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

Human obesity is a manifestation of a positive energy balance. A variety of different factors influence this balance. The varieties of human obesity may be classified as follows: 1. Childhood onset with or without an increased number of adipocytes; 2. The syndromes of neuroendocrine dysfunction including hypothalamic obesity, Cushing's disease, and hyperinsulinism; 3. Dietary obesity; 4. Obesity due to physical inactivity; and 5. Genetic forms of obesity. Among the genetic form of obesity are the Laurence-Moon-Bardet-Biedl syndrome. Alstrom's syndrome, and possibly the Prader-Willi syndrome. Studies in experimental animals have increased our understanding of two of these forms of human obesity. These are: 1. Hypothalamic obesity associated with decreased sympathetic activity, hyperphagia and an increased secretion of insulin. Subdiaphragmatic vagotomy can reverse this syndrome; 2. Genetic forms of obesity inherited as recessive or dominant traits.
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PMID:Human obesity and some of its experimental counterparts. 11 2

The definition and risks of obesity have been reviewed and a nomogram provided for reference. Organization of information about the syndromes of obesity has been approached from several points of view. An anatomic classification has been developed, in which generalized and localized forms of fat accumulation can be separated. Hypercellularity of the adipose tissue in the childhood-onset forms of obesity is usually, but not always, present. Etiologic mechanisms are also useful in classifying obesity. This nosologic approach has been derived largely from experimental studies but has contributed significantly to understanding of pathogenetic mechanisms in man. Hypothalamic obesity is now thought to result from augmented secretion of insulin. The recessively inherited forms of obesity, on the other hand, appear to result from loss of a thermogenic system involving the ouabain-suppressible thyroid-induced (Na+ + K+) -ATPase which, in turn, accounts for the myriad of defects in these animals. Techniques of cybernetic engineering provide a third approach to classification of the syndromes of obesity. The control of body fat was analyzed as an analogy to the control of temperature in a building. These various approaches, and the new insights which they have provided for understanding the syndromes of obesity, promise to provide new pathways for pharmacologic intervention in the treatment of this problem.
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PMID:Definition, measurement, and classification of the syndromes of obesity. 71 70

The elements of a feedback system for regulating body fat stores consists of an afferent limb providing feedback signals to the central controller in the brain, which integrates information from the sensory and autonomic nervous systems with signals from the internal milieu and modulates ingestive behavior and thermogenic components of the adrenergic nervous system. The search for defective mechanisms that produce obesity has utilized animals with genetic, hypothalamic, and dietary types of obesity. In all three cases, obesity is associated with an absolute or relative decrease in the activity of the sympathetic nervous system. Experimental situations associated with reduced activity of the sympathetic nervous system are generally accompanied by increased food intake and vice versa. Hypothalamic obesity results from damage to the ventromedial hypothalamus, which disrupts modulation of the autonomic nervous system by nutrient and hormonal signals. Recessively inherited obesity may result from failure to modulate the steroid-receptor complex interaction with the promoter region of the genome. Impaired acetylation of melanocyte-stimulating hormone (MSH) may be involved in the development of obesity in the obese yellow mouse. In all cases adrenalectomy arrests the progression or reverses the obesity. These findings further strengthen the autonomic and endocrine hypothesis for obesity.
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PMID:1989 McCollum Award lecture. Genetic and hypothalamic mechanisms for obesity--finding the needle in the haystack. 268 17

The present study was designed to develop an animal model of multiple risk factors, including obesity, hypertension, non-insulin-dependent diabetes mellitus, and hyperlipidemia. Hypothalamic obesity was induced by neonatal monosodium glutamate (MSG) treatment in spontaneously hypertensive rats (SHR). Female newborn SHR were treated intraperitoneally with 2 or 4 mg/kg body weight of MSG for 5 days. Obesity developed in SHR treated with 4 mg/kg of MSG but not in SHR treated with 2 mg/kg of MSG. Obese SHR had impaired glucose tolerance, hyperinsulinemia, and hypertriglyceridemia. However, the severity of hypertension was attenuated in obese SHR as compared with control SHR. The degree of obesity was closely related to the metabolic abnormalities, but inversely correlated with the blood pressure level. Macrovascular changes were investigated in obese SHR at 14 months of age. Intimal thickening was accelerated in the carotid artery of obese SHR as compared with that of nonobese SHR. Aortic contents of DNA and total cholesterol were significantly increased in obese SHR. SHR associated with MSG-induced obesity showed major manifestations of metabolic syndrome X. This animal model may be useful to study the clustering of risk factors for the development of macrovascular diseases.
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PMID:Obesity induced by neonatal monosodium glutamate treatment in spontaneously hypertensive rats: an animal model of multiple risk factors. 958 1

The hypolipidemic effects of pantothenic acid derivatives (phosphopantothenate, panthenol and pantethine) were studied in mice with hypothalamic obesity. Hypothalamic obesity in mice was induced by single injection of aurothioglucose (300 mg/kg body wt, i.p.). All the tested substances were administered during the last 10 days before decapitation (i.m., of dosage equivalent to 150 mg/kg body wt of phosphopantothenate). The studied substances inhibited the weight gain of the animals with hypothalamic obesity over the last 10 days of the experiment. The treatment with aurothioglucose increased food intake and mean body weight, blood glucose level; insulin, serum total cholesterol, triglyceride, the sum of LDL + VLDL and LDL-cholesterol concentration; triglyceride and cholesterol fractions in the liver; triglyceride and FFA content as well as lipoprotein lipase activity in adipose tissue of experimental mice. The administration of the assay compounds lowered food intake and mean body weight, insulin and glucose levels and decreased the content of triglycerides, total cholesterol and cholesterol esters in serum and adipose tissue as well as raised the activity of lipoprotein lipase in adipose tissue and serum lipolytic activity in obese mice. Among the compounds studied the reverse effect of panthenol was especially pronounced. The mechanism of hypolipidemic effects of pantothenic acid derivatives can be related to the reduced resistance to insulin and activation of lipolysis in serum and adipose tissue.
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PMID:Hypolipidemic effect of pantothenic acid derivatives in mice with hypothalamic obesity induced by aurothioglucose. 1181 9

Hypothalamic obesity, a syndrome of intractable weight gain due to hypothalamic damage, is an uncommon but devastating complication for children surviving brain tumors. We undertook a retrospective evaluation of the body mass index (BMI) curves for the St. Jude Children's Research Hospital brain tumor population diagnosed between 1965 and 1995 after completion of therapy to determine risk factors for the development of obesity. Inclusion criteria were: diagnosis less than 14 yr of age, no spinal cord involvement, ambulatory, no supraphysiologic hydrocortisone therapy (>12 mg/m(2) x d), treatment and follow-up at St. Jude Children's Research Hospital, and disease-free survival greater than 5 yr (n = 148). Risk factors examined were age at diagnosis, tumor location, histology, extent of surgery, hydrocephalus requiring ventriculoperitoneal shunting, initial high-dose glucocorticoids, cranial radiation therapy, radiation dosimetry to the hypothalamus, intrathecal chemotherapy, and presence of endocrinopathy. Analyses were performed both between groups within a risk factor and against BMI changes for age in normal children older than 5.5 yr (the age of adiposity rebound). Risk factors were: age at diagnosis (P = 0.04), radiation dosimetry to the hypothalamus (51-72 Gy, P = 0.002 even after hypothalamic and thalamic tumor exclusion), and presence of any endocrinopathy (P = 0.03). In addition, risk factors when compared with BMI slope for the general American pediatric population included: tumor location (hypothalamic, P = 0.001), tumor histology (craniopharyngioma, P = 0.009; pilocytic astrocytoma, P = 0.043; medulloblastoma, P = 0.039); and extent of surgery (biopsy, P = 0.03; subtotal resection, P = 0.018). These results verify hypothalamic damage, either due to tumor, surgery, or radiation, as the primary cause of obesity in survivors of childhood brain tumors. In particular, hypothalamic radiation doses of more than 51 Gy are permissive. These results reiterate the importance of the hypothalamus in energy balance, provide risk assessment criteria for preventative measures before the development of obesity in at-risk patients, and suggest therapeutic strategies to reduce the future development of obesity.
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PMID:Risk factors for the development of obesity in children surviving brain tumors. 1257 89

Hypothalamic obesity is a devastating complication in children surviving brain tumors and/or cranial irradiation. These subjects are thought to exhibit autonomic dysregulation of the beta-cell, with insulin hypersecretion in response to oral glucose tolerance testing (OGTT). We report the results of a randomized, double-blind, placebo-controlled trial of octreotide therapy for pediatric hypothalamic obesity. Eighteen subjects [weight, 100.6 +/- 5.6 kg; body mass index (BMI), 37.1 +/- 1.3 kg/m(2)] received octreotide (5-15 microg/kg x d s.c.) or placebo for 6 months. With octreotide, Delta weight (mean +/- SEM) was +1.6 +/- 0.6 vs. +9.1 +/- 1.7 kg for placebo (P < 0.001). Delta BMI was -0.2 +/- 0.2 vs. +2.2 +/- 0.5 kg/m(2), respectively (P < 0.001). OGTT documented Delta insulin response (peak - basal) of -417 +/- 304 pM after octreotide vs. +216 +/- 215 pM after placebo (P = 0.034). Improvement in physical activity by parent report was noted with octreotide, but not placebo (P = 0.03). For the octreotide group, changes in quality of life positively correlated with changes in insulin response (P = 0.041). Complications and adverse events were mild and self-limited. These data demonstrate the beneficial effects of octreotide in pediatric hypothalamic obesity. Octreotide suppressed insulin, and stabilized weight and BMI. Improved quality of life correlated with the degree of insulin suppression. Octreotide was safe and well tolerated.
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PMID:Octreotide therapy of pediatric hypothalamic obesity: a double-blind, placebo-controlled trial. 1501 8

Early researchers found that lesions of the ventromedial hypothalamus (VMH) resulted in hyperphagia and obesity in a variety of species including humans, which led them to designate the VMH as the brain's "satiety center." Many researchers later dismissed a role for the VMH in feeding behavior when Gold claimed that lesions restricted to the VMH did not result in overeating and that obesity was observed only with lesions or knife cuts that extended beyond the borders of the VMH and damaged or severed the ventral noradrenergic bundle (VNAB) or paraventricular nucleus (PVN). However, anatomical studies done both before and after Gold's study did not replicate his results with lesions, and in nearly every published direct comparison of VMH lesions vs. PVN or VNAB lesions, the group with VMH lesions ate substantially more food and gained twice as much weight. Several other important differences have also been found between VMH and both PVN and VNAB lesion-induced obesity. Concerns regarding (a) motivation to work for food and (b) the effects of nonirritative lesions have also been addressed and answered in many studies. Lesion studies with weanling rats and adult pair-tube-fed rats, as well as recent studies of knockout mice deficient in the orphan nuclear receptor steroidogenic factor 1, indicate that VMH lesion-induced obesity is in large part a metabolic obesity (due to autonomic nervous system disorders) independent of hyperphagia. However, there is ample evidence that the VMH also plays a primary role in feeding behavior. Neuroimaging studies in humans have shown a marked increase in activity in the area of the VMH during feeding. The VMH has a large population of glucoresponsive neurons that dynamically respond to blood glucose levels and numerous histamine, dopamine, serotonin, and GABA neurons that respond to feeding-related stimuli. Recent studies have implicated melanocortins in the VMH regulation of feeding behavior: food intake decreases when arcuate nucleus pro-opiomelanocortin (POMC) neurons activate VMH brain-derived neurotrophic factor (BDNF) neurons. Moderate hyperphagia and obesity have also been observed in female rats with damage to the efferent projections from the posterodorsal amygdala to the VMH. Hypothalamic obesity can result from damage to either the POMC or BDNF neurons. The concept of hypothalamic feeding and satiety centers is outdated and unnecessary, and progress in understanding hypothalamic mechanisms of feeding behavior will be achieved only by appreciating the different types of neural and blood-borne information received by the various nuclei, and then attempting to determine how this information is integrated to obtain a balance between energy intake and energy output.
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PMID:The rise, fall, and resurrection of the ventromedial hypothalamus in the regulation of feeding behavior and body weight. 1641 83

Hypothalamic MSG-obese rats show hyperinsulinemia and tissue insulin resistance, and they display intense parasympathetic activity. Current analysis investigates whether early subdiaphragmatic vagotomy prevents tissue insulin sensitivity impairment in adult obese MSG-rats. Hypothalamic obesity was induced by MSG (4 mg/g BW), daily, from birth up to 5 days. Control animals receiving saline solution. On the 30th day rats underwent bilateral subdiaphragmatic vagotomy or sham surgery. An intravenous glucose tolerance test (i.v.GTT) was performed when rats turned 90 days old. Total white fat tissue (WAT) from rat carcass was extracted and isolated; the interscapular brown fat tissue (IBAT) was weighed. Rather than blocking obesity, vagotomy reduced WAT and IBAT in MSG-obese rats when the latter were compared to sham MSG-rats. High blood fasting insulin and normal glucose levels were also observed in MSG-obese rats. Although glucose intolerance, high insulin secretion, and significant insulin resistance were recorded, vagotomy improved fasting insulinemia, glucose tolerance and insulin tissue sensitivity in MSG-obese rats. Results suggest that increased fat accumulation is caused, at least in part, by high blood insulin concentration, and enhanced parasympathetic activity on MSG-obese rats.
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PMID:Fat storage is partially dependent on vagal activity and insulin secretion of hypothalamic obese rat. 1787 25

Hypothalamic injury from acquired structural damage due to infiltrative disease, tumor, or their treatment aftereffects frequently results in the development of an obesity syndrome characterized by a rapid, unrelenting weight gain that may be accompanied by severe hyperphagia. Weight gain occurs from the disruption of the normal homeostatic functioning of the hypothalamic centers responsible for controlling satiety and hunger and regulating energy balance with resulting hyperphagia, autonomic imbalance, reduction of energy expenditure, and hyperinsulinemia. Curtailment of weight increase has traditionally been refractory to usual dietary and lifestyle interventions. Pharmacotherapy targeting insulin secretion and augmenting sympathetic output have been attempted to promote weight loss or attenuate weight gain. In addition, case reports suggest that bariatric surgery may be an effective treatment option for these patients. Hormonal deficits are often present, and their management may also have consequences for weight control. Hypothalamic obesity confers significant morbidity and mortality, and there is a need for greater elucidation of its risk factors and pathogenesis so that more effective interventions can be developed.
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PMID:Review of physiology, clinical manifestations, and management of hypothalamic obesity in humans. 1832 43


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