Olive oil-derived nitro-fatty acids: protection of mitochondrial function in non-alcoholic fatty liver disease

J Nutr Biochem. 2021 Aug:94:108646. doi: 10.1016/j.jnutbio.2021.108646. Epub 2021 Apr 7.

Abstract

Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive liver fat deposition in the absence of significant alcohol intake. Since extra virgin olive oil (EVOO) reduces fat accumulation, we analyzed the involvement of nitro-fatty acids (NO2-FA) on the beneficial effects of EVOO consumption on NAFLD. Nitro-fatty acids formation was observed during digestion in mice supplemented with EVOO and nitrite. Mice fed with a high-fat diet (HF) presented lower plasma NO2-FA levels than normal chow, and circulating concentrations recovered when the HF diet was supplemented with 10% EVOO plus nitrite. Under NO2-FA formation conditions, liver hemoxygenase-1 expression significantly increased while decreased body weight and fat liver accumulation. Mitochondrial dysfunction plays a central role in the pathogenesis of NAFLD while NO2-FA has been shown to protect from mitochondrial oxidative damage. Accordingly, an improvement of respiratory indexes was observed when mice were supplemented with both EVOO plus nitrite. Liver mitochondrial complexes II and V activities were greater in mice with EVOO supplementation and further improved in the presence of nitrite. Overall, our results strongly suggest a positive correlation between NO2-OA formation from EVOO and the observed improvement of mitochondrial function in NAFLD. The formation of NO2-FA can account for the health benefits associated with EVOO consumption.

Keywords: Cell signaling; High fat diet; Mediterranean diet; Mitochondria; Nitroalkenes; Non-alcoholic fatty liver disease; Nutrition Liver.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Composition
  • Body Weight
  • Dietary Supplements
  • Fatty Acids / chemistry*
  • Fatty Acids / pharmacology*
  • Female
  • Gene Expression Regulation, Enzymologic / drug effects
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / metabolism
  • Liver / drug effects
  • Liver / pathology
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria / drug effects*
  • Non-alcoholic Fatty Liver Disease / chemically induced*
  • Olive Oil
  • Organ Size

Substances

  • Fatty Acids
  • Membrane Proteins
  • Olive Oil
  • Heme Oxygenase-1
  • Hmox1 protein, mouse