Thermogenesis in human brown adipose tissue and skeletal muscle induced by sympathomimetic stimulation

The aim of the present work was to elucidate the importance of brown adipose tissue (BAT) and skeletal muscle for ephedrine-induced thermogenesis, and to examine the effect of chronic ephedrine treatment on energy expenditure. The investigations were carried out in vivo on humans, as well as on rats and dogs. In rodents BAT is the major site of cold-induced nonshivering thermogenesis and of facultative thermogenesis: the component of food-induced thermogenesis storage of nutrients. BAT thermogenesis is mediated through an activation of the sympathetic nervous system. Via a sustained stimulation of the sympathetic nervous system, acclimation to cold and overfeeding induces hyperplasia of BAT, and subsequently an increased thermogenic capacity. In a number of obesity syndromes in rodents the sympathetic mediation is defective, and this leads to extreme sensitivity to cold and to obesity. BAT has been reported to be present also in humans, and there has been focused mainly on the interscapular subcutaneous tissue. An ephedrine-induced increase of the interscapular skin temperature has been interpreted as evidence of the presence of thermogenic BAT. This lead to the assumption that BAT, also in humans, plays a significant role in the regulation of energy balance. Likewise, the hypothesis has been advanced that a diminished thermogenesis in BAT may be the cause of some types of human obesity. After validation of the xenon clearance method in rats for blood flow measurements in BAT, the method was applied on humans to examine the ephedrine-induced increase in the interscapular temperature. The warmest interscapular skin area was localized by thermography during ephedrine stimulation. In a second study subcutaneous blood flow and temperature were measured in this area during ephedrine stimulation and compared to the response of white adipose tissue in the lumbar area. The results showed that the increases in blood flow and temperatures were of similar magnitude in the two locations. Biopsies taken from the warmest interscapular spots did not contain brown adipocytes. A histological study on human autopsies confirmed that BAT is rare in the interscapular tissue, but frequently occurring in the perirenal depot. In the next study, the thermogenic function of the perirenal BAT was examined by measurements of blood flow and local temperature. Perirenal BAT thermogenesis was uninfluenced by ephedrine in 4 of 5 subjects. It was estimated that BAT thermogenesis in the single responding subject could account for maximally 15% of the ephedrine-induced increase in whole body oxygen consumption.(ABSTRACT TRUNCATED AT 400 WORDS)