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Abstract: To investigate the effects of hypoxic exercise training on microRNA (miRNA) expression and the role of miRNA expression in regulating lipid metabolism, 20 dietary-induced obese SD rats were divided into a normoxic sedentary group (N, n=10) and a hypoxic exercise training group (H, n=10). After four weeks, measurements were taken of body weight, body length, fat mass, serum lipid concentration, miRNAs differentially expressed in rat liver, and gene and protein expression levels of peroxisome proliferator activated receptor α (PPARα), fatty acid synthetase (FAS), and carnitine palmitoyl transferase 1A (CPT1A) in rat liver. Body weight, Lee’s index, fat mass, fat/weight ratio, and serum levels of total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) were all significantly lower in the H group than in the N group (P<0.01). Six miRNAs expressed significantly differently in the liver (P<0.05). Specifically, expression levels of miR-378b were significantly lower in the H group than in the N group (P<0.05). Compared with the normoxic sedentary group, hypoxic exercise training resulted in a lower ratio of FAS mRNA to CPT1A mRNA (P<0.05), as well as lower CPT1A protein levels (P<0.01), while a higher ratio of FAS to CPT1A protein levels (P<0.01) was observed. In conclusion, hypoxic training may elevate the resistance of high fat diet induced obesity in rats by reducing the expression of miR-378b, and decrease the fatty acid mitochondrial oxidation in obese rat livers by decreasing the protein expression of CPT1A and increasing the protein expression ratio of FAS/CPT1A.

低氧训练对肥胖大鼠肝脏microRNA表达及脂代谢的影响

研究目的：研究低氧训练对肥胖大鼠肝脏microRNA表达的影响及对脂代谢的调节。
创新要点：通过肝脏microRNA的表达以及脂代谢的变化，揭示microRNA调节低氧训练肥胖大鼠脂代谢的相关机制。
研究方法：二十只高脂饮食致肥胖大鼠进入正式实验，分为常氧安静组和低氧训练组，观察4周后肥胖大鼠形态指标（图1）以及血脂的变化（图2），microRNA微阵列芯片筛选低氧训练肥胖大鼠肝脏中722个成熟miRNA表达的差异（表2），利用实时荧光定量聚合酶链式反应（PCR）检测大鼠肝脏微小RNA-378b（miR-378b）和过氧化物酶体增殖物激活受体α（PPARα）、脂肪酸合成酶（FAS）、肉碱棕榈酰转移酶1A（CPT1A）的mRNA表达水平（图3），酶联免疫吸附测定（ELISA）法检测PPARα、FAS、CPT1A的蛋白水平（图4）。
重要结论：低氧训练通过降低肥胖大鼠肝脏miR-378b的表达水平，增加大鼠对高脂饮食诱导肥胖的抵抗能力；通过降低肝脏CPT1A蛋白表达水平，增加FAS/CPT1A蛋白表达比例降低肥胖大鼠肝脏脂肪酸的氧化能力。
低氧训练；肥胖大鼠；肝脏；miRNA；脂代谢

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