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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3224-3244 |
| Number of pages | 21 |
| Journal | American Journal of Translational Research |
| Volume | 9 |
| Issue number | 7 |
| State | Published - 2017 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Medicine(all)
- Molecular Medicine
- Clinical Biochemistry
- Cancer Research
Cite this
Significant association of TREM-1 with HMGB1, TLRs and RAGE in the pathogenesis of insulin resistance in obese diabetic populations. / Subramanian, Saravanan; Pallati, Pradeep K.; Sharma, Poonam K; Agrawal, Devendra K.; Nandipati, Kalyana C.
In: American Journal of Translational Research, Vol. 9, No. 7, 2017, p. 3224-3244.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Significant association of TREM-1 with HMGB1, TLRs and RAGE in the pathogenesis of insulin resistance in obese diabetic populations
AU - Subramanian, Saravanan
AU - Pallati, Pradeep K.
AU - Sharma, Poonam K
AU - Agrawal, Devendra K.
AU - Nandipati, Kalyana C.
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85025590015&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85025590015&partnerID=8YFLogxK
M3 - Article
VL - 9
SP - 3224
EP - 3244
JO - American Journal of Translational Research
JF - American Journal of Translational Research
SN - 1943-8141
IS - 7
ER -