Metabolic Remodeling with Hepatosteatosis Induced Vascular Oxidative Stress in Hepatic ERK2 Deficiency Mice with High Fat Diets
Abstract
:1. Introduction
2. Results
2.1. The Aggravation of HST without Changing Body Weight in HFHSD-LE2KO
2.2. Decreased Phosphorylation of AMPK/ACC and the Increased Expression of SREBP-1c in Liver from HFHSD-LE2KO
2.3. Elevation of Serum Glucose and Insulin Levels and Insulin Resistance in Skeletal Muscle from HFHSD-LE2KO
2.4. Adipocytes Enlargement and Changes in Serum Adipocytokines in Epididymal Fat
2.5. Serum FA Fraction and Amino Acid Analysis
2.6. Serum Amino Acid Analysis
2.7. HFHSD-LE2KO Demonstrated Increased Aortic Superoxide Production and Impaired Endothelium-Dependent Relaxation
3. Discussion
4. Materials and Methods
4.1. Animals, Genotyping, and Diets
4.2. Biochemical Analysis of Tissues
4.3. Tissue Preparation and Histology
4.4. Measurements of Metabolites and Adipocytokines
4.5. Detection of Insulin-Induced p-AKT in Skeletal Muscle
4.6. Quantitative Real-Time PCR for SREBP1c
- SREBP1c (forward), 5′-TGAGAAGCGCTACCGGTCTT-3′;
- SREBP1c (reverse), 5′-AAGCGGATGTAGTCGATGGC-3′;
- 18S rRNA (forward), 5′-TTCCGATAACGAACGAGACTCT-3′;
- 18S rRNA (reverse), 5′-TGGCTGAACGCCACTTGTC-3′.
4.7. Gene Microarray Analysis
4.8. Measurement of Vascular Superoxide Production
4.9. Preparation of Aortic Rings and Organ Chamber Experiments
4.10. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations and Acronyms
AA | Arachidonic acid |
DHE | dihydroethidium |
LE2KO | Liver-specific ERK2 knockout |
eNOS | endothelial nitric oxide synthase |
EPA | Eicosapentaenoic acid |
ERK | extracellular signal-regulated kinase |
FA | Fatty acid |
HST | hepatosteatosis |
HFHSD | high-fat/high-sucrose diet |
MetS | metabolic syndrome |
NC | normal chow |
NO | nitric oxide |
PI3K | phosphatidylinositol-3 kinase |
Alb-Cre | transgenic mice expressing Cre recombinase under the control of the albumin promoter-Cre |
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NC | HFHSD | p Value | |||
---|---|---|---|---|---|
Control | LE2KO | Control | LE2KO | ||
Body weight | 31.4 ± 0.7 | 31.0 ± 0.8 | 41.5 ± 0.9 * | 41.6 ± 0.9 | <0.0001 |
Myristic acid | 11.7 ± 3.8 | 16.2 ± 8.8 | 9.7 ± 1.1 | 7.4 ± 1.0 # | 0.03 |
Myristoleic acid | 0.7 ± 0.4 | 1.1 ± 0.9 | 1.3 ± 0.3 | 1.2 ± 0.8 | 0.28 |
Palmitic acid | 677.1 ± 64.1 | 840.0 ± 180.0 | 694.7 ± 88.8 | 756.1 ± 122.2 | 0.05 |
Palmitoleic acid | 63.6 ± 11.8 | 86.3 ± 22.8 | 76.5 ± 12.2 | 57.2 ± 6.9 # | 0.005 |
ThankStearic acid | 183.4 ± 18.7 | 221.0 ± 37.8 | 215.2 ± 17.0 | 353.3 ± 73.1# | <0.0001 |
Oleic acid | 371.7 ± 50.2 | 519.4 ± 194.0 | 556.6 ± 96.4 * | 676.2 ± 85.6 | 0.0003 |
Linoleic acid | 792.8 ± 72.6 | 972.8 ± 284.1 | 633.7 ± 71.0 | 458.1 ± 83.4 | <0.0001 |
γ-Linolenic acid | 18.0 ± 2.9 | 22.9 ± 8.6 | 14.3 ± 1.5 | 9.7 ± 1.5 # | 0.002 |
α-Linolenic acid | 9.9 ± 2.5 | 14.3 ± 7.8 | 6.7 ± 1.2 * | 2.6 ± 0.6 # | 0.002 |
Arachidic acid | 2.6 ± 0.4 | 3.3 ± 1.0 | 3.8 ± 0.6 | 5.3 ± 1.4 # | <0.0001 |
Eicosenoic acid | 7.4 ± 2.0 | 10.3 ± 5.8 | 8.3 ± 1.2 | 9.4 ± 2.3 | 0.35 |
Eicosadienoic acid | 3.2 ± 1.0 | 4.2 ± 1.9 | 3.0 ± 0.8 | 3.7 ± 1.1 | 0.31 |
5-8-11 Eicosatetraenoic acid | 2.2 ± 0.4 | 2.9 ± 0.8 | 5.2 ± 0.9 * | 21.3 ± 9.7 # | <0.0001 |
Dihomo-γ-linolenic acid | 19.7 ± 2.4 | 25.9 ± 5.5 | 27.7 ± 5.7 * | 73.4 ± 28.5 # | 0.0003 |
Arachidonic acid | 310.3 ± 40.0 | 346.3 ± 50.5 | 488.5 ± 53.4 * | 992.2 ± 282.1 # | <0.0001 |
Eicosapentaenoic acid | 30.6 ± 2.8 | 39.2 ± 10.4 | 19.4 ± 2.9 * | 8.7 ± 2.9 # | <0.0001 |
Behenic acid | 6.7 ± 0.7 | 7.0 ± 0.8 | 9.7 ± 1.4 * | 12.8 ± 3.5 | 0.0002 |
Erucic acid | 1.9 ± 0.1 | 1.2 ± 0.4 | 1.6 ± 0.3 | 2.2 ± 0.6 # | <0.0001 |
Docosatetraenoic acid | 2.9 ± 0.5 | 1.9 ± 1.5 | 4.7 ± 0.9 | 9.4 ± 2.4 # | <0.0001 |
Docosapentaenoic acid | 11.9 ± 1.6 | 15.2 ± 3.2 | 9.8 ± 1.8 | 7.6 ± 1.2 | <0.0001 |
Lignoceric acid | 5.5 ± 0.5 | 5.8 ± 0.6 | 5.8 ± 0.5 | 6.6 ± 1.6 | 0.18 |
Docosahexaenoic acid | 225.4 ± 25.1 | 266.9 ± 32.1 | 230.1 ± 21.5 | 271.9 ± 40.0 # | 0.006 |
Nervonic acid | 15.9 ± 1.1 | 17.4 ± 2.0 | 21.4 ± 1.4 * | 32.8 ± 4.9 # | <0.0001 |
EPA/AA ratio | 30.6 ± 2.8 | 39.2 ± 10.4 | 19.4 ± 2.9 * | 8.7 ± 1.1 # | <0.0001 |
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Kujiraoka, T.; Kagami, K.; Kimura, T.; Ishinoda, Y.; Shiraishi, Y.; Ido, Y.; Endo, S.; Satoh, Y.; Adachi, T. Metabolic Remodeling with Hepatosteatosis Induced Vascular Oxidative Stress in Hepatic ERK2 Deficiency Mice with High Fat Diets. Int. J. Mol. Sci. 2022, 23, 8521. https://doi.org/10.3390/ijms23158521
Kujiraoka T, Kagami K, Kimura T, Ishinoda Y, Shiraishi Y, Ido Y, Endo S, Satoh Y, Adachi T. Metabolic Remodeling with Hepatosteatosis Induced Vascular Oxidative Stress in Hepatic ERK2 Deficiency Mice with High Fat Diets. International Journal of Molecular Sciences. 2022; 23(15):8521. https://doi.org/10.3390/ijms23158521
Chicago/Turabian StyleKujiraoka, Takehiko, Kazuki Kagami, Toyokazu Kimura, Yuki Ishinoda, Yasunaga Shiraishi, Yasuo Ido, Shogo Endo, Yasushi Satoh, and Takeshi Adachi. 2022. "Metabolic Remodeling with Hepatosteatosis Induced Vascular Oxidative Stress in Hepatic ERK2 Deficiency Mice with High Fat Diets" International Journal of Molecular Sciences 23, no. 15: 8521. https://doi.org/10.3390/ijms23158521
APA StyleKujiraoka, T., Kagami, K., Kimura, T., Ishinoda, Y., Shiraishi, Y., Ido, Y., Endo, S., Satoh, Y., & Adachi, T. (2022). Metabolic Remodeling with Hepatosteatosis Induced Vascular Oxidative Stress in Hepatic ERK2 Deficiency Mice with High Fat Diets. International Journal of Molecular Sciences, 23(15), 8521. https://doi.org/10.3390/ijms23158521