EFFECT OF NORADRENALINE ON GLYCEROL TURNOVER AND LIPOLYSIS IN THE WHOLE-BODY AND SUBCUTANEOUS ADIPOSE-TISSUE IN HUMANS IN-VIVO

1. The effect of infusion of noradrenaline (0.42 mu mol min(-1) kg(-1)) on the exchange of nonesterified fatty acids, glycerol and other metabolites across subcutaneous abdominal adipose tissue was investigated in five healthy subjects using an arteriovenous catheterization technique and measurement of adipose tissue blood flow using the Xe-133 clearance technique. At the same time, the net rate of fat oxidation in the whole body was assessed by indirect calorimetry, and the turnover of glycerol in the whole body and in subcutaneous adipose tissue was estimated using [5-H-2]glycerol, which was administered as a primed constant infusion for Ih before (basal turnover) noradrenaline administration and continued during the Ih of noradrenaline infusion. 2. The noradrenaline infusion increased the plasma noradrenaline concentration from a basal value of 0.9 +/- 0.1 to 12.6 +/- 1.2 nmol/(mean +/- SEM) at 60 min. It also increased the arterialized concentration of glycerol by 50% (basal value 81 +/- 11 mu mol/l(-1)) and that of plasma non-esterified fatty acids three-fold (basal value 357 +/- 86 mu mol/l). 3. Noradrenaline increased the net release of glycerol by adipose tissue three-fold and that of non-esterified fatty acids three- to four-fold. Although the ratio of non-esterified fatty acid to glycerol release by adipose tissue increased in all subjects from a mean value of 2.7 in the basal period to 3.6 and 3.9 at 50 and 60 min of the noradrenaline infusion, respectively (P<0.02), at no time point did the ratio differ significantly from 3.0 4. Noradrenaline increased the estimated rate of appearance of glycerol in the whole body from a basal value of 1.5 +/- 0.3 to 2.6 +/- 0.3 mu mol min(-1) kg(-1) body weight, and the net rate of triacylglycerol oxidation from 1.2 +/- 0.1 to 1.7 +/- 0.13 mu mol min(-1) kg(-1). The enrichment of glycerol in venous blood draining adipose tissue was two-fold lower than that predicted from the net addition of glycerol to the blood in the basal period (P<0.02). 5. This study provides a direct demonstration of a 'hormone' stimulating lipolysis in human adipose tissue in vivo. The effect of noradrenaline in significantly increasing the ratio of non-esterified fatty acid to glycerol release by adipose tissue may be partly explained by accumulation in adipose tissue of diacylglycerol, which is associated with release of nonesterified fatty acids but not glycerol. Finally, since the low enrichment of glycerol in venous blood draining adipose tissue cannot be entirely explained by the net addition of glycerol in adipose tissue, there must be exchange between enriched glycerol in blood and unenriched glycerol in adipose tissue. This raises questions about the accuracy of glycerol turnover studies, which are typically carried out over 1 h.