Full Text:   <2881>

Summary:  <2072>

CLC number: R87

On-line Access: 2014-06-03

Received: 2014-02-21

Revision Accepted: 2014-07-08

Crosschecked: 2014-08-15

Cited: 8

Clicked: 6027

Citations:  Bibtex RefMan EndNote GB/T7714

-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2014 Vol.15 No.9 P.820-829

http://doi.org/10.1631/jzus.B1400052


Effects of hypoxic exercise training on microRNA expression and lipid metabolism in obese rat livers*


Author(s):  Ying-li Lu1, Wen Jing2, Lian-shi Feng1, Li Zhang1, Jian-fang Xu1, Tong-jian You3, Jing Zhao4

Affiliation(s):  1. Biology Center, China Institute of Sport Science, Beijing 100061, China; more

Corresponding email(s):   fengls98@126.com

Key Words:  Hypoxic training, Obese rat, Liver, MicroRNA, Lipid metabolism


Ying-li Lu, Wen Jing, Lian-shi Feng, Li Zhang, Jian-fang Xu, Tong-jian You, Jing Zhao. Effects of hypoxic exercise training on microRNA expression and lipid metabolism in obese rat livers[J]. Journal of Zhejiang University Science B, 2014, 15(9): 820-829.

@article{title="Effects of hypoxic exercise training on microRNA expression and lipid metabolism in obese rat livers",
author="Ying-li Lu, Wen Jing, Lian-shi Feng, Li Zhang, Jian-fang Xu, Tong-jian You, Jing Zhao",
journal="Journal of Zhejiang University Science B",
volume="15",
number="9",
pages="820-829",
year="2014",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1400052"
}

%0 Journal Article
%T Effects of hypoxic exercise training on microRNA expression and lipid metabolism in obese rat livers
%A Ying-li Lu
%A Wen Jing
%A Lian-shi Feng
%A Li Zhang
%A Jian-fang Xu
%A Tong-jian You
%A Jing Zhao
%J Journal of Zhejiang University SCIENCE B
%V 15
%N 9
%P 820-829
%@ 1673-1581
%D 2014
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1400052

TY - JOUR
T1 - Effects of hypoxic exercise training on microRNA expression and lipid metabolism in obese rat livers
A1 - Ying-li Lu
A1 - Wen Jing
A1 - Lian-shi Feng
A1 - Li Zhang
A1 - Jian-fang Xu
A1 - Tong-jian You
A1 - Jing Zhao
J0 - Journal of Zhejiang University Science B
VL - 15
IS - 9
SP - 820
EP - 829
%@ 1673-1581
Y1 - 2014
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1400052


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

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

References

[1] Ambros, V., 2004. The functions of animal microRNAs. Nature, 431(7006):350-355. 


[2] Armellini, F., Zamboni, M., Robbi, R., 1997. The effects of high altitude trekking on body composition and resting metabolic rate. Horm Metab Res, 29(9):458-461. 


[3] Bartel, D.P., 2009. MicroRNAs: target recognition and regulatory functions. Cell, 136(2):215-233. 


[4] Baze, M.M., Schlauch, K., Hayes, J.P., 2010. Gene expression of the liver in response to chronic hypoxia. Physiol Genomics, 41(3):275-288. 


[5] Carrer, M., Liu, N., Grueter, C.E., 2012. Control of mitochondrial metabolism and systemic energy homeostasis by microRNAs 378 and 378*. PNAS, 109(38):15330-15335. 


[6] Chen, T., Li, Z., Yan, J., 2012. MicroRNA expression profiles distinguish the carcinogenic effects of riddelliine in rat liver. Mutagenesis, 27(1):59-66. 


[7] Eichner, L.J., Perry, M.C., Dufour, C.R., 2010. miR-378(*) mediates metabolic shift in breast cancer cells via the PGC-1β/ERRγ transcriptional pathway. Cell Metab, 12(4):352-361. 


[8] Elmn, J., Lindow, M., Schtz, S., 2008. LNA-mediated microRNA silencing in non-human primates. Nature, 452(7189):896-899. 


[9] Esau, C., Davis, S., Murray, S.F., 2006. miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metab, 3(2):87-98. 


[10] Feng, L.S., Lu, Y.L., 2012. Altitude Training in China. , International Convention on Science, Education and Medicine in Sport, Glasgow, UK, :


[11] Feng, L.S., Lu, Y.L., Zhang, L., 2013. Effect of hypoxic training on fatty acid oxidation in obese rats. FASEB J, 27:lb760


[12] Filipowicz, W., Bhattacharyya, S.N., Sonenberg, N., 2008. Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight?. Nat Rev Genet, 9(2):102-114. 


[13] Friedman, R.C., Farh, K.K., Burge, C.B., 2009. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res, 19(1):92-105. 


[14] Galbs, O., Goret, L., Caillaud, C., 2008. Combined effects of hypoxia and endurance training on lipid metabolism in rat skeletal muscle. Acta Physiol, 193(2):163-173. 


[15] Ge, R.L., Wood, H., Yang, H.H., 2010. The body weight loss during acute exposure to high-altitude hypoxia in sea level residents. Acta Physiol Sin, 62(6):541-546. 


[16] Gerin, I., Clerbaux, L.A., Haumont, O., 2010. Expression of miR-33 from an SREBP2 intron inhibits cholesterol export and fatty acid oxidation. J Biol Chem, 285(44):33652-33661. 


[17] Gerin, I., Bommer, G.T., McCoin, C.S., 2010. Roles for miRNA-378/378* in adipocyte gene expression and lipogenesis. Am J Physiol Endocrinol Metab, 299(2):E198-E206. 


[18] Huang, X.G., Feng, L.S., Xu, J.F., 2007. Changes of body weight and energy metabolism of SD rats during hypoxic training. China Sport Sci, (in Chinese),27(10):61-68. 


[19] Iliopoulos, D., Drosatos, K., Hiyama, Y., 2010. MicroRNA-370 controls the expression of microRNA-122 and Cpt1α and affects lipid metabolism. J Lipid Res, 51(6):1513-1523. 


[20] Ishida, M., Shimabukuro, M., Yagi, S., 2013. MicroRNA miR-378 regulates adipocytokine fate by targeting transcriptional factors in human isceral and subcutaneous adipose tissue. Eur Heart J, 34(Suppl. 1):604


[21] Krtzfeldt, J., Rajewsky, N., Braich, R., 2005. Silencing of microRNAs in vivo with ‘antagomirs’. Nature, 438(7068):685-689. 


[22] Lin, Q., Gao, Z., Alarcon, R.M., 2009. A role of miR-27 in the regulation of adipogenesis. FEBS J, 276(8):2348-2358. 


[23] Ling, Q., Sailan, W., Ran, J., 2008. The effect of intermittent hypoxia on bodyweight, serum glucose and cholesterol in obesity mice. Pak J Biol Sci, 11(6):869-875. 


[24] Lippl, F.J., Neubauer, S., Schipfer, S., 2010. Hypobaric hypoxia causes body weight reduction in obese subjects. Obesity, 18(4):675-681. 


[25] Lu, Y.L., Feng, L.S., Zhao, P., 2012. Effect of Different Hypoxic Training on Body Weight in Rats. , International Convention on Science, Education and Medicine in Sport, Glasgow, UK, :


[26] Lu, Y.L., Zhang, L., Feng, L.S., 2013. Effects of hypoxic training on serum lipoprotein of obese rats. FASEB J, 27:lb769


[27] Moore, K.J., Rayner, K.J., Surez, Y., 2010. MicroRNAs and cholesterol metabolism. Trends Endocrinol Metab, 21(12):699-706. 


[28] Najafi-Shoushtari, S.H., Kristo, F., Li, Y., 2010. MicroRNA-33 and the SREBP host genes cooperate to control cholesterol homeostasis. Science, 328(5985):1566-1569. 


[29] Netzer, N.C., Chytra, R., Kpper, T., 2008. Low intense physical exercise in normobaric hypoxia leads to more weight loss in obese people than low intense physical exercise in normobaric sham hypoxia. Sleep Breath, 12(2):129-134. 


[30] Ou, Z., Wada, T., Gramignoli, R., 2011. MicroRNA hsa-miR-613 targets the human LXRα gene and mediates a feedback loop of LXRα autoregulation. Mol Endocrinol, 25(4):584-596. 


[31] Rayner, K.J., Surez, Y., Dvalos, A., 2010. miR-33 contributes to the regulation of cholesterol homeostasis. Science, 328(5985):1570-1573. 


[32] Rayner, K.J., Sheedy, F.J., Esau, C.C., 2011. Antagonism of miR-33 in mice promotes reverse cholesterol transport and regression of atherosclerosis. J Clin Invest, 121(7):2921-2931. 


[33] Rayner, K.J., Esau, C.C., Hussain, F.N., 2011. Inhibition of miR-33a/b in non-human primates raises plasma HDL and lowers VLDL triglycerides. Nature, 478(7369):404-407. 


[34] Richalet, J.P., Mehidioi, H., Rathat, C., 1988. Acute hypoxia decreases cardiac response to catecholamines in exercising humans. Int J Sports Med, 9(2):157-162. 


[35] Schlichting, C.D., Smith, H., 2002. Phenotypic plasticity: linking molecular mechanisms with evolutionary outcomes. Evol Ecol, 16(3):189-211. 


[36] Strobel, G., Neureither, M., Brtsch, P., 1996. Effect of acute mild hypoxia during exercise on plasma free and sulphoconjugated catecholamines. Eur J Appl Physiol Occup Physiol, 73(1-2):82-87. 


[37] Tin'kov, A.N., Aksenov, V.A., 2002. Effects of intermittent hypobaric on blood lipid concentrations in male coronary heart disease patients. High Alt Med Biol, 3(3):277-282. 


[38] Trajkovski, M., Hausser, J., Soutschek, J., 2011. MicroRNAs 103 and 107 regulate insulin sensitivity. Nature, 474(7353):649-653. 


[39] Wang, J.H., Lu, Y.L., Feng, L.S., 2012. Living high training high inhibits the SREBP-1c expression in obese rats liver. China J Sports Med, (in Chinese),31(7):590-595. 



Open peer comments: Debate/Discuss/Question/Opinion

<1>

Please provide your name, email address and a comment





Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2024 Journal of Zhejiang University-SCIENCE