Research in the 1960s and early 1970s contributed greatly to our understanding of the anatomy and physiology of brown adipose tissue and established its role in the hibernator and the newborn (for reviews see 79, 130,152,261). At that time, however, it was not possible to generalize about the contribution of brown fat to nonshivering thermogenesis, because this tissue was apparently of minor importance in the thermoregulation of most adult experimental animals (103-105129). Additionally no explanation could be given at the molecular level for the unique thermogenic capacity of the tissue. This review attempts to cover the developments in understanding of the scope and mechanism of brown fat thermogenesis after this fruitful period.

The recent upsurge in interest in brown adipose tissue has been precipitated by three main findings. First, reexamination of the methodology for assessing tissue activity in situ has indicated that brown fat is the major source of nonshivering thermogenesis in cold-adapted adult experimental animals such as the rat (72-74). Second, a major extension of the field occurred after the suggestion that brown fat plays a major role, at least in experimental animals, in diet-induced thermogenesis (239). Third, brown adipocytes (particularly their mitochondria) possess an apparently unique mechanism for uncoupling respiration from ATP synthesis (92, 150, 180, 185, 198, 221, 222). Variations in the activity of this uncoupling pathway have also been reported that may in part underlie the adaptive changes in thermogenic capacity of the tissue (92, 219, 221, 222, 235). A mechanistic basis for the extraordinary thermogenic capacity of brown fat has therefore emerged. This review is mainly concerned with the evidence for this third development, and the following specific problems are discussed. 1) Do brown fat mitochondria possess a unique mechanism for uncoupling ATP synthesis from respiration? 2) Does this mechanism function in the intact cell? 3) What is the intracellular messenger regulating this putative uncoupling mechanism? 4) Do changes in the capacity of the uncoupling mechanism