Role of extrathyroidal TSHR expression in adipocyte differentiation and its association with obesity.
Role of extrathyroidal TSHR expression in adipocyte differentiation and its association with obesity.
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甲状腺外 TSHR 表达在脂肪细胞分化中的作用及其与肥胖的关系
DOI：
10.1186/1476-511x-11-17
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发表时间：
2012-01-30
影响因子：
4.5
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Lu S;Guan Q;Liu Y;Wang H;Xu W;Li X;Fu Y;Gao L;Zhao J;Wang X
背景肥胖被认为与心血管疾病、代谢综合征和糖尿病的高风险相关。促甲状腺激素(TSHR)是促甲状腺激素(TSH，或促甲状腺激素)的受体，促甲状腺激素是甲状腺功能的关键调节因素。TSHR曾被认为仅限于甲状腺细胞表达，目前已在包括肝脏和脂肪在内的许多甲状腺外组织中检测到。先前的研究表明，当前脂肪细胞分化为成熟脂肪细胞时，TSHR的表达上调，提示TSHR在脂肪形成中可能发挥作用。方法本研究分析了TSHR在小鼠和人脂肪组织中的表达，并探讨其与肥胖的关系。结果在3T3-L1前脂肪细胞诱导分化过程中，TSHR在mRNA和蛋白水平的表达均增加。通过油红O染色和PPAR-γ和ALBP mRNA表达的RT-PCR分析，发现TSHR基因敲除抑制了3T3-L1前脂肪细胞的脂肪细胞分化。我们通过高脂饮食建立了肥胖小鼠(C57/BL6)，发现肥胖小鼠内脏脂肪组织中TSHR蛋白的表达明显高于非肥胖对照组小鼠(P<；0.05)。最后，检测120例患者脂肪组织中TSHR的表达。结果表明，TSHR在皮下脂肪组织中的表达与BMI呈正相关。结论TSHR是脂肪细胞分化的重要调节因子。TSHR在脂肪组织中的表达异常与肥胖有关，这可能涉及过度脂肪生成的机制。
BackgroundObesity is known to be associated with higher risks of cardiovascular disease, metabolic syndrome, and diabetes mellitus. Thyroid-stimulating hormone (TSHR) is the receptor for thyroid-stimulating hormone (TSH, or thyrotropin), the key regulator of thyroid functions. The expression of TSHR, once considered to be limited to thyrocytes, has been so far detected in many extrathyroidal tissues including liver and fat. Previous studies have shown that TSHR expression is upregulated when preadipocytes differentiate into mature adipocytes, suggestive of a possible role of TSHR in adipogenesis. However, it remains unclear whether TSHR expression in adipocytes is implicated in the pathogenesis of obesity.MethodsIn the present study, TSHR expression in adipose tissues from both mice and human was analyzed, and its association with obesity was evaluated.ResultsWe here showed that TSHR expression was increased at both mRNA and protein levels when 3T3-L1 preadipocytes were induced to differentiate. Knockdown of TSHR blocked the adipocyte differentiation of 3T3-L1 preadipocytes as evaluated by Oil-red-O staining for lipid accumulation and by RT-PCR analyses of PPAR-γ and ALBP mRNA expression. We generated obesity mice (C57/BL6) by high-fat diet feeding and found that the TSHR protein expression in visceral adipose tissues from obesity mice was significantly higher in comparison with the non-obesity control mice (P< 0.05). Finally, the TSHR expression in adipose tissues was determined in 120 patients. The results showed that TSHR expression in subcutaneous adipose tissue is correlated with BMI (body mass index).ConclusionTaken together, these results suggested that TSHR is an important regulator of adipocyte differentiation. Dysregulated expression of TSHR in adipose tissues is associated with obesity, which may involve a mechanism of excess adipogenesis.