Agouti expression in human adipose tissue: functional consequences and increased expression in type 2 diabetes.
Agouti expression in human adipose tissue: functional consequences and increased expression in type 2 diabetes.
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DOI：
10.2337/diabetes.52.12.2914
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发表时间：
2003-12
期刊：
影响因子：
7.7
通讯作者：
Steven R Smith;B. Gawrońska-Kozak;L. Janderová;Taylor Nguyen;A. Murrell;J. Stephens;R. Mynatt
中科院分区：
文献类型：
--
作者：
Steven R Smith;B. Gawrońska-Kozak;L. Janderová;Taylor Nguyen;A. Murrell;J. Stephens;R. Mynatt
众所周知，聚集素/黑皮质素系统是体重稳态的重要调节剂。鉴于agglutinin在人脂肪组织中表达，并且agglutinin在脂肪组织中的异位表达导致中度肥胖小鼠，研究了agglutinin在人脂肪组织中的表达与肥胖/2型糖尿病之间的联系。虽然agglutinin mRNA水平和BMI之间没有明显的关系，但在2型糖尿病受试者中agglutinin mRNA水平显著升高。在培养的人脂肪细胞中的agglutinin的调节显示，胰岛素不调节agglutinin mRNA，而地塞米松治疗有效地增加agglutinin mRNA的水平。用培养的人前脂肪细胞和从过表达agglutamine的转基因小鼠获得的细胞进行的实验表明，脂肪组织中的黑皮质素受体（MCR）信号传导可以调节前脂肪细胞的增殖和分化。综上所述，这些结果表明，琼脂糖蛋白可以在几个水平上调节脂肪形成，并表明人体脂肪组织中琼脂糖蛋白水平升高具有功能性后果。MCR信号传导对脂肪形成的影响结合MCR信号传导在下丘脑中的明确作用表明脂肪形成与食物摄入和能量消耗协调调节。
It is well recognized that the agouti/melanocortin system is an important regulator of body weight homeostasis. Given that agouti is expressed in human adipose tissue and that the ectopic expression of agouti in adipose tissue results in moderately obese mice, the link between agouti expression in human adipose tissue and obesity/type 2 diabetes was investigated. Although there was no apparent relationship between agouti mRNA levels and BMI, agouti mRNA levels were significantly elevated in subjects with type 2 diabetes. The regulation of agouti in cultured human adipocytes revealed that insulin did not regulate agouti mRNA, whereas dexamethasone treatment potently increased the levels of agouti mRNA. Experiments with cultured human preadipocytes and with cells obtained from transgenic mice that overexpress agouti demonstrated that melanocortin receptor (MCR) signaling in adipose tissue can regulate both preadipocyte proliferation and differentiation. Taken together, these results reveal that agouti can regulate adipogenesis at several levels and suggest that there are functional consequences of elevated agouti levels in human adipose tissue. The influence of MCR signaling on adipogenesis combined with the well-established role of MCR signaling in the hypothalamus suggest that adipogenesis is coordinately regulated with food intake and energy expenditure.