Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Tardelli, M; Bruschi, FV; Fuchs, CD; Claudel, T; Auer, N; Kunczer, V; Ronda, OAHO; Verkade, HJ; Stojakovic, T; Scharnagl, H; Trauner, M.
Absence of Adiponutrin (PNPLA3) and Monoacylglycerol Lipase Synergistically Increases Weight Gain and Aggravates Steatohepatitis in Mice.
Int J Mol Sci. 2021; 22(4):
Doi: 10.3390/ijms22042126
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- Führende Autor*innen der Med Uni Graz
- Trauner Michael
- Co-Autor*innen der Med Uni Graz
- Claudel Thierry
- Fuchs Claudia
- Scharnagl Hubert
- Stojakovic Tatjana
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- Abstract:
- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Adipose Tissue - metabolism
- Adipose Tissue - pathology
- Animals -
- Cells, Cultured -
- Fatty Acids - metabolism
- Humans -
- Inflammation - pathology
- Lipid Metabolism -
- Liver - pathology
- Macrophages - metabolism
- Male -
- Membrane Proteins - deficiency
- Membrane Proteins - metabolism
- Mice, Inbred C57BL -
- Mice, Knockout -
- Monoacylglycerol Lipases - deficiency
- Monoacylglycerol Lipases - metabolism
- Non-alcoholic Fatty Liver Disease - enzymology
- Non-alcoholic Fatty Liver Disease - pathology
- Oleic Acid -
- Phenotype -
- U937 Cells -
- Weight Gain -
- Find related publications in this database (Keywords)
- NAFLD
- MGL
- PNPLA3
- NASH
- inflammation