Deregulated Serotonin Pathway in Women with Morbid Obesity and NAFLD
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Subjects
2.2. Sample Size
2.3. Liver Pathological Features
2.4. Biochemical Analyses
2.5. mRNA Levels in the Liver and Jejunum
2.6. Statistical Analysis
3. Results
3.1. Baseline Characteristics of Subjects
3.2. Peripheral Levels of Serotonin in the Studied Cohort
3.3. Correlations of Serum Levels of Serotonin with Metabolic Syndrome Presence
3.4. Evaluation of HTR2A, HTR2B, and HTR3 mRNA Levels in Liver and HTR3 and HTR4 in Jejunum According to Liver Histology
3.5. Correlations of Liver Expression of HTR2A, HTR2B, and HTR3 and Jejunal Expression of HTR3 and HTR4 with Serum 5-HT Levels and Metabolic Syndrome Presence
3.6. Correlations of Peripheral Levels of Serotonin with Inflammatory Cytokines
4. Discussion
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
ALP | alkaline phosphatase |
ALT | alanine aminotransferase |
AST | aspartate aminotransferase |
ATP | adenosine triphosphate |
BMI | body mass index |
CRP | C-reactive protein |
DBP | diastolic blood pressure |
DPP-4 | dipeptidyl peptidase-4 |
EC | enterochromaffin cells |
ELISA | enzyme-linked immunosorbent assay |
GAPDH | glyceraldehyde-3-phosphate dehydrogenase |
GGT | gamma-glutamyltransferase |
GI | gastrointestinal |
GLP-1 | glucagon-like peptide-1 |
HbA1c | glycosylated hemoglobin |
HCT | hematocrit |
HDL-C | high-density lipoprotein cholesterol |
HepG2 | human hepatocellular carcinoma |
HFD | high-fat diet |
HGB | hemoglobin |
HOMA2-IR | homeostasis model assessment of insulin resistance |
HPLC | high-performance liquid chromatography |
HSCs | hepatic stellate cells |
5-HT | 5-hydroxytryptamin (serotonin) |
HTR2A | serotonin receptor 2A |
HTR2B | serotonin receptor 2B |
HTR3 | serotonin receptor 3 |
HTR4 | serotonin receptor 4 |
HTRx | serotonin receptor subtypes |
IBS | irritable bowel syndrome |
IL | interleukin |
IR | insulin resistance |
LDL-C | low-density lipoprotein-cholesterol |
MO | morbid obesity |
NAFLD | non-alcoholic fatty liver disease |
NASH | non-alcoholic steatohepatitis |
NL | normal liver |
NW | normal weight |
PGC1α/PPARy | peroxisome proliferator- activated receptor gamma coactivator 1-alpha |
PLT | platelets |
RBC | red blood cells |
ROS | reactive oxygen species |
RT-qPCR | real-time quantitative polymerase chain reaction |
SBP | systolic blood pressure |
SERT | serotonin transporter |
SS | simple steatosis |
T2DM | type 2 diabetes mellitus |
TG | triglycerides |
TNF-α | tumor necrosis factor alpha |
TPH1 | tryptophan hydroxylase 1 |
VLCD | very low calorie diet |
WBC | white blood cells |
WC | waist circumference |
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Variables | NW (n = 26) Mean ± SD | MO (n = 58) Mean ± SD | NL (n = 22) Mean ± SD | SS (n = 21) Mean ± SD | NASH (n = 15) Mean ± SD |
Age (years) | 49.91 ± 9.47 | 45.08 ± 10.85 | 42.73 ± 10.01 | 45.45 ± 12.42 | 48.00 ± 9.52 |
WC (cm2) | NA | 125.10 ± 11.71 | 124.08 ± 6.69 | 130.07 ± 12.39 | 120.42 ± 13.66 |
Cholesterol (mg/dl) | 180.74 ± 14.27 | 170.41 ± 35.59 | 168.20 ± 36.25 | 171.56 ± 31.60 | 171.30 ± 8.62 |
LDL–C (mg/dL) | 95.60 ± 28.18 | 136.34 ± 74.74 | 106.40 ± 36.21 | 99.78 ± 25.00 | 95.88 ± 30.27 |
ALP (U/L) | 54.78 ± 4.90 * | 67.84 ± 14.22 | 63.54 ± 11.54 § | 75.72 ± 13.76 # | 61.23 ± 12.76 |
Med (25th–75th) | Med (25th–75th) | Med (25th–75th) | Med (25th–75th) | Med (25th–75th) | |
Weight (kg) | 58.00 | 116.40 | 117.50 | 116.80 | 113.50 |
(52.75–60.38) * | (108.00–130.10) | (110.25–132.00) | (110.00–130.20) | (104.00–124.00) | |
BMI (kg/m2) | 21.63 | 43.90 | 43.30 | 44.59 | 44.95 |
(20.07–24.04) * | (40.89–46.85) | (40.89–47.53) | (40.84–46.81) | (41.14–48.83) | |
Glucose (mg/dL) | 80.00 | 92.00 | 85.50 | 102.00 | 99.00 |
(73.00–85.00) * | (80.50–107.00) | (76.75–93.00) § | (83.00–153.00) | (83.00–106.00) | |
Insulin (mUI/L) | 5.66 | 9.42 | 9.43 | 9.80 | 6.57 |
(4.94–7.89) * | (5.54–15.80) | (4.04–17.63) | (6.94–15.75) | (5.09–17.48) | |
HOMA2–IR | 0.72 | 1.19 | 1.23 | 1.32 | 0.86 |
(0.62–1.01) * | (0.71–2.27) | (0.46–2.27) | (0.93–2.28) | (0.61–2.42) | |
HbA1c (%) | 5.40 | 5.60 | 5.40 | 5.60 | 5.60 |
(5.20–5.70) | (5.30–5.98) | (5.30–5.70) | (5.30–6.10) | (5.20–6.33) | |
HDL–C (mg/dL) | 68.00 | 38.50 | 39.00 | 45.00 | 38.00 |
(59.00–81.00) * | (33.00–47.00) | (32.00–46.00) | (33.75–47.50) | (33.50–48.50) | |
TG (mg/dL) | 62.00 | 123.00 | 105.00 | 128.00 | 128.00 |
(49.00–71.00) * | (86.00–166.00) | (86.00–141.00) | (82.25–186.25) | (83.75–187.50) | |
AST (U/L) | 17.00 | 23.00 | 20.00 | 27.00 | 30.00 |
(14.00–22.00) * | (17.00–37.00) | (16.00–31.50) | (20.00–43.00) | (17.00–44.00) | |
ALT (U/L) | 16.00 | 28.50 | 21.00 | 32.50 | 33.00 |
(12.00–20.00) * | (18.00–35.00) | (15.50–30.00) § | (24.25–35.75) | (16.00–30.50) | |
GGT (U/L) | 13.00 | 22.00 | 21.00 | 22.00 | 26.00 |
(11.00–17.00) * | (16.00–31.00) | (16.00–29.00) | (16.25–31.75) | (12.50–30.50) | |
SBP (mmHg) | 120.00 | 118.00 | 122.50 | 121.00 | 115.00 |
(109.00–122.00) | (107.00–133.00) | (99.25–132.75) | (110.00–140.00) | (101.50–125.25) | |
DBP (mmHg) | 65.00 | 66.00 | 70.50 | 62.00 | 66.00 |
(65.00–66.00) | (59.00–75.50) | (56.75–79.50) | (59.00–77.00) | (59.00–71.50) | |
RBC (1012/L) | 4.22 (4.09–4.45) | 4.26 (3.94–4.45) | 4.19 (3.89–4.43) | 4.20 (3.91–4.41) | 4.24 (3.93–4.49) |
WBC (109/L) | 6.00 (5.24–7.00) * | 7.55 (6.17–9.12) | 6.13 (5.55–9.03) | 7.57 (6.38–9.37) | 7.17 (5.90–9.07) |
PLT (109/L) | 269.00 | 255.00 | 228.00 | 256.00 | 247.50 |
(230.00–326.00) | (218.00–310.00) | (188.00–285.00) | (234.00–318.00) | (200.50–304.25) | |
HGB (g/dL) | 13.00 | 12.10 | 12.10 | 12.05 | 11.95 |
(12.00–13.40) * | (11.00–13.00) | (11.90–12.60) | (11.30–12.77) | (10.72–13.17) | |
HCT (%) | 37.80 | 36.00 | 35.60 | 35.90 | 35.85 |
(36.00–39.00) * | (32.90–38.50) | (34.20–38.00) | (33.42–37.92) | (32.42–38.90) |
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Binetti, J.; Bertran, L.; Riesco, D.; Aguilar, C.; Martínez, S.; Sabench, F.; Porras, J.A.; Camaron, J.; Castillo, D.D.; Richart, C.; et al. Deregulated Serotonin Pathway in Women with Morbid Obesity and NAFLD. Life 2020, 10, 245. https://doi.org/10.3390/life10100245
Binetti J, Bertran L, Riesco D, Aguilar C, Martínez S, Sabench F, Porras JA, Camaron J, Castillo DD, Richart C, et al. Deregulated Serotonin Pathway in Women with Morbid Obesity and NAFLD. Life. 2020; 10(10):245. https://doi.org/10.3390/life10100245
Chicago/Turabian StyleBinetti, Jessica, Laia Bertran, David Riesco, Carmen Aguilar, Salomé Martínez, Fàtima Sabench, Jose Antonio Porras, Javier Camaron, Daniel Del Castillo, Cristóbal Richart, and et al. 2020. "Deregulated Serotonin Pathway in Women with Morbid Obesity and NAFLD" Life 10, no. 10: 245. https://doi.org/10.3390/life10100245