TREM-1 associated macrophage polarization plays a significant role in inducing insulin resistance in obese population

Background: TREM-1 acts as an amplifier of inflammation expressed on macrophages. The objective of this study was to evaluate the relationship between TREM-1 and macrophage polarization, and association of TREM-1 and M1 macrophage polarization with insulin resistance (IR) in obese population compared to non-obese population. Methods: We enrolled 38 patients after obtaining IRB approval for this study. We evaluated the mRNA and protein expression levels of general macrophage marker (CD68), M1 marker (CD86, CCR7, iNOS, IFN gamma, TNF-alpha and IL-6,), M2 marker (CD206, CD163, IL-10, IL-4) and chemokine axis (MCP-1, CCR2 and CCR5) along with TREM-1 and TREM-2 in omentum fat, subcutaneous fat, and liver biopsy tissues of non-obese (N = 5), obese non-diabetics, (N = 16) and obese diabetics (N = 17). Results: The results of our study showed over-expression of TREM-1, M1 markers and down-regulation of TREM-2 and M2 markers in the omentum, subcutaneous and liver biopsies of obese patients (diabetics and non-diabetics) compared to non-obese patients. Overall, the obese diabetic group showed a significant (p < 0.05) higher number of patients with over expression of M1 markers (TREM-1, CD68, CD86, CCR-7, iNOS, IFN-gamma, TNF-alpha, IL-6, MCP-1, CCR-2 and CCR-5) and down-regulation of M2 markers (CD206, CD163 and IL-4) in liver biopsy compared to obese non-diabetics. Conclusions: TREM-1 expression is significantly increased along with the M1 markers in liver biopsy of obese diabetic (17/17) and obese non-diabetic patients (9/16). Our data suggests that TREM-1 overexpression and M1 macrophage polarization are associated with obesity-induced IR.