Department of Nutrition and Health Sciences and Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, Nebraska, USA.
Nutr Rev. 2018 Sep 1;76(9):693-707. doi: 10.1093/nutrit/nuy023.
Nutrient overload occurs worldwide as a consequence of the modern diet pattern and the physical inactivity that sometimes accompanies it. Cells initiate multiple protective mechanisms to adapt to elevated intracellular metabolites and restore metabolic homeostasis, but irreversible injury to the cells can occur in the event of prolonged nutrient overload. Many studies have advanced the understanding of the different detrimental effects of nutrient overload; however, few reports have made connections and given the full picture of the impact of nutrient overload on cellular metabolism. In this review, detailed changes in metabolic and energy homeostasis caused by chronic nutrient overload, as well as their associations with the development of metabolic disorders, are discussed. Overnutrition-induced changes in key organelles and sensors rewire cellular bioenergetic pathways and facilitate the shift of the metabolic state toward biosynthesis, thereby leading to the onset of various metabolic disorders, which are essentially the downstream manifestations of a misbalanced metabolic equilibrium. Based on these mechanisms, potential therapeutic targets for metabolic disorders and new research directions are proposed.
营养素超负荷在全球范围内发生，是现代饮食模式和随之而来的体力活动不足的结果。细胞会启动多种保护机制来适应细胞内代谢物的升高并恢复代谢平衡，但如果营养素超负荷持续存在，细胞可能会受到不可逆转的损伤。许多研究已经深入了解营养素超负荷的不同有害影响；然而，很少有研究将营养素超负荷对细胞代谢的影响联系起来并全面阐述。在这篇综述中，讨论了慢性营养素超负荷引起的代谢和能量平衡的详细变化，以及它们与代谢紊乱发展的关联。营养过剩引起的关键细胞器和传感器的变化重新布线细胞生物能量途径，并促进代谢状态向生物合成转变，从而导致各种代谢紊乱的发生，而这些紊乱基本上是代谢平衡失衡的下游表现。基于这些机制，提出了代谢紊乱的潜在治疗靶点和新的研究方向。
