Lipogenesis in brown adipose tissue and its regulation.

acids and ketone bodies in the circulation, and there is a need to conserve glucose because of the relatively low carbohydrate content of the milk (for review see Williamson, 1985). During this period of development, brown adipose tissue has a vital role in thermogenesis, and the level of GDP-binding to brown-fat mitochondria is considerably increased (Sundin & Cannon, 1980). The weight of interscapular brown adipose tissue increases in direct proportion to the body weight up to 40 days of age (Cryer & Jones, 1978). The activity of lipoprotein lipase is increased by up to 800% during the suckling period (Cryer & Jones, 1978), whereas the activity of hexokinase is decreased (G. J. Cooney & E. A. Newsholme, unpublished work); on weaning on to a high carbohydrate diet these changes are reversed. In contrast, 3-oxoacid-CoA transferase, the initiating enzyme for acetoacetate utilization, remains at a relatively constant, albeit high, activity throughout the suckling period, whereas the activity of 3-hydroxybutyrate dehydrogenase is 50-fold lower (Williamson & Ilic, 1985). One may question why brown adipose tissue has this high capacity to utilize acetoacetate when this is an important substrate for developing brain (Williamson, 1985). The answer may lie in the ready reversibility of the 3-oxoacid-CoA transferase and acetoacetyl-CoA thiolase reactions, which means that acetoacetate can act as a buffer for the intramitochondrial pool of acetyl-CoA (Robinson & Williamson, 1980). Certainly, acetoacetate is not likely to act as a lipogenic substrate during the suckling period because the rate of lipogenesis in vivo measured with 'H,O is very low and increases dramatically on weaning (Pillay & Bailey, 1982). In addition, the activity of cytosolic acetoacetylCoA synthetase, which directs acetoacetate to lipid synthesis (Buckley & Williamson, 1975), has a similar developmental profile. Thanks are due to Loranne Agius and Stewart Mercer for initiating and sustaining the author's interest in brown adipose tissue, and to Mrs M. Barber for secretarial assistance. The author is a member of the External Scientific Staff of the Medical Research Council.