Effects of acipimox, an antilipolytic drug, on the growth hormone (GH) response to GH-releasing hormone alone or combined with arginine in obesity

Maccario, Mauro; Procopio, Massimo; Grottoli, Silvia; Oleandri, S. E.; Boffano, G. M.; Taliano, Marina; Camanni, F.; Ghigo, Ezio

doi:10.1016/s0026-0495(96)90288-7

Cited by 47 publications

(40 citation statements)

References 31 publications

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“…As estrogens may positively modulate GH secretion, the first limitation is that the subjects enrolled in the study were tested for GH secretion irrespective of their phase of the menstrual cycle and the sample we studied also included postmenopausal women. The lack of FFA measurement represents the second main limitation of this study, as FFAs decrease GH secretion and impair GH response to secretagogue in both HIV-infected patients (9) and HIV-uninfected subjects (41). Thirdly, GHRHCArg assesses the integrity of the GH pituitary reserve, thus in this setting the hypothalamic function could not be tested.…”

Section: Discussionmentioning

confidence: 98%

GH response to GHRH plus arginine is impaired in lipoatrophic women with human immunodeficiency virus compared with controls

Zirilli

Orlando

Carli

et al. 2012

European Journal of Endocrinology

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Objective: GH secretion is impaired in lipodystrophic human immunodeficiency virus (HIV) patients and inversely related to lipodystrophy-related fat redistribution in men. Less is known about the underlying mechanisms involved in reduced GH secretion in HIV-infected women. Design: A case-control, cross-sectional study comparing GH/IGF1 status, body composition, and metabolic parameters in 92 nonobese women with HIV-related lipodystrophy and 63 healthy controls matched for age, ethnicity, sex, and body mass index (BMI). Methods: GH, IGF1, IGF binding protein 3 (IGFBP3), GH after GHRH plus arginine (GHRHCArg), several metabolic variables, and body composition were evaluated. Results: GH response to GHRHCArg was lower in HIV-infected females than in controls. Using a cutoff of peak GH %7.5 mg/l, 20.6% of HIV-infected females demonstrated reduced peak GH response after GHRHCArg. In contrast, none of the control subjects demonstrated a peak GH response %7.5 mg/l. Bone mineral density (BMD), quality of life, IGF1, and IGFBP3 were lowest in the HIV-infected females with a GH peak %7.5 mg/l. BMI was the main predictive factor of GH peak in stepwise multiregression analysis followed by age, with a less significant effect of visceral fat in the HIV-infected females. Conclusions: This study establishes that i) GH response to GHRHCArg is lower in lipoatrophic HIVinfected women than in healthy matched controls, ii) BMI more than visceral adipose tissue or trunk fat influences GH peak in this population, and iii) HIV-infected women with a GH peak below or equal to 7.5 mg/l demonstrate reduced IGF1, IGFBP3, BMD, and quality of life.

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Section: Discussionmentioning

confidence: 98%

GH response to GHRH plus arginine is impaired in lipoatrophic women with human immunodeficiency virus compared with controls

Zirilli

Orlando

Carli

et al. 2012

European Journal of Endocrinology

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“…The chronic elevation of circulating FFA levels, which were further enhanced by fasting, could also have a key role in counteracting the GH response to starvation in obesity. 10,11,29 FFA has a strong inhibitory action on somatotroph secretion acting at either the pituitary or the hypothalamic level; 31,32,36 in fact, lipolysis inhibitors restore GH secretion in obesity. 10,11,29,37 In the absence of any significant increase in GH secretion obese patients in our study showed normal activation of lipolysis; this probably reflects the fasting-induced response of other contraregulatory hormones.…”

Section: Discussionmentioning

confidence: 99%

“…10,11,29 FFA has a strong inhibitory action on somatotroph secretion acting at either the pituitary or the hypothalamic level; 31,32,36 in fact, lipolysis inhibitors restore GH secretion in obesity. 10,11,29,37 In the absence of any significant increase in GH secretion obese patients in our study showed normal activation of lipolysis; this probably reflects the fasting-induced response of other contraregulatory hormones. 38 In this context, modification in IGF-I bioactivity brought about by fasting-induced changes in the most important binding proteins could play a major metabolic role.…”

Section: Discussionmentioning

confidence: 99%

“…5,6 Recent evidence favors the hypothesis for abnormalities in peripheral hormones and metabolic factors such as enhanced negative free insulin growth factor-I (IGF-I) feedback, 7 hyperinsulinism, 8 alterations in leptin activity 9 and elevated free fatty acids (FFA). 10,11 Fasting strikingly stimulates somatotroph secretion in normal healthy humans; 12,13 reduction in the negative IGF-I feedback action as well as CNS-mediated mechanisms such as concomitant reduction in somatostatin activity and GHRH hyperactivity are likely to play major role. 14,15 Somatotroph insufficiency in obesity is reversible after long-term diet-induced weight loss, 16 but the effect of fasting is still controversial.…”

Section: Introductionmentioning

confidence: 99%

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Effects of 36 hour fasting on GH/IGF-I axis and metabolic parameters in patients with simple obesity. Comparison with normal subjects and hypopituitary patients with severe GH deficiency

et al. 2001

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OBJECTIVE: Reduction of growth hormone (GH) secretion in obesity probably reflects neuroendocrine and metabolic abnormalities. Even short-term fasting stimulates GH secretion and distinguishes normal from hypopituitary subjects with growth hormone deficiency (GHD). Marked weight loss improves GH secretion in obesity but the effect of fasting is controversial. We studied the effects of a 36 h fasting on the GH=IGF-I axis and metabolic parameters in obesity. SUBJECTS: We studied nine obese patients (OB; three male and six female; age, 29.2 AE 4.8; range, 18 -59 y; body mass index (BMI), 43.4 AE 2.7 kg=m 2 ; WHR, 0.9 AE 0.1). Fifteen normal subjects (NS; eight male and seven female 28.9 AE 0.6, 25 -35 y; 21.6 AE 0.4 kg=m 2 ) and 10 adult hypopituitary patients with severe GH deficiency (GHD; seven male and three female; 37.6 AE 2.3, 29 -50 y; 24.5 AE 1.0 kg=m 2 ; GH peak < 3mg=l after ITT and=or < 9mg=l after GHRH þ arginine) served as control groups. STUDY DESIGN: We studied the effects of 36 h fasting on 8 h diurnal mean GH, insulin and glucose concentrations (mGHc, mINSc and mGLUc; assay every 30 min from 8.00 am to 4.00 pm) as well as on IGF-I, IGFBP-3, ALS, IGFBP-1, GHBP and free fatty acid (FFA) levels. RESULTS: Before fasting, basal IGF-I and ALS levels in OB were similar to those in NS and both were higher (P < 0.001) than those in GHD. IGFBP-3 levels in OB were lower (P < 0.01) than in NS but higher (P < 0.02) than in GHD. GHBP levels in OB and GHD were similar and both were higher (P < 0.01) than in NS. Glucose levels were similar in all groups. FFA levels in OB were higher (P < 0.01) than in NS but similar to those in GHD. IGFBP-1 in OB were lower (P < 0.05) than in NS and GHD which, in turn, were similar. On the other hand, mINSc in OB was higher (P < 0.01) than that in NS and GHD which, in turn, were similar. The mGHc in OB was similar to that in NS but only the latter was higher (P < 0.05) than in GHD. The individual mGHc in the three groups overlapped. After fasting, IGF-I levels in GHD were unchanged while they decreased in OB (P ¼ NS) as well as in NS (P < 0.01). IGFBP-3 and ALS levels did not change. GHBP levels in OB and GHD were unchanged while they increased in NS (P < 0.01). Glucose and FFA levels were reduced and increased, respectively, in all groups (P < 0.02 and P < 0.01). IGFBP-1 increased while mINSc decreased in all groups (P < 0.02 and P < 0.01); in OB they persisted lower and higher (P < 0.01) respectively, than in NS and GHD. Fasting significantly increased mGHc in NS (P < 0.001) but not in OB as well as in GHD. Individual mGHc in OB showed persistent overlap with GHD. CONCLUSIONS: Short-term fasting does not increase GH secretion in obesity and does not distinguish somatotroph function in obese from that in severe GHD adults. Short-term fasting in obesity has attenuated effects on insulin and IGFBP-1 secretion while it normally increases free fatty acids in spite of any change in GH secretion.

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“…108 The prolonged suppression of NEFA serum levels by chronic treatment with acipimox, further improves the somatotropin response to the stimuli (GHRH alone and combined with arginine). 109,110 Aminoacids GH is known to stimulate aminoacid uptake and protein synthesis. 111 In turn, aminoacids participate in the regulation of GH release.…”

Section: Nefamentioning

confidence: 99%

Growth hormone in obesity

1999

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Growth hormone (GH) secretion, either spontaneous or evoked by provocative stimuli, is markedly blunted in obesity. In fact obese patients display, compared to normal weight subjects, a reduced half-life, frequency of secretory episodes and daily production rate of the hormone. Furthermore, in these patients GH secretion is impaired in response to all traditional pharmacological stimuli acting at the hypothalamus (insulin-induced hypoglycaemia, arginine, galanin, L-dopa, clonidine, acute glucocorticoid administration) and to direct somatotrope stimulation by exogenous growth hormone releasing hormone (GHRH). Compounds thought to inhibit hypothalamic somatostatin (SRIH) release (pyridostigmine, arginine, galanin, atenolol) consistently improve, though do not normalize, the somatotropin response to GHRH in obesity. The synthetic growth hormone releasing peptides (GHRPs) GHRP-6 and hexarelin elicit in obese patients GH responses greater than those evoked by GHRH, but still lower than those observed in lean subjects. The combined administration of GHRH and GHRP-6 represents the most powerful GH releasing stimulus known in obesity, but once again it is less effective in these patients than in lean subjects. As for the peripheral limb of the GH ± insulin-like growth factor I (IGF-I) axis, high free IGF-I, low IGF-binding proteins 1 (IGFBP-1) and 2 (IGFBP-2), normal or high IGFBP-3 and increased GH binding protein (GHBP) circulating levels have been described in obesity. Recent evidence suggests that leptin, the product of adipocyte speci®c ob gene, exerts a stimulating effect on GH release in rodents; should the same hold true in man, the coexistence of high leptin and low GH serum levels in human obesity would ®t in well with the concept of a leptin resistance in this condition. Concerning the in¯uence of metabolic and nutritional factors, an impaired somatotropin response to hypoglycaemia and a failure of glucose load to inhibit spontaneous and stimulated GH release are well documented in obese patients; furthermore, drugs able to block lipolysis and thus to lower serum free fatty acids (NEFA) signi®cantly improve somatotropin secretion in obesity. Caloric restriction and weight loss are followed by the restoration of a normal spontaneous and stimulated GH release. On the whole, hypothalamic, pituitary and peripheral factors appear to be involved in the GH hyposecretion of obesity. A SRIH hypertone, a GHRH de®ciency or a functional failure of the somatotrope have been proposed as contributing factors. A lack of the putative endogenous ligand for GHRP receptors is another challenging hypothesis. On the peripheral side, the elevated plasma levels of NEFA and free IGF-I may play a major role. Whatever the cause, the defect of GH secretion in obesity appears to be of secondary, probably adaptive, nature since it is completely reversed by the normalization of body weight. In spite of this, treatment with biosynthetic GH has been shown to improve the body composition and the metabolic ef®cacy of lean body mass in obese pa...

show abstract

Effects of acipimox, an antilipolytic drug, on the growth hormone (GH) response to GH-releasing hormone alone or combined with arginine in obesity

Cited by 47 publications

References 31 publications

GH response to GHRH plus arginine is impaired in lipoatrophic women with human immunodeficiency virus compared with controls

GH response to GHRH plus arginine is impaired in lipoatrophic women with human immunodeficiency virus compared with controls

Effects of 36 hour fasting on GH/IGF-I axis and metabolic parameters in patients with simple obesity. Comparison with normal subjects and hypopituitary patients with severe GH deficiency

Growth hormone in obesity

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