ACMSD inhibition corrects fibrosis, inflammation, and DNA damage in MASLD/MASH.

ABSTRACT:

Background & aims

Recent findings reveal the importance of tryptophan-initiated de novo nicotinamide adenine dinucleotide (NAD⁺) synthesis in the liver, a process previously considered secondary to biosynthesis from nicotinamide. The enzyme α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD), primarily expressed in the liver and kidney, acts as a modulator of de novo NAD⁺ synthesis. Boosting NAD⁺ levels has previously demonstrated remarkable metabolic benefits in mouse models. In this study, we aimed to investigate the therapeutic implications of ACMSD inhibition in the treatment of metabolic dysfunction-associated steatotic liver disease/steatohepatitis (MASLD/MASH).

Methods

In vitro experiments were conducted in primary rodent he

SUBMITTER: Liu YJ 

PROVIDER: S-EPMC11741923 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature