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1.
Am J Clin Nutr ; 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38636844

ABSTRACT

BACKGROUND: Fatty acids may influence lean tissue volume and skeletal muscle function. We previously reported in young lean participants that overfeeding PUFA compared with SFA induced greater lean tissue accumulation despite similar weight gain. OBJECTIVES: In a double-blind randomized controlled trial, we aimed to investigate if the differential effects of overfeeding SFA and PUFA on lean tissue accumulation could be replicated in individuals with overweight and identify potential determinants. Further, using substitution models, we investigated associations between SFA and PUFA concentrations with lean tissue volume in a large population-based sample (UK Biobank). METHODS: Sixty-one males and females with overweight [BMI (kg/m2): 27.3 (interquartile range (IQR), 25.4-29.3); age: 43 (IQR, 36-48)] were overfed SFA (palm oil) or n-6 (ω-6) PUFA (sunflower oil) for 8 wk. Lean tissue was assessed by MRI. We had access to n = 13,849 participants with data on diet, covariates, and MRI measurements of lean tissue, as well as 9119 participants with data on circulating fatty acids in the UK Biobank. RESULTS: Body weight gain mean (SD) was similar in PUFA (2.01 ± 1.90 kg) and SFA (2.31 ± 1.38 kg) groups. Lean tissue increased to a similar extent [0.54 ± 0.93 L and 0.67 ± 1.21 L for PUFA and SFA groups, respectively, with a difference between groups of 0.07 (-0.21, 0.35)]. We observed no differential effects on circulating amino acids, myostatin, or IL-15 and no clear determinants of lean tissue accumulation. Similar nonsignificant results for SFA and PUFA were observed in UK Biobank, but circulating fatty acids demonstrated ambiguous and sex-dependent associations. CONCLUSIONS: Overfeeding SFA or PUFA does not differentially affect lean tissue accumulation during 8 wk in individuals with overweight. A lack of dietary fat type-specific effects on lean tissue is supported by specified substitution models in a large population-based cohort consuming their habitual diet. This trial was registered at clinicaltrials.gov identifier as NCT02211612.

2.
JAMA Netw Open ; 7(3): e241147, 2024 Mar 04.
Article in English | MEDLINE | ID: mdl-38441893

ABSTRACT

Importance: Understanding the interplay between sleep duration, dietary habits, and the risk of developing type 2 diabetes (T2D) is crucial for public health and diabetes prevention strategies. Objective: To investigate the associations of type of diet and duration of sleep with the development of T2D. Design, Setting, and Participants: Data derived from the UK Biobank baseline investigation (2006-2010) were analyzed for this cohort study between May 1 and September 30, 2023. The association between sleep duration and healthy dietary patterns with the risk of T2D was investigated during a median (IQR) follow-up of 12.5 (11.8-13.2) years (end of follow-up, September 30, 2021). Exposure: For the analysis, 247 867 participants were categorized into 4 sleep duration groups: normal (7-8 hours per day), mild short (6 hours per day), moderate short (5 hours per day), and extreme short (3-4 hours per day). Their dietary habits were evaluated based on population-specific consumption of red meat, processed meat, fruits, vegetables, and fish, resulting in a healthy diet score ranging from 0 (unhealthiest) to 5 (healthiest). Main Outcomes and Measures: Cox proportional hazards regression analysis was used to calculate hazard ratios (HRs) and 95% CIs for the development of T2D across various sleep duration groups and healthy diet scores. Results: The cohort comprised 247 867 participants with a mean [SD] age of 55.9 [8.1] years, of whom 52.3% were female. During the follow-up, 3.2% of participants were diagnosed with T2D based on hospital registry data. Cox regression analysis, adjusted for confounding variables, indicated a significant increase in the risk of T2D among participants with 5 hours or less of daily sleep. Individuals sleeping 5 hours per day exhibited a 1.16 adjusted HR (95% CI, 1.05-1.28), and individuals sleeping 3 to 4 hours per day exhibited a 1.41 adjusted HR (95% CI, 1.19-1.68) compared with individuals with normal sleep duration. Furthermore, individuals with the healthiest dietary patterns had a reduced risk of T2D (HR, 0.75 [95% CI, 0.63-0.88]). The association between short sleep duration and increased risk of T2D persisted even for individuals following a healthy diet, but there was no multiplicative interaction between sleep duration and healthy diet score. Conclusions and Relevance: In this cohort study involving UK residents, habitual short sleep duration was associated with increased risk of developing T2D. This association persisted even among participants who maintained a healthy diet. To validate these findings, further longitudinal studies are needed, incorporating repeated measures of sleep (including objective assessments) and dietary habits.


Subject(s)
Diabetes Mellitus, Type 2 , Sleep Duration , Adult , Animals , Female , Humans , Child , Male , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/etiology , Cohort Studies , Diet , Sleep
3.
Obesity (Silver Spring) ; 31(7): 1755-1766, 2023 07.
Article in English | MEDLINE | ID: mdl-37245331

ABSTRACT

OBJECTIVE: Although intake of specific macronutrients has been associated with sleep parameters, interventional evidence is lacking. Therefore, this randomized trial was conducted to examine how a more unhealthy high-fat/high-sugar (HFHS) diet impacts sleep in humans. METHODS: In a crossover study, 15 healthy young men consumed two isocaloric diets in random order for a week: an HFHS and a low-fat/low-sugar diet. Following each diet, in-lab sleep was recorded using polysomnography during a full night of sleep and during recovery sleep after extended wakefulness. Sleep duration, macrostructure, and microstructure (oscillatory pattern and slow waves) were investigated using machine learning-based algorithms. RESULTS: Sleep duration did not differ across the diets based on actigraphy and the in-lab polysomnography. Sleep macrostructure was similar after 1 week on each diet. Compared with the low-fat/low-sugar diet, consumption of the HFHS diet resulted in reduced delta power, delta to beta ratio, and slow wave amplitude but increased alpha and theta power during deep sleep. During recovery sleep, similar sleep oscillatory changes were observed. CONCLUSIONS: Short-term consumption of a more unhealthy diet alters sleep oscillatory features that regulate the restorative properties of sleep. Whether such changes can mediate adverse health outcomes associated with consumption of an unhealthier diet warrants investigation.


Subject(s)
Diet, Fat-Restricted , Sleep , Male , Humans , Cross-Over Studies , Polysomnography , Sugars
4.
Chest ; 164(2): 503-516, 2023 08.
Article in English | MEDLINE | ID: mdl-36925044

ABSTRACT

BACKGROUND: OSA is a common sleep-breathing disorder linked to increased risk of cardiovascular disease. Intermittent upper airway obstruction and hypoxia, hallmarks of OSA, have been shown in animal models to induce substantial changes to the gut microbiota composition, and subsequent transplantation of fecal matter to other animals induced changes in BP and glucose metabolism. RESEARCH QUESTION: Does OSA in adults associate with the composition and functional potential of the human gut microbiota? STUDY DESIGN AND METHODS: We used respiratory polygraphy data from up to 3,570 individuals 50 to 64 years of age from the population-based Swedish Cardiopulmonary bioimage Study combined with deep shotgun metagenomics of fecal samples to identify cross-sectional associations between three OSA parameters covering apneas and hypopneas, cumulative sleep time in hypoxia, and number of oxygen desaturation events with gut microbiota composition. Data collection about potential confounders was based on questionnaires, onsite anthropometric measurements, plasma metabolomics, and linkage with the Swedish Prescribed Drug Register. RESULTS: We found that all three OSA parameters were associated with lower diversity of species in the gut. Furthermore, in multivariable-adjusted analysis, the OSA-related hypoxia parameters were associated with the relative abundance of 128 gut bacterial species, including higher abundance of Blautia obeum and Collinsella aerofaciens. The latter species was also independently associated with increased systolic BP. Furthermore, the cumulative time in hypoxia during sleep was associated with the abundance of genes involved in nine gut microbiota metabolic pathways, including propionate production from lactate. Finally, we observed two heterogeneous sets of plasma metabolites with opposite association with species positively and negatively associated with hypoxia parameters, respectively. INTERPRETATION: OSA-related hypoxia, but not the number of apneas/hypopneas, is associated with specific gut microbiota species and functions. Our findings lay the foundation for future research on the gut microbiota-mediated health effects of OSA.


Subject(s)
Gastrointestinal Microbiome , Sleep Apnea, Obstructive , Adult , Animals , Humans , Cross-Sectional Studies , Sweden/epidemiology , Hypoxia
5.
Transl Psychiatry ; 13(1): 32, 2023 02 01.
Article in English | MEDLINE | ID: mdl-36726008

ABSTRACT

Short nighttime sleep duration impairs the immune response to virus vaccination, and long nighttime sleep duration is associated with poor health status. Thus, we hypothesized that short (<6 h) and long (>9 h) nighttime sleepers have a higher post-COVID risk than normal nighttime sleepers, despite two doses of mRNA vaccine (which has previously been linked to lower odds of long-lasting COVID-19 symptoms). Post-COVID was defined as experiencing at least one core COVID-19 symptom for at least three months (e.g., shortness of breath). Multivariate logistic regression adjusting for age, sex, BMI, and other factors showed in 9717 respondents (age span 18-99) that two mRNA vaccinations lowered the risk of suffering from post-COVID by about 21% (p < 0.001). When restricting the analysis to double-vaccinated respondents (n = 5918), short and long sleepers exhibited a greater post-COVID risk than normal sleepers (adjusted OR [95%-CI], 1.56 [1.29, 1.88] and 1.87 [1.32, 2.66], respectively). Among respondents with persistent sleep duration patterns during the pandemic compared to before the pandemic, short but not long sleep duration was significantly associated with the post-COVID risk (adjusted OR [95%-CI], 1.59 [1.24, 2.03] and 1.18 [0.70, 1.97], respectively). No significant association between sleep duration and post-COVID symptoms was observed in those reporting positive SARS-CoV-2 test results (n = 538). Our findings suggest that two mRNA vaccinations against SARS-CoV-2 are associated with a lower post-COVID risk. However, this protection may be less pronounced among those sleeping less than 6 h per night. Our findings warrant replication in cohorts with individuals with confirmed SARS-CoV-2 infection.


Subject(s)
COVID-19 , Sleep Wake Disorders , Humans , Sleep Duration , COVID-19/prevention & control , COVID-19/complications , SARS-CoV-2 , Sleep/physiology , Sleep Wake Disorders/epidemiology
6.
JCI Insight ; 8(6)2023 03 22.
Article in English | MEDLINE | ID: mdl-36787197

ABSTRACT

The molecular clock machinery regulates several homeostatic rhythms, including glucose metabolism. We previously demonstrated that Roux-en-Y gastric bypass (RYGB) has a weight-independent effect on glucose homeostasis and transiently reduces food intake. In this study we investigate the effects of RYGB on diurnal eating behavior as well as on the molecular clock and this clock's requirement for the metabolic effects of this bariatric procedure in obese mice. We find that RYGB reversed the high-fat diet-induced disruption in diurnal eating pattern during the early postsurgery phase of food reduction. Dark-cycle pair-feeding experiments improved glucose tolerance to the level of bypass-operated animals during the physiologic fasting phase (Zeitgeber time 2, ZT2) but not the feeding phase (ZT14). Using a clock gene reporter mouse model (mPer2Luc), we reveal that RYGB induced a liver-specific phase shift in peripheral clock oscillation with no changes to the central clock activity within the suprachiasmatic nucleus. In addition, we show that weight loss effects were attenuated in obese ClockΔ19 mutant mice after RYGB that also failed to improve glucose metabolism after surgery, specifically hepatic glucose production. We conclude that RYGB reprograms the peripheral clock within the liver early after surgery to alter diurnal eating behavior and regulate hepatic glucose flux.


Subject(s)
Gastric Bypass , Insulin Resistance , Mice , Animals , Glucose/metabolism , Gastric Bypass/methods , Blood Glucose/metabolism , Insulin Resistance/physiology , Feeding Behavior , Liver/metabolism
7.
J Sleep Res ; 32(2): e13743, 2023 04.
Article in English | MEDLINE | ID: mdl-36184925

ABSTRACT

Weighted blankets have emerged as a potential non-pharmacological intervention to ease conditions such as insomnia and anxiety. Despite a lack of experimental evidence, these alleged effects are frequently attributed to a reduced activity of the endogenous stress systems and an increased release of hormones such as oxytocin and melatonin. Thus, the aim of the present in-laboratory crossover study (26 young and healthy participants, including 15 men and 11 women) was to investigate if using a weighted blanket (~12% of body weight) at bedtime resulted in higher salivary concentrations of melatonin and oxytocin compared with a light blanket (~2.4% of body weight). We also examined possible differences in salivary concentrations of the stress hormone cortisol, salivary alpha-amylase activity (as an indicative metric of sympathetic nervous system activity), subjective sleepiness, and sleep duration. When using a weighted blanket, the 1 hour increase of salivary melatonin from baseline (i.e., 22:00) to lights off (i.e., 23:00) was about 32% higher (p = 0.011). No other significant differences were found between the blanket conditions, including subjective sleepiness and total sleep duration. Our study is the first to suggest that using a weighted blanket may result in a more significant release of melatonin at bedtime. Future studies should investigate whether the stimulatory effect on melatonin secretion is observed on a nightly basis when frequently using a weighted blanket over weeks to months. It remains to be determined whether the observed increase in melatonin may be therapeutically relevant for the previously described effects of the weighted blanket on insomnia and anxiety.


Subject(s)
Melatonin , Sleep Initiation and Maintenance Disorders , Male , Humans , Adult , Female , Melatonin/pharmacology , Oxytocin/pharmacology , Cross-Over Studies , Sleepiness , Sleep/physiology , Body Weight , Circadian Rhythm/physiology
8.
Science ; 378(6617): 276-284, 2022 10 21.
Article in English | MEDLINE | ID: mdl-36264811

ABSTRACT

Misalignment of feeding rhythms with the light-dark cycle leads to disrupted peripheral circadian clocks and obesity. Conversely, restricting feeding to the active period mitigates metabolic syndrome through mechanisms that remain unknown. We found that genetic enhancement of adipocyte thermogenesis through ablation of the zinc finger protein 423 (ZFP423) attenuated obesity caused by consumption of a high-fat diet during the inactive (light) period by increasing futile creatine cycling in mice. Circadian control of adipocyte creatine metabolism underlies the timing of diet-induced thermogenesis, and enhancement of adipocyte circadian rhythms through overexpression of the clock activator brain and muscle Arnt-like protein-1 (BMAL1) ameliorated metabolic complications during diet-induced obesity. These findings uncover rhythmic creatine-mediated thermogenesis as an essential mechanism that drives metabolic benefits during time-restricted feeding.


Subject(s)
Adipocytes , Circadian Clocks , Circadian Rhythm , Creatine , DNA-Binding Proteins , Diet, High-Fat , Obesity , Thermogenesis , Transcription Factors , Animals , Mice , Adipocytes/metabolism , ARNTL Transcription Factors/genetics , Creatine/metabolism , Obesity/etiology , Obesity/prevention & control , Thermogenesis/genetics , Time Factors , Diet, High-Fat/adverse effects , DNA-Binding Proteins/genetics , Transcription Factors/genetics , Mice, Knockout
9.
Front Nutr ; 9: 889926, 2022.
Article in English | MEDLINE | ID: mdl-35619965

ABSTRACT

Meal timing has significant effects on health. However, whether meal timing is associated with the risk of developing and dying of cancer is not well-researched in humans. In the present study, we used data from 941 community-dwelling men aged 71 years who participated in the Uppsala Longitudinal Study of Adult Men to examine the association of meal timing with cancer morbidity and fatal cancer. The following meal timing variables were derived from 7-day food diaries: (i) daily eating duration, i.e., the time between the first and last eating episode of an arbitrary day; (ii) the calorically weighted midpoint of the daily eating interval, a proxy of when the eating window typically occurs during an arbitrary day; and (iii) the day-to-day variability in the timing of eating. We also assessed the reported daily energy intake reliability using the Goldberg method. During a mean observational period of 13.4 years, 277 men (29.4%) were diagnosed with cancer. Furthermore, 191 men (20%) died from cancer during 14.7 years of follow-up. As shown by Cox regression adjusted for potential confounders (e.g., smoking status and daily energy intake), men with reliable dietary reports whose daily eating intervals were on average 13 h long had a 2.3-fold greater fatal cancer risk than men whose daily eating windows were on average about 11 h long. We also found that men with an average day-to-day variability in the timing of eating of 48 to 74 min had a 2- to 2.2-fold higher fatal cancer risk than those with the lowest average day-to-day variability in the timing of eating (i.e., 23 min). No clear associations were found in men with inadequate dietary reports, emphasizing the need to consider the reliability of dietary records in nutritional epidemiology. To fully unlock its potential, studies are needed to test whether recommendations to time-restrict the 24-h eating interval and reduce day-to-day variability in the timing of eating can meaningfully alter the risk of death due to cancer.

10.
Mol Metab ; 58: 101445, 2022 04.
Article in English | MEDLINE | ID: mdl-35092845

ABSTRACT

OBJECTIVE: Physical exercise-especially at high intensity-is known to impose cardiac stress, as mirrored by, e.g., increased blood levels of cardiac stress biomarkers such as cardiac Troponin T (cTnT) and NT-proBNP. We examined healthy young participants to determine whether a few nights of short sleep duration alter the effects of acute exercise on these blood biomarkers. METHODS: Sixteen men participated in a randomized order in a crossover design, comprising three consecutive nights of a) normal sleep duration (NS, 8.5 h of sleep/night) and b) sleep restriction (SR, 4.25 h of sleep/night). Blood was repeatedly sampled for determination of NT-proBNP and cTnT serum levels before and after a high-intensity exercise protocol (i.e., 75% VO2maxReserve cycling on an ergometer). RESULTS: Under pre-exercise sedentary conditions, blood levels of cTnT and NT-proBNP did not significantly differ between the sleep conditions (P > 0.10). However, in response to exercise, the surge of circulating cTnT was significantly greater following SR than NS (+37-38% at 120-240 min post-exercise, P ≤ 0.05). While blood levels of NT-proBNP rose significantly in response to exercise, they did not differ between the sleep conditions. CONCLUSION: Recurrent sleep restriction may increase the cardiac stress response to acute high-intensity exercise in healthy young individuals. However, our findings must be further confirmed in women, older subjects and in patients with a history of heart disease.


Subject(s)
Heart , Troponin T , Biomarkers , Cross-Over Studies , Exercise/physiology , Female , Heart/physiology , Humans , Male , Sleep
11.
Sleep ; 45(2)2022 02 14.
Article in English | MEDLINE | ID: mdl-34432058

ABSTRACT

STUDY OBJECTIVES: Individual circadian type is a ubiquitous trait defining sleep, with eveningness often associated with poorer sleep and mental health than morningness. However, it is unknown whether COVID-19 pandemic has differentially affected sleep and mental health depending on the circadian type. Here, the differences in sleep and mental health between circadian types are examined globally before and during the COVID-19 pandemic. METHODS: The sample collected between May and August 2020 across 12 countries/regions consisted of 19 267 adults with information on their circadian type. Statistical analyses were performed by using Complex Sample procedures, stratified by country and weighted by the number of inhabitants in the country/area of interest and by the relative number of responders in that country/area. RESULTS: Evening-types had poorer mental health, well-being, and quality of life or health than other circadian types during the pandemic. Sleep-wake schedules were delayed especially on working days, and evening-types reported an increase in sleep duration. Sleep problems increased in all circadian types, but especially among evening-types, moderated by financial suffering and confinement. Intermediate-types were less vulnerable to sleep changes, although morningness protected from most sleep problems. These findings were confirmed after adjusting for age, sex, duration of the confinement, or socio-economic status during the pandemic. CONCLUSIONS: These findings indicate an alarming increase in sleep and mental health problems, especially among evening-types as compared to other circadian types during the pandemic.


Subject(s)
COVID-19 , Pandemics , Adult , Circadian Rhythm , Humans , Mental Health , Quality of Life , SARS-CoV-2 , Sleep , Surveys and Questionnaires
12.
J Sleep Res ; 31(2): e13472, 2022 04.
Article in English | MEDLINE | ID: mdl-34476847

ABSTRACT

The hormone fibroblast growth factor 21 (FGF21) modulates tissue metabolism and circulates at higher levels in metabolic conditions associated with chronic sleep-wake disruption, such as type 2 diabetes and obesity. In the present study, we investigated whether acute sleep loss impacts circulating levels of FGF21 and tissue-specific production, and response pathways linked to FGF21. A total of 15 healthy normal-weight young men participated in a randomised crossover study with two conditions, sleep loss versus an 8.5-hr sleep window. The evening before each intervention, fasting blood was collected. Fasting, post-intervention morning skeletal muscle and adipose tissue samples underwent quantitative polymerase chain reaction and DNA methylation analyses, and serum FGF21 levels were measured before and after an oral glucose tolerance test. Serum levels of FGF21 were higher after sleep loss compared with sleep, both under fasting conditions and following glucose intake (~27%-30%, p = 0.023). Fasting circulating levels of fibroblast activation protein, a protein which can degrade circulating FGF21, were not altered by sleep loss, whereas DNA methylation in the FGF21 promoter region increased only in adipose tissue. However, even though specifically the muscle exhibited transcriptional changes indicating adverse alterations to redox and metabolic homeostasis, no tissue-based changes were observed in expression of FGF21, its receptors, or selected signalling targets, in response to sleep loss. In summary, we found that acute sleep loss resulted in increased circulating levels of FGF21 in healthy young men, which may occur independent of a tissue-based stress response in metabolic peripheral tissues. Further studies may decipher whether changes in FGF21 signalling after sleep loss modulate metabolic outcomes associated with sleep or circadian disruption.


Subject(s)
Diabetes Mellitus, Type 2 , Cross-Over Studies , Fibroblast Growth Factors/genetics , Fibroblast Growth Factors/metabolism , Humans , Male , Sleep
13.
BMJ Open ; 11(12): e050672, 2021 12 13.
Article in English | MEDLINE | ID: mdl-34903540

ABSTRACT

OBJECTIVES: Sleep is important for human health and well-being. No previous study has assessed whether the COVID-19 pandemic impacts sleep and daytime function across the globe. METHODS: This large-scale international survey used a harmonised questionnaire. Fourteen countries participated during the period of May-August 2020. Sleep and daytime problems (poor sleep quality, sleep onset and maintenance problems, nightmares, hypnotic use, fatigue and excessive sleepiness) occurring 'before' and 'during' the pandemic were investigated. In total, 25 484 people participated and 22 151 (86.9%) responded to the key parameters and were included. Effects of COVID-19, confinement and financial suffering were considered. In the fully adjusted logistic regression models, results (weighted and stratified by country) were adjusted for gender, age, marital status, educational level, ethnicity, presence of sleep problems before COVID-19 and severity of the COVID-19 pandemic in each country at the time of the survey. RESULTS: The responders were mostly women (64%) with a mean age 41.8 (SD 15.9) years (median 39, range 18-95). Altogether, 3.0% reported having had COVID-19; 42.2% reported having been in confinement; and 55.9% had suffered financially. All sleep and daytime problems worsened during the pandemic by about 10% or more. Also, some participants reported improvements in sleep and daytime function. For example, sleep quality worsened in about 20% of subjects and improved in about 5%. COVID-19 was particularly associated with poor sleep quality, early morning awakening and daytime sleepiness. Confinement was associated with poor sleep quality, problems falling asleep and decreased use of hypnotics. Financial suffering was associated with all sleep and daytime problems, including nightmares and fatigue, even in the fully adjusted logistic regression models. CONCLUSIONS: Sleep problems, fatigue and excessive sleepiness increased significantly worldwide during the first phase of the COVID-19 pandemic. Problems were associated with confinement and especially with financial suffering.


Subject(s)
COVID-19 , Pandemics , Adult , Female , Humans , SARS-CoV-2 , Sleep Quality , Surveys and Questionnaires
14.
Nat Metab ; 3(12): 1621-1632, 2021 12.
Article in English | MEDLINE | ID: mdl-34903884

ABSTRACT

In mammals, circadian rhythms are entrained to the light cycle and drive daily oscillations in levels of NAD+, a cosubstrate of the class III histone deacetylase sirtuin 1 (SIRT1) that associates with clock transcription factors. Although NAD+ also participates in redox reactions, the extent to which NAD(H) couples nutrient state with circadian transcriptional cycles remains unknown. Here we show that nocturnal animals subjected to time-restricted feeding of a calorie-restricted diet (TRF-CR) only during night-time display reduced body temperature and elevated hepatic NADH during daytime. Genetic uncoupling of nutrient state from NADH redox state through transduction of the water-forming NADH oxidase from Lactobacillus brevis (LbNOX) increases daytime body temperature and blood and liver acyl-carnitines. LbNOX expression in TRF-CR mice induces oxidative gene networks controlled by brain and muscle Arnt-like protein 1 (BMAL1) and peroxisome proliferator-activated receptor alpha (PPARα) and suppresses amino acid catabolic pathways. Enzymatic analyses reveal that NADH inhibits SIRT1 in vitro, corresponding with reduced deacetylation of SIRT1 substrates during TRF-CR in vivo. Remarkably, Sirt1 liver nullizygous animals subjected to TRF-CR display persistent hypothermia even when NADH is oxidized by LbNOX. Our findings reveal that the hepatic NADH cycle links nutrient state to whole-body energetics through the rhythmic regulation of SIRT1.


Subject(s)
Energy Metabolism , Fasting , NAD/metabolism , Sirtuin 1/genetics , Sirtuin 1/metabolism , Transcription, Genetic , Amino Acids/metabolism , Animals , Body Temperature , Circadian Rhythm , Diet , Fatty Acids/metabolism , Gene Expression Regulation , Liver/metabolism , Mice , Transcription Factors
15.
Nat Sci Sleep ; 13: 1711-1722, 2021.
Article in English | MEDLINE | ID: mdl-34675720

ABSTRACT

PURPOSE: Lifestyle and work habits have been drastically altered by restrictions due to the COVID-19 pandemic. Whether the associated changes in sleep timing modulate the risk of suffering from symptoms of insomnia, the most prevalent sleep disorder, is however incompletely understood. Here, we evaluate the association between the early pandemic-associated change in 1) the magnitude of social jetlag (SJL) - ie, the difference between sleep timing on working vs free days - and 2) symptoms of insomnia. PATIENTS AND METHODS: A total of 14,968 anonymous participants (mean age: 40 years; 64% females) responded to a standardized internet-based survey distributed across 14 countries. Using logistic multivariate regression, we examined the association between the degree of social jetlag and symptoms of insomnia, controlling for important confounders like social restriction extension, country specific COVID-19 severity and psychological distress, for example. RESULTS: In response to the pandemic, participants reported later sleep timing, especially during workdays. Most participants (46%) exhibited a reduction in their SJL, whereas 20% increased it; and 34% reported no change in SJL. Notably, we found that both increased and decreased SJL, as a result of the COVID-19 pandemic, were associated with later sleep midpoint (indicating a later chronotype) as well as more recurrent and moderate-to-severe symptoms of insomnia (about 23-54% higher odds ratio than subjects with unchanged SJL). Primarily those with reduced SJL shifted their bedtimes to a later timepoint, compared with those without changes in SJL. CONCLUSION: Our findings offer important insights into how self-reported changes to the stability of sleep/wake timing, as reflected by changes in SJL, can be a critical marker of the risk of experiencing insomnia-related symptoms - even when individuals manage to reduce their social jetlag. These findings emphasize the clinical importance of analyzing sleep-wake regularity.

16.
Sleep Med ; 87: 38-45, 2021 11.
Article in English | MEDLINE | ID: mdl-34508986

ABSTRACT

IMPORTANCE AND STUDY OBJECTIVE: The COVID-19 pandemic has produced unprecedented changes in social, work, and leisure activities, which all have had major impact on sleep and psychological well-being. This study documented the prevalence of clinical cases of insomnia, anxiety, and depression and selected risk factors (COVID-19, confinement, financial burden, social isolation) during the first wave of the pandemic in 13 countries throughout the world. DESIGN AND PARTICIPANTS: International, multi-center, harmonized survey of 22 330 adults (mean age = 41.9 years old, range 18-95; 65.6% women) from the general population in 13 countries and four continents. Participants were invited to complete a standardized web-based survey about sleep and psychological symptoms during the first wave of the COVID-19 pandemic from May to August 2020. RESULTS: Clinical insomnia symptoms were reported by 36.7% (95% CI, 36.0-37.4) of respondents and 17.4% (95% CI, 16.9-17.9) met criteria for a probable insomnia disorder. There were 25.6% (95% CI, 25.0-26.2) with probable anxiety and 23.1% (95% CI, 22.5-23.6) with probable depression. Rates of insomnia symptoms (>40%) and insomnia disorder (>25%) were significantly higher in women, younger age groups, and in residents of Brazil, Canada, Norway, Poland, USA, and United Kingdom compared to residents from Asian countries (China and Japan, 8% for disorder and 22%-25% for symptoms) (all Ps < 0.01). Proportions of insomnia cases were significantly higher among participants who completed the survey earlier in the first wave of the pandemic relative to those who completed it later. Risks of insomnia were higher among participants who reported having had COVID-19, who reported greater financial burden, were in confinement for a period of four to five weeks, and living alone or with more than five people in same household. These associations remained significant after controlling for age, sex, and psychological symptoms. CONCLUSION AND RELEVANCE: Insomnia, anxiety, and depression were very prevalent during the first wave of the COVID-19 pandemic. Public health prevention programs are needed to prevent chronicity and reduce long-term adverse outcomes associated with chronic insomnia and mental health problems.


Subject(s)
COVID-19 , Sleep Initiation and Maintenance Disorders , Adolescent , Adult , Aged , Aged, 80 and over , Anxiety/epidemiology , Cross-Sectional Studies , Depression/epidemiology , Female , Humans , Male , Middle Aged , Pandemics , SARS-CoV-2 , Sleep Initiation and Maintenance Disorders/epidemiology , Young Adult
18.
Ann N Y Acad Sci ; 1506(1): 18-34, 2021 12.
Article in English | MEDLINE | ID: mdl-34341993

ABSTRACT

The human circadian system consists of the master clock in the suprachiasmatic nuclei of the hypothalamus as well as in peripheral molecular clocks located in organs throughout the body. This system plays a major role in the temporal organization of biological and physiological processes, such as body temperature, blood pressure, hormone secretion, gene expression, and immune functions, which all manifest consistent diurnal patterns. Many facets of modern life, such as work schedules, travel, and social activities, can lead to sleep/wake and eating schedules that are misaligned relative to the biological clock. This misalignment can disrupt and impair physiological and psychological parameters that may ultimately put people at higher risk for chronic diseases like cancer, cardiovascular disease, and other metabolic disorders. Understanding the mechanisms that regulate sleep circadian rhythms may ultimately lead to insights on behavioral interventions that can lower the risk of these diseases. On February 25, 2021, experts in sleep, circadian rhythms, and chronobiology met virtually for the Keystone eSymposium "Sleep & Circadian Rhythms: Pillars of Health" to discuss the latest research for understanding the bidirectional relationships between sleep, circadian rhythms, and health and disease.


Subject(s)
Circadian Rhythm/physiology , Congresses as Topic/trends , Meals/physiology , Research Report , Sleep/physiology , Animals , Blood Pressure/physiology , Cardiovascular Diseases/genetics , Cardiovascular Diseases/physiopathology , Cardiovascular Diseases/psychology , Circadian Clocks/physiology , Humans , Meals/psychology , Neoplasms/genetics , Neoplasms/physiopathology , Neoplasms/psychology , Risk Factors
19.
Sleep Breath ; 25(2): 849-860, 2021 06.
Article in English | MEDLINE | ID: mdl-33907966

ABSTRACT

PURPOSE: Obstructive sleep apnea (OSA) may increase the risk of severe COVID-19; however, the level of potential modulation has not yet been established. The objective of the study was to determine the association between high risk of OSA, comorbidities, and increased risk for COVID-19, hospitalization, and intensive care unit (ICU) treatment. METHODS: We conducted a cross-sectional population-based web survey in adults in 14 countries/regions. The survey included sociodemographic variables and comorbidities. Participants were asked questions about COVID-19, hospitalization, and ICU treatment. Standardized questionnaire (STOP questionnaire for high risk of OSA) was included. Multivariable logistic regression was conducted adjusting for various factors. RESULTS: Out of 26,539 respondents, 20,598 (35.4% male) completed the survey. Mean age and BMI of participants were 41.5 ± 16.0 years and 24.0 ± 5.0 kg/m2, respectively. The prevalence of physician-diagnosed OSA was 4.1% and high risk of OSA was 9.5%. We found that high risk of OSA (adjusted odds ratio (aOR) 1.72, 95% confidence interval (CI): 1.20, 2.47) and diabetes (aOR 2.07, 95% CI: 1.23, 3.48) were associated with reporting of a COVID-19 diagnosis. High risk for OSA (aOR 2.11, 95% CI: 1.10-4.01), being male (aOR: 2.82, 95% CI: 1.55-5.12), having diabetes (aOR: 3.93, 95% CI: 1.70-9.12), and having depression (aOR: 2.33, 95% CI: 1.15-4.77) were associated with increased risk of hospitalization or ICU treatment. CONCLUSIONS: Participants at high risk of OSA had increased odds of having COVID-19 and were two times more likely to be hospitalized or treated in ICU.


Subject(s)
COVID-19 Testing/statistics & numerical data , COVID-19/epidemiology , Health Status , Sleep Apnea, Obstructive/epidemiology , Adult , COVID-19/diagnosis , Comorbidity , Cross-Sectional Studies , Depression/epidemiology , Diabetes Mellitus, Type 2/epidemiology , Female , Humans , Male , Middle Aged , Prevalence , Risk Factors , Sex Factors , Sleep Apnea, Obstructive/diagnosis , Snoring/epidemiology
20.
Clocks Sleep ; 3(2): 251-258, 2021 Apr 22.
Article in English | MEDLINE | ID: mdl-33921946

ABSTRACT

The COVID-19 pandemic and related restrictions, such as stay-at-home-orders, have significantly altered daily routines and lifestyles. Given their importance for metabolic health, we herein compared sleep and meal timing parameters during vs. before the COVID-19 pandemic based on subjective recall, in an anonymous Swedish survey. Among 191 adults (mean age: 47 years; 77.5% females), we show that social jetlag, i.e., the mismatch in sleep midpoint between work and free days, was reduced by about 17 min during the pandemic compared with the pre-pandemic state (p < 0.001). Concomitantly, respondents' sleep midpoint was shifted toward morning hours during workdays (p < 0.001). A later daily eating midpoint accompanied the shift in sleep timing (p = 0.001). This effect was mainly driven by a later scheduled first meal (p < 0.001). No difference in the timing of the day's last meal was found (p = 0.814). Although our survey was limited in terms of sample size and by being cross-sectional, our results suggest that the delay in sleep timing due to the COVID-19 pandemic was accompanied by a corresponding shift in the timing of early but not late meals.

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