The effects of dietary weight loss on indices of norepinephrine turnover: modulatory influence of hyperinsulinemia

Obesity (Silver Spring). 2014 Mar;22(3):652-62. doi: 10.1002/oby.20614. Epub 2013 Dec 6.

Abstract

Objectives: This study was conducted to examine (1) the effects of dietary weight loss on indices of norepinephrine (NE) turnover and (2) whether baseline hyperinsulinemia modulates sympathetic neural adaptations.

Methods: Obese individuals aged 56 ± 1 year, BMI 32.5 ± 0.4 kg/m(2) , with metabolic syndrome, underwent a 12-week hypocaloric diet (HCD, n = 39) or no treatment (n = 26). Neurochemical measurements comprised arterial dihydroxyphenylalanine (DOPA), 3,4-dihydroxyphenylglycol (DHPG), and NE concentrations, 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.

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 and NE spillover rate, compared to normoinsulinemic subjects (group by time interaction P < 0.05).

Conclusions: Weight loss is associated with down-regulation of sympathetic nervous activity but no overall alteration in disposition indices. Hyperinsulinemic subjects derive a greater sympathoinhibitory benefit during weight loss.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Body Mass Index
  • Diet, Reducing*
  • Dihydroxyphenylalanine / blood
  • Dihydroxyphenylalanine / pharmacokinetics
  • Down-Regulation
  • Energy Metabolism
  • Female
  • Humans
  • Hyperinsulinism / complications
  • Hyperinsulinism / metabolism*
  • Male
  • Metabolic Syndrome / complications
  • Metabolic Syndrome / metabolism
  • Methoxyhydroxyphenylglycol / analogs & derivatives
  • Methoxyhydroxyphenylglycol / blood
  • Methoxyhydroxyphenylglycol / pharmacokinetics
  • Middle Aged
  • Norepinephrine / blood*
  • Norepinephrine / pharmacokinetics
  • Obesity / complications
  • Obesity / metabolism
  • Sympathetic Nervous System / drug effects
  • Weight Loss / drug effects*
  • White People

Substances

  • Methoxyhydroxyphenylglycol
  • Dihydroxyphenylalanine
  • 3,4-dihydroxyphenylglycol
  • Norepinephrine