AUTHOR=Brustolin Benjamin , Touly Nina , Maillefer Marine , Parisot Lola , Di Pillo Elisa , Derive Marc , Gibot Sébastien TITLE=Triggering receptor expressed on myeloid cells-1 deletion in mice attenuates high-fat diet-induced obesity JOURNAL=Frontiers in Endocrinology VOLUME=Volume 13 - 2022 YEAR=2023 URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.983827 DOI=10.3389/fendo.2022.983827 ISSN=1664-2392 ABSTRACT=Introduction

The low-grade inflammatory state present in obesity leads to the development and perpetuation of comorbidities associated with obesity. Our laboratory has been working for several years on an amplification loop of the inflammatory response mediated by TREM-1 (Triggering Receptor of Expressed on Myeloid Cells-1). It is implicated in many acute (septic shock) and chronic (IBD) inflammatory diseases. Previously, TREM-1 has been shown to be overexpressed in adipose and liver tissue in obese and diabetic patients, but its impact has never been characterized in these pathologies.

Methods

Our hypothesis is that TREM-1 plays a major role in the generation and perpetuation of inflammation during obesity and its associated complication (Insulin resistance and cardiac dysfunction). We assessed TREM-1 protein expression by western blot and immunofluorescence in omental and subcutaneous (pre-)adipocyte. Moreover, we submitted mice to a high-fat diet and investigated the effects of the genetic Trem1 deletion (trem1 KO mice).

Results

We showed, for the first time, that TREM-1 is expressed and is functional in subcutaneous and omental (pre-)adipocytes. In the mouse model of high-fat diet-induced obesity, we found that Trem1 suppression limited weight gain, insulin resistance and inflammation in white adipose tissue and liver.

Discussion/conclusion

Our results reveal the trem1 KO model can be viewed as a preventive model and that TREM-1 seems to play an important role in the development of obesity and its associated complication. It could therefore be a new therapeutic target in this context.