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.

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.Liver and intestinal cells secrete triglyceride-rich lipoproteins. This ability is dependent on the expression of the apoB and microsomal triglyceride transfer protein (MTP) 1 genes (1, 2). MTP transfers triglycerides onto the apoB polypeptide chain during its translation into the endoplasmic reticulum. ApoB serves as the principal structural protein in the resulting lipoprotein particles that are secreted from the cells. Studies of mice, which overexpress a human apoB transgene, revealed that cardiac myocytes in addition to hepatocytes and absorptive enterocytes also express the apoB and MTP genes (3) and secrete apoB containing lipoproteins (4). The apoB mRNA is not edited in cardiac myocytes (5). Consequently, the heart secretes lipoproteins containing the full-length apoB100 protein rather than the truncated apoB48 protein (4). Because the formation of apoB-containing lipoproteins serves as an effective means of secreting large amounts of triglycerides from liver and intestinal cells, we hypothesized previously that the physiological role of lipoprotein formation in the heart could be the removal of triglycerides from myocytes that are not used as fuel, i.e. a reverse triglyceride transport pathway (6, 7).Recently, the idea has been put forward that triglyceride accumulation in cardiac muscle cells adversely affects cardiac function (8). Diabetes is associated with aberrations in cardiac fuel metabolism and a ϳ2-fold increase in cardiac triglyceride content (9, 10). In diabetic rats, this triglyceride accumulation occurs in parallel with compromised cardiac performance (11,12). Echocardiographic studies have also revealed abnormal cardiac function in young diabetic individuals without coronary heart disease (13). It is unknown as to what extent triglyceride accumulation in cardiac myocytes affects the development of diabetes-ind...

Background Osteoarthritis is a chronic disease characterized by joint pain, tenderness, and limitation of movement. At present, no cure is available. Thus only treatment of the person's symptoms and treatment to prevent further development of the disease are possible. Clinical trials indicate that aquatic exercise may have advantages for people with osteoarthritis. This is an update of a published Cochrane review. Objectives To evaluate the effects of aquatic exercise for people with knee or hip osteoarthritis, or both, compared to no intervention.

Objective-Atherosclerotic lesions contain hypoxic areas, but the pathophysiological importance of hypoxia is unknown.Hypoxia-inducible factor-1α (HIF-1α) is a key transcription factor in cellular responses to hypoxia. We investigated the hypothesis that HIF-1α has effects on macrophage biology that promotes atherogenesis in mice. Approach and Results-Studies with molecular probes, immunostaining, and laser microdissection of aortas revealed abundant hypoxic, HIF-1α-expressing macrophages in murine atherosclerotic lesions. To investigate the significance of macrophage HIF-1α, Ldlr −/− mice were transplanted with bone marrow from mice with HIF-1α deficiency in the myeloid cells or control bone marrow. The HIF-1α deficiency in myeloid cells reduced atherosclerosis in aorta of the Ldlr −/− recipient mice by ≈72% (P=0.006). In vitro, HIF-1α-deficient macrophages displayed decreased differentiation to proinflammatory M1 macrophages and reduced expression of inflammatory genes. HIF-1α deficiency also affected glucose uptake, apoptosis, and migratory abilities of the macrophages. Conclusions-HIF-1α expression in macrophages affects their intrinsic inflammatory profile and promotes development of atherosclerosis.