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STUDY OBJECTIVES: Napping is a common habit in many countries. Nevertheless, studies about the chronic effects of napping on obesity are contradictory, and the molecular link between napping and metabolic alterations has yet to be studied. We aim to identify molecular mechanisms in adipose tissue (AT) that may connect napping and abdominal obesity. METHODS: In this cross-sectional study, we extracted the RNA repeatedly across 24h from cultured AT explants and performed RNA sequencing. Circadian rhythms were analyzed using 6 consecutive time points across 24 hours. We also assessed global gene expression in each group (nappers vs. non-nappers). RESULTS: With napping, there was a loss of rhythmicity in 88% of genes that showed circadian rhythmicity among non-nappers, a reduction in rhythm amplitudes of 29%, and significant phase changes from a coherent unimodal acrophase in non-nappers, towards a scattered and bimodal acrophase in nappers. Those genes that lost rhythmicity with napping were mainly involved in pathways of glucose and lipid metabolism, and of the circadian clock. Additionally, we found differential global gene expression between nappers and non-nappers with 34 genes down- and 32 genes up-regulated in nappers. The top up-regulated gene (IER3) and top down-regulated pseudogene (VDAC2P2) in nappers have been previously shown to be involved in inflammation. CONCLUSION: These new findings may have implications for our understanding of napping's effects on obesity and metabolic disorders.
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OBJECTIVE: Time-restricted eating (TRE), a dietary approach that confines food intake to specific time windows, has shown metabolic benefits. However, its impact on body weight loss remains inconclusive. The objective of this study was to investigate the influence of early TRE (eTRE) and delayed TRE (dTRE) on fat mobilization using human adipose tissue (AT) cultures. METHODS: Subcutaneous AT was collected from 21 participants with severe obesity. We assessed fat mobilization by measuring glycerol release in AT culture across four treatment conditions: control, eTRE, dTRE, and 24-h fasting. RESULTS: TRE had a significant impact on lipolysis (glycerol release [mean (SD)] in micromoles per hour per gram: control, 0.05 [0.003]; eTRE, 0.10 [0.006]; dTRE, 0.08 [0.005]; and fasting, 0.17 [0.008]; p < 0.0001). Both eTRE and dTRE increased lipolysis compared with the control group, with eTRE showing higher glycerol mobilization than dTRE during the overall 24-h time window, especially at the nighttime/habitual sleep episode (p < 0.0001). Further analysis of TRE based on fasting duration revealed that, independently of the time window, glycerol release increased with fasting duration (in micromoles per hour per gram: 8 h = 0.08 [0.001]; 12 h = 0.09 [0.008]; and 16 h of fasting = 0.12 [0.011]; p < 0.0001). CONCLUSIONS: This study provides insights into the potential benefits of TRE on fat mobilization and may guide the design of future dietary strategies for weight management and metabolic health.
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Melatonin is a pineal hormone that modulates the circadian system and exerts soporific and phase-shifting effects. It is also involved in many other physiological processes, such as those implicated in cardiovascular, endocrine, immune, and metabolic functions. However, the role of melatonin in glucose metabolism remains contradictory, and its action on human adipose tissue (AT) explants has not been demonstrated. We aimed to assess whether melatonin (a pharmacological dose) influences insulin sensitivity in human AT. This will help better understand melatonin administration's effect on glucose metabolism. Abdominal AT (subcutaneous and visceral) biopsies were obtained from 19 participants with severe obesity (age: 42.84 ± 12.48 years; body mass index: 43.14 ± 8.26 kg/m2) who underwent a laparoscopic gastric bypass. AT biopsies were exposed to four different treatments: control (C), insulin alone (I) (10 nM), melatonin alone (M) (5000 pg/mL), and insulin plus melatonin combined (I + M). All four conditions were repeated in both subcutaneous and visceral AT, and all were performed in the morning at 8 a.m. (n = 19) and the evening at 8 p.m. (in a subsample of n = 12). We used western blot analysis to determine insulin signaling (using the pAKT/tAKT ratio). Furthermore, RNAseq analyses were performed to better understand the metabolic pathways involved in the effect of melatonin on insulin signaling. As expected, insulin treatment (I) increased the pAKT/tAKT ratio compared with control (p < .0001). Furthermore, the addition of melatonin (I + M) resulted in a decrease in insulin signaling as compared with insulin alone (I); this effect was significant only during the evening time (not in the morning time). Further, RNAseq analyses in visceral AT during the evening condition (at 8 p.m.) showed that melatonin resulted in a prompt transcriptome response (around 1 h after melatonin addition), particularly by downregulating the insulin signaling pathway. Our results show that melatonin reduces insulin sensitivity in human AT during the evening. These results may partly explain the previous studies showing a decrease in glucose tolerance after oral melatonin administration in the evening or when eating late when endogenous melatonin is present.
Subject(s)
Insulin Resistance , Melatonin , Humans , Melatonin/pharmacology , Insulin Resistance/physiology , Adult , Male , Female , Middle Aged , Insulin/metabolism , Adipose Tissue/metabolism , Adipose Tissue/drug effectsABSTRACT
BACKGROUND: Circadian health refers to individuals' well-being and balance in terms of their circadian rhythm. It is influenced by external cues. In adults, a close relationship between circadian-related alterations and obesity has been described. However, studies in children are scarce, and circadian health and its association with obesity have not been evaluated globally. We aimed to assess whether circadian health differed between children with and without obesity as determined by a global circadian score (GCS) in a school-age population. METHODS: Four hundred and thirty-two children (7-12 years) were recruited in Spain. Non-invasive tools were used to calculate the GCS: (1) 7-day rhythm of wrist temperature (T), activity (A), position (P), an integrative variable that combines T, A, and P (TAP); (2) cortisol; and (3) 7-day food and sleep records. Body mass index, body fat percentage, waist circumference (WC), melatonin concentration, and cardiometabolic marker levels were determined. RESULTS: Circadian health, as assessed by the GCS, differed among children with obesity, overweight, and normal weight, with poorer circadian health among children with obesity. Children with obesity and abdominal obesity had 3.54 and 2.39 greater odds of having poor circadian health, respectively, than did those with normal weight or low WC. The percentage of rhythmicity, a marker of the robustness of the TAP rhythm, and the amplitude, both components of the GCS, decreased with increasing obesity. Different lifestyle behaviors were involved in the association between circadian health and obesity, particularly protein intake (P = 0.024), physical activity level (P = 0.076) and chronotype (P = 0.029). CONCLUSIONS: The GCS can capture the relationship between circadian health and obesity in school-age children. Protein intake, physical activity level, and chronotype were involved in this association. Early intervention based on improving circadian health may help to prevent childhood obesity.
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We aimed to systematically review and synthesize the available evidence regarding the link between dietary patterns and insomnia symptoms among the general population using observational studies. We reviewed 16,455 references, of which 37 studies met inclusion criteria with a total sample size of 591,223. There was a significant association of the Mediterranean diet (OR: 0.86; 95 % CI, 0.79, 0.93; P < 0.001; I2 = 32.68 %), a high-quality diet (OR: 0.66; 95 % CI, 0.48, 0.90; P = 0.010; I2 = 84.62 %), and an empirically-derived healthy dietary pattern (OR: 0.91; 95 % CI, 0.85, 0.98; P = 0.010; I2 = 57.14 %) with a decreased risk of insomnia symptoms. Moreover, the dietary glycemic index (OR: 1.16; 95 % CI, 1.08, 1.25; P < 0.001; I2 = 0.0 %), the dietary glycemic load (OR: 1.10; 95 % CI, 1.01, 1.20; P = 0.032; I2 = 74.36 %), and an empirically-derived unhealthy dietary pattern (OR: 1.20; 95 % CI, 1.01, 1.42; P = 0.040; I2 = 68.38 %) were linked with a higher risk of insomnia symptoms. Most individual studies were of good quality (NOS) but provided very low certainty of evidence (GRADE). Consistent data reveals that following healthy diets is associated with decreased insomnia symptoms prevalence, while adherence to an unhealthy pattern is associated with an increased prevalence of insomnia symptoms.
Subject(s)
Diet, Mediterranean , Sleep Initiation and Maintenance Disorders , Humans , Sleep Initiation and Maintenance Disorders/epidemiology , Glycemic Index , Diet , Dietary PatternsABSTRACT
BACKGROUND: While environmental factors play an important role in weight loss effectiveness, genetics may also influence its success. We examined whether a genome-wide polygenic score for BMI was associated with weight loss effectiveness and aimed to identify common genetic variants associated with weight loss. METHODS: Participants in the ONTIME study (n = 1210) followed a uniform, multimodal behavioral weight-loss intervention. We first tested associations between a genome-wide polygenic score for higher BMI and weight loss effectiveness (total weight loss, rate of weight loss, and attrition). We then conducted a genome-wide association study (GWAS) for weight loss in the ONTIME study and performed the largest weight loss meta-analysis with earlier studies (n = 3056). Lastly, we ran exploratory GWAS in the ONTIME study for other weight loss outcomes and related factors. RESULTS: We found that each standard deviation increment in the polygenic score was associated with a decrease in the rate of weight loss (Beta (95% CI) = -0.04 kg per week (-0.06, -0.01); P = 3.7 × 10-03) and with higher attrition after adjusting by treatment duration. No associations reached genome-wide significance in meta-analysis with previous GWAS studies for weight loss. However, associations in the ONTIME study showed effects consistent with published studies for rs545936 (MIR486/NKX6.3/ANK1), a previously noted weight loss locus. In the meta-analysis, each copy of the minor A allele was associated with 0.12 (0.03) kg/m2 higher BMI at week five of treatment (P = 3.9 × 10-06). In the ONTIME study, we also identified two genome-wide significant (P < 5×10-08) loci for the rate of weight loss near genes implicated in lipolysis, body weight, and metabolic regulation: rs146905606 near NFIP1/SPRY4/FGF1; and rs151313458 near LSAMP. CONCLUSION: Our findings are expected to help in developing personalized weight loss approaches based on genetics. CLINICAL TRIAL REGISTRATION: Obesity, Nutrigenetics, Timing, and Mediterranean (ONTIME; clinicaltrials.gov: NCT02829619) study.
Subject(s)
Body Mass Index , Genome-Wide Association Study , Obesity , Weight Loss , Adult , Female , Humans , Male , Middle Aged , Multifactorial Inheritance/genetics , Obesity/genetics , Polymorphism, Single Nucleotide , Weight Loss/geneticsABSTRACT
Social jetlag, the weekly variation in sleep timing, is proposed to contribute to increased obesity risk, potentially because of the misalignment of behavioral cycles relative to the endogenous circadian timing system. This systematic review and meta-analysis aim to determine the association between social jetlag and adiposity-related measures using observational studies. We reviewed 477 references, of which 43 studies met inclusion criteria with a total sample size of 231,648. There was a positive association between social jetlag and body mass index (correlation coefficient [r]: 0.12; 95%CI, 0.07, 0.17; P < 0.001; I2 = 94.99%), fat mass (r: 0.10; 95%CI, 0.05, 0.15; P < 0.001; I2 = 0.00%), fat mass index (fat mass divided by height in meter squared, ß: 0.14 kg/m2 ; 95%CI, 0.05, 0.23; P < 0.001; I2 = 56.50%), percent of body fat (r: 0.37; 95%CI, 0.33, 0.41; P < 0.001; I2 = 96.17%), waist circumference (r: 0.15; 95%CI, 0.06, 0.24; P = 0.001; I2 = 90.83%), and the risk of having overweight/obesity (odds ratio: 1.20; 95%CI, 1.02, 1.140; P = 0.039; I2 = 98.25%). Social jetlag is positively and consistently associated with multiple obesity-related anthropometric measures. Further studies are needed to test causality, underlying mechanisms, and whether obesity interventions based on increasing regularity of the sleep/wake cycle can aid in the battle against the obesity pandemic.
Subject(s)
Circadian Rhythm , Obesity , Humans , Obesity/epidemiology , Obesity/complications , Sleep , Jet Lag Syndrome/complications , Body Mass Index , Observational Studies as TopicABSTRACT
The objective of the current systematic review was to critically review the available evidence regarding the link between social jetlag and diet among the general population using observational studies. Electronic databases, including PubMed, Scopus, and ISI Web of Sciences were searched systematically. We reviewed 348 references, of which 17 studies met inclusion criteria with a total sample size of 28,905. Qualitative analysis indicated a negative association between social jetlag and adherence to healthy eating habits, including a negative association with empirically-derived healthy dietary patterns, Japanese dietary patterns, Baltic Sea dietary patterns, and the Mediterranean diet, as well as a positive association with Meat and Starchy dietary pattern. On the other hand, the findings on the link of social jetlag with food groups and nutrients were mixed and controversial, except for a more consistent increase in sugar-sweetened beverages, total fat, and saturated fat intake. Our results indicate a possible link between social jetlag and dietary intake. Research suggests that individuals experiencing greater social jetlag exhibit reduced adherence to a healthy eating pattern. However, it is important to note that the reported association lacks consensus, emphasizing the need for additional longitudinal studies to gain further insights into this matter."
Subject(s)
Eating , Feeding Behavior , Humans , DietABSTRACT
Background and purpose: Napping is a widespread practice worldwide and has in recent years been linked to increased abdominal adiposity. Lipase E or LIPE encodes the protein hormone-sensitive lipase (HSL), an enzyme that plays an important role in lipid mobilization and exhibits a circadian expression rhythm in human adipose tissue. We hypothesized that habitual napping may impact the circadian expression pattern of LIPE, which in turn may attenuate lipid mobilization and induce abdominal fat accumulation. Methods: Abdominal adipose tissue explants from participants with obesity (n = 17) were cultured for a 24-h duration and analyzed every 4 h. Habitual nappers (n = 8) were selected to match non-nappers (n = 9) in age, sex, BMI, adiposity, and metabolic syndrome traits. Circadian LIPE expression rhythmicity was analyzed using the cosinor method. Results: Adipose tissue explants exhibited robust circadian rhythms in LIPE expression in non-nappers. In contrast, nappers had a flattened rhythm. LIPE amplitude was decreased in nappers as compared with non-nappers (71% lower). The decrease in amplitude among nappers was related to the frequency of napping (times per week) where a lower rhythm amplitude was associated with a higher napping frequency (r = -0.80; P = 0.018). Confirmatory analyses in the activity of LIPE's protein (i.e., HSL) also showed a significant rhythm in non-nappers, whereas significance in the activity of HSL was lost among nappers. Conclusion: Our results suggest that nappers display dysregulated circadian LIPE expression as well as dysregulated circadian HSL activity, which may alter lipid mobilization and contribute to increased abdominal obesity in habitual nappers.
Subject(s)
Adipose Tissue , Lipase , Sterol Esterase , Humans , Abdominal Fat/metabolism , Adipose Tissue/metabolism , Circadian Rhythm , Obesity/metabolism , Sterol Esterase/metabolismABSTRACT
OBJECTIVE: The aim of this study was to determine the association between siestas/no siestas and obesity, considering siesta duration (long: >30 minutes, short: ≤30 minutes), and test whether siesta traits and/or lifestyle factors mediate the association of siestas with obesity and metabolic syndrome (MetS). METHODS: This was a cross-sectional study of 3275 adults from a Mediterranean population (the Obesity, Nutrigenetics, TIming, and MEditerranean [ONTIME] study) who had the opportunity of taking siestas because it is culturally embedded. RESULTS: Thirty-five percent of participants usually took siestas (16% long siestas). Compared with the no-siesta group, long siestas were associated with higher values of BMI, waist circumference, fasting glucose, systolic blood pressure, and diastolic blood pressure, as well as with a higher prevalence of MetS (41%; p = 0.015). In contrast, the probability of having elevated SBP was lower in the short-siesta group (21%; p = 0.044) than in the no-siesta group. Smoking a higher number of cigarettes per day mediated the association of long siestas with higher BMI (by 12%, percentage of association mediated by smoking; p < 0.05). Similarly, delays in nighttime sleep and eating schedules and higher energy intake at lunch (the meal preceding siestas) mediated the association between higher BMI and long siestas by 8%, 4%, and 5% (all p < 0.05). Napping in bed (vs. sofa/armchair) showed a trend to mediate the association between long siestas and higher SBP (by 6%; p = 0.055). CONCLUSIONS: Siesta duration is relevant in obesity/MetS. Timing of nighttime sleep and eating, energy intake at lunch, cigarette smoking, and siesta location mediated this association.
Subject(s)
Metabolic Syndrome , Obesity , Adult , Humans , Cross-Sectional Studies , Obesity/epidemiology , Sleep/physiology , Metabolic Syndrome/epidemiology , Life Style , Risk FactorsABSTRACT
OBJECTIVE: This study aimed to determine the association between being an evening type (ET; defined subjectively by the Morning-Evening Questionnaire or objectively by the dim-light melatonin onset [DLMO] timing) and reporting emotional eating (EE) behaviors. METHODS: Cross-sectional analyses were conducted in 3964 participants (four international cohorts: ONTIME and ONTIME-MT [both Spain], SHIFT [the US], and DICACEM [Mexico]), in which chronotype (Morning-Evening Questionnaire), EE behaviors (Emotional Eating Questionnaire), and dietary habits (dietary records or food-frequency questionnaire) were assessed. Among 162 participants (ONTIME-MT subsample), additional measures of DLMO (physiological gold standard of circadian phase) were available. RESULTS: In three populations, ETs presented with a higher EE score than morning types (p < 0.02); and they made up a higher proportion of emotional eaters (p < 0.01). ETs presented with higher scores on disinhibition/overeating as well as food craving factors and experienced these behaviors more frequently than morning types (p < 0.05). Furthermore, a meta-analysis showed that being an ET was associated with a higher EE score by 1.52 points of a total of 30 points (95% CI: 0.89-2.14). The timing of DLMO in the early, intermediate, and late objective chronotypes occurred at 21:02 h, 22:12 h, and 23:37 h, with late types showing a higher EE score (p = 0.043). CONCLUSIONS: Eveningness associated with EE in populations with different cultural, environmental, and genetic backgrounds. Individuals with late DLMO also showed more EE.
Subject(s)
Melatonin , Sleep , Humans , Sleep/physiology , Circadian Rhythm/physiology , Cross-Sectional Studies , Feeding Behavior , Surveys and QuestionnairesABSTRACT
OBJECTIVE: Later circadian timing of energy intake is associated with higher body fat percentage. Current methods for obtaining accurate circadian timing are labor- and cost-intensive, limiting practical application of this relationship. This study investigated whether the timing of energy intake relative to a mathematically modeled circadian time, derived from easily collected ambulatory data, would differ between participants with a lean or overweight/obesity body fat percentage. METHODS: Participants (N = 87) wore a light- and activity-measuring device (actigraph) throughout a cross-sectional 30-day study. For 7 consecutive days within these 30 days, participants used a time-stamped-picture phone application to record energy intake. Body fat percentage was recorded. Circadian time was defined using melatonin onset from in-laboratory collected repeat saliva sampling or using light and activity or activity data alone entered into a mathematical model. RESULTS: Participants with overweight/obesity body fat percentages ate 50% of their daily calories significantly closer to model-predicted melatonin onset from light and activity data (0.61 hours closer) or activity data alone (0.86 hours closer; both log-rank p < 0.05). CONCLUSIONS: Use of mathematically modeled circadian timing resulted in similar relationships between the timing of energy intake and body composition as that observed using in-laboratory collected metrics. These findings may facilitate use of circadian timing in time-based interventions.
Subject(s)
Melatonin , Sleep , Humans , Overweight , Circadian Rhythm , Cross-Sectional Studies , Energy Intake , Obesity , Adipose TissueABSTRACT
Late eating has been linked to obesity risk. It is unclear whether this is caused by changes in hunger and appetite, energy expenditure, or both, and whether molecular pathways in adipose tissues are involved. Therefore, we conducted a randomized, controlled, crossover trial (ClinicalTrials.gov NCT02298790) to determine the effects of late versus early eating while rigorously controlling for nutrient intake, physical activity, sleep, and light exposure. Late eating increased hunger (p < 0.0001) and altered appetite-regulating hormones, increasing waketime and 24-h ghrelin:leptin ratio (p < 0.0001 and p = 0.006, respectively). Furthermore, late eating decreased waketime energy expenditure (p = 0.002) and 24-h core body temperature (p = 0.019). Adipose tissue gene expression analyses showed that late eating altered pathways involved in lipid metabolism, e.g., p38 MAPK signaling, TGF-ß signaling, modulation of receptor tyrosine kinases, and autophagy, in a direction consistent with decreased lipolysis/increased adipogenesis. These findings show converging mechanisms by which late eating may result in positive energy balance and increased obesity risk.
Subject(s)
Hunger , Overweight , Adult , Appetite , Eating/physiology , Energy Intake , Energy Metabolism/physiology , Ghrelin/metabolism , Humans , Hunger/physiology , Leptin/metabolism , Metabolic Networks and Pathways , Obesity/metabolism , Transforming Growth Factor beta/metabolism , Tyrosine/metabolism , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
Emotional eating (EE) is food consumption in response to feelings rather than hunger. EE is related to unhealthy food intake and abdominal obesity (AO). However, little evidence exists about the association between EE and dietary patterns (DPs) and EE−AO interaction related to DPs. DPs allow describing food combinations that people usually eat. We analyzed the association of EE with DPs in adults (≥18 years) with AO (WC ≥ 80/90 cm in women/men, respectively; n = 494; 66.8% women;) or without AO (n = 269; 74.2% women) in a cross-sectional study. Principal component analysis allowed identifying four DPs from 40 food groups (validated with a semiquantitative food frequency questionnaire). Among the subjects presenting AO, being "emotional/very-emotional eater" (emotional eating questionnaire) was negatively associated with the "Healthy" DP (fruits, vegetables, olive oil, oilseeds, legumes, fish, seafood) (OR:0.53; 95% CI: 0.33, 0.88, p = 0.013) and positively with the "Snacks and fast food" DP (sweet bread, breakfast cereal, corn, potato, desserts, sweets, sugar, fast food) (OR:1.88; 95% CI: 1.17, 3.03, p = 0.010). Emotional eaters with AO have significantly lower fiber intake, folic acid, magnesium, potassium, vitamin B1, and vitamin C, while they had a higher intake of sodium, lipids, mono and polyunsaturated fatty acids, and saturated fats. In non-AO participants, EE was not associated with any DP (p > 0.05). In conclusion, EE is associated with unhealthy DPs in subjects with AO.
Subject(s)
Diet , Obesity, Abdominal , Cross-Sectional Studies , Eating , Emotions , Feeding Behavior , Female , Humans , Male , Obesity , Snacks , VegetablesSubject(s)
Circadian Clocks , Humans , Circadian Clocks/physiology , Sleep , Circadian Rhythm/physiology , Body Weight , Health StatusABSTRACT
BACKGROUND: There currently are no standard, low-cost, and validated methods to assess the timing of food intake. OBJECTIVES: The aim of this study was to validate simple, recall-based questions that can characterize food timing in free-living populations. METHODS: The concordance between recall-based survey questions and food times estimated from multiple daily food records was assessed in 249 generally healthy, free-living adults from the Shift Work, Heredity, Insulin, and Food Timing (SHIFT) Study. At baseline, participants were asked: "At what time do you first start and stop eating on weekdays/workdays and weekends/non-workdays?" and "At what time do you have your main meal on weekdays/workdays and weekends/non-workdays?" Participants were then asked to complete ≤14 d of food records noting the start time of each eating occasion. The timing of the first, last, and main (largest percentage calories) eating occasions were determined from food records. Wilcoxon matched pairs signed rank and Kendall's coefficient of concordance were used to compare differences and determine agreements between the methods for these food timing parameters, as well as for the midpoint between first and last eating occasion. RESULTS: Eating occasions on work and free days showed significant agreements between the 2 methods, except for the main eating occasion on free days. Significant agreements were generally modest and ranged from 0.16 (workdays main eating occasion) to 0.45 (workdays first eating occasion). Generally, times based on recall were later than those estimated from food records, and the differences in estimated times were smaller on workdays compared with free days, and smaller for the first compared with the last eating occasion. Main eating occasions from food records often varied between lunch and dinner times, contributing to low concordance with recalled times. CONCLUSIONS: Modest agreements were found between food times derived from simple, recall-based survey questions and food times estimated from multiple-day food records. Single administration of these questions can effectively characterize the overall timing of eating occasions within a population for chrononutrition research purposes.
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OBJECTIVE: We tested whether the concurrence of food intake and elevated concentrations of endogenous melatonin, as occurs with late eating, results in impaired glucose control, in particular in carriers of the type 2 diabetes-associated G allele in the melatonin receptor-1B gene (MTNR1B). RESEARCH DESIGN AND METHODS: In a Spanish natural late-eating population, a randomized, crossover study was performed. Each participant (n = 845) underwent two evening 2-h 75-g oral glucose tolerance tests following an 8-h fast: an early condition scheduled 4 h prior to habitual bedtime ("early dinner timing") and a late condition scheduled 1 h prior to habitual bedtime ("late dinner timing"), simulating an early and a late dinner timing, respectively. Differences in postprandial glucose and insulin responses between early and late dinner timing were determined using incremental area under the curve (AUC) calculated by the trapezoidal method. RESULTS: Melatonin serum levels were 3.5-fold higher in the late versus early condition, with late dinner timing resulting in 6.7% lower insulin AUC and 8.3% higher glucose AUC. The effect of late eating impairing glucose tolerance was stronger in the MTNR1B G-allele carriers than in noncarriers. Genotype differences in glucose tolerance were attributed to reductions in ß-cell function (P for interaction, Pint glucose area under the curve = 0.009, Pint corrected insulin response = 0.022, and Pint disposition index = 0.018). CONCLUSIONS: Concurrently high endogenous melatonin and carbohydrate intake, as typical for late eating, impairs glucose tolerance, especially in MTNR1B G-risk allele carriers, attributable to insulin secretion defects.
Subject(s)
Diabetes Mellitus, Type 2 , Insulin Secretion , Receptor, Melatonin, MT2 , Blood Glucose , Cross-Over Studies , Diabetes Mellitus, Type 2/genetics , Eating , Genotype , Glucose/administration & dosage , Glucose/metabolism , Humans , Insulin/metabolism , Insulin Secretion/genetics , Meals/physiology , Melatonin/blood , Receptor, Melatonin, MT2/genetics , Risk Factors , Spain , Time FactorsABSTRACT
Circadian misalignment-the misalignment between the central circadian "clock" and behavioral and environmental cycles (including sleep/wake, fasting/eating, dark/light)-results in adverse cardiovascular and metabolic effects. Potential underlying mechanisms for these adverse effects include alterations in the orogastrointestinal microbiota. However, it remains unknown whether human oral microbiota has endogenous circadian rhythms (i.e., independent of sleep/wake, fasting/eating, and dark/light cycles) and whether circadian misalignment influences oral microbiota community composition. Healthy young individuals [27.3 ± 2.3 years (18-35 years), 4 men and 2 women, body-mass index range: 18-28 kg/m2 ] were enrolled in a stringently controlled 14-day circadian laboratory protocol. This included a 32-h constant routine (CR) protocol (endogenous circadian baseline assessment), a forced desynchrony protocol with four 28-h "days" under ~3 lx to induce circadian misalignment, and a post-misalignment 40-h CR protocol. Microbiota assessments were performed on saliva samples collected every 4 h throughout both CR protocols. Total DNA was extracted and processed using high-throughput 16S ribosomal RNA gene amplicon sequencing. The relative abundance of specific oral microbiota populations, i.e., one of the five dominant phyla, and three of the fourteen dominant genera, exhibited significant endogenous circadian rhythms. Importantly, circadian misalignment dramatically altered the oral microbiota landscape, such that four of the five dominant phyla and eight of the fourteen dominant genera exhibited significant circadian misalignment effects. Moreover, circadian misalignment significantly affected the metagenome functional content of oral microbiota (inferred gene content analysis), as indicated by changes in specific functional pathways associated with metabolic control and immunity. Collectively, our proof-of-concept study provides evidence for endogenous circadian rhythms in human oral microbiota and show that even relatively short-term experimental circadian misalignment can dramatically affect microbiota community composition and functional pathways involved in metabolism and immune function. These proof-of-principle findings have translational relevance to individuals typically exposed to circadian misalignment, including night shift workers and frequent flyers.
Subject(s)
Circadian Rhythm , Microbiota , Mouth/microbiology , Saliva/microbiology , Shift Work Schedule , Adolescent , Adult , Female , Humans , Male , Proof of Concept StudyABSTRACT
Individuals with evening chronotypes are prone to suffer chronodisruption and display worse lifestyle habits than morning-types, exhibiting higher cardiovascular diseases (CVD). However, it is unknown whether CVD patients, who are evening chronotypes, have higher cardiometabolic risk than morning-types. This study explored whether individual chronotypes were associated with cardiometabolic risk in patients from the CORDIOPREV study (n = 857). We also investigated whether potential associations were moderated by long-term consumption of two healthy diets (Mediterranean and Low-fat diets). This population was classified into chronotypes using the Morningness-Eveningness Questionnaire. Seven-day daily rhythms in wrist temperature (T), rest-activity (A) and position (P) were recorded in a subset of patients (n = 168), and an integrative variable TAP was determined. Metabolic Syndrome (MetS) was determined at baseline, and metabolic and inflammation markers were measured at baseline and yearly during the 4 years of follow-up. Differences in several lifestyle factors were analyzed according to chronotype. At all times, evening-types had higher triglycerides, C-reactive protein and homocysteine and lower high density lipoprotein cholesterol than morning-types (P < 0.05). Evening-types had a higher prevalence of MetS (OR 1.58 IC 95% [1.10 - 2.28], P = 0.01). Moreover, they were more sedentary, displayed less and delayed physical activity and ate and slept later. In addition, evening-types had lower amplitude, greater fragmentation, lower robustness and less stable circadian pattern at TAP (P < 0.01), all related to a less healthy circadian pattern. In conclusion, evening-types with CVD had higher cardiometabolic risk and less robust circadian-related rhythms than morning-types, regardless of the nutritional intervention.