Control of fatty acid utilization in brown adipose tissue

Abstract: In order to keep warm in cold surroundings, mammals have developed a mechanism for non-shivering thermogenesis. The major part of this heat production takes place in brown adipose tissue. The heat results from combustion of fatty acids. In experiments performed with isolated brown fat cells and mitochondria from hamsters and rats, the control of fatty acid utilization in the tissue has been investigated. Optimal conditions for fatty acid export from and for fatty acid combustion in brown fat cells have been established, and the effects of norepinephrine and insulin on the cells measured. Catecholamine sensitivity has been reintroduced into cells from cold-adapted animals. Factors which control peroxisomal β-oxidation and mitochondrial pyruvate carboxylation have been investigated. A hypothesis is suggested, according to which catecholamine- elicited increase in plasma membrane Na permeability leads to increased cytosolic Ca++ through the action of the mitochondrial Na+ /Ca++ exchange; such an increased cytosolic Ca++ concentration may have regulatory functions; eg. it may, by stimulation of the mitochondrial glycerol -3-phosphate dehydrogenase, direct fatty acids towards combustion (and not towards re-esterification) during thermogenesis. The heat production of norepinephrine-stimulated isolated brown fat cells has been directly measured; it is established that the capacity for heat production (about 0.3 W per gram wet weight) would be sufficient to counteract the heat loss of mammals in cold surroundings.