n-3 Polyunsaturated Fatty Acids Decrease Long-Term Diabetic Risk of Offspring of Gestational Diabetes Rats by Postponing Shortening of Hepatic Telomeres and Modulating Liver Metabolism
Abstract
1. Introduction
2. Materials and Methods
2.1. Animal Model and Offspring Diet Intervention
2.2. Determination of Serum Factors
2.3. Glucose and Insulin Tolerance Tests
2.4. Measurement of Oxidative Stress
2.5. Enzyme-Linked Immunosorbent Assay for Inflammatory Factors
2.6. Telomere Length Measurement
2.7. Metabolomics Analysis
2.7.1. Sample Preparation
2.7.2. High Performance Lipid Chromatography Coupled with Quadrupole-Time of Flight Mass Spectrometry (HPLC-QTOF-MS) Analysis
2.7.3. Data Processing and Metabolites Identification
2.8. Statistical Analysis
3. Results
3.1. Serum Biochemical Index of GDM Offspring and Effect of n-3 PUFA
3.2. Glucose and Insulin Tolerance Test during Growth of GDM Offspring and Effect of n-3 PUFA
3.3. Effect of n-3 PUFA on Oxidative Stress of the Liver of GDM Offspring
3.4. Effect of n-3 PUFA on Inflammatory Factors in the Liver of GDM Offspring
3.5. Influence of GDM on Telomere Length of the Liver of Offspring and the Effect of n-3 PUFA and n-6 PUFA on Telomere Length
3.6. Metabolomics Analysis of the Liver of GDM Offspring at Old Age and the Modulating Effect of n-3 PUFA on the Liver of GDM Offspring
4. Discussion
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
Abbreviations
References
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3 Week (Weaning) | Con | GDM |
---|---|---|
Fasting glucose (mmol/L) | 6.17 ± 1.24 | 6.01 ± 1.3 |
Postprandial glucose (mmol/L) | 7.34 ± 0.61 | 7.57 ± 0.49 |
Fasting insulin (mU/L) | 12.01 ± 0.59 | 9.7 ± 0.46 * |
Postprandial insulin (mU/L) | 13.23 ± 0.78 | 20.17 ± 1.45 ** |
TG (mmol/L) | 0.45 ± 0.1 | 0.46 ± 0.11 |
TC (mmol/L) | 1.76 ± 0.19 | 1.98 ± 0.16 |
11 Months old | Con | GDM | n-3 Adq-GDM | n-3 Def-GDM |
---|---|---|---|---|
Glucose (mmol/L) | 6.05 ± 0.37 | 8.39 ± 2.07 | 6.3 ± 0.54 | 8.38 ± 1.66 |
Insulin (mU/L) | 11.73 ± 0.55 | 8.03 ± 0.47 ** | 10 ± 0.46 *## | 7.8 ± 0.78 ** |
TG (mmol/L) | 0.79 ± 0.13 | 0.63 ± 0.19 | 0.43 ± 0.19 *# | 0.61 ± 0.19 |
TC (mmol/L) | 1.87 ± 0.04 | 1.79 ± 0.36 | 0.69 ± 0.16 **## | 1.7 ± 0.17 |
HDL (mmol/L) | 0.53 ± 0.03 | 0.52 ± 0.18 | 0.27 ± 0.04 **## | 0.47 ± 0.03 |
TC/HDL | 3.52 ± 0.12 | 3.44 ± 0.66 | 2.55 ± 0.28 **## | 3.62 ± 0.19 |
Identification | RT (Min) | m/z | Changing Trend | Significance | ||
---|---|---|---|---|---|---|
GDM vs. Con | n-3adq vs. GDM | n-3def vs. GDM | ||||
Ceramide (d18:1/16:0) | 17.78 | 560.5073 | ↑ | ↓* | - | Biomarker for diabetes; impair insulin signaling and cause insulin resistance; increase oxidative stress; promote inflammation; contribute to non-alcohol fatty liver disease |
Tetrahydro-11-deoxycortisol | 11.56 | 337.2756 | ↑ | ↓** | - | Impact cortisol and further impact insulin production and glucose metabolism; inhibit glycogen synthesis; cause insulin resistance |
9’-Carboxy-γ-tocotrienol | 16.50 | 395.2234 | ↓ | - | ↓** | Antioxidant effect; improve glycemic control; prevent hyperlipidemia; suppress inflammation |
α-Linolenic acid | 11.93 | 570.3029 | ↓ | - | ↓** | Decreases diabetic risk; improve insulin resistance; improve oxidative stress and inflammation; regulate lipid metabolism; improve non-alcohol fatty liver disease |
Hexadecenoic acid | 15.99 | 271.2649 | ↑ | - | - | Induce endoplasmic reticulum stress and insulin resistance; lipotoxicity; enhance oxidative stress and inflammation; contribute to non-alcohol fatty liver disease |
Niacinamide | 0.95 | 123.0515 | ↓ | - | - | Prevent diabetes; protect β cell; antioxidative role; anti-inflammatory effect |
Oxalacetic acid | 18.17 | 154.9962 | ↓ | - | ↓* | Impact citric acid cycle and glucose and lipid metabolism; decrease of it indicate gluconeogenesis |
Phenylethylamine | 2.52 | 122.0956 | ↑ | - | ↑** | Indicate possibility of hepatic damage and hepatic encephalopathy |
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Gao, J.; Xiao, H.; Li, J.; Guo, X.; Cai, W.; Li, D. n-3 Polyunsaturated Fatty Acids Decrease Long-Term Diabetic Risk of Offspring of Gestational Diabetes Rats by Postponing Shortening of Hepatic Telomeres and Modulating Liver Metabolism. Nutrients 2019, 11, 1699. https://doi.org/10.3390/nu11071699
Gao J, Xiao H, Li J, Guo X, Cai W, Li D. n-3 Polyunsaturated Fatty Acids Decrease Long-Term Diabetic Risk of Offspring of Gestational Diabetes Rats by Postponing Shortening of Hepatic Telomeres and Modulating Liver Metabolism. Nutrients. 2019; 11(7):1699. https://doi.org/10.3390/nu11071699
Chicago/Turabian StyleGao, Jinlong, Hailong Xiao, Jiaomei Li, Xiaofei Guo, Wenwen Cai, and Duo Li. 2019. "n-3 Polyunsaturated Fatty Acids Decrease Long-Term Diabetic Risk of Offspring of Gestational Diabetes Rats by Postponing Shortening of Hepatic Telomeres and Modulating Liver Metabolism" Nutrients 11, no. 7: 1699. https://doi.org/10.3390/nu11071699
APA StyleGao, J., Xiao, H., Li, J., Guo, X., Cai, W., & Li, D. (2019). n-3 Polyunsaturated Fatty Acids Decrease Long-Term Diabetic Risk of Offspring of Gestational Diabetes Rats by Postponing Shortening of Hepatic Telomeres and Modulating Liver Metabolism. Nutrients, 11(7), 1699. https://doi.org/10.3390/nu11071699