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

Several clinical disorders are strongly influenced by hormones involved in appetite and weight regulation. Obesity and eating disorders are of major importance, because they are associated with severe morbidity and considered to be among the greatest health problems in the Western world today. This review describes recent findings in hormonal regulation of food intake by substances acting both centrally, such as corticotropin-releasing factor, neuropeptide Y and leptin, and peripherally, such as cholecystokinin and somatostatin. Sex hormones and glucocorticoids play an important role in long-term regulation of metabolism. The role of these hormones in appetite and weight changes during life as well as during pregnancy and lactation is discussed. Furthermore, the development of obesity and eating disorders is influenced, in particular, by steroid hormones. Treatment with sex hormones, as in hormone replacement therapy, affects appetite and weight and may have beneficial effects in preventing android obesity. Currently, there is great effort in developing endogenous neurohumoral substances into effective drugs for the treatment of obesity and eating disorders. Leptin and neuropeptide Y analogues are of interest as potential antiobesity agents.
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PMID:Hormonal regulation of appetite and food intake. 955 85

Somatostatin (SS) impairs nutrient absorption. It has been suggested that hyposomatostatinaemia may be involved in the pathogenesis of obesity. However, data on postprandial SS-like immunoreactivity (SLI) levels in obese subjects are controversial and the levels of SS-28, the main molecular form of circulating SLI in healthy subjects, have not been determined. To characterise the fasting and postprandial plasma pattern of SLI and SS-28 in obese men, we studied eight obese men (age 24-32 yr, BMI 33-42 kg/m2), with normal glucose tolerance test and normal gastric emptying of solids, and eight healthy men (age 24-39 yr, BMI 21-24 kg/m2). Blood samples were taken at regular intervals in fasting conditions and for 2 h after a standard solid-liquid meal (2.3 MJ). Plasma SLI and SS-28 were measured by RIA. Our results showed that fasting and postprandial plasma SLI and SS-28 levels were not significantly different in healthy and obese subjects. In conclusion SS-28 is the predominant form of circulating SLI in obese subjects. The normal pattern of fasting and postprandial plasma SLI and SS-28 levels in such subjects suggests that somatostatin does not have a pathogenetic role in obesity.
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PMID:Plasma somatostatin-like immunoreactivity and somatostatin-28 levels in obese men. 963 18

We here investigate the potential rescue of the relative hyposomatotropism of aging and obesity by 3-day pulsatile GHRH infusions (i.v. bolus 0.33 microg/kg every 90 min) in 19 healthy men of varying ages (18 to 66 years) and body compositions (12 to 37% total body fat). Baseline (control) and GHRH-driven pulsatile GH secretion (in randomly ordered sessions) were quantitated by deconvolution analysis of 24-h (10-min sampling) serum GH concentration profiles measured in an ultrasensitive (threshold 0.005 microg/l) chemiluminescence assay. GHRH infusion significantly increased the mean (24-h) serum GH concentration (0.3 +/- 0.1 basal vs 2.4 +/- 0.4 microg/l treatment; P = 0.0001), total daily pulsatile GH production rate (21 +/- 9.5 vs 97 +/- 17 microg/l/day; P = 0.01), GH secretory burst frequency (11 +/- 0.5 vs 17 +/- 0.3 events/day; P = <0.01), and mass of GH released per burst (1.1 +/- 0.4 vs 5.9 1 microg/l; P < 0.01), as well as serum IGF-I (261 +/- 33 vs 436 +/- 37 microg/l; P = 0.005), insulin (45 +/- 13 vs 79 +/- 17 mU/l; P = 0.0002), and IGF binding protein (IGFBP)-3 (3320 +/- 107 vs 4320 +/- 114 microg/l; P = 0.001) concentrations, while decreasing IGFBP-1 levels (16 +/- 1.2 vs 14 +/- 0.09 microg/l; P = 0.02). Serum total testosterone and estradiol concentrations did not change. GHRH treatment also reduced the half-duration of GH secretory bursts, and increased the GH half-life. GHRH-stimulated 24-h serum GH concentrations and the mass of GH secreted per burst were correlated negatively with age (R[value]:P[value] = -0.67:0.002 and -0.58:0.009 respectively), and percentage body fat (R:P = -0.80:0.0001 and -0.65:0.0005 respectively), but positively with serum testosterone concentrations (R:P = +0.55:0.016 and +0.53:0.019 respectively). GHRH-stimulated plasma IGF-I increments correlated negatively with age and body mass index, and positively with serum testosterone, but not with percentage body fat. Cosinor analysis disclosed persistent nyctohemeral rhythmicity of GH secretory burst mass (with significantly increased 24-h amplitude and mesor values) but unchanged acrophase during fixed pulsatile GHRH infusions, which suggests that both GHRH- and non-GHRH-dependent mechanisms can modulate the magnitude (but only non-GHRH mechanisms can modulate the timing) of somatotrope secretory activity differentially over a 24-h period. In summary, diminished GHRH action and/or non-GHRH-dependent mechanisms (e.g. somatostatin excess, putative endogenous growth hormone-releasing peptide deficiency etc.) probably underlie the hyposomatotropism of aging, (relative) obesity, and/or hypoandrogenemia. Preserved or increased tissue IGF-I responses to GHRH-stimulated GH secretion (albeit absolutely reduced, suggesting GHRH insensitivity in obesity) may distinguish the pathophysiology of adiposity-associated hyposomatotropism from that of healthy aging.
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PMID:Unequal impact of age, percentage body fat, and serum testosterone concentrations on the somatotrophic, IGF-I, and IGF-binding protein responses to a three-day intravenous growth hormone-releasing hormone pulsatile infusion in men. 970 80

Experimental data suggest that elevated FFA levels play a leading role in the impaired GH secretion in obesity and may therefore contribute to the maintenance of overweight. GH has a direct lipolytic effect on adipose tissue; in turn, FFA elevation markedly reduces GH secretion. This suggests the existence of a classical endocrine feedback loop between FFA and GH secretion. However, the FFA mechanism of action is not yet understood. The involvement of somatostatin (SRIH) is controversial, and in vitro experiments suggest a direct effect of FFA on the pituitary. In sheep it is possible to collect hypophysial portal blood and quantify SRIH secretion in hypophysial portal blood under physiological conscious and unstressed conditions. In this study we determined the effects of FFA (Intralipid and heparin) infusion on peripheral GH and portal SRIH levels in intact rams chronically implanted with perihypophysial cannula and in rams actively immunized against SRIH to further determine SRIH-mediated FFA effects on GH axis. Immediately after initiation of Intralipid infusion, we observed a marked increase in the FFA concentration (2160 +/- 200 vs. 295 +/- 28 nmol/ml; P < 0.01) as well as a significant decrease in basal GH secretion (1.8 +/- 0.1 vs. 2.5 +/- 0.3 ng/ml; P < 0.05) and a drastic reduction of the GH response to i.v. GH-releasing hormone injection (4.8 +/- 0.7 ng/ml in FFA group vs. 35.8 +/- 9.7 ng/ml in saline group; P < 0.01). No change in plasma insulin-like growth factor I levels was observed. During the first 2 h of infusion, the GH decrease observed was concomitant with a significant increase in portal SRIH levels (22.1 +/- .2 vs. 13 +/- 1.6 pg/ml; P < 0.01). In rams actively immunized against SRIH, the effect of FFA on basal GH secretion was biphasic. During the first 90 min of infusion, the decrease in GH induced by FFA was significantly blunted in rams actively immunized against SRIH (57 +/- 9% for immunized rams vs. 23.5 +/- 2.5% for control rams). This corresponds to the period of increased SRIH portal levels. After this first 90-min period, no difference was seen between control and immunized rams. Our results show that FFA exert their inhibitory action on the GH axis at both pituitary and hypothalamic levels, the latter mainly during the first 90 min, through increased SRIH secretion.
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PMID:Hypothalamic mediated action of free fatty acid on growth hormone secretion in sheep. 983 17

Leptin is a hormone secreted by the adipocytes that regulates food intake and energy expenditure. It is known that growth hormone (GH) secretion is markedly influenced by body weight, being suppressed in obesity and cachexia, and recent data have demonstrated that GH release is regulated by leptin levels. Although one of the sites of action of leptin is likely to be the hypothalamus, since leptin receptor mRNA is particularly abundant in several hypothalamic nuclei, the mechanisms by which leptin regulates GH secretion are not yet known. The aim of the present study was to investigate whether leptin could act at the hypothalamic level modulating somatostatin and GH-releasing hormone (GHRH) expression. The administration of anti-GHRH serum (500 microl, i.v.) completely blocked leptin-induced GH release in fasting rats. In contrast, the treatment with anti-somatostatin serum (500 microl, i.v.) significantly increased GH release in this condition. Furthermore, leptin administration (10 microg, i.c.v.) to intact fasting animals reversed the inhibitory effect produced by fasting on GHRH mRNA levels in the arcuate nucleus of the hypothalamus, and increased somatostatin mRNA content in the periventricular nucleus. Finally, leptin administration (10 microgram, i.c.v.) to hypophysectomized fasting rats increased GHRH mRNA levels, and decreased somatostatin mRNA content, indicating an effect of leptin on hypothalamic GHRH- and somatostatin-producing neurons. These findings suggest a role for GHRH and somatostatin as mediators of leptin-induced GH secretion.
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PMID:Role of growth hormone (GH)-releasing hormone and somatostatin on leptin-induced GH secretion. 989 45

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 specific 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 fit in well with the concept of a leptin resistance in this condition. Concerning the influence 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) significantly 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 deficiency 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 efficacy of lean body mass in obese patients undergoing therapeutic severe caloric restriction. GH and conceivably GHRPs might therefore have a place in the therapy of obesity.
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PMID:Growth hormone in obesity. 1019 71

It has occasionally been suggested that GH directly suppresses circulating IGFBP-1 levels, although it is generally believed that such an effect is secondary to a GH-induced increase in insulin levels. We present data from several experiments in which the effects of GH on IGFBP-1 could be studied more extensively. In normal subjects (n = 36), an i.v. GH bolus caused a small but significant decrease in plasma IGFBP-1 concentrations without changes in insulin [IGFBP-1 (microgram/l): 2.6 +/- 0.3 (GH) vs 3.2 +/- 0.4 (placebo), P < 0.05]. Conversely, a 28-h somatostatin infusion with and without GH administration during fasting in normal subjects yielded higher IGFBP-1 levels in the non-GH substituted study [50.5 +/- 5.3 (GH-suppression) vs 22.6 +/- 5.6 (GH-substitution), P < 0.01], comparable with an increased concentration of IGFBP-1 during fasting in GH-deficient patients without usual GH substitution [23.4 +/- 7.6 (GH pause) vs 14.1 +/- 4.9 (GH substitution), P < 0.01]. In both fasting studies insulin levels remained stable. During a hypocaloric diet, long-term GH treatment in obesity lead to a significant decline in IGFBP-1 level (2.3 +/- 0.6 vs 1.2 +/- 0.2, P < 0.01), while no changes were found in the placebo group. Again, insulin levels remained equally low in both studies. Finally, a significant rebound increase in IGFBP-1 level in response to insulin induced hypoglycemia was only observed among GH-deficient patients, but not in control subjects, the latter of whom responded to hypoglycemia with a significant increase in serum GH levels [23.2 +/- 7.2 (GHDA) vs 2.5 +/- 0.3 (controls), P < 0.01]. In conclusion, a suppressive effect of GH on IGFBP-1 appears to be unmasked in the presence of low or suppressed insulin levels, making GH a potential regulator of IGF-1 bioactivity in a hitherto unrecognized way.
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PMID:Evidence supporting a direct suppressive effect of growth hormone on serum IGFBP-1 levels. Experimental studies in normal, obese and GH-deficient adults. 1020 8

The neuroregulation of growth hormone (GH) secretion and the state of the adipose tissue reserves are closely related. GH exerts lipolytic actions on the adipose tissue and low body weight enhances secretion of GH while obesity is associated with reduced levels of GH and blocked release of GH when challenged by all stimuli. The mediators of the regulation exerted by the adipose tissue on the GH/insulin-like growth factor-I axis are not fully understood, but in the last few years two relevant factors have emerged--free fatty acids (FFA) and the adipocyte-produced hormone leptin. FFA and GH integrate a classical feedback loop and a rise in FFA blocks GH secretion. This action is rapid, dose-related and exerted at the pituitary level with no evident hypothalamic participation. A pharmacological reduction in FFA enhances secretion of GH and eliminates the GH blockade of obesity and Cushing's syndrome. The discovery of leptin has expanded our knowledge of the way in which the adipose tissue participates in some neuroendocrine actions. Obesity is associated with elevated levels of serum leptin while undernutrition and fasting lead to low leptin. In fasted rats, the pattern of GH pulsatility is eliminated with a near absence of spontaneous peaks, but the administration of leptin by the intracerebroventricular (i.c.v.) route restores the altered pattern. When fed rats receive antileptin antibodies i.c.v the normal pattern is reversed to an absence of pulses, reminiscent of the fasting state. These results are the first demonstration that, at least in experimental animals, leptin is a relevant factor in GH regulation. Leptin has no direct pituitary action and its action at the hypothalamic level appears to be mediated by neuropeptide Y, being the final step in a reduction in the somatostatin tone. On the other hand, the action of GH on leptin levels seems to be tenuous in humans, but in the near future it will be possible to investigate the action of leptin on human GH. As the hypothalamic neuroregulation of GH secretion in humans is unlike that in the rat, a crucial point for elucidation will be the actions, if any, and the mechanisms by which leptin participates in GH regulation in humans, as well as its alterations in disease states.
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PMID:Regulation of growth hormone secretion by signals produced by the adipose tissue. 1044 66

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

We studied the kinetics of exogenous recombinant 22-kDa human growth hormone (rhGH) in premenopausal women with upper body obesity (UBO), lower body obesity (LBO), or normal body weight. A bolus of 100 mU rhGH was administered during a continuous infusion of somatostatin to suppress endogenous GH secretion. GH kinetics were investigated with noncompartmental analysis of plasma GH curves. GH peak values in response to GH infusion and plasma half-life of GH were not significantly different between normal weight and obese subjects. In contrast, GH clearance was 33% higher in LBO women and 51% higher in UBO women compared with clearance in normal weight controls. The difference in clearance between LBO and UBO was not statistically significant. Altered GH clearance characteristics contribute to low circulating GH levels in obese humans. Body fat distribution does not appear to affect GH kinetics.
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PMID:Influence of obesity and body fat distribution on growth hormone kinetics in humans. 1056 8


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