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APPETITE, OBESITY AND METABOLISM

Acipimox enhances spontaneous growth hormone secretion in obese women

¹Department of General Internal Medicine, ²Department of Clinical Chemistry, and ³Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, 2300 RC Leiden; and ⁴Dutch Organization for Applied Scientific Research-Prevention and Health/-Pharma, 2333 AL Leiden, The Netherlands

Submitted 13 October 2003 ; accepted in final form 8 December 2003

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/m²) 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·l_Vd^-1·24 h^-1, P = 0.005, where l_Vd is liter of distribution volume). Acipimox considerably enhanced total (113 ± 50 vs. 66 ± 10 mU·l_Vd^-1·24 h^-1, P = 0.02) and pulsatile GH secretion (109 ± 49 vs. 62 ± 30 mU·l_Vd^-1·24 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.

hyposomatotropism; growth hormone kinetics; somatotroph cell function; free fatty acid

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