| First Author | Najt CP | Year | 2020 |
| Journal | Mol Cell | Volume | 77 |
| Issue | 4 | Pages | 810-824.e8 |
| PubMed ID | 31901447 | Mgi Jnum | J:286191 |
| Mgi Id | MGI:6400641 | Doi | 10.1016/j.molcel.2019.12.003 |
| Citation | Najt CP, et al. (2020) Lipid Droplet-Derived Monounsaturated Fatty Acids Traffic via PLIN5 to Allosterically Activate SIRT1. Mol Cell 77(4):810-824.e8 |
| abstractText | Lipid droplets (LDs) provide a reservoir for triacylglycerol storage and are a central hub for fatty acid trafficking and signaling in cells. Lipolysis promotes mitochondrial biogenesis and oxidative metabolism via a SIRT1/PGC-1alpha/PPARalpha-dependent pathway through an unknown mechanism. Herein, we identify that monounsaturated fatty acids (MUFAs) allosterically activate SIRT1 toward select peptide-substrates such as PGC-1alpha. MUFAs enhance PGC-1alpha/PPARalpha signaling and promote oxidative metabolism in cells and animal models in a SIRT1-dependent manner. Moreover, we characterize the LD protein perilipin 5 (PLIN5), which is known to enhance mitochondrial biogenesis and function, to be a fatty-acid-binding protein that preferentially binds LD-derived monounsaturated fatty acids and traffics them to the nucleus following cAMP/PKA-mediated lipolytic stimulation. Thus, these studies identify the first-known endogenous allosteric modulators of SIRT1 and characterize a LD-nuclear signaling axis that underlies the known metabolic benefits of MUFAs and PLIN5. |
