| First Author | Iuso D | Year | 2023 |
| Journal | Sci Adv | Volume | 9 |
| Issue | 36 | Pages | eadh0140 |
| PubMed ID | 37672589 | Mgi Jnum | J:340281 |
| Mgi Id | MGI:7528090 | Doi | 10.1126/sciadv.adh0140 |
| Citation | Iuso D, et al. (2023) Nucleoside diphosphate kinases 1 and 2 regulate a protective liver response to a high-fat diet. Sci Adv 9(36):eadh0140 |
| abstractText | The synthesis of fatty acids from acetyl-coenzyme A (AcCoA) is deregulated in diverse pathologies, including cancer. Here, we report that fatty acid accumulation is negatively regulated by nucleoside diphosphate kinases 1 and 2 (NME1/2), housekeeping enzymes involved in nucleotide homeostasis that were recently found to bind CoA. We show that NME1 additionally binds AcCoA and that ligand recognition involves a unique binding mode dependent on the CoA/AcCoA 3' phosphate. We report that Nme2 knockout mice fed a high-fat diet (HFD) exhibit excessive triglyceride synthesis and liver steatosis. In liver cells, NME2 mediates a gene transcriptional response to HFD leading to the repression of fatty acid accumulation and activation of a protective gene expression program via targeted histone acetylation. Our findings implicate NME1/2 in the epigenetic regulation of a protective liver response to HFD and suggest a potential role in controlling AcCoA usage between the competing paths of histone acetylation and fatty acid synthesis. |
