Hernández-Aguilera Anna, Fernández-Arroyo Salvador, Cuyàs Elisabet, Luciano-Mateo Fedra, Cabre Noemi, Camps Jordi, Lopez-Miranda Jose, Menendez Javier A, Joven Jorge
Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Reus, Spain.
Molecular Oncology Group, Girona Biomedical Research Institute (IDIBGI), Girona, Spain; ProCURE (Program Against Cancer Therapeutic Resistance), Metabolism and Cancer Group, Catalan Institute of Oncology, Girona, Spain.
Food Chem Toxicol. 2016 Oct;96:191-204. doi: 10.1016/j.fct.2016.08.006. Epub 2016 Aug 5.
We live in a world fascinated by the relationship between disease and nutritional disequilibrium. The subtle and slow effects of chronic nutrient toxicity are a major public health concern. Since food is potentially important for the development of "metabolic memory", there is a need for more information on the type of nutrients causing adverse or toxic effects. We now know that metabolic alterations produced by excessive intake of some nutrients, drugs and chemicals directly impact epigenetic regulation. We envision that understanding how metabolic pathways are coordinated by environmental and genetic factors will provide novel insights for the treatment of metabolic diseases. New methods will enable the assembly and analysis of large sets of complex molecular and clinical data for understanding how inflammation and mitochondria affect bioenergetics, epigenetics and health. Collectively, the observations we highlight indicate that energy utilization and disease are intimately connected by epigenetics. The challenge is to incorporate metabolo-epigenetic data in better interpretations of disease, to expedite therapeutic targeting of key pathways linking nutritional toxicity and metabolism. An additional concern is that changes in the parental phenotype are detectable in the methylome of subsequent offspring. The effect might create a menace to future generations and preconceptional considerations.
我们生活在一个痴迷于疾病与营养失衡关系的世界。慢性营养毒性的细微和缓慢影响是一个重大的公共卫生问题。由于食物对“代谢记忆”的发展可能很重要,因此需要更多关于导致不良或毒性作用的营养素类型的信息。我们现在知道,过量摄入某些营养素、药物和化学物质所产生的代谢改变会直接影响表观遗传调控。我们设想,了解代谢途径如何由环境和遗传因素协调,将为代谢疾病的治疗提供新的见解。新方法将能够组装和分析大量复杂的分子和临床数据,以了解炎症和线粒体如何影响生物能量学、表观遗传学和健康。总体而言,我们强调的观察结果表明,能量利用和疾病通过表观遗传学紧密相连。挑战在于将代谢表观遗传数据纳入对疾病的更好解释中,以加快针对连接营养毒性和代谢的关键途径的治疗靶点。另一个令人担忧的问题是,在后代的甲基化组中可以检测到亲本表型的变化。这种影响可能会对后代和孕前考虑构成威胁。