Background
Methods
Materials
Cohort
Preadipocyte culture and differentiation
Sample preparation
Sample analysis
Mass spectrometry
Separation by equivalent carbon number
Statistical analysis
Results
General characteristics of participants
Variables | IS | IR | T2DM | P value | IS+IR | P value | |||
---|---|---|---|---|---|---|---|---|---|
(N = 18) | (N = 35) | (N = 11) | ANOVA | IS vs IR | IS vs T2DM | IR vs T2DM | (N = 46) | IS+IR vs T2DM | |
Age (years) | 32.09 (9.7) | 30.26 (9.3) | 43.57 (9.4) | 0.000 | 0.739 | 0.017 | 0.003 | 30.9 (9.4) | 0.001 |
BMI (kg m−2) | 41.44 (7.0) | 43.31 (6.9) | 45.53 (9.6) | 0.38 | 0.583 | 0.394 | 0.731 | 42.7 (6.9) | 0.322 |
SBP (mmHg) | 119.0 (13.8) | 122.67 (15.7) | 132.14 (11.6) | 0.13 | 0.616 | 0.111 | 0.268 | 121.5 (15.1) | 0.075 |
DBP (mmHg) | 66.1 (9.8) | 69.98 (12.7) | 73.33 (7.0) | 0.3 | 0.422 | 0.369 | 0.783 | 68.7 (11.9) | 0.35 |
MAP | 83.4 (8.1) | 88.08 (12.4) | 93.53 (8.9) | 0.11 | 0.288 | 0.130 | 0.499 | 86.6 (11.3) | 0.15 |
Cholesterol (mmol/L) | 4.4 (0.9) | 4.6 (1.2) | 5.22 (0.9) | 0.24 | 0.785 | 0.215 | 0.364 | 4.5 (1.1) | 0.122 |
LDL (mmol/L) | 2.73 (0.8) | 2.91 (0.9) | 3.1 (1.0) | 0.55 | 0.693 | 0.593 | 0.855 | 2.8 (0.8) | 0.466 |
HDL (mmol/L) | 1.33 (0.4) | 1.46 (0.9) | 1.29 (0.3) | 0.74 | 0.793 | 0.990 | 0.844 | 1.4 (0.8) | 0.678 |
Triglyceride (mmol/L) | 1.13 (0.6) | 1.27 (0.7) | 1.91 (1.1) | 0.04 | 0.729 | 0.031 | 0.072 | 1.2 (0.6) | 0.015 |
Leptin (ng/mL) | 64.36 (25.5) | 60.7 (21.9) | 39.16 (31.5) | 0.06 | 0.854 | 0.055 | 0.091 | 62.1 (23.1) | 0.021 |
Adiponetin (ng/mL) | 3.24 (2.2) | 3.62 (1.9) | 3.47 (2.4) | 0.88 | 0.866 | 0.982 | 0.992 | 3.5 (1.9) | 0.979 |
IL-6 (pg/mL) | 3.28 (1.8) | 3.72 (1.8) | 4.03 (2.2) | 0.58 | 0.683 | 0.627 | 0.913 | 3.6 (1.8) | 0.521 |
FBG (mmol/L) | 5.73 (2.5) | 12.76 (8.4) | 12.84 (6.5) | 0.000 | 0.001 | 0.072 | 1.000 | 10.3 (7.7) | 0.439 |
Insulin (mIU/L) | 6.33 (1.9) | 12.6 (10.0) | 11.92 (6.4) | 0.01 | 0.010 | 0.241 | 0.976 | 10.3 (8.6) | 0.633 |
HOMA-IR | 1.56 (0.6) | 4.86 (2.0) | 6.6 (3.2) | 0.000 | 0.000 | 0.000 | 0.080 | 3.7 (2.3) | 0.005 |
Differences in TAG content between omental and subcutaneous adipose tissues
ID | TAG | MW | Fatty acid composition | Fatty acids identities | Fold change (SC-OM) | P value |
---|---|---|---|---|---|---|
TAG47 | C53:5 | 866.7 | C17:0, C17:1, C19:4 | Heptadecanoic acid, cis-10-heptadecanoic acid, C19:4 | 0.17 | 0.01 |
TAG2A | C38:1 | 664.7 | C18:1, C16:0, C4:0 | Oleic acid, palmitic acid, butyric acid | − 0.44 | 0.02 |
TAG36 | C51:3 | 842.6 | C18:1, C16:1, C17:1 | Oleic acid, palmitoleic acid, cis-10-heptadecenoic acid | 0.32 | 0.03 |
TAG31 | C50:4 | 826.7 | C18:2, C18:2, C14:0 | Linoleic acid, linoleic acid, myristic acid | 0.37 | 0.03 |
TAG81 | C59:1 | 958.8 | C23:0, C18:0, C18:1 | Tricosanoic acid, stearic acid, oleic acid | 0.16 | 0.04 |
TAG53A | C54:6 | 878.7 | C18:2, C18:2, C18:2 | Linoleic acid, linoleic acid, linoleic acid | 0.17 | 0.04 |
TAG33 | C50:2 | 830.8 | C18:2, C16:0, C16:0 | Linoleic acid, palmitic acid, palmitic acid | 0.19 | 0.05 |
TAGs with varying levels between IS, IR and T2DM
ID | TAG | MW | Fatty acid composition | Fatty acids identities | Comparison | Fold change | FDR p value |
---|---|---|---|---|---|---|---|
TAG16A | C46:4 | 770.7 | C18:2, C18:2, C10:0 | Linoleic acid, linoleic acid, capric acid | IS vs T2DM | − 0.62 | 0.005 |
IR vs T2DM | − 0.53 | 0.01 | |||||
TAG21 | C48:5 | 796.7 | C18:2, C18:3, C12:0 | Linoleic acid, linolenic acid, lauric acid | IR vs T2DM | − 0.39 | 0.0005 |
IS vs T2DM | − 0.38 | 0.0013 | |||||
TAG22 | C48:4 | 798.7 | C18:2, C18:2, C12:0 | Linoleic acid, linoleic acid, lauric acid | IR vs T2DM | − 0.96 | 0.002 |
TAG2A | C38:1 | 664.7 | C18:1, C16:0, C4:0 | Oleic acid, palmitic acid, butyric acid | IS vs T2DM | − 1.00 | 0.0007 |
TAG32 | C50:3 | 828.8 | C16:1, C16:1, C18:1 | Palmitoleic acid, palmitoleic acid, oleic acid | IR vs T2DM | − 0.78 | 1.37E–05 |
IS vs T2DM | − 0.76 | 5.62E–05 | |||||
TAG61 | C56:7 | 904.8 | C20:4, C18:1, C18:2 | Arachidonic acid, oleic acid, linoleic acid | IS vs T2DM | 0.81 | 0.0006 |
IR vs T2DM | 0.74 | 0.001 | |||||
TAG64 | C56:4 | 910.8 | C18:1, C18:2, C20:1 | Oleic acid, linoleic acid, gadoleic acid | IS and IR vs T2DM | 0.98 | 0.004 |
TAG65 | C56:3 | 912.8 | C20:1, C18:1, C18:1 | Gadoleic acid, oleic acid, oleic acid | IR vs T2DM | 0.51 | 0.002 |
IS vs T2DM | 0.54 | 0.002 | |||||
TAG7 | C40:2 | 690.7 | C6:0, C16:0, C18:2 | Caproic acid, palmitic acid, linoleic acid | IS vs T2DM | − 1.07 | 1.26E–05 |
IR vs T2DM | − 0.83 | 0.0002 | |||||
TAG74 | C58:7 | 934.8 | C18:6, C24:0, C16:1 | C18:6, lignoceric acid, palmitoleic acid | IS and IR vs T2DM | 0.48 | 0.007 |
TAG75 | C58:4 | 938.7 | C18:3, C24:0, C16:1 | Linolenic acid, lignoceric acid, palmitic acid | IR vs T2DM | 0.69 | 0.0005 |
IS vs T2DM | 0.73 | 0.0005 | |||||
TAG9 | C42:2 | 718.7 | C18:2, C12:0, C12:0 | Linoleic acid, lauric acid, lauric acid | IS vs T2DM | − 0.77 | 0.0008 |
IR vs T2DM | − 0.71 | 0.001 |
Compared groups | Fixed variable | Fatty acid | p value |
---|---|---|---|
IR × T2DM | SC | C12:0 | 0.045 |
SC | C18:3 | 0.048 | |
OM | C12:0 | 0.016 | |
(Full model) SC+OM | C12:0 | 0.025 | |
IS × T2DM | OM | C12:0 | 0.03 |
OM | C18:3 | 0.048 | |
SC × OM | (Full model) IS+IR+T2DM | C18.3 | 0.027 |
Correlation of TAG species with mediators of metabolic disease
Metabolic trait | R2 | Importance | TAG | MW | Fatty acid composition | Fatty acids identities |
---|---|---|---|---|---|---|
Age | 0.4 | 0.12 | C56:1 | 916.8 | C20:0, C18:0, C18:1 | Arachidic acid, stearic acid, oleic acid |
0.12 | C54:8 | 874.8 | C18:3, C18:3, C18:2 | Linolenic acid, linolenic acid, linoleic acid | ||
BMI | 0.5 | 0.12 | C57:1 | 930.8 | C17:0, C24:0, C16:1 | Heptadecanoic acid, lignoceric acid, palmitoleic acid |
0.1 | C48:1 | 804.8 | C18:0, C16:1, C14:0 | Stearic acid, palmitoleic acid, myristic acid | ||
0.09 | C54:5 | 880.8 | C18:1, C18:1, C18:3 | Oleic acid, oleic acid, linolenic acid | ||
TAG | 0.5 | 0.12 | C52:1 | 860.8 | C16:0, C18:1, C18:0 | Palmitic acid, oleic acid, stearic acid |
0.11 | C54:1 | 888.8 | C18:0, C18:0, C18:1 | Stearic acid, stearic acid, oleic acid | ||
TC | 0.4 | 0.35 | C40:2 | 690.7 | C6:0, C16:0, C18:2 | Caproic acid, palmitic acid, linoleic acid |
IL-6 | 0.6 | 0.13 | C38:1 | 664.7 | C10:0, C12:0, C16:1 | Capric acid, lauric acid, palmitoleic acid |
0.1 | C42:1 | 720.7 | C16:0, C16:1, C10:0 | Palmitic acid, palmitoleic acid, capric acid | ||
0.07 | C56:1 | 916.8 | C18:0, C18:0, C20:1 | Stearic acid, stearic acid, gadoleic | ||
HOMA-IR | 0.5 | 0.09 | C44:2 | 746.7 | C18:2, C14:0, C12:0 | Linoleic acid, myristic acid, lauric acid |
0.09 | C56:7 | 904.8 | C20:4, C18:1, C18:2 | Arachidonic acid, oleic acid, linoleic acid | ||
SC adipogenic | 0.9 | 0.16 | C58:10 | 926.8 | C18:2, C18:2, C22:6 | Linoleic acid, linoleic acid, docosahexaenoic acid |
0.16 | C56:4 | 910.8 | C18:1, C18:2, C20:1 | Oleic acid, linoleic acid, gadoleic acid | ||
0.14 | C57:4 | 924.7 | C22:0, C19:4, C16:0 | Behenic acid, C19:4, palmitic acid | ||
0.09 | C40:1 | 692.7 | C18:1, C16:0, C6:0 | Oleic acid, palmitic acid, caproic acid | ||
0.08 | C60:1 | 970.8 | C24:0, C24:0, C18:1 | Lignoceric acid, lignocerric acid, oleic acid | ||
0.22 | C38:1 | 664.7 | C18:1, C16:0, C4:0 | Oleic acid, palmitic acid, butyric acid | ||
OM adipogenic | 1 | 0.18 | C48:1 | 804.8 | C18:0, C16:1, C14:0 | Stearic acid, palmitoleic acid, myristic acid |
0.14 | C49:1 | 818.7 | C18:1, C17:0, C14:0 | Oleic acid, heptadecanoic acid, myristic acid | ||
0.11 | C56:1 | 916.8 | C18:0, C18:0, C20:1 | Stearic acid, stearic acid, gadoleic | ||
0.09 | C54:0 | 890.8 | C18:0, C18:0, C18:0 | Stearic acid, stearic acid, stearic acid, | ||
0.06 | C38:0 | 666.7 | C10:0, C14:0, C14:0 | Capric acid, myristic acid, myristic acid | ||
0.05 | C56:2 | 914.8 | C18:1, C18:1, C20:0 | Oleic acid, oleic acid, arachidic acid | ||
0.04 | C51:1 | 846.7 | C18:1, C15:0, C18:0 | Oleic acid, pentadecanoic acid, stearic acid |