title: 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.
abstract: 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)
authors.affiliation: Department of Internal Medicine, Yong Dong Severance Hospital, Yonsei University, College of Medicine, Seoul, Korea.
authors.forename: E J
authors.initials: EJ
authors.lastname: Lee
authors.forename: S Y
authors.initials: SY
authors.lastname: Nam
authors.forename: K R
authors.initials: KR
authors.lastname: Kim
authors.forename: H C
authors.initials: HC
authors.lastname: Lee
authors.forename: J H
authors.initials: JH
authors.lastname: Cho
authors.forename: M S
authors.initials: MS
authors.lastname: Nam
authors.forename: Y D
authors.initials: YD
authors.lastname: Song
authors.forename: S K
authors.initials: SK
authors.lastname: Lim
authors.forename: K B
authors.initials: KB
authors.lastname: Huh
mesh_terms: D000328:Adult; D015331:Cohort Studies; D004357:Drug Synergism; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology*; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D009765:Obesity / Q000097:blood* / Q000503:physiopathology; D011719:Pyrazines / Q000494:pharmacology*; D012016:Reference Values; D013997:Time Factors
chemical_list: D005230:Fatty Acids, Nonesterified; D000960:Hypolipidemic Agents; D011719:Pyrazines; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; C027696:acipimox