Digestive n-6 Lipid Oxidation, a Key Trigger of Vascular Dysfunction and Atherosclerosis in the Western Diet: Protective Effects of Apple Polyphenols

Mol Nutr Food Res. 2021 Mar;65(6):e2000487. doi: 10.1002/mnfr.202000487. Epub 2021 Feb 2.

Abstract

Scope: A main risk factor of atherosclerosis is a Western diet (WD) rich in n-6 polyunsaturated fatty acids (PUFAs) sensitive to oxidation. Their oxidation can be initiated by heme iron of red meat leading to the formation of 4-hydroxy-2-nonenal (4-HNE), a cytotoxic aldehyde. An increased 4-HNE production is implicated in endothelial dysfunction and atherosclerosis. By contrast, a diet rich in proanthocyanidins reduces oxidative stress and arterial diseases. This study evaluates the effects of a WD on vascular integrity in ApolipoproteinE (ApoE-/- ) mice and the protective capacity of apple extract and puree rich in antioxidant proanthocyanidins.

Methods and results: ApoE-/- mice are fed during 12 weeks with a WD with or without n-6 PUFAs. Moreover, two WD + n-6 PUFAs groups are supplemented with apple puree or phenolic extract. An increase in digestive 4-HNE production associated with a rise in plasmatic 4-HNE and oxidized LDL concentrations is reported. Oxidizable n-6 PUFAs consumption is associated with a worsened endothelial dysfunction and atherosclerosis. Interestingly, supplementations with apple polyphenol extract or puree prevented these impairments while reducing oxidative stress.

Conclusion: n-6 lipid oxidation during digestion may be a key factor of vascular impairments. Nevertheless, an antioxidant strategy can limit 4-HNE formation during digestion and thus durably protect vascular function.

Keywords: 4-hydroxy-2-nonenal; Western diet; atherosclerosis; endothelial function; polyphenols.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehydes / analysis
  • Aldehydes / metabolism
  • Animals
  • Atherosclerosis / etiology
  • Atherosclerosis / physiopathology*
  • Atherosclerosis / prevention & control*
  • Diet, Western / adverse effects*
  • Dietary Supplements
  • Fatty Acids, Omega-6 / metabolism
  • Fatty Acids, Omega-6 / pharmacokinetics*
  • Lipoproteins, LDL / blood
  • Male
  • Malus / chemistry*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout, ApoE
  • Nitric Oxide / metabolism
  • Oxidation-Reduction
  • Plaque, Atherosclerotic / diagnostic imaging
  • Plaque, Atherosclerotic / prevention & control
  • Polyphenols / chemistry
  • Polyphenols / pharmacology*
  • Reactive Oxygen Species / metabolism

Substances

  • Aldehydes
  • Fatty Acids, Omega-6
  • Lipoproteins, LDL
  • Polyphenols
  • Reactive Oxygen Species
  • oxidized low density lipoprotein
  • Nitric Oxide
  • 4-hydroxy-2-nonenal