Obesity is a major problem of public health today in the world. It is believed that, with the exception of rare cases of monogenic defects, the accumulation of body mass is a result of the combination of multiple genetic and environmental factors. Thus the balance between the food intake and body weight is the main regulator of body weight. Obesity-related diseases such as systemic hypertension, hypercholesterolemia, metabolic syndrome and diabetes are associated with oxidative modification of LDL by reactive oxygen species (ROS). The generation of ROS in vascular wall cells or for circulating leukocytes may promote fat accumulation, atherogenesis, thrombus formation and insulin resistance. Eating a high fat diet also induces the expression of several proinflammatory cytokines in the hypothalamus, among them tumor necrosis factor alpha (TNF-±). This factor is involved in several metabolic disorders and their expression is shown increased in case of diet-induced obesity. TNF-± acts through two distinct receptors, TNFR1 and TNFR2, but the TNFR1 is responsible for most of the effects of this cytokine. Recent studies have demonstrated that deletion of a receptor for TNF-± protects mice against the resistance to leptin in cases of diet-induced obesity. These results also demonstrated that TNF-± binding to TNFR1 could result in a defective thermogenesis, however, in the context of diet-induced obesity, the function of this receptor is not fully understood. TNFR1 knockout mice also exhibit an increase in oxygen consumption, which may be related to the expression of UCP1 and UCP3 in brown adipose tissue and skeletal muscle, respectively. In this context, the purpose of this study is to conduct studies of mitochondrial function in liver, heart, muscle, brown adipose tissue and lymphocytes isolated from the spleen of TNFR1 KO mice in order to clarify the possible role of mitochondria in these animals resistant to diet hyperlipidemic.
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