Lipidomic Analysis of Liver and Adipose Tissue in a High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease Mice Model Reveals Alterations in Lipid Metabolism by Weight Loss and Aerobic Exercise
Abstract
:1. Introduction
2. Results
2.1. Animal Study
2.2. LC–TOF–MS Lipidomics Data
2.3. Hepatic Lipids Profile Reveal Alterations in Major Lipid Classes with Diet
2.3.1. Hepatic Phospholipids
2.3.2. Fatty Acids Dysregulation in Hepatic Tissue
2.3.3. Glycerolipid and Sphingomyelins Dysregulation
2.4. Visceral Adipose Tissue Triglyceride Profile
3. Discussion
4. Materials and Methods
4.1. Chemicals and Materials
4.2. Animal Study
4.3. Lipidomic Analysis
4.3.1. Liver and Visceral Adipose Tissue Extraction
4.3.2. Analytical Instrumentation and Conditions
4.3.3. Data Analysis
4.3.4. Lipids’ Annotation
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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HFD-ND | HFD-WL | HFD-WLEX | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
Lipids | p-Value | Log2FC | VIP | p-Value | Log2FC | VIP | p-Value | Log2FC | VIP | CV% |
DG 36:2 | 8.03 × 10−5 | −3.61 | 4.2 | 9.75 × 10−3 | −1.43 | 4.1 | 2.44 × 10−1 | −0.96 | 3.4 | 1.53 |
DG 36:3 | 2.55 × 10−2 | 0.27 | 6.8 | 1.00 × 100 | −0.04 | 3.6 | 7.42 × 10−2 | 0.24 | 7.2 | 0.89 |
DG 36:4 | 3.78 × 10−5 | 2.13 | 11 | 1.00 × 100 | 0.94 | 5.9 | 3.81 × 10−2 | 1.56 | 9.9 | 1.03 |
DG 38:2 | 3.24 × 10−5 | −1.81 | 4.8 | 3.12 × 10−2 | −1.31 | 5.2 | 1.63 × 10−1 | −1.17 | 4.7 | 1.79 |
DG 38:3 | 3.45 × 10−2 | −0.96 | 4.2 | 3.24 × 10−5 | −1.58 | 5.9 | 1.50 × 10−1 | −0.88 | 4.5 | 6.21 |
DG 38:4 | 5.07 × 10−4 | −1.66 | 4.3 | 3.44 × 10−3 | −1.58 | 5.1 | 1.77 × 10−1 | −0.98 | 4.1 | 2.06 |
DG 40:7 | 1.51 × 10−2 | −0.51 | 5.3 | 1.00 × 100 | −0.11 | 2.9 | 7.61 × 10−1 | −0.29 | 8.4 | 18.7 |
DG 40:8 | 2.37 × 10−5 | 5.03 | 8.0 | 3.07 × 10−1 | 3.50 | 4.5 | 5.61 × 10−2 | 4.12 | 6.2 | 18.3 |
FA 16:0 | 1.92 × 10−1 | 0.18 | 4.6 | 2.64 × 10−1 | 0.17 | 5.4 | 2.11 × 10−3 | 0.31 | 7.2 | 4.68 |
FA 16:1 | 5.85 × 10−1 | −0.23 | 3.3 | 2.55 × 10−2 | −0.60 | 6.6 | 1.00 × 100 | −0.02 | 1.1 | 3.43 |
FA 18:1 | 2.55 × 10−2 | −0.32 | 9.5 | 9.17 × 10−1 | −0.18 | 8.8 | 1.00 × 100 | −0.01 | 5.4 | 5.26 |
FA 18:2 | 8.64 × 10−4 | 0.82 | 12 | 2.85 × 10−1 | 0.53 | 11 | 4.37 × 10−3 | 0.77 | 14 | 8.73 |
FA 18:3 | 1.08 × 10−4 | 2.38 | 8.1 | 4.76 × 10−1 | 1.32 | 5.7 | 2.70 × 10−3 | 2.13 | 8.4 | 3.38 |
FA 18:4 | 1.92 × 10−4 | 3.26 | 2.5 | 4.76 × 10−1 | 2.11 | 1.8 | 1.64 × 10−3 | 3.18 | 2.7 | 3.51 |
FA 20:1 | 1.64 × 10−3 | −1.06 | 4.2 | 6.95 × 10−3 | −1.05 | 5.2 | 9.72 × 10−2 | −0.81 | 4.3 | 12.4 |
FA 20:2 | 7.57 × 10−4 | −1.27 | 3.7 | 2.30 × 10−2 | −1.06 | 4.2 | 6.16 × 10−2 | −0.94 | 3.8 | 2.78 |
FA 20:3 | 2.55 × 10−4 | −1.36 | 3.7 | 1.38 × 10−1 | −0.85 | 3.8 | 1.92 × 10−1 | −0.69 | 3.3 | 3.99 |
FA 20:5 | 5.96 × 10−5 | 2.95 | 11 | 1.77 × 10−1 | 2.07 | 9.1 | 2.82 × 10−2 | 2.56 | 11 | 2.58 |
FA 22:3 | 3.78 × 10−5 | −2.86 | 2.4 | 1.16 × 10−1 | −1.79 | 2.7 | 4.20 × 10−2 | −2.08 | 2.6 | 5.01 |
FA 22:4 | 9.75 × 10−3 | −1.03 | 3.7 | 5.61 × 10−2 | −0.96 | 4.4 | 2.30 × 10−2 | −0.95 | 4.4 | 3.68 |
FA 22:5 | 3.05 × 10−3 | 1.54 | 6.5 | 5.61 × 10−2 | 1.31 | 6.4 | 3.05 × 10−3 | 1.54 | 7.6 | 3.86 |
FA 22:6 | 7.57 × 10−4 | 0.87 | 10 | 6.76 × 10−2 | 0.63 | 10 | 6.76 × 10−2 | 0.65 | 9.9 | 2.43 |
LPC 18:0 | 1.00 × 100 | 0.60 | 2.2 | 3.12 × 10−2 | 1.07 | 5.0 | 1.00 × 100 | 0.34 | 2.2 | 4.23 |
LPC 18:2 | 8.12 × 10−2 | 1.25 | 5.2 | 6.20 × 10−3 | 1.41 | 7.2 | 2.39 × 10−3 | 1.44 | 6.5 | 3.09 |
LPC 20:4 | 1.64 × 10−3 | −1.06 | 4.2 | 3.12 × 10−2 | −0.94 | 4.5 | 1.00 × 100 | −0.44 | 2.8 | 4.30 |
LPE 18:2 | 6.20 × 10−3 | 2.13 | 2.9 | 2.30 × 10−2 | 1.85 | 3.2 | 5.61 × 10−2 | 1.77 | 2.7 | 2.68 |
PC 32:0 | 1.64 × 10−3 | 0.81 | 5.5 | 3.45 × 10−2 | 0.65 | 5.8 | 1.50 × 10−1 | 0.44 | 3.3 | 12.0 |
PC 32:1 | 2.85 × 10−1 | 0.22 | 2.5 | 1.87 × 10−2 | 0.37 | 4.4 | 4.63 × 10−2 | 0.29 | 3.3 | 4.38 |
PC 34:1 | 6.20 × 10−3 | −0.45 | 3.8 | 1.00 × 100 | −0.01 | 0.5 | 6.26 × 10−1 | −0.23 | 2.9 | 1.98 |
PC 34:2 | 1.26 × 10−5 | 0.88 | 5.5 | 7.42 × 10−2 | 0.64 | 5.5 | 1.26 × 10−1 | 0.61 | 4.9 | 2.66 |
PC 34:3 | 3.45 × 10−2 | 0.64 | 2.9 | 1.00 × 100 | −0.04 | 0.5 | 1.00 × 100 | 0.29 | 1.3 | 3.60 |
PC 36:2 | 1.12 × 10−3 | 0.87 | 4.7 | 4.91 × 10−3 | 0.85 | 5.7 | 4.13 × 10−1 | 0.55 | 3.7 | 1.63 |
PC 36:3 | 1.09 × 10−2 | 0.91 | 3.3 | 1.00 × 100 | 0.46 | 1.6 | 8.71 × 10−3 | 0.96 | 3.9 | 2.63 |
PC 36:4 | 2.03 × 10−5 | 1.99 | 4.7 | 3.45 × 10−2 | 1.30 | 3.8 | 3.57 × 10−1 | 0.98 | 2.8 | 4.42 |
PC 36:5 | 1.07 × 10−5 | 3.58 | 2.7 | 1.26 × 10−1 | 2.00 | 2.0 | 8.12 × 10−2 | 2.43 | 2.0 | 2.69 |
PC 38:3 | 2.93 × 10−4 | −1.58 | 8.0 | 1.00 × 100 | −0.24 | 3.1 | 4.20 × 10−2 | −0.89 | 6.9 | 1.50 |
PC 38:5 | 5.07 × 10−4 | −0.94 | 5.5 | 3.81 × 10−2 | −0.46 | 5.4 | 2.30 × 10−2 | −0.62 | 5.3 | 3.27 |
PC 40:5 | 6.76 × 10−2 | 1.25 | 2.8 | 8.71 × 10−3 | 1.33 | 3.3 | 1.35 × 10−2 | 1.36 | 3.4 | 3.35 |
PC 40:6 | 1.00 × 100 | 0.07 | 3.6 | 9.75 × 10−3 | 0.20 | 7.1 | 1.00 × 100 | 0.09 | 3.9 | 2.97 |
PC 40:8 | 3.12 × 10−2 | 0.96 | 5.5 | 3.05 × 10−3 | 1.09 | 7.4 | 1.51 × 10−2 | 0.99 | 6.3 | 1.27 |
PE 34:2 | 5.80 × 10−4 | 1.57 | 5.1 | 8.89 × 10−2 | 1.19 | 5.4 | 4.44 × 10−1 | 0.95 | 3.8 | 1.39 |
PE 36:2 | 3.78 × 10−5 | 1.34 | 5.2 | 1.87 × 10−2 | 1.07 | 5.4 | 2.26 × 10−1 | 0.94 | 4.7 | 1.57 |
PE 36:3 | 9.31 × 10−5 | 1.35 | 4.6 | 3.57 × 10−1 | 0.81 | 3.9 | 1.26 × 10−1 | 0.80 | 3.1 | 1.25 |
PE 36:4 | 6.92 × 10−5 | 2.26 | 11 | 9.72 × 10−2 | 2.06 | 12 | 3.45 × 10−2 | 2.07 | 11 | 0.95 |
PE 36:5 | 1.21 × 10−2 | 2.23 | 2.8 | 2.39 × 10−3 | 2.33 | 3.6 | 2.07 × 10−2 | 2.16 | 3.2 | 3.64 |
PE 38:5 | 6.68 × 10−1 | 1.05 | 2.6 | 3.86 × 10−4 | 1.64 | 4.9 | 1.35 × 10−2 | 1.32 | 3.8 | 1.08 |
PE 38:6 | 3.86 × 10−4 | 0.79 | 5.9 | 1.77 × 10−1 | 0.42 | 4.8 | 1.63 × 10−1 | 0.42 | 4.4 | 1.83 |
PE 38:7 | 9.31 × 10−5 | 1.22 | 2.8 | 3.31 × 10−1 | 0.67 | 2.1 | 1.38 × 10−1 | 0.74 | 2.1 | 1.30 |
PE 40:6 | 3.45 × 10−2 | 0.60 | 2.9 | 2.30 × 10−2 | 0.50 | 3.1 | 1.16 × 10−1 | 0.43 | 2.5 | 1.43 |
PE O-38:5 | 1.00 × 100 | −0.36 | 1.5 | 1.51 × 10−2 | −0.93 | 2.7 | 1.35 × 10−2 | −0.83 | 2.5 | 2.50 |
PI 34:2 | 2.78 × 10−5 | 1.81 | 3.5 | 9.72 × 10−2 | 1.30 | 3.4 | 6.16 × 10−2 | 1.29 | 3.2 | 4.91 |
PI 38:5 | 1.87 × 10−2 | 2.84 | 2.1 | 7.57 × 10−4 | 3.08 | 2.8 | 3.45 × 10−2 | 2.65 | 2.2 | 2.58 |
PS 38:6 | 4.43 × 10−4 | 1.70 | 3.3 | 7.13 × 10−1 | 0.77 | 2.0 | 1.00 × 100 | 0.35 | 1.2 | 2.88 |
SM 40:1;O2 | 2.55 × 10−4 | 1.48 | 4.8 | 5.10 × 10−1 | 0.79 | 3.4 | 1.00 × 100 | 0.50 | 2.5 | 4.90 |
SM 41:1;O2 | 3.44 × 10−3 | 1.20 | 4.3 | 2.70 × 10−3 | 1.25 | 5.2 | 1.63 × 10−1 | 0.98 | 3.7 | 1.00 |
SM 42:1;O2 | 2.78 × 10−5 | 1.23 | 6.7 | 2.85 × 10−1 | 0.98 | 6.6 | 1.68 × 10−2 | 1.07 | 6.6 | 6.28 |
TG 52:2 | 4.43 × 10−4 | −1.35 | 4.1 | 2.85 × 10−1 | −0.71 | 3.6 | 4.44 × 10−1 | −0.69 | 2.7 | 12.6 |
TG 52:4 | 6.20 × 10−3 | 0.53 | 4.3 | 1.00 × 100 | 0.23 | 2.3 | 2.08 × 10−1 | 0.45 | 3.9 | 1.65 |
TG 56:8 | 2.08 × 10−1 | 0.92 | 3.2 | 7.79 × 10−3 | 1.12 | 4.2 | 6.76 × 10−2 | 0.90 | 3.3 | 5.10 |
TG 56:9 | 3.24 × 10−5 | 1.63 | 3.9 | 4.13 × 10−1 | 1.00 | 2.6 | 1.38 × 10−1 | 1.24 | 3.4 | 3.78 |
HFD-ND | HFD-WL | HFD-WLex | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
Compounds | p-Values | Log2FC | VIP | p-Values | Log2FC | VIP | p-Values | Log2FC | VIP | CV% |
TG 38:1 | 1.00 × 100 | −0.01 | 0.3 | 7.44 × 10−3 | 2.87 | 2.6 | 2.60 × 10−1 | 1.19 | 1.0 | 5.13 |
TG 38:2 | 2.82 × 10−1 | 1.52 | 0.6 | 5.94 × 10−4 | 3.57 | 3.0 | 5.71 × 10−2 | 2.00 | 1.3 | 4.75 |
TG 40:1 | 1.00 × 100 | −0.01 | 0.2 | 5.17 × 10−3 | 3.04 | 2.8 | 1.87 × 10−1 | 1.42 | 0.9 | 5.77 |
TG 40:3 | 1.32 × 10−1 | 2.01 | 0.7 | 6.79 × 10−4 | 3.33 | 3.0 | 1.17 × 10−2 | 2.42 | 1.3 | 3.92 |
TG 42:2 | 1.00 × 100 | 0.43 | 0.2 | 2.74 × 10−3 | 2.93 | 2.8 | 2.27 × 10−2 | 1.89 | 1.0 | 6.83 |
TG 50:4 | 2.40 × 10−4 | 1.72 | 3.1 | 2.19 × 10−1 | 0.91 | 1.6 | 4.14 × 10−1 | 0.82 | 2.4 | 4.12 |
TG 50:5 | 4.51 × 10−5 | 3.23 | 1.2 | 1.21 × 10−1 | 1.95 | 2.6 | 2.60 × 10−1 | 1.68 | 0.8 | 6.50 |
TG 51:3 | 5.63 × 10−4 | 1.20 | 1.8 | 1.00 × 10⁰ | 0.49 | 1.2 | 5.94 × 10−1 | 0.55 | 1.4 | 5.03 |
TG 52:1 | 1.11 × 10−3 | −1.65 | 3.7 | 1.00 × 10⁰ | −0.26 | 0.9 | 9.44 × 10−1 | −0.56 | 3.6 | 3.97 |
TG 52:2 | 1.66 × 10−3 | −0.90 | 8.1 | 1.00 × 10⁰ | −0.17 | 0.8 | 1.00 × 100 | −0.14 | 5.7 | 2.40 |
TG 52:4 | 3.20 × 10−4 | 1.42 | 8.0 | 8.20 × 10−1 | 0.49 | 1.2 | 7.78 × 10−1 | 0.57 | 5.7 | 4.88 |
TG 52:5 | 3.29 × 10−5 | 2.33 | 4.6 | 1.45 × 10−1 | 1.07 | 1.7 | 3.56 × 10−1 | 0.95 | 2.8 | 4.21 |
TG 52:6 | 1.14 × 10−4 | 3.48 | 1.6 | 1.91 × 10−1 | 1.78 | 2.5 | 3.10 × 10−1 | 1.63 | 1.1 | 9.23 |
TG 53:4 | 8.51 × 10−4 | 1.28 | 1.6 | 1.00 × 10⁰ | 0.34 | 1.1 | 6.36 × 10−1 | 0.59 | 1.2 | 4.42 |
TG 54:2 | 1.66 × 10−3 | −2.04 | 5.3 | 1.00 × 10⁰ | −0.50 | 1.0 | 1.00 × 100 | −0.33 | 4.3 | 4.06 |
TG 54:3 | 3.12 × 10−2 | −1.42 | 8.9 | 1.00 × 10⁰ | −0.13 | 0.7 | 1.00 × 100 | 0.21 | 5.6 | 2.94 |
TG 54:4 | 2.02 × 10−5 | 2.22 | 1.6 | 2.43 × 10−1 | 1.09 | 1.7 | 1.11 × 10−1 | 1.19 | 1.4 | 3.68 |
TG 54:5 | 1.14 × 10−4 | 1.84 | 7.2 | 1.00 × 10⁰ | 0.48 | 1.1 | 2.03 × 10−1 | 0.80 | 5.2 | 3.41 |
TG 54:6 | 2.02 × 10−5 | 2.98 | 4.5 | 1.84 × 10−1 | 1.28 | 1.8 | 1.44 × 10−1 | 1.32 | 3.0 | 4.10 |
TG 54:7 | 7.18 × 10−5 | 4.84 | 1.8 | 2.09 × 10−1 | 2.61 | 2.9 | 2.62 × 10−1 | 2.44 | 1.1 | 10.2 |
TG 56:2 | 2.81 × 10−2 | −1.05 | 1.9 | 1.00 × 10⁰ | −0.06 | 0.6 | 1.00 × 100 | 0.07 | 1.1 | 3.19 |
TG 56:3 | 2.38 × 10−5 | 2.63 | 2.2 | 1.99 × 10−1 | 1.22 | 1.8 | 1.72 × 10−1 | 1.24 | 1.6 | 3.54 |
TG 56:4 | 1.66 × 10−3 | 0.95 | 1.6 | 6.35 × 10−1 | 0.55 | 1.1 | 1.21 × 10−1 | 0.70 | 1.9 | 3.21 |
TG 56:5 | 2.44 × 10−3 | 1.81 | 1.5 | 8.91 × 10−1 | 1.06 | 1.4 | 1.72 × 10−1 | 1.48 | 1.9 | 6.52 |
TG 56:6 | 2.38 × 10−5 | 2.63 | 2.2 | 1.99 × 10−1 | 1.22 | 1.8 | 1.72 × 10−1 | 1.24 | 1.6 | 3.54 |
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Mouskeftara, T.; Deda, O.; Papadopoulos, G.; Chatzigeorgiou, A.; Gika, H. Lipidomic Analysis of Liver and Adipose Tissue in a High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease Mice Model Reveals Alterations in Lipid Metabolism by Weight Loss and Aerobic Exercise. Molecules 2024, 29, 1494. https://doi.org/10.3390/molecules29071494
Mouskeftara T, Deda O, Papadopoulos G, Chatzigeorgiou A, Gika H. Lipidomic Analysis of Liver and Adipose Tissue in a High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease Mice Model Reveals Alterations in Lipid Metabolism by Weight Loss and Aerobic Exercise. Molecules. 2024; 29(7):1494. https://doi.org/10.3390/molecules29071494
Chicago/Turabian StyleMouskeftara, Thomai, Olga Deda, Grigorios Papadopoulos, Antonios Chatzigeorgiou, and Helen Gika. 2024. "Lipidomic Analysis of Liver and Adipose Tissue in a High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease Mice Model Reveals Alterations in Lipid Metabolism by Weight Loss and Aerobic Exercise" Molecules 29, no. 7: 1494. https://doi.org/10.3390/molecules29071494
APA StyleMouskeftara, T., Deda, O., Papadopoulos, G., Chatzigeorgiou, A., & Gika, H. (2024). Lipidomic Analysis of Liver and Adipose Tissue in a High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease Mice Model Reveals Alterations in Lipid Metabolism by Weight Loss and Aerobic Exercise. Molecules, 29(7), 1494. https://doi.org/10.3390/molecules29071494