The Impact of Acute Ingestion of a Ketone Monoester Drink on LPS-Stimulated NLRP3 Activation in Humans with Obesity
"> Figure 1
<p>Blood beta-hydroxybutyrate (β-OHB) following ketone or placebo drink ingestion. Each drink was ingested immediately following the fasted −30 min blood draw. All timepoints are named relative to the “0 min” time point, at which the OGTT drink was consumed (i.e. −30 min occurred 30 minutes prior to the consumption of the OGTT drink). A time × condition interaction was found (<span class="html-italic">p</span> < 0.001). *<span class="html-italic">p</span> < 0.001 Bonferroni-corrected within-condition pairwise comparisons. Individual participant data are shown with the ketone condition represented by dashed lines and the placebo condition represented by solid lines. Means are shown by bold lines with triangles. <span class="html-italic">n</span> = 11.</p> "> Figure 2
<p>Median fluorescence intensity (MFI) representative of active caspase-1 in human monocytes as quantified by flow cytometry. (<b>A</b>) Histogram comparing MFI of a fluorescence minus one (FMO) control, an unstimulated sample, and an lipopolysaccharide (LPS)-stimulated sample. (<b>B</b>) No changes were observed in unstimulated human monocytes. (<b>C</b>) A significant main effect of time was found (<span class="html-italic">p</span> = 0.043) for LPS-stimulated human monocytes with post hoc testing revealing significantly higher caspase-1 activation at 60 vs. −30 min (*<span class="html-italic">p</span> = 0.013, Bonferroni-corrected pairwise comparison). Individual participant data are shown with the ketone condition represented by dashed lines and the placebo condition represented by solid lines. Means are shown by bold lines with triangles. <span class="html-italic">n</span> = 11.</p> "> Figure 3
<p>Secreted cytokines from LPS-stimulated whole-blood cultures. (<b>A</b>) A main effect of time was found for IL-1β secretion (<span class="html-italic">p</span> = 0.014) with a significant difference detected between 0 and 60 min (*<span class="html-italic">p</span> = 0.014, Bonferroni-corrected pairwise comparison). (<b>B</b>) No changes were observed for interleukin (IL)-6 (<span class="html-italic">p</span> > 0.05). (<b>C</b>) A main effect of time was found for tumor necrosis factor (TNF)-alpha secretion (<span class="html-italic">p</span> = 0.009) with a significant difference detected between 0 and 60 min (*<span class="html-italic">p</span> = 0.009 Bonferroni-corrected post hoc). Individual participant data are shown with the ketone condition represented by dashed lines and the placebo condition represented by solid lines. Means are shown by bold lines with triangles. <span class="html-italic">n</span> = 11.</p> ">
Abstract
:1. Introduction
2. Materials and Methods
2.1. Ethical Approval
2.2. Participants
2.3. Experimental Procedure
2.4. Ketone Monoester Drink
2.5. Quantification of Active Caspase-1
2.6. Quantification of IL-1β Secretion
2.7. Quantification of Plasma Cytokines
2.8. Statistical Analysis
3. Results
3.1. Acute Ingestion of KMD Effectively Raises Blood β-OHB Levels
3.2. No Impact of KMD on Caspase-1 Activation in Unstimulated Whole-Blood Cultures
3.3. KMD Does Not Attenuate Caspase-1 Activation in LPS-Stimulated Monocytes
3.4. KMD Does Not Impact Secretion of IL-1β, IL-6, or TNF-α in LPS-Stimulated Whole-Blood Cultures
3.4.1. IL-1β
3.4.2. IL-6
3.4.3. TNFα
3.5. Plasma Cyotkines
3.5.1. C-Reactive Protein
3.5.2. Plasma Interleukin-1β
3.5.3. Plasma Interleukin-18
3.5.4. Plasma Interleukin-6
3.5.5. Plasma Tumor Necrosis Factor-α
4. Discussion
Limitations and Future Directions
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Males (n = 4) | Females (n = 7) | All (n = 11) | |
---|---|---|---|
Age (years) | 45.0 ± 15.0 | 49.1 ± 9.2 | 47.6 ± 11.1 |
Body Mass (kg) | 110.8 ± 15.0 | 83.6 ± 19.8 | 93.5 ± 22.2 |
Body Mass Index (kg/m2) | 34.2 ± 4.2 | 32.5 ± 5.8 | 33.1 ± 5.1 |
Waist Circumference (cm) | 108.9 ± 9.0 | 99.6 ± 17.6 | 103.3 ± 14.9 |
Systolic Blood Pressure (mmHg) | 133.3 ± 7.2 | 121.6 ± 11.0 | 125.8 ± 11.1 |
Diastolic Blood Pressure (mmHg) | 82.5 ± 9.3 | 83.4 ± 8.1 | 83.5 ± 8.1 |
Hemoglobin A1c (%) | 5.4 ± 0.3 | 5.8 ± 0.7 | 5.7 ± 0.6 |
Fasting Glucose (mM) | 5.4 ± 0.5 | 6.0 ± 1.1 | 5.8 ± 1.0 |
Fasting Insulin (pmol/L) | 203.3 ± 90.0 | 144.9 ± 67.9 | 166.1 ± 80.2 |
OGTT Glucose (120 min, mM) | 5.2 ± 2.1 | 7.1 ± 2.7 | 6.5 ± 2.6 |
OGTT Insulin (120 min, pmol/L) | 778.0 ± 707.3 | 859.6 ± 736.1 | 827.0 ± 685.3 |
Ketone | Placebo | |||||
---|---|---|---|---|---|---|
−30 Min | 0 Min | 60 Min | −30 Min | 0 Min | 60 Minutes | |
hs-CRP (mg/dL) * | 0.39 ± 0.25 | 0.34 ± 0.25 | 0.34 ± 0.23 | 0.50 ± 0.28 | 0.43 ± 0.29 | 0.38 ± 0.28 |
IL-1β (pg/mL) ‡ | 0.11 ± 0.07 | 0.10 ± 0.12 | 0.05 ± 0.05b | 0.05 ± 0.03 | 0.04 ± 0.03 | 0.05 ± 0.03 |
IL-18 (pg/mL) † | 2204.2 ± 831.5 | 2072.4 ± 779.7a | 2147.9 ± 781.1 | 2141.0 ± 788.4 | 2087.7 ± 773.8a | 2019.0 ± 722.1 |
Il-6 (pg/mL) | 1.15 ± 0.41 | 1.21 ± 0.41 | 1.34 ± 0.35 | 1.11 ± 0.52 | 1.21 ± 0.46 | 1.24 ± 0.63 |
TNFα (pg/mL) *,† | 3.61 ± 1.00 | 3.43 ± 0.80a | 3.49 ± 0.84 | 3.51 ± 0.94 | 3.25 ± 0.85a | 3.32 ± 0.79 |
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Neudorf, H.; Myette-Côté, É.; P. Little, J. The Impact of Acute Ingestion of a Ketone Monoester Drink on LPS-Stimulated NLRP3 Activation in Humans with Obesity. Nutrients 2020, 12, 854. https://doi.org/10.3390/nu12030854
Neudorf H, Myette-Côté É, P. Little J. The Impact of Acute Ingestion of a Ketone Monoester Drink on LPS-Stimulated NLRP3 Activation in Humans with Obesity. Nutrients. 2020; 12(3):854. https://doi.org/10.3390/nu12030854
Chicago/Turabian StyleNeudorf, Helena, Étienne Myette-Côté, and Jonathan P. Little. 2020. "The Impact of Acute Ingestion of a Ketone Monoester Drink on LPS-Stimulated NLRP3 Activation in Humans with Obesity" Nutrients 12, no. 3: 854. https://doi.org/10.3390/nu12030854