Metabolic Impact of MKP-2 Upregulation in Obesity Promotes Insulin Resistance and Fatty Liver Disease
Abstract
:1. Introduction
2. Materials and Methods
2.1. Reagents, Antibodies and Immunoblotting
2.2. Animal and Human Studies
2.2.1. Animal Studies
2.2.2. Human Liver Samples
2.3. Metabolic Measurements
2.4. Cell Culture and Transient Transfections
2.5. RNA Extraction and Real-Time PCR Analysis
2.6. Serum Cytokine Levels Measurements
2.7. Histological Analysis of Tissue Sections
2.8. Statistical Analysis
2.9. Data and Resource Availability
3. Results
3.1. Upregulation of MKP-2 Expression in Human and Mice Livers with Obesity and Fatty Liver Disease
3.2. MAPK Phosphorylation in Human NASH Livers
3.3. Enhanced MAPK Phosphorylation in MKP-2-Deficient Mice
3.4. Resistance to Diet-Induced Obesity in MKP-2-Deficient Mice
3.5. Reduced Food Intake and RER in MKP-2-Deficient Mice
3.6. Protection from the Development of Hepatic Steatosis in MKP-2-Deficient Mice
3.7. Glucose Tolerance and Insulin Sensitivity in Chow and HFD-Fed MKP-2-Deficient Mice
3.8. Enhanced Akt Signaling in MKP-2-Deficient Mice
3.9. Modulation of Cytokines/Chemokines and Growth Factor Secretion in HFD-Fed MKP-2-Deficient Mice
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
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Ingredient | kcal./g | g/kg | kcal./kg |
---|---|---|---|
Casein | 3.58 | 200 | 716.00 |
Constarch | 3.6 | 0 | 0.00 |
Dyetrose | 3.8 | 125.00 | 475.00 |
Sucrose | 4 | 68.8 | 275.20 |
Cellulose | 0 | 50 | 0.00 |
Soybean Oil | 9 | 25 | 225.00 |
TBHQ | 0 | 0.005 | 0.00 |
Lard | 9 | 245 | 2205.00 |
Salt Mix #210088 | 1.6 | 10 | 16.00 |
Dicalcium Phosphate | 0 | 13 | 0.00 |
Calcium Carbpnate | 0 | 5.5 | 0.00 |
Patassium Citrate H2O | 0 | 16.5 | 0.00 |
Vitamin Mix #300050 | 3.92 | 10 | 39.20 |
L-Cystine | 4 | 3 | 12.00 |
Choline Bitartrate | 0 | 2 | 0.00 |
773.805 | 3963.400 |
Ingredient | kcal./g | g/kg | kcal./kg |
---|---|---|---|
Casein | 3.58 | 200 | 716.00 |
L-Cystine | 4 | 3 | 12.00 |
Sucrose | 4 | 350 | 1400.00 |
Constarch | 3.6 | 315 | 1134.00 |
Dyetrose | 3.8 | 35 | 133.00 |
Soybean Oil | 9 | 25 | 225.00 |
t-Butylhy droquinone | 0 | 0.005 | 0.00 |
Lard | 9 | 20 | 180.00 |
Cellulose | 0 | 50 | 0.00 |
Salt Mix #210088 | 1.6 | 10 | 16.00 |
Dicalcium Phosphate | 0 | 13 | 0.00 |
Calcium Carbpnate | 0 | 5.5 | 0.00 |
Patassium Citrate H2O | 0 | 16.5 | 0.00 |
Vitamin Mix #300050 | 3.92 | 10 | 39.20 |
Choline Bitartrate | 0 | 2 | 0.00 |
1055.005 | 3855.200 |
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Fernando, S.; Sellers, J.; Smith, S.; Bhogoju, S.; Junkins, S.; Welch, M.; Willoughby, O.; Ghimire, N.; Secunda, C.; Barmanova, M.; et al. Metabolic Impact of MKP-2 Upregulation in Obesity Promotes Insulin Resistance and Fatty Liver Disease. Nutrients 2022, 14, 2475. https://doi.org/10.3390/nu14122475
Fernando S, Sellers J, Smith S, Bhogoju S, Junkins S, Welch M, Willoughby O, Ghimire N, Secunda C, Barmanova M, et al. Metabolic Impact of MKP-2 Upregulation in Obesity Promotes Insulin Resistance and Fatty Liver Disease. Nutrients. 2022; 14(12):2475. https://doi.org/10.3390/nu14122475
Chicago/Turabian StyleFernando, Savanie, Jacob Sellers, Shauri Smith, Sarayu Bhogoju, Sadie Junkins, Morgan Welch, Orion Willoughby, Nabin Ghimire, Cassandra Secunda, Marina Barmanova, and et al. 2022. "Metabolic Impact of MKP-2 Upregulation in Obesity Promotes Insulin Resistance and Fatty Liver Disease" Nutrients 14, no. 12: 2475. https://doi.org/10.3390/nu14122475