[HTML][HTML] Significant association of TREM-1 with HMGB1, TLRs and RAGE in the pathogenesis of insulin resistance in obese diabetic populations

S Subramanian, PK Pallati, P Sharma… - American journal of …, 2017 - ncbi.nlm.nih.gov
American journal of translational research, 2017ncbi.nlm.nih.gov
Activated cell surface and intracellular receptors lead to insulin resistance in obesity. Among
these receptors, triggering receptors expressed on myeloid cells (TREM)-1, toll like
receptors (TLRs), and receptors for advanced glycation end products (RAGE) play a
significant role in the induction of inflammatory response in innate immunity. TREM-1
potentially amplifies TLRs and RAGE synergistically with DNA-binding high-mobility group
box 1 (HMGB-1). The objective of the study was to analyze the association between TREM …
Abstract
Activated cell surface and intracellular receptors lead to insulin resistance in obesity. Among these receptors, triggering receptors expressed on myeloid cells (TREM)-1, toll like receptors (TLRs), and receptors for advanced glycation end products (RAGE) play a significant role in the induction of inflammatory response in innate immunity. TREM-1 potentially amplifies TLRs and RAGE synergistically with DNA-binding high-mobility group box 1 (HMGB-1). The objective of the study was to analyze the association between TREM-1/DAP12 and HMGB-1, RAGE and TLRs in obesity-induced insulin resistance. We examined the mRNA expression by RT-PCR and protein expression by Western blotting and immunofluorescence for TREM-1, TREM-2, DAP-12, HMGB-1, RAGE, TLR-4 and TLR-2 in omentum, subcutaneous and liver biopsy tissues of obese diabetic (n= 22) and non-diabetic subjects (n= 24) and compared with the non-obese non-diabetic controls (n= 5). There was a significantly increased expression of TREM-1, DAP-12, HMGB-1, RAGE, TLR-4 and TLR-2 and decreased expression of TREM-2 in the omentum, subcutaneous and liver biopsy of obese diabetic subjects compared to obese non-diabetics and the non-obese population. Overall, obese diabetic subjects had high expression of TREM-1 in association with HMGB1 (100% vs 58.3%, P= 0.003), RAGE (77.3% vs 41.7%, P= 0.045), TLR4 (100% vs 58.3%, P= 0.003), and TLR2 (100% vs 50%, P= 0.003) in liver biopsy samples in comparison to obese non-diabetic subjects. Obese diabetics have significantly increased TREM-1, HMGB1, RAGE, and TLRs compared to obese non-diabetics. Our findings suggest a potential pathophysiological role of TREM-1 in conjunction with HMGB1 and inflammatory cell receptors (RAGE, TLR-4 and TLR-2) in obesity-induced insulin resistance.
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