Yes, rapamycin alleviates intrahepatic inflammation in metabolic dysfunction-associated steatotic liver disease (MASLD). According to the study, rapamycin's therapeutic effects are primarily mediated through its action on bone marrow-derived macrophages, which are key immune cells involved in liver inflammation.
Rapamycin suppresses the proinflammatory activation of hepatic macrophages and enhances pathways related to fatty acid oxidation within these cells. By promoting fatty acid oxidation in macrophages, rapamycin reduces their inflammatory capacity, thereby creating a less inflammatory hepatic microenvironment. This reprogramming of macrophage metabolism toward an anti-inflammatory state is a key mechanism by which rapamycin mitigates intrahepatic inflammation in MASLD.
Thus, rapamycin offers a promising approach to targeting inflammation in MASLD and its advanced form, metabolic dysfunction-associated steatohepatitis (MASH). However, it is important to note that while rapamycin improves hepatic inflammation, steatosis, and steatohepatitis, it does not have a significant impact on established liver fibrosis.