Quantification of fatty acid activation of the uncoupling protein in brown adipocytes and mitochondria from the guinea-pig.

SA Cunningham, H Wiesinger… - European journal of …, 1986 - europepmc.org
SA Cunningham, H Wiesinger, DG Nicholls
European journal of biochemistry, 1986europepmc.org
Brown adipocytes from cold-adapted guinea-pigs (C-cells) are more sensitive to uncoupling
by exogenous palmitate than are cells from warm-adapted animals (W-cells) with much less
uncoupling protein. Half-maximal respiratory stimulation of C-cells requires 80 nM free
palmitate. Noradrenaline-stimulated lipolysis is not rate-limiting for the respiration of either C-
cells or W-cells. Half-maximal stimulation of fatty acid oxidation by mitochondria from warm-
adapted guinea-pigs (W-mitochondria) and cold-adapted guinea-pigs (C-mitochondria) both …
Brown adipocytes from cold-adapted guinea-pigs (C-cells) are more sensitive to uncoupling by exogenous palmitate than are cells from warm-adapted animals (W-cells) with much less uncoupling protein. Half-maximal respiratory stimulation of C-cells requires 80 nM free palmitate. Noradrenaline-stimulated lipolysis is not rate-limiting for the respiration of either C-cells or W-cells. Half-maximal stimulation of fatty acid oxidation by mitochondria from warm-adapted guinea-pigs (W-mitochondria) and cold-adapted guinea-pigs (C-mitochondria) both require 12 nM free palmitate. Palmitate uncouples C-mitochondria much more readily than M-mitochondria, paralleling its action on the adipocytes. The uncoupling is partially saturable, about 100 nM free palmitate being required for half-maximal response of C-mitochondria. W-and C-mitochondria show identical binding characteristics for palmitate. The respiratory increase of mitochondria is calculated as a function of bound palmitate. After correcting for the residual uncoupling protein present in W-mitochondria, palmitate is estimated to be almost ineffective as an uncoupler of brown fat mitochondria in the absence of the protein. It is concluded that fatty acids display characteristics required of a necessary and sufficient physiological activator of the uncoupling protein.
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