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Query: UMLS:C0028754 (obesity)
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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

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

Calcitonin is an endogenous regulator of calcium homeostasis, which acts principally on bone. At present, the principal indications for the therapeutic use of calcitonin are disorders involving hypercalcemia Paget's disease, acute pancreatitis, high-bone-turnover osteoporosis, pain associated with osteoporosis or bone metastases, and Sudeck's atrophy. The aim of this study was to compare the analgesic effects on postoperative pain of salmon calcitonin versus opioids administered epidurally. Our prospective study included 53 ASA I-II patients who were scheduled for total hip arthoplasty under epidural anaesthesia and who did not fulfill 1 or more of the exclusion criteria: a history of pituitary gland dysfunction; diabetes mellitus; obesity; contraindications to performing an epidural block and/or an allergy to calcitonin. These patients were randomly allocated into 3 groups (A, B, and C), each of which received postoperatively a different analgesic epidural mixture of 10 mL to control postoperative pain. Group A was given bupivacaine 0.5% (5 mL) + fentanyl 100 (2 mL) + NaCl 0.9% (3 mL). Group B was given bupivacaine 0.5% (5 mL) + salmon calcitonin 100IU (1 mL) + NaCl 0.9% (4 mL). Group C was given salmon calcitonin 100IU (1 mL) + NaCl 0.9% (9 mL). Perioperatively, 4 blood samples were taken from each patient at the following specific times: 1. Before the induction of anesthesia; 2. At the end of the operation and before the epidural administration of the analgesic mixture; 3. At the end of the first postoperative hour (1 hour after the administration of the analgesic mixture); and 4. At the end of the second postoperative hour (2 hours after the administration of the mixture). In each blood sample, glucose, cortisol, growth hormone, and prolactin plasma levels were determined in order to investigate the changes of these parameters as a result of the endocrine reaction to stress, and to pain relief. The analgesic solution was administered immediately after the second blood sample was taken. At the same time as the 4 blood samples were taken, haemodynamic parameters and pain scores were recorded. Epidural salmon calcitonin in combination with local anaesthetic produces an analgesic effect similar to fentanyl and with stable hemodynamic results. It also eliminates postoperative hyperglycaemia. The cortisol plasma level does not increase during the first postoperative hour, but increases significantly during the second postoperative hour. Growth hormone and prolactin plasma levels were stable in all patients in all 3 groups. This study shows that calcitonin is a suitable alternative for the treatment of acute postoperative pain.
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PMID:Epidural calcitonin: does it provide better postoperative analgesia? An analysis of the haemodynamic, endocrine, and nociceptive responses of salmon calcitonin and opioids in epidural anesthesia for hip arthroplasty surgery. 1715 40

Growth hormone's (GH) lipolytic activity in white adipose tissue (WAT) results in decreased body fat in giant GH transgenic mice and increased subcutaneous fat in dwarf growth hormone receptor/binding protein gene-disrupted mice (GHR -/-). We therefore hypothesized that GH action would affect expression of CIDE-A (cell-death-inducing DFF45-like effector-A), a protein found in white adipose tissue (WAT) and involved in lipid metabolism. CIDE-A RNA levels were determined in subcutaneous, retroperitoneal and epididymal adipose tissue isolated from wild-type and GHR -/- mice. The adipose tissue was also analyzed for adipocyte size. We determined that the lack of GH action has depot-specific effects on the levels of CIDE-A RNA and affected adipocyte cell size. CIDE-A expression is significantly reduced in GHR -/- subcutaneous fat compared to wild-type but is not altered in retroperitoneal or epididymal fat. Likewise, adipocytes are significantly enlarged in GHR -/- subcutaneous adipose tissue relative wild-type mice. A high-fat diet also influenced the level of CIDE-A RNA in mouse adipose tissue. The high-fat diet significantly reduced CIDE-A expression in wild-type subcutaneous fat but did not alter CIDE-A expression in subcutaneous fat of GHR -/- mice. The diet also reduced CIDE-A expression in wild-type retroperitoneal fat but the levels of CIDE-A in epididymal fat were unchanged. In contrast, the high-fat diet reduced CIDE-A expression in both retroperitoneal and epididymal fat of GHR -/- mice. These data demonstrate that CIDE-A levels are reduced in two different mouse models of obesity and this reduction may contribute to altered lipid metabolism.
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PMID:CIDE-A gene expression is decreased in white adipose tissue of growth hormone receptor/binding protein gene disrupted mice and with high-fat feeding of normal mice. 1754 97

Growth hormone (GH) is licensed for treatment for Prader-Willi syndrome (PWS) for improvement of body composition,1(-)3 height velocity, mobility, behaviour and quality of life.4 Recent case reports, however, have pointed out the occurrence of sudden death during initiation of GH, mainly during sleep and possibly related to severe obesity and sleep-disordered breathing (SDB).5(-)15 Concerns for an increased mortality in PWS children starting GH therapy led to a call for cessation of its use. Children with PWS are at risk of developing SDB secondary to both deficient autonomic sleep control and upper airway obstruction (UAO). It has been suggested that GH exacerbates pre-existing gas-exchange deficiencies in three ways: (a) by stimulation of adenotonsillar hypertrophy;16 17 (b) by a rise in basal metabolic rate with a resultant rise in oxygen demand;18 and (c) by normalisation of previously decreased hydration with augmentation of volume load.19 Are we withholding GH therapy, a treatment known to be of benefit in PWS, without adequate evidence to justify our actions? We consider it safe to treat severely obese children with GH once SDB is addressed using respiratory support such as continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP). In this paper, we evaluate the current evidence for the use of GH in PWS from a respiratory bias and propose a pathway for the identification and monitoring of these "at risk" patients.
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PMID:Prader-Willi syndrome: who can have growth hormone? 1808 32

Growth hormone (GH)-deficiency is usually associated with elevated adiposity, hyperleptinemia, and increased fracture risk. Since leptin is thought to enhance cortical bone formation, we have investigated the contribution of elevated adiposity and hyperleptinemia on femoral strength in rodent models of GH deficiency. Quantification of the transpubertal development of femoral strength in the moderately GH-deficient/hyperleptinemic Tgr rat and the profoundly GH-deficient/hypoleptinemic dw/dw rat revealed that the mechanical properties of cortical bone in these two models were similarly compromised, a 25-30% reduction in failure load being entirely due to impairment of geometric variables. In contrast, murine models of partial (GH antagonist transgenic) and complete (GH receptor-null) loss of GH signaling and elevated adiposity showed an impairment of femoral cortical strength proportionate to the reduction of GH signaling. To determine whether impaired femoral strength is exacerbated by obesity/hyperleptinemia, femoral strength was assessed in dw/dw rats following two developmental manipulations that elevate abdominal adiposity and circulating leptin, neonatal monosodium glutamate (MSG) treatment, and maintenance on an elevated fat diet. The additional impairment of femoral strength following MSG treatment is likely to have resulted from a reduction in residual activity of the hypothalamo-pituitary-GH-IGF-I axis, but consumption of elevated dietary fat, which did not reduce circulating IGF-I, failed to exacerbate the compromised femoral strength in dw/dw rats. Taken together, our data indicate that the obesity and hyperleptinemia usually associated with GH deficiency do not exert a significant influence over the strength of cortical bone.
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PMID:Does adiposity status influence femoral cortical strength in rodent models of growth hormone deficiency? 1900 45


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