دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: Lipid Droplet-Derived Monounsaturated Fatty Acids Traffic via PLIN5 to Allosterically Activate SIRT1.
المؤلفون: 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.
المصدر: Molecular cell [Mol Cell] 2020 Feb 20; Vol. 77 (4), pp. 810-824.e8. Date of Electronic Publication: 2019 Dec 31.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 9802571 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-4164 (Electronic) Linking ISSN: 10972765 NLM ISO Abbreviation: Mol Cell Subsets: MEDLINE
أسماء مطبوعة: Publication: Cambridge Ma : Cell Press
Original Publication: Cambridge, Mass. : Cell Press, c1997-
مواضيع طبية MeSH: Fatty Acids, Monounsaturated/*metabolism , Lipid Droplets/*chemistry , Perilipin-5/*metabolism , Sirtuin 1/*metabolism, Allosteric Regulation ; Animals ; Biological Transport ; Cell Line ; Cells, Cultured ; Diet ; Fatty Acids/metabolism ; Lipase/metabolism ; Male ; Mice, Inbred C57BL ; Olive Oil ; Perilipin-5/physiology ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism ; Transcription, Genetic
مستخلص: 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.)
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معلومات مُعتمدة: R01 DK114401 United States DK NIDDK NIH HHS; R01 DK053189 United States DK NIDDK NIH HHS; R01 CA182543 United States CA NCI NIH HHS; T32 AG029796 United States AG NIA NIH HHS; R01 AG055452 United States AG NIA NIH HHS; L30 DK110338 United States DK NIDDK NIH HHS; T32 DK007203 United States DK NIDDK NIH HHS; R01 DK098203 United States DK NIDDK NIH HHS; F32 DK109556 United States DK NIDDK NIH HHS; T32 DK083250 United States DK NIDDK NIH HHS; R01 DK108790 United States DK NIDDK NIH HHS
فهرسة مساهمة: Keywords: ATGL; MUFA; PGC-1α; PLIN5; SIRT1; fatty acids; lipid droplets; lipolysis; olive oil; oxidative metabolism
المشرفين على المادة: 0 (Fatty Acids)
0 (Fatty Acids, Monounsaturated)
0 (Olive Oil)
0 (Perilipin-5)
0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha)
0 (Plin5 protein, mouse)
EC 3.1.1.3 (Lipase)
EC 3.1.1.3 (PNPLA2 protein, mouse)
EC 3.5.1.- (Sirtuin 1)
تواريخ الأحداث: Date Created: 20200106 Date Completed: 20200914 Latest Revision: 20210514
رمز التحديث: 20240829
مُعرف محوري في PubMed: PMC7036014
DOI: 10.1016/j.molcel.2019.12.003
PMID: 31901447
قاعدة البيانات: MEDLINE
الوصف
تدمد:1097-4164
DOI:10.1016/j.molcel.2019.12.003