PMID- 24187137
OWN - NLM
STAT- MEDLINE
DCOM- 20140213
LR  - 20211203
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 288
IP  - 50
DP  - 2013 Dec 13
TI  - Skeletal muscle-derived myonectin activates the mammalian target of rapamycin 
      (mTOR) pathway to suppress autophagy in liver.
PG  - 36073-82
LID - 10.1074/jbc.M113.500736 [doi]
AB  - Cells turn on autophagy, an intracellular recycling pathway, when deprived of 
      nutrients. How autophagy is regulated by hormonal signals in response to major 
      changes in metabolic state is not well understood. Here, we provide evidence that 
      myonectin (CTRP15), a skeletal muscle-derived myokine, is a novel regulator of 
      cellular autophagy. Starvation activated liver autophagy, whereas nutrient 
      supplementation following food deprivation suppressed it; the former and latter 
      correlated with reduced and increased expression and circulating levels of 
      myonectin, respectively, suggestive of a causal link. Indeed, recombinant 
      myonectin administration suppressed starvation-induced autophagy in mouse liver 
      and cultured hepatocytes, as indicated by the inhibition of LC3-dependent 
      autophagosome formation, p62 degradation, and expression of critical 
      autophagy-related genes. Reduction in protein degradation is mediated by the 
      PI3K/Akt/mTOR signaling pathway; inhibition of this pathway abrogated the ability 
      of myonectin to suppress autophagy in cultured hepatocytes. Together, our results 
      reveal a novel skeletal muscle-liver axis controlling cellular autophagy, 
      underscoring the importance of hormone-mediated tissue cross-talk in maintaining 
      energy homeostasis.
FAU - Seldin, Marcus M
AU  - Seldin MM
AD  - From the Department of Physiology and Center for Metabolism and Obesity Research, 
      The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
FAU - Lei, Xia
AU  - Lei X
FAU - Tan, Stefanie Y
AU  - Tan SY
FAU - Stanson, Kevin P
AU  - Stanson KP
FAU - Wei, Zhikui
AU  - Wei Z
FAU - Wong, G William
AU  - Wong GW
LA  - eng
GR  - P30 DK079637/DK/NIDDK NIH HHS/United States
GR  - R01 DK084171/DK/NIDDK NIH HHS/United States
GR  - DK084171/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 - 20131101
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Cytokines)
RN  - 0 (Erfe protein, mouse)
RN  - 0 (Gtf2h1 protein, mouse)
RN  - 0 (Map1lc3b protein, mouse)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Muscle Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Transcription Factors)
RN  - 148710-81-0 (Transcription Factor TFIIH)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Autophagy/*drug effects
MH  - Cell Line
MH  - Cytokines/*pharmacology
MH  - Dietary Supplements
MH  - Gene Expression Regulation/drug effects
MH  - Homeostasis/drug effects
MH  - Humans
MH  - Liver/*cytology
MH  - Male
MH  - Mice
MH  - Microtubule-Associated Proteins/metabolism
MH  - Muscle Proteins/*pharmacology
MH  - Muscle, Skeletal/*metabolism
MH  - Proteolysis/drug effects
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Rats
MH  - Recombinant Proteins/pharmacology
MH  - Signal Transduction/*drug effects
MH  - Starvation/metabolism/pathology
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Transcription Factor TFIIH
MH  - Transcription Factors/metabolism
PMC - PMC3861655
OTO - NOTNLM
OT  - Autophagy
OT  - Liver
OT  - Liver Metabolism
OT  - Skeletal Muscle
OT  - mTOR
EDAT- 2013/11/05 06:00
MHDA- 2014/02/14 06:00
PMCR- 2014/12/13
CRDT- 2013/11/05 06:00
PHST- 2013/11/05 06:00 [entrez]
PHST- 2013/11/05 06:00 [pubmed]
PHST- 2014/02/14 06:00 [medline]
PHST- 2014/12/13 00:00 [pmc-release]
AID - S0021-9258(19)54327-7 [pii]
AID - M113.500736 [pii]
AID - 10.1074/jbc.M113.500736 [doi]
PST - ppublish
SO  - J Biol Chem. 2013 Dec 13;288(50):36073-82. doi: 10.1074/jbc.M113.500736. Epub 
      2013 Nov 1.