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 β-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.

Ectopic fat storage in heart, blood vessels and kidneys in the pathogenesis of cardiovascular diseases

“…Second, hearts from obese, leptindeficient, ob/ob mice showed marked accumulation of neutral lipid droplets within cardiac myocytes. 23 In those mice, systolic function was only marginally affected, but there was a clear association between cardiac lipid accumulation and diastolic dysfunction. Finally, myocardial lipid content is also increased in lean Zucker rats fed a high-fat diet and is associated with myocardial oxidative injury.…”

Increased Expression of Adhesion Molecules in Uremic Atherosclerosis in Apolipoprotein-E–Deficient Mice

“…Aortic lipids were quantified with thin layer chromatography (TLC) as described previously (17,18). All samples were analyzed in tetraplicate on separate TLC plates.…”

Modeling the Transition From Decompensated to Pathological Hypertrophy

“…Pathological conditions can also be accompanied by alterations in cardiac substrate use; however, it remains unclear as to whether the shift in energy substrate is a cause or consequence of the pathological insult. Metabolic heart disease causes an increase in FA oxidation,6, 7, 8, 9 whereas increased glucose use is observed under conditions that induce pathological hypertrophy, myocardial ischemia, or heart failure 10. Analyses of some mouse models suggest that ventricular hypertrophy precedes the metabolic changes that result in reduced cardiac FA oxidation and increased glucose use 11, 12.…”