阻斷Y1受體成為減肥新方向

Researchers in Australia are turning up the heat on obesity, literally. Unlike weight loss drugs which can have adverse side-effects, their study finds gene therapy may hold the key to safer obesity treatments.

澳大利亞的研究人員正在加大對肥胖癥的研究力度。他們的研究發(fā)現(xiàn)，基因療法不像減肥藥那樣會有副作用，這可能是更安全的肥胖治療方法的關(guān)鍵。

A team from the Garvan Institute of Medical Research says blocking a certain genetic receptor in fat cells can raise heat production, thereby increasing fat metabolism. Study authors add that this treatment would avoid targeting a patient’s central nervous system, like other drugs do. Instead, this approach to weight loss focuses on the Y1 receptor in the molecule neuropeptide Y (NPY).

Garvan醫(yī)學(xué)研究所的一個研究小組說，在脂肪細胞中阻斷某種基因受體可以提高熱量的產(chǎn)生，從而增加脂肪代謝。研究作者補充說，這種治療方法可以避免像其他藥物一樣，針對患者的中樞神經(jīng)系統(tǒng)。相反，這種減肥方法的重點是NPY中的Y1受體。

“The Y1 receptor acts as a ‘brake’ for heat generation in the body. In our study, we found that blocking this receptor in fat tissues transformed the ‘energy-storing’ fat into ‘energy-burning’ fat, which switched on heat production and reduced weight gain,” explains co-senior author Dr. Yan-Chuan Shi, leader of the Neuroendocrinology Group at Garvan, in a media release.

“Y1受體在人體內(nèi)產(chǎn)生熱量上有“剎車”的作用。在我們的研究中，我們發(fā)現(xiàn)，在脂肪組織中阻斷這種受體，將“儲能”脂肪轉(zhuǎn)化為“能量燃燒”脂肪，從而開啟熱量生產(chǎn)和減肥的作用。”Garvan神經(jīng)內(nèi)分泌小組組長史延川博士在媒體發(fā)布中解釋說。

“Most of the current medications used to treat obesity target the brain to suppress appetite and can have severe side effects that limit their use. Our study reveals an alternative approach that targets the fat tissues directly, which may potentially be a safer way to prevent and treat obesity.”

“目前用于治療肥胖的藥物大多針對大腦以抑制食欲，但可能產(chǎn)生嚴重的副作用，因此限制其使用。我們的研究揭示了一種直接針對脂肪組織的替代方法，這可能是預(yù)防和治療肥胖更安全的方法。”

Linking the Y1 receptor to obesity

Y1受體與肥胖的關(guān)系

Obesity is a major public health issue around the world. As of 2018, over 40 percent of the adult population in the United States classifies as obese. Nearly one in five children are also obese, according to the same estimates from the CDC. Previous studies have revealed how being overweight or obese can lead to severe health complications, including diabetes, heart disease, and even cancer.

肥胖是世界范圍內(nèi)的一個主要公共健康問題。截止到2018年，美國超過40% 的成年人口被歸類為肥胖。根據(jù)疾病預(yù)防控制中心的同樣估計，近五分之一的兒童也患有肥胖癥。先前的研究已經(jīng)揭示了超重或肥胖會導(dǎo)致嚴重的健康并發(fā)癥，包括糖尿病、心臟病，甚至癌癥。

In the new report, Dr. Shi’s group studied the role Y1 receptors play when it comes to fat storage and metabolic health. NPY molecules typically release these receptors when they think the body is starving. This helps to reduce energy usage and increases fat storage.

在新的報告中，史博士的研究小組研究了Y1受體在脂肪儲存和代謝健康方面的作用。NPY通常在認為身體饑餓時釋放這些受體，以減少熱量使用，增加脂肪儲存。

To their surprise, researchers also discovered Y1 receptors are released in greater numbers in the fat tissue of obese people. After this revelation, the team tried blocking Y1 receptors using the experimental treatment BIBO3304 on obese mice.

令他們驚訝的是，研究人員還發(fā)現(xiàn)，Y1受體在肥胖者的脂肪組織中釋放的數(shù)量更多。在這一發(fā)現(xiàn)之后，研究小組嘗試用實驗性治療BIBO3304來阻斷Y1受體。

“In our study, we found that mice that were administered BIBO3304 and fed a high-fat diet gained about 40% less body weight over seven weeks than mice on a high-fat diet alone. This significant reduction of body weight gain was caused by an increase in body heat generation and reduction in fat mass,” Dr. Shi reports.

“在我們的研究中，我們發(fā)現(xiàn)給予 BIBO3304并喂食高脂肪食物的老鼠，在7周內(nèi)比單獨喂食高脂肪食物的老鼠體重減輕了40% 。體重顯著減少是由于體內(nèi)產(chǎn)熱量增加和脂肪量減少引起的。“

The team adds one of the key takeaways from this study is the discovery that BIBO3304 does not cross the blood-brain barrier. This means the genetic changes to the Y1 receptors don’t reach the brain and focuses specifically on peripheral tissues.

研究小組補充說，這項研究的一個重要結(jié)果是發(fā)現(xiàn) BIBO3304并沒有通過血腦屏障。這意味著Y1受體的基因變化不會到達大腦，而是專門集中在外周組織。

In addition to providing a safer weight loss therapy, researchers say targeting the NPY-Y1 receptor system can also stimulate bone cell growth, strengthen cardiovascular function, and improve insulin resistance.

除了提供更安全的減肥療法外，研究人員說，靶向NPY-Y1受體系統(tǒng)還能刺激骨細胞生長，增強心血管功能，改善胰島素抵抗。

The study appears in the journal Nature Communications.

這項研究發(fā)表在《自然通訊》雜志上。