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

The present study examines the role of thyroid cell injury in the initiation of autoimmune thyroiditis by iodine in Obese strain (OS) chickens, a strain genetically susceptible to spontaneous autoimmune thyroiditis. OS and normal strain chickens were placed on an iodine depletion regimen started in ovo. This regimen is known to prevent thyroiditis in OS chickens. The chickens were injected with NaI every 24 h for up to 7 days starting at 3 weeks of age. Both strains showed evidence of mild thyrocyte injury 12 h after NaI. However, significant and sustained infiltration, beginning 24 h after NaI, was seen only in the OS. The infiltrating cells were primarily mononuclear. Polymorphonuclear cells were not observed. Immunohistological analysis showed the infiltrate to be composed of CD8 T cells, CD4 T cells, B cells, and macrophages in the ratio 40:20:22:17. The infiltration was sustained and progressive for at least 7 days. Thyroid infiltration after NaI repletion was significantly reduced in OS chickens tolerized to thyroglobulin at hatching. Prior treatment with the antioxidant drug ethoxyquin completely prevented both the thyrocyte injury and the infiltration induced by iodine. Treatment with antioxidant drugs had no effect on the uptake and incorporation of iodine by the thyroid. In summary, 1) iodine caused thyrocyte injury in both OS and normal chickens. 2) The injury was followed by cellular infiltration in the OS but not in normal chickens. 3) The infiltration appeared to be immune mediated in being primarily lymphocytic and at least partially thyroglobulin sensitive. 4) Prevention of thyroid injury by antioxidant drug treatment also prevented infiltration. We conclude that thyroid cell injury may be an initial event in the induction of autoimmune thyroiditis by iodine.
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PMID:Thyroid cell injury is an initial event in the induction of autoimmune thyroiditis by iodine in obese strain chickens. 758 41

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

Hypothyroidism is the condition most commonly treated with exogenous thyroid hormone. The goal of therapy is to normalize levels of serum thyrotropin (thyroid-stimulating hormone), which should be monitored by a high-sensitivity test. Adjustments in optimal dose may be necessary for a number of physiologic reasons (eg, decreased gastrointestinal absorption, pregnancy). Thyroid hormone therapy is also appropriate after surgery for thyroid cancer and for patients with goiter or benign thyroid nodules. In the absence of hypothyroidism, such treatment should not be used for obesity, fatigue, irregular menses, or infertility.
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PMID:Thyroid hormone therapy. What, when, and how much. 841 59

In rat hepatocyte culture, the S14 gene is necessary for induction of lipogenesis by carbohydrate metabolism and thyroid hormone. To determine if this gene plays a role in regulation of lipid storage in humans we compared the response to fasting of the human S14 gene between obese and nonobese subjects. We measured the relative content of human S14 mRNA in abdominal subcutaneous fat before and after a 48-hour fast. We found that mRNA-S14 is strongly downregulated in nonobese subjects in response to the fast, but only minimally down-regulated in obese subjects. There is an excellent correlation between the body mass index, and the fasting induced fall in S14 mRNA. There was no difference in the postfasting glucose, insulin, and ketone levels between the 2 groups of subjects. Therefore, the S14 gene is abnormally downregulated during fasting in adipose tissue of obese individuals. Further study of this gene could provide important information on the mechanism of the acquisition or maintenance of obesity in humans.
Thyroid 1999 Feb
PMID:Adipose S14 mRNA is abnormally regulated in obese subjects. 1009 Mar 13

The article summarizes the endocrinology axis in relation to leptin in the obesity. There is a glucocorticoid hypothesis in the obesity origin. Human plasma leptin levels are elevated in Cushing's syndrome and there is a robust leptin secretory responses to dexamethasone. Obesity impacts on reproductive function in man and women. Leptin levels are higher in women than in men and a critical blood leptin level is necessary to trigger reproductive ability in women. The relationship between body mass index and circulating leptin varies during the course of spontaneous cycles in women, the best correlation occurring during the luteal phase when progesterone and leptin concentrations are highest. Obesity is associated with a decrease in growth hormone (GH) and reversible with weight loss. The influence of body composition on GH secretion in the obesity may be mediated through leptin, acting as a peripheral signal from adipose tissue. Thyroid dysfunction appear not associated with alterations in serum leptin levels. There is a significant relationship between insulin and leptin, but it is not immediate, since type 2 diabetics show similar leptin levels to those of nondiabetic humans of the same body mass index.
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PMID:[Leptin in the endocrinology of obesity]. 1060 74

Thyroid hormones influence the function of many organs and mediate their diverse actions through two types of thyroid hormone receptors, TRalpha and TRbeta. Little is known about effects of ligands that preferentially interact with the two different TR subtypes. In the current study the comparison of the effects of the novel synthetic TRbeta-selective compound GC-1 with T3 at equimolar doses in hypothyroid mice revealed that GC-1 had better triglyceride-lowering and similar cholesterol-lowering effects than T3. T3, but not GC-1, increased heart rate and elevated messenger RNA levels coding for the I(f) channel (HCN2), a cardiac pacemaker that was decreased in hypothyroid mice. T3 had a larger positive inotropic effect than GC-1. T3, but not GC-1, normalized heart and body weights and messenger RNAs of myosin heavy chain alpha and beta and the sarcoplasmic reticulum adenosine triphosphatase (Serca2). Additional dose-response studies in hypercholesteremic rats confirmed the preferential effect of GC-1 on TRbeta-mediated parameters by showing a much higher potency to influence cholesterol and TSH than heart rate. The preferred accumulation of GC-1 in the liver vs. the heart probably also contributes to its marked lipid-lowering effect vs. the absent effect on heart rate. These data indicate that GC-1 could represent a prototype for new drugs for the treatment of high lipid levels or obesity.
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PMID:The thyroid hormone receptor-beta-selective agonist GC-1 differentially affects plasma lipids and cardiac activity. 1096 73

Thyroid hormones have important thermogenic function. Nevertheless, thyroid dysfunctions are often associated with minor changes in body weight and fat mass. On the other hand, both overfeeding and fasting have important effects on iodothyronine metabolism and regulation of deiodinase activity. Although under debate, there are clinical and theoretical reasons to administer low-dose thyroid hormones (T3) in selected obese patients. This short review deals with both pathophysiological and clinical aspects of thyroid hormone used in the therapy of obesity.
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PMID:Thyroid hormones and treatment of obesity. 1099 25

Whilst a number of neuroendocrine afferent signals are implicated in body-weight homeostasis, the major efferent pathway is the sympathetic nervous system (SNS), which affects both energy expenditure and substrate utilization. Thyroid hormones and their interactions with the SNS may also have a role to play. Some of the variability in resting energy expenditure can be explained by differences in SNS activity, and beta-blockade can reduce energy expenditure and diet-induced thermogenesis in Caucasians. Excess energy intake leads to SNS activation and increased diet-induced thermogenesis. A relationship has also been demonstrated between spontaneous physical activity and SNS activity. In many animal models the SNS activates brown adipose tissue thermogenesis, hence increasing diet-induced thermogenesis and dissipating excess energy as heat. This effect is mediated via beta3-adrenoceptors and activation of an uncoupling protein unique to brown adipose tissue. Homologous proteins have been identified in human tissues and may play a role in human energy expenditure. How the SNS is implicated in this process is unclear at present. beta3-Adrenoceptor polymorphism has been associated both with lower resting energy expenditure in some populations and with reduced autonomic nervous system activity. SNS effects on substrate cycling may also play a role. In the development of obesity the effects of the SNS in promoting lipolysis and fat oxidation are likely to be at least as important as its effects on thermogenesis. beta-Blockade has relatively small effects on energy expenditure, but more pronounced effects on reducing lipid oxidation, so tending to favour fat storage and weight gain. Low lipid oxidation is a risk factor for weight gain, and there is some evidence that low basal sympathetic nerve activity in muscle is associated with this process. Overall, the relationship between SNS activity and obesity is complex, with evidence of low SNS activity occurring in some, but not all, studies.
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PMID:Signalling in body-weight homeostasis: neuroendocrine efferent signals. 1099 55

In mitochondria ATP synthesis is not perfectly coupled to oxygen consumption due to proton leak across the mitochondrial inner membrane. Quantitative studies have shown that proton leak contributes to approximately 25% of the resting oxygen consumption of mammals. Proton leak plays a role in accounting for differences in basal metabolic rate. Thyroid studies, body mass studies, phylogenic studies and obesity studies have all shown that increased mass-specific metabolic rate is linked to increased mitochondrial proton leak. The mechanism of the proton leak is unclear. Evidence suggests that proton leak occurs by a non-specific diffusion process across the mitochondrial inner membrane. However, the high degree of sequence homology of the recently cloned uncoupling proteins UCP 2 and UCP 3 to brown adipose tissue UCP 1, and their extensive tissue distribution, suggest that these novel uncoupling proteins play a role in proton leak. Early indications from reconstitution experiments and several in vitro expression studies suggest that the novel uncoupling proteins uncouple mitochondria. Furthermore, mice overexpressing UCP 3 certainly show a phenotype consistent with increased metabolism. The evidence for a role for these novel UCPs in mitochondrial proton leak is reviewed.
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PMID:Mitochondrial proton leak: a role for uncoupling proteins 2 and 3? 1123 89

Thyroid function tests might be affected by diabetes and obesity. To evaluate the influence of these parameters in routine conditions, 72 diabetic and 53 non-diabetic outpatients without known thyroid diseases or severe chronic illness were recruited over a 7-month period. For each patient, dosages of thyrotropin (TSH), total and free thyroxine (TT4 and FT4, respectively), total and free triiodothyronine (TT3 and FT3) and T3 resin uptake (T3RU) were performed by radioimmunoassays. The simultaneous influence of various parameters known to affect thyroid-function tests was evaluated by multivariate linear regression. The studied variables included gender, age, glucosteroids, estrogens, tobacco habits, iodine contacts, body mass index (BMI) and diabetes mellitus. Tobacco habits and iodine contacts did not influence any tests. As expected, estrogens induced an increase in TT4 and TT3 values (p < 0.001 and 0.020, respectively) associated with a decrease in T3RU (p < 0.001). Consequently, females had lower T3RU than males (p < 0.0001). Corticotherapy was associated with decreased TSH values (p = 0.022). TT3 and FT3 decreased with age (p < 0.001), whereas T3RU and FT4 increased (p = 0.020 and 0.004, respectively). In contrast to an increase in TSH (p = 0.006), TT4 and FT4 decreased at higher BMI levels (p = 0.018 and 0.004, respectively), which is consistent with subclinical hypothyroidism. In diabetic patients, TSH was lower than in nondiabetic subjects (p = 0.039). Thus, the present study indicates that besides known parameters such as age and drugs, thyroid-function tests can also be altered by diabetes mellitus and obesity.
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PMID:Minor alterations in thyroid-function tests associated with diabetes mellitus and obesity in outpatients without known thyroid illness. 1138 17


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