The Human Monoacylglycerol Acyltransferase 2 Inhibitor VB‐85387 Is Associated With Weight Loss in Mice With Obesity

Background: GLP-1 therapies for obesity are limited by side effects and weight regain is common after treatment ends. Therefore, alternative treatments with new mechanisms are needed for sustained weight loss. Human MOGAT2 regulates triglyceride metabolism and its inhibition reduces weight in people with obesity, making MOGAT2 a promising target for obesity therapy. Objective: This study evaluated the therapeutic potential of the VB-85387 MOGAT2 inhibitor for weight loss. Methods: RT-PCR. Results: -oxidation gene expression was increased, and SREBP-dependent gene expression was reduced. Conclusion: VB-85387 serves as a starting point for medicinal chemistry lead optimization. Weight loss may be attributed to PPARα activation and a sustained elevation in GLP-1 levels.