miR33a/miR33b* and miR122 as Possible Contributors to Hepatic Lipid Metabolism in Obese Women with Nonalcoholic Fatty Liver Disease
Abstract
:1. Introduction
2. Results
2.1. Baseline Characteristics of the Subjects
2.2. Evaluation of the Liver Expression of miR33a/b* and miR122 According to Body Mass Index (BMI)
2.3. Evaluation of the Liver Expression of miR33a/b* and miR122 According to Liver Histology
2.3.1. Morbidly Obese MO Patients
2.3.2. Moderately Obese ModO Patients
2.4. Evaluation of the Liver Expression of Genes Involved in Lipogenesis, Lipid Oxidation, and Secretion of Lipoproteins According to BMI
2.5. Evaluation of the Liver Expression of Genes Involved in Lipogenesis, Lipid Oxidation, and Secretion of Lipoproteins Based on Liver Histology
2.5.1. MO Patients
2.5.2. ModO Patients
2.6. Significant Correlations of the miR33 a/b* and miR122 Expression with the Expression of Genes Involved in Lipid Metabolism
2.7. Evaluation of miRNA Circulating Levels of miR33b* and miR122 According to BMI
2.8. Evaluation of miRNA Circulating Levels of miR33b* and miR122 According to Liver Histology
2.8.1. MO Patients
2.8.2. ModO Patients
2.9. Correlations between Circulating Levels of miRNA and Its Expression in Liver
2.10. Correlations of miRNA Circulating Levels with Biochemical Parameters and the Stratification of the Severity of Histological Disease
2.11. Evaluation of miR122 Circulating Levels as a Biomarker of Nonalcoholic Fatty Liver Disease (NAFLD)
3. Discussion
4. Materials and Methods
4.1. Subjects
4.2. RNA Isolation and Real-Time PCR
4.3. Statistical Analysis
5. Conclusions
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Variables | Normal-Weight (n = 30) Mean ± SEM | Moderate Obesity (n = 30) Mean ± SEM | Morbid Obesity (n = 62) Mean ± SEM | ||||
---|---|---|---|---|---|---|---|
– | NL (n = 9) | SS (n = 9) | NASH (n = 12) | NL (n = 22) | SS (n = 18) | NASH (n = 22) | |
Age (years) | 41.0 ± 2.2 *,£ | 49.8 ± 3.7 | 49.06 ± 5.2 | 52.23 ± 10.5 | 46.3 ± 2.6 | 47.2 ± 2.4 | 48.8 ± 2.5 |
Weight (kg) § | 58.2 ± 1.5 *,£ | 90.4 ± 2.5 | 96.5 ± 4.0 | 89.1 ± 2.6 | 120.3 ± 3.8 | 121.1 ± 4.5 | 119.8 ± 3.1 |
WC (cm) § | 75.2 ± 2.1 *,£ | 107.8 ± 1.8 | 111.0 ± 3.8 | 107.2 ± 3.8 | 132.4 ± 5.6 | 132.3 ± 4.3 | 132.6 ± 3.0 |
BMI (kg/m2) § | 22.1 ± 0.4 *,£ | 35.4 ± 0.7 | 36.2 ± 0.8 | 35.1 ± 0.9 | 48.5 ± 1.6 | 48.9 ± 2.1 | 47.2 ± 1.0 |
Glucose (mg/dL) § | 83.3 ± 2.0 *,£ | 140.9 ± 22.8 | 131.8 ± 25.5 | 161.8 ± 25.5 | 88.5 ± 3.0 | 126.4 ± 5.9 # | 128.8 ± 7.2 # |
Insulin (mUI/L) | 6.1 ± 0.6 *,£ | 10.7 ± 2.8 | 15.2 ± 3.9 | 26.7 ± 9.4 | 12.2 ± 1.6 | 19.1 ± 2.9 | 27.6 ± 6.9 |
HbA1c (%) | 4.7 ± 0.1 *,£ | 6.7 ± 0.8 | 5.3 ± 0.2 | 7.5 ± 1.1 | 5.1 ± 0.1 | 6.1 ± 0.3 | 5.9 ± 0.4 |
HOMA2-IR | 0.8 ± 0.1 *,£ | 1.39 ± 0.4 | 2.5 ± 0.8 | 3.6 ± 1.6 | 1.5 ± 0.2 | 2.6 ± 0.37 # | 3.6 ± 0.8 # |
HDL-C (mg/dL) | 55.5 ± 2.0 *,£ | 39.7 ± 4.5 | 44.6 ± 2.4 | 38.2 ± 2.9 | 44.6 ± 2.4 | 37.4 ± 2.4 | 39.1 ± 1.6 |
LDL-C (mg/dL) | 103.7 ± 3.5 | 103.3 ± 14.1 | 101.8 ± 8.2 | 105.5 ± 20.8 | 98.1 ± 7.2 | 106.2 ± 6.9 | 105.5 ± 6.5 |
Triglycerides (mg/dL) | 87.2 ± 9.9 *,£ | 109.6 ± 17.9 | 134.9 ± 19.9 | 197.3 ± 37.6 | 133.8 ± 11.2 | 177.1 ± 16.5 | 185.0 ± 19.4 |
AST (U/L) | 22.3 ± 1.5 *,£ | 27.7 ± 5.4 | 47.7 ± 9.6 | 52.0 ± 12.8 | 19.7 ± 1.2 | 43.0 ± 8.4 # | 52.3 ± 7.6 # |
ALT (U/L) | 21.5 ± 2.9 *,£ | 28.1 ± 7.7 | 36.7 ± 7.6 | 48.1 ± 10.2 | 19.2 ± 1.2 | 43.6 ± 6.1 # | 54.2 ± 6.9 # |
GGT (U/L) | 22.2 ± 6.3 £ | 30.4 ± 15.5 | 20.6 ± 5.5 | 25.4 ± 5.2 | 21.4 ± 6.5 | 34.6 ± 3.9 | 41.2 ± 7.0 |
ALP (U/L) | 61.2 ± 4.5 | 72.2 ± 13.3 | 63.2 ± 5.1 | 67.2 ± 6.2 | 64.4 ± 3.4 | 67.3 ± 4.2 | 74.5 ± 2.9 |
Steatosis grade | 1.33 ± 0.2 | 1.42 ± 0.1 | 1.94 ± 0.2 ‡ | 1.72 ± 0.1 | |||
Mild (1) | – | – | 6 (67%) | 7 (58%) | – | 6 (33%) | 9 (41%) |
Moderate (2) | – | – | 3 (33%) | 5 (42%) | – | 7 (39%) | 10 (45%) |
Severe (3) | – | – | – | – | – | 5 (28%) | 3 (14%) |
Lobular inflammatory grade | 0.11 ± 0.1 | 2.10 ± 0.1 | 0.17 ± 0.1 | 1.36 ± 0.1 † | |||
Absence (0) | – | – | 8 (89%) | – | – | 15 (83%) | – |
Mild (1) | – | – | 1 (11%) | 1 (8%) | – | 3 (17%) | 16 (73%) |
Moderate (2) | – | – | – | 9 (75%) | – | – | 4 (18%) |
Severe (3) | – | – | – | 2 (17%) | – | – | 2 (9%) |
Hepatocellular ballooning | 0.11 ± 0.1 | 1.00 ± 0.1 | 0.17 ± 0.1 | 1.09 ± 0.1 | |||
Absence (0) | – | – | 8 (89%) | 1 (8%) | – | 15 (83%) | – |
Mild (1) | – | – | 1 (11%) | 10 (84%) | – | 3 (17%) | 20 (91%) |
Moderate (2) | – | – | – | 1 (8%) | – | – | 2 (9%) |
Severe (3) | – | – | – | – | – | – | – |
Histological Features | AUROC | Cut-Off | Sensitivity (%) | Specificity (%) | PPV (%) | NPV (%) | LR+ | LR− |
---|---|---|---|---|---|---|---|---|
NAFLD a | 0.82 (0.74–0.90) | 0.0045 | 96.6 | 54.7 | 41.6 | 98.0 | 2.13 | 16.14 |
0.0147 | 83.1 | 69.8 | 47.8 | 92.5 | 2.75 | 4.12 | ||
0.1202 | 35.6 | 90.6 | 55.7 | 80.8 | 3.77 | 1.41 | ||
Hepatocellular Ballooning b | 0.76 (0.66–0.85) | 0.0045 | 97.1 | 37.2 | 34.0 | 97.4 | 1.55 | 12.64 |
0.0693 | 67.6 | 74.4 | 46.8 | 87.3 | 2.64 | 2.30 | ||
0.2738 | 29.4 | 93.6 | 60.5 | 79.9 | 4.59 | 1.33 | ||
Lobular Inflammation c | 0.76 (0.66–0.85) | 0.0045 | 97.1 | 37.2 | 34.0 | 97.4 | 1.55 | 12.64 |
0.0693 | 67.6 | 74.4 | 46.8 | 87.3 | 2.64 | 2.30 | ||
0.2738 | 29.4 | 93.6 | 60.5 | 79.9 | 4.59 | 1.33 |
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Auguet, T.; Aragonès, G.; Berlanga, A.; Guiu-Jurado, E.; Martí, A.; Martínez, S.; Sabench, F.; Hernández, M.; Aguilar, C.; Sirvent, J.J.; et al. miR33a/miR33b* and miR122 as Possible Contributors to Hepatic Lipid Metabolism in Obese Women with Nonalcoholic Fatty Liver Disease. Int. J. Mol. Sci. 2016, 17, 1620. https://doi.org/10.3390/ijms17101620
Auguet T, Aragonès G, Berlanga A, Guiu-Jurado E, Martí A, Martínez S, Sabench F, Hernández M, Aguilar C, Sirvent JJ, et al. miR33a/miR33b* and miR122 as Possible Contributors to Hepatic Lipid Metabolism in Obese Women with Nonalcoholic Fatty Liver Disease. International Journal of Molecular Sciences. 2016; 17(10):1620. https://doi.org/10.3390/ijms17101620
Chicago/Turabian StyleAuguet, Teresa, Gemma Aragonès, Alba Berlanga, Esther Guiu-Jurado, Andreu Martí, Salomé Martínez, Fàtima Sabench, Mercé Hernández, Carmen Aguilar, Joan Josep Sirvent, and et al. 2016. "miR33a/miR33b* and miR122 as Possible Contributors to Hepatic Lipid Metabolism in Obese Women with Nonalcoholic Fatty Liver Disease" International Journal of Molecular Sciences 17, no. 10: 1620. https://doi.org/10.3390/ijms17101620