Development of brown adipose tissue in the rat

Interscapular brown adipose tissue (BAT) was studied during perinatal and early postnatal life of the rat. Several parameters of apparent functional importance were analysed, particularly respiratory enzymes which are related to the main function of BAT, heat generation. I . Functional development of brown adipose tissue in the rat. The ratio fresh weight of BAT/body weight peaked at day 1 after birth and declined subsequently; cold exposure reversed the decline. Protein content of the tissue increased sharply during perinatal development. Specific activities of several respiratory enzymes in the tissue increased rapidly during late fetal and early postnatal life, reached a peak by day 17 and declined thereafter. Cold acclimation of older animals returned the activities up to the same level as observed on day 17. A similar bi-phasic pattern was observed when the total BAT activities of the respiratory enzymes were related to body weight. These data together with some additional parameters, such as DNA, RNA, glycogen and norepinephrine content of the tissue, activities of monoamine oxidase and some enzymes involved in glycolysis, fatty acid and triglyceride synthesis, as well as morphological observations were interpreted in the following way: The tissue starts a very rapid rate of proliferation and differentiation prior to birth, reaches a high degree of maturation and activity during the second postnatal week and involution commences during the fourth week after birth. Involution of BAT continues indefinitely at neutral ambient temperature and can be reversed by cold exposure. This developmental pattern relates well to changing functional demands for non-shivering thermogenesis, pronounced mostly during the earliest postnatal stage and also during prolonged cold exposure of more mature animals. II. Development of mitochondria in brown adipose tissue. Isolated BAT mitochondria were studied and developmental changes observed in activities as well as amounts of respiratory chain enzymes and phospholipids. The biochemical results corresponded to morphological changes in the inner mitochondrial membrane. Hence the observed developmental changes of the tissue respiratory capacity seem to be a reflection of changes in the mitochondria. In addition BAT mitochondria proved to be a convenient model for studies of mitochondriogenesis in a mammalian tissue. III. Hormones and regulation of brown adipose tissue development. After the developmental pattern of BAT was established the problem of regulatory mechanism(s) governing the developmental alterations was approached. The in vivo effects of norepinephrine, epinephrine, thyroxine and cortisone as well as the effect of ambient temperature were studied during both the proliferative and the involutive phases of BAT development. Norepinephrine and cyclic AMP seem to be involved in the initiation and control of BAT differentiation. Cortisone exerted a detrimental effect upon the tissue and the possibility that corticoids are somehow involved in the second, involutive phase of BAT development was suggested. IV. The hormonal receptor system in brown adipose tissue and its development. An adenyl cyclase, selectively sensitive to catecholamines, increased in activity up to the 20th postnatal day. Cyclic AMP levels in the tissue reached a peak just prior to birth and decreased postnatally. Cyclic AMP - dependent protein kinase activity increased perinatally and decreased after day 20. An inhibitor of protein kinase was most active perinatally. Phosphorylase and phosphorylase kinase were both present primarily in the activated form before birth and both increased immediately prior to parturition; then declined rapidly. The inactive form prevailed during postnatal life. Cold exposure caused increases in total phosphorylase, protein kinase, adenyl cyclase and cyclic AMP levels. V. Interpretation. Developmental patterns of enzymes involved in the hormonal stimulation pathway together with the in vivo experiments of Part III seem to support an involvement of a hormonal regulatory system in BAT development. A speculative scheme was proposed for the mechanism by which catecholamines may exert a trophic effect upon the tissue in addition to their short-term functional stimulatory action.Medicine, Faculty ofCellular and Physiological Sciences, Department ofGraduat