-Surupa Chakraborty, Amity University Kolkata
Adipose tissue (AT) is an active endocrine organ which stores excess nutrients as triacylglycerols and releases fatty acids during fasting. It is populated by several immune cells including T cells and macrophages, which help in secretion of a variety of adipokines and chemokines. A cardinal feature of obesity includes the activation of inflammatory markers, which induces the release of free fatty acids from triglyceride depots during lipolysis, thereby promoting the proinflammatory macrophage infiltration and activation.
Several studies showed that proinflammatory adipokines moderates insulin resistance either by directly affecting the insulin signalling pathway or indirectly by stimulation of inflammatory pathways like c-Jun N-terminal kinase (JNK) and I-kappa B kinase β (IKKβ)/NFκB pathway. Shihab Kochumon et al., recently revealed that AT-IL-2, a potent pleiotropic cytokine plays a significant role in obesity-mediated chronic low-grade inflammation, also known as, meta-inflammation, which in turn is characterized by elevated plasma levels of systemic inflammatory C-reactive protein (CRP) and adipokines like interleukin IL-1, IL-1β, IL-6, IL-12 and tumour necrosis factor (TNF- α).
IL-2 and inflammatory markers, present on subcutaneous adipose tissue (AT) samples were collected from 56 (lean/overweight/obese) individuals and quantified by qRT-PCR and immunohistochemistry. CRP levels were measured by ELISA. Immunohistochemistry (IHC) data (P=0.0032 in obese individuals, P= 0.0001 in lean individuals) and qRT-PCR analysis revealed an increase of IL-2 transcripts in mRNA extracts obtained from overweight people and a significant spike in its levels in obese people (p=0.021), compared to that obtained from lean controls.
IL-2 gene expression was analysed in obese individuals and distinct segregation of two clusters above and below the threshold of 6.7-fold changes was observed. The two diverse clusters revealed variable associations with several clinical markers. The further analysis detected positive correlations between IL-2 gene expression and various inflammatory mediators like TLRs in the AT which was extended to include the downstream effectors of the TLR signalling pathways.
Moreover, in the obese cohort, both fasting blood glucose (FBG) and glycated hemoglobin (Hb1Ac) showed a strong positive correlation with IL-2 transcript levels in individuals with high AT-IL-2 gene expression. Based on this intensive research analysis, it can be summarised that obesity parallels with elevated AT-IL-2 expression which might serve as a necessary hallmark or a potent biomarker for the progression for metabolic inflammation and insulin resistance.
Source:
- Elevated adipose tissue-associated IL-2 expression in obesity correlates with metabolic inflammation and insulin resistance. Shihab Kochumon1,6, AshrafAl Madhoun2,3,6, FatemaAl-Rashed1,4, ReebyThomas1 , Sardar Sindhu2 , EbaaAl-Ozairi5 , FahdAl-Mulla3 & RasheedAhmad1, (2020), Nature, 10:16364, https://doi.org/10.1038/s41598-020-73347-y
- Adipose tissue gene expression of CXCL10 and CXCL11 modulates inflammatory markers in obesity: implications for metabolic inflammation and insulin resistance. Shihab Kochumon1,6, AshrafAl Madhoun2,3,6, FatemaAl-Rashed1,4, ReebyThomas1 , Sardar Sindhu2 , EbaaAl-Ozairi5 , FahdAl-Mulla3 , RasheedAhmad1 & Rafaat Azim, (2020), Therapeutic Advances in Endocrinology and Metabolism, Vol. 11: 1–11, https://doi.org/10.1177/20420188209309
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Nicely explained.