PMID- 28461471
OWN - NLM
STAT- MEDLINE
DCOM- 20180504
LR  - 20220129
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 114
IP  - 20
DP  - 2017 May 16
TI  - Lsd1 prevents age-programed loss of beige adipocytes.
PG  - 5265-5270
LID - 10.1073/pnas.1702641114 [doi]
AB  - Aging is accompanied by major changes in adipose tissue distribution and 
      function. In particular, with time, thermogenic-competent beige adipocytes 
      progressively gain a white adipocyte morphology. However, the mechanisms 
      controlling the age-related transition of beige adipocytes to white adipocytes 
      remain unclear. Lysine-specific demethylase 1 (Lsd1) is an epigenetic eraser 
      enzyme positively regulating differentiation and function of adipocytes. Here we 
      show that Lsd1 levels decrease in aging inguinal white adipose tissue 
      concomitantly with beige fat cell decline. Accordingly, adipocyte-specific 
      increase of Lsd1 expression is sufficient to rescue the age-related transition of 
      beige adipocytes to white adipocytes in vivo, whereas loss of Lsd1 precipitates 
      it. Lsd1 maintains beige adipocytes by controlling the expression of peroxisome 
      proliferator-activated receptor alpha (Ppara), and treatment with a Ppara agonist is 
      sufficient to rescue the loss of beige adipocytes caused by Lsd1 ablation. In 
      summary, our data provide insights into the mechanism controlling the age-related 
      beige-to-white adipocyte transition and identify Lsd1 as a regulator of beige fat 
      cell maintenance.
FAU - Duteil, Delphine
AU  - Duteil D
AD  - Urologische Klinik, Zentrale Klinische Forschung, Universitatsklinikum Freiburg, 
      Medizinische Fakultat, Albert-Ludwigs-University Freiburg, 79106 Freiburg, 
      Germany.
FAU - Tosic, Milica
AU  - Tosic M
AD  - Urologische Klinik, Zentrale Klinische Forschung, Universitatsklinikum Freiburg, 
      Medizinische Fakultat, Albert-Ludwigs-University Freiburg, 79106 Freiburg, 
      Germany.
FAU - Willmann, Dominica
AU  - Willmann D
AD  - Urologische Klinik, Zentrale Klinische Forschung, Universitatsklinikum Freiburg, 
      Medizinische Fakultat, Albert-Ludwigs-University Freiburg, 79106 Freiburg, 
      Germany.
FAU - Georgiadi, Anastasia
AU  - Georgiadi A
AD  - Institute for Diabetes and Cancer, Helmholtz Zentrum Muenchen, German Research 
      Center for Environmental Health, 85764 Neuherberg, Germany.
AD  - German Center for Diabetes Research, 85764 Neuherberg, Germany.
FAU - Kanouni, Toufike
AU  - Kanouni T
AD  - Celgene Quanticel Research, San Diego, CA 92121.
FAU - Schule, Roland
AU  - Schule R
AD  - Urologische Klinik, Zentrale Klinische Forschung, Universitatsklinikum Freiburg, 
      Medizinische Fakultat, Albert-Ludwigs-University Freiburg, 79106 Freiburg, 
      Germany; roland.schuele@uniklinik-freiburg.de.
AD  - BIOSS Centre for Biological Signalling Studies, Albert-Ludwigs-University, 79106 
      Freiburg, Germany.
AD  - Deutsche Konsortium fur Translationale Krebsforschung, 79106 Freiburg, Germany.
LA  - eng
GR  - 322844/ERC_/European Research Council/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170501
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 (PPAR alpha)
RN  - EC 1.14.11.- (Histone Demethylases)
RN  - EC 1.14.11.- (KDM1a protein, mouse)
SB  - IM
MH  - Adipocytes/metabolism
MH  - Adipocytes, Beige
MH  - Adipocytes, White
MH  - Adipose Tissue, Beige/*drug effects/*metabolism
MH  - Adipose Tissue, White/metabolism
MH  - Age Factors
MH  - Aging/metabolism/physiology
MH  - Animals
MH  - Cell Differentiation
MH  - Histone Demethylases/*metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - Obesity/metabolism
MH  - PPAR alpha/metabolism
MH  - Thermogenesis
PMC - PMC5441764
OTO - NOTNLM
OT  - Lsd1
OT  - Ppara
OT  - adipocyte
OT  - aging
OT  - beige fat
COIS- The authors declare no conflict of interest.
EDAT- 2017/05/04 06:00
MHDA- 2018/05/05 06:00
PMCR- 2017/11/16
CRDT- 2017/05/03 06:00
PHST- 2017/05/04 06:00 [pubmed]
PHST- 2018/05/05 06:00 [medline]
PHST- 2017/05/03 06:00 [entrez]
PHST- 2017/11/16 00:00 [pmc-release]
AID - 1702641114 [pii]
AID - 201702641 [pii]
AID - 10.1073/pnas.1702641114 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2017 May 16;114(20):5265-5270. doi: 
      10.1073/pnas.1702641114. Epub 2017 May 1.