ABSTRACT
BACKGROUND: Accumulating evidence suggests that autonomic dysfunction and persistent systemic inflammation are common clinical features in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID. However, there is limited knowledge regarding their potential association with circulating biomarkers and illness severity in these conditions. METHODS: This single-site, prospective, cross-sectional, pilot cohort study aimed to distinguish between the two patient populations by using self-reported outcome measures and circulating biomarkers of endothelial function and systemic inflammation status. Thirty-one individuals with ME/CFS, 23 individuals with long COVID, and 31 matched sedentary healthy controls were included. All study participants underwent non-invasive cardiovascular hemodynamic challenge testing (10 min NASA lean test) for assessment of orthostatic intolerance. Regression analysis was used to examine associations between outcome measures and circulating biomarkers in the study participants. Classification across groups was based on principal component and discriminant analyses. RESULTS: Four ME/CFS patients (13%), 1 with long COVID (4%), and 1 healthy control (3%) presented postural orthostatic tachycardia syndrome (POTS) using the 10-min NASA lean test. Compared with matched healthy controls, ME/CFS and long COVID subjects showed higher levels of ET-1 (p < 0.05) and VCAM-1 (p < 0.001), and lower levels of nitrites (NOx assessed as NO2- + NO3-) (p < 0.01). ME/CFS patients also showed higher levels of serpin E1 (PAI-1) and E-selectin than did both long COVID and matched control subjects (p < 0.01 in all cases). Long COVID patients had lower TSP-1 levels than did ME/CFS patients and matched sedentary healthy controls (p < 0.001). As for inflammation biomarkers, both long COVID and ME/CFS subjects had higher levels of TNF-α than did matched healthy controls (p < 0.01 in both comparisons). Compared with controls, ME/CFS patients had higher levels of IL-1ß (p < 0.001), IL-4 (p < 0.001), IL-6 (p < 0.01), IL-10 (p < 0.001), IP-10 (p < 0.05), and leptin (p < 0.001). Principal component analysis supported differentiation between groups based on self-reported outcome measures and biomarkers of endothelial function and inflammatory status in the study population. CONCLUSIONS: Our findings revealed that combining biomarkers of endothelial dysfunction and inflammation with outcome measures differentiate ME/CFS and Long COVID using robust discriminant analysis of principal components. Further research is needed to provide a more comprehensive characterization of these underlying pathomechanisms, which could be promising targets for therapeutic and preventive strategies in these conditions.
Subject(s)
COVID-19 , Fatigue Syndrome, Chronic , Humans , Fatigue Syndrome, Chronic/epidemiology , Post-Acute COVID-19 Syndrome , Cross-Sectional Studies , Pilot Projects , Prospective Studies , Cohort Studies , Patient Acuity , Biomarkers , InflammationABSTRACT
There is accumulating evidence of autonomic dysfunction in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS); however, little is known about its association with circadian rhythms and endothelial dysfunction. This study aimed to explore the autonomic responses through an orthostatic test and analysis of the peripheral skin temperature variations and vascular endothelium state in ME/CFS patients. Sixty-seven adult female ME/CFS patients and 48 healthy controls were enrolled. Demographic and clinical characteristics were assessed using validated self-reported outcome measures. Postural changes in blood pressure, heart rate, and wrist temperature were recorded during the orthostatic test. Actigraphy during one week was used to determine the 24-h profile of peripheral temperature and activity. Circulating endothelial biomarkers were measured as indicators of endothelial functioning. Results showed that ME/CFS patients presented higher blood pressure and heart rate values than healthy controls in the supine and standing position (p < 0.05 for both), and also a higher amplitude of the activity rhythm (p < 0.01). Circulating levels of endothelin-1 (ET-1) and vascular cell adhesion molecule-1 (VCAM-1) were significantly higher in ME/CFS (p < 0.05). In ME/CFS, ET-1 levels were associated with the stability of the temperature rhythm (p < 0.01), and also with the self-reported questionnaires (p < 0.001). This suggests that ME/CFS patients exhibited modifications in circadian rhythm and hemodynamic measures, which are associated with endothelial biomarkers (ET-1 and VCAM-1). Future investigation in this area is needed to assess dysautonomia and vascular tone abnormalities, which may provide potential therapeutic targets for ME/CFS.
Subject(s)
Circadian Rhythm , Endothelin-1 , Fatigue Syndrome, Chronic , Primary Dysautonomias , Skin Temperature , Adult , Female , Humans , Biomarkers , Endothelin-1/physiology , Fatigue Syndrome, Chronic/physiopathology , Primary Dysautonomias/physiopathology , Vascular Cell Adhesion Molecule-1ABSTRACT
This cross-sectional study was designed to investigate whether diet quality and eating behaviors could mediate the association between sleep quality and body mass index (BMI) in young adults. For all participants (n = 925; aged 21.4 ± 2.5 years; 77.8% women) we evaluated: BMI, sleep quality, diet quality, and eating behavior dimensions (emotional eating, cognitive restraint, and uncontrolled eating). Linear regression models were used to test associations between exposure and outcome variables. Path analysis was conducted with all potential mediators and covariates entered at the same time. Results showed that emotional eating (ß = 0.04 [95% CI: 0.03; 0.06]), cognitive restraint (ß = 0.03 [95% CI: 0.01; 0.04]), uncontrolled eating (ß = 0.02 [95% CI: 0.01; 0.04]) and diet quality (ß = -0.14 [95% CI: 0.19;-0.08]) were significantly associated with sleep quality. Additionally, BMI was significantly associated with PSQI score (ß = 0.09 [95% CI: 0.01; 0.17]), emotional eating (ß = 0.89 [95% CI: 0.60; 1.18]), and cognitive restraint (ß = 1.37 [95% CI: 1.02; 1.71]). After testing for mediation, results revealed that emotional eating and cognitive restraint evidenced a significant mediating effect on the association between sleep quality and BMI. Additionally, diet quality was significantly associated with emotional eating (ß = -0.35 [95% CI: 0.56;-0.13]), cognitive restraint (ß = 0.53 [95% CI: 0.27; 0.79]), and uncontrolled eating (ß = -0.49 [95% CI: 0.74;-0.25]). In conclusion, young adults with poor sleep quality are more likely to deal with negative emotions with food, which, in turn, could be associated with higher cognitive restraint, becoming a vicious cycle that has a negative impact on body weight. Our results also emphasize the role of eating behaviors as determinants of diet quality, highlighting the importance of considering sleep quality and eating behaviors when designing obesity prevention strategies in this population.
Subject(s)
Feeding Behavior , Sleep Quality , Adolescent , Adult , Body Mass Index , Cognition , Cross-Sectional Studies , Eating/psychology , Emotions , Feeding Behavior/psychology , Female , Humans , Male , Surveys and Questionnaires , Young AdultABSTRACT
BACKGROUND: Previous research has shown that sleep can play a role in obesity and weight loss. However, the association of sleep with weight loss in patients with severe obesity after bariatric surgery remains unexplored. We aimed to evaluate the role of sleep in weight loss evolution in a cohort of patients who underwent sleeve gastrectomy. METHODS: A cohort of 252 patients with severe obesity (75.7% women; age [mean ± SD] 47.7 ± 10.8 years; BMI 44.2 ± 5.9 kg/m2) was followed for 1 year after surgery. Anthropometric, biochemical, physical activity, sleep (bedtime, wakeup time, and sleep duration) and dietary intake variables were collected pre- and post-surgery (1 year). Linear and non-linear regression models were used to examine the associations between sleep variables and weight loss. Participants were grouped into 'early' and 'late' sleepers according to a bedtime threshold (before or after 24:00 h), and the differences in weight loss, physical activity, meal timing, and dietary intake between groups were studied. RESULTS: 1-h increments in bedtime were linearly associated with less excess weight loss (EWL) [-2.23%; 95%CI: -3.37; -0.70; p = 0.005] 1 year after the sleeve gastrectomy. Late sleepers lost less weight (-5.64% of EWL [95%CI: -10.11; -1.17]; p = 0.014) when compared to early sleepers and showed a higher energy intake after 21:00 h (8.66% of total energy intake [95% CI: 4.87; 12.46]; p < 0.001). CONCLUSIONS: Late bedtime is associated with less success of weight loss 1 year after the sleeve gastrectomy. Late sleepers consumed more of their calories closer to bedtime. Our results highlight the relevance of considering recommendations on bedtime and meal timing for patients after bariatric surgery.
Subject(s)
Gastrectomy/statistics & numerical data , Sleep/physiology , Time Factors , Weight Loss/physiology , Adult , Cohort Studies , Female , Gastrectomy/methods , Humans , Longitudinal Studies , Male , Middle Aged , Obesity/complications , Obesity/epidemiology , Obesity/surgery , Prospective Studies , Spain/epidemiologyABSTRACT
To date, few studies have examined the circadian pattern of motor activity in children and adolescents newly diagnosed with attention-deficit/hyperactivity disorder (ADHD). The objective was to study the circadian pattern of motor activity in subjects with ADHD (medication naïve) and to investigate the relationships between alterations in circadian patterns, the ADHD subtype (combined or inattentive), sleep disturbances and body mass index (BMI). One-hundred twenty children and adolescents (60 medication naïve ADHD and 60 controls) were included in a gender- and age-matched case-control study. ADHD was diagnosed according to the DSM-IV-TR, the Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version, and the Conner's Parents Rating Scale-Revised. Circadian rhythms of motor activity and sleep parameters were measured using actigraphy and the Sleep Disturbance Scale for Children. BMI and dietary intake were also evaluated. ADHD patients showed a trend towards eveningness and greater sleep disturbances than controls. Additionally, patients with ADHD-combined had significantly higher mean values of motor activity and showed a significant delay in bedtime. Furthermore, among ADHD-C patients hyperactivity symptoms were significantly associated with the least 5 h of activity. Regarding patients with ADHD-inattentive, increased fragmentation of the circadian pattern was associated with inattention symptoms, and they also showed a significant increase in BMI of 2.52 kg/m2 [95% CI 0.31, 4.73] in comparison with controls. Our findings highlight the potential use of actigraphy as a clinical tool to aid in the diagnosis of ADHD. It should be noted that evaluating motor activity variables could also allow the differentiation between ADHD subtypes.
Subject(s)
Attention Deficit Disorder with Hyperactivity , Adolescent , Attention Deficit Disorder with Hyperactivity/diagnosis , Body Mass Index , Case-Control Studies , Child , Circadian Rhythm , Humans , Motor Activity , SleepABSTRACT
Allergic asthma is one of the most common chronic diseases of the airways, however it still remains underdiagnosed and hence undertreated. Therefore, an allergic asthma rat model would be useful to be applied in future therapeutic strategy studies. The aim of the present study was to develop an objective model of allergic asthma in atopic rats that allows the induction and quantification of anaphylactic shock with quantitative variables. Female Brown Norway rats were intraperitoneally sensitized with ovalbumin (OVA), alum and Bordetella pertussis toxin and boosted a week later with OVA in alum. At day 28, all rats received an intranasal challenge with OVA. Anaphylactic response was accurately assessed by changes in motor activity and body temperature. Leukotriene concentration was determined in the bronchoalveolar lavage fluid (BALF), and total and IgE anti-OVA antibodies were quantified in blood and BALF samples. The asthmatic animals' motility and body temperature were reduced after the shock for at least 20 h. The asthmatic animals developed anti-OVA IgE antibodies both in BALF and in serum. These results show an effective and relatively rapid model of allergic asthma in female Brown Norway rats that allows the quantification of the anaphylactic response.
Subject(s)
Asthma/metabolism , Disease Models, Animal , Hypersensitivity/metabolism , Immunoglobulin E/analysis , Administration, Intranasal , Allergens , Animals , Asthma/chemically induced , Body Temperature , Bronchoalveolar Lavage Fluid , Cytokines/metabolism , Epithelial Cells/metabolism , Female , Hypersensitivity, Immediate , Leukotrienes/chemistry , Lung/immunology , Ovalbumin , RatsABSTRACT
Alcohol consumption is highly prevalent in university students. Early detection in future health professionals is important: their consumption might not only influence their own health but may determine how they deal with the implementation of preventive strategies in the future. The aim of this paper is to detect the prevalence of risky alcohol consumption in first- and last-degree year students and to compare their drinking patterns.Risky drinking in pharmacy students (n=434) was assessed and measured with the AUDIT questionnaire (Alcohol Use Disorders Identification Test). A comparative analysis between college students from the first and fifth years of the degree in pharmacy, and that of a group of professors was carried to see differences in their alcohol intake patterns.Risky drinking was detected in 31.3% of students. The highest prevalence of risky drinkers, and the total score of the AUDIT test was found in students in their first academic year. Students in the first academic level taking morning classes had a two-fold risk of risky drinking (OR=1.9 (IC 95%1.1-3.1)) compared with students in the fifth level. The frequency of alcohol consumption increases with the academic level, whereas the number of alcohol beverages per drinking occasion falls.Risky drinking is high during the first year of university. As alcohol consumption might decrease with age, it is important to design preventive strategies that will strengthen this tendency.
El consumo de alcohol es muy prevalente entre los estudiantes universitarios. La detección precoz en futuros profesionales sanitarios es muy importante puesto que puede incidir no solo en su salud, sino también en su enfoque en futuras acciones preventivas como profesionales de la salud.Detectar la prevalencia del consumo de riesgo de alcohol en estudiantes de farmacia y en el profesorado y comparar el patrón de consumo entre estos grupos, y según el curso académico.Se realiza un cribado del consumo de alcohol mediante el cuestionario AUDIT (Alcohol Use Disorders Identification Test) a estudiantes universitarios de farmacia (n=434) en el marco de un proyecto de innovación docente. Se realiza un análisis comparativo entre los estudiantes de primero y quinto curso, y el profesorado. El 31,3% de los estudiantes fueron identificados como bebedores de riesgo. La mayor prevalencia de consumidores de riesgo y las mayores puntuaciones totales se observaron en los alumnos de primer curso. Los estudiantes de primero de turno de mañana presentaron un riesgo de 1,9 (IC 95%1,1-3,1) comparado con los de quinto. La frecuencia de consumo de alcohol se incrementa con el curso académico, mientras que el número de consumiciones por día de consumo se reduce. Durante el primer año en la Facultad los estudiantes presentan una elevada prevalencia de consumo de riesgo. Puesto que con la edad se observa una tendencia decreciente en dichos consumos, es importante diseñar intervenciones preventivas que la favorezcan.
Subject(s)
Alcohol Drinking in College , Alcohol Drinking/epidemiology , Faculty, Pharmacy , Students, Pharmacy , Adolescent , Cross-Sectional Studies , Female , Humans , Male , Prevalence , Schools, Pharmacy , Young AdultABSTRACT
Circadian rhythms are present in most functions of living beings. We have demonstrated the presence of circadian rhythms in skin variables (transepidermal water loss, TEWL; stratum corneum hydration, SCH; and skin temperature) in hairless rats under different environmental conditions of light and temperature. Circadian rhythms in TEWL and SCH showed mean amplitudes of about 20% and 14% around the mean, respectively, and appeared under light-dark cycles as well as under constant darkness. Environmental temperature was able to override TEWL, but not SCH rhythm, evidencing the dependency of TEWL on the temperature. Mean daily values of TEWL and SCH, and also the amplitude of TEWL rhythm, increased with the age of the animal. Under constant light, situation that induces arrhythmicity in rats, SCH and TEWL were inversely correlated. The results suggest the importance to take into account the functional skin rhythms in research in dermatological sciences.
Subject(s)
Circadian Rhythm/physiology , Light , Skin Temperature/physiology , Temperature , Water Loss, Insensible/physiology , Animals , Male , Rats , Rats, HairlessABSTRACT
This study aimed to investigate circadian rhythm manifestations in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patients (including a subpopulation of long-COVID patients) and matched healthy controls while also exploring their association with cardiovascular health variables. Thirty-one ME/CFS patients (75% females), 23 individuals diagnosed with post-COVID ME/CFS (56% females) and 31 matched healthy controls (68% females) were enrolled in this study. Demographic and clinical characteristics were assessed using validated self-reported outcome measures. Actigraphy data, collected over one week, were used to analyze the 24-h profiles of wrist temperature, motor activity, and sleep circadian variables in the study participants. Associations between lipid profile with endothelial dysfunction biomarkers (such as endothelin-1, ICAM-1 and VCAM-1) and with sleep and circadian variables were also studied. No differences were found in these variables between the two group of patients. Patients showed lower activity and worse sleep quality than matched healthy controls, together with a worse lipid profile than controls, that was associated with disturbances in the circadian temperature rhythm. ICAM-1 levels were associated with plasma lipids in healthy controls, but not in patients, who showed higher levels of endothelin-1 and VCAM-1. These findings suggest that lipid profiles in ME/CFS are linked to disrupted circadian rhythms and sleep patterns, likely due to endothelial dysfunction. Furthermore, they highlight the intricate relationship between sleep, circadian rhythms, and cardiovascular health in this condition.
Subject(s)
COVID-19 , Circadian Rhythm , Fatigue Syndrome, Chronic , Sleep , Humans , Female , Male , Fatigue Syndrome, Chronic/physiopathology , Circadian Rhythm/physiology , Middle Aged , Adult , Prospective Studies , Sleep/physiology , COVID-19/complications , COVID-19/physiopathology , Heart Disease Risk Factors , Cardiovascular Diseases/physiopathology , Post-Acute COVID-19 Syndrome , Actigraphy , Risk Factors , SARS-CoV-2 , Biomarkers/blood , Vascular Cell Adhesion Molecule-1/bloodABSTRACT
BACKGROUND: Circadian theories for major depressive disorder have suggested that the rhythm of the circadian pacemaker is misaligned. Stable phase relationships between internal rhythms, such as temperature and rest/activity, and the external day-night cycle, are considered to be crucial for adapting to life in the external environmental. Therefore, the relationship and possible alterations among (i) light exposure, (ii) activity rhythm, and (iii) temperature rhythm could be important factors in clinical depression. This study aimed to investigate the rhythmic alterations in depression and evaluate the ability of chronobiological parameters to discriminate between healthy subjects and depressed patients. METHODS: Thirty female subjects, including healthy subjects, depressed patients in the first episode, and major recurrent depression patients. Symptoms were assessed using Hamilton Depression Scale, Beck Depression Inventory and Montgomery-Äsberg Scale. Motor activity, temperature, and light values were determined for 7 days by actigraph, and circadian rhythms were calculated. RESULTS: Depressed groups showed a lower amplitude in the circadian rhythm of activity and light exposure, but a higher amplitude in the rhythm of peripheral temperature. The correlation between temperature and activity values was different in the day and night among the control and depressed groups. For the same level of activity, depressed patients had lowest temperature values during the day. The amplitudes of temperature and activity were the highest discriminant parameters. CONCLUSIONS: These results indicate that the study of rhythms is useful for diagnosis and therapy for depressive mood disorders.
Subject(s)
Body Temperature/physiology , Depressive Disorder, Major/diagnosis , Motor Activity/physiology , Adult , Chronic Disease , Circadian Rhythm/physiology , Depressive Disorder/diagnosis , Depressive Disorder/physiopathology , Depressive Disorder, Major/physiopathology , Female , Humans , Light , Psychiatric Status Rating ScalesABSTRACT
Rats housed in a 22-h light-dark cycle (11:11, T22) exhibit 2 distinct circadian locomotor activity (LMA) bouts simultaneously: one is entrained to the LD cycle and a second dissociated bout maintains a period greater than 24 h. These 2 activity bouts are associated with independent clock gene oscillations in the ventrolateral (vl-) and dorsomedial (dm-) suprachiasmatic nucleus (SCN), respectively. Previous results in our laboratory have shown that the vl- and dm-SCN oscillators are weakly coupled under T22 and that the period of the dissociated bout depends on coupling between the 2 subdivisions. Here, we sought to study the behavior of the T22 SCN pacemaker upon release into free-running conditions and compare it to the behavior of the system upon release from typical 24-h (12:12, T24) entrainment. T22-desynchronized rats or T24-entrained rats were released into constant darkness (DD). Activity rhythms in T22 rats rapidly resynchronized upon release into DD, and the free-running period (FRP) of the fused rhythm was longer than the FRP of T24 rats. We then asked whether the in vivo period changes were also present in the ex vivo SCN. Per1-luc rats were desynchronized in T22 for assessment of SCN Per1-luc ex vivo. Similar to behavioral FRP, the period of ex vivo SCN explanted from T22 rats was longer than that for T24 animals. Mathematical models supported the observed behavior of the dual oscillator system as the result of mutual coupling between the vl- and dm-SCN oscillators. This bidirectionally coupled model predicted both the FRP of the T22 system and its phase-shifting response to light. Together, these data support a model of pacemaker organization in which a light-sensitive vl-SCN oscillator is mutually coupled with a light-insensitive dm-SCN oscillator, and together they determine the period of the coupled system as a whole and its response to light pulses.
Subject(s)
Circadian Rhythm , Suprachiasmatic Nucleus , Animals , Rats , LocomotionABSTRACT
Sleep apnea, a condition that modifies sleep and circadian rhythms, is highly prevalent in patients with diabetes. However, it is not known if there is an association between sleep apnea, circadian alterations and glycemic regulation in this type of patient. Here, a polysomnographic study was carried out on 21 women and 25 men (mean age = 64.3 ± 1.46 years) with diagnoses of type 2 diabetes to detect the presence of sleep apnea. Moreover, patients wore an actigraph and a temperature sensor on the wrist for one week, to study the manifestation of the circadian rhythms. The correlations of circadian and polysomnographic variables with the severity of apnea, measured by the apnea-hypopnea index, and with glycemic dysregulation, measured by the percentage of glycated hemoglobin, were analyzed. The mean apnea-hypoapnea index of all the participants was 39.6 ± 4.3. Apnea-hypoapnea index correlated with % N1, negatively with % N3, and also the stability of the active circadian rhythm. However, no significant correlation was found between the apnea-hypopnea index and wrist temperature rhythm and glycated hemoglobin. Glycated hemoglobin levels were negatively associated with the percentage of variance explained by the wrist temperature circadian rhythm (calculated via 24 and 12 h rhythms). This association was independent of body mass index and was strongest in patients with severe apnea. In conclusion, patients with diabetes showed altered circadian rhythms associated with a poor glycemic control and this association could partially be related to the coexistence of sleep apnea.
ABSTRACT
BACKGROUND: Although overweight and obesity are assumed to arise from an energy imbalance, evidence has shown that the frequency and timing of meals are also potential risk factors for obesity. However, the lack of a consistent approach to define eating patterns relative to internal circadian rhythms limits the extent of these findings. OBJECTIVES: The objective of this study was to investigate the association of the circadian pattern of energy intake with adiposity and with internal circadian rhythms. METHODS: A total of 260 Spanish adults (aged 20-30 y; 78.1% women) were included in a 6-d cross-sectional study. Participants documented sleep and dietary intake within the study period. From these data, we evaluated the chronotype, eating patterns (meal timing, eating duration, and eating frequency), and we obtained the daily profile of energy intake. In addition, we evaluated the circadian pattern of wrist temperature (internal circadian rhythm marker). Circadian patterns of energy intake and wrist temperature were analyzed, and their association among them and with anthropometric variables and diet quality was studied. RESULTS: The greater fragmentation of the circadian pattern of energy intake was associated with lower BMI (in kg/m2; -10.55; 95% CI: -16.96, -4.13; P = 0.001). In addition, a greater eating frequency (≥5 eating occasions/d) was significantly associated with lower BMI (-1.88; 95% CI: -3.27, -0.48) and higher energy intake after 20:00 (4.14% of kcal; 95% CI: 1.67, 7.16). Furthermore, a greater eating frequency was associated with lower fragmentation (P = 0.042) and greater stability of the circadian pattern of wrist temperature (P = 0.016). CONCLUSIONS: The daily pattern of energy intake is associated with adiposity and robust circadian rhythms. Our results shed light on the relevance of eating frequency as a potential zeitgeber for the circadian system. Although more evidence is needed, eating frequency could be considered for future chrono-nutritional recommendations for the prevention of circadian misalignment and obesity.
ABSTRACT
BACKGROUND: Time restricted feeding (TRF) refers to dietary interventions in which food access is limited during a specific timeframe of the day. TRFs have proven useful in improving metabolic health in adult subjects with obesity. Their beneficial effects are mediated, in part, through modulating the circadian rhythm. Nevertheless, the translation of these dietary interventions onto obese/overweight children and adolescents remains uncharacterized. The objective of this study is to explore the feasibility of temporal dietary interventions for improving metabolic health in the context of childhood obesity. METHODS: We have previously developed a mouse model of early adiposity (i.e., childhood obesity) through litter size reduction. Mice raised in small litters (SL) became obese as early as by two weeks of age, and as adults, they developed several obesity-related co-morbidities, including insulin resistance, glucose intolerance and hepatic steatosis. Here, we explored whether two independent short-term chrono-nutritional interventions might improve metabolic health in 1-month-old pre-pubertal SL mice. Both TRFs comprised 8 h feeding/14 h fasting. In the first one (TRF1) Control and SL mice had access to the diet for 8 h during the dark phase. In the second intervention (TRF2) food was available during the light:dark transitions. RESULTS: TRF1 did not alter food intake nor ameliorate adiposity in SL-TRF1. In contrast, SL-TRF2 mice showed unintentional reduction of caloric intake, which was accompanied by reduced total body weight and adiposity. Strikingly, hepatic triglyceride content was completely normalized in SL-TRF1 and SL-TRF2 mice, when compared to the ad lib-fed SL mice. These effects were partially mediated by (i) clock-dependent signals, which might modulate the expression of Pparg or Cpt1a, and (ii) clock-independent signals, such as fasting itself, which could influence Fasn expression. CONCLUSIONS: Time-restricted feeding is an effective and feasible nutritional intervention to improve metabolic health, namely hepatic steatosis, in a model of childhood obesity. These data open new avenues for future safe and efficient chrono-nutritional interventions aimed to improve metabolic health in children with overweight/obesity.
Subject(s)
Adiposity , Fasting , Fatty Liver/complications , Fatty Liver/prevention & control , Pediatric Obesity/complications , Sexual Maturation , Animals , Circadian Clocks/genetics , Diet , Disease Models, Animal , Fatty Liver/genetics , Gene Expression Regulation , Insulin Resistance , Litter Size , Liver/metabolism , Mice, Inbred C57BL , Models, Biological , Oxidation-Reduction , Pediatric Obesity/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Triglycerides/metabolismABSTRACT
Advances in research have linked alterations of circadian rhythms with obesity. However, few studies have focused on the recovery of the circadian expression after a weight loss treatment. Our aim was to study the alterations of the circadian rhythmicity due to morbid obesity and the recovery of the circadian pattern after weight loss in a cohort of patients who underwent sleeve gastrectomy. For this purpose, 41 patients with severe obesity (75% women; age [mean (SD)] 49.7 ± 10 years; BMI 44.3 ± 6.2 kg/m2) were monitored before bariatric surgery and 9 months afterward. On both occasions, activity and wrist temperature were determined by actigraphy and were related with weight loss. Anthropometric, biochemical, and sleep-related variables, along with dietary intake and physical activity, were analyzed in relation with circadian rhythmicity. Results show significant differences in the circadian expression before and after 9 months of bariatric surgery, with more stable and less fragmented rhythms after weight loss. Moreover, only after surgery were the circadian variables associated to sleep timing and chronotype. The findings of this study indicate that weight loss treatment in patients with morbid obesity improves the circadian rhythm expression, and in such a way that it could be associated with better sleep quality. Moreover, it allows the recovery of the relationship between sleep patterns and circadian rhythm that was lost due to the obesity.
Subject(s)
Bariatric Surgery , Obesity, Morbid , Adult , Circadian Rhythm , Female , Gastrectomy , Humans , Male , Middle Aged , Obesity, Morbid/surgery , SleepABSTRACT
Childhood obesity is a strong risk factor for adult obesity, type 2 diabetes, and cardiovascular disease. The mechanisms that link early adiposity with late-onset chronic diseases are poorly characterised. We developed a mouse model of early adiposity through litter size reduction. Mice reared in small litters (SLs) developed obesity, insulin resistance, and hepatic steatosis during adulthood. The liver played a major role in the development of the disease. OBJECTIVE: To gain insight into the molecular mechanisms that link early development and childhood obesity with adult hepatic steatosis and insulin resistance. METHODS: We analysed the hepatic transcriptome (Affymetrix) of control and SL mice to uncover potential pathways involved in the long-term programming of disease in our model. RESULTS: The circadian rhythm was the most significantly deregulated Gene Ontology term in the liver of adult SL mice. Several core clock genes, such as period 1-3 and cryptochrome 1-2, were altered in two-week-old SL mice and remained altered throughout their life course until they reached 4-6 months of age. Defective circadian rhythm was restricted to the periphery since the expression of clock genes in the hypothalamus, the central pacemaker, was normal. The period-cryptochrome genes were primarily entrained by dietary signals. Hence, restricting food availability during the light cycle only uncoupled the central rhythm from the peripheral and completely normalised hepatic triglyceride content in adult SL mice. This effect was accompanied by better re-alignment of the hepatic period genes, suggesting that they might have played a causal role in mediating hepatic steatosis in the adult SL mice. Functional downregulation of Per2 in hepatocytes in vitro confirmed that the period genes regulated lipid-related genes in part through peroxisome proliferator-activated receptor alpha (Ppara). CONCLUSIONS: The hepatic circadian rhythm matures during early development, from birth to postnatal day 30. Hence, nutritional challenges during early life may misalign the hepatic circadian rhythm and secondarily lead to metabolic derangements. Specific time-restricted feeding interventions improve metabolic health in the context of childhood obesity by partially re-aligning the peripheral circadian rhythm.
Subject(s)
Circadian Rhythm/physiology , Lactation , Liver/metabolism , Non-alcoholic Fatty Liver Disease/metabolism , Adiposity , Adult , Animals , Circadian Rhythm/genetics , Diabetes Mellitus, Type 2/metabolism , Fasting , Female , Humans , Hypothalamus/metabolism , Infant, Newborn , Insulin Resistance/physiology , Metabolic Diseases/metabolism , Mice , Mice, Inbred ICR , Non-alcoholic Fatty Liver Disease/genetics , Obesity/metabolism , Pediatric ObesityABSTRACT
Sleep alterations are linked to circadian disturbances; however, these variables are also related with adiposity, which could impair the study of the previous relationship. Here, we investigated whether the association between adiposity and impaired circadian health is independent of sleep and circadian related variables in a sample of young women. One hundred ninety-two women (18-30 years of age) participated in this cross-sectional study. To evaluate circadian rhythmicity, subjects wore a temperature sensor for six consecutive days, and variables related with the amplitude and stability of the rhythm were calculated. We also assessed adiposity markers (body mass index [BMI], fat mass, waist, and hip circumference), sleep and circadian variables (sleep schedules and quality, social jet lag, and chronotype), energy intake, and physical activity. Partial correlations were conducted to test the associations between circadian and sleep-related variables with adiposity markers. Results showed the circadian pattern of temperature clearly depended on BMI and, to a lesser extent, on sleep variables. Specifically, we showed that higher adiposity was significantly associated with lower amplitude, percentage of variance explained by the rhythm, and intradaily variability and L10 values of the temperature 24 h rhythm. Furthermore, sleep quality was the only variable significantly related with both adiposity and circadian pattern of wrist temperature, while social jet lag and chronotype were only associated with the circadian pattern of temperature. Therefore, we consider BMI should be taken into account when sleep health or disturbances are studied by means of circadian rhythm analyses.
Subject(s)
Adiposity , Sleep , Body Mass Index , Circadian Rhythm , Cross-Sectional Studies , Female , Humans , Temperature , WristABSTRACT
Meal timing relative to sleep/wake schedules is relevant in the search for obesity risk factors. However, clock time does not accurately characterize the timing of food intake in the context of internal circadian timing. Therefore, we studied elapsed between dinner and the midpoint of sleep (TDM) as a practical approach to evaluate meal timing relative to internal timing, and its implications on obesity. To do so, adiposity, sleep, diet, physical activity, and TDM were measured in 133 women. The participants were grouped into four categories according to their sleep timing behavior (early-bed/early-rise; early-bed/late-rise; late-bed/early-rise; late-bed/late-rise). Differences among the categories were tested using ANOVA, while restricted cubic splines were calculated to study the association between TDM and adiposity. Our results show that, although participants had dinner at about the same time, those that had the shortest TDM (early-bed/early-rise group) were found to have significantly higher BMI and waist circumference values (2.3 kg/m2 and 5.2 cm) than the other groups. In addition, a TDM of 6 h was associated with the lowest values of adiposity. The TDM could be a practical approach to personalizing meal timing based on individual sleep/wake schedules. Thus, according to our findings, dining 6 h before the midpoint of sleep is an important finding and could be vital for future nutritional recommendations and for obesity prevention and treatment.
Subject(s)
Adiposity/physiology , Circadian Rhythm/physiology , Meals/physiology , Sleep/physiology , Time Factors , Adolescent , Adult , Anthropometry , Body Mass Index , Diet/adverse effects , Exercise , Feeding Behavior , Female , Humans , Obesity/etiology , Waist Circumference , Young AdultABSTRACT
The Nutrients Editorial Office would like to update the error in the original published version[1] [...].
ABSTRACT
Cocoa contains bioactive components, which vary according to genetic and environmental factors. The present study aimed to ascertain the anti-allergic properties of native Peruvian cocoa populations ("Blanco de Piura" or BPC, "Amazonas Peru" or APC, "Criollo de Montaña" or CMC, "Chuncho" or CCC, and an ordinary cocoa or OC). To do so, after an initial in vitro approach, an in vivo study focused on the induction of an anaphylactic response associated with allergic asthma in Brown Norway rats was carried out. Based on their polyphenol content, antioxidant activity and in vitro effects, the APC and CMC were selected to be included in the in vivo study. Cocoa diets were tested in a model of allergic asthma in which anaphylactic response was assessed by changes in body temperature, motor activity and body weight. The concentration of specific immunoglobulin E (IgE), mast cell protease and leukotrienes was also quantified in serum and/or bronchoalveolar lavage fluid. CMC and OC populations exhibited a protective effect on the allergic asthma rat model as evidenced by means of a partial protection against anaphylactic response and, above all, in the synthesis of IgE and the release of mast cell protease.