Tumor Necrosis Factor

Tumor necrosis factor toxicity includes hemodynamic instability, fever, diarrhea, metabolic aci-dosis, capillary leak syndrome, activation of coagulation, late hypoglycemia, induction of a catabolic state, neurotoxicity, cachexia, and renal and hematological disorders, all phenomena associated with sepsis syndrome (142). In addition, together with IL-1, TNF induces on the endothelial cell the expression of adhesion molecules involved in organ infiltration by leukocytes. The lethal effect of TNF...

Role of Leptin in the Regulation of Body Weight

Chronic administration of recombinant ob protein has been shown to produce a significant reduction in body weight in ob ob and normal mice because of a reduction in food intake but also an increase in energy expenditure (26-28). Centrally administered leptin (into the lateral or third cerebral ventricles) has been shown to be particularly effective in promoting anorexia and weight loss at doses which when administered peripherally were without effect on feeding behavior (26). This suggests that...

The Cognate Immune Response

As mentioned earlier, the innate and cognate immune systems are interlinked, so that many of the effects of leptin discussed in Section 4 will have implications for the behavior of responding lymphocytes. It is also clear that an organism mounts a coordinated immune response to an infectious pathogen that initially comprises innate immunity and then evolves, if appropriate to involve the cognate immune system. An important point of communication between the innate and cognate arms of the immune...

Role of Leptin as a Signal of Starvation

In 1996, Ahima et al. proposed a role for leptin as a signal of energy deficiency (14). Circulating leptin levels fall rapidly in response to starvation when energy intake is limited and energy stores (fat) are declining. It was suggested that leptin may have evolved to signal the shift between sufficient and insufficient energy stores (18). The hypothesis that reduced circulating leptin levels signal nutrient deprivation is supported by the demonstration that prevention of the...

In Vivo Models Of Leptin Deficiency 31 The obob and dbdb Mouse

Recessive mutations in the mouse diabetes (db) and obese (ob) genes have long been recognized to cause a syndrome of obesity and diabetes resembling morbid obesity in humans (32,72). These mice are phenotypically identical, each weighing three times more than normal mice, with a fivefold increase in body fat content. In his pioneering parabiosis work, Coleman showed that the obesity in the ob ob mouse was the result of the lack of a circulating satiety factor and that the phenotype of the db db...