DOI QR코드

DOI QR Code

Effects of Chronic Sleep Fragmentation and Diet Restriction on Appetite-Regulating Hormones and Cardiometabolic Indicators

만성 분절수면과 식이제한이 식욕조절 호르몬 및 심혈관 위험지표에 미치는 영향

  • Jun, Nuri (Department of Foods and Nutrition, College of Natural Sciences, Kookmin University) ;
  • Baik, Inkyung (Department of Foods and Nutrition, College of Natural Sciences, Kookmin University)
  • 전누리 (국민대학교 자연과학대학 식품영양학과) ;
  • 백인경 (국민대학교 자연과학대학 식품영양학과)
  • Received : 2016.09.12
  • Accepted : 2017.01.17
  • Published : 2017.02.28

Abstract

Data are limited on biological mechanisms underlying the associations of sleep insufficiency with obesity and dyslipidemia. To explore these mechanisms, we investigated appetite-regulating hormones, stress-related hormones, and cardiometabolic indicators in association with sleep fragmentation, which is a type of sleep disorder. In an experimental study, we randomly allocated 40 Wistar male rats aged 7 weeks into four groups; rats with ad libitum sleep and ad libitum intake (Control), those exposed to sleep fragmentation (SF), those with diet restriction (DR), and those exposed to sleep fragmentation and diet restriction (SF+DR). Amongst them, 13-day chronic sleep fragmentation was applied to the SF and SF+DR groups while 50% reduction in chow intake was applied to the DR and SF+DR groups for 13 days. After these experiments, blood lipid and lipoprotein profiles, leptin, ghrelin, adiponectin, cortisol, epinephrine, and norepinephrine levels were compared among the four groups. In the results, the SF group showed the highest levels of serum ghrelin (P<0.001) and the lowest levels of serum adiponectin (P<0.01). All experimental groups showed higher levels of low density lipoprotein-cholesterol (LDL-C) than the Control (P<0.001). LDL-C levels and the ratio of LDL-C and high density lipoprotein-cholesterol were positively correlated with ghrelin levels (P<0.05) in the SF group, but not in the DR and SF+DR groups. In the SF group, the highest levels of serum free fatty acids were also observed and correlated with lower levels of serum adiponectin, which reflects insulin resistance (P<0.05). Based on these findings, we suggest that chronic sleep fragmentation may induce disturbances in lipid metabolism and appetite-regulating hormones independent of food intake, and these metabolic disturbances may be worse due to insulin resistance related to overeating, which is indicated by elevated ghrelin levels in sleep fragmentation. For persons with sleep insufficiency, anti-atherogenic dietary interventions may be recommended to prevent cardiovascular disease.

본 연구는 7주령의 백서 40마리를 이용하여 만성 분절수면과 식이제한이 식욕조절 호르몬을 포함한 심혈관 위험지표에 미치는 영향에 대해 실험하였다. 13일 동안의 만성적인 분절수면 및 식이제한의 조건에 노출된 백서의 체중 변화와 혈중 leptin, ghrelin, adiponectin, cortisol, epinephrine, norepinephrine 등의 호르몬 농도, 심혈관 위험지표인 혈중 총콜레스테롤, LDL-cholesterol, HDL-cholesterol, 중성지방, 유리지방산의 농도를 대조군 및 3군의 실험군(만성 분절수면 군, 식이제한 군, 분절수면과 식이제한 모두를 적용한 군)에서 비교하였다. 그 결과 실험기간 동안 만성 분절수면 군에서 백서의 체중이 증가하며, 혈중 leptin 및 adiponectin 농도가 감소하고 ghrelin 농도가 증가하여 결국 혈중 LDL-cholesterol 농도가 증가하였다. 분절수면과 식이제한을 동시에 적용한 백서에서는 체중이 감소하고 adiponectin 농도는 대조군과 유의적인 차이를 보이지 않았으며 ghrelin 농도는 분절수면만 했던 백서에 비해 감소한 것으로 나타나 식이제한이 식욕을 조절하는 것으로 나타났다. 하지만 이들 백서에서 혈중 leptin 농도가 현격히 감소하고 혈중 LDL-cholesterol 농도가 증가하는 양상을 나타내 만성 분절수면 환자들의 심한 식이제한이 심혈관질환의 위험을 더욱 증가시킬 수 있다는 결과를 보여주었다.

Keywords

References

  1. Taheri S, Lin L, Austin D, Young T, Mignot E. 2004. Short sleep duration is associated with reduced leptin, elevated ghrelin, and increased body mass index. PLoS Med 1: e62. https://doi.org/10.1371/journal.pmed.0010062
  2. Yaggi HK, Araujo AB, McKinlay JB. 2006. Sleep duration as a risk factor for the development of type 2 diabetes. Diabetes Care 29: 657-661. https://doi.org/10.2337/diacare.29.03.06.dc05-0879
  3. Gottlieb DJ, Redline S, Nieto FJ, Baldwin CM, Newman AB, Resnick HE, Punjabi NM. 2006. Association of usual sleep duration with hypertension: The Sleep Heart Health Study. Sleep 29: 1009-1014. https://doi.org/10.1093/sleep/29.8.1009
  4. Ayas NT, White DP, Manson JE, Stampfer MJ, Speizer FE, Malhotra A, Hu FB. 2003. A prospective study of sleep duration and coronary heart disease in women. Arch Intern Med 163: 205-209. https://doi.org/10.1001/archinte.163.2.205
  5. Kripke DF, Garfinkel L, Wingard DL, Klauber MR, Marler MR. 2002. Mortality associated with sleep duration and insomnia. Arch Gen Psychiatry 59: 131-136. https://doi.org/10.1001/archpsyc.59.2.131
  6. Patel SR, Hu FB. 2008. Short sleep duration and weight gain: a systematic review. Obesity 16: 643-653. https://doi.org/10.1038/oby.2007.118
  7. Newman AB, Nieto FJ, Guidry U, Lind BK, Redline S, Shahar E, Pickering TG, Quan SF, Sleep Heart Health Study Research Group. 2001. Relation of sleep-disordered breathing to cardiovascular disease risk factors: the Sleep Heart Health Study. Am J Epidemiol 154: 50-59. https://doi.org/10.1093/aje/154.1.50
  8. Roche F, Sforza E, Pichot V, Maudoux D, Garcin A, Celle S, Picard-Kossovsky M, Gaspoz JM, Barthelemy JC, PROOF Study Group. 2009. Obstructive sleep apnoea/hypopnea influences high-density lipoprotein cholesterol in the elderly. Sleep Med 10: 882-886. https://doi.org/10.1016/j.sleep.2008.07.017
  9. Haseli-Mashhadi N, Dadd T, Pan A, Yu Z, Lin X, Franco OH. 2009. Sleep quality in middle-aged and elderly Chinese: distribution, associated factors and associations with cardio-metabolic risk factors. BMC Public Health 9: 130. https://doi.org/10.1186/1471-2458-9-130
  10. Martins PJ, Fernandes L, de Oliveira AC, Tufik S, D'Almeida V. 2011. Type of diet modulates the metabolic response to sleep deprivation in rats. Nutr Metab 8: 86. https://doi.org/10.1186/1743-7075-8-86
  11. Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, Mori Y, Ide T, Murakami K, Tsuboyama-Kasaoka N, Ezaki O, Akanuma Y, Gavrilova O, Vinson C, Reitman ML, Kagechika H, Shudo K, Yoda M, Nakano Y, Tobe K, Nagai R, Kimura S, Tomita M, Froguel P, Kadowaki T. 2001. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 7: 941-946. https://doi.org/10.1038/90984
  12. Knutson KL, Van Cauter E. 2008. Associations between sleep loss and increased risk of obesity and diabetes. Ann N Y Acad Sci 1129: 287-304. https://doi.org/10.1196/annals.1417.033
  13. Van Cauter E, Knutson KL. 2008. Sleep and the epidemic of obesity in children and adults. Eur J Endocrinol 159: S59-S66. https://doi.org/10.1530/EJE-08-0298
  14. Nedeltcheva AV, Kilkus JM, Imperial J, Kasza K, Schoeller DA, Penev PD. 2009. Sleep curtailment is accompanied by increased intake of calories from snacks. Am J Clin Nutr 89: 126-133. https://doi.org/10.3945/ajcn.2008.26574
  15. Shi Z, McEvoy M, Luu J, Attia J. 2008. Dietary fat and sleep duration in Chinese men and women. Int J Obes (Lond) 32: 1835-1840. https://doi.org/10.1038/ijo.2008.191
  16. Baik I, Jun N, Yoon D, Shin C. 2013. Sleep fragmentation affects LDL-cholesterol and adipocytokines independent of food intake in rats. Sleep Biol Rhythms 11: 74-81. https://doi.org/10.1111/sbr.12007
  17. Yoon DW, Lee SK, Yun CH, Baik IK, Shin C. 2012. Validation of a walking wheel method to fragment sleep in rats. Sleep Med Res 3: 7-14. https://doi.org/10.17241/smr.2012.3.1.7
  18. Balogh Z, Foris G, Kosztaczky B, Paragh G Jr, Seres I, Zsiros E, Konya G, Paragh G. 2007. The concentration dependent biphasic effect of leptin on endogenous cholesterol synthesis in human monocytes. Peptides 28: 2081-2083. https://doi.org/10.1016/j.peptides.2007.07.004
  19. Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S, Yamashita S, Noda M, Kita S, Ueki K, Eto K, Akanuma Y, Froguel P, Foufelle F, Ferre P, Carling D, Kimura S, Nagai R, Kahn BB, Kadowaki T. 2002. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med 8: 1288-1295. https://doi.org/10.1038/nm788
  20. Dubuc GR, Phinney SD, Stern JS, Havel PJ. 1998. Changes of serum leptin and endocrine and metabolic parameters after 7 days of energy restriction in men and women. Metabolism 47: 429-434. https://doi.org/10.1016/S0026-0495(98)90055-5
  21. Asterholm IW, Scherer PE. 2010. Enhanced metabolic flexibility associated with elevated adiponectin levels. Am J Pathol 176: 1364-1376. https://doi.org/10.2353/ajpath.2010.090647
  22. 2008 sleep in America poll. National Sleep Foundation. https://sleepfoundation.org/sites/default/files/2008%20POLL%20SOF.PDF (accessed Aug 2016).