To examine whether moderate obesity and differences in body fat distribution are associated with abnormalities of protein metabolism, leucine turnover was measured in three groups of age-matched premenopausal women. Ten upper-body-obese (UB Ob), 10 lower-body-obese (LB Ob), and 10 nonobese (Non Ob) women were studied in an overnight postabsorptive condition (basal) and again during an infusion of low physiologic amounts of insulin (insulin clamp). Results showed that basal leucine carbon flux was greater (P less than 0.05) in UB Ob and LB Ob women than in Non Ob women (2.96 +/- 0.08 vs 3.14 +/- 0.16 vs 2.68 +/- 0.08 mumol.kg lean body mass-1.min-1, respectively; mean +/- SEM). Leucine carbon flux was not suppressed during the insulin-clamp study in UB Ob women but was in the LB Ob and Non Ob women. We conclude that moderate obesity is associated with increased proteolysis and that insulin's antiproteolytic actions are impaired in upper-body obesity. These findings could have implications for future studies of and treatment of obesity.