Exploring the "MEAT FACTOR": enhancement of non-heme iron bioavailability

肌肉组织中的某些成分可以增强非血红素铁（Fe）的吸收-这种现象被称为“肉因子”。缺铁性贫血是一种常见的营养失调症，其中20%至50%的世界人口没有足够的膳食铁。与年轻人相比，加拿大的老年人贫血的患病率更高，有趣的是，发达国家的铁缺乏通常不仅仅是膳食铁的问题，而是一个吸收问题。我们有兴趣探索肉类因素，以创造可以帮助人们更好地吸收铁的食物。一种肉类因子分子是一种称为糖胺聚糖（GAG）的碳水化合物，存在于与肉类相关的所有组织中。糖胺聚糖是由附着在蛋白质上的无支链糖链组成的。它们不仅存在于肉类中，而且存在于软骨，肌腱和皮肤等结缔组织中，并且代表了肉类加工业被低估和未被充分利用的副产品。临床上已经证明，当作为口服补充剂服用时，GAG可以帮助解决骨关节炎（例如硫酸软骨素）等关节问题，但需要更多的研究来证明GAG如何用于其他应用，如改善铁的吸收。我们还在结缔组织胶原蛋白肽中添加某些糖，以增加铁的生物利用度。我们研究计划的主要目标是更好地了解负责增加铁吸收的分子。将协调代表具体和相互关联目标的平行研究项目。具体目标是：i）了解来自不同组织类型（如皮肤、软骨和肉）的GAG如何促进Fe生物利用度的化学和机制; ii）研究特定肉胶原蛋白肽对Fe生物利用度的作用; iii）将糖以酶促和化学方式添加到胶原蛋白肽中，以确定其对Fe生物利用度的后续影响; iv）开发结缔组织培养技术的潜力，为未来的潜在市场生产生物活性GAG。第一个项目评估来自不同组织的GAG增加Fe的生物利用度的能力。使用我们实验室优化的方法提取GAG，并使用“Caco-2”细胞培养筛选系统进行测试。在Caco-2细胞内，铁转运蛋白的表达和铁储存蛋白铁蛋白的产生是我们监测以评估铁生物利用度的关键因素。该系统使我们能够在不使用实验室动物的情况下高效地进行初步研究。第二个项目评估了胶原蛋白肽与铁的结合，以增加其溶解度和生物利用度。第三个项目评估酶促和化学产生的糖肽增加铁生物利用度的能力。最后，第四个项目是一种组织工程方法，开发创造一致和可持续的未来GAG供应的潜力。由于与肉类生产和消费相关的伦理、环境和农业问题，结缔组织原材料的供应在可预见的未来可能会减少。生物活性GAG可以从我们实验室从不同鱼类物种分离的培养成纤维细胞中产生。最终，当我们纯化和控制这种“肉因子”时，它代表了验证，改进和建立更可持续的资源和技术的基础，用于设计特殊的食品配方以增加铁的可用性。这项研究将主要有利于加拿大弱势群体，如妇女，婴儿和老年人，对铁缺乏症。

Certain components in muscle tissue can enhance non-heme-iron absorption (Fe) – this phenomenon is called the “meat factor”. Iron deficiency anemia is a common nutritional disorder where 20% to 50% of the world’s population does not have adequate dietary iron. Seniors in Canada have a higher prevalence of anemia compared to younger people, and interestingly, iron deficiencies in the developed world are commonly not an issue of dietary iron alone, but rather, represent an absorption problem. We are interested in exploring the meat factor to create foods that can help people absorb Fe better. One meat factor molecule is a carbohydrate called glycosaminoglycans (GAGs), found in all the tissues associated with meat. GAGs are made of unbranched chains of sugars that are attached to proteins. They are not only found in meat, but also in connective tissue like cartilage, tendon, and skin, and represent an undervalued and underutilized by-product of the meat processing industry. GAGs have been shown clinically to help with joint problems like osteoarthritis (e.g. Chondroitin sulfate) when taken as an oral supplement, but more research is needed to show how GAGs can be used in other applications like improving Fe absorption. We are also adding certain sugars onto connective tissue collagen peptides to increase Fe bioavailability. The main goal of our research program is to better understand the molecules responsible for increasing Fe absorption. Parallel research projects will be coordinated representing specific and interrelated objectives. Specific objectives are: i) To understand the chemistry and mechanism of how GAGs from different tissue types, such as skin, cartilage, and meat, promote Fe bioavailability; ii) To investigate the role of specific meat collagen peptides on Fe bioavailability; iii) To add sugars to collagen peptides, both enzymatically and chemically, to determine their subsequent effects on Fe bioavailability; iv) To develop the potential of connective tissue culturing techniques to produce bioactive GAGs for future potential markets. The first project evaluates the ability of GAGs from different tissues to increase the bioavailability of Fe. GAGs are extracted using methods optimized in our laboratory, and tested using a “Caco-2” cell culture screening system. Iron transporter expression and the production of an iron storage protein, ferritin, within Caco-2 cells, are key factors we monitor to evaluate Fe bioavailability. This system allows us to do preliminary research efficiently without using laboratory animals. The second project evaluates the binding of collagen peptides to Fe to increase its solubility and bioavailability. The third project evaluates the ability of enzymatically and chemically produced glycopeptides to increase Fe bioavailability. Lastly, the fourth project is a tissue engineering approach developing the potential to create a consistent and sustainable future supply of GAGs. The supply of connective tissue raw materials may decrease in the foreseeable future due to ethical, environmental, and agricultural issues related to meat production and consumption. Bioactive GAGs can be produced from cultured fibroblasts isolated in our laboratory from different fish species. Ultimately, as we purify and control this “meat factor”, it represents the foundation to verify, improve, and build upon more sustainable resources and technologies, for designing special food formulations to increase Fe availability. This research will mostly benefit vulnerable Canadians, such as women, infants, and seniors, against Fe deficiency.