PMID- 25060689
OWN - NLM
STAT- MEDLINE
DCOM- 20141114
LR  - 20220129
IS  - 1532-8600 (Electronic)
IS  - 0026-0495 (Print)
IS  - 0026-0495 (Linking)
VI  - 63
IP  - 10
DP  - 2014 Oct
TI  - Leptin modulates autophagy in human CD4+CD25- conventional T cells.
PG  - 1272-9
LID - S0026-0495(14)00177-2 [pii]
LID - 10.1016/j.metabol.2014.06.010 [doi]
AB  - OBJECTIVE: In this report we show that the adipocytokine leptin directly 
      modulates autophagy in human CD4(+)CD25(-) conventional (Tconv) T cells. RESULTS: 
      In vitro treatment with recombinant human leptin determined an inhibition of 
      autophagy during T cell receptor (TCR) stimulation, and this phenomenon was dose- 
      and time-dependent. The events were secondary to the activation of the 
      mammalian-target of rapamycin (mTOR)-pathway induced by leptin, as testified by 
      its reversion induced by mTOR inhibition with rapamycin. At molecular level these 
      phenomena associated with Bcl-2 up-regulation and its interaction with Beclin-1, 
      whose complex exerts a negative effect on autophagy. MATERIALS/METHODS: The 
      impact of leptin on autophagy of Tconv cells was determined at biochemical level 
      by western blotting and by flow cytometry; the interaction between BCL-2 and 
      Beclin-1 by co-immunoprecipitation assays. CONCLUSIONS: Our results, suggest that 
      in unconditioned, freshly-isolated human Tconv cells, autophagy and proliferation 
      are controlled by leptin during TCR-engagement, and that both phenomena occur 
      alternatively indicating a balance between these processes during immune 
      activation.
CI  - Copyright (c) 2014 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Cassano, Silvana
AU  - Cassano S
AD  - Laboratorio di Immunologia, Istituto di Endocrinologia e Oncologia Sperimentale, 
      Consiglio Nazionale delle Ricerche (IEOS-CNR), 80131 Napoli, Italy.
FAU - Pucino, Valentina
AU  - Pucino V
AD  - Dipartimento di Scienze Mediche Traslazionali, Universita di Napoli "Federico 
      II", 80131 Napoli, Italy.
FAU - La Rocca, Claudia
AU  - La Rocca C
AD  - Laboratorio di Immunologia, Istituto di Endocrinologia e Oncologia Sperimentale, 
      Consiglio Nazionale delle Ricerche (IEOS-CNR), 80131 Napoli, Italy; Dipartimento 
      di Medicina Molecolare e Biotecnologie Mediche, Universita di Napoli "Federico 
      II", 80131 Napoli, Italy.
FAU - Procaccini, Claudio
AU  - Procaccini C
AD  - Laboratorio di Immunologia, Istituto di Endocrinologia e Oncologia Sperimentale, 
      Consiglio Nazionale delle Ricerche (IEOS-CNR), 80131 Napoli, Italy.
FAU - De Rosa, Veronica
AU  - De Rosa V
AD  - Laboratorio di Immunologia, Istituto di Endocrinologia e Oncologia Sperimentale, 
      Consiglio Nazionale delle Ricerche (IEOS-CNR), 80131 Napoli, Italy; Unita di 
      NeuroImmunologia, IRCCS-Fondazione Santa Lucia, 00143 Roma, Italy.
FAU - Marone, Gianni
AU  - Marone G
AD  - Dipartimento di Scienze Mediche Traslazionali, Universita di Napoli "Federico 
      II", 80131 Napoli, Italy; Centro Interdipartimentale di Ricerca in Scienze 
      Immunologiche di Base e Cliniche (CISI), Universita di Napoli "Federico II", 
      80131 Napoli, Italy.
FAU - Matarese, Giuseppe
AU  - Matarese G
AD  - Dipartimento di Medicina e Chirurgia, Facolta di Medicina e Chirurgia, Universita 
      di Salerno, Baronissi Campus, 84081 Baronissi, Salerno, Italy; IRCCS-MultiMedica, 
      20138 Milano, Italy. Electronic address: gmatarese@unisa.it.
LA  - eng
GR  - 310496/ERC_/European Research Council/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140619
PL  - United States
TA  - Metabolism
JT  - Metabolism: clinical and experimental
JID - 0375267
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (BECN1 protein, human)
RN  - 0 (Beclin-1)
RN  - 0 (IL2RA protein, human)
RN  - 0 (Interleukin-2 Receptor alpha Subunit)
RN  - 0 (Leptin)
RN  - 0 (Membrane Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Apoptosis Regulatory Proteins/metabolism
MH  - Autophagy/drug effects/*physiology
MH  - Beclin-1
MH  - CD4-Positive T-Lymphocytes/drug effects/*metabolism/*physiology
MH  - Cell Line
MH  - Cell Proliferation/drug effects
MH  - Humans
MH  - Immunoprecipitation/methods
MH  - Interleukin-2 Receptor alpha Subunit/*metabolism
MH  - Leptin/*metabolism
MH  - Membrane Proteins/metabolism
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - Receptors, Antigen, T-Cell/*metabolism/*physiology
MH  - Signal Transduction/drug effects/physiology
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/metabolism
MH  - Up-Regulation/drug effects/physiology
PMC - PMC4180014
OTO - NOTNLM
OT  - Autophagy
OT  - Leptin
OT  - Metabolism
OT  - T cells
OT  - mTOR
EDAT- 2014/07/26 06:00
MHDA- 2014/11/15 06:00
PMCR- 2014/10/01
CRDT- 2014/07/26 06:00
PHST- 2014/05/16 00:00 [received]
PHST- 2014/06/13 00:00 [revised]
PHST- 2014/06/14 00:00 [accepted]
PHST- 2014/07/26 06:00 [entrez]
PHST- 2014/07/26 06:00 [pubmed]
PHST- 2014/11/15 06:00 [medline]
PHST- 2014/10/01 00:00 [pmc-release]
AID - S0026-0495(14)00177-2 [pii]
AID - 10.1016/j.metabol.2014.06.010 [doi]
PST - ppublish
SO  - Metabolism. 2014 Oct;63(10):1272-9. doi: 10.1016/j.metabol.2014.06.010. Epub 2014 
      Jun 19.