Metabolic reprogramming of immune cells in MASH

Area of Science:

• Hepatology
• Immunology
• Metabolic Disorders

Background:

• Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly NAFLD, affects 30% of adults globally.
• A significant portion of MASLD patients develop metabolic dysfunction-associated steatohepatitis (MASH), progressing to cirrhosis and hepatocellular carcinoma (HCC).
• Immune cell metabolic reprogramming is critical in MASH pathogenesis, despite its classification as a metabolic disorder.

Purpose of the Study:

• To review the metabolic profiles of immune cells, specifically macrophages and T cells, in MASH.
• To discuss the implications of targeting cellular metabolism in these immune cells.
• To examine clinical trial outcomes related to metabolic interventions in MASH.

Main Methods:

• Literature review focusing on immune cell metabolism in MASH.
• Analysis of metabolic alterations in macrophages and T cells.
• Examination of clinical trial data on metabolic therapies.

Main Results:

• MASH macrophages exhibit enhanced glycolysis, impaired oxidative phosphorylation, and increased lipid metabolism, promoting inflammation.
• T cells and NK cells in MASH show metabolic dysfunction, impairing immune surveillance and potentially contributing to HCC.
• Limited research exists on the metabolic profiles of other immune cell types in MASH.

Conclusions:

• Immune cell metabolism is a key factor in MASH development and progression.
• Targeting cellular metabolism presents a promising therapeutic avenue for MASH.
• Further research, leveraging advanced techniques, is needed to fully elucidate MASH pathogenesis and develop novel treatments.