丙酮酸脱氢酶激酶4的表达由AMP激活的蛋白激酶和脂肪酸协同诱导。
Pyruvate dehydrogenase kinase 4 expression is synergistically induced by AMP-activated protein kinase and fatty acids.
作者信息
Houten S M, Chegary M, Te Brinke H, Wijnen W J, Glatz J F C, Luiken J J F P, Wijburg F A, Wanders R J A
机构信息
Department of Clinical Chemistry, Laboratory Genetic Metabolic Diseases, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
出版信息
Cell Mol Life Sci. 2009 Apr;66(7):1283-94. doi: 10.1007/s00018-009-9066-x.
Organs are flexible as to which substrates they will use to maintain energy homeostasis. Under well-fed conditions, glucose is a preferred substrate for oxidation. During fasting, fatty acid oxidation will become a more important energy source. Glucose oxidation is decreased by fatty acids, a process in which the pyruvate dehydrogenase complex (PDH) and its regulator pyruvate dehydrogenase kinase 4 (PDK4) play important roles. It is currently unknown how energy status influences PDH activity. We show that AMP-activated protein kinase (AMPK) activation by hypoxia and AICAR treatment combined with fatty acid administration synergistically induce PDK4 expression. We provide evidence that AMPK activation modulates ligand-dependent activation of peroxisome proliferator-activated receptor. Finally, we show that this synergistic induction of PDK4 decreases cellular glucose oxidation. In conclusion, AMPK and fatty acids play a direct role in fuel selection in response to cellular energy status in order to spare glucose.
器官在使用何种底物来维持能量稳态方面具有灵活性。在营养充足的条件下，葡萄糖是氧化的首选底物。在禁食期间，脂肪酸氧化将成为更重要的能量来源。脂肪酸会降低葡萄糖氧化，丙酮酸脱氢酶复合体（PDH）及其调节因子丙酮酸脱氢酶激酶4（PDK4）在这一过程中发挥重要作用。目前尚不清楚能量状态如何影响PDH活性。我们发现，缺氧和AICAR处理联合脂肪酸给药激活AMP激活的蛋白激酶（AMPK）可协同诱导PDK4表达。我们提供的证据表明，AMPK激活可调节过氧化物酶体增殖物激活受体的配体依赖性激活。最后，我们表明，这种对PDK4的协同诱导会降低细胞葡萄糖氧化。总之，AMPK和脂肪酸在响应细胞能量状态的燃料选择中发挥直接作用，以节省葡萄糖。
Zotero 插件