Obesogens in a naturally obese animal: An experimental approach to assess the impact of marine pollutants on fat tissue function in seals

生物体在不断变化和日益开发和污染的环境中生存和繁荣的能力取决于对能量平衡的适当调节。越来越多的证据表明，暴露在污染物中会改变人类和其他动物的脂肪储存和使用方式。最近对人类的研究表明，许多海洋污染物会干扰脂肪组织对激素信号的反应。特别是，污染物通过打开增加脂肪储存的途径使减肥变得困难，这可能导致糖尿病和肥胖等问题。世纪早期制造了大量的持久性有机污染物（POP），用于高容量电导体和油墨、绝缘体和塑料。虽然许多持久性有机污染物因为毒性很大而不再生产，但它们非常稳定，可以在环境中保留很长时间，最终通过空气和水进入海洋。其他污染物，如邻苯二甲酸盐，这是一种重要的增塑剂，很容易从城市地区和海洋垃圾中流入大海。特别是，持久性有机污染物不容易分解，在脂肪中积累，并在食物链中变得更加集中，最终进入肝脏和脂肪。海豹是重要的顶级海洋掠食者，在海上觅食时必须建立一层厚厚的鲸脂层，然后在上岸繁殖、换羽和休息时将脂肪作为代谢燃料来维持生命。他们的代谢与肥胖和糖尿病患者相似。它们需要依靠脂肪作为燃料和绝缘体，这使得它们容易受到海洋污染物对脂肪组织工作方式的影响。小海豹脂肪中的持久性有机污染物含量越高，它们的生存机会就越低。像鲸脂这样的脂肪组织对储存脂肪很重要，它将脂肪释放到血液中供身体其他部位使用，并产生控制储存或使用多少脂肪的脂肪调节激素。最近，一些脂肪调节激素的基因被证明在波罗的海污染地区的海豹的鲸脂中比在北极清洁地区的海豹的鲸脂中更多地被打开，这表明海洋污染物改变了海豹的能量平衡。然而，控制海豹脂肪组织如何工作的机制，以及海洋污染物干扰这种控制的方式，还没有得到很好的理解。如果污染物可以阻止海豹在陆地上禁食时从鲸脂中释放脂肪为它们提供燃料，那么它们可能不得不使用更多来自肌肉组织的蛋白质。这可能会使它们在换羽、繁殖和发育过程中面临饥饿的风险，即使它们很胖。我们将调查污染物是否会改变风险最大的年轻灰海豹的脂肪储存和动员。我们将在不伤害它们的情况下从活体进食和禁食的海豹身上采集少量鲸脂样本，并用污染物和脂肪调节激素处理鲸脂。我们将测量与能量平衡有关的基因和激素水平，鲸脂释放脂肪的能力及其代谢率。通过比较这些措施之间的治疗，我们将开始找出能量平衡是如何正常调节海豹，它是如何被海洋污染物改变，以及海豹是否更容易在喂养或禁食。这将有助于预测污染物对海豹种群规模的影响，有助于更好地了解污染物如何影响年轻海豹的生存和改变他们的能量需求。由于海豹自然会经历脂肪量的极端变化，与糖尿病和肥胖症有代谢相似性，并且像人类一样吃鱼，这项工作还将告知持久性有机污染物和邻苯二甲酸酯对人类脂肪调节的可能影响。这项工作对海豹和其他动物的健康和生存具有深远的影响，也对人类肥胖、糖尿病和相关代谢异常的管理具有深远的影响。

The ability of organisms to survive and thrive in a changing and increasingly exploited and polluted environment depends on appropriate regulation of energy balance. Growing evidence suggests that exposure to pollutants can alter how fat is stored and used in humans and in other animals. Recent research in humans suggests that many marine pollutants can interfere with the way fat tissue responds to hormonal signals. In particular, pollutants make it difficult to lose weight by switching on pathways that increase fat storage, and this could contribute to problems like diabetes and obesity. Large amounts of persistent organic pollutants (POPs) were made in the early part of the 20th century for use in high capacity electrical conductors and inks, insulators and plastics. Although many POPs are not made anymore because they are very toxic, they are extremely stable and remain in the environment for a long time, ending up in the sea from transport in air and water. Other pollutants, such as phthalates, which are important plasticisers, easily make their way into the sea in run off from urban areas and from marine litter. In particular, POPs do not break down very easily, accumulate in fat and become more concentrated as they are passed up the food chain, ending up in liver and fat. Seals are important top marine predators that have to build up a thick blubber layer while feeding at sea, and then use the fat as a metabolic fuel to keep them alive when they come ashore to breed, moult and rest. They have metabolic similarities to obese and diabetic patients. Their need to rely on fat for fuel and insulation makes them vulnerable to the effects of marine pollutants on the way fat tissue works. The higher the level of POPs in the blubber of seal pups, the lower their chance of survival. Fat tissue like blubber is important for storing fat, releasing it into the bloodstream for use by other parts of the body and producing fat-regulating hormones that control how much fat is stored or used. Recently, the genes of some fat-regulating hormones were shown to be switched on more in blubber of seals from polluted areas in the Baltic Sea than in clean areas in the Arctic, suggesting marine pollutants alter energy balance in seals. However, the mechanisms that control how fat tissue works in seals, and the way marine contaminants interfere with this control, are not well understood. If contaminants can prevent seals from releasing fat from blubber to give them fuel when they are fasting on land, they may have to use more of their protein from muscle tissue instead. This could put them at risk of starvation during moulting, breeding and development, even when they are fat. We will investigate whether pollutants alter fat storage and mobilisation in young grey seals, which are most at risk. We will take small blubber samples from live feeding and fasting seals, without harming them, and treat the blubber with pollutants and fat regulating hormones. We will measure levels of genes and hormones involved in energy balance, the ability of blubber to release fat, and its metabolic rate. By comparing these measures between treatments we will begin to find out how energy balance is normally regulated in seals, how it is altered by marine contaminants, and whether seals are more vulnerable during feeding or fasting. This will help predict the effects of pollutants on seal population size, by contributing a better understanding of how contaminants affect survival of young seals and change their energetic requirements. Because seals naturally experience extreme changes in fat mass, have metabolic similarities to diabetes and obesity, and eat fish, like people do, this work will also inform the likely impacts of POPs and phthalates on human fat regulation. This work has far reaching consequences for health and survivorship in seals and other animals, but also for the management of obesity, diabetes and related metabolic abnormalities in humans.