Acipimox enhances spontaneous growth hormone secretion in obese women.
We hypothesized that a high circulating free fatty acid (FFA) concentration is involved in the pathogenesis of hyposomatotropism associated with obesity. To evaluate this hypothesis, 10 healthy premenopausal women (body mass index 33.8 +/- 1.0 kg/m(2)) were studied in the follicular phase of their menstrual cycle at two occasions with a time interval of at least 8 wk, where body weight remained stable. Subjects were randomly assigned to treatment with either acipimox (an inhibitor of lipolysis, 250 mg orally 4 times daily) or placebo in a double-blind crossover design, starting 1 day before admission until the end of the blood sampling period. Blood samples were taken during 24 h with a sampling interval of 10 min for assessment of growth hormone (GH) concentrations, and GH secretion was estimated by deconvolution analysis. Identical methodology was used to study GH secretion in a historical control group of age-matched normal weight women. GH secretion was clearly blunted in obese women (total daily release 66 +/- 10 vs. lean controls: 201 +/- 23 mU x l(Vd)(-1) x 24 h(-1), P = 0.005, where l(Vd) is lite of distribution volume). Acipimox considerably enhanced total (113 +/- 50 vs. 66 +/- 10 mU x l(Vd)(-1) x 24 h(-1), P = 0.02) and pulsatile GH secretion (109 +/- 49 vs. 62 +/- 30 mU x l(Vd)(-1) x 24 h(-1), P = 0.02), but GH output remained lower compared with lean controls. Further analysis did not show any relationship between the effects of acipimox on GH secretion and regional body fat distribution. In conclusion, acipimox unleashes spontaneous GH secretion in obese women. It specifically enhances GH secretory burst mass. This might mean that lowering of systemic FFA concentrations by acipimox modulates neuroendocrine mechanisms that orchestrate the activity of the somatotropic ensemble.
Kok
Petra
P
Department of General Internal Medicine, Leiden University Medical Center, C4-83, PO Box 9600, 2300 RC Leiden, The Netherlands.
Buijs
Madelon M
MM
Kok
Simon W
SW
Van Ierssel
Inge H A P
IH
Frölich
Marijke
M
Roelfsema
Ferdinand
F
Voshol
Peter J
PJ
Meinders
A Edo
AE
Pijl
Hanno
H
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000328:Adult; D001823:Body Composition / Q000187:drug effects; D019277:Entropy; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006207:Half-Life; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D011719:Pyrazines / Q000494:pharmacology*
D005230:Fatty Acids, Nonesterified; D000960:Hypolipidemic Agents; D011719:Pyrazines; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; C027696:acipimox