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名患病。它与荷尔蒙失衡有关，会导致月经不规律、怀孕困难以及皮肤问题，包括多余的毛发和斑点。然而，尤其困扰患有多囊卵巢综合征的女性的一个主要问题是，她们难以保持健康的体重和糖尿病风险的增加。患有多囊卵巢综合征的女性更有可能肥胖和胰岛素抵抗，并在怀孕期间或以后患上糖尿病。这不仅对妇女的健康和福祉有重大影响，而且对卫生服务资源也有影响。肥胖使多囊卵巢综合征的所有特征变得更加糟糕，而减肥则改善了多囊卵巢综合征。然而，患有多囊卵巢综合征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，呼吁对肥胖和多囊卵巢综合征进行新的研究。利用我们之前发表在《新科学家》杂志上的研究，并将其与其他已发表的研究相结合，我们开发了一个新的令人兴奋的想法，即针对多囊卵巢综合征患者的肥胖进行治疗，以改善这些女性的症状和长期健康福祉。在肥胖问题上，能量摄入和能量消耗是不匹配的。节食旨在减少能量摄入，运动旨在增加能量消耗，目前的减肥策略涉及两者的组合。说到能量消耗，60%-65%的能量只是用来维持身体的活力和功能。大约20%-25%是在运动中使用的，10%-15%是在吃完饭后燃烧掉的，这就是为什么我们在大餐后感到热的原因。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，这些信号增加了热量的产生，从而燃烧掉卡路里。患有多囊卵巢综合征的女性餐后产热的几率比同样体重的没有多囊卵巢综合征的女性少25%。这表明患有多囊卵巢综合征的女性的能量消耗减少了，这也解释了为什么她们更有可能增加体重，并发现减肥更困难。当我们吃东西时，大脑感觉到食物的摄取，然后向其他组织发出信号，启动热量产生并燃烧卡路里。有一种荷尔蒙参与告诉大脑食物摄入的情况，那就是胰岛素。当我们进食时，胰岛素会增加，以便将糖从血液中转移到组织中。患有多囊卵巢综合征的女性倾向于胰岛素抵抗，这意味着她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那么敏感，因此燃烧卡路里的信号就会减少。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。当胰岛素喷洒到鼻子上时，鼻顶的神经将其输送到大脑。这适用于绵羊模型，该模型具有多囊卵巢综合征的特征。他们对脂肪发出的信号较少，告诉它在进食后燃烧卡路里的信号较少，脂肪中燃烧卡路里的化合物也较少。鼻腔胰岛素能够改善这种情况，增加产热，而不会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，他们都是多囊卵巢综合征和组织分析方面的专家。它的设计是为了测试在食物中喷洒胰岛素鼻腔是否会打开对脂肪的信号，以及脂肪中燃烧卡路里的基因和化合物。我们将能够确定鼻内胰岛素是否可以增加患有多囊卵巢综合征的肥胖女性进食后的能量消耗，以及它对没有多囊卵巢综合征的肥胖女性是否有任何好处。如果这些实验表明同样的情况发生在患有多囊卵巢综合征的女性身上，这将有助于开发新的治疗方法，帮助患有多囊卵巢综合征的肥胖女性减肥。这将改善与多囊卵巢综合征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.