Skip to main content
SpringerLink
Log in

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

  • Original Contribution
  • Published:
European Journal of Nutrition Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Valdivielso P, Puerta S, Rioja J et al (2010) Postprandial apolipoprotein B48 is associated with asymptomatic peripheral arterial disease: a study in patients with type 2 diabetes and controls. Clin Chim Acta 411(5–6):433–437

    Article  CAS  PubMed  Google Scholar 

  2. O’Keefe JH, Bell DSH (2007) Postprandial hyperglycemia/hyperlipidemia (postprandial dysmetabolism) is a cardiovascular risk factor. Am J Cardiol 100(5):899–904

    Article  CAS  PubMed  Google Scholar 

  3. Meigs JB, Nathan DM, D’Agostino RB Sr et al (2002) Fasting and postchallenge glycemia and cardiovascular disease risk: the Framingham offspring study. Diabetes Care 25(10):1845–1850

    Article  PubMed  Google Scholar 

  4. ECODE Study Group (2001) The European Diabetes Epidemiology Group Glucose tolerance and cardiovascular mortality: comparison of fasting and 2-hour diagnostic criteria. Arch Intern Med 161(3):397–405

    Article  Google Scholar 

  5. Carnevale R, Bartimoccia S, Nocella C, Di Santo S et al (2014) LDL oxidation by platelets propagates platelet activation via an oxidative stress-mediated mechanism. Atherosclerosis 237(1):108–116

    Article  CAS  PubMed  Google Scholar 

  6. Harte AL, Varma MC, Tripathi G et al (2012) High fat intake leads to acute postprandial exposure to circulating endotoxin in type 2 diabetic subjects. Diabetes Care 35(2):375–382

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Nocella C, Carnevale R, Bartimoccia S et al (2017) Lipopolysaccharide as trigger of platelet aggregation via eicosanoid over-production. Thromb Haemost 117(8):1558–1570

    Article  PubMed  Google Scholar 

  8. Carnevale R, Pignatelli P, Nocella C et al (2014) Extra virgin olive oil blunt post-prandial oxidative stress via NOX2 down-regulation. Atherosclerosis 235(2):649–658

    Article  CAS  PubMed  Google Scholar 

  9. Nóvoa FJ, Boronat M, Saavedra P et al (2005) Differences in cardiovascular risk factors, insulin resistance, and insulin secretion in individuals with normal glucose tolerance and in subjects with impaired glucose regulation: the Telde study. Diabetes Care 28(10):2388–2393

    Article  PubMed  Google Scholar 

  10. Carnevale R, Pastori D, Nocella C et al (2017) Low-grade endotoxemia, gut permeability and platelet activation in patients with impaired fasting glucose. Nutr Metab Cardiovasc Dis 27(10):890–895

    Article  CAS  PubMed  Google Scholar 

  11. American Diabetes Association (2005) Diagnosis and classification of diabetes mellitus. Diabetes Care 28:S37–S42

    Google Scholar 

  12. Serafini M, Maiani G, Ferro-Luzzi A (1998) Alcohol-free red wine enhances plasma antioxidant capacity in humans. J Nutr 128(6):1003–1007

    Article  CAS  PubMed  Google Scholar 

  13. Pignatelli P, Carnevale R, Cangemi R et al (2010) Atorvastatin inhibits gp91phox circulating levels in patients with hypercholesterolemia. Arterioscler Thromb Vasc Biol 30:360–367

    Article  CAS  PubMed  Google Scholar 

  14. Carnevale R, Pignatelli P, Lenti L et al (2007) LDL are oxidatively modified by platelets via GP91(phox) and accumulate in human monocytes. FASEB J 21(3):927–934

    Article  CAS  PubMed  Google Scholar 

  15. Wiedermann CJ, Kiechl S, Dunzendorfer S et al (1999) Association of endotoxemia with carotid atherosclerosis and cardiovascular disease: prospective results from the Bruneck Study. J Am Coll Cardiol 34(7):1975–1981

    Article  CAS  PubMed  Google Scholar 

  16. Ghoshal S, Witta J, Zhong J et al (2009) Chylomicrons promote intestinal absorption of lipopolysaccharides. J Lipid Res 50(1):90–97

    Article  CAS  PubMed  Google Scholar 

  17. Clemente-Postigo M, Queipo-Ortuño MI, Murri M et al (2012) Endotoxin increase after fat overload is related to postprandial hypertriglyceridemia in morbidly obese patients. J Lipid Res 53(5):973–978

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Van Greevenbroek MM, De Bruin TW (1998) Chylomicron synthesis by intestinal cells in vitro and in vivo. Atherosclerosis 141:S9–S16

    Google Scholar 

  19. Violi F, Loffredo L, Pignatelli P et al (2015) Extra virgin olive oil use is associated with improved post-prandial blood glucose and LDL cholesterol in healthy subjects. Nutr Diabetes 5:e172

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Perez-Herrera A, Delgado-Lista J, Torres-Sanchez LA et al (2012) The postprandial inflammatory response after ingestion of heated oils in obese persons is reduced by the presence of phenol compounds. Mol Nutr Food Res 56(3):510–514

    Article  CAS  PubMed  Google Scholar 

  21. Xiao C, Dash S, Morgantini C et al (2014) Sitagliptin, a DPP-4 inhibitor, acutely inhibits intestinal lipoprotein particle secretion in healthy humans. Diabetes 63(7):2394–2401

    Article  PubMed  PubMed Central  Google Scholar 

  22. Servili M, Sordini B, Esposto S et al (2013) Biological activities of phenolic compounds of extra virgin olive oil. Antioxidants 3(1):1–23

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank prof. Lorenzo Loffredo for his useful advice.

Funding

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

Author information

Author notes

  1. Roberto Carnevale and Daniele Pastori equally contributed to this work.

Authors and Affiliations

  1. Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy

    Roberto Carnevale

  2. I Clinica Medica, Atherothrombosis Center, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy

    Daniele Pastori, Vittoria Cammisotto, Simona Bartimoccia, Marta Novo, Maria Del Ben & Francesco Violi

  3. Department of AngioCardioNeurology, IRCCS NeuroMed, 86077, Pozzilli, IS, Italy

    Cristina Nocella

  4. Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, Rome, Italy

    Alessio Farcomeni & Francesco Angelico

Authors
  1. Roberto Carnevale
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniele Pastori
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cristina Nocella
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vittoria Cammisotto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Simona Bartimoccia
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Marta Novo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Maria Del Ben
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Alessio Farcomeni
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Francesco Angelico
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Francesco Violi
    View author publications

    You can also search for this author in PubMed Google Scholar

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.

Corresponding author

Correspondence to Francesco Violi.

Ethics declarations

Conflict of interest

The authors state that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Carnevale, R., Pastori, D., Nocella, C. et al. Gut-derived lipopolysaccharides increase post-prandial oxidative stress via Nox2 activation in patients with impaired fasting glucose tolerance: effect of extra-virgin olive oil. Eur J Nutr 58, 843–851 (2019). https://doi.org/10.1007/s00394-018-1718-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00394-018-1718-x

Keywords

Search

Navigation