NADPH Oxidase 2 Mediates Myocardial Oxygen Wasting in Obesity
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animals
2.2. Plasma Parameters
2.3. Isolated Heart Perfusions
2.4. Assessment of ROS Production in Myocardial Tissue
2.5. Mitochondrial Function and ROS Production
2.6. Real-Time Quantitative PCR
2.7. Statistical Analysis
3. Results
3.1. Effect of NOX2 Ablation and Inhibition on Obesity, Glucose Tolerance and Inflammatory Status
3.2. Effects of Obesity and NOX Inhibition on Myocardial Reactive Oxygen Species
3.3. Effects of NOX2 Ablation and Inhibition on Ventricular Function
3.4. Effects of NOX2 Ablation and Inhibition on Myocardial Energetics
3.5. Effects of NOX2 Inhibition on Myocardial Substrate Utilization and Mitochondrial Function
4. Discussion
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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CONWT n = 7–9 | CONKO n = 7 | DIOWT n = 10–15 | DIOKO n = 10–16 | |
---|---|---|---|---|
Body weight (g) | 35.1 ± 1.8 | 35.0 ± 1.0 | 50.8 ± 1.2 * | 49.4 ±1.4 * |
Heart weight (mg) | 158 ± 3 | 159± 4 | 177 ± 6 * | 183 ± 5 * |
PWAT weight (g) | 0.70 ± 0.12 | 0.61 ± 0.04 | 0.21 ± 15 * | 0.22 ± 0.19 * |
Nox2PWAT | 1.0 ± 0.2 | n.d. | 5.0 ± 1.2 * | n.d. |
TnfαPWAT | 1.0 ± 0.2 | 0.7 ± 0.1 | 10.2 ± 2.6 * | 3.0 ± 0.6 *,# |
Liver weight (g) | 1.7 ± 0.2 | 1.5 ± 0.1 | 2.7 ± 0.2 * | 2.6 ± 0.2 * |
Nox2liver | 1.0 ± 0.2 | n.d. | 1.9 ± 0.3 * | n.d. |
Tnfα liver | 1.0 ± 0.3 | 0.9 ± 0.2 | 2.9 ± 0.4 * | 2.8 ± 0.3* |
Plasma FFA fed (μM) | 532 ± 112 | 967 ± 292 | 835 ± 96 | 1057 ± 260 |
Blood glucose fasted (mmol/L) | 5.6 ± 0.2 | 7.0 ± 0.1 | 6.6 ± 0.5 | 7.1 ± 0.3 |
Insulin fasted (μU/mL) | 1.7± 0.3 | 2.1 ± 0.4 | 6.5 ± 1.5 * | 4.5 ± 0.5 |
HOMA-IR | 2 ± 1 | 3 ± 1 | 30 ± 13 * | 13 ± 3 |
18 Weeks of Diet | CON n = 8–11 | DIO n = 8–12 | DIOAPO n = 8–9 |
Body weight (g) | 30.1 ± 0.4 | 42.7 ± 1.2 * | 40.1 ± 1.8 |
Heart weight (mg) | 134 ± 3 | 144 ± 4 * | 149 ± 6 |
PWAT weight (g) | 0.2 ± 0.2 | 1.0 ± 0.7 * | 0.8 ± 1.1 |
Liver weight (g) | 1.1 ± 0.1 | 1.7 ± 0.2 * | 1.4 ± 0.1 |
Plasma FFA fed (μM) | 638 ± 88 | 1086 ± 143 * | 648 ± 88 # |
Blood glucose fasted (mM) | 4.7 ± 0.2 | 5.1 ± 0.2 | 4.7 ± 0.1 |
Glucose tolerance test (AUC) | 603 ± 45 | 945 ± 57 * | 761 ± 52 # |
28 Weeks of Diet | n = 8–10 | n = 8–14 | n = 8–10 |
Body weight (g) | 31.6 ± 0.8 | 49.9 ± 1.2 * | 46.5 ± 1.6 |
Heart weight (mg) | 139 ± 4 | 158 ± 3 * | 154 ± 4 |
PWAT weight (g) | 0.4 ± 0.7 | 1.4 ± 0.6 * | 1.2 ± 83 |
Liver weight (g) | 1.1 ± 0.1 | 2.4 ± 0.2 * | 1.8 ± 0.2 # |
Plasma FFAfed (μM) | 583 ± 44 | 637 ± 74 | 655 ± 39 |
Blood glucose fasted (mM) | 5.6 ± 0.3 | 6.0 ± 0.3 | 5.8 ± 0.3 |
Glucose tolerance test (AUC) | 747 ± 55 | 926 ± 50 * | 861 ± 67 |
CONWT n = 6 | CONKO n = 5 | DIOWT n = 6–11 | DIOKO n = 8–10 | |
---|---|---|---|---|
Cardiac output (mL/min) | 11.6 ± 0.6 | 11.8 ± 0.9 | 10.9 ± 0.4 | 12.2 ± 0.2# |
Coronary flow (mL/min) | 4.0 ± 0.3 | 3.5 ± 0.3 | 3.8 ± 0.3 | 3.7 ± 0.2 |
Heart rate (bpm) | 418 ± 1 | 408 ± 10 | 419 ± 7 | 413 ± 6 |
dP/dtmax (mmHg/sec) | 3515 ± 259 | 3093 ± 126 | 3785 ± 230 | 3806 ± 143 |
dP/dtmin (mmHg/sec) | −2982 ± 215 | −2611 ± 106 | −3134 ± 174 | −3230 ± 110 |
Tau Weiss (msec) | 10.8 ± 0.3 | 11.7 ± 0.3 | 11.7 ± 0.8 | 10.4 ± 0.3 # |
LVEDP (mmHg) | 7.9 ± 0.8 | 8.6 ± 0.6 | 12.5 ± 1.2 * | 9.7 ± 0.7 # |
LVDP (mmHg) | 59 ± 2 | 59 ± 1 | 65 ± 2 | 66 ± 2 |
LVEDV (μL) | 105 ± 4 | 106 ± 13 | 76 ± 14 | 97 ± 4 |
EDPVR (mmHg/µL) | 0.12 ± 0.01 | 0.14 ± 0.01 | 0.24 ± 0.04 * | 0.11 ± 0.01 # |
PRSWi | 34.0 ± 1.1 | 28.8 ± 2.1 | 30.1 ± 2.9 | 36.7 ± 2.4 |
18 Weeks of Diet | CON n = 8 | DIO n = 6 | DIOAPO n = 6 |
Aortic flow (mL/min) | 10.8 ± 0.4 | 10.1 ± 0.6 | 10.7 ± 0.1 |
Coronary flow (mL/min) | 3.0 ± 0.2 | 3.3 ± 0.2 | 3.3 ± 0.3 |
Heart rate (bpm) | 396 ± 11 | 359 ± 17 | 399 ± 13 |
dP/dtmax (mmHg/sec) | 3749 ± 138 | 3925 ± 65 | 3615 ± 159 |
dP/dtmin (mmHg/sec) | −2854 ± 105 | −2961 ± 89 | −2863 ± 131 |
Tau Weiss (msec) | 11.0 ± 0.6 | 11.0 ± 0.4 | 11.3 ± 0.5 |
LVEDP (mmHg) | 7.8 ± 1.1 | 8.5 ±1.1 | 9.0 ± 1.8 |
LVDP (mmHg) | 57 ± 2 | 59 ± 2 | 57 ± 3 |
LVEDV (μL) | 72 ± 10 | 58 ± 13 | 55 ± 14 |
EDPVR (mmHg/µL) | 0.16 ± 0.01 | 0.19 ± 0.01 | 0.19 ± 0.04 |
PRSWi | 29.9 ± 1.8 | 24.4 ± 1.2 | 27.4 ± 3.3 |
28 Weeks of Diet | n = 7 | n = 9 | n = 8 |
Aortic flow (mL/min) | 12.5 ± 0.3 | 9.4 ± 0.9 * | 12.1 ± 0.1 # |
Coronary flow (mL/min) | 3.2 ± 0.2 | 3.5 ± 0.2 | 3.2 ± 0.3 |
Heart rate (bpm) | 434 ± 11 | 404 ± 9 | 415 ± 0.8 |
dP/dtmax (mmHg/sec) | 3968 ± 50 | 3697 ± 121 * | 3935 ± 92 |
dP/dtmin (mmHg/sec) | −3142 ± 51 | −2735 ± 116 * | −2948 ± 68 |
Tau Weiss (msec) | 10.0 ± 0.2 | 11.3 ± 0.4 * | 10.8 ± 0.3 |
LVEDP (mmHg) | 9.3 ± 0.6 | 10.7 ± 0.9 | 10.3 ± 0.6 |
LVDP (mmHg) | 59 ± 1 | 56 ± 1 | 58 ± 1 |
LVEDV (μL) | 94 ± 6 | 67 ± 8 * | 87 ± 2 # |
EDPVR (mmHg/µL) | 0.18 ± 0.01 | 0.30 ± 0.04 * | 0.18 ± 0.02 # |
PRSWi | 28.3 ± 2.7 | 23.7 ± 2.4 | 32.4 ± 1.5 # |
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Hafstad, A.D.; Hansen, S.S.; Lund, J.; Santos, C.X.C.; Boardman, N.T.; Shah, A.M.; Aasum, E. NADPH Oxidase 2 Mediates Myocardial Oxygen Wasting in Obesity. Antioxidants 2020, 9, 171. https://doi.org/10.3390/antiox9020171
Hafstad AD, Hansen SS, Lund J, Santos CXC, Boardman NT, Shah AM, Aasum E. NADPH Oxidase 2 Mediates Myocardial Oxygen Wasting in Obesity. Antioxidants. 2020; 9(2):171. https://doi.org/10.3390/antiox9020171
Chicago/Turabian StyleHafstad, Anne D., Synne S. Hansen, Jim Lund, Celio X. C. Santos, Neoma T. Boardman, Ajay M. Shah, and Ellen Aasum. 2020. "NADPH Oxidase 2 Mediates Myocardial Oxygen Wasting in Obesity" Antioxidants 9, no. 2: 171. https://doi.org/10.3390/antiox9020171