دورية أكاديمية
Ablation of PM20D1 reveals N -acyl amino acid control of metabolism and nociception.
| العنوان: | Ablation of PM20D1 reveals N -acyl amino acid control of metabolism and nociception. |
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| المؤلفون: | Long JZ; Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.; Department of Cell Biology, Harvard Medical School, Boston, MA 02115., Roche AM; Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.; Department of Cell Biology, Harvard Medical School, Boston, MA 02115., Berdan CA; Department of Chemistry, University of California, Berkeley, CA 94720.; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720.; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720., Louie SM; Department of Chemistry, University of California, Berkeley, CA 94720.; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720.; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720., Roberts AJ; Department of Neuroscience, The Scripps Research Institute, La Jolla, CA 92037., Svensson KJ; Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.; Department of Cell Biology, Harvard Medical School, Boston, MA 02115., Dou FY; Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.; Department of Cell Biology, Harvard Medical School, Boston, MA 02115., Bateman LA; Department of Chemistry, University of California, Berkeley, CA 94720.; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720.; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720., Mina AI; Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Boston, MA 02115., Deng Z; Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Boston, MA 02115., Jedrychowski MP; Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.; Department of Cell Biology, Harvard Medical School, Boston, MA 02115., Lin H; Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL 33458., Kamenecka TM; Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL 33458., Asara JM; Department of Medicine, Beth Israel Deaconness Medical Center, Boston, MA 02115., Griffin PR; Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL 33458., Banks AS; Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Boston, MA 02115., Nomura DK; Department of Chemistry, University of California, Berkeley, CA 94720.; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720.; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720., Spiegelman BM; Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115; Bruce_Spiegelman@dfci.harvard.edu.; Department of Cell Biology, Harvard Medical School, Boston, MA 02115. |
| المصدر: | Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2018 Jul 17; Vol. 115 (29), pp. E6937-E6945. Date of Electronic Publication: 2018 Jul 02. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : National Academy of Sciences |
| مواضيع طبية MeSH: | Amidohydrolases/*metabolism , Glutamine/*metabolism , Nociception/*physiology , Oleic Acids/*metabolism , Signal Transduction/*physiology, Amidohydrolases/genetics ; Animals ; Body Temperature/physiology ; Glutamine/genetics ; Glutamine/pharmacology ; Mice ; Mice, Knockout ; Nociception/drug effects ; Oleic Acids/genetics ; Oleic Acids/pharmacology ; TRPV Cation Channels/genetics ; TRPV Cation Channels/metabolism |
| مستخلص: | N -acyl amino acids (NAAs) are a structurally diverse class of bioactive signaling lipids whose endogenous functions have largely remained uncharacterized. To clarify the physiologic roles of NAAs, we generated mice deficient in the circulating enzyme peptidase M20 domain-containing 1 (PM20D1). Global PM20D1-KO mice have dramatically reduced NAA hydrolase/synthase activities in tissues and blood with concomitant bidirectional dysregulation of endogenous NAAs. Compared with control animals, PM20D1-KO mice exhibit a variety of metabolic and pain phenotypes, including insulin resistance, altered body temperature in cold, and antinociceptive behaviors. Guided by these phenotypes, we identify N -oleoyl-glutamine (C18:1-Gln) as a key PM20D1-regulated NAA. In addition to its mitochondrial uncoupling bioactivity, C18:1-Gln also antagonizes certain members of the transient receptor potential (TRP) calcium channels including TRPV1. Direct administration of C18:1-Gln to mice is sufficient to recapitulate a subset of phenotypes observed in PM20D1-KO animals. These data demonstrate that PM20D1 is a dominant enzymatic regulator of NAA levels in vivo and elucidate physiologic functions for NAA signaling in metabolism and nociception. Competing Interests: Conflict of interest statement: B.M.S. is a consultant for Calico Life Sciences, LLC. (Copyright © 2018 the Author(s). Published by PNAS.) |
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| معلومات مُعتمدة: | R00 DK105203 United States DK NIDDK NIH HHS; R00 DK111916 United States DK NIDDK NIH HHS; R01 DK061562 United States DK NIDDK NIH HHS; R01 CA172667 United States CA NCI NIH HHS; P30 DK034854 United States DK NIDDK NIH HHS; K99 DK111916 United States DK NIDDK NIH HHS; R37 DK031405 United States DK NIDDK NIH HHS; R01 DK031405 United States DK NIDDK NIH HHS; K99 DK105203 United States DK NIDDK NIH HHS |
| فهرسة مساهمة: | Keywords: N-acyl amino acid; PM20D1; knockout; metabolism; pain |
| المشرفين على المادة: | 0 (Oleic Acids) 0 (TRPV Cation Channels) 0 (TRPV1 protein, mouse) 0RH81L854J (Glutamine) EC 3.5.- (Amidohydrolases) EC 3.5.- (PM20D1 protein, mouse) |
| تواريخ الأحداث: | Date Created: 20180704 Date Completed: 20180918 Latest Revision: 20181114 |
| رمز التحديث: | 20221213 |
| مُعرف محوري في PubMed: | PMC6055169 |
| DOI: | 10.1073/pnas.1803389115 |
| PMID: | 29967167 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1091-6490 |
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| DOI: | 10.1073/pnas.1803389115 |