Gut-derived lipopolysaccharides increase post-prandial oxidative stress via Nox2 activation in patients with impaired fasting glucose tolerance: effect of extra-virgin olive oil
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).
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.
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.
Post-prandial phase is characterized by an oxidative stress-related inflammation potentially triggered by LPS, a phenomenon mitigated by EVOO administration.
KeywordsExtra-virgin olive oil Lipopolysaccharide Oxidative stress
We thank prof. Lorenzo Loffredo for his useful advice.
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.
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.
- 11.American Diabetes Association (2005) Diagnosis and classification of diabetes mellitus. Diabetes Care 28:S37–S42Google Scholar
- 18.Van Greevenbroek MM, De Bruin TW (1998) Chylomicron synthesis by intestinal cells in vitro and in vivo. Atherosclerosis 141:S9–S16Google Scholar