Deficiency of ATP-citrate lyase (ACLY) in chondrocytes limits cartilage damage induced by obesity via high-fat diet in mice

Abstract

Purpose: ATP-citrate lyase (ACLY) is an enzyme located in the cytosol and nucleus that generates acetyl-CoA from mitochondrial-derived citrate. Altered ACLY activity is observed in metabolic disorders, and several core features of metabolic syndrome such as dyslipidemia, obesity and insulin resistance have been linked to OA. Our recent study revealed that ACLY is upregulated in human knee OA chondrocytes. This could cause accumulation of nucleocytosolic acetyl-CoA, leading to increased matrix catabolism via dysregulated histone and transcription factor acetylation.