Gut-derived lipopolysaccharides increase post-prandial oxidative stress via Nox2 activation in patients with impaired fasting glucose tolerance: effect of extra-virgin olive oil

  • Roberto Carnevale
  • Daniele Pastori
  • Cristina Nocella
  • Vittoria Cammisotto
  • Simona Bartimoccia
  • Marta Novo
  • Maria Del Ben
  • Alessio Farcomeni
  • Francesco Angelico
  • Francesco Violi
Original Contribution

Abstract

Purpose

Post-prandial phase is characterized by enhanced oxidative stress but the underlying mechanism is unclear. We investigated if gut-derived lipopolysaccharide (LPS) is implicated in this phenomenon and the effect of extra virgin olive oil (EVOO) in patients with impaired fasting glucose (IFG).

Methods

This is a randomized cross-over interventional study including 30 IFG patients, to receive a lunch with or without 10 g of EVOO. Serum LPS, Apo-B48, markers of oxidative stress such as oxidized LDL (oxLDL) and soluble Nox2-derived peptide (sNox2-dp), a marker of nicotinamide-adenine-dinucleotide-phosphate oxidase isoform Nox2 activation, and plasma polyphenols were determined before, 60 and 120 min after lunch.

Results

In patients not given EVOO oxidative stress as assessed by sNox2-dp and oxLDL significantly increased at 60 and 120 min concomitantly with an increase of LPS and Apo-B48. In these patients, changes of LPS were correlated with Apo-B48 (Rs = 0.542, p = 0.002) and oxLDL (Rs = 0.463, p = 0.010). At 120 min, LPS (β − 15.73, p < 0.001), Apo-B48 (β − 0.14, p = 0.004), sNox2-dp (β − 5.47, p = 0.030), and oxLDL (β − 42.80, p < 0.001) significantly differed between the two treatment groups. An inverse correlation was detected between polyphenols and oxLDL (R − 0.474, p < 0.005). In vitro study showed that LPS, at the same concentrations found in the human circulation, up-regulated Nox2-derived oxidative stress via interaction with Toll-like receptor 4.

Conclusions

Post-prandial phase is characterized by an oxidative stress-related inflammation potentially triggered by LPS, a phenomenon mitigated by EVOO administration.

Keywords

Extra-virgin olive oil Lipopolysaccharide Oxidative stress 

Notes

Acknowledgements

We thank prof. Lorenzo Loffredo for his useful advice.

Author contributions

FV designed research, interpreted the results and wrote paper; RC designed research, wrote paper and performed experiments; CN, VC, SB, MN performed experiments; DP and AF performed statistical analysis; FA and MB recruited patients. All authors approved the final version of the article, including the authorship list.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.

Compliance with ethical standards

Conflict of interest

The authors state that they have no conflict of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Roberto Carnevale
    • 1
  • Daniele Pastori
    • 2
  • Cristina Nocella
    • 3
  • Vittoria Cammisotto
    • 2
  • Simona Bartimoccia
    • 2
  • Marta Novo
    • 2
  • Maria Del Ben
    • 2
  • Alessio Farcomeni
    • 4
  • Francesco Angelico
    • 4
  • Francesco Violi
    • 2
  1. 1.Department of Medical-Surgical Sciences and BiotechnologiesSapienza University of RomeLatinaItaly
  2. 2.I Clinica Medica, Atherothrombosis Center, Department of Internal Medicine and Medical SpecialtiesSapienza University of RomeRomeItaly
  3. 3.Department of AngioCardioNeurologyIRCCS NeuroMedPozzilliItaly
  4. 4.Department of Public Health and Infectious Diseases“Sapienza” University of RomeRomeItaly

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