This report first discusses the biological rationale in support of inhibition of MGAT2 as a therapeutic approach that may offer a distinct and superior efficacy versus GI tolerability profile and then reviews advances in the discovery of small molecule MGAT2 inhibitors for the treatment of metabolic diseases and nonalcoholic steatohepatitis (NASH).
Our results suggest that MGAT2 modulates energy expenditure through multiple mechanisms, including one independent of dietary fat; these findings also raise the prospect of inhibiting MGAT2 as a strategy for combating obesity and related metabolic disorders resulting from excessive calorie intake.