Abstract
Interferon regulatory factor (IRF)-5 is known to be involved in M1 macrophage polarization, however, changes in the adipose expression of IRF5 in obesity and their relationship with the local expression of proinflammatory cytokines/chemokines are unknown. Therefore, IRF5 gene expression was determined in the subcutaneous adipose tissue samples from 53 non-diabetic individuals (6 lean, 18 overweight, and 29 obese), using real-time RT-PCR. IRF5 protein expression was also assessed using immunohistochemistry and/or confocal microscopy. Adipose gene expression of signature immune metabolic markers was also determined and compared with adipose IRF5 gene expression. Systemic levels of C-reactive protein and adiponectin were measured by ELISA. The data show that adipose IRF5 gene (P = 0.008) and protein (P = 0.004) expression was upregulated in obese compared with lean individuals. IRF5 expression changes correlated positively with body mass index (BMI; r = 0.37/P = 0.008) and body fat percentage (r = 0.51/P = 0.0004). In obese, IRF5 changes associated positively with HbA1c (r = 0.41/P = 0.02). A good agreement was found between gene and protein expression of IRF5 in obese subjects (r = 0.65/P = 0.001). IRF5 gene expression associated positively with adipose inflammatory signatures including local expression of TNF-α, IL-6, CXCL8, CCL-2/5, IL-1β, IL-18, CXCL-9/10, CCL7, CCR-1/2/5, TLR-2/7/8/9, IRF3, MyD88, IRAK-1, and inflammatory macrophage markers (P < 0.05). Interestingly, IRF5 gene expression correlated positively with CRP (r = 0.37, P = 0.03) and negatively with adiponectin levels (r = −0.43, P = 0.009). In conclusion, elevated adipose IRF5 expression in obesity concurs with the typical inflammatory signatures, locally and systemically. Hence, the IRF5 upregulation may represent a novel adipose tissue marker for metabolic inflammation.
Highlights
Obesity and related comorbidities, such as hypertension, cardiovascular disease, insulin resistance, and type-2 diabetes (T2D), are associated with the presence of chronic low-grade inflammation called metabolic inflammation or metaflammation
Our data show that interferon regulatory factor-5 (IRF5) gene expression was significantly upregulated in overweight (P = 0.05) and obese (P = 0.008) individuals compared with lean (Figure 1A)
We report for the first time to our knowledge, that the adipose tissue expression of the transcription regulator
Summary
Obesity and related comorbidities, such as hypertension, cardiovascular disease, insulin resistance, and type-2 diabetes (T2D), are associated with the presence of chronic low-grade inflammation called metabolic inflammation or metaflammation. Obese individuals show both the subcutaneous and intra-abdominal (visceral) fat deposition and the changes occurring in the expanding adipose tissue compartment are pivotal to metabolic inflammation and development of insulin resistance. Regarding proinflammatory cytokines/chemokines that are considered as critical biomarkers of adipose inflammation, TNF-α is a potent proinflammatory cytokine which is secreted by macrophages and adipocytes, especially by visceral adipose tissue This cytokine is directly involved in insulin and glucose metabolism, induces insulin resistance and stimulates lipolysis [3]. IL-6 is another proinflammatory cytokine which is predominantly secreted by adipocytes, in addition to macrophages, T cells, endothelial cells, fibroblasts, and skeletal muscle
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.