In our study population, sudden death was precipitated by acute coronary thrombosis in only 27% of patients with obstructive coronary atherosclerotic plaque. Most of the young victims of sudden death with obstructive coronary atherosclerosis showed single-vessel disease that affected the left anterior descending coronary artery and was due to fibrous plaques with neointimal smooth muscle cell hyperplasia and a preserved tunica media in the absence of acute thrombosis.
Objective
Obesity is associated with enhanced reactive oxygen species (ROS) accumulation in adipose tissue. However, a causal role for ROS in adipose tissue expansion after high fat feeding is not established. The aim of this study is to investigate the effect of the cell permeable superoxide dismutase mimetic and peroxynitrite scavenger Mn(III)tetrakis(4-benzoic acid)porphyrin chloride (MnTBAP) on adipose tissue expansion and remodeling in response to high fat diet (HFD) in mice.
Design and Methods
Male C57BL/6j mice were fed normal chow or high fat diet (HFD) and treated with saline or MnTBAP for 5 weeks. The effects of MnTBAP on body weights, whole body energy expenditure, adipose tissue morphology and gene expression were determined.
Results
MnTBAP attenuated weight gain and adiposity through a reduction in adipocyte hypertrophy, adipogenesis and fatty acid uptake in epididymal (eWAT) but not in inguinal (iWAT) white adipose tissue. Furthermore, MnTBAP reduced adipocyte death and inflammation in eWAT and diminished circulating levels of free fatty acids and leptin. Despite these improvements, the development of systemic insulin resistance and diabetes after HFD was not prevented with MnTBAP treatment.
Conclusions
Taken together, these data suggest a causal role for ROS in the development of diet-induced visceral adiposity but not in the development of insulin resistance and type 2 diabetes.
We studied the action of H2O2 on the exocytosis of glutamate by cerebrocortical synaptosomes. The treatment of synaptosomes with H2O2 (50–150 µM) for a few minutes results in a long‐lasting depression of the Ca2+‐dependent exocytosis of glutamate, induced by KCl or by the K+‐channel inhibitor 4‐aminopyridine. The energy state of synaptosomes, as judged by the level of phosphocreatine and the ATP/ADP ratio, was not affected by H2O2, although a transient decrease was observed after the treatment. H2O2 did not promote peroxidation, as judged by the formation of malondialdehyde. In indo‐1‐loaded synaptosomes, the treatment with H2O2 did not modify significantly the KCl‐induced increase of [Ca2+]i. H2O2 inhibited exocytosis also when the latter was induced by increasing [Ca2+]i with the Ca2+ ionophore ionomycin. The effects of H2O2 were unchanged in the presence of superoxide dismutase and the presence of the Fe3+ chelator deferoxamine. These results appear to indicate that H2O2, apparently without damaging the synaptosomes, induces a long‐lasting inhibition of the exocytosis of glutamate by acting directly on the exocytotic process.
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