PMID- 29548998
OWN - NLM
STAT- MEDLINE
DCOM- 20190521
LR  - 20190521
IS  - 1090-2139 (Electronic)
IS  - 0889-1591 (Linking)
VI  - 70
DP  - 2018 May
TI  - mTORC1 pathway disruption abrogates the effects of the ciliary neurotrophic 
      factor on energy balance and hypothalamic neuroinflammation.
PG  - 325-334
LID - S0889-1591(18)30064-3 [pii]
LID - 10.1016/j.bbi.2018.03.014 [doi]
AB  - Ciliary neurotrophic factor (CNTF) potently decreases food intake and body weight 
      in diet-induced obese mice by acting through neuronal circuits and pathways 
      located in the arcuate nucleus (ARC) of the hypothalamus. CNTF also exerts 
      pro-inflammatory actions within the brain. Here we tested whether CNTF modifies 
      energy balance by inducing inflammatory responses in the ARC and whether these 
      effects depend upon the mechanistic target of rapamycin complex 1 (mTORC1) 
      pathway, which regulates both energy metabolism and inflammation. To this 
      purpose, chow- and high fat diet (HFD)- fed mice lacking the S6 kinase 1 
      (S6K1(-/-)), a downstream target of mTORC1, and their wild-type (WT) littermates 
      received 12 days continuous intracerebroventricular (icv) infusion of the CNTF 
      analogue axokine (CNTF(Ax15)). Behavioral, metabolic and molecular effects were 
      evaluated. Central chronic administration of CNTF(Ax15) decreased body weight and 
      feed efficiency in WT mice only, when fed HFD, but not chow. These metabolic 
      effects correlated with increased number of iba-1 positive microglia specifically 
      in the ARC and were accompanied by significant increases of IL-1beta and TNF-alpha mRNA 
      expression in the hypothalamus. Hypothalamic iNOS and SOCS3 mRNA, molecular 
      markers of pro-inflammatory response, were also increased by CNTF(Ax15). All 
      these changes were absent in S6K1(-/-) mice. This study reveals that CNTF(Ax15) 
      requires a functional S6K1 to modulate energy balance and hypothalamic 
      inflammation in a diet-dependent fashion. Further investigations should determine 
      whether S6K1 is a suitable target for the treatment of pathologies characterized 
      by a high neuroinflammatory state.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Andre, Caroline
AU  - Andre C
AD  - INSERM, Neurocentre Magendie, Physiopathologie de la Plasticite Neuronale, U1215, 
      F-33000 Bordeaux, France; University of Bordeaux, Neurocentre Magendie, 
      Physiopathologie de la Plasticite Neuronale, U1215, F-33000 Bordeaux, France.
FAU - Catania, Caterina
AU  - Catania C
AD  - INSERM, Neurocentre Magendie, Physiopathologie de la Plasticite Neuronale, U1215, 
      F-33000 Bordeaux, France; University of Bordeaux, Neurocentre Magendie, 
      Physiopathologie de la Plasticite Neuronale, U1215, F-33000 Bordeaux, France.
FAU - Remus-Borel, Julie
AU  - Remus-Borel J
AD  - INRA, Nutrition et Neurobiologie Integree, UMR 1286, F-33076 Bordeaux, France; 
      University of Bordeaux, Nutrition et Neurobiologie Integree, UMR 1286, F-33076 
      Bordeaux, France.
FAU - Ladeveze, Elodie
AU  - Ladeveze E
AD  - INSERM, Neurocentre Magendie, Physiopathologie de la Plasticite Neuronale, U1215, 
      F-33000 Bordeaux, France; University of Bordeaux, Neurocentre Magendie, 
      Physiopathologie de la Plasticite Neuronale, U1215, F-33000 Bordeaux, France.
FAU - Leste-Lasserre, Thierry
AU  - Leste-Lasserre T
AD  - INSERM, Neurocentre Magendie, Physiopathologie de la Plasticite Neuronale, U1215, 
      F-33000 Bordeaux, France; University of Bordeaux, Neurocentre Magendie, 
      Physiopathologie de la Plasticite Neuronale, U1215, F-33000 Bordeaux, France.
FAU - Mazier, Wilfrid
AU  - Mazier W
AD  - INSERM, Neurocentre Magendie, Physiopathologie de la Plasticite Neuronale, U1215, 
      F-33000 Bordeaux, France; University of Bordeaux, Neurocentre Magendie, 
      Physiopathologie de la Plasticite Neuronale, U1215, F-33000 Bordeaux, France.
FAU - Binder, Elke
AU  - Binder E
AD  - INSERM, Neurocentre Magendie, Physiopathologie de la Plasticite Neuronale, U1215, 
      F-33000 Bordeaux, France; University of Bordeaux, Neurocentre Magendie, 
      Physiopathologie de la Plasticite Neuronale, U1215, F-33000 Bordeaux, France.
FAU - Gonzales, Delphine
AU  - Gonzales D
AD  - INSERM, Neurocentre Magendie, Physiopathologie de la Plasticite Neuronale, U1215, 
      F-33000 Bordeaux, France; University of Bordeaux, Neurocentre Magendie, 
      Physiopathologie de la Plasticite Neuronale, U1215, F-33000 Bordeaux, France.
FAU - Clark, Samantha
AU  - Clark S
AD  - INSERM, Neurocentre Magendie, Physiopathologie de la Plasticite Neuronale, U1215, 
      F-33000 Bordeaux, France; University of Bordeaux, Neurocentre Magendie, 
      Physiopathologie de la Plasticite Neuronale, U1215, F-33000 Bordeaux, France.
FAU - Guzman-Quevedo, Omar
AU  - Guzman-Quevedo O
AD  - INSERM, Neurocentre Magendie, Physiopathologie de la Plasticite Neuronale, U1215, 
      F-33000 Bordeaux, France; University of Bordeaux, Neurocentre Magendie, 
      Physiopathologie de la Plasticite Neuronale, U1215, F-33000 Bordeaux, France.
FAU - Abrous, Djoher Nora
AU  - Abrous DN
AD  - INSERM, Neurocentre Magendie, Physiopathologie de la Plasticite Neuronale, U1215, 
      F-33000 Bordeaux, France; University of Bordeaux, Neurocentre Magendie, 
      Physiopathologie de la Plasticite Neuronale, U1215, F-33000 Bordeaux, France.
FAU - Laye, Sophie
AU  - Laye S
AD  - INRA, Nutrition et Neurobiologie Integree, UMR 1286, F-33076 Bordeaux, France; 
      University of Bordeaux, Nutrition et Neurobiologie Integree, UMR 1286, F-33076 
      Bordeaux, France.
FAU - Cota, Daniela
AU  - Cota D
AD  - INSERM, Neurocentre Magendie, Physiopathologie de la Plasticite Neuronale, U1215, 
      F-33000 Bordeaux, France; University of Bordeaux, Neurocentre Magendie, 
      Physiopathologie de la Plasticite Neuronale, U1215, F-33000 Bordeaux, France. 
      Electronic address: daniela.cota@inserm.fr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180313
PL  - Netherlands
TA  - Brain Behav Immun
JT  - Brain, behavior, and immunity
JID - 8800478
RN  - 0 (Ciliary Neurotrophic Factor)
RN  - 0 (Leptin)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (ribosomal protein S6 kinase, 70kD, polypeptide 1)
SB  - IM
MH  - Animals
MH  - Arcuate Nucleus of Hypothalamus/metabolism
MH  - Body Weight
MH  - Ciliary Neurotrophic Factor/*metabolism/*physiology
MH  - Diet, High-Fat
MH  - Eating
MH  - Energy Metabolism
MH  - Homeostasis
MH  - Hypothalamus/metabolism/physiology
MH  - Leptin
MH  - Male
MH  - Mechanistic Target of Rapamycin Complex 1/metabolism/physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Microglia/physiology
MH  - Neuroglia/physiology
MH  - Neuroimmunomodulation/physiology
MH  - Obesity/physiopathology
MH  - Ribosomal Protein S6 Kinases, 70-kDa/genetics/*physiology
OTO - NOTNLM
OT  - CNTF
OT  - Glia cells
OT  - Hypothalamus
OT  - Inflammation
OT  - Microglia
OT  - Obesity
OT  - S6K1
OT  - mTOR
EDAT- 2018/03/20 06:00
MHDA- 2019/05/22 06:00
CRDT- 2018/03/18 06:00
PHST- 2017/11/14 00:00 [received]
PHST- 2018/03/02 00:00 [revised]
PHST- 2018/03/12 00:00 [accepted]
PHST- 2018/03/20 06:00 [pubmed]
PHST- 2019/05/22 06:00 [medline]
PHST- 2018/03/18 06:00 [entrez]
AID - S0889-1591(18)30064-3 [pii]
AID - 10.1016/j.bbi.2018.03.014 [doi]
PST - ppublish
SO  - Brain Behav Immun. 2018 May;70:325-334. doi: 10.1016/j.bbi.2018.03.014. Epub 2018 
      Mar 13.