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)

GH has potent effects on adipocyte biology, stimulating lipolysis but also promoting preadipocyte proliferation. In addition, GH, acting through IGF-I, inhibits 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1), which converts the inactive glucocorticoid, cortisone (E), to active cortisol (F) in adipose tissue. Although F is an essential requirement for adipocyte differentiation, it also inhibits preadipocyte proliferation. We hypothesized that inhibition of 11 beta-HSD1 activity in adipose tissue by GH may alter fat tissue mass through changes in local F concentrations. We conducted a randomized, double-blind, placebo-controlled study using low-dose GH (Genotropin 0.4 mg/d) for 8 months in 24 patients with obesity. Although GH treatment significantly raised IGF-I, we were unable to demonstrate significant differences in body composition or metabolic profiles between GH- and placebo-treated groups. In addition, there was no alteration in total fat mass over time in the GH-treated group [total fat mass 41.0 +/- 3.0 vs. 41.3 +/- 3.4 kg (8 months), mean +/- SE, P = ns]. However, in comparison with baseline values, systolic blood pressure increased (119 +/- 3 vs. 130 +/- 4 mm Hg, P < 0.05 vs. baseline) and serum F/E ratio decreased (6.1 +/- 0.5 vs. 3.9 +/- 0.5, P < 0.05 vs. baseline) in the GH-treated group only. Furthermore, although the urinary tetrahydrometabolites of F/E ratio fell in the GH-treated group, it rose in the placebo group (mean ratio change, -0.13 +/- 0.05 vs. +0.09 +/- 0.09, GH vs. placebo, P = 0.07). Treatment with low-dose GH in obesity fails to alter fat mass despite a significant elevation in IGF-I and a shift in the global set point of E to F conversion consistent with inhibition of 11 beta-HSD1.
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PMID:Low-dose growth hormone inhibits 11 beta-hydroxysteroid dehydrogenase type 1 but has no effect upon fat mass in patients with simple obesity. 1272 63

Prader Willi syndrome (PWS) is a rare endocrine-metabolic disorder that is characterised by neonatal hypotonia, hyperphagia, marked obesity, short stature, hypogonadism and behavioural problems. 7-20% percent of these children develop diabetes mellitus. A large number of individuals with PWS show growth hormone (GH) deficiency. Recent studies indicate beneficial effects of GH replacement therapy not only for their linear growth but also for correction of metabolic dysfunction. In the present communication this article details about the therapeutic outcome in a girl with PWS who received recombinant growth hormone (rGH), Genotropin. Some carry-over therapeutic benefits have been observed even after discontinuation of rGH.
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PMID:Growth hormone treatment in a girl with Prader Willi syndrome. 1279 14

Growth hormone, acting through its receptor (GHR), plays an important role in carbohydrate metabolism and in promoting postnatal growth. GHR gene-deficient (GHR(-/-)) mice exhibit severe growth retardation and proportionate dwarfism. To assess the physiological relevance of growth hormone actions, GHR(-/-) mice were used to investigate their phenotype in glucose metabolism and pancreatic islet function. Adult GHR(-/-) mice exhibited significant reductions in the levels of blood glucose and insulin, as well as insulin mRNA accumulation. Immunohistochemical analysis of pancreatic sections revealed normal distribution of the islets despite a significantly smaller size. The average size of the islets found in GHR(-/-) mice was only one-third of that in wild-type littermates. Total beta-cell mass was reduced 4.5-fold in GHR(-/-) mice, significantly more than their body size reduction. This reduction in pancreatic islet mass appears to be related to decreases in proliferation and cell growth. GHR(-/-) mice were different from the human Laron syndrome in serum insulin level, insulin responsiveness, and obesity. We conclude that growth hormone signaling is essential for maintaining pancreatic islet size, stimulating islet hormone production, and maintaining normal insulin sensitivity and glucose homeostasis.
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PMID:Disruption of growth hormone receptor gene causes diminished pancreatic islet size and increased insulin sensitivity in mice. 1513 53

Growth hormone (GH) is essential in the development and growth of the skeleton and for the maintenance of bone mass and density, and its secretion is known to decline with aging. We have previously produced transgenic rats with low circulating GH that represent several age-associated phenotypes such as obesity, insulin-resistance and leptin-resistance. In the present study, the cross-sectional area, bone mineral density, and strength indexes of the hind leg skeletons of the transgenic rats were examined by an X-ray computed tomography scanning. The mean cross-sectional area of the transgenic rats showed no increase after 2 months old up to 8 months old and the strength indexes were significantly lower than their non-transgenic siblings at all ages examined. The trabecular bone mineral density in the transgenic rats drastically decreased at 8 months old, while the cortical bone mineral density was comparable to the non-transgenic rats, suggesting the onset of osteoporosis at this period. The results obtained in this study indicate that the transgenic rats could be useful model to gain insight into the complex mechanism leading to osteoporosis with aging.
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PMID:Analyses of hind leg skeletons in human growth hormone transgenic rats. 1528 92

The intra-abdominal visceral deposition of adipose tissue, which characterises upper body obesity, is a major contributor to the development of hypertension, glucose intolerance and hyperlipidaemia. Conversely, individuals with lower body obesity may have comparable amounts of adipose tissue but remain relatively free from the metabolic consequences of obesity. This raises an obvious question-are there particular weight reducing treatments which specifically target intra-abdominal fat? In theory, surgical removal of upper body fat should be effective. In reality, neither liposuction nor apronectomy ('tummy tuck') have any beneficial metabolic effects, they simply remove subcutaneous adipose tissue which is often rapidly replaced. Vertical banded gastroplasty and gastric bypass operations may be dramatically effective in improving blood pressure, insulin sensitivity and glucose tolerance. However, these benefits result from a parallel reduction in visceral and total body fat. Studies of body fat distribution in postmenopausal women confirm that the marked decrease in adiposity, following a programme of very low calorie diet and exercise, reflects a comparable reduction in visceral and thigh fat. The reduction in waist circumference after a low fat/exercise programme suggests a similar situation in men. Exercise has an important role in treatment but, once again, the fat loss is generalised. Nevertheless, the improved metabolic parameters seen in exercising obese subjects, independent of weight loss, suggest other beneficial actions. Growth hormone (GH) has a marked lipolytic action. GH replacement treatment for GH deficient adults with pronounced abdominal fat deposition, has been shown to reduce intra-abdominal fat by 47% compared to 27% decrease in abdominal subcutaneous fat. Similar beneficial actions on abdominal fat have been reported following treatment with testosterone in obese men. The potential hazards of such treatments make them unsuitable therapy for obesity. Dexfenfluramine is effective in reducing total body fat but the results from a six month randomised controlled trial indicates that it does not specifically influence changes in waist circumference associated with weight loss. In conclusion, any treatment which reduces total body fat will, by its nature, reduce intra-abdominal visceral fat. There are presently no specific treatments which can be recommended for intra-abdominal fat but increasing knowledge of the biochemical aberrations associated with visceral adiposity may lead to more specific therapies for the future.
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PMID:The effects of weight loss treatments on upper and lower body fat. 1548 59

Prader-Willi syndrome (PWS) is a complex genetic disease, clinically characterised by short stature, abnormal body composition, with more body fat than lean body mass, hyperphagia and obesity. Partial growth hormone (GH) deficiency is common, and GH treatment to PWS children and adults has shown beneficial effects on body composition. In this study, we have evaluated indices of GH's lipolytic effect in 6 PWS adults analysing glycerol, lactate and glucose in dialysate from microdialysis in subcutaneous abdominal adipose tissue. The patients were four men and two women, 19-37 years old; all hypogonadal. BMI was 24.2-49.1, mean 35.9 kg/m(2). All had normal serum insulin levels. They received GH therapy (Genotropin Pfizer) during 12 months and doses were individually titrated to normal serum IGF-I for age. Immediately before treatment start and at 12 months, 30-36 h after the last GH injection, sampling of dialysate was carried out at night (11 p.m. to 7 a.m.), as well as after intravenously injection of a standardised GH dose (0.8 mg). At baseline individual mean night time glycerol and lactate were similar to levels in adults without PWS (160.7-278.1 micromol/L and 0.80-3.99 mmol/L, respectively), and did not change with 12 months GH treatment. Glucose levels were normal, except in a patient with diabetes, and did not change during the study. Compared to baseline the immediate effect of GH injection resulted in a significant increase in glycerol levels after 12 months. In conclusion, night time lipolytic response in this small group of PWS adults seemed normal and did not change after 12 months GH treatment. On the other hand short-term GH induced lipolysis increased, indicating normal lipolytic response in PWS.
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PMID:Growth hormone induced lipolysis during short- and long-term administration in adult Prader-Willi patients. 1623 42

The controversial question of the relationship between obesity and disease has been considerably clearer after the demonstration in several prospective, epidemiological studies that the subgroup of central, visceral obesity is particularly prone to develop cardiovascular disease, stroke, and non-insulin dependent diabetes mellitus. Visceral obesity is associated with multiple central endocrine aberrations. The hypothalamo-adrenal axis is apparently sensitive to stimuli, sex steroid hormone secretion blunted, and hyperandrogenicity is found in women. In addition, there seem to be signs of central dysfunctions in the regulation of hemodynamic factors after stress, and growth hormone secretion appears to be particularly blunted. Several of these endocrine abnormalities are associated with insulin resistance, particularly glycogen synthesis in muscle. Fiber composition with low type I/type II ratio might be secondary to the prevailing hyperinsulinemia, but low capillary density in muscle may well be of importance. In combination with elevated turn-over of free fatty acids (FFA) this will probably provide powerful mechanisms whereby insulin resistance is created. Portal FFA, from the highly lipolytic visceral depots may, in addition, affect hepatic metabolism to induce increased gluconeogenesis, production of very low density lipoproteins as well as to perhaps inhibit clearance of insulin. By these mechanisms a Metabolic Syndrome Visceral adipocytes seem to have a high density of several steroid hormone receptors, directing steroid hormone effects particularly to these depots. The net effect of cortisol is apparently a stimulation of lipid storage, with opposing effects of sex steroid hormones which also facilitate lipid mobilization, regulations most often found at the gene transcription level. Growth hormone inhibits cortisol effects on lipid accumulation, and amplifies the lipid mobilizing effects of steroid hormones. The combined perturbations of hormonal secretions will therefore probably direct triglycerides toward visceral depots. Circulatory and nervous regulatory mechanisms require, however, more attention. The multiple central endocrine and nervous aberrations of visceral obesity suggest neuroendocrine dysregulations, and have features characteristic of the hypothalamic arousal seen after certain types of stress, alcohol intake, and smoking. Such factors can be traced to subjects with visceral fat accumulation. Standardized stress, eliciting a "defeat reaction" in primates is followed by an apparently identical syndrome. This integrated picture of the multiple symptoms of visceral obesity is based on epidemiological, clinical, experimental, cellular, and molecular evidence. The ingredients of positive energy balance, including physical inactivity, stress, smoking, and alcohol consumption are frequent features of modern, urbanized society. Visceral obesity may therefore be an expression of a "Civilization Syndrome."
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PMID:Visceral obesity: a "civilization syndrome". 1635 May 73

Epidemiological studies have identified an association between size at birth and adult risk for type 2 diabetes mellitus and cardiovascular disease. In contemporary populations, children who are relatively small at birth and show rapid infancy weight gain are at greatest risk for the development of childhood obesity, increased visceral fat and insulin resistance: possible early markers of adult disease risk. Individuals presenting to growth clinics with short stature and a history of low birthweight will not have shown post-natal catch-up growth and may be a very heterogeneous group. Nevertheless, there are some data to suggest that as a group they are insulin resistant with decreased lean mass. Growth hormone treatment leads to reversible worsening of the insulin resistance, and short-term data do not indicate an increased risk for type 2 diabetes. However, further long-term follow-up is required, and particular care should be taken in monitoring children with a strong family history of type 2 diabetes and those from ethnic groups in which there is a high background prevalence of the disease.
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PMID:Babies born small for gestational age: insulin sensitivity and growth hormone treatment. 1643 46

Growth hormone (GH), Insulin Growth Factor-I (IGF-I) and lipids are linked by important reciprocal influences. Their knowledge allowed relevant pathophysiological and clinical acquisitions more and more interesting in scientific research and in medical practice. In this survey the influence of (GH) on lipid metabolism, particularly on free fatty acids (FFA) and lypoprotein metabolism has been analysed. Attention has been given to the disorders of the lipid-metabolism in GH hypo- and hyper-secretory states. On the other hand the role of lipids in the control of GH secretion has been extensively considered with particular attention to the role of exaggerated FFA levels in the pathogenesis of GH insufficiency in obesity.
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PMID:[Growth hormone and lipids]. 1650 48

Growth hormone (GH), acting through its receptor (GHR), is essential for somatic growth and development and maintaining metabolic homeostasis. GHR gene-deficient (GHR(-/-)) mice exhibit drastically diminished insulin-like growth factor-I (IGF-I) levels, proportional growth retardation, elevated insulin sensitivity, and reduced islet beta-cell mass. Unlike the liver, which is mostly unaffected by changes in IGF-I level, skeletal muscles express high levels of IGF-I receptor (IGF-IR). The net result of a concurrent deficiency in the actions of both GH and IGF-I, which exert opposite influences on insulin responsiveness, has not been evaluated. We studied insulin-stimulated early responses in the insulin receptor (IR), insulin receptor substrate-1 (IRS-1), and p85 subunit of phosphatidylinositol 3-kinase. Upon in vivo insulin stimulation, skeletal muscles of GHR(-/-) mice exhibit transient delayed responses in IR and IRS-1 phosphorylation but normal levels of p85 association with IRS-1. This is in contrast to normal/elevated insulin responses in hepatocytes and indicates tissue-specific effects of GHR gene deficiency. In addition to stimulating normal islet cell growth, GH may participate in islet cell overgrowth, which compensates for insulin resistance induced by obesity. To determine whether the islet cell overgrowth is dependent on GH signaling, we studied the response of male GHR(-/-) mice to high-fat diet (HFD)-induced obesity. After 17 wk on a HFD, GHR(-/-) mice became more significantly obese than wild-type mice and exhibited increased beta-cell mass to a slightly higher extent. These data demonstrate that GH signaling is not required for compensatory islet growth. Thus, in both muscle insulin responsiveness and islet growth compensation, normal levels of GH signals do not seem to play a dominant role.
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PMID:Growth hormone receptor gene deficiency causes delayed insulin responsiveness in skeletal muscles without affecting compensatory islet cell overgrowth in obese mice. 1662 95


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