A role for brown adipose tissue in the genesis of obesity? Studies on experimental animals

Whether or not the processes which constitute thermogenesis play a significant role in the regulation of energy balance has long been a matter of controversy.As some of the other contributors to this symposium will testify the controversy is still far from settled.It is our view, however, that in certain experimental circumstances the evidence in favour of a quantitatively important role for thermogenesis in energy balance is strong, while in others, particularly those relating to man, it is not impressive.The biochemical mechanisms responsible for thermogenesis and their tissue localization have also been matters of considerable uncertainty.Over the years skeletal muscle and the liver have generally been regarded as the most likely sites for adaptive thermogenesis, and a number of mechanisms within these tissues have been proposed.These mechanisms include protein turnover, the a-glycerophosphate shuttle, the Na+ pump, and various other specific substrate cycles.None of the mechanisms have been widely accepted, however, and this is partly because in many cases, e.g. the fructose-6-phosphate/fructose-1 ,&-biphosphate cycle, there does not seem to be the potential for generating substantial amounts of heat.The most recent tissue to receive attention as the main site of adaptive thermogenesis is brown adipose tissue (BAT).Although the importance of this organ to thermoregulatory non-shivering thermogenesis in many new-born and hibernating mammals has been accepted for some time, BAT was considered to be of little significance in the thermogenesis of adult animals (Jansky, 1973).This view has been altered radically in the past 3 years, however, by the results of Foster & Frydman (1978, 1979).Using radioactively labelled microspheres to determine regional blood flow, together with measurements of arterio-venous differences in oxygen tension across tissues, these authors were able to demonstrate that BAT was the most important site of non-shivering thermogenesis in adult rats (Foster & Frydman, I 978, 1979).Furthermore, skeletal muscle was shown to play at best only a very minor role.These results have had considerable impact and changes in the activity of BAT in three different situations relevant to energy balance and obesity have now been demonstrated and are described in this paper. Mechanism of heat production in BATA number of mechanisms for thermogenesis in B A T itself have been postulated, both mitochondria1 and extra-mitochondrial.However, the mechanism which has