TREM-1 associated macrophage polarization plays a significant role in inducing insulin resistance in obese population
Authors: Saravanan Subramanian
Poonam Sharma
Kalyana C Nandipati
Devendra K Agrawal
Pradeep K Pallati
Journal: Journal of translational medicine (2017)
Discipline: CLINICAL MEDICINE
Keywords: Inflammation; Insulin resistance; Macrophages; Obesity; TREM-1.
Affiliations: Department of Clinical and Translational Science, Creighton University School of Medicine, Omaha, NE, USA., Department of Surgery, Creighton University School of Medicine, 601¬†N. 30th Street, Suite # 3700, Omaha, NE, 68131, USA., Department of Pathology, Creighton University School of Medicine, Omaha, NE, USA., Department of Clinical and Translational Science, Creighton University School of Medicine, Omaha, NE, USA. ., Department of Surgery, Creighton University School of Medicine, 601¬†N. 30th Street, Suite # 3700, Omaha, NE, 68131, USA. .

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, IFNŒ≥, TNF-Œ± 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 &lt; 0.05) higher number of patients with over expression of M1 markers (TREM-1, CD68, CD86, CCR-7, iNOS, IFN-Œ≥, TNF-Œ±, 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. 

Retracted: Yes

PubPeer comments:
 2020 retraction. https: translational-medicine.biomedcentral.com articles 10.1186 s12967-020-02365-1 This article [1] has been retracted at the request of the authors. Upon re-review of the data, we realized certain patients did not meet inclusion criteria. Per IRB guidelines, after removing three subjects who either had BMIu2009 u200965 or BMIu2009 u200940 (even though they had undergone bariatric surgery) and one control subject from the study, we re-analyzed the data set. The removal of these subjects from the analysis had no effect on our findings or conclusions. The journalu2019s Editor-in-Chief has invited the authors to re-publish their study with updated results. All authors agree to this retraction. Reference 1. Subramanian S, Pallati PK, Sharma P, Agrawal DK, Nandipati KC. TREM-1 associated macrophage polarization plays a significant role in inducing insulin resistance in obese population. J Transl Med. 2017;15:85. https: doi.org 10.1186 s12967-017-1187-7 ,