title: Cardiac lipid accumulation associated with diastolic dysfunction in obese mice.
abstract: Obesity may confer cardiac dysfunction due to lipid accumulation in cardiomyocytes. To test this idea, we examined whether obese ob/ob mice display heart lipid accumulation and cardiac dysfunction. Ob/ob mouse hearts had increased expression of genes mediating extracellular generation, transport across the myocyte cell membrane, intracellular transport, mitochondrial uptake, and beta-oxidation of fatty acids compared with ob/+ mice. Accordingly, ob/ob mouse hearts contained more triglyceride (6.8 +/- 0.4 vs. 2.3 +/- 0.4 microg/mg; P < 0.0005) than ob/+ mouse hearts. Histological examinations showed marked accumulation of neutral lipid droplets within cardiac myocytes but not increased deposition of collagen between myocytes in ob/ob compared with ob/+ mouse hearts. On echocardiography, the ratio of E to A transmitral flow velocities (an indicator of diastolic function) was 1.8 +/- 0.1 in ob/ob mice and 2.5 +/- 0.1 in ob/+ mice (P = 0.0001). In contrast, the indexes of systolic function and heart brain natriuretic peptide mRNA expression were only marginally affected and unaffected, respectively, in ob/ob compared with ob/+ mice. The results suggest that ob/ob mouse hearts have increased expression of cardiac gene products that stimulate myocyte fatty acid uptake and triglyceride storage and accumulate neutral lipids within the cardiac myocytes. The results also suggest that the cardiac lipid accumulation is paralleled by cardiac diastolic dysfunction in ob/ob mice.
authors.affiliation: Departments of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark 2100.
authors.forename: Christina
authors.initials: C
authors.lastname: Christoffersen
authors.forename: Entela
authors.initials: E
authors.lastname: Bollano
authors.forename: Marie L S
authors.initials: ML
authors.lastname: Lindegaard
authors.forename: Emil D
authors.initials: ED
authors.lastname: Bartels
authors.forename: Jens P
authors.initials: JP
authors.lastname: Goetze
authors.forename: Claus B
authors.initials: CB
authors.lastname: Andersen
authors.forename: Lars B
authors.initials: LB
authors.lastname: Nielsen
mesh_terms: D000818:Animals; D001055:Apolipoproteins B / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D003094:Collagen / Q000032:analysis; D003971:Diastole / Q000502:physiology*; D004452:Echocardiography; D050612:Fatty Acid Transport Proteins; D005227:Fatty Acids / Q000378:metabolism; D015870:Gene Expression; D020738:Leptin / Q000172:deficiency; D050356:Lipid Metabolism; D008071:Lipoprotein Lipase / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D026901:Membrane Transport Proteins; D051379:Mice; D018345:Mice, Knockout; D008820:Mice, Obese; D008854:Microscopy, Electron; D008929:Mitochondria, Heart / Q000378:metabolism; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000235:genetics; D009765:Obesity / Q000503:physiopathology*; D010084:Oxidation-Reduction; D010713:Phosphatidylcholines / Q000032:analysis; D010716:Phosphatidylinositols / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D013599:Systole / Q000502:physiology; D014280:Triglycerides / Q000032:analysis / Q000378:metabolism
chemical_list: D001055:Apolipoproteins B; D002352:Carrier Proteins; D050612:Fatty Acid Transport Proteins; D005227:Fatty Acids; D020738:Leptin; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D010713:Phosphatidylcholines; D010716:Phosphatidylinositols; D012333:RNA, Messenger; C493572:Slc27a4 protein, mouse; D014280:Triglycerides; C106092:microsomal triglyceride transfer protein; D020097:Natriuretic Peptide, Brain; D003094:Collagen; D008071:Lipoprotein Lipase