ATP-citrate lyase is an epigenetic regulator to promote obesity-related kidney injury.

ABSTRACT: Obesity is a leading cause of chronic kidney disease (CKD), but how obesity promotes renal injury remains poorly understood. Here we showed that ATP-citrate lyase (ACL), an enzyme converting citrate to acetyl-CoA, is highly induced in the kidney of overweight or obese patients with CKD and ob/ob BTBR mice. ACL induction is associated with increased ectopic lipid accumulation (ELA), glomerulosclerosis, and albuminuria. Acetyl-CoA is the substrate for de novo lipogenesis as well as for histone acetylation. By raising acetyl-CoA concentration ACL promotes H3K9/14 and H3K27 hyperacetylation leading to up-regulation of several rate-limiting lipogenic enzymes and fibrogenic factors. On the other hand, the excess acetyl-CoA generated as a result of ACL induction provides the substrate for

SUBMITTER: Chen Y 

PROVIDER: S-EPMC6662982 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature