PMID- 29967167
OWN - NLM
STAT- MEDLINE
DCOM- 20180918
LR  - 20181114
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 115
IP  - 29
DP  - 2018 Jul 17
TI  - Ablation of PM20D1 reveals N-acyl amino acid control of metabolism and 
      nociception.
PG  - E6937-E6945
LID - 10.1073/pnas.1803389115 [doi]
AB  - 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.
CI  - Copyright (c) 2018 the Author(s). Published by PNAS.
FAU - Long, Jonathan Z
AU  - Long JZ
AD  - Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical 
      School, Boston, MA 02115.
AD  - Department of Cell Biology, Harvard Medical School, Boston, MA 02115.
FAU - Roche, Alexander M
AU  - Roche AM
AD  - Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical 
      School, Boston, MA 02115.
AD  - Department of Cell Biology, Harvard Medical School, Boston, MA 02115.
FAU - Berdan, Charles A
AU  - Berdan CA
AD  - Department of Chemistry, University of California, Berkeley, CA 94720.
AD  - Department of Molecular and Cell Biology, University of California, Berkeley, CA 
      94720.
AD  - Department of Nutritional Sciences and Toxicology, University of California, 
      Berkeley, CA 94720.
FAU - Louie, Sharon M
AU  - Louie SM
AD  - Department of Chemistry, University of California, Berkeley, CA 94720.
AD  - Department of Molecular and Cell Biology, University of California, Berkeley, CA 
      94720.
AD  - Department of Nutritional Sciences and Toxicology, University of California, 
      Berkeley, CA 94720.
FAU - Roberts, Amanda J
AU  - Roberts AJ
AD  - Department of Neuroscience, The Scripps Research Institute, La Jolla, CA 92037.
FAU - Svensson, Katrin J
AU  - Svensson KJ
AD  - Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical 
      School, Boston, MA 02115.
AD  - Department of Cell Biology, Harvard Medical School, Boston, MA 02115.
FAU - Dou, Florence Y
AU  - Dou FY
AD  - Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical 
      School, Boston, MA 02115.
AD  - Department of Cell Biology, Harvard Medical School, Boston, MA 02115.
FAU - Bateman, Leslie A
AU  - Bateman LA
AD  - Department of Chemistry, University of California, Berkeley, CA 94720.
AD  - Department of Molecular and Cell Biology, University of California, Berkeley, CA 
      94720.
AD  - Department of Nutritional Sciences and Toxicology, University of California, 
      Berkeley, CA 94720.
FAU - Mina, Amir I
AU  - Mina AI
AD  - Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's 
      Hospital, Boston, MA 02115.
FAU - Deng, Zhaoming
AU  - Deng Z
AD  - Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's 
      Hospital, Boston, MA 02115.
FAU - Jedrychowski, Mark P
AU  - Jedrychowski MP
AD  - Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical 
      School, Boston, MA 02115.
AD  - Department of Cell Biology, Harvard Medical School, Boston, MA 02115.
FAU - Lin, Hua
AU  - Lin H
AD  - Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL 
      33458.
FAU - Kamenecka, Theodore M
AU  - Kamenecka TM
AD  - Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL 
      33458.
FAU - Asara, John M
AU  - Asara JM
AD  - Department of Medicine, Beth Israel Deaconness Medical Center, Boston, MA 02115.
FAU - Griffin, Patrick R
AU  - Griffin PR
AD  - Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL 
      33458.
FAU - Banks, Alexander S
AU  - Banks AS
AD  - Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's 
      Hospital, Boston, MA 02115.
FAU - Nomura, Daniel K
AU  - Nomura DK
AD  - Department of Chemistry, University of California, Berkeley, CA 94720.
AD  - Department of Molecular and Cell Biology, University of California, Berkeley, CA 
      94720.
AD  - Department of Nutritional Sciences and Toxicology, University of California, 
      Berkeley, CA 94720.
FAU - Spiegelman, Bruce M
AU  - Spiegelman BM
AD  - Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical 
      School, Boston, MA 02115; Bruce_Spiegelman@dfci.harvard.edu.
AD  - Department of Cell Biology, Harvard Medical School, Boston, MA 02115.
LA  - eng
GR  - R00 DK105203/DK/NIDDK NIH HHS/United States
GR  - R00 DK111916/DK/NIDDK NIH HHS/United States
GR  - R01 DK061562/DK/NIDDK NIH HHS/United States
GR  - R01 CA172667/CA/NCI NIH HHS/United States
GR  - P30 DK034854/DK/NIDDK NIH HHS/United States
GR  - K99 DK111916/DK/NIDDK NIH HHS/United States
GR  - R37 DK031405/DK/NIDDK NIH HHS/United States
GR  - R01 DK031405/DK/NIDDK NIH HHS/United States
GR  - K99 DK105203/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180702
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Oleic Acids)
RN  - 0 (TRPV Cation Channels)
RN  - 0 (TRPV1 protein, mouse)
RN  - 0RH81L854J (Glutamine)
RN  - EC 3.5.- (Amidohydrolases)
RN  - EC 3.5.- (PM20D1 protein, mouse)
SB  - IM
MH  - Amidohydrolases/genetics/*metabolism
MH  - Animals
MH  - Body Temperature/physiology
MH  - Glutamine/genetics/*metabolism/pharmacology
MH  - Mice
MH  - Mice, Knockout
MH  - Nociception/drug effects/*physiology
MH  - Oleic Acids/genetics/*metabolism/pharmacology
MH  - Signal Transduction/*physiology
MH  - TRPV Cation Channels/genetics/metabolism
PMC - PMC6055169
OTO - NOTNLM
OT  - N-acyl amino acid
OT  - PM20D1
OT  - knockout
OT  - metabolism
OT  - pain
COIS- Conflict of interest statement: B.M.S. is a consultant for Calico Life Sciences, 
      LLC.
EDAT- 2018/07/04 06:00
MHDA- 2018/09/19 06:00
PMCR- 2018/07/02
CRDT- 2018/07/04 06:00
PHST- 2018/07/04 06:00 [pubmed]
PHST- 2018/09/19 06:00 [medline]
PHST- 2018/07/04 06:00 [entrez]
PHST- 2018/07/02 00:00 [pmc-release]
AID - 1803389115 [pii]
AID - 201803389 [pii]
AID - 10.1073/pnas.1803389115 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2018 Jul 17;115(29):E6937-E6945. doi: 
      10.1073/pnas.1803389115. Epub 2018 Jul 2.