Escherichia coli peritonitis activates thermogenesis in brown adipose tissue: relationship to fever

Fever is a complex and important nonspecific, host defense mechanism against infection. The generation of the heat necessary to increase body temperature may involve thermogenesis in brown adipose tissue. To investigate whether the febrile response to Escherichia coli peritonitis involves thermogenesis in brown adipose tissue, we assessed whole rat oxygen consumption and brown adipose tissue mitochondrial guanosine 5′-diphosphate binding. Non-lethal doses of E. coli, 1 × 106 to 1 × 108 colony forming units, induced a fever for greater than 8 h. In contrast, a dose of 1 × 109 colony forming units resulted in a progressive hypothermia culminating in death. A 48% increase in oxygen consumption (p < 0.05) in E. coli-infected rats occurred almost immediately, preceded the development of the fever, and was sustained throughout the fever. There was a highly significant correlation (r = 0.736, p < 0.01) between oxygen consumption and body temperature for both control and infected animals. Guanosine 5′-diphosphate binding assessed by multi-point Scatchard analysis of [3H]guanosine 5′-diphosphate binding to isolated mitochondria was increased by 45.4 ± 7.3% at 1.75 h and by 31.9 ± 9.0% at 3.5 h (p < 0.05). The greater increase was during the rising phase of the fever. Unexpectedly, a lethal dose of 5 × 109 colony forming units of E. coli also increased guanosine 5′-diphosphate binding sites by 54.4 ± 14.2% (p < 0.05) despite a hypothermia of −1.71 ± 0.29 °C. These data indicate that peritonitis induces a fever that is correlated with oxygen consumption and increased guanosine 5′-diphosphate binding sites, suggestive of brown adipose tissue thermogenesis activation. This thermogenesis appears to be contributing at least some of the heat necessary for the febrile response in rats.Key words: rat, guanosine 5′-diphosphate binding, oxygen consumption.