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Cardiac Lipid Accumulation Associated with Diastolic Dysfunction in Obese Mice

Departments of Clinical Biochemistry (C.C., M.L.S.L., E.D.B., J.P.G., L.B.N.) and Pathology (C.B.A.), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark 2100; and Department of Clinical Physiology (E.B.), Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden

Address all correspondence and requests for reprints to: Lars B. Nielsen, M.D., Ph.D., D.M.Sc., Department of Clinical Biochemistry KB3011, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark 2100. E-mail: larsbo{at}rh.dk.

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 ß-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 µg/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.

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