Mobilising vitamin D sequestered in adipose tissue in humans

在英国，多达一半的人血液中维生素D水平较低，找到改善维生素D状况的方法是公认的健康优先事项。维生素D是亲脂性的(喜欢脂肪)，在我们的脂肪组织(脂肪储存)中大量积累。脂肪组织中维生素D的滞留导致血液中维生素D水平较低。这一点非常相关，因为英国大多数人都超重，预计到2035年，几乎一半的人口将肥胖。因此，现在和未来的一个关键挑战是找到成功地从脂肪中动员维生素D的方法，以帮助减少脂肪膨胀对维生素D供应的影响。我们的初步数据表明，体力活动是从脂肪组织中动员维生素D的有效方法--即使不减轻体重。这些初步数据表明，运动对血液中重要形式的维生素D浓度有强大的影响，运动刺激脂肪组织释放这种形式的维生素D。基于这些观察，我们提出，定期锻炼将改善脂肪组织中维生素D的动员，这将增加血液中重要形式维生素D的数量和可获得性。在这个项目中，我们将使用一项为期12周的随机对照试验，在男性和女性中检查运动(与对照组相比)对肥胖患者维生素D状态和代谢的影响。我们将评估运动对血液中各种形式的维生素D的影响，以及这些变化是否会改善已知受维生素D状态(一种称为单核细胞的白细胞)影响的细胞的功能。我们将使用稳定同位素(非放射性示踪剂)来研究运动对维生素D周转的影响。通过采集脂肪组织的小切片，我们将能够检查运动对从脂肪中动员维生素D的能力的影响。这也将使我们了解涉及维生素D动员的生物学途径和机制，以及它们是如何受到运动的影响的。我们设计了我们的研究包括一个瘦身比较组，这样我们就可以了解肥胖和运动对维生素D动员、状态和新陈代谢的独立影响。这项研究将帮助我们了解运动对维生素D状态的影响，以及增加体力活动是否代表着从脂肪组织中动员维生素D的潜在有用的策略。关键的利益相关者，包括通知英国政府的机构，已经确认了解是否(以及如何)从脂肪组织中动员维生素D是一个重要的知识缺口。因此，这项研究将有很大潜力转化为与维生素D和健康有关的政策和指南。在未来，我们设想，运动的益处可以作为一种辅助策略来推广，以改善人群和个人的维生素D状况，并与补充饮食等策略一起进行。我们的研究结果也将对肥胖和缺乏运动对健康的影响的政策和指导产生影响。除了这些对政策和实践的直接影响外，了解身体活动有助于动员脂肪组织中隔离化合物的基本生物学途径和机制，可以为与隔离在脂肪中的维生素D和其他脂类化合物有关的新的药理和非药理策略、干预措施和产品提供基础。

Up to half of people in the UK have low levels of vitamin D in their blood and finding ways to improve vitamin D status is a recognised health priority. Vitamin D is lipophilic (fat-loving) and accumulates in our adipose tissue (fat stores) in large amounts. The entrapment of vitamin D in adipose tissue contributes to low levels of vitamin D in blood. This is very relevant as most people in the UK are overweight and by 2035 almost half the population is predicted to be obese. Thus, a key challenge now and in the future is to find ways to successfully mobilise vitamin D from adipose to help reduce the impact of adipose expansion on the availability of vitamin D. Our preliminary data indicate that physical activity is an effective way to mobilise vitamin D from adipose tissue - even without weight loss. These preliminary data show that exercise has a powerful effect on the concentration of the important form of vitamin D in blood and that exercise stimulates the release of this form of vitamin D from adipose tissue. Based on these observations, we propose that regular exercise will improve the mobilisation of vitamin D from adipose tissue and that this will increase the amount and availability of the important form of vitamin D in blood. In this project, we will use a 12-week randomised controlled trial in men and women to examine the impact of exercise (versus control) on vitamin D status and metabolism in obesity. We will assess the impact of exercise on the various forms of vitamin D that are found in blood, and whether these changes lead to an improvement in the function of cells known to be affected by vitamin D status (a type of white blood cell called monocytes). We will use stable isotopes (non-radioactive tracers) to examine how the turnover of vitamin D is affected by exercise. By taking small biopsies of adipose tissue we will be able to examine the impact of exercise on the ability to mobilise vitamin D from adipose. This will also allow us to understand the biological pathways and mechanisms that are involved in vitamin D mobilisation and how they are affected by exercise. We have designed our research to include a lean comparator group so that we can understand the independent effects of obesity and exercise on vitamin D mobilisation, status and metabolism. This research will help us to understand the impact of exercise on vitamin D status and whether increasing physical activity represents a potentially useful strategy to mobilise vitamin D from adipose tissue. Understanding whether (and how) vitamin D can be mobilised from adipose tissue has been identified by key stakeholders, including agencies that inform the UK government, as an important knowledge gap. Thus, this research will have great potential for translation into policies and guidance related to vitamin D and health. In the future, we envisage that the benefits of exercise can be promoted as an adjunct strategy to improve population and individual vitamin D status alongside complementary strategies such as dietary supplementation. The outcomes from our research will also have implications for policies and guidance around the effects of obesity and physical inactivity on health. In addition to these direct effects on policies and practices, an understanding of the fundamental biological pathways and mechanisms through which physical activity helps to mobilise compounds sequestered in adipose tissue could provide the basis for novel pharmacological and non-pharmacological strategies, interventions and products related to vitamin D and other lipophilic compounds sequestered in adipose.