Acipimox potentiates growth hormone (GH) response to GH-releasing hormone with or without pyridostigmine by lowering serum free fatty acid in normal and obese subjects
EJ Lee, SY Nam, KR Kim, HC Lee, JH Cho, MS Nam, YD Song, SK Lim and KB Huh
Department of Internal Medicine, Yong Dong Severance Hospital, Yonsei University, College of Medicine, Seoul, Korea.
Obesity is associated with an impairment of normal GH secretion and blunted
responses to all stimuli. Recent reports suggest that increased
somatostatinergic activity is the basis for the GH derangement of obesity.
However, the basic mechanism of this alteration is still being debated. The
high plasma free fatty acid (FFA) is frequently observed in obesity. FFA
participates in the regulation of pituitary GH secretion. To determine
whether the derangement of GH secretion in obesity is associated with high
plasma FFA levels, several tests with GHRH with or without pyridostigmine
(PYR) and acipimox (ACX), antilipolytic agents able to decrease FFA, were
undertaken in six obese and seven normal control subjects. In obese
subjects, the GH response (mean peak +/- SEM: 8.9 +/- 1.1 ug/L) to
GHRH-(1-29) (1 ug/kg, i.v.) was significantly blunted when compared with
the response in normal control subjects (25.7 +/- 1.8 ug/L; P < 0.05).
After PYR (120 mg), the response to GHRH was enhanced in the obese subjects
(21.4 +/- 4.9 ug/L; P < 0.05) and was similar to that of the controls
with GHRH only, but remained significantly reduced compared with controls
treated with PYR plus GHRH (43.2 +/- 6.0 ug/L; P < 0.05). Basal FFA
levels were higher than those of normal controls (P < 0.05). ACX (500
mg) decreased FFA levels in both obese and normal subjects; the lowest FFA
levels of obese subjects at 15 min were similar to those of normal
controls. ACX also potentiated GHRH-stimulated GH response in both obese
and normal subjects. The GH responses potentiated by ACX in obesity (22.7
+/- 5.5 ug/L) were similar to those of PYR plus GHRH in obese subjects and
GHRH in normal controls, but they were lower than those of control treated
with ACX plus GHRH (50.8 +/- 6.7 ug/L; P < 0.05). After the combined
pretreatment with ACX and PYR, GH responses in obesity (44.1 +/- 6.0 ug/L)
were significantly higher than those in GHRH test, PYR plus GHRH, and ACX
plus GHRH in obese subjects (P < 0.05), and they were similar to PYR
plus GHRH or ACX plus GHRH in normal controls. However their enhanced GH
responses were reduced compared with the control with ACX plus PYR plus
GHRH (64.9 +/- 4.5 ug/L; P < 0.05). Our results are in agreement with
the hypothalamic hypothesis: an increase in somatostatinergic tone is
responsible for the blunted GH response to GHRH in obesity.(ABSTRACT
TRUNCATED AT 250 WORDS)
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