Department of General Surgery, Hepatic-biliary-pancreatic Institute, Lanzhou University Second Hospital, Lanzhou, China; Department of Pediatrics, Lanzhou University Second Hospital, Lanzhou, China.
Department of General Surgery, Hepatic-biliary-pancreatic Institute, Lanzhou University Second Hospital, Lanzhou, China.
Biochem Biophys Res Commun. 2014 Apr 4;446(2):574-9. doi: 10.1016/j.bbrc.2014.03.001. Epub 2014 Mar 12.
High altitude (HA) affects energy metabolism. The impact of acute and chronic HA acclimatization on the major metabolic pathways is still controversial. In this study, we aimed to unveil the impact of HA on the key enzymes involved in the fatty acid (FA) metabolism in liver. Rats were exposed to an altitude of 4300 m for 30 days and the expressions of two key proteins involved in FA β-oxidation (carnitine palmitoyl transferase I, CPT-I; and peroxisome proliferator-activated receptor alpha, PPARα), two proteins involved in FA synthesis (acetyl CoA carboxylase-1, ACC-1; and AMP-activated protein kinase, AMPK), as well as the total ketone body in the liver and the plasma FFAs were examined. Rats without HA exposure were used as controls. We observed that the acute exposure of rats to HA (3 days) led to a significant increase in the expressions of CPT-I and PPARα and in the total hepatic ketone body. Longer exposure (15 days) caused a marked decrease in the expression of CPT-I and PPARα. By 30 days after HA exposure, the expression levels of CPT-I and PPARα returned to the control level. The hepatic ACC-1 level showed a significant increase in rats exposed to HA for 1 and 3 days. In contrast, the hepatic level of AMPK showed a significant reduction throughout the experimental period. Plasma FFA concentrations did not show any significant changes following HA exposure. Thus, increased hepatic FA oxidation and synthesis in the early phase of HA exposure may be among the important mechanisms for the rats to respond to the hypoxic stress in order to acclimatize themselves to the stressful environments.
高海拔(HA)会影响能量代谢。急性和慢性 HA 适应对主要代谢途径的影响仍存在争议。在这项研究中,我们旨在揭示 HA 对肝脏中脂肪酸(FA)代谢关键酶的影响。将大鼠暴露于 4300 米的高度 30 天,并检查涉及 FA β-氧化的两种关键蛋白(肉碱棕榈酰转移酶 I,CPT-I;和过氧化物酶体增殖物激活受体α,PPARα)、两种涉及 FA 合成的蛋白(乙酰辅酶 A 羧化酶-1,ACC-1;和 AMP 激活蛋白激酶,AMPK)以及肝脏和血浆游离脂肪酸中的总酮体的表达。未暴露于 HA 的大鼠用作对照。我们观察到,大鼠急性暴露于 HA(3 天)导致 CPT-I 和 PPARα的表达以及总肝酮体显著增加。更长时间的暴露(15 天)导致 CPT-I 和 PPARα的表达明显减少。HA 暴露 30 天后,CPT-I 和 PPARα的表达水平恢复到对照水平。暴露于 HA 的大鼠在 1 天和 3 天后,肝 ACC-1 水平显著增加。相比之下,在整个实验期间,肝 AMPK 水平显著降低。HA 暴露后,血浆 FFA 浓度没有明显变化。因此,在 HA 暴露的早期阶段,肝脏 FA 氧化和合成的增加可能是大鼠应对缺氧应激的重要机制之一,以使它们适应应激环境。