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

• Tác giả: Johan Auwerx, Hector Gallart-Ayala, Riekelt H Houtkooper, Julijana Ivanisevic, Masaki Kimura, Xiaoxu Li, Yasmine J Liu, Robert P Myers, Sandra Rodríguez-López, Angelique M L Scantlebery, Keno Strotjohann, G Mani Subramanian, Jonathan Sulc, Takanori Takebe, Archana Vijayakumar, Qi Wang
• Ngôn ngữ: eng
• Ký hiệu phân loại: 912.01 Philosophy and theory
• Thông tin xuất bản: Netherlands : Journal of hepatology , 2025
• Bộ sưu tập: NCBI
• ID: 719801

Tóm tắt

BACKGROUND & AIMS: Recent findings reveal the importance of tryptophan-initiated de novo nicotinamide adenine dinucleotide (NAD METHODS: In vitro experiments were conducted in primary rodent hepatocytes, Huh7 human liver carcinoma cells and induced pluripotent stem cell-derived human liver organoids (HLOs). C57BL/6J male mice were fed a western-style diet and housed at thermoneutrality to recapitulate key aspects of MASLD/MASH. Pharmacological ACMSD inhibition was given therapeutically, following disease onset. HLO models of steatohepatitis were used to assess the DNA damage responses to ACMSD inhibition in human contexts. RESULTS: Inhibiting ACMSD with a novel specific pharmacological inhibitor promotes de novo NAD CONCLUSIONS: Our findings highlight the benefits of ACMSD inhibition in enhancing hepatic NAD IMPACT AND IMPLICATIONS: Enhancing NAD