Nat Medicine：开发出治疗肥胖的安全有效的激素结合疗法

2012年11月20日--近日，来自印第安纳大学的科学家发现了将两种激素分子结合起来治疗疾病的新方法，这将为治疗肥胖及相关疾病的疗法的开发提供帮助。相关研究成果刊登于国际著名杂志Nature Medicine上。

研究者将消化系统的肽类激素GLP-1与雌激素进行结合，用于对小鼠进行实验研究。肽类激素GLP-1和雌激素都可以进行治疗肥胖以及成年型的糖尿病，将两者结合起来治疗减肥及其它疾病表现出更为有效的结果，而且副作用较小，比如不会引发肿瘤形成相关的组织过度生长。

研究者DiMarchi说，我们发现将两者激素结合起来可以明显增强其单一作用所叠加的作用。这种激素的结合可以改善减肥效果，而且副作用较小。研究者认为GLP-1扮演着伴侣的作用，其可以靶位下丘脑和胰腺部位的雌激素，然后进行作用，下丘脑和胰腺都参与了代谢的过程。

这种定向的靶位雌激素可以有效逆转代谢综合征，代谢综合征包括和血压、高甘油三酯、多糖症及低密度性胆固醇相关的肥胖病症，大约20%的人群都患有各种形式的代谢综合征，其患中风、心脏病发作的风险是无代谢综合征人群的3倍，而其患成年型糖尿病的风险是无代谢综合征人群的5倍。

研究这最后表示，这种激素结合的疗法对于未来研究开发新型的治疗疾病的疗法有很大帮助，相关研究由Marcadia Biotech等提供资助。

与肥胖相关的拓展阅读：

• Diabetes Care：不符合手术标准的肥胖患者也能从减肥手术中获益
• Ann Surg：肥胖乳腺癌患者术前抗生素预防可降低手术部位感染发生率
• Lancet：利尿剂并不是对肥胖高血压患者合理的治疗方案
• Cell Metab：操纵Tyk2成功逆转小鼠肥胖
• Cell Metab：挑战常规，小鼠研究证实胰岛素导致肥胖 更多信息请点击：有关肥胖更多资讯

Targeted estrogen delivery reverses the metabolic syndrome

We report the development of a new combinatorial approach that allows for peptide-mediated selective tissue targeting of nuclear hormone pharmacology while eliminating adverse effects in other tissues. Specifically, we report the development of a glucagon-like peptide-1 (GLP-1)-estrogen conjugate that has superior sex-independent efficacy over either of the individual hormones alone to correct obesity, hyperglycemia and dyslipidemia in mice. The therapeutic benefits are driven by pleiotropic dual hormone action to improve energy, glucose and lipid metabolism, as shown by loss-of-function models and genetic action profiling. Notably, the peptide-based targeting strategy also prevents hallmark side effects of estrogen in male and female mice, such as reproductive endocrine toxicity and oncogenicity. Collectively, selective activation of estrogen receptors in GLP-1–targeted tissues produces unprecedented efficacy to enhance the metabolic benefits of GLP-1 agonism. This example of targeting the metabolic syndrome represents the discovery of a new class of therapeutics that enables synergistic co-agonism through peptide-based selective delivery of small molecules. Although our observations with the GLP-1–estrogen conjugate justify translational studies for diabetes and obesity, the multitude of other possible combinations of peptides and small molecules may offer equal promise for other diseases.

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