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

Corticotropin-releasing factor (CRF) has been implicated in the development of obesity in genetically obese rodents. We have investigated the effect of 100 micrograms of intravenous CRF on energy expenditure in women, comparing the response in obese and lean volunteers. In response to CRF, energy expenditure as measured by indirect calorimetry increased rapidly with a peak response in both groups reached by two minutes with a ten minute post-CRF response averaging 9.0% in the lean and 11.0% in the obese. Subsequently, energy expenditure remained elevated for a longer duration in the lean compared to the obese. Overall, the total 30 min cumulative metabolic rise was similar in the lean and obese. The increments in energy expenditure were associated with elevation of plasma noradrenaline levels, suggesting the possible involvement of the sympathetic nervous system. The adrenocorticotrophic (ACTH) and cortisol responses to CRF were similar in obese and lean. Intravenous administration of CRF therefore acutely increases energy expenditure in both lean and obese healthy subjects.
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PMID:The acute effects of corticotropin-releasing factor on energy expenditure in lean and obese women. 132 49

The combined syndrome of android (upper body) obesity, diabetes, hyperlipidaemia and hypertension is discussed in terms of a deranged endocrine regulation of metabolism. The syndrome is characterized by insulin insensitivity and an increased control of metabolism by cortisol. The antagonism between the two hormones appears to be partly responsible for the hyperglycaemia, hypertriglyceridaemia and hypercholesterolaemia. The synergism between insulin and cortisol in stimulating energy deposition, associated with a decreased effect of corticotropin-releasing factor in stimulating energy expenditure, is likely to contribute to the development of obesity. The efficacy of D-fenfluramine in treating the obese-diabetic-hyperlipidaemic-hypertensive syndrome probably depends on its actions on the serotoninergic system in the hypothalamus which both decreases food consumption and tends to normalize hormonal balance through the hypothalamic-pituitary-adrenal axis.
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PMID:Neuroendocrine regulation and obesity. 133 26

It has previously been established that norepinephrine (NE) in the central nervous system is involved in feeding and the development of obesity. The present experiments were carried out to investigate the relationship between the uptake of NE by a crude hypothalamic homogenate and NE-mediated sympathetic activity in interscapular brown adipose tissue (IBAT). Sympathetic nervous system activity was assessed by measuring the binding of the purine nucleotide guanosine-5'-diphosphate (GDP) to mitochondria isolated from IBAT. Four situations known to alter food intake and sympathetic activity, namely, corticotropin releasing factor infusion, adrenalectomy, fenfluramine treatment and obesity due to genetic transmission were studied. In each case, [3H]NE uptake by the hypothalamic preparation and GDP binding to IBAT mitochondria were measured. A highly significant negative correlation between the uptake of NE by hypothalamic homogenates and the binding of GDP to IBAT mitochondria was obtained in both lean and obese animals. These findings are discussed with regard to the regulation of food intake and sympathetic nervous system mediated thermogenesis.
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PMID:Relationship between uptake of norepinephrine by hypothalamic homogenates and the activity of brown adipose tissue. 233 99

In Zucker obese rats (fa/fa) there are disturbances in the regulation of ACTH and corticosterone. In addition, beta-endorphin concentrations are higher in the pituitary and hypothalamus in obese than in lean rats. Since ACTH and beta-endorphin are thought to be controlled by corticotropin releasing factor (CRF), these effects may be due to abnormalities in CRF regulation. This possibility was investigated by immunizing rats against CRF. Obese rats immunized against CRF developed higher titer antibodies than lean rats. Hypothalamic CRF concentrations were higher in CRF-immunized obese but not lean rats compared with those of control rats, suggesting that compensation for sequestration of peripheral CRF developed in obese rats. In obese, but not lean rats, immunization against CRF decreased weight gains during weeks 1-4 and increased gains during weeks 9-12 and food intakes were decreased during weeks 5-8 compared with those for obese rats immunized against bovine serum albumin (BSA). Adrenal glands weighed 30% less in both obese and lean rats immunized against CRF compared with those immunized against BSA. These responses to immunization against CRF occurred even though plasma, hypothalamic and pituitary concentrations of ACTH and beta-endorphin were unaffected at the end of the study.
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PMID:Weight gain and food intake in corticotropin releasing factor immunized Zucker rats. 282 27

Metabolic defects in obese (fa/fa) Zucker rats have previously been shown to be reversed by adrenalectomy; however, hypercorticosteronemia has not been demonstrated. We now report that the total daily excretion of corticosterone and urea nitrogen are significantly greater (P less than 0.01) in obese Zucker rats than in age-matched lean Zucker rats. This excessive excretion of corticosterone is not of autonomous adrenal origin, since dexamethasone treatment (20 micrograms/kg X day) for 2 days induced a proportionate reduction in corticosterone excretion (approximately 50%) in both obese and lean Zucker rats. Corticosterone excretion was further suppressed to levels not different from those in lean rats after 2 days of dexamethasone (40 micrograms/kg X day). Both the peak and total pituitary beta-endorphin secretion in response to an iv bolus of corticotropin-releasing factor (CRF) were diminished in obese Zuckers. The response to CRF in obese Zucker rats was dampened and superimposable on that of dexamethasone-treated lean Zucker rats, suggesting the existence of chronic hypercorticosteronemia as a component of this genetic obesity. These observations provide evidence for a compensatory alteration of the pituitary-adrenal axis. We suggest that corticosterone turnover may be increased in obese Zucker rats.
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PMID:Hypercorticosteronuria and diminished pituitary responsiveness to corticotropin-releasing factor in obese Zucker rats. 293 45

Recent research has indicated that visceral obesity is associated with multiple endocrine disturbances. Insulin resistance, as well as visceral fat accumulation, may be consequences of these abnormalities. The complex endocrine aberrations are probably of central origin, and suggest a neuroendocrine background with a "hypothalamic arousal" syndrome. Such a syndrome has been found after excess alcohol intake, tobacco smoking, and certain types of stress reactions. Subjects with visceral obesity might be characterized by a high prevalence of such factors, although only indirect evidence is available for the stress component, maybe caused by a poor socioeconomic and psychosocial situation. In primate experiments, a submissive stress reaction is followed by a syndrome essentially identical to that seen in humans with visceral obesity, including visceral fat accumulation. These observations strongly support a similar chain of events in humans. Recent studies have indicated several abnormalities in cerebrospinal fluid (CSF) concentrations of catecholamines and neuropeptides. In particular, serotonin metabolites and corticotropin-releasing factor (CRF) concentrations are apparently lower than normal. In women with visceral obesity, these low concentrations are associated with food choices that indicate a preference for carbohydrates. This finding emphasizes the importance of serotonin agonists in the treatment of human obesity. It seems possible that such drugs may have effects on metabolic and other symptoms particularly prevalent in abdominal obesity, and that these effects might be independent of the decrease in energy intake. It would seem highly desirable to explore these possibilities further. Such observations may also provide a link between the abnormalities of low serotonin and CRF concentrations in the central nervous system on one hand and peripheral metabolic and other abnormalities on the other.
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PMID:Neuroendocrine abnormalities in human obesity. 753 80

We have determined the effects of bilateral electrolytic lesions of the ventromedial hypothalamus (VMH) on activity in the hypothalamo-pituitary-adrenal (HPA) system. Acutely, during the first 5 days, lesions of the anterior-medial VMH caused loss of the diurnal rhythms in food intake and plasma corticosterone (B) levels. Plasma B concentrations were elevated during the time of the normal trough of the basal diurnal rhythm in HPA axis activity and the diurnal rhythm in food intake was abolished, in agreement with the results of others. Consistent with hyperactivity in the HPA axis, lesioned rats had increased adrenal weight, decreased thymus and body weights and decreased plasma transcortin concentrations. To determine how lesions of the VMH provoke these increases in activity of the HPA system, the sensitivity of ACTH in adrenalectomized, lesioned rats to replacement with exogenous B was determined under basal conditions during the trough (morning-AM) and peak (evening-PM) of the diurnal rhythm in HPA axis activity. ACTH in lesioned rats in the AM was insensitive to feedback over the very low range of plasma B of 1-4 micrograms/dl, whereas sham-lesioned controls exhibited the normal, high sensitivity of ACTH to B at this time of day. There was no difference between the sensitivity of ACTH to this low range of B in the PM in VMH- and sham-lesioned rats. Two to 5 weeks after VMH lesions, as found by others, mean daily plasma B levels did not differ from sham-lesioned controls; however, plasma B during the AM was still mildly elevated in these rats. Inhibition of plasma B in the PM by dexamethasone was less effective in lesioned rats. Although HPA system responses to hypoglycemia, corticotropin-releasing factor and ACTH were normal, the lesioned rats exhibited obesity, hyperinsulinemia, hyperglycemia, hypertension and tachycardia, all signs consistent with mild hyperactivity of the PHA axis. Occupancy of type I, high-affinity corticosteroid receptors is known to control basal activity of the HPA system during the trough of the diurnal rhythm and to interact with glucocorticoid receptors to affect basal activity during the peak of the diurnal rhythm and during AM stress. We conclude that VMH lesions disrupt transmission of inhibitory signals, mediated by occupancy of type I corticosteroid receptors, that are initiated by a B feed-back site.
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PMID:Ventromedial hypothalamic lesions inhibit corticosteroid feedback regulation of basal ACTH during the trough of the circadian rhythm. 778 59

Acute effects of intracerebroventricularly administered corticotropin-releasing hormone (CRH) on deprivation-induced food intake, whole-body oxygen consumption, brown adipose tissue metabolism, and several locomotive behaviors were examined in 6- to 7-wk-old female genetically obese (ob/ob) and lean mice. Corticotropin-releasing hormone depressed food intake in a dose-dependent manner, with a tendency for greater suppression of intake in intact ob/ob mice than in lean mice. Adrenalectomy abolished this tendency for CRH to be more potent in ob/ob mice than in lean mice. Corticotropin-releasing hormone also lowered the oxygen consumption of ob/ob and lean mice, without affecting brown adipose tissue metabolism as assessed by measurement of GDP binding to brown adipose tissue mitochondria. Grooming activity was lowered in CRH-injected mice. The CRH-induced lowering of oxygen consumption and grooming activity in mice contrasts with CRH-induced elevations of oxygen consumption and grooming in rats, suggesting species-specific responses to this peptide. Because effects of CRH were similar in adrenalectomized ob/ob and lean mice, it is unlikely that obesity-producing abnormalities in ob/ob mice are related to abnormal CRH action mechanisms. However, potential abnormalities in CRH synthesis and/or release cannot be excluded.
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PMID:Corticotropin-releasing hormone decreases feeding, oxygen consumption and activity of genetically obese (ob/ob) and lean mice. 814 74

As the hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator is an integrator of hormonal, metabolic, and neural signals, it is not surprising that the function of the hypothalamogonadal axis is subject to the influence of a large array of environmental factors. Before puberty, the central nervous system (CNS) restrains the GnRH pulse generator. Undernutrition, low socioeconomic status, stress, and emotional deprivation, all delay puberty. During reproductive life, among peripheral factors that effect the reproductive system, stress plays an important role. Stress, via the release of corticotropin-releasing factor (CRF), eventually triggered by interleukin 1, inhibits GnRH release, resulting in hypogonadism. Effects of CRF are probably mediated by the opioid system. Food restriction and underweight (anorexia nervosa), obesity, smoking, and alcohol all have negative effects on the GnRH pulse generator and gonadal function. Age and diet are important determinants of fertility in both men and women. The age-associated decrease in fertility in women has as a major determinant chromosomal abnormalities of the oocyte, with uterine factors playing a subsidiary role. Age at menopause, determined by ovarian oocyte depletion, is influenced by occupation, age at menarche, parity, age at last pregnancy, altitude, smoking, and use of oral contraceptives. Smoking, however, appears to be the major determinant. Premature menopause is most frequently attributable to mosaicism for Turner Syndrome, mumps ovaritis, and, above all, total hysterectomy, which has a prevalence of about 12-15% in women 50 years old. Premature ovarian failure with presence of immature follicles is most frequently caused by autoimmune diseases or is the consequence of irradiation or chemotherapy with alkylating cytostatics. Plasma estrogens have a physiological role in the prevention of osteoporosis. Obese women have osteoporosis less frequently than women who are not overweight. Early menopause, suppression of adrenal function (corticoids), and thyroid hormone treatment all increase the frequency of osteoporosis. Aging in men is accompanied by decreased Leydig cell and Sertoli cell function, which has a predominantly primary testicular origin, although changes also occur at the hypothalamopituitary level. Plasma testosterone levels, sperm production, and sperm quality decrease, but fertility, although declining, is preserved until senescence. Stress and disease states accelerate the decline on Leydig cell function. Many occupational noxious agents have a negative effect on fertility.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Environment, human reproduction, menopause, and andropause. 824 11

The presence of three regulatory peptides, corticotropin-releasing hormone, neuropeptide Y and endothelin-1, was studied by radioimmunoassay in the tumor tissue of an ACTH-secreting bronchial carcinoid. A 36-year-old female was admitted to hospital because of moon face, central obesity and hypertension. High levels of plasma ACTH and cortisol and urinary 17-OHCS and 17-KS were found. One mg dexamethasone did not suppress plasma ACTH and cortisol levels, but 8 mg did so slightly. Corticotropin-releasing hormone (100 micrograms, iv) stimulated plasma ACTH levels (0 min; 34.8 pmol/l; 30 min; 41.1 pmol/l). The computerized tomography showed the presence of a tumor in the right lung. This lung tumor was removed surgically and has been shown by microscopical examination to be a bronchial carcinoid with ACTH-positive cells. The tumor tissue concentrations of corticotropin-releasing hormone, neuropeptide Y and endothelin-1 were 3.34 pmol/g wet weight, 8.07 pmol/g wet weight and 0.92 pmol/g wet weight, respectively, although plasma concentrations of these three peptides were not elevated. Reverse phase high performance liquid chromatography showed that immunoreactive peptides in the tumor tissue were mainly eluted in the position of the standard peptides. These findings indicate that this case of ACTH-secreting bronchial carcinoid had high levels of corticotropin-releasing hormone, neuropeptide Y and endothelin-1 in its tumor tissue and suggested that these peptides may act locally, in a paracrine or autocrine manner, in the tumor.
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PMID:An ACTH-secreting bronchial carcinoid: presence of corticotropin-releasing hormone, neuropeptide Y and endothelin-1 in the tumor tissue. 838 6


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