Glucose-Chi3l1 interaction tunes metabolic imbalance in Kupffer cells and ameliorates metabolic dysfunction-associated fatty liver

ABSTRACT: Kupffer cell (KCs) death has been observed in metabolic dysfunction-associated fatty liver disease (MAFLD). However, the metabolic alterations triggering KCs death in MAFLD remain elusive. This study aims to elucidate the glucose metabolic changes during KCs death and explore potential regulatory mechanisms.We confirmed KCs death in various MAFLD mouse models and deciphered the correlation between KCs death and glucose metabolic changes via single-cell RNA sequencing (scRNA-seq) and experimental approaches. Notably, we identified a key regulatory molecule, Chi3l1, which interacts with glucose and inhibits glucose uptake in KCs, thereby delaying KCs death during the early stages of MAFLD. This mechanism ultimately alleviates KCs death and the consequent lipid accumulation in the liver.Our findings highlight the intricate interplay between glucose metabolism and KCs death in MAFLD and provide novel insights into the underlying mechanisms driving this complex disease.

ORGANISM(S): Mus musculus

PROVIDER: GSE275551 | GEO | 2026/07/01

REPOSITORIES: GEO