Table 2.
Enriched metabolic pathways associated with different outcomes.
| Region codes a | Enriched pathways | Outcome | Number of the empirical compound perturbed in the enriched pathway b | Gamma p value c |
|---|---|---|---|---|
| (i) Enriched pathways associated with BMI in women with- and without HDP | ||||
| A (2) | Vitamin D3 (cholecalciferol) metabolism* | Non-HDP | 6/9/16 | 0.02 |
| HDP | 4/9/16 | <0.01 | ||
| Lysine metabolism* | Non-HDP | 8/18/52 | 0.05 | |
| HDP | 3/18/52 | 0.04 | ||
| B (3) | TCA cycle* | Non-HDP | 5/6/31 | 0.02 |
| Vitamin B5 - CoA biosynthesis from pantothenate | Non-HDP | 3/3/12 | 0.03 | |
| Ubiquinone Biosynthesis* | Non-HDP | 4/6/10 | 0.03 | |
| C (9) | Tryptophan metabolism* | HDP | 12/58/94 | 0.01 |
| Tyrosine metabolism* | HDP | 14/76/160 | 0.01 | |
| Glycerophospholipid metabolism* | HDP | 6/27/156 | 0.01 | |
| Xenobiotics metabolism* | HDP | 5/28/110 | 0.02 | |
| Glutathione Metabolism | HDP | 2/6/19 | 0.02 | |
| Carnitine shuttle | HDP | 3/16/72 | 0.03 | |
| Ascorbate (Vitamin C) and Aldarate Metabolism | HDP | 2/9/29 | 0.04 | |
| Methionine and cysteine metabolism | HDP | 3/18/94 | 0.04 | |
| Drug metabolism—cytochrome P450* | HDP | 4/28/53 | 0.05 | |
| (ii) Enriched metabolic pathways associated with HDP in pregnant women stratified by BMI category | ||||
| A (1) | Tryptophan metabolism* | Normal | 2/58/94 | 0.05 |
| Overweight | 4/58/94 | 0.00 | ||
| Obese | 5/58/94 | 0.04 | ||
| B (1) | Prostaglandin formation from arachidonate | Normal | 2/40/78 | 0.03 |
| Overweight | 2/41/78 | 0.01 | ||
| D (6) | Glycerophospholipids metabolism* | Overweight | 3/27/156 | 0.00 |
| Obese | 5/27/156 | 0.00 | ||
| Ubiquinone Biosynthesis* | Overweight | 2/6/10 | 0.00 | |
| Obese | 2/6/10 | 0.01 | ||
| Urea cycle/amino group metabolism | Overweight | 3/32/85 | 0.00 | |
| Obese | 3/32/85 | 0.04 | ||
| Lysine metabolism* | Overweight | 2/18/52 | 0.01 | |
| Obese | 2/18/52 | 0.05 | ||
| Androgen and estrogen biosynthesis and metabolism | Overweight | 3/48/95 | 0.01 | |
| Obese | 4/48/95 | 0.05 | ||
| Tyrosine metabolism* | Overweight | 3/79/160 | 0.01 | |
| Obese | 6/76/160 | 0.05 | ||
| E (3) | Fatty acid activation | Normal | 2/17/74 | 0.01 |
| Leukotriene metabolism | Normal | 2/26/92 | 0.02 | |
| Arachidonic acid metabolism | Normal | 2/58/94 | 0.05 | |
| F (6) | Histidine metabolism | Overweight | 3/9/33 | 0.00 |
| Methionine and cysteine metabolism | Overweight | 3/18/94 | 0.00 | |
| Vitamin B12 (cyanocobalamin) metabolism | Overweight | 2/2/9 | 0.00 | |
| Glycine, serine, alanine and threonine metabolism | Overweight | 3/27/88 | 0.00 | |
| Vitamin B3 (nicotinate and nicotinamide) metabolism | Overweight | 2/12/28 | 0.01 | |
| Aspartate and asparagine metabolism | Overweight | 2/47/114 | 0.01 | |
| G (10) | Vitamin D3 (cholecalciferol) metabolism* | Obese | 3/9/16 | 0.00 |
| Pyrimidine metabolism | Obese | 3/15/70 | 0.01 | |
| TCA cycle* | Obese | 2/6/31 | 0.01 | |
| Xenobiotics metabolism* | Obese | 4/28/34 | 0.01 | |
| Pyranic acid peroxisome oxidation | Obese | 2/8/34 | 0.01 | |
| Drug metabolism - cytochrome P450* | Obese | 3/28/53 | 0.03 | |
| Butanoate metabolism | Obese | 2/14/34 | 0.03 | |
| Glycosphingolipid metabolism | Obese | 2/14/67 | 0.03 | |
| De novo fatty acid biosynthesis | Obese | 2/15/106 | 0.03 | |
| Bile acid biosynthesis | Obese | 3/34/82 | 0.05 | |
(i) The BMI-associated metabolic pathways in women with- and without HDP and (ii) The HDP-associated metabolic pathways in women of healthy weight, overweight and obese were enriched by MetaboAnalyst 5.0 via the functional analysis (MS peaks) module.
Regional codes: for (i), capital letters (A, B, and C) and numbers correspond to the Venn diagram in Figure 2B; for (ii), capital letters (A–G) and numbers correspond to the Venn diagram in Figure 3B.
Number of the empirical compound perturbed in the enriched pathway: x/y/z, “x” indicates the total number of empirical compounds in the pathway, “y” indicates the number of empirical compounds annotated in the untargeted metabolomics dataset, “z” indicates the number of empirical compounds significantly perturbed (p < 0.05) with HDP.
Gamma p-value, the Gamma adjusted p-value indicates the significance of the pathway enrichment. A lower p-value indicates a greater significance in the enrichment. The cut-off for pathway significance is p < 0.05.
Overlapped Pathways between (i) Enriched pathways associated with BMI in women with- and without HDP and (ii) Enriched metabolic pathways associated with HDP in pregnant women stratified by BMI category.