PMID- 27553638
OWN - NLM
STAT- MEDLINE
DCOM- 20170522
LR  - 20170522
IS  - 1432-0878 (Electronic)
IS  - 0302-766X (Linking)
VI  - 366
IP  - 3
DP  - 2016 Dec
TI  - Altered glycogen metabolism causes hepatomegaly following an Atg7 deletion.
PG  - 651-665
AB  - Autophagy is a lysosomal degradation process involved in the turnover of 
      organelles or other cell constituents, in providing sources for energy production 
      under starving conditions and in cell metabolism. A key protein in the 
      macroautophagic machinery is the autophagy-related protein (Atg) 7. Constitutive 
      deletion of Atg7 is lethal at birth. A conditional deletion of Atg7 in 
      hepatocytes leads to hepatomegaly and in aged animals to liver tumors. With this 
      study, we aim at analyzing the hepatomegaly development in more detail. The 3- to 
      4-fold enlargement of the liver takes place between days 25 and 35 after birth 
      (P25-P35) and persists at least until P90. This is accompanied by a change in the 
      expression of enzymes involved in the glycogen/glucose metabolism. While glycogen 
      synthesis is inhibited, glucose is preferentially kept as glucose-6-phosphate 
      inside the cells, inducing a swelling of the cells caused by hyperosmolarity. An 
      increase of lipogenic enzymes suggests that glucose-6-phosphate is delivered to 
      lipogenic pathways, which is supported by the occurrence of a steatosis around 
      P30. The development of hepatomegaly is accompanied by a polyploidisation of 
      hepatocytes, an enhanced expression of genes related to inflammatory processes 
      and an infiltration of macrophages and granulocytes. Our data provide evidence 
      that the attenuation of macroautophagy in hepatocytes leads to a glucose 
      retention that causes cell swelling. The resulting hepatomegaly, which develops 
      in a time interval of about 10 days, perturbs liver perfusion and induces an 
      inflammatory reaction together with polyploidisation.
FAU - Kern, Lara
AU  - Kern L
AD  - Department of Cytobiology and Cytopathobiology, Philipps University, 35033, 
      Marburg, Germany.
FAU - Spreckels, Johanne
AU  - Spreckels J
AD  - Department of Cytobiology and Cytopathobiology, Philipps University, 35033, 
      Marburg, Germany.
FAU - Nist, Andrea
AU  - Nist A
AD  - Genomics Unit, Philipps University, 35043, Marburg, Germany.
FAU - Stiewe, Thorsten
AU  - Stiewe T
AD  - Genomics Unit, Philipps University, 35043, Marburg, Germany.
AD  - Institute of Molecular Oncology, Philipps University, 35043, Marburg, Germany.
FAU - Skevaki, Chrysanthi
AU  - Skevaki C
AD  - Institute of Laboratory Medicine, Pathobiochemistry and Molecular Diagnostics, 
      Philipps University, 35043, Marburg, Germany.
FAU - Greene, Brandon
AU  - Greene B
AD  - Institute of Medical Biometry and Epidemiology, Philipps University, 35037, 
      Marburg, Germany.
FAU - Mernberger, Marco
AU  - Mernberger M
AD  - Institute of Molecular Oncology, Philipps University, 35043, Marburg, Germany.
FAU - Elsasser, Hans-Peter
AU  - Elsasser HP
AD  - Department of Cytobiology and Cytopathobiology, Philipps University, 35033, 
      Marburg, Germany. elsaesse@mailer.uni-marburg.de.
LA  - eng
PT  - Journal Article
DEP - 20160823
PL  - Germany
TA  - Cell Tissue Res
JT  - Cell and tissue research
JID - 0417625
RN  - 0 (Atg7 protein, mouse)
RN  - 0 (Dietary Carbohydrates)
RN  - 9005-79-2 (Glycogen)
RN  - EC 6.2.1.45 (Autophagy-Related Protein 7)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Autophagy-Related Protein 7/*metabolism
MH  - Cell Death
MH  - Cell Proliferation
MH  - Dietary Carbohydrates
MH  - Female
MH  - *Gene Deletion
MH  - Gene Expression Regulation
MH  - Glucose/metabolism
MH  - Glycogen/*metabolism
MH  - Hepatomegaly/*metabolism/pathology
MH  - Inflammation/pathology
MH  - Liver/metabolism
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Organ Specificity
MH  - Polyploidy
OTO - NOTNLM
OT  - Atg7
OT  - Glycogen
OT  - Hepatomegaly
OT  - Liver
OT  - Metabolism
EDAT- 2016/08/25 06:00
MHDA- 2017/05/23 06:00
CRDT- 2016/08/25 06:00
PHST- 2016/01/20 00:00 [received]
PHST- 2016/07/12 00:00 [accepted]
PHST- 2016/08/25 06:00 [pubmed]
PHST- 2017/05/23 06:00 [medline]
PHST- 2016/08/25 06:00 [entrez]
AID - 10.1007/s00441-016-2477-8 [pii]
AID - 10.1007/s00441-016-2477-8 [doi]
PST - ppublish
SO  - Cell Tissue Res. 2016 Dec;366(3):651-665. doi: 10.1007/s00441-016-2477-8. Epub 
      2016 Aug 23.