Towards a novel treatment targeting obesity in women with polycystic ovary syndrome (PCOS)

多囊卵巢综合征（PCOS）是一种常见的疾病，每12名女性中就有1名受到影响。它与荷尔蒙失衡有关，导致月经不规律和怀孕困难以及皮肤问题，包括多余的头发和斑点。然而，特别困扰PCOS女性的一个主要问题是他们难以保持健康的体重和糖尿病的风险增加。患有PCOS的女性更容易肥胖和胰岛素抵抗，并在怀孕期间或以后的生活中患上糖尿病。除了对妇女的健康和福祉产生重大影响外，这也对保健服务资源产生影响。肥胖使PCOS的所有特征变得更糟，减肥可以改善PCOS。然而，患有PCOS的女性发现减肥很困难。欧洲和美国的生殖医学专业协会联合起来呼吁对肥胖和PCOS进行新的研究。利用我们以前的研究，这是在新科学家杂志上的特色，并将其与其他已发表的研究相结合，我们已经开发了一种新的和令人兴奋的想法，用于治疗PCOS中的肥胖症，以改善这些女性的症状和长期健康和福祉。当谈到肥胖时，能量摄入和能量消耗不匹配。饮食旨在降低能量摄入，运动旨在提高能量消耗，目前的减肥策略包括两者的结合。当谈到能量消耗时，60-65%的能量用于维持身体的活力和功能。大约20-25%在运动时消耗，10-15%在进食后消耗，这就是为什么我们在饱餐一顿后会感到热。这个过程被称为餐后产热，它是从大脑到组织（如脂肪）的神经信号的结果，增加了热量的产生以燃烧卡路里。PCOS患者的餐后产热比相同体重的非PCOS患者少25%。这表明患有PCOS的女性能量消耗减少，并解释了为什么他们更容易发胖，减肥更困难。当我们吃东西时，大脑会感知食物的摄入，然后向其他组织发出信号，以打开热量产生并燃烧卡路里。胰岛素是一种能告诉大脑食物摄入量的激素。当我们吃东西时，胰岛素会增加，以便将血糖从血液转移到组织中。患有多囊卵巢综合征的女性往往是胰岛素抵抗，这意味着他们需要更多的胰岛素来将糖从血液中排出。我们认为他们的大脑对胰岛素不太敏感，所以燃烧卡路里的信号减少了。这意味着如果我们能增加大脑中的胰岛素，我们就能改善餐后产热。当胰岛素被喷到鼻子上时，鼻子顶部的神经将其输送到大脑。这在具有PCOS特征的绵羊模型中有效。他们有更少的信号告诉脂肪燃烧卡路里后吃和更少的化合物在脂肪燃烧卡路里。鼻内胰岛素能够改善这一点，并增加产热，而不影响血液中的葡萄糖和胰岛素。这项研究汇集了来自四所不同大学的科学家和临床医生，他们是PCOS和组织分析的专家。它的目的是测试鼻胰岛素喷雾剂与食物是否会打开信号的脂肪和基因和化合物的脂肪燃烧热量的妇女。我们将能够确定鼻内胰岛素是否可以增加患有PCOS的肥胖女性进食后的能量消耗，以及发现它是否对没有PCOS的肥胖女性有任何好处。如果这些实验表明PCOS女性也会发生同样的事情，这将有助于开发新的治疗方法，可以帮助患有PCOS的肥胖女性减轻体重。这将改善与PCOS相关的症状以及他们目前和长期的健康状况。

Polycystic ovary syndrome (PCOS) is a common condition that affects 1 in every 12 women. It is associated with a hormone imbalance that causes irregular periods and difficulty in getting pregnant as well as skin problems, including extra hair and spots. However, a major concern that particularly bothers women with PCOS is their difficulty in maintaining a healthy weight and the increased risk of diabetes. Women with PCOS are more likely to be obese and insulin resistant and develop diabetes during pregnancy or in later life. As well as having a major impact on the health and wellbeing of women this has implications for health service resources. Obesity makes all the features of PCOS much worse and weight loss improves PCOS. However, women with PCOS find losing weight difficult. European and American professional societies of reproductive medicine have come together to call for new research into obesity and PCOS. Using our previous research, which was featured in the New Scientist magazine, and combining it with other published research we have developed a new and exciting idea for a treatment that will specifically target obesity in PCOS to improve the symptoms and long-term health and wellbeing of these women. When it comes to obesity there is a mismatch of energy intake and energy expenditure. Diets are designed to lower energy intake and exercise is designed to raise energy expenditure, and currently weight loss strategies involve a combination of both. When it comes to energy expenditure 60-65% of energy is used just keeping the body alive and functioning. Around 20-25% is used during exercise and 10-15% is burned off after eating, which is why we feel hot after a big meal. This process is called postprandial thermogenesis and it is the result of nerve signals from the brain to tissues, such as fat, that increase heat generation to burn off calories. Women with PCOS have 25% less postprandial thermogenesis than women of the same weight without PCOS. This suggests a reduced energy expenditure in women with PCOS and explains why they are more likely to gain weight and find losing weight more difficult.When we eat the brain senses the intake of food and then signals to the other tissues to switch on heat generation and burn off calories. One hormone that is involved in telling the brain about food intake is insulin. Insulin increases when we eat in order to move the sugar from the blood into the tissues. Women with PCOS tend to be insulin resistant which means they need more insulin to move the sugar out of the blood stream. We think their brain is less sensitive to insulin and so the signals to burn off the calories are reduced. That means if we can increase insulin in the brain we can improve postprandial thermogenesis. When insulin is sprayed up the nose, nerves at the top of the nose transport it into the brain. This works in sheep models, which have the features of PCOS. They have less signals to the fat to tell it to burn calories after eating and less compounds in the fat that burn calories. Intranasal insulin was able to improve this and increase thermogenesis without affecting the glucose and insulin in the blood. This research brings together scientists and clinicians, from four different universities, who are experts in PCOS and tissue analysis. It is designed to test if a nasal insulin spray with food will switch on the signals to the fat and the genes and compounds in the fat that burn off calories in women. We will be able to determine whether intranasal insulin can as well as increase energy expenditure after eating in obese women with PCOS as well as finding out if it has any benefit in obese women who don't have PCOS.If these experiments show the same things happen in women with PCOS this would help develop new treatments that can help facilitate weight loss in obese women with PCOS. This would improve the symptoms associated with PCOS as well their current and long-term health.