Marta Garaulet

Timing of food intake predicts weight loss effectiveness

Background:There is emerging literature demonstrating a relationship between the timing of feeding and weight regulation in animals. However, whether the timing of food intake influences the success of a weight-loss diet in humans is unknown.Objective:To evaluate the role of food timing in weight-loss effectiveness in a sample of 420 individuals who followed a 20-week weight-loss treatment.Methods:Participants (49.5% female subjects; age (mean±s.d.): 42±11 years; BMI: 31.4±5.4 kg m−2) were grouped in early eaters and late eaters, according to the timing of the main meal (lunch in this Mediterranean population). 51% of the subjects were early eaters and 49% were late eaters (lunch time before and after 1500 hours, respectively), energy intake and expenditure, appetite hormones, CLOCK genotype, sleep duration and chronotype were studied.Results:Late lunch eaters lost less weight and displayed a slower weight-loss rate during the 20 weeks of treatment than early eaters (P=0.002). Surprisingly, energy intake, dietary composition, estimated energy expenditure, appetite hormones and sleep duration was similar between both groups. Nevertheless, late eaters were more evening types, had less energetic breakfasts and skipped breakfast more frequently that early eaters (all; P<0.05). CLOCK rs4580704 single nucleotide polymorphism (SNP) associated with the timing of the main meal (P=0.015) with a higher frequency of minor allele (C) carriers among the late eaters (P=0.041). Neither sleep duration, nor CLOCK SNPs or morning/evening chronotype was independently associated with weight loss (all; P>0.05).Conclusions:Eating late may influence the success of weight-loss therapy. Novel therapeutic strategies should incorporate not only the caloric intake and macronutrient distribution—as is classically done—but also the timing of food.

Short sleep duration is associated with increased obesity markers in European adolescents: effect of physical activity and dietary habits. The HELENA study

Background:Adequate sleep is a critical factor for adolescents health and health-related behaviors.Objective:(a) to describe sleep duration in European adolescents from nine countries, (b) to assess the association of short sleep duration with excess adiposity and (c) to elucidate if physical activity (PA), sedentary behaviors and/or inadequate food habits underlie this association.Design:A sample of 3311 adolescents (1748 girls) aged 12.5–17.49 years from 10 European cities in Austria, Belgium, France, Germany, Greece, Hungary, Italy, Spain and Sweden was assessed in the Healthy Lifestyle in Europe by Nutrition in Adolescence Study between 2006 and 2008. We measured anthropometric data, sleep duration, PA (accelerometers and questionnaire), television watching and food habits (Food Frequency Questionnaire).Results:Average duration of daily sleep was 8 h. Shorter sleepers showed higher values of BMI, body fat, waist and hip circumferences and fat mass index (P<0.05), particularly in females. Adolescents who slept <8 h per day were more sedentary, as assessed by accelerometry, and spent more time watching TV (P<0.05). The proportion of adolescents who eat adequate amounts of fruits, vegetables and fish was lower in shorter sleepers than in adolescents who slept ⩾8 h per day, and so was the probability of having adequate food habits (P<0.05). Correlation analysis indicated that short sleep is associated with higher obesity parameters.Conclusions:In European adolescents, short sleep duration is associated with higher adiposity markers, particularly in female adolescents. This association seems to be related to both sides of the energy balance equation due to a combination of increased food intake and more sedentary habits.

Harmonization of Anthropometric Measurements for a Multicenter Nutrition Survey in Spanish Adolescents

OBJECTIVE Although the need for accurate anthropometric measurement has been repeatedly stressed, reports on growth and physical measurements in human populations rarely include estimates of measurement error. We describe the standardization process and reliability of anthropometric measurements carried out in a pilot study. METHODS For the intraobserver assessment of anthropometric measurements, we studied 101 adolescents (58 boys and 43 girls) from five cities. For interobserver assessment, we studied 10 adolescents from the same class in Zaragoza and different from those in the intraobserver sample. RESULTS For skinfold thickness, intraobserver technical errors of measurement (TEMs) in general were smaller than 1 mm; for circumferences, TEMs in general were smaller than 1 cm. Intraobserver reliability for skinfold thickness was greater than 95% for almost all cases; for circumferences, intraobserver reliability generally was greater than 95%. Interobserver TEMs ranged from 1 to 2 mm for the six skinfold thicknesses measured; for circumferences, TEMs were smaller than 1 cm for the arm, biceps, and waist and between 1 and 2 cm for the hip and thigh. Interobserver reliabilities for skinfold thickness and circumference were always greater than 90%, except for biceps skinfold. CONCLUSIONS Our results are in agreement with those recommended in the literature. Therefore, these anthropometric measures seem to be adequate to assess body composition in a multicenter survey in adolescents.

Relationship between fat cell size and number and fatty acid composition in adipose tissue from different fat depots in overweight/obese humans

Objective:To evaluate the body fat distribution and fat cell size and number in an overweight/obese population from both genders, and to determine the possible relationship between fat cell data from three different adipose tissue localizations (subcutaneous (SA), perivisceral and omental) and adipose tissue composition and dietary fatty acid.Design:The sample consisted of 84 overweight/obese patients (29 men and 55 women) who have undergone abdominal surgery. The adipocyte size and total fat cell number was studied. Fat cell data were related with anthropometric, adipose tissue and subjects habitual diet fatty acid composition.Measurements:Fat cell size was measured according to a Sjöström method from the three adipose depots. Total fat cell number was also calculated. The fatty acid composition of adipose tissue was examined by gas chromatography. The subjects diet was studied by a 7 days dietary record.Results:Our data showed a negative relationship between the adipocyte size and the n-6 and n-3 fatty acids content of the SA adipose tissue (r=−0.286, P=0,040; r=−0.300, P=0.030) respectively, and the n-6 in the omental depots (r=−0.407, P=0.049) in the total population. Positive associations with the total of saturated (r=0.357, P=0.045) and negative (r=−0.544, P=0.001) with the n-9 fatty acids were observed when the relationship between the adipocyte number and the fatty acid composition of the different anatomical fat regions was studied. Dietary fatty acids composition positively correlated with fat cell size for the myristic acid (14:0) in men in the visceral depot (r=0.822, P=0.023), and for the saturated fatty acids (SFAs) in women in the omental depot (r=0.486, P=0.035).Conclusion:In the present study, for the first time in humans we found that n-3 and n-6 fatty acids are related to a reduced adipocyte size according to the depot localization. In contrast, adipose tissue and dietary SFAs sinificantly correlated with an increase in fat cell size and number. No significant associations were found between n-9 acids content and adipocyte size. However, n-9 adipose tissue fatty acids content was inversely associated with fat cell number showing that this type of fatty acid could limit hyperplasia in obese populations. The differences observed in the three different regions, perivisceral, omental and SA fat, indicate that this population adipose tissue have depot-specific differences.

The chronobiology, etiology and pathophysiology of obesity

The effect of CD on human health is an emerging issue. Many records link CD with diseases such as cancer, cardiovascular, cognitive impairment and obesity, all of them conducive to premature aging. The amount of sleep has declined by 1.5 h over the past century, accompanied by an important increase in obesity. Shift work, sleep deprivation and exposure to bright light at night increase the prevalence of adiposity. Animal models have shown that mice with Clock gene disruption are prone to developing obesity and MetS. This review summarizes the latest developments with regard to chronobiology and obesity, considering (1) how molecular clocks coordinate metabolism and the specific role of the adipocyte; (2) CD and its causes and pathological consequences; (3) the epidemiological evidence of obesity as a chronobiological illness; and (4) theories of circadian disruption and obesity. Energy intake and expenditure, relevance of sleep, fat intake from a circadian perspective and psychological and genetic aspects of obesity are examined. Finally, ideas about the use of chronobiology in the treatment of obesity are discussed. Such knowledge has the potential to become a valuable tool in the understanding of the relationship between the chronobiology, etiology and pathophysiology of obesity.

Chronobiology, genetics and metabolic syndrome

Purpose of review Circadian rhythms are such an innate part of our lives that we rarely pause to speculate why they even exist. Recently, some studies have suggested that the disruption of the circadian system may be causal for the manifestations of metabolic syndrome (MetS). This review summarizes the latest evidence of the existing interaction among chronobiology, genetics and MetS. Recent findings Shift work, sleep deprivation and bright light exposure at night are related to increased adiposity and prevalence of MetS. Animal models have revealed that mice with circadian locomotor output cycles kaput (clock) gene disruption are prone to develop a phenotype resembling MetS. Moreover, studies in humans have shown that clock genes are expressed in adipose tissue, and that both their levels of expression and their genetic variants correlate with different components of the MetS. Current studies are illustrating the particular role of different clock gene variants and their predicted haplotypes in MetS. Summary The circadian system has an important impact on metabolic disturbances and vice versa. Although the precise mechanism linking the MetS to chronodisruption is not well known, hypotheses point to the internal desynchronization between different circadian rhythms. The novelty of this area of research is contributing to the development of new and intriguing studies, particularly those focused on the association between different clock genes polymorphisms and MetS traits.

Timing of food intake and obesity: a novel association.

Recent studies link energy regulation to the circadian clock at the behavioral, physiological and molecular levels, emphasizing that the timing of food intake itself may have a significant role in obesity. In this regards, there is emerging literature in animals demonstrating a relationship between the timing of feeding and weight regulation. Unusual feeding time can produce a disruption of the circadian system which might produce unhealthy consequences in humans. In a longitudinal study, we recently showed that the timing of the main meal was predictive of weight loss during a 20-week dietary intervention and that this effect was independent from total 24-h caloric intake. The importance of caloric distribution across the day on weight loss therapy was supported by a recent 12-week experimental study showing that subjects assigned to high caloric intake during breakfast lost significantly more weight than those assigned to high caloric intake during the dinner. Furthermore, one of the most influential discoveries relevant for this area of research in the last years is the presence of an active circadian clock in different organs related to food intake. This is the case for stomach, intestine, pancreas or liver. New data also suggest that there is a temporal component in the regulation of adipose tissue functions. Thus, a specific temporal order in the daily patterns of adipose tissue genes appears to be crucial for adipose tissue to exclusively either accumulate fat or to mobilize fat at the proper time. Taking into account that feeding is the source of energy for adipose tissue, the time of feeding, particularly for high-energy content meals, may be decisive, and changes in this timing could have metabolic consequences for the development of obesity and for weight loss.

CLOCK genetic variation and metabolic syndrome risk: modulation by monounsaturated fatty acids

BACKGROUND Disruption of the circadian system may be causal for manifestations of the metabolic syndrome (MetS). OBJECTIVE The objective was to study the associations of 5 CLOCK polymorphisms with MetS features by analyzing fatty acid (FA) composition from dietary and red blood cell (RBC) membrane sources. DESIGN Participants (n = 1100) in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study were included. Dietary intake was estimated with a validated questionnaire. Anthropometric and biochemical measurements and genotypes were determined. Postprandial lipids and the FA composition of RBC membranes were analyzed. RESULTS CLOCK single nucleotide polymorphisms were significantly associated with obesity and individual components of MetS. For single nucleotide polymorphism rs4580704, minor allele carriers had a 46% lower risk of hypertension than did noncarriers. The monounsaturated fatty acid (MUFA) content of RBC membranes, particularly oleic acid, changed according to CLOCK genetic variants (P < 0.05). We identified significant gene-diet interactions associated with MetS at the CLOCK locus. By dichotomizing MUFA intake, we found different effects across rs4580704 genotypes for glucose (P = 0.020) and insulin resistance (P = 0.026). The protective effect of the minor allele on insulin sensitivity was only present when MUFA intake was >13.2% of energy. We also found different effects across CLOCK 3111T-->C genotypes for saturated fatty acid intake (% of energy) (P = 0.017). The deleterious effect of gene variants on waist circumference was only found with high saturated fatty acid intakes (>11.8%). CONCLUSIONS CLOCK polymorphisms interact with FAs to modulate MetS traits. The dietary source and membrane content of MUFAs are implicated in the relations between alterations in the circadian system and MetS.

Clock genes are implicated in the human metabolic syndrome

Background:Clock genes play a role in adipose tissue (AT) in animal experimental models. However, it remains to be elucidated whether these genes are expressed in human AT.Objective:We investigated the expression of several clock genes, Bmal1, Per2 and Cry1, in human AT from visceral and subcutaneous abdominal depots. A second objective was to elucidate whether these clock genes expressions were related to the metabolic syndrome features.Methods:Visceral and subcutaneous AT samples were obtained from morbid obese men (n=8), age: 42±13 years and body mass index⩾40 kg/m2, undergoing laparoscopic surgery due to obesity. Biopsies were taken as paired samples at the beginning of the surgical process (1100 hour). Metabolic syndrome features such as waist circumference, plasma glucose, triglycerides, total cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein (LDL) cholesterol were also studied. Homeostasis model assessment index of insulin resistance was also calculated. The expression of the different clock genes, hBmal1, hPer2 and hCry1, was determined by quantitative real-time PCR.Results:Clock genes were expressed in both human AT depots. hBmal1 expression was significantly lower than hPer2 and hCry1 in both AT (P<0.001). All genes were highly correlated to one another in the subcutaneous fat, while no correlation was found between Bmal1 and Per2 in the visceral AT. Clock genes AT expression was associated with the metabolic syndrome parameters: hPer2 expression level from visceral depot was inversely correlated to waist circumference (P<0.01), while the three clock genes studied were significantly and negatively correlated to total cholesterol and LDL cholesterol (P<0.01).Conclusion:We have demonstrated for the first time in humans that clock genes are expressed in both subcutaneous and visceral fat. Their association with abdominal fat content and cardiovascular risk factors may be an indicator of the potential role of these clock genes in the metabolic syndrome disturbances.

CLOCK, PER2 and BMAL1 DNA methylation: association with obesity and metabolic syndrome characteristics and monounsaturated fat intake.

The circadian clock system instructs 24-h rhythmicity on gene expression in essentially all cells, including adipocytes, and epigenetic mechanisms may participate in this regulation. The aim of this research was to investigate the influence of obesity and metabolic syndrome (MetS) features in clock gene methylation and the involvement of these epigenetic modifications in the outcomes. Sixty normal-weight, overweight and obese women followed a 16-weeks weight reduction program. DNA methylation levels at different CpG sites of CLOCK, BMAL1 and PER2 genes were analyzed by Sequenoms MassARRAY in white blood cells obtained before the treatment. Statistical differences between normal-weight and overweight + obese subjects were found in the methylation status of different CpG sites of CLOCK (CpGs 1, 5-6, 8 and 11-14) and, with lower statistical significance, in BMAL1 (CpGs 6-7, 8, 15 and 16-17). The methylation pattern of different CpG sites of the three genes showed significant associations with anthropometric parameters such as body mass index and adiposity, and with a MetS score. Moreover, the baseline methylation levels of CLOCK CpG 1 and PER2 CpGs 2-3 and 25 correlated with the magnitude of weight loss. Interestingly, the percentage of methylation of CLOCK CpGs 1 and 8 showed associations with the intake of monounsaturated and polyunsaturated fatty acids. This study demonstrates for the first time an association between methylation status of CpG sites located in clock genes (CLOCK, BMAL1 and PER2) with obesity, MetS and weight loss. Moreover, the methylation status of different CpG sites in CLOCK and PER2 could be used as biomarkers of weight-loss success, particularly CLOCK CPGs 5-6. (Author correspondence: garaulet@um.es)