Chem. J. Chinese Universities ›› 2018, Vol. 39 ›› Issue (11): 2395.doi: 10.7503/cjcu20180272
• Analytical Chemistry • Previous Articles Next Articles
LI Wenwen1,3, ZHU Airu2, LONG Yijing2, WANG Chunyan2, HAN Yuanping2, DUAN Yixiang2,3,*()
Received:
2018-04-09
Online:
2018-11-10
Published:
2018-10-16
Contact:
DUAN Yixiang
E-mail:yduan@scu.edu.cn
Supported by:
CLC Number:
TrendMD:
LI Wenwen, ZHU Airu, LONG Yijing, WANG Chunyan, HAN Yuanping, DUAN Yixiang. Metabolomics Study of Serum and Liver in Type 2 Diabetes Mice Induced by High Fat Diet with Vitamin D Deficiency†[J]. Chem. J. Chinese Universities, 2018, 39(11): 2395.
Parameter | Control(mean±SE) | HD(mean±SE) |
---|---|---|
Mass/g | 33.57±0.71 | 45.47±2.14* |
Visceral fat coefficient(%) | 2.70±0.32 | 7.50±0.74* |
FPB/(mmol·L-1) | 5.20±0.24 | 8.90±0.31* |
HOMA-IR(fold) | 1.0 | 1.7* |
Total cholesterol/(mmol·L-1) | 3.33±0.22 | 4.94±0.33* |
Triglyceride/(mmol·L-1) | 0.63±0.05 | 0.90±0.07* |
Free fatty acid/(mmol·L-1) | 0.89±0.04 | 1.19±0.03* |
LDL-C/(mmol·L-1) | 0.42±0.04 | 0.78±0.11* |
HDL-C/LDL-C | 7.14±0.48 | 5.33±0.38* |
Table 1 Biochemical parameters for HD group and control group
Parameter | Control(mean±SE) | HD(mean±SE) |
---|---|---|
Mass/g | 33.57±0.71 | 45.47±2.14* |
Visceral fat coefficient(%) | 2.70±0.32 | 7.50±0.74* |
FPB/(mmol·L-1) | 5.20±0.24 | 8.90±0.31* |
HOMA-IR(fold) | 1.0 | 1.7* |
Total cholesterol/(mmol·L-1) | 3.33±0.22 | 4.94±0.33* |
Triglyceride/(mmol·L-1) | 0.63±0.05 | 0.90±0.07* |
Free fatty acid/(mmol·L-1) | 0.89±0.04 | 1.19±0.03* |
LDL-C/(mmol·L-1) | 0.42±0.04 | 0.78±0.11* |
HDL-C/LDL-C | 7.14±0.48 | 5.33±0.38* |
Fig.1 Total ion chromatogram of a serum samplePeak: 1. hexanol; 2. pyruvic acid**; 3. L-lactic acid**; 4. L-Alanine**; 5. hydroxylamine; 6. 2-hydroxybutyric acid*; 7. oxalic acid; 8. 3-hydroxybutyric acid; 9. L-valine; 10. urea**; 11. ethanol amine; 12. glycerol**; 13. L-isoleucine; 14. L-proline**; 15. glycine; 16. succinic acid*; 17. glyceric acid*; 18. L-serine**; 19. L-threonine**; 20. 2,4-dihydroxybutyric acid; 21. β-alanine; 22. malic acid; 23. erythritol; 24. L-methionine**; 25. 5-oxoproline; 26. erythronic acid; 27. creatinine*; 28. threonic acid**; 29. α-ketoglutarate; 30. L-glutamic acid*; 31. L-phenylalanine; 32. ribose; 33. ribitol; 34. L-ornithine; 35. citric acid; 36. 1-deoxyglucose*; 37. fructose**; 38. mannose; 39. glucose**; 40. glucitol; 41. L-tyrosine; 42. palmitic acid; 43. inositol*; 44. heptadecanoic acid; 45. linoleic acid; 46. oleic acid; 47. stearic acid. Metabolites confirmed with standards are in bold, statistical significance between control and HD group, * P<0.05, ** P<0.01.
Fig.2 Total ion chromatogram of a liver samplePeak: 1. hexanol; 2. L-lactic acid*; 3. L-alanine; 4. hydroxylamine*; 5. 2-hydroxybutyric acid*; 6. oxalic acid; 7. 3-hydroxybutyric acid; 8. 2-aminobutyric acid*; 9. L-valine*; 10. 4-hydroxybutyric acid; 11. urea*; 12. ethanol amine**; 13. glycerol; 14. L-isoleucine*; 15. L-proline; 16. glycine; 17. succinic acid*; 18. glyceric acid*; 19. fumaric acid**; 20. L-serine; 21. L-threonine; 22. β-alanine**; 23. malic acid**; 24. erythritol**; 25. L-methionine*; 26. 5-oxoproline; 27. 4-aminobutyric acid; 28. 2,6-ditertbutylphenol; 29. cysteine; 30. L-glutamic acid; 31. L-phenylalanine; 32. xylose**; 33. lauric acid**; 34. ribose**; 35. xylitol; 36. ribitol; 37. myristic acid; 38. fructose**; 39. mannose**; 40. glucose**; 41. glucitol; 42. L-tyrosine; 43. palmitelaidic acid*; 44. palmitoleic acid; 45. palmitic acid**; 46. inositol; 47. heptadecanoic acid; 48. linoleic acid; 49. oleic acid*; 50. stearic acid; 51. arachidonic acid. Metabolites confirmed with standards are in bold, * P<0.05, ** P<0.01.
Fig.3 Principal component analysis score plots for metabolic profiling of serum(A) and liver(B) samples in HD group and control group(A) R2X[1]=0.14, R2X[2]=0.1; (B) R2X[1]=0.181, R2X[2]=0.0884.
Fig.4 Orthogonal partial least squares-discriminant analysis(OPLS-DA) score plots for metabolic profiling of serum(A) and liver(B) samples in HD group and control group and S-plots of variablesin serum(C) and liver(D)(A) R2X[1]=0.35; R2X[X side comp. 1]=0.217; (B) R2X[1]=0.305; R2X[X side comp.1]=0.172; (C) R2X[1]=0.35; (D) R2X[1]=0.305. (C) and (D): red triangles are metabolic biomarkers with VIP>1 and statistical significance P<0.05.
Fig.6 Liver metabolic biomarkers for T2DM(* P<0.05, ** P<0.01)(A) Ethanolamine; (B) lactic acid; (C) palmitic acid; (D) oleic acid; (E) ribose; (F) fructose; (G) glucose.
Fig.7 Heat map for serum and liver metabolites in HD group and control groupA, B, C and D represent amino acids, fatty acids, organic acids, and carbohydrates and alditol, respectively. Red color and blue color indicate up-regulated and down-regulated, grey color represents absence.
Fig.8 Metabo analyst pathway analysis for serum(A) and liver(B) metabolitesNumbers in the plots are metabolic pathways listed in Table 2 and Table 3, respectively.
No. | Pathway name | P | Impact | KEGG |
---|---|---|---|---|
1 | Aminoacyl-tRNA biosynthesis* | 0 | 0.113 | map00970 |
2 | Alanine, aspartate and glutamate metabolism* | 0 | 0.234 | map00250 |
3 | Arginine and proline metabolism* | 0 | 0.175 | map00330 |
4 | Glycine, serine and threonine metabolism* | 0 | 0.233 | map00260 |
5 | Cysteine and methionine metabolism* | 0.001 | 0.067 | map00270 |
6 | Glycolysis or Gluconeogenesis* | 0.002 | 0.095 | map00010 |
7 | Pentose phosphate pathway | 0.002 | 0.022 | map00030 |
8 | Propanoate metabolism | 0.002 | 0.001 | map00640 |
9 | Butanoate metabolism* | 0.003 | 0.103 | map00650 |
10 | Galactose metabolism* | 0.004 | 0.003 | map00052 |
11 | Ascorbate and aldarate metabolism | 0.005 | 0.024 | map00053 |
12 | Glyoxylate and dicarboxylate metabolism* | 0.006 | 0.033 | map00630 |
13 | Taurine and hypotaurine metabolism | 0.010 | 0.054 | map00430 |
14 | Citrate cycle(TCA cycle)* | 0.010 | 0.105 | map00020 |
15 | Valine, leucine and isoleucine biosynthesis | 0.018 | 0.022 | map00290 |
16 | Glycerolipid metabolism* | 0.025 | 0.209 | map00561 |
17 | Pyruvate metabolism* | 0.025 | 0.320 | map00620 |
18 | Phenylalanine metabolism | 0.048 | 0 | map00360 |
Table 2 Significant pathways for serum metabolites
No. | Pathway name | P | Impact | KEGG |
---|---|---|---|---|
1 | Aminoacyl-tRNA biosynthesis* | 0 | 0.113 | map00970 |
2 | Alanine, aspartate and glutamate metabolism* | 0 | 0.234 | map00250 |
3 | Arginine and proline metabolism* | 0 | 0.175 | map00330 |
4 | Glycine, serine and threonine metabolism* | 0 | 0.233 | map00260 |
5 | Cysteine and methionine metabolism* | 0.001 | 0.067 | map00270 |
6 | Glycolysis or Gluconeogenesis* | 0.002 | 0.095 | map00010 |
7 | Pentose phosphate pathway | 0.002 | 0.022 | map00030 |
8 | Propanoate metabolism | 0.002 | 0.001 | map00640 |
9 | Butanoate metabolism* | 0.003 | 0.103 | map00650 |
10 | Galactose metabolism* | 0.004 | 0.003 | map00052 |
11 | Ascorbate and aldarate metabolism | 0.005 | 0.024 | map00053 |
12 | Glyoxylate and dicarboxylate metabolism* | 0.006 | 0.033 | map00630 |
13 | Taurine and hypotaurine metabolism | 0.010 | 0.054 | map00430 |
14 | Citrate cycle(TCA cycle)* | 0.010 | 0.105 | map00020 |
15 | Valine, leucine and isoleucine biosynthesis | 0.018 | 0.022 | map00290 |
16 | Glycerolipid metabolism* | 0.025 | 0.209 | map00561 |
17 | Pyruvate metabolism* | 0.025 | 0.320 | map00620 |
18 | Phenylalanine metabolism | 0.048 | 0 | map00360 |
No. | Pathway name | P | Impact | KEGG |
---|---|---|---|---|
1 | Propanoate metabolism# | 0 | 0.086 | map00640 |
2 | Pentose phosphate pathway | 0.003 | 0.022 | map00030 |
3 | Amino sugar and nucleotide sugar metabolism* | 0.009 | 0 | map00520 |
4 | Fatty acid biosynthesis | 0.011 | 0 | map00061 |
5 | Starch and sucrose metabolism* | 0.011 | 0.017 | map00500 |
6 | Citrate cycle(TCA cycle)* | 0.015 | 0.031 | map00020 |
7 | Alanine, aspartate and glutamate metabolism | 0.021 | 0.003 | map00250 |
8 | Valine, leucine and isoleucine biosynthesis# | 0.027 | 0.027 | map00290 |
9 | Pantothenate and CoA biosynthesis# | 0.027 | 0.073 | map00770 |
10 | Aminoacyl-tRNA biosynthesis# | 0.032 | 0 | map00970 |
11 | Glycolysis or Gluconeogenesis | 0.034 | 0 | map00010 |
Table 3 Significant pathways for liver metabolites
No. | Pathway name | P | Impact | KEGG |
---|---|---|---|---|
1 | Propanoate metabolism# | 0 | 0.086 | map00640 |
2 | Pentose phosphate pathway | 0.003 | 0.022 | map00030 |
3 | Amino sugar and nucleotide sugar metabolism* | 0.009 | 0 | map00520 |
4 | Fatty acid biosynthesis | 0.011 | 0 | map00061 |
5 | Starch and sucrose metabolism* | 0.011 | 0.017 | map00500 |
6 | Citrate cycle(TCA cycle)* | 0.015 | 0.031 | map00020 |
7 | Alanine, aspartate and glutamate metabolism | 0.021 | 0.003 | map00250 |
8 | Valine, leucine and isoleucine biosynthesis# | 0.027 | 0.027 | map00290 |
9 | Pantothenate and CoA biosynthesis# | 0.027 | 0.073 | map00770 |
10 | Aminoacyl-tRNA biosynthesis# | 0.032 | 0 | map00970 |
11 | Glycolysis or Gluconeogenesis | 0.034 | 0 | map00010 |
Fig.9 Network of metabolites and pathways in this workRed is TCA cycle; green is glycolysis; blue is amino acids into TCA cycle; pink is pentose phosphate pathway; purple is fatty acid synthesis.
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