Role of ANGPTL8 in NAFLD Improvement after Bariatric Surgery in Experimental and Human Obesity
Abstract
:1. Introduction
2. Results
2.1. Prevalence of NAFLD and Metabolic Improvement after Bariatric Surgery in the Studied Population
2.2. Plasma Concentrations of ANGPTL8 Are Increased in Obesity-Associated NAFLD
2.3. Hepatic Expression of ANGTL8 Is Upregulated in Patients with Morbid Obesity and NAFLD in Relation to Their Degree of Liver Steatosis
2.4. Increased Hepatic Expression of ANGPTL8 in a Preclinical Model of Diet-Induced Obesity Is Downregulated after Bariatric Surgery
2.5. ANGPTL8 Inhibits Palmitate-Induced Lipogenesis, but Not Its Anti-Proliferative Action, in Human HepG2 Hepatocytes
3. Discussion
4. Conclusions
5. Materials and Methods
5.1. Patients
5.2. Experimental Animals
5.3. Blood Analysis
5.4. Real-Time PCR
5.5. Immunohistochemistry of ANGPTL8
5.6. Cell Culture and Treatment
5.7. Proliferation Assay
5.8. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Lean | Obese NG | Obese IGT | Obese T2D | p | |
---|---|---|---|---|---|
n | 30 | 48 | 47 | 45 | - |
Sex (male/female) | 16/14 | 17/31 | 17/30 | 20/25 | 0.199 |
Age (years) | 43 ± 3 | 40 ± 2 | 44 ± 2 | 48 ± 2 b | 0.031 |
BMI (kg/m2) | 22.6 ± 0.5 | 44.5 ± 1.3 a | 43.2 ± 0.9 a | 45.4 ± 1.4 a | <0.0001 |
Body fat (%) | 21.2 ± 1.4 | 50.7 ± 0.9 a | 51.0 ± 1.3 a | 50.1 ± 1.2 a | <0.0001 |
Waist circumference (cm) | 77 ± 3 | 125 ± 2 a | 125 ± 2 a | 132 ± 3 a | <0.0001 |
Glucose (mg/dL) | 87 ± 2 | 92 ± 1 | 105 ± 1 a,b | 142 ± 9 a,b | <0.0001 |
Glucose 2-h OGTT (mg/dL) | - | 121 ± 4 | 154 ± 5 b | 250 ± 16 b | <0.0001 |
Insulin (µU/mL) | 5.7 ± 0.6 | 20.9 ± 2.7 a | 19.6 ± 1.7 a | 26.3 ± 3.1 a | <0.0001 |
Insulin 2-h OGTT (µU/mL) | - | 97.0 ± 9.5 | 141.1 ± 12.4 b | 133.3 ± 19.2 b | 0.034 |
HOMA | 1.2 ± 0.1 | 4.3 ± 0.4 | 5.2 ± 0.5 a | 9.2 ± 1.7 a,b | <0.0001 |
QUICKI | 0.38 ± 0.01 | 0.32 ± 0.01 a | 0.31 ± 0.01 a | 0.30 ± 0.01 a,b | <0.0001 |
FFA (mmol/L) | 15.7 ± 0.1 | 16.7 ± 1.1 | 22.5 ± 2.2 | 28.9 ± 4.0 a,b | 0.001 |
Glycerol (mg/dL) | 18.2 ± 3.5 | 19.8 ± 2.1 | 22.1 ± 2.5 | 21.9 ± 2.3 | 0.591 |
Adipo-IR index | 20.2 ± 3.4 | 71.3 ± 7.7 | 98.9 ± 13.7 | 188.4 ± 36.3 a,b | <0.0001 |
Triacylglycerol (mg/dL) | 70 ± 5 | 111 ± 7 a | 132 ± 11 a | 147 ± 11 a,b | <0.0001 |
Total cholesterol (mg/dL) | 186 ± 7 | 191 ± 4 | 203 ± 6 | 198 ± 6 | 0.234 |
LDL cholesterol (mg/dL) | 110 ± 6 | 118 ± 3 | 127 ± 5 | 116 ± 5 | 0.145 |
HDL cholesterol (mg/dL) | 61 ± 3 | 50 ± 4 | 49 ± 2 a | 44 ± 2 a | 0.001 |
CRP (mg/L) | 1.8 ± 0.3 | 8.3 ± 1.1 | 9.5 ± 1.5 a | 8.8 ± 1.8 a | 0.035 |
Uric acid (mg/dL) | 4.3 ± 0.2 | 5.7 ± 0.2 a | 5.9 ± 0.2 a | 6.0 ± 0.2 a | 0.001 |
Leptin (ng/mL) | 6.1 ± 0.7 | 45.4 ± 3.2 a | 48.9 ± 3.6 a | 46.0 ± 5.8 a | <0.0001 |
AST (IU/L) | 13 ± 1 | 16 ± 1 | 17 ± 1 | 17 ± 1 | 0.244 |
ALT (IU/L) | 10 ± 2 | 21 ± 2 | 28 ± 2 a | 27 ± 2 a | <0.0001 |
Alkaline phosphatase (IU/L) | 86 ± 5 | 68 ± 5 | 77 ± 6 | 73 ± 5 | 0.334 |
γ-GT (IU/L) | 11 ± 1 | 21 ± 2 | 29 ± 4 a | 30 ± 4 a | 0.015 |
Daily alcohol intake (g) | 0.0 ± 0.0 | 1.1 ± 0.9 | 3.6 ± 2.7 | 4.6 ± 2.7 | 0.576 |
Antihypertensive therapy, n (%) | 0 (0%) | 11 (23%) | 17 (32%) | 19 (49%) | 0.003 |
Antidiabetic therapy, n (%) | 0 (0%) | 2 (4%) | 1 (2%) | 20 (51%) | <0.0001 |
Lipid-lowering therapy, n (%) | 0 (0%) | 6 (13%) | 7 (15%) | 11 (28%) | 0.061 |
Sleeve Gastrectomy (n = 34) | Roux-en-Y Gastric Bypass (n = 41) | |||||
---|---|---|---|---|---|---|
Pre-Surgery | Post-Surgery | p | Pre-Surgery | Post-Surgery | p | |
Sex (male/female) | 10/24 | 10/24 | - | 15/26 | 15/26 | - |
BMI (kg/m2) | 41.0 ± 1.7 | 31.1 ± 1.6 | <0.0001 | 44.7 ± 0.8 | 31.9 ± 0.6 | <0.0001 |
Body fat (%) | 50.9 ± 1.2 | 39.5 ± 1.8 | <0.0001 | 50.7 ± 0.8 | 38.1 ± 1.0 | <0.0001 |
Waist circumference (cm) | 120 ± 3 | 98 ± 3 | <0.0001 | 127 ± 2 | 100 ± 2 | <0.0001 |
Glucose (mg/dL) | 106 ± 9 | 92 ± 4 | 0.022 | 115 ± 5 | 95 ± 4 | <0.0001 |
Insulin (µU/mL) | 30.9 ± 6.6 | 10.0 ± 1.6 | 0.005 | 23.0 ± 3.3 | 8.6 ± 1.1 | <0.0001 |
HOMA | 8.3 ± 2.1 | 2.1 ± 0.4 | 0.011 | 6.2 ± 1.3 | 2.3 ± 0.6 | <0.0001 |
QUICKI | 0.30 ± 0.01 | 0.36 ± 0.01 | <0.0001 | 0.31 ± 0.01 | 0.36 ± 0.01 | <0.0001 |
FFA (mmol/L) | 18.8 ± 1.2 | 14.3 ± 1.5 | 0.052 | 21.5 ± 2.2 | 13.2 ± 1.0 | 0.001 |
Glycerol (mg/dL) | 19.4 ± 2.2 | 14.0 ± 0.8 | 0.043 | 22.4 ± 2.1 | 12.9 ± 1.3 | 0.001 |
Adipo-IR index | 138.7 ± 40.0 | 32.6 ± 6.3 | 0.020 | 91.9 ± 12.7 | 28.7 ± 5.6 | <0.0001 |
Triacylglycerol (mg/dL) | 110 ± 15 | 98 ± 10 | 0.380 | 136 ± 9 | 90 ± 4 | <0.0001 |
Total cholesterol (mg/dL) | 185 ± 8 | 186 ± 9 | 0.919 | 199 ± 5 | 158 ± 4 | <0.0001 |
LDL cholesterol (mg/dL) | 115 ± 7 | 119 ± 7 | 0.576 | 122 ± 5 | 92 ± 3 | <0.0001 |
HDL cholesterol (mg/dL) | 47 ± 3 | 52 ± 3 | 0.111 | 49 ± 3 | 48 ± 1 | 0.666 |
CRP (mg/L) | 4.6 ± 1.5 | 3.0 ± 1.2 | 0.252 | 7.9 ± 1.1 | 2.4 ± 0.3 | <0.0001 |
Uric acid (mg/dL) | 5.0 ± 0.3 | 4.7 ± 0.3 | 0.203 | 6.1 ± 0.2 | 4.9 ± 0.1 | <0.0001 |
Leptin (ng/mL) | 77.0 ± 12.7 | 25.3 ± 5.9 | 0.004 | 51.0 ± 4.6 | 16.2 ± 2.5 | <0.0001 |
AST (IU/L) | 17 ± 1 | 17 ± 1 | 0.983 | 18 ± 1 | 18 ± 1 | 0.849 |
ALT (IU/L) | 22 ± 3 | 19 ± 2 | 0.318 | 27 ± 2 | 26 ± 2 | 0.606 |
Alkaline phosphatase (IU/L) | 64 ± 6 | 65 ± 5 | 0.916 | 82 ± 5 | 84 ± 5 | 0.529 |
γ-GT (IU/L) | 29 ± 6 | 22 ± 4 | 0.027 | 24 ± 3 | 14 ± 2 | <0.0001 |
Antihypertensive therapy, n (%) | 15 (44%) | 12 (34%) | 0.001 | 17 (41%) | 9 (22%) | 0.011 |
Antidiabetic therapy, n (%) | 8 (24%) | 5 (15%) | 0.085 | 12 (29%) | 4 (10%) | 0.001 |
Lipid-lowering therapy, n (%) | 8 (24%) | 3 (9%) | 0.113 | 11 (27%) | 3 (7%) | 0.081 |
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Perdomo, C.M.; Gómez-Ambrosi, J.; Becerril, S.; Valentí, V.; Moncada, R.; Fernández-Sáez, E.M.; Méndez-Giménez, L.; Ezquerro, S.; Catalán, V.; Silva, C.; et al. Role of ANGPTL8 in NAFLD Improvement after Bariatric Surgery in Experimental and Human Obesity. Int. J. Mol. Sci. 2021, 22, 12945. https://doi.org/10.3390/ijms222312945
Perdomo CM, Gómez-Ambrosi J, Becerril S, Valentí V, Moncada R, Fernández-Sáez EM, Méndez-Giménez L, Ezquerro S, Catalán V, Silva C, et al. Role of ANGPTL8 in NAFLD Improvement after Bariatric Surgery in Experimental and Human Obesity. International Journal of Molecular Sciences. 2021; 22(23):12945. https://doi.org/10.3390/ijms222312945
Chicago/Turabian StylePerdomo, Carolina M., Javier Gómez-Ambrosi, Sara Becerril, Víctor Valentí, Rafael Moncada, Eva M. Fernández-Sáez, Leire Méndez-Giménez, Silvia Ezquerro, Victoria Catalán, Camilo Silva, and et al. 2021. "Role of ANGPTL8 in NAFLD Improvement after Bariatric Surgery in Experimental and Human Obesity" International Journal of Molecular Sciences 22, no. 23: 12945. https://doi.org/10.3390/ijms222312945