Thyroid hormone and the adipocyte.
Thyroid hormone and the adipocyte.
复制标题
甲状腺激素和脂肪细胞。
DOI：
10.1210/jc.2003-031800
复制
发表时间：
2003
期刊：
影响因子：
--
通讯作者：
C. Mariash
中科院分区：
文献类型：
--
作者：
C. Mariash
自从甲状腺状态和体重之间的关系被确定以来，甲状腺激素在调节脂质代谢中的作用一直是人们感兴趣的。1888年发表的粘液水肿报告提出，肥胖是诊断甲状腺功能减退症的标准(1)。几年后，Murray(2)报告说，过度使用甲状腺提取物可以诱发除突眼和甲状腺肿以外的所有甲亢症状和体征。因此，由来已久，甲状腺功能障碍与体重的变化以及由此推断的身体脂肪含量的变化有关。通过基础代谢率的测量，体脂、甲状腺状态和新陈代谢之间的关系得到了牢固的确立。这些研究清楚地表明，甲亢与代谢率(耗氧量)增加有关，而甲减与代谢率下降有关。此外，代谢率的变化与脂肪和碳水化合物代谢的变化有关(4)。然而，导致这些变化的机制是复杂的，因为甲状腺状态的变化影响到多个系统和多个靶组织。动物研究已经对脂肪组织的甲状腺调节有了一些深入的了解。甲状腺激素调节脂肪合成(脂肪生成)和脂肪分解的速度。例如，Diamant等人。(5)在肝脏和脂肪组织中，成脂途径中的酶均受甲状腺激素的调节。富含蔗糖的无脂饮食也会诱导这些酶。此外，我们还发现甲状腺激素和膳食蔗糖协同作用来控制这些酶的含量(7)。因此，甲亢大鼠全身脂肪生成增强也就不足为奇了。然而，早期的研究表明，甲亢可能导致白色脂肪组织中脂肪生成减少(9)。因此，甲状腺状态对白色脂肪组织对脂肪生成的总体贡献的影响尚不清楚，并因动物的饮食状况而进一步复杂化。甲状腺激素在调节脂肪分解中的作用也是复杂和有争议的。Ben Cheikh等人。(10)结果表明，在摄食状态下，甲状腺功能低下大鼠脂肪细胞对儿茶酚胺诱导的脂肪分解反应的敏感性显著降低，而甲亢大鼠脂肪细胞对儿茶酚胺诱导的脂肪分解反应的敏感性无明显变化。他们注意到，无论是进食还是禁食状态下获得的脂肪细胞的基本脂肪分解速度都有类似的发现。在这项研究中，甲状腺功能亢进脂肪细胞的脂肪分解没有增强的比率，这与已知的与甲状腺功能亢进和体脂减少相关的体重减轻形成了鲜明对比。例如，奥本海默等人。(11)表明体内脂肪的丢失发生在给予甲状腺激素后的早期，并与全身耗氧量的增加相一致。因此，甲状腺功能亢进症必须与脂肪分解增强有关，同时刺激其他代谢途径。也有一些人类研究关注甲状腺激素对脂肪细胞脂肪分解的影响。这些体外研究表明，甲亢患者的基础脂解反应没有变化，但甲亢受试者脂肪细胞中肾上腺素刺激的脂解反应显著增强。在某种程度上，这种增强的反应与脂肪细胞上增强的2-肾上腺素受体数量有关(13)。然而，几乎所有的人体研究都依赖于体外技术来检测脂肪细胞的反应。随着新技术的出现，上面讨论的一些有争议的问题将得到解答。在本期《JCEM》中，Haluzik等人。(14)利用一种新的微透析技术，在体内研究甲状腺状态对脂肪分解的影响。他们测量了去甲肾上腺素(NE)的局部释放，结果显示，与正常甲状腺对照组相比，甲亢患者脂肪细胞中去甲肾上腺素的浓度更高，而甲减患者的去甲肾上腺素浓度显著降低。此外，他们还表明，在甲亢患者中，异丙肾上腺素灌流会导致NE释放更多，并伴随着更高的脂解率。他们的研究很清楚
The role of thyroid hormone in the regulation of lipid metabolism has been of interest ever since a relationship between thyroidal state and body weight was identified. The myxedema report published in 1888 proposed that obesity is a criterion for the diagnosis of hypothyroidism (1). Several years later, Murray (2) reported that overtreatment with thyroid extract could induce all the signs and symptoms of hyperthyroidism except exophthalmos and goiter. Thus, there is a long-standing history associating thyroid dysfunction with alterations in body weight and, by inference, with changes in body fat content. The relationship between body fat, thyroidal state, and metabolism became firmly established with the measurement of basal metabolic rates (3). These studies clearly showed that hyperthyroidism was associated with an increase in metabolic rate (oxygen consumption) and that hypothyroidism was associated with a decrease in metabolic rate. Moreover, the changes in metabolic rate were associated with alterations in lipid and carbohydrate metabolism (4). However, the mechanisms leading to these changes are complex because alterations in thyroidal state affect multiple systems and multiple target tissues. Some insight into the thyroidal regulation of fat tissue has been obtained from animal studies. Thyroid hormone regulates the rate of both fat synthesis (lipogenesis) and lipolysis. For example, Diamant et al. (5) demonstrated that the enzymes in the lipogenic pathway are regulated by thyroid hormone in both the liver and adipose tissue. A fat-free diet rich in sucrose also induces these enzymes (6). Moreover, we showed that thyroid hormone and dietary sucrose act synergistically to control the content of these enzymes (7). Therefore, it is not surprising that total body lipogenesis is enhanced in hyperthyroid rats (8). However, earlier studies have suggested that hyperthyroidism may lead to decreased lipogenesis in white adipose tissue (9). Thus, the effect of thyroidal state on the overall contribution of white adipose tissue to lipogenesis is not clear and is complicated further by the dietary status of the animal. The role of thyroid hormone in regulating lipolysis is also complex and controversial. Ben Cheikh et al. (10) showed that in the fed state adipocytes from hypothyroid rats had markedly reduced sensitivity to catecholamine-induced lipolysis, whereas there was no change in catecholamine-induced lipolysis in adipocytes from hyperthyroid rats. They noted similar findings in the basal rates of lipolysis from adipocytes obtained in either the fed or fasting state. The lack of enhanced rates of lipolysis from hyperthyroid adipocytes in that study stands in contrast to the known weight loss associated with hyperthyroidism and the loss of body fat. For example, Oppenheimer et al. (11) showed that the loss of body fat occurred early after administration of thyroid hormone and coincided with increased total body oxygen consumption. Thus, hyperthyroidism must be associated with enhanced lipolysis while at the same time stimulating other metabolic pathways. There are also a few human studies that have looked at the effect of thyroid hormone on adipocyte lipolysis. These in vitro studies showed that basal lipolysis is unchanged in hyperthyroid patients, but -adrenergic-stimulated lipolysis was markedly enhanced in adipocytes from hyperthyroid subjects (12). In part, this enhanced response is related to enhanced2-adrenoceptor number on adipocytes (13). However, almost all of the human studies rely on in vitro techniques to examine the adipocyte responses. With the advent of newer technology, some of the controversial issues discussed above will be answered. In this issue of JCEM, Haluzik et al. (14) make use of a new microdialysis technique to study the effect of thyroidal state on lipolysis in vivo. They measured local release of norepinephrine (NE) and showed that NE concentrations at the adipocyte are greater in hyperthyroid patients and significantly less in hypothyroid patients compared with euthyroid controls. Moreover, they show that perfusion with isoprenaline leads to greater NE release in hyperthyroid patients with a concomitant greater rate of lipolysis. Their study clearly
影响因子：
4.8
作者：
B. Blennemann;Y K Moon;H. Freake
通讯作者：
B. Blennemann;Y K Moon;H. Freake