Effects of acute sleep loss on leptin, ghrelin, and adiponectin in adults with healthy weight and obesity: A laboratory study.

OBJECTIVE: This study investigated whether blood concentrations of leptin, ghrelin, and adiponectin are affected by acute total sleep deprivation in a sex- and weight-specific manner. METHODS: A total of 44 participants (mean age 24.9 years; 20 women; 19 with obesity) participated in a crossover design, including one night of sleep deprivation and one night of sleep in the laboratory. After each night, fasting blood was collected. RESULTS: After sleep deprivation, fasting levels of leptin were lower (mean [SE], vs. sleep: 17.3 [2.6] vs. 18.6 [2.8] ng/mL), whereas those of ghrelin and adiponectin were higher (839.4 [77.5] vs. 741.4 [63.2] pg/mL and 7.5 [0.6] vs. 6.8 [0.6] µg/mL, respectively; all p < 0.05). The changes in leptin and adiponectin following sleep loss were more pronounced among women. Furthermore, the ghrelin increase was stronger among those with obesity after sleep loss. Finally, the sleep loss-induced increase in adiponectin was more marked among normal-weight participants. CONCLUSIONS: Acute sleep deprivation reduces blood concentrations of the satiety hormone leptin. With increased blood concentrations of ghrelin and adiponectin, such endocrine changes may facilitate weight gain if persisting over extended periods of sleep loss. The observed sex- and weight-specific differences in leptin, ghrelin, and adiponectin call for further investigation.

Acute sleep loss increases CNS health biomarkers and compromises the ability to stay awake in a sex-and weight-specific manner.

Night shift work impairs vigilance performance, reduces the ability to stay awake, and compromises brain health. To investigate if the magnitude of these adverse night shift work effects differs between sexes and weight groups, 47 men and women with either normal weight or obesity participated in one night of sleep and one night of total sleep loss. During the night of sleep loss, participants' subjective sleepiness, vigilance performance, and ability to stay awake during 2-min quiet wake with eyes closed were repeatedly assessed. In addition, blood was collected in the morning after sleep loss and sleep to measure central nervous system (CNS) health biomarkers. Our analysis showed that women were sleepier during the night of sleep loss (P < 0.05) and spent more time in microsleep during quiet wake testing (P < 0.05). Finally, higher blood levels of neurofilament light chain, a biomarker of axonal damage, were found among women in the morning after sleep loss (P < 0.002). Compared with normal-weight subjects, those with obesity were more prone to fall asleep during quiet wake (P < 0.05) and exhibited higher blood levels of the CNS health biomarker pTau181 following sleep loss (P = 0.001). Finally, no differences in vigilance performance were noted between the sex and weight groups. Our findings suggest that the ability to stay awake during and the CNS health biomarker response to night shift work may differ between sexes and weight groups. Follow-up studies must confirm our findings under more long-term night shift work conditions.

Effects of One Night of Forced Wakefulness on Morning Resting Blood Pressure in Humans: The Role of Biological Sex and Weight Status.

Permanent night shift work is associated with adverse health effects, including elevated blood pressure (BP) and hypertension. Here, we examined the BP response to one night of forced wakefulness in a sitting position in a cohort without night shift work experience. According to a counterbalanced crossover design, 47 young adults with either obesity (N = 22; 10 women) or normal weight (N = 25; 11 women) participated in one night of sleep and one night of forced wakefulness under in-laboratory conditions. Resting ankle and brachial arterial BP were assessed in the morning, i.e., the time of the day when adverse cardiovascular events peak. After forced wakefulness, diastolic and mean arterial BP were ~4 mmHg higher at the ankle site and ~3 mmHg higher at the brachial site than after regular sleep (p < 0.05). The increase in BP following overnight forced wakefulness was more pronounced among men vs. women and more significant for diastolic BP at both sites among participants with normal weight vs. those with obesity. If confirmed in larger cohorts, including 24 h BP monitoring, people with occupations involving night shifts might benefit from regular BP monitoring. Particular attention should be paid to possible sex- and weight-specific effects of night shift work on BP.

How Sleep-Deprived People See and Evaluate Others' Faces: An Experimental Study.

Background: Acute sleep loss increases the brain's reactivity toward positive and negative affective stimuli. Thus, despite well-known reduced attention due to acute sleep loss, we hypothesized that humans would gaze longer on happy, angry, and fearful faces than neutral faces when sleep-deprived. We also examined if facial expressions are differently perceived after acute sleep loss. Methods: In the present, within-subjects study, 45 young adults participated in one night of total sleep deprivation and one night with an 8-hour sleep opportunity. On the morning after each night, an eye tracker was used to measure participants' time spent fixating images of happy, angry, fearful, and neutral faces. Participants also evaluated faces' attractiveness, trustworthiness, and healthiness on a 100-mm visual analog scale. Results: Following sleep loss, participants struggled more fixating the faces than after sleep. The decrease in total fixation duration ranged from 6.3% to 10.6% after sleep loss (P<0.001). Contrary to our hypothesis, the reduction in total fixation duration occurred irrespective of the displayed emotion (P=0.235 for sleep*emotion interaction) and was also present for the upper (P<0.001) but not the lower part of the faces (except for the lower part of angry faces). Overall, faces were evaluated as less trustworthy (-2.6 mm) and attractive (-3.6 mm) after sleep loss (p<0.05). Discussion: Facial expressions are crucial for social interactions. Thus, spending less time fixating on faces after acute sleep loss may come along with several problems for social interactions, eg, inaccurate and delayed judgment of the emotional state of others. In addition, more negative social impressions of others may lead to social withdrawal in sleep-deprived humans.

Blocking LDHA glycolytic pathway sensitizes glioblastoma cells to radiation and temozolomide.

PURPOSE: Up-regulation of lactate dehydrogenase LDHA, is a frequent event in human malignancies and relate to poor postoperative outcome. In the current study we examined the hypothesis that LDHA and anaerobic glycolysis, may contribute to the resistance of glioblastoma to radiotherapy and to temozolomide. METHODS AND MATERIALS: The expression of LDH5 isoenzyme (fully encoded by the LDHA gene) was assessed in human glioblastoma tissues. Experimental in vitro studies involved the T98 and U87 glioblastoma cell lines. Their sensitivity to radiotherapy and to temozolomide, following silencing of LDHA gene or following exposure to the LDHA chemical inhibitor 'oxamate' and to the glycolysis inhibitor '2-deoxy-d-glucose' (2DG), was studied. RESULTS: Glioblastoma tissues showed strong cytoplasmic and nuclear LDH5 expression in 0-90% (median 20%) of the neoplastic cells. T98 and U87 cell lines showed that blocking glycolysis, either with LDHA gene silencing or exposure to oxamate (30 mM) and blockage of glycolysis with 2DG (500 µM), results in enhanced radiation sensitivity, an effect that was more robust in the T98 radioresistant cell line. Furthermore, all three glycolysis targeting methods, significantly sensitized both cell lines to Temozolomide. CONCLUSIONS: The current study provides evidence that a large subgroup of human glioblastomas are highly glycolytic, and that inhibitors of glycolysis, like LDHA targeting agents, may prove of therapeutic importance by enhancing the efficacy of radiotherapy and temozolomide against this lethal disease.