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

Abstract

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, IFNγ, TNF-α 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-γ, TNF-α, 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.