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

The Zucker rat is an animal model of autosomal recessive obesity characterized by excessive hypothalamic-pituitary-adrenal (HPA) axis and parasympathetic activities and deficient sympathetic outflow. Alterations in norepinephrine (NE) release, reuptake, and metabolism in the hypothalamic paraventricular nucleus (PVN) could also contribute to dysregulation of the HPA axis in obese Zucker rats via effects on corticotropin-releasing hormone neurons or could be secondary to some other primary defect. The present study assessed whether the obese phenotype defect. The present study assessed whether the obese phenotype (fa/fa) compared to the lean phenotype (Fa/?) of this strain was also associated with alterations in basal and immobilization (IMMO) stress-induced noradrenergic activation in the PVN, using in vivo microdialysis. To evaluate concurrent activity of the peripheral sympathetic nervous system and the HPA axis, we also measured plasma concentrations of catecholamines, ACTH, and corticosterone. IMMO-induced increases in PVN NE levels were significantly lower in obese Zucker rats, as were elevations in plasma concentrations of dihydroxyphenylglycol and epinephrine. Basal and IMMO-stimulated plasma ACTH concentrations were similar in obese and lean rats. Basal plasma corticosterone concentrations were also similar in obese and lean rats; however, IMMO-stimulated corticosterone levels were significantly greater in obese than in lean animals. Basal plasma free corticosterone levels, measured by ultrafiltration, were significantly higher in obese than in lean rats, confirming the state of chronic hypercorticosteronism in these animals. These findings indicate that obese Zucker rats have diminished central noradrenergic and peripheral sympathetic nervous system responses to IMMO stress along with a chronically hyperactive HPA axis. We suggest that defective regulation of PVN NE reflects and contributes to the development and/or maintenance of obesity in Zucker rats via central hypoactivity of the sympathetic system. The hypercorticosteronism of these animals, apparently sustained by some nonadrenergic stimulatory input, might participate in the suppression of the sympathetic system.
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PMID:Decreased central and peripheral catecholaminergic activation in obese Zucker rats. 766 55

Since in patients with Cushing's disease, unlike in normal subjects, tonic inhibitory opioid control of ACTH secretion does not operate, use of the opiate agonist loperamide (LOP) has recently been proposed in the diagnosis of hypercortisolemic states. We compared the sensitivity, specificity and diagnostic accuracy of the LOP test (16 mg orally) with corresponding results of the dexamethasone test (DXM, 1 mg orally overnight) in 23 normal subjects and in a total of 42 patients, affected by Cushing's disease (n = 8), incidentally discovered adrenal masses with impaired function of the hypothalamic-pituitary-adrenal (HPA) axis (n = 6), obesity (n = 21) and depression (n = 7). While in controls both DXM and LOP strongly suppressed plasma cortisol and ACTH, in Cushing's disease and in incidentalomas no patient showed a decrease in cortisol levels below 50 ng/ml or a reduction in plasma cortisol greater than 50% of basal values in response to LOP and DXM. In obese subjects both drugs significantly reduced plasma cortisol and ACTH without giving false positive results. In the depressed group only 3/7 patients showed a decrement in cortisol levels below 50 ng/ml after LOP in contrast to 6/7 after DXM. Thus, in patients with impairment of the HPA-axis, i.e. in Cushing's disease and in patients with adrenal incidentalomas and hormonal abnormalities, LOP and DXM test sensitivity was 100%. In controls and in obese patients specificity was 100% both with LOP and DXM, while in depressed patients it was 43% and 86% with LOP and DXM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison between the suppressive effects of dexamethasone and loperamide on cortisol and ACTH secretion in some pathological conditions. 769 14

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

Nephrotic syndrome in children is a very common disease in Thailand. Most of the patients respond well to oral prednisolone treatment but side effects of the drug especially adrenal insufficiency remains a threat to all. We studied the adrenal function by studying the response to ACTH stimulation test in 14 Thai children, nine girls and five boys, with idiopathic nephrotic syndrome: immediately, 3, 6 and 9 months after discontinuation of oral prednisolone treatment. Average age on entry to the study was 104.4 months (25-183 months). Prednisolone was given every day for 29 days (6-64 days) then every other day for 542 days (178-1,562 days). Side effects of steroid treatment were gross obesity BMI > 30 (one patient), moderate hypertension (one patient), and marked cushingoid features (two patients). ACTH stimulation tests were normal in 64 per cent of patients within 7 days, 64 per cent at 3 months, 73 per cent at 6 months, and 90 per cent at 9 months after discontinuation of oral prednisolone. We suggest that adrenal insufficiency has to be considered in all children on prolonged prednisolone unit at least 9 months of treatment-free period.
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PMID:Adrenal function after prednisolone treatment in childhood nephrotic syndrome. 779 46

The concentrations of beta-endorphin, ACTH, insulin (IRI), glucagon (IRG), cortisol and growth hormone were determined by radioimmunoassay during oral glucose tolerance test (OGTT) performed in 13 obese patients with normal glucose tolerance and without arterial hypertension. The test was performed in random, before and after intravenous administration of 0.8 mg of naloxone. Six persons with normal body weight served as controls. Higher basal concentrations of beta-endorphin and significant increase in beta-endorphin levels during OGTT, without concomitant increase in ACTH concentrations, have been found in obese patients. No effect of naloxone on beta-endorphin liberation during OGTT was observed, though the drug caused lowering in maximal increment of beta-endorphin and paradoxically lowered the concentrations of ACTH and cortisol. The basal concentrations of beta-endorphin did not correlate with the concentrations of insulin, ACTH, cortisol and growth hormone. Elevated concentrations of insulin, lowered concentration of growth hormone and normal levels of glucose and glucagon were observed in basal conditions, and excessive responses of insulin, glucose and glucagon were observed in obese patients during OGTT. Naloxone lowered insulin response and inhibited the fall of growth hormone during OGTT but did not influence the concentrations of glucose and glucagon. No correlation was found during OGTT after naloxone between insulin and beta-endorphin, ACTH or cortisol, whereas negative correlation was observed between insulin and growth hormone. The obtained results suggest that the elevated concentrations of beta-endorphin in simple obesity may be of both hypophyseal and peripheral origin. Hyper-beta-endorphinemia observed in obesity is probably not directly responsible for hyperinsulinemia, it may, however, be responsible for lower sensitivity of tissues to the action of insulin.
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PMID:[Effect of naloxone on beta-endorphin and insulin concentrations during glucose tolerance testing in patients with simple obesity]. 805 20

We examined the effects of an oral glucose load on plasma insulin, androgens, and beta-endorphin (beta EP) concentrations in patients carefully selected as having polycystic ovary syndrome (PCOS) and normal glucose tolerance. Our aim was to verify whether insulin resistance is a common feature of PCOS and to differentiate the metabolic abnormalities related to PCOS from those associated with obesity. Plasma immunoreactive insulin (IRI), C-peptide (C-PR), testosterone, androstenedione, dehydroepiandrosterone sulfate, ACTH, and beta EP responses to a 3-h oral glucose tolerance test (OGTT) were evaluated in 10 obese (OB-PCOS) and 10 nonobese (NO-PCOS) patients with PCOS and in 7 obese and 7 nonobese ovulatory controls. OB-PCOS and NO-PCOS did not differ significantly from weight-matched controls in the IRI response, but had a significantly higher C-PR response in terms of mean postglucose load levels and mean incremental areas. During OGTT, mean plasma levels of testosterone, androstenedione, and dehydroepiandrosterone sulfate declined in both PCOS groups as well as in controls, and no significant correlation between the plasma androgen and IRI or C-PR responses was found. The ACTH response in OB-PCOS and NO-PCOS was similar to that in controls, with a progressive decrease until 180 min. A similar decline in plasma beta EP was found in controls, whereas no change in plasma beta EP was observed in OB-PCOS and NO-PCOS. These findings indicate that independently of the presence of obesity, PCOS patients have enhanced insulin secretion in response to OGTT and show a peculiar pattern of changes in plasma beta EP.
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PMID:Insulin, C-peptide, androgens, and beta-endorphin response to oral glucose in patients with polycystic ovary syndrome. 810 16

Obesity is a product of welfare. About 1/3 of our population has got excessive weight, 6 to 8% is truly obese and in 0.1% we may speak of pathologic obesity. Obesity is not only an esthetic problem, but is goes together with higher morbidity and mortality. In men with a body mass index (BMI = W (kg)/L2 (m)) of more than 35, the glucose metabolism was disturbed in 70%, the lipid spectrum had a clearly atherogenic profile, the average (free) testosterone level was significantly diminished and there was also a certain degree of hypogonadism. A short term treatment (4 to 6 weeks) based on a hypocaloric diet (400) and rich in proteins normalized the glucose metabolism in a very great number of patients, while the insulinemia fell with 40% and the lipidogram always became normal, but for the HDL-C, which showed a slight drop, while the testosterone levels became normal with a strong rise of the sex hormone binding globulin. And yet, at that very moment the patients were still definitely obese: this suggests that the metabolic disturbances are not the consequence of obesity in itself, but may be related to the dietary habits of the patients. Concerning the mechanism of hypogonadism, the cause of its disturbance seems to be situated in the hypothalamo-hypophyseal area and be characterized by a lower amplitude of LH-pulses, which are correlated with the testosterone levels. This hypothalamic disorder is however not limited to the LH-secretion, but the amplitude of growth hormone- and of ACTH-pulses is also reduced. Our study suggests that not obesity itself, but dietary factors might be responsible for the detected abnormalities. This might have important implications. Indeed, it is well known that in population groups, whose diet contains fewer calories and less fat--such as the Chinese and the Japanese--sex hormone binding globulin exists in far higher concentrations whereas free testosterone is found in a lower concentration. In these populations the prevalence of clinically obvious prostate cancer--which is androgen-sensitive--is much lower than in Western countries: it seems obvious to look for a correlation between both observations. Another remarkable phenomenon is the difference in testosterone metabolism between the Eastern and Western people; this leads us to the remarkable findings that in Asian people the same amount of androgens nearly always produces azoospermia and infertility, whereas this appears in only 2/3 of the cases among Western people.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Metabolic effects of obesity in men]. 812 79

The hypothesis proposed in this review is that normal diurnal rhythms in the hypothalamic-pituitary-adrenal (HPA) axis are highly regulated by activity in medial hypothalamic nuclei to effect an interaction between corticosteroids and insulin such that optimal metabolism results in response to changes in the fed or fasted state of the animal. There are marked diurnal rhythms in function of the HPA axis under both basal and stress conditions. The HPA axis controls corticosteroid output from the adrenal and, in turn, forward elements of this axis are inhibited by feedback from circulating plasma corticosteroid levels. Basal activity in the HPA axis of mammals fed ad lib peaks about 2 h before the peak of the diurnal feeding rhythm, and is controlled by input from the suprachiasmatic nuclei. The rhythm in stress responsiveness is lowest at the time of the basal peak and highest at the time of the basal trough in the HPA axis activity. There are also diurnal rhythms in corticosteroid feedback sensitivity of basal and stress-induced ACTH secretion which peak at the time of the basal trough. These rhythms are all overridden when feeding, and thus insulin secretion, is disrupted. Corticosteroids interact with insulin on food intake and body composition, and corticosteroids also increase insulin secretion. Corticosteroids stimulate feeding at low doses but inhibit it at high doses; however, it is the high levels of insulin, induced by high levels of corticosteroids, that may inhibit feeding. The effects of corticosteroids on liver, fat, and muscle cell metabolism, with emphasis on their interactions with insulin, are briefly reviewed. Corticosteroids both synergize with and antagonize the effects of insulin. The effects of stress hormones, and their interactions with insulin on lipid and protein metabolism, followed by some of the metabolic effects of injury stress, with or without nutritional support, are evaluated. In the presence of elevated insulin stimulated by glucocorticoids and nutrition, stress causes less severe catabolic effects. In the central nervous system, regulation of function in the HPA axis is clearly affected by the activity of medial hypothalamic nuclei that also alter feeding, metabolism, and obesity in rats. Lesions of the arcuate (ARC) and ventromedial (VMN) paraventricular (PVN) nuclei result in obesity and hyperactivity in the HPA axis. Moreover, adrenalectomy inhibits or prevents development of the lesion-induced obesity. There are interactions among these nuclei; one mode of communication is via inputs of neuropeptide Y (NPY) cells in the ARC to the VMN, dorsomedial nuclei, and PVN.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Feast and famine: critical role of glucocorticoids with insulin in daily energy flow. 825 78

A 46-year-old man with known arterial hypertension for 10 years had, over the last two years, developed increasing obesity, particularly of the trunk, with other symptoms typical of Cushing's syndrome. Hormone analysis demonstrated hypercortisolism and decreased plasma ACTH concentration. The dexamethasone inhibition test failed to show any significant suppression of serum cortisol. Plasma ACTH was not increased in the corticotrophin-releasing hormone and the metyrapone tests. In the short ACTH test there was an excessive cortisol increase. Abdominal computed tomography revealed both adrenals to be enlarged (6 x 4 cm) and coarsely nodular. Adrenolytic treatment with ketoconazole (400 mg daily) caused symptoms of adrenal insufficiency, but a reduced dosage of 200 mg daily lowered the cortisol level to between 5 and 11 micrograms/dl and normalized the blood pressure and clinical signs of Cushing's syndrome disappeared. Subsequent bilateral adrenalectomy confirmed the diagnosis of massive macronodular adrenal hyperplasia. Substitution treatment with twice daily 25 mg cortisone acetate and 0.05 mg fludrocortisone was started postoperatively.
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PMID:[Bilateral massive macronodular adrenal gland hyperplasia. A rare cause of Cushing's syndrome]. 830 53

Massive obesity is always accompanied by insulin resistance with hyperinsulinaemia in proportion to the amount of visceral fat, which has repercussions on oxidative and non-oxidative glucose metabolism. The increase of free fatty acids in direct relation to the adipocytic mass reduces the hepatic insulin uptake; it increases the suprahepatic glucose flow and the production of very low density lipoproteins. The adipose tissue exerts a feminizing effect in men and a masculinizing effect in women. Women have disorders of ovulation and hirsutism, with increase of free testosterone and elevation of luteotropic hormone levels. Men have hypoandrism due to excessive aromatization of androgens and oestrogens. The adipose tissue accelerates the turnover of cortisol and facilitates cortisone production, which stimulates ACTH secretion and maintains stimulation of the adrenal cortex. Hyperinsulinism and resistance to insulin also intervene in hormonal regulation. They elevate the insulin-like growth factor 1 (IGF-1) which inhibits the production of growth hormone and reduces its plasma half-life; hyperinsulinism and IGF-1 facilitate ovarian androgen production; hypothalamic disturbances occur by diminution of sensitivity to hypoglycaemia, and there are abnormalities in monoaminergic and serotoninergic control. Bone tissue density is preserved for a long time, as it is in proportion to the fatty mass and to the oestrogen and IGF-1 levels, but it may be gradually reduced by secondary hyperparathyroidism. Thyroid function and thyrotropic regulations are unaffected.
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PMID:[Endocrine and metabolic consequences of massive obesity]. 831 Feb 48


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