PMID- 32112869
OWN - NLM
STAT- MEDLINE
DCOM- 20200326
LR  - 20211204
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 248
DP  - 2020 May 1
TI  - Glucose availability regulates nicotinamide N-methyltransferase expression in 
      adipocytes.
PG  - 117474
LID - S0024-3205(20)30222-8 [pii]
LID - 10.1016/j.lfs.2020.117474 [doi]
AB  - BACKGROUND/OBJECTIVES: Nicotinamide N-methyltransferase (NNMT) is a novel 
      regulator of energy homeostasis in adipocytes. NNMT expression in adipose tissue 
      is increased in obesity and diabetes. Knockdown of NNMT prevents mice from 
      developing diet-induced obesity, which is closely linked to insulin resistance. 
      An early sign of systemic insulin resistance is reduced expression of glucose 
      transporter 4 (GLUT4) selectively in adipose tissue. Adipose tissue-specific 
      knockout and overexpression of GLUT4 cause reciprocal changes in NNMT expression. 
      The aim of the current study was to elucidate the mechanism that regulates NNMT 
      expression in adipocytes. METHODS: 3T3-L1 adipocytes were cultured in media with 
      varying glucose concentrations or activators and inhibitors of intracellular 
      pathways. NNMT mRNA and protein levels were measured with quantitative polymerase 
      chain reaction and Western blotting. RESULTS: Glucose deprivation of 3T3-L1 
      adipocytes induced a 2-fold increase in NNMT mRNA and protein expression. This 
      effect was mimicked by inhibition of glucose transport with phloretin, and by 
      inhibition of glycolysis with the phosphoglucose isomerase inhibitor 
      2-deoxyglucose. Conversely, inhibition of the pentose phosphate pathway did not 
      affect NNMT expression. Pharmacological activation of the cellular energy sensor 
      AMP-activated protein kinase (AMPK) and inhibition of the mammalian target of 
      rapamycin (mTOR) pathway caused an increase in NNMT levels that was similar to 
      the effect of glucose deprivation. Activation of mTOR with MHY1485 prevented the 
      effect of glucose deprivation on NNMT expression. Furthermore, upregulation of 
      NNMT levels depended on functional autophagy and protein translation. CONCLUSION: 
      Glucose availability regulates NNMT expression via an mTOR-dependent mechanism.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Ehebauer, Franziska
AU  - Ehebauer F
AD  - Universitatsklinikum Wurzburg, Medizinische Klinik und Poliklinik I, 
      Oberdurrbacher Str. 6, 97080 Wurzburg, Germany.
FAU - Ghavampour, Sharang
AU  - Ghavampour S
AD  - Universitatsklinikum Wurzburg, Medizinische Klinik und Poliklinik I, 
      Oberdurrbacher Str. 6, 97080 Wurzburg, Germany.
FAU - Kraus, Daniel
AU  - Kraus D
AD  - Universitatsklinikum Wurzburg, Medizinische Klinik und Poliklinik I, 
      Oberdurrbacher Str. 6, 97080 Wurzburg, Germany. Electronic address: 
      d.kraus@uni-mainz.de.
LA  - eng
PT  - Journal Article
DEP - 20200227
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (4,6-dimorpholino-N-(4-nitrophenyl)-1,3,5-triazin-2-amine)
RN  - 0 (Glucose Transporter Type 4)
RN  - 0 (Morpholines)
RN  - 0 (RNA, Messenger)
RN  - 0 (Slc2a4 protein, mouse)
RN  - 0 (Triazines)
RN  - 9G2MP84A8W (Deoxyglucose)
RN  - EC 2.1.1.1 (Nicotinamide N-Methyltransferase)
RN  - EC 2.1.1.1 (Nnmt protein, mouse)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - EC 5.3.1.9 (Glucose-6-Phosphate Isomerase)
RN  - IY9XDZ35W2 (Glucose)
RN  - S5J5OE47MK (Phloretin)
SB  - IM
MH  - 3T3-L1 Cells
MH  - AMP-Activated Protein Kinases/genetics/metabolism
MH  - Adipocytes/cytology/*drug effects/metabolism
MH  - Animals
MH  - Autophagy/drug effects/genetics
MH  - Biological Transport/drug effects
MH  - Cell Differentiation
MH  - Deoxyglucose/pharmacology
MH  - Energy Metabolism/genetics
MH  - Gene Expression Regulation
MH  - Glucose/metabolism/*pharmacology
MH  - Glucose Transporter Type 4/antagonists & inhibitors/*genetics/metabolism
MH  - Glucose-6-Phosphate Isomerase/antagonists & inhibitors/genetics/metabolism
MH  - Homeostasis/genetics
MH  - Mice
MH  - Morpholines/pharmacology
MH  - Nicotinamide N-Methyltransferase/antagonists & inhibitors/*genetics/metabolism
MH  - Pentose Phosphate Pathway/drug effects/genetics
MH  - Phloretin/pharmacology
MH  - Protein Biosynthesis
MH  - RNA, Messenger/antagonists & inhibitors/genetics/metabolism
MH  - TOR Serine-Threonine Kinases/*genetics/metabolism
MH  - Triazines/pharmacology
OTO - NOTNLM
OT  - Adipocytes
OT  - Energy metabolism
OT  - mTOR
COIS- Declaration of competing interest The authors declare that they have no conflicts 
      of interest with the contents of this article.
EDAT- 2020/03/01 06:00
MHDA- 2020/03/27 06:00
CRDT- 2020/03/01 06:00
PHST- 2019/10/21 00:00 [received]
PHST- 2020/02/24 00:00 [revised]
PHST- 2020/02/25 00:00 [accepted]
PHST- 2020/03/01 06:00 [pubmed]
PHST- 2020/03/27 06:00 [medline]
PHST- 2020/03/01 06:00 [entrez]
AID - S0024-3205(20)30222-8 [pii]
AID - 10.1016/j.lfs.2020.117474 [doi]
PST - ppublish
SO  - Life Sci. 2020 May 1;248:117474. doi: 10.1016/j.lfs.2020.117474. Epub 2020 Feb 
      27.