Department of Nutrition, Food Sciences and Gastronomy, School of Pharmacy and Food Sciences, Food Campus Torribera, University of Barcelona, E-08921 Santa Coloma de Gramenet, Spain.
Institute of Biomedicine of the University of Barcelona (IBUB), CIBER Physiopathology of Obesity and Nutrition (CIBER-OBN), Instituto de Salud Carlos III, E-28029 Madrid, Spain.
Int J Mol Sci. 2019 Mar 19;20(6):1386. doi: 10.3390/ijms20061386.
The ability to detect changes in nutrient levels and generate an adequate response to these changes is essential for the proper functioning of living organisms. Adaptation to the high degree of variability in nutrient intake requires precise control of metabolic pathways. Mammals have developed different mechanisms to detect the abundance of nutrients such as sugars, lipids and amino acids and provide an integrated response. These mechanisms include the control of gene expression (from transcription to translation). This review reports the main molecular mechanisms that connect nutrients' levels, gene expression and metabolism in health. The manuscript is focused on sugars' signaling through the carbohydrate-responsive element binding protein (ChREBP), the role of peroxisome proliferator-activated receptors (PPARs) in the response to fat and GCN2/activating transcription factor 4 (ATF4) and mTORC1 pathways that sense amino acid concentrations. Frequently, alterations in these pathways underlie the onset of several metabolic pathologies such as obesity, insulin resistance, type 2 diabetes, cardiovascular diseases or cancer. In this context, the complete understanding of these mechanisms may improve our knowledge of metabolic diseases and may offer new therapeutic approaches based on nutritional interventions and individual genetic makeup.
检测营养水平变化并对此做出适当反应的能力对于生物的正常运作至关重要。为了适应营养摄入的高度可变性，生物体需要对代谢途径进行精确控制。哺乳动物已经开发出不同的机制来检测糖、脂类和氨基酸等营养物质的丰度，并提供综合反应。这些机制包括基因表达的控制（从转录到翻译）。本综述报告了连接健康状态下营养水平、基因表达和代谢的主要分子机制。本文重点介绍了糖通过碳水化合物反应元件结合蛋白（ChREBP）的信号传递、过氧化物酶体增殖物激活受体（PPARs）在脂肪反应中的作用、以及感知氨基酸浓度的 GCN2/激活转录因子 4（ATF4）和 mTORC1 途径。这些途径的改变常常是多种代谢疾病（如肥胖症、胰岛素抵抗、2 型糖尿病、心血管疾病或癌症）发生的基础。在这种情况下，对这些机制的全面了解可以增进我们对代谢疾病的认识，并为基于营养干预和个体遗传构成的新治疗方法提供依据。
