Visceral Adipose Tissue E2F1-miRNA206/210 Pathway Associates with Type 2 Diabetes in Humans with Extreme Obesity
Abstract
:1. Introduction
2. Methods
2.1. Human Cohorts and VAT Samples
2.2. Cohorts Assembly
2.3. miRNA Extraction and Quantification and Nanostring©
2.4. Cellular Studies
2.5. E2F1 Chip-Seq Data Collection from Public Databases
2.6. Statistical Analyses
3. Results
3.1. E2F1-miRNA Associations in VAT Are Distinct from the E2F1-miRNA Cancer-Associated Co-Regulation Network
3.2. E2F1-Associated Changes in miRNA Expression Are Validated in an Independent Patient Population with Extreme Obesity
3.3. E2F1 Regulation of miRNA-206 and miRNA-210-5p Expression
3.4. miRNA-206 and miRNA-210-5p Expression in VAT May Link High VAT-E2F1 T2DM in Patients with Severe Obesity
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
VAT | visceral adipose tissue |
BMI | body mass index |
FFA | free fatty acids |
FPG | fasting plasma glucose |
FPI | fasting plasma insulin |
DE | differentially expressed |
FC | fold change |
W/ | with |
W/O | without |
CDK1 | cyclin dependent kinase 1 |
ChIP | chromatin immunoprecipitation |
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Cohort 1- Beer-Sheva, Israel | ||||
---|---|---|---|---|
(Group #1) w/o Obesity | (Group #2) w/ Obesity, Low E2F1 | (Group #3) w/ Obesity, High E2F1 | p-Value | |
n | 8 | 8 | 8 | |
Age (years) | 40.1 ± 11 | 41.2 ± 12 | 40.2 ± 17 | ns, 0.95 |
Sex (M:F ratio) | 3:5 | 3:5 | 3:5 | |
BMI (kg/m2) | 23 ± 3 | 40.5 ± 6 | 41.5 ± 5 | *, #, 0.0004 |
FPG (mg/dL) | 98.1 ± 22 | 105.2 ± 36 | 81.6 ± 11 | ns, 0.2571 |
TG (mg/dL) | 140.6 ± 77 | 172.6 ± 54 | 157.9 ± 80 | ns, 0.6034 |
LDL (mg/dL) | 101 ± 29 | 113.2 ± 19 | 119.7 ± 13 | ns, 0.3491 |
HDL (mg/dL) | 36.7 ± 17 | 40.7 ± 8 | 42.4 ± 9 | ns, 0.5073 |
Diabetes (T2DM) (yes/no) | 0/8 | 1/7 | 0/8 |
Cohort 2- Leipzig, Germany | |||
---|---|---|---|
(Group #1) w/ Extreme Obesity, Low E2F1, w/o T2DM | (Group #2) w/ Extreme Obesity, High E2F1, w/ T2DM | p-Value | |
n | 10 | 10 | |
Age (years) | 50.2 ± 8 | 50.3 ± 8 | ns, 0.4802 |
Sex (M:F ratio) | 5:5 | 5:5 | |
BMI (kg/m2) | 62.1 ± 7 | 62.8 ± 8 | ns, 0.4631 |
FPG (mg/dL) | 110.2 ± 9 | 129.3 ± 35 | *, 0.0019 |
TG (mg/dL) | 101.2 ± 30 | 154.7 ± 49 | *, 0.0276 |
LDL (mg/dL) | 129.5 ± 15 | 99.9 ± 50 | ns, 0.1518 |
HDL (mg/dL) | 52.9 ± 4 | 44.7 ± 23 | ns, 0.0939 |
Diabetes (T2DM) (yes/no) | 0/10 | 10/0 |
Cohort 1- Beer-Sheva, Israel | ||||
---|---|---|---|---|
miRNA-206 | miRNA-210-5p | |||
Pv | rp | Pv | rp | |
FPG | 0.409 | 0.049 | 0.267 | −0.133 |
FPI | NA | NA | NA | NA |
TG | 0.227 | −0.160 | 0.053 | −0.338 |
LDL | 0.208 | −0.187 | 0.065 | 0.340 |
HDL | 0.159 | 0.218 | 0.171 | 0.207 |
Cohort 2- Leipzig, Germany | ||||
---|---|---|---|---|
miRNA-206 | miRNA-210-5p | |||
Pv | rp | Pv | rp | |
FPG | 0.004 | 0.604 | 0.048 | 0.402 |
FPI | 0.180 | 0.229 | 0.035 | 0.435 |
TG | 0.058 | 0.424 | 0.222 | 0.213 |
LDL | 0.143 | −0.284 | −0.214 | −0.231 |
HDL | 0.128 | −0.326 | 0.062 | −0.431 |
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Maixner, N.; Haim, Y.; Blüher, M.; Chalifa-Caspi, V.; Veksler-Lublinsky, I.; Makarenkov, N.; Yoel, U.; Bashan, N.; Liberty, I.F.; Kukeev, I.; et al. Visceral Adipose Tissue E2F1-miRNA206/210 Pathway Associates with Type 2 Diabetes in Humans with Extreme Obesity. Cells 2022, 11, 3046. https://doi.org/10.3390/cells11193046
Maixner N, Haim Y, Blüher M, Chalifa-Caspi V, Veksler-Lublinsky I, Makarenkov N, Yoel U, Bashan N, Liberty IF, Kukeev I, et al. Visceral Adipose Tissue E2F1-miRNA206/210 Pathway Associates with Type 2 Diabetes in Humans with Extreme Obesity. Cells. 2022; 11(19):3046. https://doi.org/10.3390/cells11193046
Chicago/Turabian StyleMaixner, Nitzan, Yulia Haim, Matthias Blüher, Vered Chalifa-Caspi, Isana Veksler-Lublinsky, Nataly Makarenkov, Uri Yoel, Nava Bashan, Idit F. Liberty, Ivan Kukeev, and et al. 2022. "Visceral Adipose Tissue E2F1-miRNA206/210 Pathway Associates with Type 2 Diabetes in Humans with Extreme Obesity" Cells 11, no. 19: 3046. https://doi.org/10.3390/cells11193046
APA StyleMaixner, N., Haim, Y., Blüher, M., Chalifa-Caspi, V., Veksler-Lublinsky, I., Makarenkov, N., Yoel, U., Bashan, N., Liberty, I. F., Kukeev, I., Dukhno, O., Levy, D., & Rudich, A. (2022). Visceral Adipose Tissue E2F1-miRNA206/210 Pathway Associates with Type 2 Diabetes in Humans with Extreme Obesity. Cells, 11(19), 3046. https://doi.org/10.3390/cells11193046