Central Actions of Leptin Induce an Atrophic Pattern and Improves Heart Function in Lean Normoleptinemic Rats via PPARβ/δ Activation
Abstract
:1. Introduction
2. Materials and Methods
2.1. Experimental Animals
2.2. Intracerebroventricular Leptin Administration
2.3. Pharmacological Administration of the PPARβ/δ Antagonist GSK0660
2.4. Biochemical Assessment
2.5. Quantitative Transcription Analysis with Real-Time Polymerase Chain Reaction (qRT-PCR)
2.6. Western Blot Analysis
2.7. Cardiac Magnetic Resonance Imaging and Analysis
2.8. Statistical Analysis
3. Results and Discussion
3.1. Validation of Central Leptin Infusion and Pharmacological Inhibition of PPARβ/δ Activity
3.2. Effect of Leptin-GSK0660 Co-Treatment on Biological Characteristics of the Rats
3.3. Effect of Leptin-GSK0660 Co-Treatment on Cardiac Electrical Properties
3.4. Effect of Leptin-GSK0660 Co-Treatment on Cardiac Remodeling and Function
4. Conclusions and Future Directions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Repetition time | 8 ms |
Echo time | 2.5 ms |
Slices thickness | 1.5 mm |
FOV | 40 × 40 mm |
Matrix | 256 × 256 |
Resolution | 0.156 × 0.156 |
Hypothalamic Gene | SS | PF | LEP |
---|---|---|---|
Ob-Rb | 1.0 ± 0.3 a | 2.7 ± 0.2 b | 3.7 ± 0.4 c |
Crh | 0.9 ± 0.1 a | 0.6 ± 0.1 b | 1.96 ± 0.1 c |
Trh | 1.1 ± 0.1 a | 0.9 ± 0.1 a | 2.6 ± 0.3 b |
PF + DMSO | PF + GSK0660 | LEP + DMSO | LEP + GSK0660 | |
---|---|---|---|---|
PrWAT (g) | 4.62 ± 0.86 a | 4.86 ± 1 a | 3.04 ± 0.85 a | 3.71 ± 0.68 a |
eWAT (g) | 4.21 ± 0.36 a | 4.80 ± 0.86 a | 3.10 ± 0.54 a | 3.53 ± 0.40 a |
BAT (g) | 0.42 ± 0.05 a | 0.40 ± 0.07 a | 0.29 ± 0.02 a | 0.39 ± 0.04 a |
Serum glucose (mg/dL) | 99 ± 19 a | 105 ± 12 a | 112 ± 12 a | 118 ± 10 a |
Serum leptin (ng/mL) | 1.07 ± 0.1 a | 1.60 ± 0.5 a | 1.10 ± 0.3 a | 1.14 ± 0.3 a |
Serum insulin (ng/mL) | 2.49 ± 0.8 a | 2.67 ± 0.6 a | 2.46 ± 0.6 a | 5.19 ± 2.1 b |
QRS Duration (ms) | ∆QRS (ms) | R Amplitude (mV) | ∆R (mV) | |||
t0 | t7 | t0 | t7 | |||
PF+DMSO | 22.7 ± 5.1 | 19.6 ± 5.1 | −3.1 ± 3.2 a | 147 ± 19 | 149 ± 24 | 2.0 ± 15 a |
PF+GSK0660 | 28.8 ± 5.7 | 26.3 ± 5.0 | −2.5 ± 3.6 a | 103 ± 26 | 95 ± 7 | −8 ± 14 a |
LEP+DMSO | 29.2 ± 7.1 | 20.4 ± 3.8 * | −8.8 ± 3.6 a | 137 ± 23 | 93 ± 12 * | −44 ± 13 b |
LEP+GSK0660 | 21.4 ± 3.0 | 17.1 ± 8 | −4.3 ± 3.8 a | 126 ± 12 | 132 ± 27 | 6 ± 13 a |
QT Duration (ms) | ∆QT (ms) | QTc Duration (ms) | ∆QTc (ms) | |||
t0 | t7 | t0 | t7 | |||
PF+DMSO | 71.9 ± 13.4 | 70.9 ± 11.1 | −1.0 ± 7.8 a | 6.2 ± 1.2 | 5.6 ± 0.8 | −0.6 ± 0.6 a |
PF+GSK0660 | 65.2 ± 7.3 | 55.1 ± 7.3 | −10.1 ± 4.9 a,b | 5.4 ± 0.6 | 4.2 ± 0.5 * | −1.2 ± 0.4 a |
LEP+DMSO | 79.9 ± 10.5 | 65.5 ± 12.1 | −14.4 ± 7.2 b | 6.9 ± 1.0 | 5.6 ± 1.1 | −1.3 ± 0.7 a |
LEP+GSK0660 | 55.3 ± 7.2 | 60.3 ± 3.6 | 5.0 ± 3.6 a,c | 4.6 ± 0.6 | 5.1 ± 0.3 | 0.5 ± 0.3 b |
R-R INTERVAL (ms) | ∆R-R (ms) | Heart Rate (bpm) | ∆HR (bpm) | |||
---|---|---|---|---|---|---|
t0 | t7 | t0 | t7 | |||
PF+DMSO | 136 ± 6 | 159 ± 7 * | 23 ± 4.1 a | 210 ± 22 | 274 ± 30 * | 64 ± 16.64 a |
PF+GSK0660 | 145 ± 4 | 196 ± 31 * | 51 ± 14.0 b | 205 ± 12 | 275 ± 34 * | 70 ± 16.12 a |
LEP+DMSO | 135 ± 5 | 139 ± 4 | 4 ± 2.9 c | 231 ± 30 | 219 ± 20 | −12 ± 16.12 b |
LEP+GSK0660 | 141 ± 4 | 142 ± 6 | 1 ± 3.2 c | 199 ± 4 | 224 ± 14 * | 25 ± 6.51 c |
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Rubio, B.; Pintado, C.; Mazuecos, L.; Benito, M.; Andrés, A.; Gallardo, N. Central Actions of Leptin Induce an Atrophic Pattern and Improves Heart Function in Lean Normoleptinemic Rats via PPARβ/δ Activation. Biomolecules 2024, 14, 1028. https://doi.org/10.3390/biom14081028
Rubio B, Pintado C, Mazuecos L, Benito M, Andrés A, Gallardo N. Central Actions of Leptin Induce an Atrophic Pattern and Improves Heart Function in Lean Normoleptinemic Rats via PPARβ/δ Activation. Biomolecules. 2024; 14(8):1028. https://doi.org/10.3390/biom14081028
Chicago/Turabian StyleRubio, Blanca, Cristina Pintado, Lorena Mazuecos, Marina Benito, Antonio Andrés, and Nilda Gallardo. 2024. "Central Actions of Leptin Induce an Atrophic Pattern and Improves Heart Function in Lean Normoleptinemic Rats via PPARβ/δ Activation" Biomolecules 14, no. 8: 1028. https://doi.org/10.3390/biom14081028