CLOCK 3111T/C genetic variant influences the daily rhythm of autonomic nervous function: relevance to body weight control.

BACKGROUND/OBJECTIVES: Humans carrying the genetic risk variant C at the circadian CLOCK (Circadian Locomotor Output Cycles Kaput) 3111T/C have been shown to have more difficulties to achieve desired weight loss than TT carriers. We tested the hypothesis that the daily rhythm of autonomic nervous function differs in CLOCK 3111C carriers, leading to reduced effectiveness in weight control. SUBJECTS/METHODS: We recruited 40 overweight/obese Caucasian women (body mass index>25), 20 carrying CLOCK 3111C (CC and TC) and 20 non-carriers with matched age and body mass index who participated in a dietary obesity treatment program of up to 30 weeks. Following the treatment, ambulatory electrocardiography was continuously monitored for up to 3.5 days when subjects underwent their normal daily activities. To assess autonomic function, heart rate variability analysis (HRV) was performed hourly to obtain mean inter-beat interval between two consecutive R waves (mean RR) and s.d. of normal-to-normal heartbeat intervals (SDNN), and two parasympathetic measures, namely, proportion of differences between adjacent NN intervals that are >50 ms (pNN50), and high-frequency (HF: 0.15-0.4 Hz) power. RESULTS: In the TT carriers, all tested HRV indices showed significant daily rhythms (all P-values <0.0001) with lower mean RR, SDNN, pNN50, and HF during the daytime as compared with the nighttime. The amplitudes of these rhythms except for SDNN were reduced significantly in the C carriers (mean RR: ~19.7%, P=0.001; pNN50: 58.1%, P=0.001; and HF: 41.1%, P=0.001). In addition, subjects with less weight loss during the treatment program had smaller amplitudes in the rhythms of mean RR (P<0.0001), pNN50 (P=0.007) and HF (P=0.003). Furthermore, the rhythmicity-weight loss associations were much stronger in the C carriers as compared to the TT carriers (mean RR: P=0.028, pNN50: P=0.0002; HF: P=0.015). CONCLUSIONS: The daily rhythm of parasympathetic modulation may play a role in the influence of the CLOCK variation on body weight control.

Evening chronotype associates with obesity in severely obese subjects: interaction with CLOCK 3111T/C.

BACKGROUND: Chronotype has been related to obesity and metabolic disturbances. However, little is known about the relationship between circadian preferences and genetic background in CLOCK genes with obesity and weight loss among severely obese patients after bariatric surgery. OBJECTIVES: The research goals were (1) to examine whether evening chronotype is related to obesity and weight loss evolution in severely obese followed during 6 years after bariatric surgery and (2) to examine potential interactions between circadian preferences and CLOCK 3111T/C for obesity in this population. SUBJECTS/METHODS: Participants (n=252, 79% female; age (mean±s.d.): 52±11 years; body mass index (BMI): 46.4±6.0 kg m-2) were grouped into evening and morning types. Obesity and weight loss parameters, energy and macronutrients intake, energy expenditure, chronotype, meal timing, sleep duration and CLOCK genotype were studied. RESULTS: Evening-type subjects showed significantly higher initial body weight (P=0.015) and BMI (P=0.014) than morning types. Moreover, evening-type, when compared with morning types, lost less weight (percentage of excess weight loss) after bariatric surgery (P=0.015). Weight-loss progression between the two chronotype groups differed significantly from the fourth year after the bariatric surgery toward a higher weight regain among evening types (P<0.05). We also detected a significant interaction between CLOCK 3111T/C SNP and chronotype for body weight at baseline (P<0.001). Specifically, among carriers of the risk allele C, evening types showed higher body weight than morning types (P=0.012). In addition, CLOCK 3111T/C SNP significantly associated with obesity and sleep duration in the older subjects. CONCLUSIONS: Evening chronotype is associated with higher obesity in severely obese subjects and with lower weight loss effectiveness after bariatric surgery. In addition, circadian preferences interact with CLOCK 3111T/C for obesity. The circadian and genetic assessment could provide tailored weight loss recommendations in subjects who underwent bariatric surgery.

Meal timing affects glucose tolerance, substrate oxidation and circadian-related variables: A randomized, crossover trial.

BACKGROUND/OBJECTIVES: Timing of food intake associates with body weight regulation, insulin sensitivity and glucose tolerance. However, the mechanism is unknown. The aim of this study was to investigate the effects of changes in meal timing on energy-expenditure, glucose-tolerance and circadian-related variables. SUBJECTS/METHODS: Thirty-two women (aged 24±4 years and body mass index 22.9±2.6 kg m(-2)) completed two randomized, crossover protocols: one protocol (P1) including assessment of resting-energy expenditure (indirect-calorimetry) and glucose tolerance (mixed-meal test) (n=10), the other (P2) including circadian-related measurements based on profiles in salivary cortisol and wrist temperature (Twrist) (n=22). In each protocol, participants were provided with standardized meals (breakfast, lunch and dinner) during the two meal intervention weeks and were studied under two lunch-eating conditions: Early Eating (EE; lunch at 13:00) and Late Eating (LE; lunch 16:30). RESULTS: LE, as compared with EE, resulted in decreased pre-meal resting-energy expenditure (P=0.048), a lower pre-meal protein-corrected respiratory quotient (CRQ) and a changed post-meal profile of CRQ (P=0.019). These changes reflected a significantly lower pre-meal utilization of carbohydrates in LE versus EE (P=0.006). LE also increased glucose area under curve above baseline by 46%, demonstrating decreased glucose tolerance (P=0.002). Changes in the daily profile of cortisol and Twrist were also found with LE blunting the cortisol profile, with lower morning and afternoon values, and suppressing the postprandial Twrist peak (P<0.05). CONCLUSIONS: Eating late is associated with decreased resting-energy expenditure, decreased fasting carbohydrate oxidation, decreased glucose tolerance, blunted daily profile in free cortisol concentrations and decreased thermal effect of food on Twrist. These results may be implicated in the differential effects of meal timing on metabolic health.

Circadian rhythmicity as a predictor of weight-loss effectiveness.

OBJECTIVES: Some of the major challenges associated with successful dietary weight management include the identification of individuals not responsive to specific interventions. The aim was to investigate the potential relationship between weight loss and circadian rhythmicity, using wrist temperature and actimetry measurements, in women undergoing a weight-loss program, in order to assess whether circadian rhythmicity could be a marker of weight-loss effectiveness. METHODS: Participants were 85 overweight and obese women (body mass index, BMI: 30.24±4.95 kg m(-2)) subjected to a weight-reduction program. Efficacy of the treatment was defined as total weight loss, percentage of initial weight and weekly weight loss rates. Circadian rhythmicity in wrist temperature motor activity and position were analyzed using different sensors. RESULTS: Lower weight loss was related with a more flattened pattern measured as amplitude from cosinor (r=0.235, P=0.032), a higher fragmentation of rhythms determined by higher intradaily variability (IV) (r=-0.339, P=0.002), and an impaired wrist temperature circadian rhythm determined by the means of Circadian Function Index (r=0.228, P=0.038). Further analyses showed that low responders displayed lower amplitude (0.71±0.36 versus 1.24±0.62, P=0.036) and higher fragmentation of the circadian rhythm (0.24±0.11 versus 0.15±0.07, P=0.043) than high responders. Whereas we did not find significant differences in total activity rates between high responders and low responders, we found significant differences for the mean values of body position for high responders (39.12±3.79°) as compared with low responder women (35.31±2.53°, P=0.01). CONCLUSIONS: Circadian rhythms at the beginning of the treatment are good predictors of future weight loss. Further treatment should consider chronobiological aspects to diagnose obesity and effectiveness of treatments.

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.

Differences in circadian rhythmicity in CLOCK 3111T/C genetic variants in moderate obese women as assessed by thermometry, actimetry and body position.

INTRODUCTION: Genetics is behind our circadian machinery. CLOCK (Circadian Locomotor Output Cycles Kaput) 3111T/C single-nucleotide polymorphism (SNP) has been previously related to obesity and weight loss. However, phenotypic association and functionality of CLOCK 3111 locus is still unknown. The aim of this study was to determine, in free-living conditions, if the presence of CLOCK 3111C in overweight women could be related to (a) circadian disorders, and (b) changes in sleep quality, to improve understanding of the previously demonstrated associations with obesity and reduced weight loss of the C carriers. METHODS: Wrist temperature, actimetry and position (TAP) and TAP variables were measured as markers of circadian functionality during 8 consecutive days. A rest-activity and food diary was also completed, whereas sleep quality was determined by domiciliary polysomnography. We recruited 85 women who were overweight with body mass index (BMI) of 28.59±4.30 kg m(-2) and age 43±12 years. From this sample, we found that 43 women were carrying the minor allele (C) for CLOCK 3111T/C SNP and 42 women were TT carriers (major allele carriers). Both groups of patients were matched for number, age, obesity parameters and energy intake. RESULTS: Compared with TT subjects, who showed more robust circadian rhythm profiles, patients with the C allele displayed significant circadian abnormalities: lower amplitude and greater fragmentation of the rhythm, a less stable circadian pattern and a significantly weakened circadian function, as assessed by the circadian function index (CFI). C subjects were also less active, started their activities later in the morning and were sleepier during the day, showing a delayed acrophase that characterizes 'evening-type' subjects. CONCLUSION: C genetic variants in CLOCK 3111T/C display a less robust circadian rhythm than TT and a delayed acrophase that characterizes 'evening-type' subjects. We support the notion that identifying CLOCK genotypes in patients may assist the therapist in characterization of the roots of the metabolic problem.

Apolipoprotein A-II polymorphism: relationships to behavioural and hormonal mediators of obesity.

BACKGROUND: The interaction between apolipoprotein A-II (APOA2) m265 genotype and saturated fat for obesity traits has been more extensively demonstrated than for any other locus, but behavioural and hormonal mechanisms underlying this relationship are unexplored. In this study, we evaluated relationships between APOA2 and obesity risk with particular focus on patterns of eating and ghrelin, a hormonal regulator of food intake. DESIGN: Cross-sectional study. SUBJECTS: Overweight and obese subjects (n=1225) were evaluated at baseline in five weight loss clinics in southeastern Spain. METHODS: Behavioural data were assessed using a checklist of weight loss obstacles. Logistic regression models were fitted to estimate the risk of a specific behaviour associated with APOA2 genotype. Relationships between APOA2 genotype and saturated fat intakes for anthropometric traits and plasma ghrelin were evaluated by analysis of variance. To construct categorical variables to evaluate interactions, saturated fat intake was dichotomized into high and low according to the population median intake or as tertiles. RESULTS: Homozygous minor (CC) subjects were more likely to exhibit behaviours that impede weight loss ('Do you skip meals', odds ratio (OR)=2.09, P=0.008) and less likely to exhibit the protective behaviour of 'Do you plan meals in advance' (OR=0.64, P=0.034). Plasma ghrelin for CC subjects consuming low saturated fat was lower compared with (1) CC subjects consuming high saturated fat, (2) TT+TC carriers consuming low saturated fat and (3) TT+TC carriers consuming high saturated fat (all P<0.05). CONCLUSIONS: APOA2 m265 genotype may be associated with eating behaviours and dietary modulation of plasma ghrelin. Expansion of knowledge of APOA2 and obesity to include modulation of specific behaviours and hormonal mediators not only broadens understanding of gene-diet interactions, but also facilitates the pragmatic, future goal of developing dietary guidelines based on genotype.

SIRT1 and CLOCK 3111T> C combined genotype is associated with evening preference and weight loss resistance in a behavioral therapy treatment for obesity.

BACKGROUND: A new negative feedback loop has been proposed, which suggests connections between the circadian clock and SIRTUIN1 (SIRT1)-dependent functions associated with cell survival, development and metabolism. OBJECTIVE: To develop a SIRT1 and circadian locomotor output cycles kaput (CLOCK) combined genotype and to assess its associations with the chronotype of subjects and their potential resistance to weight loss in a behavioral treatment for obesity based on a Mediterranean diet. DESIGN: Overweight /obese subjects (n=1465), aged 20-65 years, who attended outpatient obesity clinics, were genotyped for SIRT1 (rs1467568) and CLOCK (3111T>C, rs1801260). Anthropometric, biochemical and dietary-intake variables were analyzed. Effectiveness of the program and weight loss progression during 30 weeks of treatment was assessed. RESULTS: We found highly consistent associations between the morning/evening questionnaires across the different genotype categories. Subjects carrying minor alleles at SIRT1 and CLOCK loci (R group) displayed a higher resistance to weight loss and a lower weekly weight loss rate as compared with homozygotes for both major alleles (P group). Significant differences were found across genotypes in weight loss progression during the 30 weeks of treatment (P=0.039). Dietary habits indicated that R carriers had a lower intake of total carbohydrates and monounsaturated fats, and a higher intake of saturated fats than those carrying the intermediate (M) and the P genotype (P=0.02). Plasma ghrelin concentrations were also significantly higher in subjects carrying the R genotype. CONCLUSION: Variants of both SIRT1 and CLOCK have an additive effect on resistance to weight loss that could be related to the chronotype of the subject, higher plasma levels of ghrelin and less adherence to Mediterranean diet patterns.

Timing and duration of sleep and meals in obese and normal weight women. Association with increase blood pressure.

The aim was to evaluate the efficiency and duration of sleep and meals in normal-weight and obese women and the impact of these factors on metabolic syndrome (MetS) variables. The study was conducted in 70 women, normal-weight women (n=20) and obese women (n=50). Anthropometric variables, plasma glucose, lipids and ghrelin concentrations were determined. Blood pressure measurement was performed before lunch and before dinner for a week on alternate days. Subjects were instructed to keep a sleep and feeding diary. In general, obese women displayed longer and a significantly higher number of awakenings per week than normal-weight women and a higher duration of naps. Sleep efficiency was significantly lower in obese women. The higher intake in energy in the obese women was due to snacking differences. Moreover, higher sleep efficiency was correlated with a decrease in the diastolic blood pressure evening/morning ratio. Interestingly, among normal-weight women, visceral fat increased with the number of awakenings while plasma ghrelin was inversely correlated with meal duration (P=0.027). In conclusion, obese women had lower sleep efficiency, ate more quickly and spent more time eating and sleeping during the daytime hours than normal-weight women. Of note, sleep efficiency was associated with MetS features. Further interventions in obesity could include educating patients in food timing and in healthier sleep-hygiene practices, helping them to modify bad sleep habits.

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 adolescent's 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.

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.

CLOCK gene is implicated in weight reduction in obese patients participating in a dietary programme based on the Mediterranean diet.

INTRODUCTION: The success of obesity therapy is dependent on the genetic background of the patient. Circadian Locomotor Output Cycles Kaput (CLOCK), one of the transcription factors from the positive limb of the molecular clock, is involved in metabolic alterations. OBJECTIVE: To investigate whether five candidate polymorphisms from CLOCK were associated with anthropometric, metabolic measures and weight loss in response to a behavioural weight reduction programme based on the Mediterranean diet. METHODS: Five hundred overweight/obese subjects, aged 20-65 years, who attended outpatient clinics specializing in obesity, were studied. Anthropometric, biochemical and dietary intake variables were analysed. Effectiveness of the programme and weight loss progression during 28 weeks of treatment was assessed. RESULTS: Four of five CLOCK SNPs selected were significantly associated with obesity variables (P<0.05). The genetic variation in the rs1801260 CLOCK was associated with obesity at baseline and also affected weight loss. Patients with the variant allele (G) lost significantly less weight i(P=0.008) compared with wild type. Repeated measures analysis showed that weight loss over time was significantly different between rs1801260 CLOCK variations (P=0.038). Carriers of the G allele displayed greater difficulty in losing weight than non-carriers. In this particular polymorphism, the frequency of short-time sleepers (< or =6 h per day) was greater in minor allele carriers than in non-carriers (59% vs 41%; P<0.05). CLOCK polymorphisms were also associated with significant differences in total plasma cholesterol at the completion of dietary treatment (P<0.05). CONCLUSIONS: We have replicated previous studies showing a relationship between CLOCK gene polymorphisms and obesity. CLOCK rs1801260 SNP may predict the outcome of body weight reduction strategies based on low-energy diets.

[Regional distribution of the body fat: use of image techniques as tools for nutritional diagnosis]. / Distribución regional de la grasa corporal: uso de técnicas de imagen como herramienta de diagnóstico nutricional.

Fat mass is the most variable component in the human body, both when comparing several individuals and when considering changes in the same person throughout life. Obesity is characterized by an excess of body fat that affects health and well-being of individuals. Risk associated with excess body fat is due, in part, to location of fat rather than to total amount. Today is stated that causes and metabolic consequences of regional distribution of fat are of particular clinical importance. To identify a compartment of morbid adipose tissue and to be able to act on it is one of the main aims of the present research. In this review, we have revised the existing literature on location and characteristics of total body fat in human adult. We have focused on abdominal region, basing this review on the use of modern imaging techniques available nowadays, such as computerized tomography and magnetic resonance imaging, with their advantages and limitations. The purpose of this review is to assess whether it is possible to know the body composition and fat distribution on the basis of image methods. Computed tomography technique was first applied in studies of obesity, but today, due to the inconvenience of irradiating the patient, this technique is being replaced by magnetic resonance that, in addition to avoid radiation, provides images of extraordinary quality. Both methods allow to subdivide the classic general fat depots in others more specific. Subcutaneous fat depot can be superficial or deep, while visceral can be divided in mesenteric, omental or epiploic, retroperitoneal and perirrenal fat. In addition, these modern techniques of imaging permit to study muscular fat, considered by some authors as the new fat compartment. Muscular fat includes fat located between skeletal muscle fibers, called extramyocellular fat, as well as lipids located within skeletal muscle fibers (intramyocellular fat). Its importance lies not only in size, similar to visceral fat, but on its pathophysiological implications. Finally, techniques of image analysis have prove to be extremely useful in studying the location and extent of abdominal fat compartments, becoming reference to validate equations obtained from the so-called "indirect methods".

Expression of cortisol metabolism-related genes shows circadian rhythmic patterns in human adipose tissue.

OBJECTIVE: To analyze, in morbid obese patients, the expression of several human genes regulating cortisol metabolism, such as glucocorticoid receptor (GR), 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1), 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2), stearoyl-acute regulatory protein (StAR), 5alpha-reductase type I (5alpha-R) and peroxisome proliferator-activated receptor-gamma (PPARgamma) in two different adipose depots. A second objective was to characterize the circadian rhythmicity of these genes in both adipose tissue (AT) regions. DESIGN: Visceral and subcutaneous abdominal AT biopsies were obtained from obese patients (body mass index >or=40 kg m(-2)). To carry out rhythmic expression analysis, AT explants were cultured for 24 h and gene expression at times (T) 0, 6, 12 and 18 h, was performed with quantitative real-time PCR. RESULT: GR, 11betaHSD1 and PPARgamma genes were highly expressed in both subcutaneous and visceral depots. StAR and 5alpha-R genes were detected at lower levels. The expression of 11betaHSD2 was quantified in both AT depots with a higher expression in the visceral depot (P=0.032). Both sexes had similar gene expression levels, except for 5alpha-R (P=0.002). The genes studied showed circadian rhythmicity being more robust in visceral than in subcutaneous AT. Genes ranged in anti-phase between both depots (P=0.002). This rhythmicity was maintained in an AT culture. CONCLUSION: We have shown for the first time circadian rhythmicity in glucocorticoid-related gene expression in human AT ex vivo. These results may have potential therapeutic implications with respect to the pathogenesis and treatment of diseases, such as obesity, type 2 diabetes and cardiovascular diseases.

Adiponectin is associated with serum and adipose tissue fatty acid composition in rats.

The objective of the present work is to analyse the relationships between changes in adiponectin and fatty acid composition in serum and adipose tissue in rats. Samples from serum and different adipose depots (periovarian, mesenteric and subcutaneous) were obtained from ageing rats (14- and 20-month-old) to determine fatty acid composition (gasliquid chromatography). In serum, insulin (radioimmunoassay) and adiponectin levels (enzyme-linked immunosorbent assay) were also measured, while adiponectin gene expression was analysed (real time-qPCR) in all fat depots. There were significant age-related reductions in adipose tissue saturated (SFA) and trans fatty acids and increases in monounsaturated fatty acids in parallel with diminished adiponectin expression in periovarian and mesenteric adipose tissue (p<0.05). Age-independent negative correlations were found between adiponectin gene expression in mesenteric adipose tissue and C12:0, C14:0 and C18:2 trans fatty acids (p<0.05). There was a positive association between serum adiponectin and adipose tissue oleic acid, while palmitoleic acid was negatively associated with adiponectin expression and positively correlated with insulin concentration. For the first time, positive relationships are reported between the proportion of n-6 polyunsaturated fatty acids (PUFA) in adipose tissue and adiponectin concentration and expression. In summary, adiponectin expression and serum levels are associated with fatty acid composition, with SFA, trans and palmitoleic fatty acids appearing as negative markers for adiponectin, and oleic acid and n-6 PUFA as positive ones. In addition, most associations were found in the visceral depots, highlighting the importance of visceral fat in the metabolic status.

Behavioural therapy in the treatment of obesity (I): new directions for clinical practice.

OBJECTIVES: Behavioural therapy (BT) in obesity treatment helps individuals to develop skills to achieve healthier body weights. Instead of helping to decide what to change, it helps to identify how to change; lifestyle modification is essential for any treatment of obesity, be it dieting, medication, surgery, etc. Physicians often tend to be unwilling to use BT considering it time-consuming and skill-intensive. However, BT can be standardized and used more readily in clinical practice. Besides, new approaches have been developed which contribute to increase the success of the treatments, like non face-to-face techniques, or the new cognitive therapy. SETTING: Classical knowledge on BT has been updated with recent publications and information on these new approaches, combined with our own experience in the clinical treatment of obesity. RESULTS: Most research on BT has been conducted in university-based programs which, despite their importance, tell us little about its effectiveness in actual clinical practice. Future research might focus on determining how BT can be best applied in a real-world setting. Examples of new directions are increased maintenance periods, use of Internet, and new cognitive therapy. Besides, elucidating the genetic component in the prognosis of weight management -the nutrigenomic approach- could assist in the development of more effective and individually tailored therapeutic strategies; indeed, single nucleotide polymorphisms in candidate genes have been related with eating patterns. CONCLUSIONS: This review gives a renewed perspective of BT for obesity, offers key-pointers and describes specific ways in which medical professionals can promote and encourage self-care of patients.

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/m(2), 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.

Insulin effect on adipose tissue (AT) adiponectin expression is regulated by the insulin resistance status of the patients.

OBJECTIVE: The objective of the present study was to determine a possible depot-specific effect of insulin-stimulation on adiponectin gene expression in adipose tissue (AT) explants from subcutaneous and visceral AT. A secondary aim was to analyse the associations of adiponectin plasma levels, as well as control and insulin-stimulated gene expression levels with different features of the metabolic syndrome. DESIGN: Visceral and subcutaneous AT biopsies were obtained from 20 subjects (10 men and 10 women) with morbid obesity. Metabolic syndrome and other clinical features were studied. Adiponectin expression from isolated adipocytes was measured both in control and after insulin-stimulation conditions by quantitative PCR. RESULTS: Subcutaneous adipocytes expressed significantly higher amounts of adiponectin mRNA than visceral tissue (P = 0.027). Insulin increased adiponectin expression specifically in the omental tissue (P = 0.011). In these patients, waist : hip ratio was directly correlated with adiponectin expression in the visceral depot (r = 0.660; P = 0.014), while fasting glucose levels were inversely associated with adiponectin mRNA in the subcutaneous tissue (r =-0.604; P = 0.022). Adiponectin expression after addition of insulin was positively correlated with some metabolic risk factors (cholesterol, LDL-cholesterol, insulin, C-peptide). Interestingly, local insulin induced an up-regulation of adiponectin expression in the AT of those patients with higher metabolic syndrome disturbances. CONCLUSIONS: Our results clearly demonstrate that insulin exerts a stimulating effect on adiponectin gene expression in a depot-specific manner. The AT response to insulin stimulus depends on the physiopathological situation, being higher in those individuals with impaired insulin-sensitivity and lipid metabolism.

Heritability of siesta and night-time sleep as continuously assessed by a circadian-related integrated measure.

Siesta is a relevant aspect of sleep due to its posited relationship with health or cognitive function. However, unlike night-time sleep, studies about daytime-sleep determinants and characteristics are scarce, and the genetic/environmental structure of siesta is still unknown. Our aim was to explore the relative contribution of genetic and environmental factors to variation in sleep-wake rhythm, measured by a continuous assessment of temperature-activity-position (TAP), which allows for diurnal sleep analysis. The sample comprised 53 pairs of female twins (28 MZ and 25 DZ), selected from the Murcia Twin Register. Mean age of participants was 52 (SD: 6.03). Zygosity was determined by DNA. We conducted separate univariate analyses to study the sources of variance of daytime and night-time sleep parameters. About 60% of the sample reported to take siesta at least once a week. Heritability of taking siesta and daytime sleep duration was 65 and 61% respectively. Other sleep parameters obtained by TAP showed heritability estimates between 36 and 69%, suggesting a relevant impact of genetic factors on sleep rhythm. This is the first study to investigate the relative contribution of genetic factors to siesta. By using TAP, we introduce a novel approach to the study of diurnal sleep characteristics.

Anthropometric indexes for visceral fat estimation in overweight/obese women attending to age and menopausal status.

The objective of the present study was to assess the usefulness and accuracy of different anthropometric measurements in the diagnosis of abdominal visceral obesity in overweight/obese women attending to age and menopausal status. The secondary objective was to evaluate the usefulness of waist circumference (WC) in two different sites. Different anthropometric indicators were assessed in 55 overweight/obese women (n=22 premenopausal, n=33 postmenopausal; BMI > 25 kg/m(2)) and compared with computed tomography measurements of abdominal visceral adipose tissue (VA) performed as a single scan at L4-L5. Our results show that VA significantly differs between both groups of women. Waist2-hip ratio (W2HR) was significantly correlated to VA in both groups of women. After multiple regression analysis, sagittal diameter was an independent parameter to predict VA. However, no significant differences were obtained in this diameter between both groups. None of the waist circumferences were significantly associated to VA. Moreover, the two sites of WC were statistically different. In conclusion, waist-to-hip ratio, measured immediately above the iliac crest (W2HR) seems to be the more appropriated anthropometric index for the estimation of visceral fat in women, independently of age. Although sagittal diameter is a fine parameter to predict visceral fat area, it is not adequate to discriminate between women of different age or menopausal status. In contrast with previous findings, waist circumferences do not seem to be useful for predicting VA.