| Literature DB >> 31901447 |
Charles P Najt1, Salmaan A Khan1, Timothy D Heden1, Bruce A Witthuhn1, Minervo Perez1, Jason L Heier1, Linnea E Mead1, Mallory P Franklin2, Kenneth K Karanja1, Mark J Graham3, Mara T Mashek1, David A Bernlohr1, Laurie Parker1, Lisa S Chow4, Douglas G Mashek5.
Abstract
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-1α/PPARα-dependent pathway through an unknown mechanism. Herein, we identify that monounsaturated fatty acids (MUFAs) allosterically activate SIRT1 toward select peptide-substrates such as PGC-1α. MUFAs enhance PGC-1α/PPARα 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.Entities:
Keywords: ATGL; MUFA; PGC-1α; PLIN5; SIRT1; fatty acids; lipid droplets; lipolysis; olive oil; oxidative metabolism
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Year: 2019 PMID： 31901447 PMCID： PMC7036014 DOI： 10.1016/j.molcel.2019.12.003
Source DB: PubMed Journal: Mol Cell ISSN： 1097-2765 Impact factor: 17.970