Adverse Effects of Methylglyoxal on Transcriptome and Metabolic Changes in Visceral Adipose Tissue in a Prediabetic Rat Model
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animals and Diet
2.2. Biochemical Analysis
2.3. Basal and Insulin-Stimulated Glucose Utilisation in Adipose Tissue and Lipolysis
2.4. Fatty Acid Composition
2.5. Transcriptome and Gene Expression Profiling
2.6. Histological Methods
2.7. Statistical and Pathway Analysis
3. Results
3.1. Effects of Methylglyoxal on Insulin Sensitivity and Lipolysis
3.2. Effects of Methylglyoxal on Fatty Acid Composition of Phospholipids in Visceral Adipose Tissue
3.3. Effects of meThylglyoxal on Dicarbonyl Stress and Inflammatory and Hypoxic Parameters
3.4. Effects of Methylglyoxal on the Visceral Adipose Tissue Transcriptome
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
AGEs: | advanced glycation end products; |
DHA: | docosahexaenoic acid; |
EPA: | eicosapentaenoic acid; |
ERK: | extracellular signal-regulated kinase; |
Glo-1: | glyoxalase 1; |
HIF1: | hypoxia-inducible factor 1; |
IL-6: | interleukin-6; |
IRS-1: | insulin receptor substrate 1; |
JNK: | c-Jun terminal kinases; |
MAPK: | mitogen-activated protein kinase; |
MCP-1: | monocyte chemoattractant protein-1; |
MG: | methylglyoxal; |
NFκB: | nuclear factor κB; |
NRF2: | nuclear factor-erythroid 2-related factor-2; |
PAS: | period acid-Schiff; |
PKC: | protein kinase C; |
RAGE: | receptor for advanced glycation endproducts; |
ROS: | reactive oxygen species; |
SAPK: | stress-activated protein kinases; |
SREBP: | sterol regulatory element-binding protein; |
T2D: | type 2 diabetes; |
TLR4: | tool-like receptor 4; |
TNFα: | tumor necrosis factor α; |
WAT: | white adipose tissue |
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HHTg | HHTg + MG | p ˂ | |
---|---|---|---|
body weight (g) | 402 ± 22 | 381 ± 8 | n.s. |
adiposity (g/100g bwt) | 1.85 ± 0.29 | 1.87 ± 0.35 | n.s. |
non-fasting glucose (mmol/L) | 7.7 ± 0.3 | 8.6 ± 0.24 | 0.01 |
insulin (nmol/L) | 0.24 ± 0.08 | 0.42 ± 0.05 | 0.05 |
serum triglycerides (mmol/l) | 4.34 ± 0.74 | 3.21 ± 1.24 | n.s. |
methylglyoxal in serum (nmol/mL) | 0.25 ± 0.03 | 0.37 ± 0.03 | 0.01 |
methylglyoxal in adipose tissue (nmol/mg) | 0.63 ± 0.09 | 0.86 ± 0.13 | 0.05 |
HMW adiponectin (μg/mL) | 2.90 ± 0.96 | 2.78 ± 1.14 | n.s. |
leptin (ng/mL) | 2.15 ± 1.07 | 2.13 ± 1.42 | n.s. |
IL-6 (pg/mL) | 87.2 ± 21.78 | 99.9 ± 11.78 | n.s. |
MCP-1 (ng/mL) | 85.25 ± 40.20 | 124.88 ± 29.65 | 0.05 |
TNFα (pg/mL) | 0.78 ± 0.04 | 2.11 ± 0.33 | 0.05 |
HHTg | HHTg + MG | p ˂ | |
---|---|---|---|
% of total fatty acids | % of total fatty acids | ||
14:00 | 0.40 ± 0.18 | 0.76 ± 0.29 | 0.02 |
16:00 | 16.68 ± 5.14 | 24.05 ± 4.01 | 0.02 |
18:2n6 | 19.60 ± 1.85 | 23.17 ± 1.51 | 0.01 |
20:4n6 | 9.36 ± 2.39 | 10.76 ± 2.08 | n.s. |
18:3n3 | 3.24 ± 0.96 | 2.12 ± 0.40 | 0.05 |
20:5n3 | 0.91 ± 0.21 | 0.44 ± 0.14 | 0.01 |
22:6n3 | 13.15 ± 2.57 | 5.57 ± 1.35 | 0.001 |
SFA | 33.35 ± 3.82 | 39.92 ± 2.96 | 0.01 |
PUFA n6 | 31.44 ± 3.89 | 35.59 ± 3.08 | n.s. |
PUFA n3 | 18.42 ± 2.37 | 8.80 ± 1.50 | 0.001 |
Anti-inflammatory index | 171.20 ± 32.54 | 65.87 ± 14.46 | 0.001 |
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Hüttl, M.; Markova, I.; Miklankova, D.; Makovicky, P.; Pelikanova, T.; Šeda, O.; Šedová, L.; Malinska, H. Adverse Effects of Methylglyoxal on Transcriptome and Metabolic Changes in Visceral Adipose Tissue in a Prediabetic Rat Model. Antioxidants 2020, 9, 803. https://doi.org/10.3390/antiox9090803
Hüttl M, Markova I, Miklankova D, Makovicky P, Pelikanova T, Šeda O, Šedová L, Malinska H. Adverse Effects of Methylglyoxal on Transcriptome and Metabolic Changes in Visceral Adipose Tissue in a Prediabetic Rat Model. Antioxidants. 2020; 9(9):803. https://doi.org/10.3390/antiox9090803
Chicago/Turabian StyleHüttl, Martina, Irena Markova, Denisa Miklankova, Pavol Makovicky, Terezie Pelikanova, Ondrej Šeda, Lucie Šedová, and Hana Malinska. 2020. "Adverse Effects of Methylglyoxal on Transcriptome and Metabolic Changes in Visceral Adipose Tissue in a Prediabetic Rat Model" Antioxidants 9, no. 9: 803. https://doi.org/10.3390/antiox9090803