Activity‐based Photoacoustic Probes Reveal Elevated Intestinal MGL and FAAH Activity in a Murine Model of Obesity

Obesity is a chronic health condition characterized by the accumulation of excessive body fat which can lead to and exacerbate cardiovascular disease, type-II diabetes, high blood pressure, cancer through systemic inflammation. Unfortunately, visualizing key mediators inflammatory response, such as monoacylglycerol lipase (MGL) fatty acid amide hydrolase (FAAH), in selective manner profound challenge owing an overlapping substrate scope that involves arachidonic (AA). Specifically, these enzymes work concert generate AA, context obesity, has been implicated control appetite energy metabolism. In this study, we developed first activity-based sensing probes detect MGL (PA-HD-MGL) FAAH (PA-HD-FAAH) activity via photoacoustic imaging. Activation PA-HD-MGL PA-HD-FAAH their target resulted 1.74-fold 1.59-fold signal enhancements, respectively. Due exceptional selectivity profiles deep-tissue imaging capabilities, were employed measure murine model obesity. Contrary conflicting reports suggesting levels be attenuated or elevated, our results support latter. Indeed, discovered marked increase both targets gastrointestinal tract. These findings set stage uncover role endocannabinoid pathway obesity-mediated