Nature:你会不会成为胖子?它可能说了算
2016/05/13
5月11日,发表在Nature上的一项研究发现了肥胖形成一种潜在的新生物标志物——神经降压素(Neurotensin ,NT);研究人员表示,NT有望成为肥胖预防和治疗的可能靶点。


图片来源:academichelp

在全球范围内,有超过17亿人超重(BMI高于25)或者肥胖(BMI高于30),此外,每年有超过250万人死于肥胖。5月11日,发表在Nature上的一项研究发现了肥胖形成一种潜在的新生物标志物——神经降压素(Neurotensin ,NT);研究人员表示,NT有望成为肥胖预防和治疗的可能靶点。

据悉,NT是一种主要存在于胃肠道和中枢神经系统中的肽类,会随着脂肪摄入而释放,从而促进肠道中脂肪酸吸收。在中枢神经系统中,NT的作用是调节压力和痛苦,有证明表明它可能还参与了抑郁症、帕金森病等大脑相关疾病的发展。此外,此前有研究表明,NT还能够刺激多种癌症的生长;同时,pro-NT(NT的一种前体激素)空腹水平增加与心血管疾病及乳腺癌的发展有关。

这项研究中,科学家在小鼠、果蝇和人体中进行了一系列的实验,调查NT如何在肠道中发挥作用。研究调查了28449名男性和女性,随访时间平均为16.5±1.5年。分析结果发现,肥胖和胰岛素抵抗的研究对象空腹pro-NT水平显著提高;同时,与空腹pro-NT浓度最低的非肥胖研究对象相比,空腹pro-NT浓度最高的非肥胖受试者形成肥胖的风险翻了一倍。

动物模型试验表明,NT缺乏的小鼠从食物中吸收脂肪的能力降低,似乎能够预防肥胖、胰岛素抵抗以及脂肪肝。另一方面,经工程改造能够产生NT的果蝇体内积累的脂肪要比正常果蝇多。

这项研究的通讯作者、肯塔基大学Markey癌症中心主任Mark Evers的实验室研究NT已有二十多年,他说:“这项研究让我们重新认识了NT的作用。NT能够增加摄入脂肪的吸收,而典型的西方饮食中含有非常丰富的脂肪,NT可以通过增加肥胖及相关的代谢疾病产生不利的影响。”

此外,由于NT能够有助于某些癌症的生长,加上最新发现的与肥胖的关联,Evers推测,增加的NT可能会导致某些与肥胖相关的癌症更高的发生率。未来,他们将探索这一可能存在的关联性。Evers指出,目前已有像Sphingotec这样的公司正在开发Pro-NT检测,帮助患者预测患乳腺癌的风险,相信很快NT将成为肥胖的生物标志物。

备注:本文根据sciencedailymedicaldaily编译。

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  • An obligatory role for neurotensin in high-fat-diet-induced obesity

    Obesity and its associated comorbidities (for example, diabetes mellitus and hepatic steatosis) contribute to approximately 2.5 million deaths annually1 and are among the most prevalent and challenging conditions confronting the medical profession2, 3. Neurotensin (NT; also known as NTS), a 13-amino-acid peptide predominantly localized in specialized enteroendocrine cells of the small intestine4 and released by fat ingestion5, facilitates fatty acid translocation in rat intestine6, and stimulates the growth of various cancers7. The effects of NT are mediated through three known NT receptors (NTR1, 2 and 3; also known as NTSR1, 2, and NTSR3, respectively)8. Increased fasting plasma levels of pro-NT (a stable NT precursor fragment produced in equimolar amounts relative to NT) are associated with increased risk of diabetes, cardiovascular disease and mortality9; however, a role for NT as a causative factor in these diseases is unknown. Here we show that NT-deficient mice demonstrate significantly reduced intestinal fat absorption and are protected from obesity, hepatic steatosis and insulin resistance associated with high fat consumption. We further demonstrate that NT attenuates the activation of AMP-activated protein kinase (AMPK) and stimulates fatty acid absorption in mice and in cultured intestinal cells, and that this occurs through a mechanism involving NTR1 and NTR3 (also known as sortilin). Consistent with the findings in mice, expression of NT in Drosophila midgut enteroendocrine cells results in increased lipid accumulation in the midgut, fat body, and oenocytes (specialized hepatocyte-like cells) and decreased AMPK activation. Remarkably, in humans, we show that both obese and insulin-resistant subjects have elevated plasma concentrations of pro-NT, and in longitudinal studies among non-obese subjects, high levels of pro-NT denote a doubling of the risk of developing obesity later in life. Our findings directly link NT with increased fat absorption and obesity and suggest that NT may provide a prognostic marker of future obesity and a potential target for prevention and treatment.

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