PMID- 33672787
OWN - NLM
STAT- MEDLINE
DCOM- 20210414
LR  - 20240226
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 4
DP  - 2021 Feb 20
TI  - Absence of Adiponutrin (PNPLA3) and Monoacylglycerol Lipase Synergistically 
      Increases Weight Gain and Aggravates Steatohepatitis in Mice.
LID - 10.3390/ijms22042126 [doi]
LID - 2126
AB  - Altered lipid metabolic pathways including hydrolysis of triglycerides are key 
      players in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Whether 
      adiponutrin (patatin-like phospholipase domain containing protein-3-PNPLA3) and 
      monoacylglycerol lipase (MGL) synergistically contribute to disease progression 
      remains unclear. We generated double knockout (DKO) mice lacking both Mgl and 
      Pnpla3; DKO mice were compared to Mgl(-/-) after a challenge by high-fat diet 
      (HFD) for 12 weeks to induce steatosis. Serum biochemistry, liver transaminases 
      as well as histology were analyzed. Fatty acid (FA) profiling was assessed in 
      liver and adipose tissue by gas chromatography. Markers of inflammation and lipid 
      metabolism were analyzed. Bone marrow derived macrophages (BMDMs) were isolated 
      and treated with oleic acid. Combined deficiency of Mgl and Pnpla3 resulted in 
      weight gain on a chow diet; when challenged by HFD, DKO mice showed increased 
      hepatic FA synthesis and diminished beta-oxidation compared to Mgl(-/-).DKO mice 
      exhibited more pronounced hepatic steatosis with inflammation and recruitment of 
      immune cells to the liver associated with accumulation of saturated FAs. Primary 
      BMDMs isolated from the DKO mice showed increased inflammatory activities, which 
      could be reversed by oleic acid supplementation. Pnpla3 deficiency aggravates the 
      effects of Mgl deletion on steatosis and inflammation in the liver under HFD 
      challenge.
FAU - Tardelli, Matteo
AU  - Tardelli M
AD  - Hans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and 
      Hepatology, Department of Internal Medicine III, Medical University of Vienna, 
      1090 Vienna, Austria.
FAU - Bruschi, Francesca V
AU  - Bruschi FV
AUID- ORCID: 0000-0002-5006-5473
AD  - Hans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and 
      Hepatology, Department of Internal Medicine III, Medical University of Vienna, 
      1090 Vienna, Austria.
FAU - Fuchs, Claudia D
AU  - Fuchs CD
AUID- ORCID: 0000-0002-0636-1320
AD  - Hans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and 
      Hepatology, Department of Internal Medicine III, Medical University of Vienna, 
      1090 Vienna, Austria.
FAU - Claudel, Thierry
AU  - Claudel T
AUID- ORCID: 0000-0002-5601-9830
AD  - Hans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and 
      Hepatology, Department of Internal Medicine III, Medical University of Vienna, 
      1090 Vienna, Austria.
FAU - Auer, Nicole
AU  - Auer N
AD  - Hans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and 
      Hepatology, Department of Internal Medicine III, Medical University of Vienna, 
      1090 Vienna, Austria.
FAU - Kunczer, Victoria
AU  - Kunczer V
AD  - Hans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and 
      Hepatology, Department of Internal Medicine III, Medical University of Vienna, 
      1090 Vienna, Austria.
FAU - Ronda, Onne A H O
AU  - Ronda OAHO
AD  - Center for Liver, Digestive and Metabolic Diseases, Departments of Pediatrics, 
      University Medical Center Groningen, 9712 Groningen, The Netherlands.
FAU - Verkade, Henkjan J
AU  - Verkade HJ
AUID- ORCID: 0000-0002-7034-2861
AD  - Center for Liver, Digestive and Metabolic Diseases, Departments of Pediatrics, 
      University Medical Center Groningen, 9712 Groningen, The Netherlands.
FAU - Stojakovic, Tatjana
AU  - Stojakovic T
AD  - Clinical Institute of Medical and Chemical Laboratory Diagnostics, University 
      Hospital Graz, 8036 Graz, Austria.
FAU - Scharnagl, Hubert
AU  - Scharnagl H
AD  - Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical 
      University of Graz, 8036 Graz, Austria.
FAU - Trauner, Michael
AU  - Trauner M
AUID- ORCID: 0000-0002-1275-6425
AD  - Hans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and 
      Hepatology, Department of Internal Medicine III, Medical University of Vienna, 
      1090 Vienna, Austria.
LA  - eng
GR  - F7310-B21/Austrian Science Fund/
PT  - Journal Article
DEP - 20210220
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Fatty Acids)
RN  - 0 (Membrane Proteins)
RN  - 0 (adiponutrin)
RN  - 2UMI9U37CP (Oleic Acid)
RN  - EC 3.1.1.23 (Monoacylglycerol Lipases)
SB  - IM
MH  - Adipose Tissue/metabolism/pathology
MH  - Animals
MH  - Cells, Cultured
MH  - Fatty Acids/metabolism
MH  - Humans
MH  - Inflammation/pathology
MH  - Lipid Metabolism
MH  - Liver/pathology
MH  - Macrophages/metabolism
MH  - Male
MH  - Membrane Proteins/*deficiency/metabolism
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Monoacylglycerol Lipases/*deficiency/metabolism
MH  - Non-alcoholic Fatty Liver Disease/*enzymology/*pathology
MH  - Oleic Acid
MH  - Phenotype
MH  - U937 Cells
MH  - *Weight Gain
MH  - Mice
PMC - PMC7924608
OTO - NOTNLM
OT  - MGL
OT  - NAFLD
OT  - NASH
OT  - PNPLA3
OT  - inflammation
COIS- The authors declare no conflict of interest.
EDAT- 2021/03/07 06:00
MHDA- 2021/04/15 06:00
PMCR- 2021/02/20
CRDT- 2021/03/06 01:14
PHST- 2021/01/12 00:00 [received]
PHST- 2021/01/29 00:00 [revised]
PHST- 2021/02/02 00:00 [accepted]
PHST- 2021/03/06 01:14 [entrez]
PHST- 2021/03/07 06:00 [pubmed]
PHST- 2021/04/15 06:00 [medline]
PHST- 2021/02/20 00:00 [pmc-release]
AID - ijms22042126 [pii]
AID - ijms-22-02126 [pii]
AID - 10.3390/ijms22042126 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Feb 20;22(4):2126. doi: 10.3390/ijms22042126.