Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fifteen patients with primary GH resistance (Laron syndrome, LS) were studied before and during 6 months of daily replacement treatment with IGF-I. The main findings were that patients with LS and normal or high serum GH binding protein (GHBP) were less obese than those with a negative GHBP, and that serum leptin levels varied with body mass as in other types of obesity.
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PMID:Serum leptin in obese patients with Laron syndrome before and during IGF-I treatment. 982 17

Diminished GH secretion is a well known association of obesity. As in obese humans, Zucker fatty rats develop a progressive GH deficiency, present at 6 weeks of age and maximal at 10 to 12 weeks. The aim of this study was to investigate the GH dependence of IGF-I gene expression in liver and extrahepatic tissues of the obese Zucker rat as a model of progressive GH reduction during adult life. Six- and 11-week-old obese Zucker rats and their lean littermates were used to compare body weight, glycemia, insulinemia, serum GH and IGF-I levels and IGF-I mRNA expression in liver, heart, aorta, kidney and skeletal muscle. In comparison with lean controls, obese Zucker rats showed at both ages comparable glycemia, severe hyperinsulinemia (mU/ml, mean+/-s.e.m.; 6 weeks 138+/-10 vs 45+/-6 P<0.001; 11 weeks 147+/-14 vs 46+/-3, P<0.001) and lower GH (ng/ml; 6 weeks 1.7+/-0.9 vs 2.7+/-1.1; 11 weeks 1.5+/-0.9 vs 4.2+/-1.2) in the presence of similar circulating IGF-I levels (ng/ml; 6 weeks 774+/-26 vs 694+/-28; 11 weeks 1439+/-182 vs 1516+/-121). Hepatic IGF-I mRNA expression was already reduced at 6 weeks of age due to a significant decrease in the IGF-Ib transcript compared with lean controls (relative units; IGF-Ia: 99+/-2% vs 100+/-5%; IGF-Ib: 69+/-10% vs 100+/-2%, P<0.05) and this reduction was more marked in 11-week-old animals when both IGF-I transcripts were significantly diminished (relative units; IGF-Ia: 80+/-6% vs 100+/-1%, P<0.05; IGF-Ib: 65+/-5% vs 100+/-2%, P<0.01). Extrahepatic tissues expressed almost exclusively the IGF-Ia transcript, the amount of which relative to controls was: (1) similar at 6 weeks and decreased at 11 weeks in kidney and skeletal muscle extracts (relative units; kidney: 6 weeks 88+/-10% vs 100+/-2%; 11 weeks 76+/-3% vs 100+/-4%, P<0.05; vastus lateralis: 6 weeks 95+/-7% vs 100+/-10%; 11 weeks 59+/-4% vs 100+/-2%, P<0.001); (2) similar at both ages in thoracic aorta (relative units; 6 weeks 121+/-6% vs 105+/-5%; 11 weeks: 91+/-14% vs 100+/-4%); and (3) increased at both ages in left ventricle extracts (relative units; 6 weeks 114+/-2% vs 99+/-9%, P<0. 05; 11 weeks 119+/-7% vs 95+/-3%, P<0.05). -specific dependence of IGF-I mRNA on GH levels during adulthood, reflected by the different behavior of IGF-I expression for each tissue in conditions of progressive decrease of GH levels.
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PMID:Tissue-specific response of IGF-I mRNA expression to obesity-associated GH decline in the male Zucker fatty rat. 985 76

Bioelectrical impedance for measurement of total body fat and computed tomography for visceral and subcutaneous fat at umbilicus levels were performed in 34 obese and 10 lean men. Insulin secretion in response to an oral glucose tolerance test (OGTT) and a GH stimulation test by L-dopa, growth hormone-binding protein (GHBP) and IGF-I were measured. Obese subjects were divided into three groups according to the OGTT. The obese type II diabetes mellitus group had the highest GHBP levels and the most visceral fat. GHBP levels were most strongly correlated with the ratio of visceral fat area to body weight (VWR) above any other parameters (r = 0.725, P<0.001). The insulin and free fatty acid (FFA) areas under curves (AUC) during the OGTT, and the IGF-I level, were also positively correlated with GHBP levels (r = 0.474, P<0.005; r = 0.572, P<0.005; r = 0.453. P<0.005). GH-AUC to the L-dopa stimulation test was negatively correlated with GHBP levels (r = -0.432. P<0.005). Stepwise multiple linear regression analysis showed that VWR, FFA-AUC and insulin-AUC significantly contributed to the variability of GHBP (r2 = 0.58). In conclusion, we demonstrated that: (i) visceral fat amount mainly determined GHBP levels in obese men with varying glucose tolerance: (ii) hyperglycemia per se did not influence the GHBP level, whereas insulin and FFA could play a role in regulation of GHBP: and (iii) although GH was not the main regulator of GHBP, the unchanged IGF-I level despite GH hyposecretion suggests that increased GHBP levels reflect GH hypersensitivity in order to compensate for decreased GH secretion in obesity.
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PMID:GH-binding protein in obese men with varying glucose tolerance: relationship to body fat distribution, insulin secretion and the GH-IGF-I axis. 1006 61

Growth hormone (GH) can induce an accelerated lipolysis. Impaired secretion of GH in obesity results in the consequent loss of the lipolytic effect of GH. Dietary restriction as a basic treatment for obesity is complicated by poor compliance, protein catabolism, and slow rates or weight loss. GH has an anabolic effect by increasing insulin-like growth factor (IGF)-I. We investigated the effects of GH treatment and dietary restriction on lipolytic and anabolic actions, as well as the consequent changes in insulin and GH secretion in obesity. 24 obese subjects (22 women and 2 men; 22-46 years old) were fed a diet of 25 kcal/kg ideal body weight (IBW) with 1.2 g protein/kg IBW daily and were treated with recombinant human GH (n = 12, 0.18 U/kg IBW/week) or placebo (n = 12, vehicle injection) in a 12-week randomized, double-blind and placebo-controlled trial. GH treatment caused a 1.6-fold increase in the fraction of body weight lost as fat and a greater loss of visceral fat area than placebo treatment (35.3 vs. 28.5%, p < 0.05). In the placebo group, there was a loss in lean body mass (-2.62 +/- 1.51 kg) and a negative nitrogen balance (-4.52 +/- 3.51 g/day). By contrast, the GH group increased in lean body mass (1.13 +/- 1.04 kg) and had a positive nitrogen balance (1.81 +/- 2.06 g/day). GH injections caused a 1.6-fold increase in IGF-I, despite caloric restriction. GH response to L-dopa stimulation was blunted in all subjects and it was increased after treatment in both groups. GH treatment did not induce a further increase in insulin levels during an oral glucose tolerance test (OGTT) but significantly decreased free fatty acid (FFA) levels during OGTT. The decrease in FFA area under the curve during OGTT was positively correlated with visceral fat loss. This study demonstrates that in obese subjects given a hypocaloric diet, GH accelerates body fat loss, exerts anabolic effects and improves GH secretion. These findings suggest a possible therapeutic role of low-dose GH with caloric restriction for obesity.
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PMID:Low-dose growth hormone treatment with diet restriction accelerates body fat loss, exerts anabolic effect and improves growth hormone secretory dysfunction in obese adults. 1035 97

The GH response to provocative stimuli in obese is often as low as in panhypopituitaric patients with severe GHD; however, IGF-I levels are normal or slightly reduced. In 53 patients with simple obesity (11 M and 42 F, age: 40.3+/-1.6 yr, BMI: 39.1+/-1.0 Kg/m2), we evaluated the GH response to GHRH (1 microg/kg iv)+arginine (ARG, 0.5 g/kg iv), and total IGF-I levels. The mean (+/-SE) GH peak after GHRH+ARG was markedly lower (74% reduction, p<0.0001) in obese (16.8+/-2.0 microg/l) than in normal subjects (62.7+/-4.3 microg/l). IGF-I levels in obese patients (134.0+/-7.6 microg/l) were lower (33% reduction, p<0.001) than in normal subjects (200.8+/-5.7 microg/l). Taking into account the 3rd centile limit of normal response, the GH response to GHRH+ARG was reduced in 62.3% (33/53) of the obese patients, and 21.2% (7/33) of them had low IGF-I levels. Assuming the 1st centile limit, it was reduced in 33.9% (18/53) obese subjects, and 22% (4/18) of them had low IGF-I levels. Considering 3.0 microg/L as arbitrary cut-off, the GH response was reduced in 5.7% (3/53) of the obese patients, and still one of them had low IGF-I levels. Our findings: a) confirm that the secretory capacity of somatotroph cells is often deeply impaired in obesity; b) demonstrate that IGF-I assay generally rules out severe impairment of GH/IGF-I axis in obese patients with marked reduction of the GH secretion; c) indicate that the percentage of obese patients with concomitant reduction of GH secretion and IGF-I levels is not negligible. Thus, IGF-I assay should be routinely performed in obese patients; those presenting with low IGF-I levels should undergo further evaluation of their hypothalamo-pituitary function and morphology, particularly in the presence of empty sella.
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PMID:Assessment of GH/IGF-I axis in obesity by evaluation of IGF-I levels and the GH response to GHRH+arginine test. 1043 51

Growth hormone (GH) deficiency in adults is characterized by central obesity, dyslipidemia, coagulopathy and glucose intolerance, all features of the "metabolic syndrome", explaining the increased cardiovascular morbidity and mortality associated with GH deficiency in adults. Employing the 2-step euglycemic-hyperinsulinemic clamp, we have demonstrated severe insulin resistance in GH-deficient adults, with a reduction in insulin-mediated glucose utilization of -50%. Basal glucose turnover and partitioning of whole body glucose utilization into glycolytic flux (GF) and glycogen synthesis/glucose storage (GS) pathways are normal, but insulin activation of these 2 pathways is reduced, predominantly in the GS pathway. Activation of muscle glycogen synthase by insulin is markedly decreased, as is glycogen content of muscle. Insulin-induced muscle hexokinase activity appears also to be attenuated in GH-deficient adults with raised intramuscular cellular glucose and normal-reduced concentrations of glucose-6-phosphate. Beta-cell function is not excessive in GH-deficient adults and is inappropriately low for the insulin resistance. Following treatment of GH-deficient adults with recombinant GH (rhGH), the insulin resistance is either unchanged or more pronounced by 3, 6 or 24 months of treatment, despite the significant reduction in general and central obesity. The GF and GS pathways and muscle glycogen synthase and hexokinase activities remain severely impaired. Abnormalities in free fatty acid (FFA) metabolism are present in rhGH-treated GH-deficient adults and correlate significantly with the degree of insulin resistance as do the concentrations of rhGH-induced insulin-like growth factor (IGF)-I, the post-basal insulinemia and the duration of the GHD, but is independent of obesity. In conclusion, long-term rhGH treatment in GH-deficient adults results in persistent insulin resistance and abnormalities in the GF and GS pathways due to reduced glycogen synthase and hexokinase activities, in the presence of an ongoing reduction of central obesity. We postulate that the insulin resistance is due to chronic rhGH-induced alterations in FFA metabolism, non-physiological levels of IGF-I and chronic basal hyperinsulinemia.
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PMID:Insulin sensitivity in growth hormone (GH)-deficient adults and effect of GH replacement therapy. 1044 67

Growth hormone (GH) secretion in the elderly is generally diminished although there are marked individual differences ranging from normal GH secretion and normal levels of insulin-like growth factor (IGF)-I through low GH and subnormal IGF-I. It is assumed that the reduced central cholinergic activity leading to unrestrained somatostatin release leads to impaired GH secretion. The somatopause, if it occurs at all, is, in contrast to the menopause, a subtly developing physiological event. The menopause often causes severe symptoms that justify hormone replacement therapy, but the somatopause is a physiological event at the end of the lifespan with no acute symptoms that can be attributed to GH deficiency with certainty. Whether the non-specific symptoms of old age, i.e. truncal obesity, muscle atrophy, decreasing energy, and mental disorders, can be--even partially--blamed on decreased GH secretion is unclear. Thus, GH therapy in elderly patients, in the absence of pituitary disease cannot be recommended. In addition, the following has to be considered: 1) GH has to be given by subcutaneous injection, which may be technically difficult in elderly patients. 2) It is difficult to find the right individual dosage of GH since elderly patients may show increased sensitivity to GH therapy (compared with children) or may be GH-resistant. 3) Manifestation of diabetes mellitus may be enhanced in elderly patients. 4) The elevation of IGF-I levels may enhance the progression of malignant disease; it has been shown that the concentration of IGF-I in the circulation correlates to the frequency of prostatic cancer. Furthermore, acromegalic patients have a higher frequency of colonic polyps and gastrointestinal malignancies. 5) Even if problems such as dosage, mode of application and the questions of safety are resolved, the present costs of GH therapy will not allow to advocate GH treatment of all elderly patients with low levels of IGF-I. However, since some patients seem to benefit from GH therapy in senescence, further studies are needed. There may be a subset of elderly patients in whom GH treatment is useful. However, unless these patients are included in a study protocol, GH treatment should not be given to elderly patients in the absence of pituitary disease.
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PMID:The somatopause is no indication for growth hormone therapy. 1044 83

Differentiation of precursor cells into mature fat cells is accompanied by enhanced expression of insulin-like growth factor (IGF)-I and is stimulated by multiple hormones including growth hormone, glucocorticoids, IGF-I and insulin. We used transgenic mice that overexpress insulin-like growth factor binding protein-1 to investigate the role of IGF-I in the accumulation of fat tissue. In response to a sucrose-enriched diet, transgenic mice gained significantly less body weight and the epididymal fat mass was significantly reduced compared with wild-type mice. The increase in adipocyte size was also significantly reduced in transgenic mice compared with wild-type mice. Fewer colonies were generated from adipose tissue from transgenic mice and the mitogenic response of these cells to IGF-I was significantly reduced compared with those from wild-type mice. Induction of glycerol-3-phosphate dehydrogenase, a measure of adipocyte differentiation, by IGF-I but not insulin, was reduced in preadipocytes from transgenic mice. These data indicate that IGF-I has a critical role in the proliferation of adipocyte precursors, the differentiation of preadipocytes and the development of obesity in response to calorie excess.
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PMID:Impaired adipogenesis in insulin-like growth factor binding protein-1 transgenic mice. 1046 38

Spontaneous and stimulated GH secretion is blunted in hypercortisolemic states due to increased hypothalamic somatostatinergic tone. However, no data are available on the characteristics of GH secretion in patients with incidentally discovered adrenal adenomas. They represent an interesting model for studying GH secretion, as a slight degree of cortisol excess may frequently be observed in such patients who do not present with any clear Cushingoid sign. In the present study, 10 patients (3 men and 7 women, aged 48-63 yr) with an adrenal mass discovered serendipitously underwent, on separate occasions, a GHRH injection alone or combined with an infusion of the functional somatostatin antagonist, arginine. Thirteen age-matched healthy volunteers served as controls. Briefly, arginine (30 g) was infused from -30 to 0 min, and GHRH (100 microg) was injected as a bolus at 0 min, with measurement of serum GH [immunoradiometric assay (IRMA)] every 15 min for 150 min. Plasma IGF-I (RIA after acid-ethanol extraction) was measured in a morning sample. The diagnosis of cortical adenoma was based on computed tomography features and pattern of uptake on adrenal scintigraphy. Patients with obesity and/or diabetes were excluded. The study design included also an endocrine work-up aimed to study the hypothalamic-pituitary-adrenal axis [urinary free cortisol (UFC) excretion, serum cortisol at 0800 h, plasma ACTH at 0800 h, morning cortisol after overnight 1 mg dexamethasone]. Five of 10 patients showed abnormalities of the hypothalamic-pituitary-adrenal axis, including borderline or increased UFC excretion in 4 of them accompanied by blunted ACTH in 2 cases and failure of cortisol to suppress after dexamethasone in 1; the fifth patient displayed low ACTH and resistance to dexamethasone suppression. However, all patients had a unilateral uptake of the tracer on the side of the mass with suppression of the contralateral normal adrenal gland. As a group, the patients displayed greater UFC excretion and lower ACTH concentrations than the controls. GH release after GHRH treatment was blunted in patients bearing adrenal incidentaloma compared with controls (GH peak, 5.7 +/- 5.2 vs. 18.0 +/- 7.0 microg/L; P < 0.0001), whereas GHRH plus arginine was able to elicit a comparable response in the 2 groups (GH peak, 33.5 +/- 20.3 vs. 33.7 +/- 17.5 microg/L; P = NS). The ratio between GH peaks after GHRH plus arginine and after GHRH plus saline was significantly greater in patients than in controls (751 +/- 531% vs. 81 +/- 45%; P = 0.0001). Similar data were obtained when comparing GH area under the curve after GHRH plus saline or GHRH plus arginine between the 2 groups. In summary, the present data suggest that in patients with incidental adrenal adenomas the GH response to GHRH is blunted due to increased somatostatinergic tone, as it can be restored to normal by pretreatment with the functional somatostatin antagonist arginine. The blunted GH release to GHRH may be an early and long lasting sign of autonomous cortisol secretion by the adrenal adenoma.
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PMID:Growth hormone (GH) responses to GH-releasing hormone alone or combined with arginine in patients with adrenal incidentaloma: evidence for enhanced somatostatinergic tone. 1072 81

GH/IGF-I axis activity changes have been reported both in anorexia nervosa (AN) and in obesity (OB). AN is characterized by GH hypersecretion and very low IGF-I levels as a result of undernutrition and acquired peripheral GH resistance. On the other hand OB is a GH hyposecretory state but IGF-I levels are generally preserved. The activity of GH/IGF-I axis in AN and OB has never been directly compared with that of other pathophysiological conditions such as hypopituitarism and critical illness in which a reduction of both GH and IGF-I secretion has been demonstrated. To this aim, we evaluated IGF-I levels and both basal and GHRH (1 microgram/kg) IV-induced GH secretion in 20 female patients with anorexia nervosa (mean age: 19.1 +/- 0.8 years) and in 15 female and 5 male patients with simple obesity (mean age: 39.0 +/- 3.0 years). We then compared the results with those of hypopituitaric patients with severe GH deficiency (GHD), including 10 female and 10 patients (mean age: 32.0 +/- 2.1 years), and with 4 female and 7 male patients with critical illness (CRI) following multiple trauma 72 hours after ICU admission (mean age: 59.2 +/- 1.2 years). Twenty-six normal subjects (NS) including 14 female and 12 male patients (mean age: 37.8 +/- 3.7 years) were studied as controls. Basal IGF-I levels in AN patients (93.5 +/- 11 micrograms/L) were lower (p < 0.001) than in the NS (201.7 +/- 13.5 micrograms/L) and OB (194.5 +/- 28.6 micrograms/L), which, in turn, were similar. IGF-I levels in AN patients were lower than in CRI patients (162.8 +/- 17.4 micrograms/L) and higher than in GHD patients (76.7 +/- 13.5 micrograms/L) but these differences did not attain statistical significance. Basal GH levels in AN patients (7.6 +/- 2.5 micrograms/L) were higher (p < 0.001) than in NS (1.8 +/- 0.3 micrograms/L), OB patients (1.1 +/- 0.5 micrograms/L), CRI patients (1.8 +/- 0.5 micrograms/L) and GHD patients (0.3 +/- 0.1 microgram/L), which were the lowest (p < 0.01). The GHRH-induced GH rise in AN patients (AUC: 2032.9 +/- 253.5 micrograms/L/h) was three fold higher (p < 0.001) than in NS (662.1 +/- 80.3 micrograms/L). On the other hand in OB (332.4 +/- 74.7 micrograms/L/h) the GH response to GHRH was similar to that in CRI (199.6 +/- 98.8 micrograms/L/h); both were clearly higher (p < 0.01) than in GHD patients (25.1 +/- 5.2 micrograms/L/h) but lower (p < 0.01) than in NS. These findings demonstrate that in AN patients, in spite of a clear increase of both basal and GHRH-induced GH secretion, IGF-I synthesis and release are as markedly impaired as in patients with panhypopituitarism and severe GHD. On the other hand in OB and in CRI, IGF-I synthesis and release are preserved despite marked impairment to GHRH-induced GH secretion. These results reinforce the major role of nutrition in conditioning the activity of GH/IGF-I axis in different patho-physiological states.
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PMID:The activity of GH/IGF-I axis in anorexia nervosa and in obesity: a comparison with normal subjects and patients with hypopituitarism or critical illness. 1072 52


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