Enhanced Adipose Expression of Interferon Regulatory Factor (IRF)-5 Associates with the Signatures of Metabolic Inflammation in Diabetic Obese Patients
Abstract
:1. Introduction
2. Materials and Methods
2.1. Subjects, Anthropometric Measurements, and Clinical Assays
2.2. Anthropometry and Clinical Assays
2.3. Collection of Adipose Tissue Biopsies
2.4. Multiplex Quantitative Real-Time Reverse-Transcription Polymerase Chain Reaction (qRT-PCR)
2.5. Immunohistochemistry (IHC)
2.6. Confocal Microscopy (CM)
2.7. Statistical Analysis
3. Results
3.1. Increased Adipose Tissue IRF5 Expression in Diabetic Obese Patients
3.2. Elevated Adipose TNF-α Protein Expression in Diabetic Obese Patients Conforms with IRF5 Expression
3.3. CXCL8 Expression in Diabetic Obese Individuals Associates Positively with IRF5 Expression in the Adipose Tissue
3.4. Increased Adipose CCL2 Protein Expression in Diabetic Obese Patients
3.5. Relationship of IRF5 Gene Expression with Metabolic Markers and Inflammatory Signature in the Adipose Tissue
4. Discussion
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
AP-1 | Activator protein-1 |
ATMs | Adipose tissue macrophages |
AU | Arbitrary unit |
BMI | Body mass index |
CM | Confocal microscopy |
CRP | C-reactive protein |
DAB | 3,3ʹ-diaminobenzidine |
DAPI | 4’,6-diamidino-2-phenylindole |
FAM | 6-fluorescein amidite |
GAPDH | Glyceraldehyde 3-phosphate dehydrogenase |
HbA1c | Hemoglobin A1c |
IHC | Immunohistochemistry |
IRAK-1 | Interleukin-1 receptor-associated kinase-1 |
IRFs | Interferon regulatory factors |
MAPKs | Mitogen-activated protein kinases |
MGB | Minor groove binder |
NFQ | Non-fluorescent quencher |
PBF | Percent body fat |
qRT-PCR | Quantitative real-time reverse-transcription polymerase chain reaction |
T2D | Type-2 diabetes |
WAT | White adipose tissue |
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Parameter | Diabetic Lean/Overweight | Diabetic Obese |
---|---|---|
Total number (N) | 11 (7 male, 4 female) | 35 (19 male, 16 female) |
Age (Yrs.) | 53.43 ± 1.15 | 52.34 ± 1.70 |
Body mass index (BMI) (kg/m2) | 27.55 ± 0.46 | 33.83 ± 0.42 |
Body fat (%) | 31.88 ± 1.61 | 37.59 ± 0.97 |
Fasting plasma glucose (mmol/L) | 8.28 ± 0.67 | 8.74 ± 0.50 |
Fasting plasma insulin (mIU/L) | 24.63 ± 8.13 | 25.68 ± 4.37 |
Homeostatic model assessment of insulin resistance (HOMA-IR) (Glucose×Insulin/22.5) | 5.47 ± 1.82 | 9.25 ± 1.49 |
Glycated hemoglobin (HbA1c) (%) | 7.53 ± 0.51 | 8.24 ± 0.24 |
C-reactive protein (CRP) (pg/mL) | 6.41 ± 1.19 | 5.46 ± 0.78 |
Total cholesterol (mmol/L) | 4.80 ± 0.48 | 4.99 ± 0.20 |
HDL (mmol/L) | 1.11 ± 0.10 | 1.18 ± 0.05 |
LDL (mmol/L) | 2.89 ± 0.40 | 2.93 ± 0.19 |
Triglycerides (mmol/L) | 1.76 ± 0.25 | 1.84 ± 0.24 |
Hypertension (N) | 4 | 17 |
Hyperlipidemia (N) | 2 | 6 |
Therapy | Metformin, Lipitor, Diamicron, Zocor, NovoRapid, Concor, Insulin, Aldomet, Lantus, Diovan | Metformin, Lipitor, Diamicron, Lantus, NovoRapid, Concor, Insulin, Aldomet, Tenormin, Zestril |
Marker Type | Diabetic Lean/Overweight | Diabetic Obese |
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Clinical/metabolic markers |
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Inflammatory cytokines/chemokines or chemokine receptors |
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Monocyte/macrophage markers |
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TLR/non-TLR innate immune markers |
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TLR-associated signaling molecules and transcription factors |
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Sindhu, S.; Kochumon, S.; Thomas, R.; Bennakhi, A.; Al-Mulla, F.; Ahmad, R. Enhanced Adipose Expression of Interferon Regulatory Factor (IRF)-5 Associates with the Signatures of Metabolic Inflammation in Diabetic Obese Patients. Cells 2020, 9, 730. https://doi.org/10.3390/cells9030730
Sindhu S, Kochumon S, Thomas R, Bennakhi A, Al-Mulla F, Ahmad R. Enhanced Adipose Expression of Interferon Regulatory Factor (IRF)-5 Associates with the Signatures of Metabolic Inflammation in Diabetic Obese Patients. Cells. 2020; 9(3):730. https://doi.org/10.3390/cells9030730
Chicago/Turabian StyleSindhu, Sardar, Shihab Kochumon, Reeby Thomas, Abdullah Bennakhi, Fahd Al-Mulla, and Rasheed Ahmad. 2020. "Enhanced Adipose Expression of Interferon Regulatory Factor (IRF)-5 Associates with the Signatures of Metabolic Inflammation in Diabetic Obese Patients" Cells 9, no. 3: 730. https://doi.org/10.3390/cells9030730
APA StyleSindhu, S., Kochumon, S., Thomas, R., Bennakhi, A., Al-Mulla, F., & Ahmad, R. (2020). Enhanced Adipose Expression of Interferon Regulatory Factor (IRF)-5 Associates with the Signatures of Metabolic Inflammation in Diabetic Obese Patients. Cells, 9(3), 730. https://doi.org/10.3390/cells9030730