Verification of the Impact of Blood Glucose Level on Liver Carcinogenesis and the Efficacy of a Dietary Intervention in a Spontaneous Metabolic Syndrome Model
Abstract
:1. Introduction
2. Materials and Methods
2.1. Ethics Statement
2.2. Animals and Experimental Design
2.3. Blood Glucose Level Measurement
2.4. Urine Sugar Measurement
2.5. Glucose Tolerance Test
2.6. Morphological Assessment of the Liver
2.7. Morphological Assessment of the Pancreas
2.8. Analysis of mRNA Expression in Liver
2.9. Analysis of Plasma SCFAs
2.10. Statistical Analyses
3. Results
3.1. Pathological Characteristics of Islets of Langerhans
3.2. Changes in Blood Glucose Level and Body Weight between Hyperglycemic and Non-Hyperglycemic TSOD Mice
3.3. Frequency of Liver Tumors
3.4. Changes in Islets of Langerhans in the Pancreas
3.5. Changes in Bodyweight and Glucose Levels
3.6. Histopathological Findings in the Liver
3.7. mRNA Expression of Lipid Metabolism-Related Genes in the Liver
3.8. Histopathological Findings in the Pancreas
3.9. Quantitation of Plasma SCFAs
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
TSOD | Tsumura Suzuki Obese Diabetes |
MS | metabolic syndrome |
NAFLD | non-alcoholic fatty liver disease |
MAFLD | metabolic associated fatty liver disease |
NASH | non-alcoholic steatohepatitis |
FOS | fructooligosaccharide |
GOS | galactooligosaccharide |
LS | lactosucrose |
HCC | hepatocellular carcinoma |
HE | hematoxylin and eosin |
SCFAs | short chain fatty acids |
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Genes | Forward (5′→3′) | Reverse (5′→3′) |
---|---|---|
β-actin | CATCCGTAAAGACCTCTATGCCAAC | ATGGAGCCACCGATCCACA |
Cd36 | TCCCAGAATTCTCAGCTGCTCC | CACATTTCAGAAGGCAGCAACTTC |
Chrebp | CGACACTCACCCACCTCTTC | TTGTTCAGCCGGATCTTGTC |
Cpt-1a | TCCTGAAGGAGGTACTGTCTG | CATAGCCGTCATCAGCAACC |
Fasn | GACTCGGCTACTGACACGAC | CGAGTTGAGCTGGGTTAGGG |
Fatp5 | GGGTGTGAGGGTAAGGTTGG | CCAGGGAATCCTGGATACGG |
G6pase | CCAACGTATGGATTCCGGTGT | GCAAGGTAGATCCGGGACAG |
Mttp | TGCTGTCCATTGGGGAACTC | CGACGGATCATTTTGCTTGC |
Pepck1 | TGGAAGGTCGAATGTGTGGG | TAGCCCTTAAGTTGCCTTGGG |
Pepck2 | GTGGTAACTCCTTGCTGGGC | TTGGTGATGCCCAAAATCAGCAT |
32-Weeks | 36-Weeks | 40-Weeks | |
---|---|---|---|
Hyperglycemic group | 4/8 (50%) | 8/8 (100%) | 6/8 (75%) |
Non-hyperglycemic group | 0/8 (0%) | 1/8 (12.5%) | 4/8 (50%) |
No | Mild | Severe | |
---|---|---|---|
Hyperglycemic group | 1/24 (4%) | 5/24 (20.8%) | 18/24 (75%) |
Non-hyperglycemic group | 6/24 (25%) | 18/24 (75%) | 0/24 (0%) |
Organ | Liver | Liver | Liver | Liver |
---|---|---|---|---|
Assessment Item | Steatosis | Lobular Inflammation | Ballooning | Fibrosis |
Control-M1 | 1 | 2 | 0 | 1 |
Control-M2 | 1 | 2 | 0 | 1 |
Control-M3 | 0 | 2 | 0 | 0 |
Control-M4 | 1 | 2 | 0 | 0 |
Control-M5 | 1 | 2 | 0 | 0 |
FOS-M6 | 0 | 2 | 0 | 0 |
FOS-M7 | 0 | 2 | 0 | 0 |
FOS-M8 | 0 | 2 | 0 | 1 |
FOS-M9 | 1 | 2 | 0 | 0 |
GOS-M10 | 0 | 2 | 0 | 1 |
GOS-M11 | 0 | 1 | 0 | 0 |
GOS-M12 | 0 | 0 | 0 | 0 |
GOS-M13 | 0 | 2 | 0 | 1 |
LS-M14 | 0 | 0 | 0 | 0 |
LS-M15 | 0 | 2 | 0 | 1 |
LS-M16 | 0 | 1 | 0 | 1 |
LS-M17 | 0 | 2 | 0 | 1 |
Group | n | No | Mild | Severe |
---|---|---|---|---|
Control | 5 | 0 | 4 | 1 |
FOS | 4 | 1 | 0 | 3 |
GOS | 4 | 4 | 0 | 0 |
LS | 4 | 4 | 0 | 0 |
Acetate | Propionate | Butyrate | Isobutyrate | 2-Methyl Butyrate | Capronate | |
---|---|---|---|---|---|---|
(μM) | (μM) | (μM) | (μM) | (μM) | (μM) | |
Control-M1 | 475.5 | 2.7 | 0.9 | 3.4 | 2.3 | 1.7 |
Control-M2 | 283.9 | 3.5 | 1.4 | 1.9 | N.D. | 1.2 |
Control-M3 | 945.3 | 5.5 | 2.4 | 3.7 | N.D. | 3.0 |
Control-M4 | 589.9 | 5.6 | 2.6 | 2.7 | 1.7 | 2.4 |
Control-M5 | 889.8 | N.D. | 0.9 | N.D. | N.D. | 3.5 |
Ave (SD) | 636.9 (279.3) | 4.3 (1.4) | 1.6 (0.8) | 2.9 (0.8) | 2.0 (0.4) | 2.4 (0.9) |
FOS-M6 | 363.6 | 2.7 | 0.9 | 1.4 | N.D. | 1.6 |
FOS-M7 | 467.2 | N.D. | 1.5 | 2.0 | N.D. | 2.3 |
FOS-M8 | 203.3 | 2.6 | 1.1 | 1.7 | 1.2 | 1.3 |
FOS-M9 | 275.8 | 3.8 | N.D. | 2.3 | N.D. | 1.4 |
Ave (SD) | 327.5 (113.9) | 3.0 (0.7) | 1.2 (0.3) | 1.9 (0.4) | 1.2 | 1.7 (0.5) |
GOS-M10 | 286.8 | 4.7 | 1.3 | 1.7 | 1.1 | 1.6 |
GOS-M11 | 358.7 | 3.1 | 1.3 | 1.1 | 0.6 | 1.8 |
GOS-M12 | 431.5 | 3.6 | 0.9 | 1.2 | N.D. | 1.0 |
GOS-M13 | 360.9 | 3.6 | 0.7 | 1.9 | 0.9 | 1.9 |
Ave (SD) | 359.5 (59.1) | 3.8 (0.7) | 1.0 (0.3) | 1.5 (0.4) | 0.9 (0.3) | 1.6 (0.4) |
LS-M14 | 417.6 | 4.7 | 0.7 | 2.1 | 1.2 | 1.5 |
LS-M15 | 655.1 | 6.7 | 2.7 | N.D. | N.D. | 2.5 |
LS-M16 | 579.0 | 5.6 | 2.3 | 2.3 | N.D. | 2.5 |
LS-M17 | 425.8 | 4.2 | 1.9 | 2.4 | N.D. | 2.5 |
Ave (SD) | 519.4 (117) | 5.3 (1.1) | 1.9 (0.9) | 2.3 (0.1) | 1.2 | 2.3 (0.5) |
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Ichimura-Shimizu, M.; Kageyama, T.; Oya, T.; Ogawa, H.; Matsumoto, M.; Sumida, S.; Kakimoto, T.; Miyakami, Y.; Nagatomo, R.; Inoue, K.; et al. Verification of the Impact of Blood Glucose Level on Liver Carcinogenesis and the Efficacy of a Dietary Intervention in a Spontaneous Metabolic Syndrome Model. Int. J. Mol. Sci. 2021, 22, 12844. https://doi.org/10.3390/ijms222312844
Ichimura-Shimizu M, Kageyama T, Oya T, Ogawa H, Matsumoto M, Sumida S, Kakimoto T, Miyakami Y, Nagatomo R, Inoue K, et al. Verification of the Impact of Blood Glucose Level on Liver Carcinogenesis and the Efficacy of a Dietary Intervention in a Spontaneous Metabolic Syndrome Model. International Journal of Molecular Sciences. 2021; 22(23):12844. https://doi.org/10.3390/ijms222312844
Chicago/Turabian StyleIchimura-Shimizu, Mayuko, Takeshi Kageyama, Takeshi Oya, Hirohisa Ogawa, Minoru Matsumoto, Satoshi Sumida, Takumi Kakimoto, Yuko Miyakami, Ryosuke Nagatomo, Koichi Inoue, and et al. 2021. "Verification of the Impact of Blood Glucose Level on Liver Carcinogenesis and the Efficacy of a Dietary Intervention in a Spontaneous Metabolic Syndrome Model" International Journal of Molecular Sciences 22, no. 23: 12844. https://doi.org/10.3390/ijms222312844
APA StyleIchimura-Shimizu, M., Kageyama, T., Oya, T., Ogawa, H., Matsumoto, M., Sumida, S., Kakimoto, T., Miyakami, Y., Nagatomo, R., Inoue, K., Cheng, C., & Tsuneyama, K. (2021). Verification of the Impact of Blood Glucose Level on Liver Carcinogenesis and the Efficacy of a Dietary Intervention in a Spontaneous Metabolic Syndrome Model. International Journal of Molecular Sciences, 22(23), 12844. https://doi.org/10.3390/ijms222312844