Complementary Immunometabolic Effects of Exercise and PPARβ/δ Agonist in the Context of Diet-Induced Weight Loss in Obese Female Mice
Abstract
:1. Introduction
2. Results
2.1. GW0742 Treatment in Obese Mice Improves Diet-Induced Weight Loss, Visceral Fat Mass Reduction, and Insulin Sensitivity
2.2. GW0742 Treatment but not Exercise Increases PPARβ/δ Activity in Both Skeletal Muscle and Lymphoid Tissues, Whereas Exercise but not GW0742 Treatment Improves AMPK Regulation in These Tissues
2.3. Prevalence of CD4+Foxp3+ Regulatory T cells increases with GW0742 Treatment in Lymph Nodes
2.4. Exercise Training Reduces Systemic and Skeletal Muscle Inflammation and Impacts Metabolism with Possible Additive Effect of GW0742 Treatment
3. Discussion
4. Materials and Methods
4.1. Animals and Treatments
4.2. Glucose Tolerance Test
4.3. Physical Tests Measurements
4.4. Lymph Node Collection and Cell Preparation
4.5. Flow Cytometry Analysis
4.6. Western Blots Analysis
4.7. RNA Extraction and Quantitative Real-Time PCR
4.8. Quantification of Cytokines with Luminex
4.9. Immunohistological Staining Protocol
4.10. Citrate Synthase Activity
4.11. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
AMPK | AMP-activated protein kinase |
BW | Body weight |
CD3 | Cluster of differentiation 3 |
CD4 | Cluster of differentiation 4 |
CPT-1 | Carnitine palmitoyl transferase-1 |
CS | Citrate synthase |
DIO | Diet-induced obesity |
DMSO | Dimethyl sulfoxide |
EX | Exercise |
FAO | Fatty acid oxidation |
FCS | Fœtal calf serum |
FoxP3 | Forkhead box P3 |
GTT | Glucose tolerance test |
HFD | High fat diet |
HOMA-IR | Homeostatic model assessment for insulin resistance |
IFNγ | Interferon gamma |
IL-6 | Interleukin 6 |
IL-10 | Interleukin 10 |
IR | Insulin resistance |
MCP1 | Monocyte chemoattractant protein 1 |
MFI | Mean fluorescence intensity |
ND | Normal chow diet |
PBS | Phosphate-buffered saline |
PDK4 | Pyruvate dehydrogenase kinase 4 |
PPAR | Peroxisome Proliferator-Activated Receptor |
T2DM | Type 2 diabetes mellitus |
TGF-β | Transforming growth factor beta |
TLA | Tibialis lateralis anterior |
Th1 | T helper 1 cells |
Th2 | T helper 2 cells |
Tregs | Regulatory T cells |
Th17 | T helper 17 cells |
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ND-EX Control | HFD-ND | HFD-ND EX | HFD-ND GW | HFD-ND EX GW | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Mean | SD | Mean | SD | Mean | SD | Mean | SD | Mean | SD | ||
ΔBW (T1−T0) (g) | 1.68 | 1.19 | −2.33 | 1.08 | −2.28 | 1.42 | −6.2 # | 2.86 | −4.4 # | 1.98 | |
Adipose tissues (mg/g) | Subcutaneous | 17.29 | 3.73 | 21.98 $ | 6.74 | 14.61 * | 2.43 | 14.33 * | 2.86 | 14.67 * | 4.21 |
Visceral | 12.55 | 3.36 | 21.12 $ | 7.16 | 11.41 * | 3.33 | 11.77 * | 1.10 | 10.93 * | 3.08 | |
Brown | 3.50 | 1.17 | 3.54 | 0.63 | 2.98 | 0.27 | 3.32 | 0.42 | 2.85 | 0.44 | |
Skeletal muscles (mg/g) | TLA | 1.87 | 0.74 | 1.45 | 0.18 | 1.65 | 0.08 | 1.59 | 0.06 | 1.56 | 0.11 |
Vastus lateralis | 6.88 | 0.48 | 6.40 | 0.37 | 7.03 | 0.24 | 6.83 | 0.64 | 7.27 * | 0.41 | |
Soleus | 0.28 | 0.02 | 0.26 | 0.02 | 0.33 | 0.05 | 0.33 | 0.15 | 0.27 | 0.05 |
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Le Garf, S.; Murdaca, J.; Mothe-Satney, I.; Sibille, B.; Le Menn, G.; Chinetti, G.; Neels, J.G.; Rousseau, A.-S. Complementary Immunometabolic Effects of Exercise and PPARβ/δ Agonist in the Context of Diet-Induced Weight Loss in Obese Female Mice. Int. J. Mol. Sci. 2019, 20, 5182. https://doi.org/10.3390/ijms20205182
Le Garf S, Murdaca J, Mothe-Satney I, Sibille B, Le Menn G, Chinetti G, Neels JG, Rousseau A-S. Complementary Immunometabolic Effects of Exercise and PPARβ/δ Agonist in the Context of Diet-Induced Weight Loss in Obese Female Mice. International Journal of Molecular Sciences. 2019; 20(20):5182. https://doi.org/10.3390/ijms20205182
Chicago/Turabian StyleLe Garf, Sébastien, Joseph Murdaca, Isabelle Mothe-Satney, Brigitte Sibille, Gwenaëlle Le Menn, Giulia Chinetti, Jaap G. Neels, and Anne-Sophie Rousseau. 2019. "Complementary Immunometabolic Effects of Exercise and PPARβ/δ Agonist in the Context of Diet-Induced Weight Loss in Obese Female Mice" International Journal of Molecular Sciences 20, no. 20: 5182. https://doi.org/10.3390/ijms20205182
APA StyleLe Garf, S., Murdaca, J., Mothe-Satney, I., Sibille, B., Le Menn, G., Chinetti, G., Neels, J. G., & Rousseau, A.-S. (2019). Complementary Immunometabolic Effects of Exercise and PPARβ/δ Agonist in the Context of Diet-Induced Weight Loss in Obese Female Mice. International Journal of Molecular Sciences, 20(20), 5182. https://doi.org/10.3390/ijms20205182