UMLS:C0242339 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242339 (dyslipidemia)
13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Growth hormone (GH) has been in clinical use for almost 40 years to promote linear growth in growth hormone deficient children. Treatment has usually been stopped after the epiphyseal plates have fused or when the person reaches a proper height. Previously, GH replacement therapy in adults was not deemed clinically indicated. GH-deficiency in adults is now accepted as a clinical entity, manifested by cardiovascular dysfunction, dyslipidemia, reduced capacity for exercise and muscular weakness, altered body composition, increased prevalence of osteoporosis, and impaired psychological well-being. The treatment of adults used to be unrealistic, because of the limited supply of human pituitary-derived GH. Moreover, the risk of transferring Creutzfeldt-Jakobs disease led to a stop in the therapeutic use of pituitary GH preparations. The availability of recombinant human prion-free GH has made replacement therapy possible in GH-deficient adults. In this review, the GH deficiency syndrome in adults is described, together with the results of recent clinical studies of GH replacement treatment in adults.
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PMID:[Growth hormone deficiency in adults]. 901 53

Lipoprotein lipase (LPL) is involved in clearing triglyceride-rich chylomicrons and very-low-density lipoprotein particles from the bloodstream, providing free fatty acids to particular adipose tissue for storage and to skeletal muscle tissue for oxidation and energy production. Although the same gene (chromosome 8p22) encodes LPL, the enzyme activity is regulated in a tissue-specific manner. Dysfunction of the LPL enzyme has been implicated in the pathogenesis of dyslipidemia (high triglyceride and low high-density lipoprotein (HDL) cholesterol), early arteriosclerosis, and the pathogenesis of obesity. Treatment with growth hormone (GH) both in vivo and in vitro results in a pronounced reduction (often up to 50%) of LPL activity in adipose tissue in humans. The specific level of messenger ribonucleic acid, however, is not generally affected by GH treatment in adipose tissue, indicating that the effect of GH is mediated at a post-translational level. The GH-mediated reduction in adipose tissue LPL activity may be involved in the reduction in adipose tissue mass commonly seen after prolonged GH treatment in GH-deficient adults and GH treatment in obese subjects. LPL activity in adipose and skeletal muscle tissue is generally regulated in a reciprocal manner by, for example, fasting, feeding, insulin and epinephrine. A high level of LPL activity, particularly in skeletal muscle tissue, has been found to be associated with a beneficial lipoprotein profile (low triglyceride and high HDL cholesterol). In investigations where obese but otherwise healthy women were treated with GH, and in another study where adults with GH deficiency were treated for 4 months with GH, we found no effects of GH on either skeletal muscle LPL activity nor on skeletal muscle LPL gene expression. In conclusion, GH has a pronounced inhibitory effect on adipose tissue LPL activity, which is mediated at a post-translational level. The GH-induced reduction in adipose tissue mass may be partly mediated by this effect on adipose tissue LPL. GH has no effects on LPL activity in skeletal muscle, which may be related to the fact that GH has no or only minor effects on plasma triglyceride and HDL cholesterol levels. Finally, GH is not, unlike for example insulin and catecholamines, involved in antagonistic regulation of LPL in muscle and adipose tissue.
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PMID:Effect of growth hormone on adipose tissue and skeletal muscle lipoprotein lipase activity in humans. 1044 64

Dyslipidaemia is often associated with adult growth hormone (GH) deficiency. Reduced removal of very-low-density lipoprotein (VLDL) apolipoprotein B-100 (apo B-100) can, in part, explain the "unfavourable" lipid profile of these patients. By modifying VLDL composition and through its action on low-density lipoprotein (LDL) receptors, GH may improve the lipid profile by increasing direct hepatic uptake of VLDL apo B-100, thereby decreasing conversion to LDL. Although GH stimulates VLDL apo B-100 secretion, this is exceeded by its effects in upregulating LDL receptors and modifying VLDL composition. We hypothesize that the improved lipid profile, in particular the decrease in cholesterol-rich VLDL particles, may contribute to a possible antiatherogenic action of GH. GH appears to have an important role in hepatic apo B-100 metabolism. However, we are just at the beginning of understanding the underlying mechanism. Further studies are required to investigate the effect of GH on other lipoprotein classes, in particular VLDL subfractions, intermediate-density lipoprotein, LDL and high-density lipoprotein. The key question, however, remains as to whether GH replacement therapy can reduce cardiovascular mortality. Long-term studies with sufficient numbers of patients are required to answer this question.
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PMID:Dynamics of lipoprotein metabolism in adult growth hormone deficiency. 1044 65

Persons with chronic SCI have several metabolic disturbances. As a consequence of inactivity and the body compositional changes of decreased skeletal muscle with a relative increase in adiposity, a state of insulin resistance and hyperinsulinemia has been demonstrated to exist, associated with abnormalities in oral carbohydrate handling. Elevated plasma insulin levels in persons with SCI probably contribute to the cause of frequent dyslipidemia and hypertension. This constellation of metabolic changes represents an atherogenic pattern of CHD risk factors with many of the distinctive features of a cardiovascular dysmetabolic syndrome that is called syndrome X. Reduction in modifiable risk factors for CHD should decrease the occurrence of catastrophic cardiovascular events. There is evidence to suggest that endogenous anabolic hormone levels are depressed in a proportion of individuals with SCI. Depression of serum testosterone and growth hormone/IGF-I levels may exacerbate the adverse lipid and body compositional changes, reduce exercise tolerance, and have deleterious effects on quality of life. Because of immobilization, individuals with paraplegia have osteoporosis of the pelvis and lower extremities, and those with tetraplegia also have osteoporosis of the upper extremities. In addition, there is evidence to suggest that bone loss progresses with time in persons with chronic SCI. This may be caused by chronic immobilization per se or may be a consequence of adverse hormonal changes, including deficiency of anabolic hormones or deficiency of vitamin D and calcium with secondary hyperparathyroidism. Serum thyroid function abnormalities resembling the euthyroid sick "low T3 syndrome" have been reported in those with acute and chronic spinal cord injury. Depressed serum T3 and elevated rT3 in chronic SCI may be caused by associated illness. Current practice has been hesitant to treat abnormal serum thyroid chemistries associated with nonthyroidal illness. Recognition of metabolic abnormalities in individuals with SCI is vital as a first step in improving clinical care. The application of appropriate interventions to correct or ameliorate these abnormalities promises to improve longevity and quality of life in persons with SCI.
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PMID:Metabolic changes in persons after spinal cord injury. 1068 Jan 61

In obesity, growth hormone (GH) secretion is impaired which is considered a consequence rather than a cause of obesity. GH regulates the expression of GH receptor and the synthesis of insulin-like growth factor I (IGF-I) in adipocytes. Although GH hyposecretion in obesity may decrease the generation of IGF-I in each adipocyte, increased amounts of IGF-I and GH-binding protein could be secreted from the excessively enlarged amounts of adipose tissue. This may contribute to the normal/high serum-IGF-I and high GH-binding protein levels in obesity. Hyperinsulinemia and increased GH receptor activity may also affect the GH-IGF-I axis. Favorable effects of GH treatment have been observed in obese children and adults. GH treatment decreases adiposity, reduces triglyceride accumulation by inhibiting lipoprotein lipase and enhances lipolysis both via increased hormone-sensitive lipase activity and via induction of beta adrenoreceptors. GH treatment also has a favorable effect on obesity-associated dyslipidemia, but the effects on insulin sensitivity have been conflicting.
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PMID:Growth hormone and adipocyte function in obesity. 1089 49

Changes in body fat in persons infected with the human immunodeficiency virus (HIV) have been associated with deleterious changes in blood lipids and insulin resistance, raising concern that these changes will increase the risk for accelerated atherosclerosis. Changes in body fat are often identified in advanced disease but may also occur early after HIV infection is detected. Conflicting evidence suggests that fat maldistribution may be related to use of protease inhibitors, nonnucleoside reverse transcriptase inhibitors, or a combination of these two classes of drugs, but the etiologies of the various changes in body fat remain uncertain. To date there have been no remedies for the loss of subcutaneous fat, but recent evidence has suggested that discontinuation of stavudine or zidovudine therapy may be associated with limited restoration of extremity fat. For fat accumulation, a number of strategies have been attempted, including treatment with human growth hormone, androgens, or metformin, and changes in diet and exercise. As in persons not infected with HIV, it is expected that the cornerstone of management, especially in the presence of central obesity, dyslipidemia, and insulin resistance, will include a diet low in saturated fat, with low-glycemic index carbohydrates, and high in fiber. Very limited evidence in persons infected with HIV has suggested that a supervised exercise program may be beneficial.
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PMID:Body habitus changes related to lipodystrophy. 1265 76

Aquaporin adipose (AQPap) is a putative glycerol channel in adipocytes. It has recently been shown to be upregulated in insulin resistance stimulated by thiazolidinediones and inhibited by insulin. To further clarify regulation of AQPap gene expression, 3T3-L1 adipocytes were chronically treated with various hormones known to influence insulin sensitivity and adipocyte metabolism, and AQPap mRNA was measured by quantitative real-time reverse transcription-polymerase chain reaction. Interestingly, treatment of 3T3-Ll adipocytes with 10 micro M isoproterenol, 10 ng/ml TNFalpha, and 100 nM dexamethasone for 16 h inhibited AQPap gene expression by 62 %, 60 %, and 39 %, respectively; angiotensin 2, growth hormone, and triiodothyronine did not have any effect. The inhibitory effects were dose-dependent with significant suppression detectable at concentrations as low as 1 nM isoproterenol, 1 ng/ml TNFalpha, and 10 nM dexamethasone. Furthermore, inhibition of AQPap gene expression could be almost completely reversed by pretreating 3T3-L1 adipocytes with the beta-adrenoceptor antagonist propranolol. Moreover, stimulation of Gs-proteins with cholera toxin and adenylyl cyclase with forskolin and dibutyryl-cAMP dramatically downregulated AQPap mRNA. Taken together, our results suggest that AQPap is an adipocyte-expressed glycerol channel selectively regulated and profoundly downregulated by hormones implicated in the pathogenesis of insulin resistance and dyslipidemia.
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PMID:Suppression of aquaporin adipose gene expression by isoproterenol, TNFalpha, and dexamethasone. 1277 65

Prader-Willi syndrome (PWS) is a genetic disorder characterized by mild mental retardation, short stature, abnormal body composition, muscular hypotonia and distinctive behavioural features. Excessive eating causes progressive obesity with increased cardiovascular morbidity and mortality. In the PWS genotype loss of one or more normally active paternal genes in region q11-13 on chromosome 15 is seen. It is supposed that the genetic alteration leads to dysfunction of several hypothalamic centres and growth hormone (GH) deficiency (GHD) is common. PWS is well described in children, in whom GH treatment improves body composition, linear growth, physical strength and agility. Few studies have focused on adults. We examined a cohort of 19 young adults with clinical PWS (13 with positive genotype) and mean BMI of 35 kg/m2. At baseline the activity of the GH-insulin-like growth factor-I (IGF-I) system was impaired with low GH values, low total IGF-I and in relation to the obesity low levels of free IGF-I and non-suppressed IGF-binding-protein-1 (IGFBP-1). 2/3 were hypogonadal. Bone mineral density (BMD) was low. Four patients had impaired glucose tolerance and nine patients high homeostasis model assessment (HOMA) index, indicating insulin resistance. Seven patients had a moderate dyslipidemia. The 13 patients with the PWS genotype were shorter and had significantly lower IGF-I. Seventeen (9 men and 8 women), subsequently completed a 12 months GH treatment trial, and GH had beneficial effects on body composition without significant adverse effects. The effects were more pronounced in the patients with the PWS genotype. Analysis of peptides involved in appetite regulation showed that leptin levels were high reflecting obesity and as a consequence NPY levels were low. In relation to the patients obesity circulating oxytocin levels were abnormally low and ghrelin levels abnormally high. Thus, oxytocin and ghrelin might be involved in the hyperphagia. NPY, leptin and ghrelin did not change during GH treatment. In conclusion this pilot study showed that adults with PWS have a partial GH deficiency, and GH treatment has beneficial effects on body composition in adult PWS without significant side-effects. Larger and longer term studies on the effect of GH replacement in adult PWS are encouraged.
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PMID:Endocrine and metabolic aspects of adult Prader-Willi syndrome with special emphasis on the effect of growth hormone treatment. 1470 May 52

Insulin-like growth factor-1 (IGF-1) and its receptors share considerable homology with insulin and insulin receptors, and their respective signaling pathways interact at the post receptor level. While the growth hormone (GH)-IGF-1 axis principally regulates tissue growth and differentiation, insulin exerts it primary effects on fuel metabolism. However, these two endocrine systems interact at multiple levels and in diabetes mellitus the GH-IGF-1 axis is grossly disturbed, with increased secretion of GH, reduced plasma levels of IGF-1, and complex tissue-specific changes in IGF binding proteins (IGFBPs). These observations have given rise to the view that GH-IGF-1 axis dysfunction, particularly low plasma levels of circulating IGF-1, probably play a significant role in several aspects of the pathophysiology of diabetes mellitus, including insulin resistance and poor glycemic control, and may also influence the development of microvascular complications. The availability of recombinant human IGF-1 (rhIGF-1; mecasermin), used either alone or in combination with insulin, has led to experimental studies and clinical trials in humans testing these hypotheses. These studies have examined the impact of subcutaneous rhIGF-1 injections on sensitivity and metabolic parameters. In patients with type 1 and 2 diabetes mellitus, insulin sensitivity is significantly improved, insulin requirements are reduced, and glycemic control of dyslipidemia is generally improved in short-term studies. rhIGF-1 is a particularly attractive possibility in patients with type 2 diabetes mellitus, where insulin resistance is the fundamental problem. Some patients with genetic syndromes of severe insulin resistance also benefit from treatment with rhIGF-1, which can bypass blocks in the insulin signaling pathway. The common adverse effects reported for rhIGF-1 are dose-related and include edema, jaw pain, arthralgia, myalgia, hypotension, injection site pain, and less commonly, Bell's palsy and raised intracranial pressure. Although disturbance of the GH-IGF-1 axis participates in the development of diabetic complications, the functional consequences of the complex changes in IGFBP expression at the tissue level are uncertain, and it is not known whether systemic IGF-1 therapy or other manipulations of the GH-IGF-1 axis would be helpful or harmful. Experimentally, IGF-1 has a protective effect on neuropathy, and could find an application in the healing of neuropathic ulcers. The potential benefits of IGF-1 therapy in diabetes mellitus have yet to be realised.
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PMID:Therapeutic potential of insulin-like growth factor-1 in patients with diabetes mellitus. 1583 92

The human body, when under threat, elicits a set of neuroendocrine responses, including an increased secretion of glucocorticoids (GCs) and catecholamines from the adrenal gland and the activation of the sympathetic nervous system. These hormonal secretions allow a "fight or flight" response by mobilizing endogenous substrate and inducing a state of insulin resistance in the liver and skeletal muscles. Although the stress response was essential in ancient times to survive physical aggression, this threat has disappeared in our industrialized societies. However, in today's environment, the same stress responses can be elicited by emotional stimuli or professional and social stress. Such psychological stress may be protracted and unrelated to an increased metabolic demand. Thus, the energy mobilized is not used but is stored in visceral fat depots by the combined action of hypercortisolism and hyperinsulinemia. In addition, chronic activation of the stress system causes suppression of the gonadal, growth hormone (GH), and thyroid axes. These metabolic disturbances, in concert, lead to the clinical expression of a number of comorbidities including central obesity, hypertension, dyslipidemia, and endothelial dysfunction, all components of the metabolic syndrome and cardiometabolic risk factors. Moreover, chronic stress has deleterious effects on the brain and, in particular, affects hippocampal structure and function leading to cognitive and mood disturbances. Importantly, this stress-induced clinical phenotype is likely to be exaggerated in the presence of physical inactivity, resulting in a "stress-induced/exercise deficient" phenotype. Assuming that the stress response is a neuroendocrine mechanism that occurs in anticipation of physical action, then physical activity should be the natural means to prevent the consequences of stress. Indeed, accumulating evidence documents the beneficial effects of regular exercise in preventing or ameliorating the metabolic and psychological comorbidities induced by chronic stress. These benefits are thought to derive from a central effect of exercise to reduce the sensitivity to stress and also peripheral actions influencing metabolic functions and, in particular, insulin sensitivity and the partitioning of fuels toward oxidation rather than storage. It is concluded that chronic psychosocial stress, in the presence of physical inactivity, is likely to contribute to the epidemic of cardiometabolic and emotional disease of our current society. The way to prevent and combat this burden is by regular exercise.
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PMID:The protective role of exercise on stress system dysregulation and comorbidities. 1714 41

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