Effects of hypoxic exercise on Nesfatin-1 and Ghrelin in
hypothalamus of rats with alimentary obesity

doi:10.3969/j.issn.2095-4344.2558

Abstract

Abstract:

BACKGROUND: Balanced diet and scientific exercise are generally accepted as safe, effective and economical body mass management interventions. However, exercises sometimes increase the appetite of dieters. Combining hypoxic environment stimulation with aerobic exercise intervention may achieve the best effect on weight loss. As the central part of the body that regulates food intake and energy balance, the hypothalamus is concerned about the relationship between its regulating factors and the pathogenesis of obesity.

OBJECTIVE: To observe the levels of nesfatin-1 and ghrelin in the hypothalamus of obese rats, so as to explore the neuroendocrine mechanisms of feeding and body mass by hypoxia and/or exercise.

METHODS: Sixty Sprague-Dawley male rats with alimentary obesity were divided into six groups: quiet group, aerobic exercise group, 16.3% hypoxia quiet group, 16.3% hypoxic exercise group, 13.3% hypoxia quiet group and 13.3% hypoxic exercise group. A low-oxygen generator was used to create hypoxia environment at a volume fraction of 16.3% oxygen and 13.3% oxygen. Under hypoxia environment, the rats were continuously fed with high-fat food, and subjected to a treadmill exercise, 20 m/min (0° slope), 40 min/d, 5 days per week for 8 continuous weeks. Body mass and food intake were recorded, and Lee’s index was calculated. Levels of nesfatin-1 and ghrelin in the rat hypothalamus were measured after intervention by means of ELISA kit.

RESULTS AND CONCLUSION: (1) The body mass and Lee’s index after intervention: the effect of simple hypoxic environment stimulation on body mass and Lee’s index of rats was not as obvious as that of simple aerobic exercise stimulation. When hypoxic environment was combined with exercise, the effect was better than that of single stimulation. (2) Daily food intake during the intervention period: The daily food intake remained stable in the normoxic quiet group, and decreased in all other groups decreased, especially in the 16.3% hypoxic exercise group and 13.3% hypoxic exercise group. (3) Levels of nesfinin-1 and ghrelin in the hypothalamus: hypoxia combined with exercise could change nesfinin-1 levels in the hypothalamus of rats, and the nesfinin-1 level was highest in the 13.3% hypoxic exercise group. Exercise or hypoxia alone could affect the ghrelin level in the hypothalamus of rats, and the effect of single exercise stimulation was better than that of single hypoxia stimulation. Moreover, the combination of exercise and hypoxia made a further reduction in the ghrelin level. (4) Bivariate analysis of variance: Body mass and ghrelin level were affected by exercise; body mass, Lee’s index and food intake were affected by O₂ concentration; and body mass, nesfinin-1 and ghrelin levels were affected by exercise×O₂ concentration. These findings indicate that 8-week hypoxic exercise may decrease the rats’ food intake, inhibit the increase of body mass and reduce the Lee’s index by regulating nesfinin-1 and ghrelin levels in the hypothalamus, but the specific mechanism is not clear.

Key words: sports biochemistry, hypoxic exercise, hypothalamus, Nesfatin-1, Ghrelin, rats

CLC Number:

Fan Jinqin, Weng Xiquan, Xu Guoqin, Wu Juhua, Lin Wentao. Effects of hypoxic exercise on Nesfatin-1 and Ghrelin in hypothalamus of rats with alimentary obesity[J]. Chinese Journal of Tissue Engineering Research, 2020, 24(20): 3202-3208.

Figures/Tables 5

多重比较发现：与常氧安静组比较，常氧运动组、16.3%低氧运动组和13.3%低氧运动组的体质量及Lee’s指数均较低且差异有显著性意义(P < 0.05和P < 0.01)；与常氧运动组比较，16.3%低氧安静组、13.3%低氧安静组的体质量较高且差异有显著性意义(P < 0.05)，16.3%低氧运动组、13.3%低氧运动组的体质量较低且差异有非常显著性意义(P < 0.01)；与16.3%低氧安静组比较，16.3%低氧运动组、13.3%低氧运动组的体质量较低且差异有非常显著性意义(P < 0.01)；与16.3%低氧运动组比较，13.3%低氧安静组体质量和Lee’s指数较高且差异有显著性意义(P < 0.01，P < 0.05)；与13.3%低氧安静组比较，16.3%低氧运动组、13.3%低氧运动组的体质量较低且差异有非常显著性意义(P < 0.01)。结果提示，单纯低氧环境刺激对大鼠体质量、Lee’s指数的影响没有单纯有氧运动刺激明显，而当低氧和运动结合时，其效果优于单一刺激，如在氧气体积分数更低的常压环境中运动，其效果更为显著。大鼠干预期体质量变化，见图1。8周干预期内，3个安静组的体质量为持续增加状态；3个运动组的体质量增幅均小于安静组，其中常氧运动组每只大鼠每周体质量增长保持在0-10 g之间；16.3%低氧运动组和13.3%低氧运动组的体质量在干预第1周即下降，尤以13.3%低氧运动组明显，随后两组的体质量降幅变缓，至第4周出现了体质量下降峰(下降幅度16.3%低氧运动组>13.3%低氧运动组)，之后每只大鼠每周增长保持在0-10 g之间；在第8周时常氧运动组和13.3%低氧运动组大鼠体质量出现下降峰(下降幅度13.3%低氧运动组>常氧运动组)。结果提示运动和低氧均可抑制大鼠的体质量增长，而低氧抑制体质量增长的效果在干预初期较后期明显，且氧气体积分数较低时将更早出现体质量的负增长。 "

干预后各组大鼠下丘脑ghrelin水平进行多重比较，见表4。与常氧安静组比较，常氧运动组、16.3%低氧安静组、16.3%低氧运动组和13.3%低氧运动组的ghrelin水平均较低且差异有非常显著性意义(P < 0.01)；与常氧运动组比较，16.3%低氧安静组、16.3%低氧运动组和13.3%低氧安静组的ghrelin水平均较高且差异有非常显著性意义(P < 0.01)；与16.3%低氧安静组比较，13.3%低氧安静组的ghrelin水平较高且差异有显著性意义(P < 0.05)；与16.3%低氧运动组比较，13.3%低氧安静组ghrelin水平较高且差异有显著性意义(P < 0.05)，13.3%低氧运动组ghrelin水平较低且差异有非常显著性意义(P < 0.01)；与13.3%低氧安静组比较，13.3%低氧运动组ghrelin水平较低且差异有非常显著性意义(P < 0.01)。结果提示单纯的运动或低氧均可影响大鼠下丘脑ghrelin水平，而单一运动刺激效果要强于单一低氧刺激，当二者结合时降低效果更明显，但这种效果在2种常压低氧组间没有显著差异。 2.5 低氧或/和运动与各指标的双因素方差分析结果由表5可知，除nesfatin-1外，其余指标的Corrected Model Sig.均小于0.05，提示这些指标的组间差异有显著性意义。体质量受运动、氧气体积分数和运动×氧气体积分数的影响且差异有非常显著性意义(P < 0.01)，提示运动和低氧干预均可影响大鼠体质量，两种因素有交互作用；Lee’s指数和摄食量受氧气体积分数影响且差异有非常显著性意义(P < 0.01)，提示这两者对氧气体积分数改变敏感；Nesfatin-1受运动×氧气体积分数的影响且差异有显著性意义(P < 0.05)，提示低氧和运动二者结合时，可影响大鼠下丘脑nesfatin-1水平；Ghrelin受运动和运动×氧气体积分数的影响且差异有非常显著性意义(P < 0.05)，提示运动或/和低氧结合可影响大鼠下丘脑ghrelin水平。 "

References

[1] OHASHI K, SHIBATA R, MUROHARA T, et al. Role of anti-inflammatory adipokines in obesity-related diseases. Trends Endocrinol Metab. 2014;25(7):348-355.
[2] BHASKARAN K, DOUGLAS I, FORBES H, et al. Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5•24 million UK adults. Lancet.2014;384(9945):755-765.
[3] NCD RISK FACTOR COLLABORATION (NCD-RISC). Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19•2 million participants. Lancet. 2016;387 (10026):1377-1396.
[4] HAMAD N, TRAVIS SP. Weight loss at high altitude: pathophysiology and practical implications. Eur J Gastroenterol Hepatol. 2006;18(1):5-10.
[5] LING Q, SAILAN W, RAN J, et al. The effect of intermittent hypoxia on bodyweight, serum glucose and cholesterol in obesity mice. Pak J Biol Sci. 2008;11(6):869-875.
[6] MORTOLA JP. Implications of hypoxic hypometabolism during mammalian ontogenesis. Respir Physiol Neurobiol. 2004; 141(3):345-356.
[7] COSTALAT G, LEMAITRE F, TOBIN B, et al. Intermittent hypoxia revisited: a promising non-pharmaceutical strategy to reduce cardio-metabolic risk factors? Sleep Breath. 2018; 22(1): 267-271.
[8] KONG Z, ZANG Y, HU Y. Normobaric hypoxia training causes more weight loss than normoxia training after a 4-week residential camp for obese young adults. Sleep Breath. 2014; 18(3):591-597.
[9] KOJIMA M, HOSODA H, DATE Y, et al. Ghrelin is a growth- hormone-releasing acylated peptide from stomach. Nature. 1999;402(6762):656-660.
[10] KAMEGAI J, TAMURA H, SHIMIZU T, et al. Chronic central infusion of ghrelin increases hypothalamic neuropeptide Y and Agouti-related protein mRNA levels and body weight in rats. Diabetes. 2001;50(11):2438-2443.
[11] 付鹏宇,龚丽景,朱镕鑫,等.Ghrelin-GHSR通路在急性低氧暴露大鼠胃炎症反应中的调节作用[J].中国生物化学与分子生物学报,2018,34(10):1103-1110.
[12] ALIPARASTI MR, ALIPOUR MR, ALMASI S, et al. Ghrelin Administration Increases the Bax/Bcl-2 Gene Expression Ratio in the Heart of Chronic Hypoxic Rats. Adv Pharm Bull. 2015;5(2):195-199.
[13] OH-I S, SHIMIZU H, SATOH T, et al. Identification of nesfatin-1 as a satiety molecule in the hypothalamus. Nature. 2006;443 (7112):709-712.
[14] STENGEL A, TACHÉ Y. Nesfatin-1--role as possible new potent regulator of food intake. Regul Pept. 2010;163(1-3):18-23.
[15] ZHANG T, WANG M, LIU L, et al. Hypothalamic nesfatin-1 mediates feeding behavior via MC3/4R-ERK signaling pathway after weight loss in obese Sprague-Dawley rats. Peptides. 2019;119:170080.
[16] ÖZTÜRK ÖZKAN G. Effects of Nesfatin-1 on Food Intake and Hyperglycemia. J Am Coll Nutr. 2019 Aug 1:1-7.
[17] 冯连世,张漓,高炳宏,等.不同环境下有氧运动对超重和肥胖青少年体重与体脂含量的影响[J].体育科学,2013,33(11):58-65.
[18] DE GROOTE E, BRITTO FA, BULLOCK L, et al. Hypoxic Training Improves Normoxic Glucose Tolerance in Adolescents with Obesity. Med Sci Sports Exerc. 2018;50(11):2200-2208.
[19] 吴娜娜,管延飞,朱欢,等.高住低练对肥胖青少年血浆食欲调节激素的影响[J].中国应用生理学杂志,2015,31(3):281-283.
[20] 王茹,刘冬梅,吴娜娜,等.高住低练对肥胖青少年内源性大麻素及相关食欲调节激素的影响[J].体育科学,2016,36(2):51-57,71.
[21] URDAMPILLETA A, GONZÁLEZ-MUNIESA P, PORTILLO MP, et al. Usefulness of combining intermittent hypoxia and physical exercise in the treatment of obesity. J Physiol Biochem. 2012;68(2):289-304.
[22] 王茹,王红霞,许亚丽,等.高住低练对肥胖青少年形态学指标和糖脂代谢的影响[J].北京体育大学学报,2013,36(9):81-87.
[23] 陈瑜文,林文弢,邱烈峰,等.间歇低氧运动对肥胖大鼠食欲的影响及其机制分析[J].体育学刊,2011,18(4):133-136.
[24] WASSE LK, SUNDERLAND C, KING JA, et al. Influence of rest and exercise at a simulated altitude of 4,000 m on appetite, energy intake, and plasma concentrations of acylated ghrelin and peptide YY. J Appl Physiol (1985). 2012; 112(4):552-559.
[25] 吴菊花,杨亚南,翁锡全,等.低氧运动对营养性肥胖大鼠骨骼肌PGC-1α及其下游因子的影响[J].体育学刊, 2016,23(3) : 130-136.
[26] 上官若男,苏全生,尚画雨,等.运动负荷强度与运动疲劳程度量化分级研究进展[J].中国康复医学杂志, 2013, 28(2): 188-192.
[27] BEDFORD TG, TIPTON CM, WILSON NC, et al. Maximum oxygen consumption of rats and its changes with various experimental procedures. J Appl Physiol Respir Environ Exerc Physiol. 1979;47(6):1278-1283.
[28] HØYDAL MA, WISLØFF U, KEMI OJ, et al. Running speed and maximal oxygen uptake in rats and mice: practical implications for exercise training. Eur J Cardiovasc Prev Rehabil. 2007;14(6):753-760.
[29] 何明,涂长春,黄起壬,等. Lee's 指数用于评价成年大鼠肥胖程度的探讨[J].中国临床药理学与治疗学杂志,1997,2(3):177-179.
[30] 张静,沙继斌,张林,等.有氧运动与多糖干预对肥胖大鼠的血脂调节及抗炎作用[J].沈阳体育学院学报,2016,35(2):86-91.
[31] 谢宜轩,李帅.持续和间歇低氧运动对肥胖大鼠体重及相关代谢指标的影响[J].扬州大学学报(农业与生命科学版), 2016,37(1): 31-34.
[32] TAN BK, HALLSCHMID M, KERN W, et al. Decreased cerebrospinal fluid/plasma ratio of the novel satiety molecule, nesfatin-1/NUCB-2, in obese humans: evidence of nesfatin-1/NUCB-2 resistance and implications for obesity treatment. J Clin Endocrinol Metab. 2011;96(4):E669-673.
[33] 孙文娟,于普艳,戴红艳,等.肥胖症病人血浆nesfatin-1水平变化及与BMI关系[J].齐鲁医学杂志,2013,28(3):235-236,240.
[34] 李娜,田字彬,孙桂荣,等.Nesfatin-1对肥胖大鼠胃排空及胃平滑肌条收缩性的影响[J].世界华人消化杂志,2012,20(8): 631-637.
[35] CUI H, SOHN JW, GAUTRON L, et al. Neuroanatomy of melanocortin-4 receptor pathway in the lateral hypothalamic area. J Comp Neurol. 2012;520(18):4168-4183.
[36] 习燕华,刘建英. Nesfatin-1在肥胖及血糖调节中的作用[J].生理科学进展,2013,44(3):220-222.
[37] CHAOLU H, ASAKAWA A, USHIKAI M, et al. Effect of exercise and high-fat diet on plasma adiponectin and nesfatin levels in mice. Exp Ther Med. 2011;2(2):369-373.
[38] HAGHSHENAS R, JAFARI M, RAVASI A, et al. The effect of eight weeks endurance training and high-fat diet on appetite-regulating hormones in rat plasma. Iran J Basic Med Sci. 2014;17(4):237-243.
[39] TSCHÖP M, SMILEY DL, HEIMAN ML. Ghrelin induces adiposity in rodents. Nature. 2000;407(6806):908-913.
[40] 汪军,田吉明. 8周跑台运动对肥胖大鼠下丘脑ghrelin 和obestatin 的影响[J].北京体育大学学报,2009,32(4):57-60.
[41] 唐光旭,汪军.急性运动对肥胖大鼠下丘脑ghrelin和obestatin的影响[J].中国运动医学杂志,2010,29(5):551-555.
[42] 王宁琦,胡扬,官余凌,等.4周低氧运动结合饮食控制对肥胖青年体重、血脂及胰岛素抵抗的影响[J].中国运动医学杂志, 2012, 31(4):289-294.