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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Growth hormone (GH) secretion is reduced in girls with Turner's syndrome (TS) at pubertal age. We have recently proposed that the impairment of GH release in TS girls might be secondary to obesity. In the present study, we assessed the influence of overweight-related insulin status on spontaneous GH secretion in a group of 15 TS girls. Eighteen age-matched short normal subjects and six short obese prepubertal children were chosen as controls. Anthropometry, spontaneous GH secretion, insulin-like growth factor-I (IGF-I) serum levels, basal fasting insulin, and glucose concentrations were determined. The percentage of ideal body weight (IBW) was used as an index of nutritional status. Baseline fasting glucose (milligrams per deciliter) to insulin (milliunits per liter) ratio (G/I) was chosen as an index of insulin resistance. GH secretion was significantly lower in TS girls than in non-obese children (P < .005), whereas no significant difference was seen between TS and obese subjects. IGF-I levels were not statistically different in all groups. GH secretion was confirmed to be related to the degree of overweight (r = -.52, P < .05 in TS girls and r = -.74, P < .0001 in control group). G/I was closely related to both the percentage of IBW (r = -.59, P = .02) and GH level (r = .57, P = .03) in TS patients. These results confirm that the blunted GH secretion in TS patients is dependent on nutritional status, and suggest that insulin resistance secondary to overweight might represent the pathophysiologic link between the obesity-related metabolic status and impaired GH secretion.
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PMID:Is obesity-related insulin status the cause of blunted growth hormone secretion in Turner's syndrome? 763 44

Although GH is known to regulate somatic growth during development, its role in regulating adult body composition is less well defined. The effects of GH on individual body compartments--water, fat, protein and mineral--are achieved both by the action of GH and by a GH-induced hormone, insulin-like growth factor-I (IGF-I). We used a genetic model of GH deficiency, the 'little' (gene symbol lit) mouse, to determine the GH regulation of IGF-I and its insulin-like growth factor-binding proteins (IGFBPs) and to define the interaction between these hormones and each body compartment in adults. Our results showed that GH-deficient lit/lit mice had reduced levels of serum IGF-I (range 38-130 micrograms/l) compared with normal lit/+ littermates (range 432-567 micrograms/l) between 2 and 52 weeks of age. The lit/lit mice did not experience the fivefold increase in IGF-I between 2 and 4 weeks of age that was seen in lit/+ mice. In lit/lit serum, overall binding of 125I-labelled IGF-I to the four IGFBPs was reduced, solely in response to a reduced amount of IGFBP-3. No overall differences were found between lit/lit and lit/+ mice in the binding of 125I-labelled IGF-I to IGFBP-2, -1 or -4. Age-related declines in IGF-I and IGFBPs were seen in lit/lit mice. However, adult levels of IGF-I were maintained in lit/+ mice to at least 52 weeks of age, as were levels of IGFBP-1 and -4, while IGFBP-3 and -2 declined with age. With respect to body composition, comparison of lit/lit with lit/+ mice showed that the lit/lit mice were characterized by abnormally large adipose tissue stores and reduced body water, protein and mineral from 2 weeks onward. These changes occurred despite normal energy intake in lit/lit mice up to 52 weeks of age, indicating that neither undernutrition nor hyperphagia is characteristic of this GH-induced model of obesity. Furthermore, lit/lit males accrued more body fat beginning at an earlier age than lit/lit females. With advancing age, the per cent body fat increased in both lit/lit and lit/+ mice, while the per cent body water and mineral declined. In lit/lit but not lit/+ mice, per cent protein also declined with age. The changes in body water and fat are attributable to lack of adequate GH in the genetically GH-deficient lit/lit mouse. On the other hand, the changes in body protein are more likely to be effects of IGF-I.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Growth hormone deficiency in 'little' mice results in aberrant body composition, reduced insulin-like growth factor-I and insulin-like growth factor-binding protein-3 (IGFBP-3), but does not affect IGFBP-2, -1 or -4. 767 39

Metabolic changes such as obesity and fasting modulate pulsatile growth hormone (GH) release in man, but the underlying mechanisms are still elusive. We studied the temporal pattern of pulsatile GH release in five normal-weight men (mean +/- SD: age, 29.8 +/- 4.9 years; body mass index [BMI], 24.3 +/- 1.8 kg/m2) and five obese men (age, 27.8 +/- 4.8 years; BMI, 38.9 +/- 4.8 kg/m2) during their regular energy consumption and the last 24 hours of a 96-hour fasting period. GH plasma levels were determined at 10-minute intervals and glucose level was measured every 20 minutes. GH pulse analysis was performed with three different algorithms. Insulin-like growth factor-I (IGF-I), IGF-II, IGF-binding proteins (IGFBP-1, -2, and -3), and IGF-binding capacity (IGF-BC) were evaluated in samples collected at 7:00 AM, 3:00 PM, and 11:00 PM. Twenty-four-hour mean GH was basally higher in normal subjects (1.1 +/- 0.6 mU/L) than in overweight subjects (0.4 +/- 0.2, P < .01 v normal). The significant fasting-induced GH increase in normal-weight men (to 5.6 +/- 2.2 mU/L, P < .05 v basal) was inversely related to BMI (r = -.86, P = .0006). GH pulse amplitudes but not frequencies were different for both groups and were increased by fasting in normal subjects but not in obese subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pulsatile growth hormone secretion in normal-weight and obese men: differential metabolic regulation during energy restriction. 775 8

A cross-sectional analysis examining the impact of gender and early pubertal stage on insulin sensitivity (Si) and body composition was carried out as part of a longitudinal study to determine how Si relates to body composition changes during puberty. The study population consisted of 97 healthy children (age range, 9.7-14.5 yr; 28 Tanner stage 2 boys, 25 stage 3 boys, 22 Tanner stage 2 girls, and 22 stage 3 girls). Si was determined by the modified minimal model of Bergman. Body fatness was assessed by body mass index (BMI), skinfold thickness, hydrodensitometry, and bioelectrical impedance. Results showed that stage 3 girls and stage 2 boys had significantly more body fat than stage 2 girls and stage 3 boys. Si was significantly lower (P < 0.02) and insulin-like growth factor-I levels higher (P < 0.006) in stage 3 girls compared to those in the other 3 groups. The best predictor of Si in all subjects was BMI (r2 = -0.63; P < 0.0001). In a stepwise multiple regression analysis, Si was best predicted from BMI, gender, and Tanner stage. According to this model, Si decreased as BMI increased and was lower in girls and Tanner stage 3 children. In boys, Si was best predicted from total fat mass and Tanner stage. In girls, Si correlated inversely with BMI, parental obesity, and insulin-like growth factor-I levels. Neither testosterone nor estradiol levels were associated with Si. These results demonstrate that Si, like body composition, has gender-dependent changes during puberty. It is, thus, possible that these pubertal changes in Si relate to changes in body composition.
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PMID:Gender and Tanner stage differences in body composition and insulin sensitivity in early pubertal children. 782 8

Administration of monosodium L-glutamate (MSG) to neonatal mice produces a hypothalamic syndrome consisting of stunted growth and later development of obesity. We assayed plasma insulin (IRI), thyroxine (T4) and insulin-like growth factor-I (IGF-I) to investigate their roles in the growth of the mice. Two mg/g body weight of MSG was injected into newborn male mice daily for five successive days after birth. Plasma IRI levels were increased on the after 8 weeks of age in MSG-treated mice. There was no significant difference between the plasma T4 levels in MSG-treated mice and those in controls at any age studied. In contrast to this, plasma IGF-I levels in MSG-treated mice were reduced at one week and after. These results suggest that a decreased plasma IGF-I level contributes to the retarded linear growth which develops soon after the administration of MSG, and hyperinsulinemia contributes to the later development of obesity in MSG-treated mice.
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PMID:Plasma levels of insulin-like growth factor-I are reduced at one week of age in monosodium L-glutamate-treated mice. 792 Sep

Obesity is associated with blunted growth hormone (GH) levels and pulsatility and elevated plasma free fatty acids (FFA) levels. To evaluate whether the two phenomena are correlated, in the present study we investigated the effects of an acute pharmacologic blockade of lipolysis on nocturnal GH levels and pulsatility in 10 obese and 10 control subjects. At 9 PM on two different nights with a 1-night interval in between, all subjects received either a single oral tablet of placebo or acipimox slow release (ACX-SR, 500 mg) in randomized order. Blood samples were drawn from 10 PM to 6 AM for evaluation of FFA, glycerol, GH, immunoreactive insulin (IRI), glucose, and insulin-like growth factor-I (IGF-I) levels. After placebo, FFA and glycerol levels were higher (P < .02) and GH levels, areas, peak amplitude, and peak increment (assessed by the Cluster algorithm) were lower in obese than in control subjects (P < .01). After ACX-SR, FFA and glycerol levels were reduced in both groups (P < .02 v placebo), and in obese subjects they became similar to those observed in control subjects after placebo. ACX-SR had no effect on GH levels and pulsatility in control subjects. GH levels, areas, peak, amplitude, peak increment, and interpeak valley levels were all increased after ACX-SR in obese subjects (P < .05 or less v placebo) and became similar to those observed in normal subjects after placebo, but no correlation was found between the reduction in FFA levels and the increase in GH levels and pulsatility.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute pharmacologic blockade of lipolysis normalizes nocturnal growth hormone levels and pulsatility in obese subjects. 793 70

Childhood obesity may be characterised by basal and reactive hyperinsulinemia, reduced growth hormone (HGH) responses to various provocative stimuli and increased plasma concentration of somatomedine-C/insulin-like growth factor-I (SM-C/IGF-I). For this reason the relationship between the degree of obesity (i. e. BMI), serum immunoreactive insulin (IRI) and plasma SM-C/IGF-I was investigated in children with obesity (n = 26, age: 13.0 +/- 0.97 years, BMI: 32.8 +/- 5.3 kg/m2). SM-C/IGF-I was increased in obese children compared to the normal range of this age. Significant positive correlations were found between BMI and IRI, between BMI and SM-C/IGF-I, and between IRI and SM-C/IGF-I. These results suggest that SM-C/IGF-I production in obesity is regulated by IRI dependent on BMI and this regulating effect of insulin may be important in obesity since HGH production to provocative stimuli is reduced.
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PMID:[Relationship between immunoreactive insulin and plasma somatomedin-C/insulin-like growth factor-I concentration in childhood obesity]. 806 41

It is known that spontaneous and stimulated GH secretion is reduced in obesity. On the other hand, it has been recently reported that, in obese subjects, plasma GH levels did not change during a hyperglycemic clamp. To further study the sensitivity of somatotrope cells to inhibitory influences in obesity, we studied the effect of somatostatin, pirenzepine, or glucose on the GH response to GHRH or arginine in 32 obese patients and 30 controls. Basal GH levels were lower in obese than in normal subjects (1.0 +/- 0.6 vs. 4.8 +/- 0.7 micrograms/L, P < 0.05), while insulin-like growth factor-I levels were similar in both groups (137.3 +/- 13.2 vs. 138.8 +/- 12.2 micrograms/L). In obese as well as in control subjects pirenzepine abolished the GH response to either GHRH (AUC0-120: 43.7 +/- 9.6 vs. 258.3 +/- 59.9 micrograms/L/h, P < 0.04 and 113.0 +/- 75.0 vs. 870.5 +/- 255 micrograms/L.h, P < 0.01, respectively) or arginine (6.5 +/- 2.5 vs. 118.7 +/- 55.9 micrograms/L.h, P < 0.05 and 47.7 +/- 7.3 vs. 334.0 +/- 157.5 micrograms/L.h, P < 0.01, respectively). Differently from pirenzepine, glucose blunted the GH response to either GHRH or arginine in control subjects (260.8 +/- 38.3 vs. 479.5 +/- 83.9 micrograms/L.h, P < 0.03 and 294.8 +/- 46.3 vs. 625.1 +/- 139.1 micrograms/L.h, P < 0.05, respectively), but failed to modify it in obese patients (193.7 +/- 39.4 vs. 172.4 +/- 33.6 micrograms/L.h and 121.1 +/- 43.4 vs. 155.1 +/- 39.7 micrograms/L.h, respectively). On the other hand, somatostatin deeply blunted the GHRH-induced GH release in obese patients (58.5 +/- 25.4 vs. 548.7 +/- 196.6 micrograms/L.h, P < 0.05) as well as in controls (181.4 +/- 44.4 vs. 759.7 +/- 46.6 micrograms/L.h, P < 0.04). In conclusion, our results show that, in obesity, the stimulated GH release is refractory to the inhibitory effect of glucose but not of pirenzepine, in spite of their likely common mechanism of action, i.e. increase of hypothalamic somatostatin release. Exogenous somatostatin is able to abolish GH secretion both in normal and obese subjects. These data suggest the existence of a peculiar inhability of hyperglycemia to trigger somatostatinergic release in obesity.
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PMID:In obesity the somatotrope response to either growth hormone-releasing hormone or arginine is inhibited by somatostatin or pirenzepine but not by glucose. 853 Jun 34

Obese Zucker rats maintain normal rates of linear growth and circulating concentrations of insulin-like growth factor-I (IGF-I) and of IGF-binding protein-3 (IGFBP-3) in spite of low GH secretion. The mechanisms underlying this GH-independent growth in obesity are unknown. To assess whether the liver expression of the GH receptor (GHR) messenger RNA (mRNA) is increased and/or if the liver expression of IGFBP-3 mRNA is maintained in the obese, Zucker rats of both genders and phenotypes (four groups, n = 6/group) were studied at 12 weeks of age. By Northern analysis, mRNA levels for GHR and GHBP were not increased in obese rats compared to their sex-matched lean littermates; the expression of these two transcripts was sexually dimorphic and the changes in GHBP mRNA/GHR mRNA ratios associated with obesity were sex-specific. In both genders, IGFBP-1 and IGFBP-3 mRNAs were decreased in the obese. We concluded that the GH-independent growth of obese Zucker rats is not due to increased GHR mRNA or to maintained IGFBP-3 mRNA levels in the liver.
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PMID:The growth hormone (GH)-independent growth of the obese Zucker rat is not due to increased levels of GH receptor messenger RNA in the liver. 867 29

Genetically obese Zucker rats, like obese humans, have normal or elevated circulating insulin-like growth factor-I (IGF-I) levels in the presence of low GH secretion. Hyperinsulinemia, increased energy status, or other nutritional factors associated with obesity could be responsible for these findings directly by increasing hepatic IGF-I production at the transcriptional or posttranscriptional level. Alternatively, circulating IGF-I could be modulated indirectly by affecting its binding proteins. To further elucidate this point, we quantitated hepatic IGF-I, IGF-binding protein-3 (IGFBP-3), and GH receptor messenger RNAs (mRNAs) expression in obese Zucker rats under different serum GH and insulin conditions using lean rats as controls. Eleven-week-old male rats were studied basally (intact) or after hypophysectomy (hx) at 9 weeks. In each condition, animals were killed before or 6 h after one dose of recombinant human GH (1.5 micrograms/g body weight ip). At this time, in addition to the mRNA expression of the above-mentioned genes, body weight, glycemia, insulinemia, serum GH (rat and human), and serum IGF-I levels were determined. Obese Zucker rats were significantly heavier than controls in all the conditions studied and did not show differences in glycemia. Severely hyperinsulinemic intact obese rats (146.9 +/- 14 vs. 46.3 +/- 3 microU/ml, P < 0.001) showed compared with intact lean rats significantly lower serum GH (2.39 +/- 0.9 vs. 4.98 +/- 0.68 ng/ml, P < 0.01), decreased hepatic IGF-I mRNA and IGFBP-3 mRNA accumulation (IGF-Ia: 79 +/- 5.9% vs. 100 +/- 0.9%, P < 0.05; IGF-Ib: 67 +/- 5.5% vs. 100.1 +/- 1.9%, P < 0.001; IGFBP-3: 54.7 +/- 2.75% vs. 100.5 +/- 1.55%, P < 0.001), and similar circulating IGF-I levels (1439 +/- 182 vs. 1516 +/- 121 ng/ml). Under comparable serum GH levels in GH-treated intact, hx, and GH-treated hx animals, hyperinsulinemia and/or increased body weight present in obese rats were not associated with increased hepatic IGF-I and IGFBP-3 mRNA amount. No differences in GH receptor/GH-binding protein mRNAs were found in any experimental condition. These results suggest that in vivo the imbalance of the serum GH/IGF-I axis present in obesity is primarily due to events distal to the hepatic IGF-I and IGFBP-3 mRNAs expression, which is tightly correlated to GH levels.
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PMID:Basal and growth hormone-induced hepatic messenger ribonucleic acid expression of insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 is independent of hyperinsulinemia and increased energy status in the genetically obese Zucker rat. 904 10


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