肥胖与甲状腺功能

肥胖与甲状腺功能密切相关.肥胖可引起亚临床甲状腺功能减退,甲状腺激素水平在正常范围内的波动可作为体重变化的一个预测指标.肥胖通过升高循环中瘦素水平参与下丘脑-垂体-甲状腺轴的调控;而甲状腺激素通过促进能量代谢、在围产期抑制瘦素的合成与分泌等机制影响体重.甲状腺激素可用于治疗肥胖,但尚需进一步研究.     

甲状腺功能减退症与高尿酸血症

甲状腺功能减退症与高尿酸血症或痛风伴发比例高,甲状腺激素可直接作用于肾脏导致尿酸排泄减少,也可通过调节瘦素水平影响肾脏对尿酸排泄,同时高尿酸血症或痛风通过作用于下丘脑-垂体-甲状腺轴,影响甲状腺激素的合成及分泌,高尿酸血症也可刺激瘦素基因表达或减少其清除,从而影响甲状腺激素水平.甲状腺激素水平降低和血尿酸水平升高是代谢综合征的危险因素,胰岛素抵抗是代谢综合征的核心,故胰岛素抵抗可能是联系高尿酸血症与甲状腺功能减退症的关键环节.     

甲状腺功能减退症甲状腺素替代剂量与血清瘦素的关系

瘦素(leptin)是肥胖基因编码的蛋白质产物,由脂肪细胞分泌,主要参与机体的能量代谢.甲状腺功能减退症患者由于血清甲状腺激素降低,处于能量低代谢状态.目前关于甲状腺功能减退症患者甲状腺素替代量与瘦素关系的研究资料较少.本研究拟通过测定甲状腺功能减退症患者的血清瘦素质量浓度,探讨甲状腺功能减退症患者血清瘦素与甲状腺素替代量之间的关系.     

Leptin与甲状腺疾病

瘦素（Leptin)是肥胖基因的蛋白产物，除参与热调节及能量平衡外，还与甲状腺激素之间存在相互作用。Leptin可通过影响下丘脑室旁核（PVN）中前促甲状腺释放激素（TRH）基因的表达而发挥对甲状腺激素的调节作用；甲状腺激素则通过影响体脂含量及促甲状腺激素（TSH）等发挥对Leptin的调节作用。当甲状腺疾病（甲状腺功能甲亢或减退）发生时，甲状腺激素过多或不足均可造成血中Leptin水平发生相应改变。     

初诊甲亢患者血清瘦素质量浓度的观察

瘦素(Leptin)是肥胖(ob)基因的产物,它可通过抑制食欲和增加能量消耗以调节脂肪代谢[1,2].甲状腺激素能够增加组织耗氧, 促进物质和能量代谢.二者之间是否有关也是人们所关注的问题.本文旨在研究初诊的弥漫性甲状腺肿伴甲状腺功能亢进 (甲亢) 患者的血清瘦素质量浓度, 并探讨它们二者之间的相关性.     

促甲状腺激素与肥胖

肥胖患者常出现甲状腺功能异常,这种异常在体重减轻后有所恢复,而甲状腺功能的异常又可引起脂肪堆积或体重增加.研究发现,人类脂肪细胞表达功能性的促甲状腺激素受体（TSHR）,促甲状腺激素（TSH）可能作用于表达TSHR的脂肪细胞,调节脂肪细胞的生长、增殖、分化及脂肪因子的分泌.目前,TSH与体重指数、腰臀比、腰围等的关系尚存争议,但较多研究肯定了TSH与大部分肥胖相关参数存在正相关.     

甲状腺与肥胖

研究发现甲状腺激素能影响与肥胖发生及代谢相关基因的表达 ,小剂量甲状腺激素治疗在降低肥胖动物体重的同时能缓解胰岛素抵抗 ,相关研究使人们重新关注甲状腺激素在肥胖治疗中的价值。文中介绍了肥胖患者及治疗中的甲状腺功能变化和甲状腺激素在肥胖治疗中的地位及前景。     

甲状腺与肥胖

研究发现甲状腺激素能影响与肥胖发生及代谢相关基因的表达，小剂量甲状腺激素治疗在降低肥胖动物体重的同时能缓解胰岛素抵抗，相关研究使人们重新关注甲状腺激素在肥胖治疗中的价值。文中介绍了肥胖患者及治疗中的甲状腺功能变化和甲状腺激素在肥胖治疗中的地位及前景。     

Leptin与下丘脑-垂体-甲状腺轴的相互作用

瘦素 (Leptin)主要参与体重调节。研究发现Leptin与下丘脑 垂体 甲状腺轴 (HPTA)之间存在相互作用。Leptin可能通过影响下丘脑室旁核中前促甲状腺激素释放激素 (TRH)基因的表达而发挥对HPTA的调节作用 ,而HPTA则可能通过影响体脂含量及促甲状腺激素 (TSH)等发挥对Leptin的调节作用。甲状腺疾病时血Leptin水平会发生改变 ,可能升高、降低或正常 ,各家报道结果很不一致。Leptin受体突变可伴发下丘脑性甲状腺功能减退 ,但Leptin或其受体的异常是否会引起甲状腺疾病有待进一步研究证实     

肥胖的基因治疗研究进展

瘦素是由肥胖基因 (ob)编码 ,脂肪组织分泌的蛋白质 ,已知其主要功能是调控进食、能量消耗及体重。肥胖基因发生突变时 ,ob基因表达减弱 ,血瘦素水平下降 ,引起肥胖及糖尿病等。应用基因治疗技术将瘦素—cDNA通过特定的载体导入体内 ,可在体内表达瘦素 ,以治疗肥胖及相关代谢紊乱     

Administration of physiologic levels of triiodothyronine increases leptin expression in calorie-restricted obese rats, but does not influence weight loss

Obesity has become a major public health problem, most commonly treated via dietary restriction to promote weight loss. Although leptin and thyroid hormones are involved in the regulation of energy balance, the role of these hormones after the stabilization of weight loss remains unclear. This study was designed to analyze the effect of thyroid hormone on sustained weight loss and leptin gene expression in obese animals after a loss of 5% to 10% of body weight. Thirty-day-old male Wistar rats were separated into 4 groups: control, obese, calorie restriction (CR), and calorie restriction with triiodothyronine administration (CRT). The obese group had increased weight and adiposity, leptin and insulin levels, and leptin gene expression. Dietary restriction in the CR group resulted in decreased body weight and adiposity, diminished leptin, and increased thyroid hormone receptor β expression. The CRT group, submitted to dietary restriction with concomitant administration of a physiologic triiodothyronine dose, had thyroid hormone receptor β expression at levels comparable with those observed in the control group and simultaneously increased leptin expression as compared with that in the CR group, suggesting that thyroid hormone modulates leptin expression under conditions of calorie restriction. Increased leptin expression in the CRT group did not result in increased circulating leptin or a statistically significant reduction in body weight during the treatment period. These data provide impetus for further study, as a longer treatment period may result in increased circulating leptin and, thus, further reduction in body weight during calorie restriction in an obesity model.     

Leptin in the endocrinology of obesity

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.     

Obesity and thyroid function

A moderate elevation of thyrotropin (TSH) concentrations, which is associated with triiodothyronine (T3) values in or slightly above the upper normal range, is frequently found in obese humans. These alterations seem rather a consequence than a cause of obesity since weight loss leads to a normalization of elevated thyroid hormone levels. Elevated thyroid hormone concentrations increase the resting energy expenditure (REE). The underlying pathways are not fully understood. As a consequence of the increased REE, the availability of accumulated energy for conversion into fat is diminished. In conclusion, the alterations of thyroid hormones in obesity suggest an adaptation process. Since rapid weight loss is associated with a decrease of TSH and T3, the resulting decrease in REE may contribute towards the difficulties maintaining weight loss. Leptin seems to be a promising link between obesity and alterations of thyroid hormones since leptin concentrations influence TSH release.     

Dissociation of leptin and body weight in hyperthyroid patients after radioiodine treatment

OBJECTIVE: Leptin regulates energy production rates and body weight, which are frequently altered in hyperthyroidism. Data on a possible interaction between leptin and thyroid hormones are controversial. We assessed leptin serum concentrations, BMI, proportional fat tissue mass and thyroid hormones in hyperthyroid patients in a long-term follow-up after radioiodine therapy. DESIGN: The study included 28 hyperthyroid patients (mean age 66 y) before and up to one y after radioiodine therapy. Leptin and thyroid hormones, general parameters, BMI, proportional fat tissue (PFT) measurements by DEXA and thyroid morphology were recorded. Twenty-four age-matched euthyroid individuals (mean age 63 y) served as controls. RESULTS: At baseline, leptin concentrations were significantly decreased in all hyperthyroid patients as compared to controls. One year after radioiodine therapy, 71% of the patients were euthyroid (group A) and 29% remained hyperthyroid (group B). BMI and PFT increased in both groups. While leptin concentrations remained low in group B, they normalised in group A after 6 to 12 months. Changes in leptin and thyroid hormone concentrations were positively correlated in group A patients (r=0.49, P=0.03) but not in patients remaining hyperthyroid. CONCLUSION: Our data indicate a dissociation in the regulation of plasma leptin and BMI as well as proportional fat tissue in hyperthyroid patients which may be attributable to differences in lean and adipose mass weight gain after radioiodine therapy or direct influences of thyroid hormones on leptin regulation. International Journal of Obesity (2001) 25, 115-120     

A low serum leptin level at baseline and a large early decline in leptin predict a large 1-year weight reduction in energy-restricted obese humans

The difficulty in maintaining weight loss during obesity treatment may be caused by a counteracting neuroendocrine response. It has been proposed that leptin could be a regulator of this response. We examined the relations between leptin levels during an initial very low calorie diet, other simultaneous endocrine changes, and the 1-yr weight reduction. Sixty-nine obese (24 men and 45 women) were treated with very low calorie diet for 16 weeks, followed by a hypocaloric diet for 32 weeks. Serum levels of leptin, insulin, cortisol, and thyroid hormones were measured at weeks 0, 8, and 18. The relative weight reductions after 18 and 48 weeks were 20.1% and 14.4% in men and 15.4% and 11.8% in women. Low initial leptin levels and large declines in serum leptin were associated with a large 1-yr weight loss in both genders. Leptin levels (baseline or changes) were not independently associated with the changes in insulin, cortisol, or thyroid hormones. Our results may indicate that leptin by itself could be of minor importance for the neuroendocrine response to severe caloric restriction in humans.     

Human leptin: from an adipocyte hormone to an endocrine mediator

Leptin is a mainly adipocyte-secreted protein that was discovered 5 years ago. Most of the research following this discovery focused on the role of leptin in body weight regulation, aiming to illuminate the pathophysiology of human obesity. However, more and more data are emerging that leptin is not only important in the regulation of food intake and energy balance, but that it also has a function as a metabolic and neuroendocrine hormone. It is now clear that it is especially involved in glucose metabolism, as well as in normal sexual maturation and reproduction. Besides this, interactions with the hypothalamic-pituitary-adrenal, thyroid and GH axes and even with haematopoiesis and the immune system have also been described. It has been shown that leptin secretion by the adipocyte is partly regulated by other hormones, such as insulin, cortisol, and sex steroids, mainly testosterone. Also, other hormones like thyroid hormone and GH are possibly involved in leptin synthesis. Leptin itself exerts effects on different endocrine axes, mainly on the hypothalamic-pituitary-gonadal axis and on insulin metabolism, but also on the hypothalamic-pituitary-adrenal, thyroid and GH axes. Leptin may thus be considered a new endocrine mediator, besides its obvious role in body weight regulation.     

Thyroid hormones influence serum leptin levels in patients with Graves' disease during suppression of beta-adrenergic receptors.

Leptin is a protein product of the ob gene, mainly produced by adipocytes. Leptin is thought to play an important role in the homeostasis of body weight by suppressing appetite and increasing energy consumption. The aim of this study was to investigate the possible effect of thyroid hormone on the regulation of the leptin system during suppression of beta-adrenergic receptors in Graves' patients. We studied 15 adult female patients with Graves' disease. Thyroid function, serum levels of leptin, and percent body fat (%BF) were examined at four different clinical conditions during therapy (A, untreated; B, beta-adrenergic antagonist only [A, B; hyperthyroid], C, beta-adrenergic antagonist and antithyroid drug; D, antithyroid drug only [C, D; euthyroid]). The use of beta-adrenergic antagonist significantly reduced heart rate in spite of hyperthyroid state, indicating sufficient suppression of beta-adrenergic receptors. During treatment with beta-adrenergic antagonist, leptin percentage of body fat (%BF) ratio significantly decreased in euthyroid state compared to that in hyperthyroid state (from 38.7 +/- 21.3 to 18.1 +/- 19.3, p = 0.003). Moreover, there was a significantly positive correlation between delta leptin/%BF and delta free thyroxine (FT4) (r = 0.51, p = 0.008). Under a euthyroid state induced by antithyroid drug treatment, leptin/%BF did not change in spite of withdrawal of beta-adrenergic antagonist. Our data indicate that thyroid hormones could increase serum leptin level during suppression of beta-adrenergic receptors in Graves' patients. Our data also suggest that the beta-adrenergic action of thyroid hormones might be partly mediated by regulation of leptin.     

Thyroid hormones and treatment of obesity

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.     

Effect of obesity and weight reduction in hypertension

Obesity is known to be associated with diabetes, hypertension and hyperlipidemia in the majority of the patients. There could be inaccuracy in measuring the blood pressure in obesity, therefore a cuff of sufficient size is important in blood pressure measurement. All parameters of obesity have been found to have a correlation with hypertension and it has been suggested that change in weight would cause a change in blood pressure. A weight reduction of 12 kg results in a blood pressure fall of 21/13 mm Hg. Such changes in blood pressures have been noted in untreated hypertensives. A few studies have negated the role of change in weight to have any influence on hypertension. Obesity causes a higher cardiac output and higher blood volume leading to hypertension. There may be increased intracellular sodium and reduced sodium-potassium-ATPase activity in obesity which causes increased sodium loading in hypertension. Abnormalities related to the insulin-carbohydrate metabolism and the renin-angiotensin aldosteron system have also been demonstrated in obese patients. Weight reduction also causes reduced dietary salt intake and diminished sympathetic activity. The benefits of weight reduction appear to be directly related to the amount of weight lost.