Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Vujic, N; Korbelius, M; Leopold, C; Duta-Mare, M; Rainer, S; Schlager, S; Goeritzer, M; Kolb, D; Eichmann, TO; Diwoky, C; Zimmer, A; Zimmermann, R; Lass, A; Radovic, B; Kratky, D.
Monoglyceride lipase deficiency affects hepatic cholesterol metabolism and lipid-dependent gut transit in ApoE-/- mice.
Oncotarget. 2017; 8(20):33122-33136
Doi: 10.18632/oncotarget.16529
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- Leading authors Med Uni Graz
- Kratky Dagmar
- Vujic Nemanja
- Co-authors Med Uni Graz
- Duta-Mare Madalina-Cristina
- Eichmann Thomas
- Göritzer Madeleine
- Kolb Dagmar
- Korbelius Melanie
- Leopold Christina
- Radovic Branislav
- Rainer Silvia
- Schlager Stefanie
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- Abstract:
- Monoglyceride lipase (MGL) hydrolyzes monoglycerides (MGs) to glycerol and fatty acids. Among various MG species MGL also degrades 2-arachidonoylglycerol (2-AG), the most abundant endocannabinoid and potent activator of cannabinoid receptors (CBR) 1 and 2. MGL-knockout (-/-) mice exhibit pronounced 2-AG accumulation, but lack central cannabimimetic effects due to CB1R desensitization. We have previously shown that MGL affects plaque stability in apolipoprotein E (ApoE)-/- mice, an established animal model for dyslipidemia and atherosclerosis. In the current study, we investigated functional consequences of MGL deficiency on lipid and energy metabolism in ApoE/MGL double knockout (DKO) mice. MGL deficiency affected hepatic cholesterol metabolism by causing increased cholesterol elimination via the biliary pathway. Moreover, DKO mice exhibit lipid-triggered delay in gastric emptying without major effects on overall triglyceride and cholesterol absorption. The observed phenotype of DKO mice is likely not a consequence of potentiated CB1R signaling but rather dependent on the activation of alternative signaling pathways. We conclude that MGL deficiency causes complex metabolic changes including cholesterol metabolism and regulation of gut transit independent of the endocannabinoid system.
- Find related publications in this database (using NLM MeSH Indexing)
- Alcohol Oxidoreductases - metabolism
- Animals - administration & dosage
- Apolipoproteins E - genetics
- Arachidonic Acids - metabolism
- Asialoglycoproteins - deficiency, genetics
- Atherosclerosis - metabolism
- Cholesterol - metabolism
- Disease Models, Animal - administration & dosage
- Dyslipidemias - metabolism
- Endocannabinoids - metabolism
- Gene Knockout Techniques - administration & dosage
- Glycerides - metabolism
- Intestinal Mucosa - metabolism
- Lectins, C-Type - deficiency, genetics
- Liver - metabolism
- Male - administration & dosage
- Membrane Proteins - deficiency, genetics
- Mice - administration & dosage
- Find related publications in this database (Keywords)
- endocannabinoid
- cannabinoid receptor
- desensitization
- lipolysis
- cholesterol