SUN-669 Effect Of In Vivo Myeloid Cell Tgm2 Silencing On Diet-induced Obesity, Metabolism, And Inflammation

Abstract Disclosure: B.T. Cole: None. D.M. Elizondo: None. T.P. Patel: None. E. Jansujwicz: None. J.A. Yanovski: None. Transglutaminase 2 (TGM2) is the most abundantly expressed enzyme of its group, which catalyzes calcium ion dependent post-translational protein modifications. TGM2 is present in adipose tissue macrophages (ATMs), which are known to modulate adipocyte expansion, growth, and obesity-related inflammation. Here, we hypothesized that myeloid-specific TGM2 silencing using a Tgm2t/t floxed x LyzM-Cre+ conditional knockout mouse model would modulate diet-induced obesity and adipose tissue inflammation. At age 6 weeks, Tgm2t/t x LyzM-Cre+ and control (Tgm2t/t floxed) mice were placed on a 60% high-fat diet for 10 weeks and monitored for changes in body weight, body composition, glucose or insulin tolerance. Gross eWAT and liver weights were recorded post-mortem and epididymal white adipose tissue stromal vascular fraction (eWAT SVF) was used for flow cytometric analysis to evaluate inflammatory changes in ATMs. Compared to controls, Tgm2t/t x LyzM-Cre+ mice showed no significant differences in body weight for either male or female mice. However, by DEXA, fat mass was significantly reduced in male Tgm2t/t x LyzM-Cre+ mice but significantly increased in female Tgm2t/t x LyzM-Cre+ mice when compared to controls. These data were further corroborated by gross eWAT weight analyses. Interestingly, insulin and glucose tolerance tests revealed trends towards improved insulin and glucose sensitivity in Tgm2t/t x LyzM-Cre+ mice when compared to controls, particularly among males. Lastly, analysis of eWAT SVF flow cytometric analysis revealed an increased trend towards greater expression of pro-inflammatory markers within ATMs in Tgm2t/t x LyzM-Cre+ male mice when compared to controls. We conclude that TGM2 expression in myeloid cells contributes to whole body weight and metabolism, via modulation of adipose tissue expansion, inflammation, and function. Presentation: Sunday, July 13, 2025