THE EFFECTS OF DIETARY WEIGHT LOSS ON INDICES OF NORADRENALINE TURNOVER: MODULATORY INFLUENCE OF HYPERINSULINEMIA (#75)
Background: Chronic sympathetic nervous system overactivity is a characteristic of the metabolic syndrome that contributes to insulin resistance, target organ damage and a worse clinical prognosis. Plasma noradrenaline (NE) levels reflect the dynamic interplay of synthesis, release and disposition.
Objectives: This study was conducted to examine 1) the effects of dietary weight loss on indices of noradrenaline turnover and 2) whether baseline hyperinsulinemia modulates sympathetic neural adaptations.
Subjects & Methods: Obese individuals aged 56 ± 1 yr, body mass index 32.5 ± 0.4 kg/m2, with metabolic syndrome, underwent a 12-week hypocaloric diet (HCD, n=39) or no treatment (n=26). Neurochemical measurements comprised arterial dihydroxyphenylalanine (DOPA) and 3,4-dihydroxyphenylglycol (DHPG) concentrations, intraneuronal precursor and metabolite respectively of NE, arterial NE, the steady-state ratio of [3H]-DHPG to [3H]-NE, as an index of neuronal uptake, and calculated whole-body plasma NE clearance and spillover rates. Hyperinsulinemia was defined as an insulin AUC0-120 during oral glucose tolerance test >10,000 mU/L ∙ min.
Results: Body weight decreased by -7.4 ± 0.5% in HCD group (P<0.001) and was accompanied by reductions in DOPA, NE and DHPG averaging -14 ± 5% (P=0.001), -23 ± 4% (P<0.001) and -5 ± 4% (P=0.03), respectively. NE spillover rate decreased by -88 ± 39 ng/min (P=0.01), whereas neuronal uptake and NE plasma clearance were unchanged. Despite similar weight loss, hyperinsulinemic subjects exhibited greater reductions in NE, NE spillover rate and diastolic blood pressure, compared to normoinsulinemic subjects (group by time interaction P<0.05). Change in insulin AUC0-120 during weight loss, independently predicted the reduction in NE level.
Conclusions: Weight loss is associated with down regulation of NE production and reduced spillover rate into plasma, but no overall alteration in disposition indices. Hyperinsulinemic subjects derive a greater sympathoinhibitory benefit during weight loss.