipids. Confusion on the role of peroxidized lipids in atherosclerotic cardiovascular disease is punctuated by a lack of understanding regarding the metabolic fate and potential physiological effects of dietary per-oxidized lipids and their decomposition products. This study sought to determine the metabolic fate and physiological ramifications of 13-hydroperoxyoctadecadienoic acid (13-HPODE) and 13-HODE (13-hydroxyoctadecadienoic acid) supplementation in intestinal and hepatic cell lines, as well as any effects resulting from 13-HPODE or 13-HODE degradation products. In the presence of Caco-2 cells, 13-HPODE was rapidly reduced to 13-HODE. Upon entering the cell, 13-HODE appears to undergo decomposition, followed by esterification. Moreover, 13-HPODE undergoes autodecomposition to produce aldehydes such as 9-oxononanoic acid (9-ONA). Results indicate that 9-ONA was oxidized to azelaic acid (AzA) rapidly in cell culture media, but AzA was poorly absorbed by intestinal cells and remained detectable in cell culture media for up to 18 h. An increased apolipoprotein A1 (ApoA1) secretion was observed in Caco-2 cells in the presence of 13-HPODE, 9-ONA, and AzA, whereas such induction was not observed in HepG2 cells. However, 13-HPODE treatments suppressed paraoxonase 1 (PON1) activity, suggesting the induction of ApoA1 secretion by 13-HPODE may not represent functional high-density lipoprotein (HDL) capable of reducing oxidative stress. Alternatively, AzA induced both ApoA1 secretion and PON1 activity while suppressing ApoB secretion in differentiated Caco-2 cells but not in HepG2. These results suggest oxidation of 9-ONA to AzA might be an important phenomenon, resulting in the accumulation of potentially beneficial dietary peroxidized lipid-derived aldehydes.

Original languageEnglish (US)
Article number1258
Issue number8
StatePublished - Aug 2021
Externally publishedYes


  • ApoA1
  • Azelaic acid
  • Free fatty acid peroxides
  • Linoleic acid
  • Oxidized lipids
  • Oxononanoic acid
  • Paraoxonase 1

ASJC Scopus subject areas

  • Food Science
  • Molecular Biology
  • Physiology
  • Biochemistry
  • Clinical Biochemistry
  • Cell Biology


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