Saravanan Subramanian, PhD, Turna Mukherjee, Pradeep K Pallati, MD, Poonam Sharma, MD, Devendra Agrawal, PhD, Kalyana C Nandipati, MD. Creighton University School of Medicine
Introduction: Adipocyte induced pro-inflammatory cytokines and chemokines activates pathogenic inflammatory cells receptors and stimulates inflammatory signalling pathways that result in obesity induced insulin resistance. However, exact role of cell surface receptors and intracellular targets in inducing insulin resistance is unknown.
Methods and Procedures: We examined the mRNA expression by RT-PCR and protein expression by immunofluorescence for inflammatory mediators and receptors (TREM-1, TREM-2, DAP-12, HMGB-1, RAGE, TLRs) and total and phosphorylated intracellular signalling targets (p65 NFκB, IκB-α, JNK-1, PKCs and IRS-1) in omentum, subcutaneous and liver biopsy of obese diabetic (n=22) and non-diabetic subjects (n=24) and compared with non-obese non-diabetic controls (n=5).
Results: Obese diabetics showed significantly (P<0.05) increased expression levels of inflammatory cell receptors (TREM-1, DAP-12, HMGB-1, RAGE, TLR-4, TLR-2) and inflammatory signalling pathways (NFκB p65, p- NFκB p65, p-IκB-α, JNK-1, p-JNK-1, p-sIRS1, PKC-θ, δ and ε) in omentum, subcutaneous and liver biopsy tissues compared to obese non-diabetics. We also found a significant (P<0.05) decrease in TREM-2, IκB-α, IRS-1 and p-yIRS1 expression in obese diabetic subjects compared to obese non-diabetics (Table).
Conclusions: Obese diabetic patients had significantly increased levels of inflammatory receptors and inflammatory signalling cascades compared to obese non-diabetics and non-obese subjects. The cell surface targets like TREM-1 and TLRs can be a potential targets for developing therapeutic strategies to prevent insulin resistance.
Table. Expression of inflammatory cell receptors and inflammatory signalling pathways in obese non-diabetics (OND; N=24) and obese diabetics (OD; N=22) compared to non-obese subjects.
|OND n(%)||OD n(%)||R; P value||OND n(%)||OD (%)||R; P value||OND n(%)||OD n(%)||R; P value|
|TREM1||22; 91.7%||22; 100%||NS||13; 54.2%||17; 77.3%||NS||12; 50%||22; 100%||R=0.569 P<0.0001|
|TLR4||23; 95.8%||22; 100%||NS||13; 54.2%||17; 77.3%||NS||7; 29.2%||22; 100%||R=0.733; p<0.0001|
|NFkB p65||22; 91.7%||22; 100%||NS||13; 54.2%||17; 77.3%||NS||12; 50%||22; 100%||R=0.569 P<0.0001|
|JNK||23; 95.8%||22; 100%||NS||13; 54.2%||17; 77.3%||NS||12; 50%||22; 100%||R=0.569 P<0.0001|
Presented at the SAGES 2017 Annual Meeting in Houston, TX.
Abstract ID: 79145
Program Number: P083
Presentation Session: Poster (Non CME)
Presentation Type: Poster