Downregulation of the Glo1 Gene Is Associated with Reduced Adiposity and Ectopic Fat Accumulation in Spontaneously Hypertensive Rats
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animals
2.2. Generation of Glo1 Knockout SHR Rats
2.3. Glucose Utilization in Epididymal Adipose Tissue
2.4. Tissue Triglyceride and Cholesterol Measurements
2.5. Parameters of Dicarbonyl and Oxidative Stress
2.6. Biochemical Analysis
2.7. Histological Methods
2.8. Gene Expression Determined by Real-Time PCR
2.9. Determination of GLUT4 and AMPK Activity: Tissue Homogenization and Fractionation
2.10. Determination of GLUT4 and AMPK Activity: Electrophoresis and Western Blotting
2.11. Statistical Analysis
3. Results
3.1. Glyoxalase 1 Gene Expression, Enzyme Activity, and Dicarbonyl and Oxidative Stress
3.2. Parameters of Glucose and Lipid Metabolism
3.3. Effect of Glo1 Downregulation on GLUT4 and AMPK Activation
3.4. Microalbuminuria and Histological Analysis
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
AGE | Advanced glycation end-products |
AMPK | AMP-activated protein kinase |
CAT | Catalase |
CPM | Crude plasma membranes |
GL | Glyoxal |
GLO1 | Glyoxalase 1 |
GLUT4 | Glucose transporter 4 |
GSH | Reduced glutathione |
GSH-Px | Glutathione peroxidase |
GSSG | Oxidized glutathione |
LV | Light vesicles |
MG | Methylglyoxal |
PNS | Postnuclear supernatant |
RAGE | Receptor for advanced glycation end-products |
SOD | Superoxide dismutase |
TBARS | Thiobarbituric acid reactive substances |
WAT | White adipose tissue |
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Trait | SHR | SHR-Glo1+/− |
---|---|---|
Plasma or Blood | ||
Glyoxal (nmol/mL) (plasma) | 0.097 ± 0.009 | 0.157 ± 0.012 * |
Methylglyoxal (nmol/mL) (plasma) | 0.291 ± 0.011 | 0.726 ± 0.048 ** |
GSH (μmol/L) (blood) | 778.8 ± 5.8 | 718.1 ± 16.5 * |
GSSG (μmol/L) (blood) | 53.8 ± 4.9 | 53.9 ± 8.5 |
GSH/GSSG ratio | 14.9 ± 1.2 | 13.6 ± 1.6 |
Glo1 activity (μmol/min/μg Hb) (erytrocytes) | 0.406 ± 0.019 | 0.192 ± 0.007 ** |
White Adipose Tissue | ||
Glyoxal (nmol/mg) | 0.165 ± 0.003 | 0.199 ± 0.019 |
Methylglyoxal (nmol/mg) | 2.159 ± 0.301 | 2.567 ± 0.186 |
Glo1 activity (μmol/min/μg protein) | 0.831 ± 0.070 | 0.707 ± 0.069 |
Myocardium | ||
Glyoxal (nmol/mg) | 0.380 ± 0.019 | 0.960 ± 0.074 ** |
Methylglyoxal (nmol/mg) | 1.054 ± 0.170 | 2.159 ± 0.102 ** |
GSH (μmol/mg protein) | 12.2 ± 0.8 | 10.1 ± 0.7 |
GSSG (μmol/mg protein) | 2.8 ± 0.3 | 2.3 ± 0.2 |
GSH/GSSG ratio | 4.5 ± 0.7 | 4.4 ± 0.2 |
Glo1 activity (μmol/min/μg protein) | 0.685 ± 0.055 | 0.453 ± 0.061 * |
Kidney | ||
Glyoxal (nmol/mg) | 0.626 ± 0.017 | 0.717 ± 0.009 |
Methylglyoxal (nmol/mg) | 2.206 ± 0.179 | 2.114 ± 0.105 |
GSH (μmol/mg protein) | 42.1 ± 2.2 | 27.0 ± 1.5 ** |
GSSG (μmol/mg protein) | 4.3 ± 0.3 | 3.2 ± 0.1 ** |
GSH/GSSG ratio | 9.9 ± 1.5 | 8.6 ± 0.6 |
Liver | ||
Glyoxal (nmol/mg) | 0.728 ± 0.095 | 0.772 ± 0.095 |
Methylglyoxal (nmol/mg) | 3.093 ± 0.179 | 3.314 ± 0.371 |
GSH (μmol/mg protein) | 93.5 ± 6.1 | 68.6 ± 1.1 ** |
GSSG (μmol/mg protein) | 4.7 ± 0.1 | 4.7 ± 0.2 |
GSH/GSSG ratio | 19.8 ± 0.9 | 15.0 ± 0.6 ** |
Glo1 activity (μmol/min/μg protein) | 0.562 ± 0.021 | 0.285 ± 0.011 ** |
Trait | SHR | SHR-Glo1+/− |
---|---|---|
Myocardium | ||
SOD (U/mg protein) | 0.075 ± 0.006 | 0.054 ± 0.004 ** |
GSH-Px (μM NADPH/min/mg protein) | 131 ± 12 | 138 ± 11 |
GR (μM NADPH/min/mg protein) | 125 ± 8 | 114 ± 8 |
CAT (mM H2O2/min/mg protein) | 594 ± 26 | 530 ± 31 |
TBARS (nM/mg protein) | 0.561 ± 0.026 | 0.651 ± 0.021 * |
Kidney cortex | ||
SOD (U/mg protein) | 0.024 ± 0.002 | 0.026 ± 0.002 |
GSH-Px (μM NADPH/min/mg protein) | 73 ± 6 | 68 ± 7 |
GR (μM NADPH/min/mg protein) | 28 ± 3 | 39 ± 5 |
CAT (mM H2O2/min/mg protein) | 451 ± 26 | 430 ± 27 |
TBARS (nM/mg protein) | 0.338 ± 0.021 | 0.391 ± 0.008 * |
Liver | ||
SOD (U/mg protein) | 0.142 ± 0.009 | 0.115 ± 0.008 * |
GSH-Px (μM NADPH/min/mg protein) | 292 ± 17 | 245 ± 20 |
GR (μM NADPH/min/mg protein) | 139 ± 13 | 154 ± 23 |
CAT (mM H2O2/min/mg protein) | 1515 ± 126 | 1707 ± 154 |
TBARS (nM/mg protein) | 1.759 ± 0.173 | 1.867 ± 0.128 |
Trait | SHR | SHR-Glo1+/− |
---|---|---|
Body weight (g) | 362 ± 4 | 344 ± 6 * |
Relative weight of epididymal fat (g/100 g BW) | 0.98 ± 0.02 | 0.88 ± 0.03 * |
Relative liver weight (g/100 g BW) | 3.24 ± 0.04 | 3.11 ± 0.03 * |
Non-fasting glucose (mmol/L) | 6.3 ± 0.2 | 6.2 ± 0.1 |
Insulin (μmol/L) | 0.275 ± 0.023 | 0.188 ± 0.017 * |
NEFA (mmol/L) | 0.38 ± 0.02 | 0.42 ± 0.02 |
Serum triglycerides (mmol/L) | 0.48 ± 0.03 | 0.34 ± 0.01 * |
Serum cholesterol (mmol/L) | 1.17 ± 0.04 | 1.10 ± 0.03 |
Triglycerides in the liver (μmol/g) | 6.1 ± 0.5 | 4.1 ± 0.4 ** |
Cholesterol in the liver (μmol/g) | 10.2 ± 0.5 | 7.6 ± 0.3 ** |
Triglycerides in the myocardium (μmol/g) | 0.56 ± 0.08 | 0.32 ± 0.06 * |
Basal lipogenesis (nmol glucose/g/2 h) | 354 ± 12 | 505 ± 34 ** |
Insulin-stimulated lipogenesis (nmol glucose/g/2 h) | 734 ± 37 | 1123 ± 73 ** |
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Šilhavý, J.; Malínská, H.; Hüttl, M.; Marková, I.; Oliyarnyk, O.; Mlejnek, P.; Šimáková, M.; Liška, F.; Kazdová, L.; Moravcová, R.; et al. Downregulation of the Glo1 Gene Is Associated with Reduced Adiposity and Ectopic Fat Accumulation in Spontaneously Hypertensive Rats. Antioxidants 2020, 9, 1179. https://doi.org/10.3390/antiox9121179
Šilhavý J, Malínská H, Hüttl M, Marková I, Oliyarnyk O, Mlejnek P, Šimáková M, Liška F, Kazdová L, Moravcová R, et al. Downregulation of the Glo1 Gene Is Associated with Reduced Adiposity and Ectopic Fat Accumulation in Spontaneously Hypertensive Rats. Antioxidants. 2020; 9(12):1179. https://doi.org/10.3390/antiox9121179
Chicago/Turabian StyleŠilhavý, Jan, Hana Malínská, Martina Hüttl, Irena Marková, Olena Oliyarnyk, Petr Mlejnek, Miroslava Šimáková, František Liška, Ludmila Kazdová, Radka Moravcová, and et al. 2020. "Downregulation of the Glo1 Gene Is Associated with Reduced Adiposity and Ectopic Fat Accumulation in Spontaneously Hypertensive Rats" Antioxidants 9, no. 12: 1179. https://doi.org/10.3390/antiox9121179
APA StyleŠilhavý, J., Malínská, H., Hüttl, M., Marková, I., Oliyarnyk, O., Mlejnek, P., Šimáková, M., Liška, F., Kazdová, L., Moravcová, R., Novotný, J., & Pravenec, M. (2020). Downregulation of the Glo1 Gene Is Associated with Reduced Adiposity and Ectopic Fat Accumulation in Spontaneously Hypertensive Rats. Antioxidants, 9(12), 1179. https://doi.org/10.3390/antiox9121179