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=13

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=<sec><title>Introduction</title><p>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.</p></sec><sec><title>Methods</title><p>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 <italic>Trem1</italic> deletion (<italic>trem1</italic> KO mice).</p></sec><sec><title>Results</title><p>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 <italic>Trem1</italic> suppression limited weight gain, insulin resistance and inflammation in white adipose tissue and liver. </p></sec><sec><title>Discussion/conclusion</title><p>Our results reveal the <italic>trem1</italic> 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. </p></sec>