Adipocyte-Specific Expression of PGC1α Promotes Adipocyte Browning and Alleviates Obesity-Induced Metabolic Dysfunction in an HO-1-Dependent Fashion
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animal Experimentation and Generation of Transgenic Mice with Adipocyte-Specific Expression of PGC1α
2.2. Generation of Lentiviral-Mediated PGC1-α Overexpression or Silencing in Adipocytes
2.3. Measurement of Fasting Blood Glucose
2.4. Western Blot
2.5. RT-PCR and R.N.A. Arrays Analysis
2.6. Hematoxylin–Eosin and Masson Trichrome Stain in Liver
2.7. Histology, Masson Trichrome Staining, and Immunofluorescence in Adipose Tissues
2.8. Measurement of Mitochondrial Oxygen Consumption Rate in Adipocytes
2.9. Detection of Nuclear PGC-1α by Immunogold Staining
2.10. Statistics
3. Results
3.1. Transgenic-Adipo-PGC-1α Mice Exhibit Glucose Intolerance
3.2. Adipose-Specific Expression of PGC-1α Rescues Mice from HFD.-Induced Adipocyte Hypertrophy, Fibrosis, Liver Steatosis, and Lipid Droplet Size
3.3. Nuclear Localization of PGC-1α in Adipocytes
3.4. mRNA Levels of PGC-1α, HO-1, Mitochondrial Genes, and NOV/CCN3 in the Adipose Tissue of Transgenic-Adipo-PGC-1α Mice
3.5. PGC-1α Mediated Regulation of Mitochondrial Function in Cultured Adipocytes
3.6. Expression Levels of Mitochondrial Biogenesis and Fusion Genes, UCP1, and Antioxidant-Associated Proteins in Transgenic-Adipo-PGC-1α Mice
3.7. Expression Levels of Inflammatory Mediators, Insulin Signaling Components, and AMPK in the Adipose Tissue of Transgenic-Adipo-PGC-1α Mice
3.8. Identification of Changes in the Correlation Coefficients of Gene Expression by RNA Array Analyses
3.9. Upregulated Genes in the Adipose Tissues of Transgenic-Adipo-PGC1 Mice
3.10. Effect of HO-1 Inhibition on the Phosphorylation of Insulin Receptor and Markers of Brown-like Fat in Transgenic-Adipo-PGC-1α Mice
3.11. Effect of SnPP on the Expression of the PGC-1α Target
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Shen, S.-H.; Singh, S.P.; Raffaele, M.; Waldman, M.; Hochhauser, E.; Ospino, J.; Arad, M.; Peterson, S.J. Adipocyte-Specific Expression of PGC1α Promotes Adipocyte Browning and Alleviates Obesity-Induced Metabolic Dysfunction in an HO-1-Dependent Fashion. Antioxidants 2022, 11, 1147. https://doi.org/10.3390/antiox11061147
Shen S-H, Singh SP, Raffaele M, Waldman M, Hochhauser E, Ospino J, Arad M, Peterson SJ. Adipocyte-Specific Expression of PGC1α Promotes Adipocyte Browning and Alleviates Obesity-Induced Metabolic Dysfunction in an HO-1-Dependent Fashion. Antioxidants. 2022; 11(6):1147. https://doi.org/10.3390/antiox11061147
Chicago/Turabian StyleShen, Shin-Hsueh, Shailendra P. Singh, Marco Raffaele, Maayan Waldman, Edith Hochhauser, Juancarlos Ospino, Michael Arad, and Stephen J. Peterson. 2022. "Adipocyte-Specific Expression of PGC1α Promotes Adipocyte Browning and Alleviates Obesity-Induced Metabolic Dysfunction in an HO-1-Dependent Fashion" Antioxidants 11, no. 6: 1147. https://doi.org/10.3390/antiox11061147
APA StyleShen, S.-H., Singh, S. P., Raffaele, M., Waldman, M., Hochhauser, E., Ospino, J., Arad, M., & Peterson, S. J. (2022). Adipocyte-Specific Expression of PGC1α Promotes Adipocyte Browning and Alleviates Obesity-Induced Metabolic Dysfunction in an HO-1-Dependent Fashion. Antioxidants, 11(6), 1147. https://doi.org/10.3390/antiox11061147