Effects of Cations on Brown Adipose Tissue in Relation to Possible Metabolic Consequences of Membrane Depolarisation

Abstract

Norepinephrine-stimulated respiration of isolated hamster brown fat cells is only slightly dependent upon the extracellular concentration of Mg2+ and Ca2+, but very dependent upon K+ and Na+. The inhibition of respiration in the absence of K+ is caused by diminished norepinephrine-stimulated fatty acid release. In the absence of Na+, norepinephrine-stimulated fatty acid release proceeds virtually unaffected. Na+-stimulated Ca2+ release from isolated brown fat mitochondria is higher in preparations from cold-adapted rats than from control rats. Extramitochondrial (cytosolic) Ca2+ level is regulated by Na+ in the range 5-25 mM. K+ in the range 0-20 mM decreased mitochondrial Ca2+ uptake and thus promotes the effect of Na+ on the extramitochondrial steady-state level of Ca2+. Energy dissipating Na+-induced Ca2+-cycling is only of minor thermogenic importance. Mitochondrial glycerol-3-phosphate dehydrogenase is indirectly regulated by Na+ through an increase in extramitochondrial Ca2+. Lack of Na+ in the incubation medium for brown fat cells abolishes the inhibitory effect of norepinephrine addition on triacylglycerol synthesis. Apparently, norepinephrine-induced plasma membrane depolarization in brown fat cells leads, through the increased Na+ entry, to elevated cytosolic levels of Na+. This Na+ has metabolic consequences: it increases the cytosolic Ca2+ level, and this Ca2+ may regulate enzyme systems, including glycerol-3-phosphate dehydrogenase. Lowered levels of glycerol 3-phosphate within brown fat cells may reduce the rate of fatty acid esterification and, in consequence, acyl-CoA may be directed towards oxidation.