Grant: Project Grant

Metabolic dysfunction-associated steatohepatitis (MASH) and chronic kidney disease (CKD) affects more than 5 million Canadians. Despite their high prevalence and severe impact on morbidity and mortality, current therapies are largely ineffective and do not target the underlying cause of the disease which is inflammation. The cause of MASH and CKD is complex, involving interactions between multiple organs and cell types, therefore targeting single inflammatory molecules/pathways have largely been ineffective. Inflammatory cells utilize a metabolic process called glycolysis (similar to what is used during a 100 m dash) while anti-inflammatory cells utilize oxidative metabolism (similar to what is used by someone running a marathon). Therefore, shifting cells in the liver and kidney to a more oxidative state may suppress inflammation. A critical protein controlling the switch between glycolytic and oxidative metabolism is ATP-citrate lyase (ACLY). We have found a novel way to inhibit ACLY and will test whether this reduces liver and kidney inflammation in mice.