Impact of Obesity and Bariatric Surgery on Metabolic Enzymes and P-Glycoprotein Activity Using the Geneva Cocktail Approach
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design and Population
- Adolescent volunteers having a BMI of <25 and severely obese patients with a BMI of ≥40 who are candidates for bariatric surgery;
- Between the ages of 18 and 60;
- HbA1C < 6.5%;
- All healthy and obese individuals alike must not have active cases of thyroid illness, cirrhosis, IBD, Helicobacter pylori infection, or any other infectious disease (now or during the last four weeks).
- Participants taking medications believed to influence metabolic activity, including corticosteroids or NSAIDs used for their anti-inflammatory effects, will not be allowed to participate in this study;
- Females will be questioned regarding having a normal menstrual cycle and will be disqualified if they are pregnant or breastfeeding;
- Individuals who are often treated with drugs that have an inhibitory or stimulating impact on DMEs and whose substrates are implemented in the phenotyping cocktail;
- Patients who have previously had hypersensitivity to any of the drugs included in the combination;
- Patients who had organ transplant surgeries;
- Patients with an active cancer;
- Participants who had been heavy smokers or alcoholics for at least two months before the research.
2.2. Ethical Approval
2.3. Cocktail Administration
2.4. Laboratory Sample Analysis
2.5. Data Management
2.6. Statistical Analysis
2.7. Safety
3. Results
3.1. Demographic and Paraclinical Results
3.2. The Echocardiography Results of the Patients before and after Surgery
3.3. The Pro-Inflammatory Cytokines Level of the Patients before and after Surgery and Healthy Group
3.4. CYP450 Genotype of the Study Population
3.5. Phenotype Results
3.6. CYP1A2
3.7. CYP2B6
3.8. CYP2C9
3.9. CYP2C19
3.10. CYP2D6
3.11. CYP3A4/5
3.12. P-gp Pump
4. Discussion
5. Strengths and Weaknesses of the Project
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
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BMI (kg/m2) | Classification |
---|---|
<18.5 | Underweight |
≥18.5 and <25.0 | Normal weight |
≥25.0 and <30.0 | Overweight |
≥30.0 | Obese (in general) |
≥30.0 and <35.0 | Obese class I (moderate obesity) |
≥35.0 and <40.0 | Obese class II (severe obesity) and Obese class III (morbid obesity) |
≥40.0 | Classification Underweight |
Parameters | Healthy Participants | Obese Patients before Treatment | Obese Patients after Treatment |
---|---|---|---|
No (%) of subjects | 21 | 24 | |
Sex No. (%) M:F | 14:7 (67:33) | 3:21 (13:87) | |
Age (years) | 30 ± 8.9 | 36.6 ± 8.7 | |
BMI (Kg/m2) | 24.3 ± 3.0 | 45.1 ± 4.2 * | 32.5 ± 3.6 * |
High blood pressure No. (%) | 0 | 2 (8.3) | |
Fatty liver No. (%) | 0 | 3 (12.5) | |
ESR (mm/Hr) | - | 30.1 ± 15.7 | 20.2 ± 18.1 * |
AST (U/L) | - | 20.9 ± 7.8 | 16.8 ± 4.6 * |
ALT (U/L) | - | 26.6 ± 13.9 | 15.7 ± 5.9 * |
HbA1c (%) | - | 5.3 ± 0.5 | 5.0 ± 0.4 * |
TSH (micIU/mL) | - | 4.3 ± 4.1 | 2.4 ± 1.3 |
Cr (mg/dL) | - | 0.9 ± 0.1 | 0.9 ± 0.1 |
Smokers No. (%) | 0 | 12 (50) | |
Alcohol cons. No. (%) | 0 | 4 (16.7) | |
SV-index (cc/m2) | - | 31 ± 5.7 | 40.6 ± 5.7 * |
CO-index (cc/m2) | - | 2425 ± 475 | 2788 ± 663 * |
IL-1β (pg/mL) | 0.9 ± 0.6 | 2.1 ± 3.1 | 3.1 ± 5.2 |
IL-6 (pg/mL) | 2.5 ± 1.5 | 7.3 ± 10.1 | 9.6 ± 11.0 |
Medication use, No. (%) of subjects | |||
Metformin | 0 | 4 (16.7) | |
Statins | 1 (4.7) | 2 (8.3) | |
ARB | 0 | 4 (16.7) | |
CCB | 0 | 2 (8.3) | |
Β-blockers | 0 | 4 (16.7) | |
Aspirin | 0 | 3 (12.5) | |
Other NSAIDs | 0 | 4 (16.7) | |
Antidepressants | 0 | 1 (4.2) | |
PPI | 1 (4.7) | 4 (16.7) | |
OCP | 2 (9.5) | 2 (8.3) |
CYP450 | Control Group Genotype (%) | Obese Patients’ Genotype (%) |
---|---|---|
CYP1A2 | Ex (100) | Ex (100) |
CYP2B6 | Ex (100) | Ex (95.7)-Ra (4.3) |
CYP2C9 | IM (26.3)-Ex (73.7) | IM (27.3)-Ex (72.7) |
CYP2C19 | IM (21.1)-Ex (36.8)- UR (42.1) | IM (27.3)-Ex (31.8)- UR (40.9) |
CYP2D6 | IM (31.6)-Ex (36.8)-UR (31.6) | IM (40)-Ex (60) |
CYP3A | PM (21.1)-IM (68.4)-Ex (10.5) | PM (13.6)-IM (72.7)-Ex (13.6) |
Isoform | Phenotypic Parameter ** | Control Group (C) * | Obese- BS * | Obese- AS * | p-Value C vs. BS | p-Value C vs. AS | p-Value BS vs. AS |
---|---|---|---|---|---|---|---|
CYP1A2 | C2h paraxanthine/C2h caffeine | 0.129 ± 0.073 | 0.166 ± 0.145 | 0.341 ± 0.396 | 0.31 | 0.02 | 0.01 |
CYP2B6 | C3h OH-bupropion/C3h bupropion | 2.855 ± 0.988 | 3.954 ± 2.257 | 5.969 ± 3.703 | 0.05 | 0.001 | 0.01 |
CYP2C9 | C3h OH-flurbiprofen/C3h flurbiprofen | 0.074 ± 0.019 | 0.092 ± 0.043 | 0.110 ± 0.047 | 0.08 | 0.000001 | 0.01 |
CYP2C19 | C3h OH-omeprazole/C3h omeprazole | 0.686 ± 0.558 | 1.683 ± 2.767 | 1.887 ± 2.003 | 0.13 | 0.02 | 0.56 |
CYP2D6 | C3h dextrorphan/C3h dextromethorphan | 1.242 ± 0.835 | 1.091 ± 1.082 | 1.761 ± 1.592 | 0.65 | 0.22 | 0.15 |
CYP3A4/5 | C2h OH-midazolam/C2h midazolam | 0.633 ± 0.253 | 0.419 ± 0.257 | 1.000 ± 0.590 | 0.01 | 0.01 | 0.00003 |
Pump | Phenotypic Parameter # | Control Group (C) | Obese-BS * | Obese-AS * | p-Value C vs. BS | p-Value C vs. AS | p-Value BS vs. AS |
---|---|---|---|---|---|---|---|
P-gp | AUC0-3 fexofenadine | 248 ± 91 | 99.9 ± 98.7 | 143.1 ± 174.4 | 5.1 × 10−6 | 0.02 | 0.18 |
Significancy | CYP1A2 | CYP2B6 | CYP2C9 | CYP2C19 | CYP2D6 | CYP3A4 | P-gp |
---|---|---|---|---|---|---|---|
Before vs. After | |||||||
Before vs. Control | |||||||
After vs. Control | |||||||
Categories | Significant (ρ-value < 0.05) | Non-significant (ρ-value > 0.05) | |||||
Before vs. After | |||||||
Before vs. Control | |||||||
After vs. Control |
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Ghasim, H.; Rouini, M.; Safari, S.; Larti, F.; Khoshayand, M.; Gholami, K.; Neyshaburinezhad, N.; Gloor, Y.; Daali, Y.; Ardakani, Y.H. Impact of Obesity and Bariatric Surgery on Metabolic Enzymes and P-Glycoprotein Activity Using the Geneva Cocktail Approach. J. Pers. Med. 2023, 13, 1042. https://doi.org/10.3390/jpm13071042
Ghasim H, Rouini M, Safari S, Larti F, Khoshayand M, Gholami K, Neyshaburinezhad N, Gloor Y, Daali Y, Ardakani YH. Impact of Obesity and Bariatric Surgery on Metabolic Enzymes and P-Glycoprotein Activity Using the Geneva Cocktail Approach. Journal of Personalized Medicine. 2023; 13(7):1042. https://doi.org/10.3390/jpm13071042
Chicago/Turabian StyleGhasim, Hengameh, Mohammadreza Rouini, Saeed Safari, Farnoosh Larti, Mohammadreza Khoshayand, Kheirollah Gholami, Navid Neyshaburinezhad, Yvonne Gloor, Youssef Daali, and Yalda H. Ardakani. 2023. "Impact of Obesity and Bariatric Surgery on Metabolic Enzymes and P-Glycoprotein Activity Using the Geneva Cocktail Approach" Journal of Personalized Medicine 13, no. 7: 1042. https://doi.org/10.3390/jpm13071042