Fuel supply to brown adipose tissue.

In the guinea pig, cold-adaptation is associated with a doubling of cell number, a doubling of mitochondria per cell, and a seven-fold increase in uncoupling protein per mitochondrion (Rial & Nicholls, 1984; Rafael et al., 1985), the last correlating with the six-fold increase in noradrenaline-stimulated respiration per mitochondrion (Rafael et al., 1985). While isolated mitochondria may be used to model plausible uncoupling mechanisms as discussed above, evidence which can be obtained using the more physiological intact adipocyte preparation is likely to be much less ambiguous. ‘Fatty acid uncoupling’ of brown adipocytes after addition of exogenous fatty acids was first observed by Fain et al. (1967) and by Prusiner et al. (1968a). The fatty acids could mimic the respiratory stimulation seen on noradrenaline addition, and the proposal was therefore made that fatty acids could act as both substrates and uncouplers, although these early studies could provide no mechanistic basis for the tissue selectivity of the process. The uncoupling by added fatty acids has been more recently explored by Bukowiecki et al., (198 1). Although the concentrations of added fatty acids seem extremely high (typically 0 .41 mM), it must be born in mind that the fatty acids are equilibrating with the albumin present in all incubation media. We have recently determined the unbound fatty acid in equilibrium with the albumin during the uncoupling of cold-adapted brown adipocytes from the guinea pig (H. Wiesinger & S. A. Cunningham, unpublished work) and have concluded that the cells are stimulated by palmitate over the range 20-200 nM-unbound fatty acid. Cells from warmadapted guinea pigs are substantially less sensitive to fatty acid uncoupling compared with the cold-adapted adipocytes, consistent with an interaction between the permeating fatty acids and the uncoupling protein in the mitochondria in situ. This result suggests that the differential ability of noradrenaline to uncouple the two types of guinea-pig cell can be explained simply by the sensitivity of the mitochondria in situ to fatty acid uncoupling.