Lipid Droplet-Derived Monounsaturated Fatty Acids Traffic via PLIN5 to Allosterically Activate SIRT1.

Autor:	Najt CP; Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA., Khan SA; Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA., Heden TD; Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA., Witthuhn BA; Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA., Perez M; Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA., Heier JL; Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA., Mead LE; Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA., Franklin MP; Department of Food Science and Nutrition, University of Minnesota, Minneapolis, MN, USA., Karanja KK; Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA., Graham MJ; Ionis Pharmaceuticals, Inc., Carlsbad, CA, USA., Mashek MT; Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA., Bernlohr DA; Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA., Parker L; Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA., Chow LS; Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, University of Minnesota, Minneapolis, Minnesota, USA., Mashek DG; Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA; Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, University of Minnesota, Minneapolis, Minnesota, USA. Electronic address: dmashek@umn.edu.
Jazyk:	angličtina
Zdroj:	Molecular cell [Mol Cell] 2020 Feb 20; Vol. 77 (4), pp. 810-824.e8. Date of Electronic Publication: 2019 Dec 31.
DOI:	10.1016/j.molcel.2019.12.003
Abstrakt:	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. Competing Interests: Declaration of Interests The authors declare no competing interests. (Copyright © 2019 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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