Overexpression of apolipoprotein B in the heart impedes cardiac triglyceride accumulation and development of cardiac dysfunction in diabetic mice.
The heart secretes apolipoprotein B (apoB) containing lipoproteins. Herein, we examined whether the overexpression of a human apoB transgene in the heart affects triglyceride accumulation and development of cardiac dysfunction in streptozotocin-treated diabetic mice. Blood glucose, plasma free fatty acids, and plasma triglycerides were similarly affected in diabetic wild type mice and diabetic apoB transgenic mice as compared with non-diabetic mice of the same genotype. After 12 weeks, heart triglycerides were increased by 48% in diabetic wild type mice. These mice displayed an increased expression of brain natriuretic peptide and deterioration of heart function on echocardiography. In diabetic apoB transgenic mice, heart triglyceride levels were identical to those in non-diabetic wild type and apoB transgenic mice, and brain natriuretic peptide expression as well as echocardiographic indexes of heart function were only marginally affected or unaffected. The findings suggest that triglyceride accumulation in the heart is important for development of diabetic cardiomyopathy in mice, and that lipoprotein formation by cardiomyocytes plays an integrated role in cardiac lipid metabolism.
Nielsen
Lars Bo
LB
Department of Clinical Biochemistry KB3011, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. larsbo@rh.dk
Bartels
Emil D
ED
Bollano
Entela
E
D000818:Animals; D001055:Apolipoproteins B / Q000096:biosynthesis*; D009202:Cardiomyopathies / Q000150:complications*; D018076:DNA, Complementary / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D004452:Echocardiography; D005260:Female; D005838:Genotype; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012737:Sex Factors; D014280:Triglycerides / Q000378:metabolism*
D001055:Apolipoproteins B; D018076:DNA, Complementary; D012333:RNA, Messenger; D014280:Triglycerides; D012313:RNA