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.