ATP Citrate Lyase (ACLY)-mediated macrophage reprogramming in metaflammation (P01)

• Subject Area: Immunology ; Endocrinology, Diabetology, Metabolism ; Cell Biology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 432325352

We found that TLR4 signalling in macrophages leads to early metabolic reprogramming resulting in high amounts of citrate. By activating ATP-citrate lyase (ACLY) via phosphorylation, TLR4 signalling, further enhances acetyl-Coenzyme A (CoA) levels, resulting in a rapid de novo histone acetylation which facilitates the induction of a defined set of genes that are implicated in inflammation and cellular defence mechanisms. In this project two labs with complementary expertise will aim to understand how ACLY affects macrophage phenotypes in metaflammation and promotes disease progression in the context of obesity and hyperglycaemia.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1454: Metaflammation and Cellular Programming
• Applicant Institution: Rheinische Friedrich-Wilhelms-Universität Bonn
• Project Heads: Professor Dr. Karsten Hiller; Professor Dr. Eicke Latz