Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Tardelli, M; Bruschi, FV; Claudel, T; Fuchs, CD; Auer, N; Kunczer, V; Stojakovic, T; Scharnagl, H; Habib, A; Grabner, GF; Zimmermann, R; Lotersztajn, S; Trauner, M.
Lack of monoacylglycerol lipase prevents hepatic steatosis by favoring lipid storage in adipose tissue and intestinal malabsorption.
J Lipid Res. 2019; 60(7):1284-1292
Doi: 10.1194/jlr.M093369
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- Co-authors Med Uni Graz
- Claudel Thierry
- Fuchs Claudia
- Grabner Gernot
- Scharnagl Hubert
- Stojakovic Tatjana
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- Abstract:
- Monoacylglycerol lipase (MGL) is the rate-limiting enzyme in the degradation of monoacylglycerols. To examine the role of MGL in hepatic steatosis, WT and MGL KO (MGL-/-) mice were challenged with a Western diet (WD) over 12 weeks. Lipid metabolism, inflammation, and fibrosis were assessed by serum biochemistry, histology, and gene-expression profiling of liver and adipose depots. Intestinal fat absorption was measured by gas chromatography. Primary adipocyte and 3T3-L1 cells were analyzed by flow cytometry and Western blot. Human hepatocytes were treated with MGL inhibitor JZL184. The absence of MGL protected mice from hepatic steatosis by repressing key lipogenic enzymes in liver (Srebp1c, Pparγ2, and diacylglycerol O-acyltransferase 1), while promoting FA oxidation. Liver inflammation was diminished in MGL-/- mice fed a WD, as evidenced by diminished epidermal growth factor-like module-containing mucin-like hormone receptor-like 1 (F4/80) staining and C-C motif chemokine ligand 2 gene expression, whereas fibrosis remained unchanged. Absence of MGL promoted fat storage in gonadal white adipose tissue (gWAT) with increased lipogenesis and unchanged lipolysis, diminished inflammation in gWAT, and subcutaneous AT. Intestinal fat malabsorption prevented ectopic lipid accumulation in livers of MGL-/- mice fed a WD. In vitro experiments demonstrated increased adipocyte size/lipid content driven by PPARγ. In conclusion, our data uncover that MGL deletion improves some aspects of nonalcoholic fatty liver disease by promoting lipid storage in gWAT and fat malabsorption.
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- 3-Hydroxybutyric Acid - blood
- 3T3-L1 Cells - administration & dosage
- Adiponectin - blood
- Adipose Tissue - metabolism
- Animals - administration & dosage
- Blotting, Western - administration & dosage
- Cells, Cultured - administration & dosage
- Fatty Acids - blood
- Glycerol - blood
- Humans - administration & dosage
- Immunohistochemistry - administration & dosage
- Insulin - blood
- Intestinal Absorption - genetics, physiology
- Lipid Metabolism - genetics, physiology
- Lipolysis - genetics, physiology
- Liver - enzymology, metabolism
- Mice - administration & dosage
- Mice, Inbred C57BL - administration & dosage
- Monoacylglycerol Lipases - deficiency, genetics, metabolism
- Obesity - genetics, metabolism
- Oxidation-Reduction - administration & dosage
- Peroxisome Proliferator-Activated Receptors - metabolism
- Triglycerides - blood
- Find related publications in this database (Keywords)
- nonalcoholic fatty liver disease
- monoacylglycerol lipase
- obesity
- lipolysis and fatty acid metabolism
- nuclear receptors
- peroxisome proliferator-activated receptor
- adipocyte
- adipocytes
- obesity
- fatty acid
- metabolism