Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The characteristics of thyroglobulin (Tg) autoantibodies in Obese strain (OS) chickens with thyroiditis have been defined and compared with those of polyclonal antibodies to chicken Tg produced by immunizing normal chickens and a rabbit, and with mouse monoclonal antibodies (MoAb) to chicken Tg. Chicken Tg autoantibodies (aAb), when tested against Tg from 24 species all showed specificity for chicken Tg which ranged from absolute to limited although in most instances cross-reactions with Tgs of other species were either absent or at a low level. Antibodies to chicken Tg produced by immunization showed a similar limited range of cross-reactions. Four of five chTg-MoAbs were specific for chicken Tg and the fifth was almost so. In competitive experiments, the polyclonal rabbit antibody could fully inhibit binding of all chicken Tg-aAb to chicken Tg but not vice versa. It was inferred that polyclonal rabbit Tg antiserum includes antibodies to all the epitopes seen by chicken Tg-aAb and many more besides. In similar experiments with four chicken Tg-MoAbs, the binding of one chicken Tg-aAb was unaffected, and three other patterns of inhibitions were defined. The binding to chicken Tg of a fifth chicken Tg-MoAb was enhanced rather than inhibited by chicken Tg-aAb. Some but not all chicken Tg-aAb preparations could differentiate between Tgs containing different amounts of thyroxine. We conclude that the autoantibodies to Tg in OS chickens are directed in the main against determinants unique to the species. Not all the species-specific determinants are involved in the autoimmune response but the number of epitopes involved is at least four. In these respects the immune response to Tg in OS chickens resembles that in autoimmune thyroid disease in humans. The conformation of chicken Tg may be affected by combination with antibody or by the content of thyroid hormone.
 ...
PMID:Selective autoimmune response to the chicken-specific structures of thyroglobulin in Obese strain chickens. 276 75

Many of the disturbances which characterize adult C57BL/6 ob/ob mice, including obesity, hypometabolism and hypothermia could arise from reduced circulating levels of thyrotropin and thyroid hormones. In the present study, measurement of these hormones in ad libitum-fed obese and lean mice housed at 22 degrees C revealed that mutant mice had levels of TSH equal to those of their ?/+ siblings, while total T4 and T3 concentrations were slightly higher than those of lean controls. The hormonal responses of obese mice to overnight food deprivation or to meal ingestion were also similar to those of lean control mice. Males of both phenotypes typically had higher TSH, T4 and T3 concentrations than did females, and in male mice the circulating levels of each hormone were much more responsive to the feeding condition. The present data are consistent with recent reports of defective target tissue responses and impaired hormone deiodination rather than depressed pituitary-thyroid hormone levels in accounting for the metabolic disturbances which characterize ob/ob mice.
 ...
PMID:Thyroid hormone responses to feeding in ob/ob mice. 280 44

A number of erythrocyte Na-K ATPase units were measured in 22 patients with hyperthyroid Graves' disease, 3 with primary hypothyroidism, 3 with simple obesity, 13 with chronic renal failure on hemodialysis, and 20 normal controls, using ouabain binding assay as described by DeLuise et al. The number of Na-K ATPase units, derived by maximal binding of 3H-ouabain, was decreased in patients with simple obesity (Mean +/- SD, 0.26 +/- 0.07 pmol/10(9) RBC), as compared with that in normal controls (0.39 +/- 0.10), and a significant negative correlation between the number of the binding sites and the ratio of the measured body weight to the optimal body weight calculated by the modified Broca's method was observed in normal controls and patients with obesity (r = -0.51, p less than 0.05). The results agreed closely with that reported by DeLuise et al and provided validation of our estimates of the erythrocyte Na-K pump units. The maximal 3H-ouabain binding was significantly diminished in patients with hyperthyroid Graves' disease (0.28 +/- 0.07) when compared with that in normal controls, while the bindings were significantly elevated in patients with hypothyroidism (0.91 +/- 0.26). These results were in disagreement with those previously reported by animal studies where Na-K ATPase was found to be stimulated by thyroid hormones. It might be possible to partly explain this discrepancy by the degradation of Na-K ATPase in erythrocytes in addition to the apparent differences between erythrocytes and the other tissues and by the length of time that the tissue was exposed to the action of the hormones. Therefore, erythrocyte from normal controls and patients with hyperthyroid Graves' disease were divided into low and high density portions by a discontinuous 'percoll' density gradient centrifugation, and the bindings of the erythrocytes in two portions were separately measured. The bindings of erythrocyte in the higher density portion, representing relatively old-aged erythrocyte, were diminished to 92 +/- 19% of the bindings of the original whole erythrocytes in normal controls. An even more marked reduction of the maximal bindings of 3H-ouabain in old-aged erythrocytes was observed in patients with hyperthyroid Graves' disease (72 +/- 26%). Moreover, this % reduction based on aging related significantly to serum T4 concentrations in those patients (r = 0.85, p less than 0.05). These findings suggest that the number of erythrocyte Na-K ATPase units may reflect the overall peripheral metabolic state, regulated by thyroid hormone-dependent thermogenesis.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:[Clinical studies on assay for Na-K ATPase in human blood cells. I. Erythrocyte Na-K ATPase assay in patients with thyroid dysfunction and in those with chronic renal failure]. 284 3

Destruction of the ventromedial hypothalamus produces hyperphagia, hyperinsulinemia and hypertriglyceridemia. These changes appear to be partly the result of increased firing rate of the vagus nerve and reduced firing rate of the sympathetic nerves. These reciprocal changes in the function of the autonomic nervous system appear to provide an adequate explanation for the hyperinsulinemia in this syndrome, and for the reduced heat expenditure. Destruction of the lateral hypothalamus, has effects opposite to those of the ventromedial hypothalamus with a reduction in food intake, a decrease in body fat, and an increase in the activity of the sympathetic nervous system. These reciprocal functions of the hypothalamus are associated with different adrenergic receptors. A medial hypothalamic alpha-adrenergic system mediates the epinephrine stimulation of feeding, and a beta-adrenergic system mediates the lateral hypothalamic inhibition of eating. Peptides from the endorphin family can stimulate food intake, but most other peptides are inhibitory. Growth hormone and thyroid hormone stimulate food intake under appropriate conditions. Insulin and adrenal steroids appear to play the most important role of all the hormones in regulating food intake. Deficiency of adrenal glucocorticoids is associated with decreased food intake and a wasting of body flesh. Increased levels of glucocorticoids, on the other hand, produce a variety of truncal obesity. In animals with ventromedial hypothalamic lesions and obesity, adrenalectomy will reverse the obesity. In genetically obese rats and mice, adrenalectomy will attenuate the progression of the syndrome. These effects appear to be through a reduction of food intake, and an increase in energy expenditure. Injections of insulin will stimulate food intake and may lead to obesity.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Autonomic and endocrine factors in the regulation of food intake. 286 66

Thyroid deficiency states are now a well recognized cause of the sleep apnea syndrome. The spectrum of disease ranges from mild, asymptomatic hypothyroidism to severe myxedema, and the disorder is associated with both obstructive and central types of sleep apnea. A variety of factors may be involved, including upper airway obstruction with or without obesity, and alterations in ventilatory drive. The definitive therapy is thyroid hormone replacement, which has been shown to diminish or completely eliminate apneic episodes and arterial oxygen desaturation, as well as to effect many improvements in sleep patterns and overall sleep efficiency. The incidence of thyroid deficiency states in patients with sleep apnea syndrome is not known, but it seems reasonable to evaluate thyroid function in all patients. Thyroid replacement therapy seems logical for the treatment of sleep apnea in patients with previously unrecognized subclinical hypothyroidism. Much remains to be learned about the diagnosis and treatment of sleep apnea syndromes associated with thyroid hormone deficiency, and further studies are needed.
 ...
PMID:Sleep apnea and hypothyroidism. 305 27

Mild cold exposure (22 degrees C, with reference to 28 degrees C, thermoneutral) was studied by overnight whole-body indirect calorimetry in euthyroid women. Basal, sleeping, energy expenditure (EE) was significantly increased (+3.8%, P less than 0.05) in six normal weight women but reduced (-3.5%, P less than 0.05) in five obese type II diabetic women. Mixed responses were found in five women with simple obesity. Biochemical measurements were made on fasting blood samples taken at 0900 h after 12 h exposure to the two temperatures. Serum T4, free T3 and TSH were within the normal reference range in all subjects. Serum T4 did not show any differences between the groups, nor any effect from temperature. There was a significant increase in free T3 (P less than 0.05) at 22 degrees C in the control subjects, but no differences in the obese diabetic women. Serum thyroglobulin fell significantly in the diabetic group. Both TSH and free T3 responses to mild cold were significantly different between the groups, but both correlated positively (P less than 0.05) with the changes in sleeping energy expenditure at 22 degrees C with reference to 28 degrees C. Changes in TSH and free T3 were themselves significantly correlated within individuals (P less than 0.01). The normal physiological non-shivering thermogenesis of adult humans on exposure to a cool environment may thus be mediated by a pituitary-thyroid mechanism. The abnormal response of obese diabetic women was associated with impaired TSH and thyroid hormone responses, and may be a factor contributing to weight gain.
 ...
PMID:Metabolic and thyroidal responses to mild cold are abnormal in obese diabetic women. 325 62

Obese (ob/ob) mice exhibit impaired hepatic thyroid hormone action that is mediated, at least in part, by a reduced nuclear 3,5,3'-triiodothyronine (T3) receptor occupancy. The possibility that lowered occupancy in obese mice may be caused by decreased transport of T3 across the hepatic plasma membrane was examined by measuring the unidirectional influx of [125I]T3 into livers of 8- to 10-wk-old obese and lean mice using a tissue-sampling portal vein-injection technique. Influx of [125I]thyroxine (T4), a substrate for T4 5'-deiodinase, was also measured. Unidirectional clearance of T3 and T4 was 64 and 80% lower, respectively, in obese mice than in lean mice. Hepatic T3 and T4 uptake was nonsaturable in both lean and obese mice, suggesting that transport occurs by lipid-mediated free diffusion. Clearance of another lipid-soluble hormone, hydrocortisone, was also lower in obese mice than in lean mice. Decreased membrane permeability to the above hormones in obese mice may result from reported changes in membrane lipid composition. In conclusion, decreased hepatic thyroid hormone uptake may contribute to impaired thyroid hormone action and T3 production in livers of obese mice.
 ...
PMID:Impaired transport of thyroid hormones into livers of obese (ob/ob) mice. 338 5

Altered thyroid hormone metabolism is known to be an important factor contributing to the defective expression of thermogenesis in the obese mouse, and the action of zinc on thyroid hormone conversion may be an important factor in the energy metabolism of obesity. The effects of zinc and thyroxine treatment on dietary-obese mice were examined. The dietary-obese mice were successfully induced by high-fat diet (80% fat), and every mouse was administered daily 1.25 mg zinc sulfate and/or 5 micrograms thyroxine. After 8 weeks of treatment, serum zinc, serum triacylglycerols and body fat composition were determined. On high-fat diets, fat deposition was found in male mice treated with zinc sulfate. However, when mice were treated with zinc and thyroxine at the same time, serum triacylglycerols and body fat composition decreased significantly on both basal and high-fat diets. When mice were treated with thyroxine alone, body fat composition decreased significantly, but there was no significant effect on serum triacylglycerols on either diet. Obesity was significantly correlated with dietary fat, zinc and thyroid hormone. It is suggested that zinc may play an important role, through its action on thyroid hormone conversion and via insulin action, in the energy metabolism of dietary-obese mice.
 ...
PMID:Effects of zinc and thyroxine treatment on dietary-obese mice. 344 18

A boy referred at the age of 4 years because of obesity and under observation for 16 years, was found to be suffering from a hypothalamic syndrome of unknown origin characterized by progressive obesity, polyphagia, deficiency of growth and thyroid hormone, hyperprolactinemia, hypodipsia, hypernatremia and hyperosmolality without diabetes insipidus. At ages 11 and 16 there were 3 day episodes of spontaneous muscular weakness, hypersomnolence and hypothermia associated with central sleep apnea and severe bradycardia. Subsequently, decreased ventilatory responsiveness to carbon dioxide (CO2) was found as a consequence of blunted neural drive. Therapy with clomipramine HCl (Anafranil Ciba-Geigy) for 6 months led to a normalization of serum sodium levels, pulse rate, ventilatory response to dioxide with no recurrence of the central apnea within 4 following years.
 ...
PMID:Recurrent hypothermia, hypersomnolence, central sleep apnea, hypodipsia, hypernatremia, hypothyroidism, hyperprolactinemia and growth hormone deficiency in a boy--treatment with clomipramine. 346 79

A 52-year-old man with myxedema was evaluated for anterior chest pain that was considered to be compatible with myocardial ischemia. The night after admission he developed extreme bradycardia, hypotension, and apneic episodes lasting up to 25 s. Continuous positive airway pressure and administration of medroxyprogesterone acetate prevented further episodes and relieved much of the somnolence and lethargy that had contributed to the evidence for myxedema. Alveolar hypoventilation caused by decreased sensitivity to carbon dioxide, inadequate central neural drive, peripheral muscle force, and obesity all may have contributed to the apnea. Chest pain has not recurred, and results of electrocardiography have remained normal following full thyroid hormone replacement. The early recognition of myxedema causing sleep apnea will allow specific treatment to avoid the cardiovascular risks related to prolonged apnea and will help avoid confusion with other etiologies of cardiovascular abnormalities.
 ...
PMID:Extreme bradycardia during sleep apnea caused by myxedema. 363 55


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>