title: A Glyoxalase-1 Knockdown Does Not Have Major Short Term Effects on Energy Expenditure and Atherosclerosis in Mice.
abstract: Objective. Glyoxalase-1 is an enzyme detoxifying methylglyoxal (MG). MG is a potent precursor of advanced glycation endproducts which are regarded to be a key player in micro- and macrovascular damage. Yet, the role of Glo1 in atherosclerosis remains unclear. In this study, the effect of Glo1 on mouse metabolism and atherosclerosis is evaluated. Methods. Glo1 knockdown mice were fed a high fat or a standard diet for 10 weeks. Body weight and composition were investigated by Echo MRI. The PhenoMaster system was used to measure the energy expenditure. To evaluate the impact of Glo1 on atherosclerosis, Glo1(KD) mice were crossed with ApoE-knockout mice and fed a high fat diet for 14 weeks. Results. Glo1 activity was significantly reduced in heart, liver, and kidney lysates derived from Glo1(KD) mice. Yet, there was no increase in methylglyoxal-derived AGEs in all organs analyzed. The Glo1 knockdown did not affect body weight or body composition. Metabolic studies via indirect calorimetry did not show significant effects on energy expenditure. Glo1(KD) mice crossed to ApoE(-/-) mice did not show enhanced formation of atherosclerosis. Conclusion. A Glo1 knockdown does not have major short term effects on the energy expenditure or the formation of atherosclerotic plaques.
authors.affiliation: Department of Vascular and Endovascular Surgery, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Wortmann
authors.affiliation: Department of Vascular and Endovascular Surgery, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Maani
authors.initials: M
authors.lastname: Hakimi
authors.affiliation: Department of Medicine I and Clinical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Fleming
authors.affiliation: Department of Vascular and Endovascular Surgery, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Andreas S
authors.initials: AS
authors.lastname: Peters
authors.affiliation: Joint Research Division, Molecular Metabolic Control, German Cancer Research Center DKFZ, Network Aging Research, ZMBH, and University Hospital Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Tjeerd P
authors.initials: TP
authors.lastname: Sijmonsma
authors.affiliation: Joint Research Division, Molecular Metabolic Control, German Cancer Research Center DKFZ, Network Aging Research, ZMBH, and University Hospital Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Herzig
authors.affiliation: Department of Medicine I and Clinical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Peter P
authors.initials: PP
authors.lastname: Nawroth
authors.affiliation: Department of Vascular and Endovascular Surgery, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Dittmar
authors.initials: D
authors.lastname: Böckler
authors.affiliation: Department of Vascular and Endovascular Surgery, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Dihlmann
mesh_terms: D000818:Animals; D001018:Aortic Diseases / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D002153:Calorimetry, Indirect; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000235:genetics; D020022:Genetic Predisposition to Disease; D007668:Kidney / Q000201:enzymology; D007791:Lactoylglutathione Lyase / Q000172:deficiency* / Q000235:genetics; D008099:Liver / Q000201:enzymology; D008279:Magnetic Resonance Imaging; D008297:Male; D018345:Mice, Knockout; D009206:Myocardium / Q000201:enzymology; D010641:Phenotype; D058226:Plaque, Atherosclerotic; D011765:Pyruvaldehyde / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D011765:Pyruvaldehyde; D007791:Lactoylglutathione Lyase