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。


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。




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。”



  • 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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