IN-VIVO RESISTANCE OF LIPOLYSIS TO EPINEPHRINE - A NEW FEATURE OF CHILDHOOD-ONSET OBESITY

A decreased mobilization of triglycerides may contribute to fat accumu lation in adipocytes, leading to obesity. However, this hypothesis rem ains to be proven. In this study, epinephrine-induced lipid mobilizati on was investigated in vivo in nine markedly obese children (160 +/- 5 % ideal body weight) aged 12.1 +/- 0.1 yr during the dynamic phase of fat deposition, compared with six age-matched nonobese children. As an in vivo index of lipolysis, we measured glycerol flux using a nonradi oactive tracer dilution approach, and plasma free fatty acid concentra tions. In the basal state, the obese children had a 30% lower rate of glycerol release per unit fat mass than the lean children. To study th e regulation of lipolysis, epinephrine was infused stepwise at fixed d oses of 0.75 and then 1.50 mu g/min in both groups. In lean children, glycerol nux and plasma free fatty acid increased to an average of 249 -246% of basal values, respectively, in response to a mean plasma epin ephrine of 396 +/- 41 pg/ml. The corresponding increase was only 55-72 % in the obese children, although their mean plasma epinephrine reache d 606 +/- 68 pg/ml. All obese and nonobese children, except an Arg64Tr p heterozygote, were homozygotes for Trp at position 64 of their beta( 3)-adrenoreceptor. The resistance of lipolysis to epinephrine showed n o relationship with the Arg64 polymorphism of the beta(3)-adrenorecept or gene. In summary, in vivo lipolysis, which mostly reflects the mobi lization of lipid stores from subcutaneous adipose tissue, shows a dec reased sensitivity to epinephrine in childhood onset obesity. Since ou r study was carried out in obese children during the dynamic phase of fat accumulation, the observed resistance to catecholamines might poss ibly be causative rather than the result of obesity.