Abstract
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.
Highlights
Tein rather than the truncated apoB48 protein [4]
The present results suggest that accelerated lipoprotein formation by cardiac myocytes can remove excess triglycerides from the diabetic heart
This idea is in accordance with a recent seminal study [23], which demonstrated that hearts from apolipoprotein B (apoB) transgenic mice secrete more triglycerides in apoB-containing lipoproteins than control mice
Summary
Animals—5–7-week-old wild type mice (C57BL/6 mice, 20 female and 20 male mice) and human apoB transgenic mice (C57BL/6NTacTgN mice, 20 female and 20 male mice) were obtained from M&B (Ry, Denmark) housed at the Panum Institute, University of Copenhagen (Copenhagen, Denmark) and fed standard laboratory chow (Altromin number 1314, Rugaarden, Denmark). The apoB transgenic mice were generated with an ϳ87-kilobase pair human genomic fragment from a genomic P1 bacteriophage clone, p158. This transgene directs human apoB overexpression in the liver and in the heart but not in the intestine [7, 14]. Control mice received the citrate buffer vehicle (200 l/mouse/day) following the same treatment regimen. Tissue and Blood Samples—Blood samples for plasma insulin and lipid analyses were drawn into tubes containing Na2-EDTA and centrifuged at ϳ4000 ϫ g for 10 min at 4 °C. Cross-sectional slices of the ventricular portion of heart including right and left ventricular tissue and liver biopsies were snap-frozen in liquid nitrogen and stored at Ϫ141 °C for subsequent lipid and RNA extraction. A ϳ3-mm slice from the apex of the heart was fixed in 3% paraformaldehyde
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