Lifestyle mediators of associations among siestas, obesity, and metabolic health.

OBJECTIVE: The aim of this study was to determine the association between siestas/no siestas and obesity, considering siesta duration (long: >30 minutes, short: ≤30 minutes), and test whether siesta traits and/or lifestyle factors mediate the association of siestas with obesity and metabolic syndrome (MetS). METHODS: This was a cross-sectional study of 3275 adults from a Mediterranean population (the Obesity, Nutrigenetics, TIming, and MEditerranean [ONTIME] study) who had the opportunity of taking siestas because it is culturally embedded. RESULTS: Thirty-five percent of participants usually took siestas (16% long siestas). Compared with the no-siesta group, long siestas were associated with higher values of BMI, waist circumference, fasting glucose, systolic blood pressure, and diastolic blood pressure, as well as with a higher prevalence of MetS (41%; p = 0.015). In contrast, the probability of having elevated SBP was lower in the short-siesta group (21%; p = 0.044) than in the no-siesta group. Smoking a higher number of cigarettes per day mediated the association of long siestas with higher BMI (by 12%, percentage of association mediated by smoking; p < 0.05). Similarly, delays in nighttime sleep and eating schedules and higher energy intake at lunch (the meal preceding siestas) mediated the association between higher BMI and long siestas by 8%, 4%, and 5% (all p < 0.05). Napping in bed (vs. sofa/armchair) showed a trend to mediate the association between long siestas and higher SBP (by 6%; p = 0.055). CONCLUSIONS: Siesta duration is relevant in obesity/MetS. Timing of nighttime sleep and eating, energy intake at lunch, cigarette smoking, and siesta location mediated this association.

Saliva as a non-invasive tool for assessment of metabolic and inflammatory biomarkers in children.

BACKGROUND & AIMS: Epidemiological studies in school-age children are challenging, particularly those that aim to analyse metabolic markers on blood samples obtained via invasive and stressful procedures. The objective of this paper is to evaluate the use of saliva, as a non-invasive tool in epidemiological studies performed in school-age children, to capture metabolic changes associated with body mass index (BMI), dietary characteristics and physical activity in both boys and girls. METHODS: This is an observational study in which healthy children of ages between 8 and 12 years (n = 129, 60 girls and 69 boys) from three schools in a Mediterranean area of Spain were included. A panel of biomarkers was measured in serum and saliva and correlated with BMI, dietary characteristics and physical activity. RESULTS: Significant positive correlation between serum and salivary levels were detected for CRP (r = 0.770) in all included children, and boys (r = 0.805) and girls (r = 0.775) separately (P < 0.001, in all cases) and for insulin in girls (r = 0.442; P < 0.05). Among all studied salivary biomarkers, insulin was significantly correlated with the three factors studied: positively with BMI and negatively with dietary characteristics (intake and composition) and physical activity (P < 0.05). Obesity and diet composition were both positively associated to pro-inflammatory biomarkers, CRP and IL1b; while diet composition shared with physical activity levels the correlation with IL6 (positive with energy, fat, carbohydrate and saturated fatty acid intake, and negative with cholesterol intake and average physical activity in boys), NGF and glucose (in both cases correlations were negative with diet composition and physical activity variables) (P < 0.05, in all cases). Sex differences were detected in serum glucose and TNFα. CONCLUSIONS: Biomarkers in saliva are able to capture differences in BMI, dietary characteristics and physical activity levels in school-age children. Saliva may potentially constitute a useful non-invasive and stress-free tool to evaluate metabolic markers of inflammation and/or metabolism related to BMI and lifestyle in a sex-dependent manner.

Genome-wide association study of breakfast skipping links clock regulation with food timing.

BACKGROUND: Little is known about the contribution of genetic variation to food timing, and breakfast has been determined to exhibit the most heritable meal timing. As breakfast timing and skipping are not routinely measured in large cohort studies, alternative approaches include analyses of correlated traits. OBJECTIVES: The aim of this study was to elucidate breakfast skipping genetic variants through a proxy-phenotype genome-wide association study (GWAS) for breakfast cereal skipping, a commonly assessed correlated trait. METHODS: We leveraged the statistical power of the UK Biobank (n = 193,860) to identify genetic variants related to breakfast cereal skipping as a proxy-phenotype for breakfast skipping and applied several in silico approaches to investigate mechanistic functions and links to traits/diseases. Next, we attempted validation of our approach in smaller breakfast skipping GWAS from the TwinUK (n = 2,006) and the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium (n = 11,963). RESULTS: In the UK Biobank, we identified 6 independent GWAS variants, including those implicated for caffeine (ARID3B/CYP1A1), carbohydrate metabolism (FGF21), schizophrenia (ZNF804A), and encoding enzymes important for N6-methyladenosine RNA transmethylation (METTL4, YWHAB, and YTHDF3), which regulates the pace of the circadian clock. Expression of identified genes was enriched in the cerebellum. Genome-wide correlation analyses indicated positive correlations with anthropometric traits. Through Mendelian randomization (MR), we observed causal links between genetically determined breakfast skipping and higher body mass index, more depressive symptoms, and smoking. In bidirectional MR, we demonstrated a causal link between being an evening person and skipping breakfast, but not vice versa. We observed association of our signals in an independent breakfast skipping GWAS in another British cohort (P = 0.032), TwinUK, but not in a meta-analysis of non-British cohorts from the CHARGE consortium (P = 0.095). CONCLUSIONS: Our proxy-phenotype GWAS identified 6 genetic variants for breakfast skipping, linking clock regulation with food timing and suggesting a possible beneficial role of regular breakfast intake as part of a healthy lifestyle.

Lifestyle recommendations for the prevention and management of metabolic syndrome: an international panel recommendation.

The importance of metabolic syndrome (MetS) lies in its associated risk of cardiovascular disease and type 2 diabetes, as well as other harmful conditions such as nonalcoholic fatty liver disease. In this report, the available scientific evidence on the associations between lifestyle changes and MetS and its components is reviewed to derive recommendations for MetS prevention and management. Weight loss through an energy-restricted diet together with increased energy expenditure through physical activity contribute to the prevention and treatment of MetS. A Mediterranean-type diet, with or without energy restriction, is an effective treatment component. This dietary pattern should be built upon an increased intake of unsaturated fat, primarily from olive oil, and emphasize the consumption of legumes, cereals (whole grains), fruits, vegetables, nuts, fish, and low-fat dairy products, as well as moderate consumption of alcohol. Other dietary patterns (Dietary Approaches to Stop Hypertension, new Nordic, and vegetarian diets) have also been proposed as alternatives for preventing MetS. Quitting smoking and reducing intake of sugar-sweetened beverages and meat and meat products are mandatory. Nevertheless, there are inconsistencies and gaps in the evidence, and additional research is needed to define the most appropriate therapies for MetS. In conclusion, a healthy lifestyle is critical to prevent or delay the onset of MetS in susceptible individuals and to prevent cardiovascular disease and type 2 diabetes in those with existing MetS. The recommendations provided in this article should help patients and clinicians understand and implement the most effective approaches for lifestyle change to prevent MetS and improve cardiometabolic health.

Human adipose tissue expresses intrinsic circadian rhythm in insulin sensitivity.

In humans, insulin sensitivity varies according to time of day, with decreased values in the evening and at night. Mechanisms responsible for the diurnal variation in insulin sensitivity are unclear. We investigated whether human adipose tissue (AT) expresses intrinsic circadian rhythms in insulin sensitivity that could contribute to this phenomenon. Subcutaneous and visceral AT biopsies were obtained from extremely obese participants (body mass index, 41.8 ± 6.3 kg/m(2); 46 ± 11 y) during gastric-bypass surgery. To assess the rhythm in insulin signaling, AKT phosphorylation was determined every 4 h over 24 h in vitro in response to different insulin concentrations (0, 1, 10, and 100 nM). Data revealed that subcutaneous AT exhibited robust circadian rhythms in insulin signaling (P < 0.00001). Insulin sensitivity reached its maximum (acrophase) around noon, being 54% higher than during midnight (P = 0.009). The amplitude of the rhythm was positively correlated with in vivo sleep duration (r = 0.53; P = 0.023) and negatively correlated with in vivo bedtime (r = -0.54; P = 0.020). No circadian rhythms were detected in visceral AT (P = 0.643). Here, we demonstrate the relevance of the time of the day for how sensitive AT is to the effects of insulin. Subcutaneous AT shows an endogenous circadian rhythm in insulin sensitivity that could provide an underlying mechanism for the daily rhythm in systemic insulin sensitivity.-Carrasco-Benso, M. P., Rivero-Gutierrez, B., Lopez-Minguez, J., Anzola, A., Diez-Noguera, A., Madrid, J. A., Lujan, J. A., Martínez-Augustin, O., Scheer, F. A. J. L., Garaulet, M. Human adipose tissue expresses intrinsic circadian rhythm in insulin sensitivity.

Methods for monitoring the functional status of the circadian system in dietary surveys studies: application criteria and interpretation of results.

To evaluate the circadian system status of the subject may be of special interest in nutrition. Particularly for those studies related to the assessment of diseases related to malnutrition, as it is the case of most of the degenerative diseases such as obesity, cancer, or cardiovascular diseases. For this purpose, one of the approaches consists to measure a) the external synchronizers of the internal clock, such as light intensity, and changes from fasting to eating and from resting to activity. Indeed, "chronodisruptors" have been defined as "exogenous and endogenous exposures or effectors which are chronobiologically active and can thus disrupt the timing and order. Another approach to assess the circadian system health is to measure the b) outputs of the internal clock (circadian marker rhythms). Among such outputs, the rhythm of body temperature, motor activity, melatonin, cortisol and clock gene expression are the most commonly used. From the genetic perspective, we are now able to measure failures in the internal clock, in order to assess c) the genetics of the molecular clock. Indeed, new nutrigenetics techniques are giving us the opportunity to measure the association between different genetic variants of our clock genes and several illnesses such as obesity, cardiovascular diseases, diabetes or cancer. In addition to these techniques, self-reported questionnaires based in the morning-evening preferences have been developed as complementary procedures to assess human chronotypes.

Evaluar el estado del sistema circadiano del sujeto puede ser de especial interés en la nutrición. En particular, para los estudios relativos a la evaluación de las enfermedades relacionadas con la malnutrición como es el caso de la mayoría de las enfermedades degenerativas tales como la obesidad, cáncer, o enfermedades cardiovasculares. Para este propósito, uno de los enfoques consiste en medir a) los sincronizadores externos del reloj interno, tales como intensidad de la luz, y los cambios de ayuno/ingesta y de reposo/actividad. De hecho, se ha definido el término de "cronodisruptor" que se refiere a "exposiciones o efectores exógenos y endógenos que son cronobiológicamente activos y que por lo tanto pueden interrumpir el tiempo". Otro enfoque para evaluar la salud del sistema circadiano es medir b) las salidas del reloj interno (ritmos circadianos). Entre ellos las más utilizadas son la medición del ritmo de la temperatura corporal, la actividad motora, la melatonina, el cortisol y la expresión de genes reloj. Desde el punto de vista genético, ahora somos capaces de medir c) las alteraciones del reloj interno, con el fin de evaluar la genética del reloj molecular. De hecho, las nuevas técnicas de nutrigenética nos están dando la oportunidad de medir la asociación entre las diferentes variantes genéticas de nuestros genes reloj y varias enfermedades como la obesidad, las enfermedades cardiovasculares, la diabetes o el cáncer. Además de estas técnicas, se han desarrollado cuestionarios basados en las preferencias de mañana-tarde como procedimientos complementarios para evaluar cronotipos humanos.

[Quality of the diet "before and during" a weight loss treatment based on Mediterranean Diet; behavioural therapy and nutritional education]. / Calidad de la dieta "antes y durante" un tratamiento de pérdida de peso basado en una dieta mediterránea; terapia conductual y educación nutricional.

INTRODUCTION: The "Garaulet" Method (Mediterranean Diet, therapy of behavior and nutritional education), has shown to be effective in the treatment of the obesity. OBJECTIVES: To evaluate and to compare the quality of the diets ingested before and during the treatment by means of Index-of-Feeding-Healthful (IAS) and its relationship with others variables. MATERIALS AND METHODS: The sample was of 450 patients (383 women, 67 men), age 39.3 + 11.5 years and 31.2 + 5.3 of IMC. IAS of" before" and "during" treatment was calculated with a 24 h-recall previous to the treatment and a Seven-days-dietary-record questionnaire during treatment. The IAS consists of 10 variables that include cereal consumption, fruits, vegetables, dairy products and meats and other variables related to the nutritional guidelines for the Spanish population (SENC, 2004). RESULTS: Habitual dietary habits of the patients were acceptable with an IAS of 67 9 ± 13. However, lipids (43.9 ± 8.4%) and saturated fats (67.4 ± 20.1%) intakes were higher than recommended, while monounsaturated fats were lower (27.8 ± 15.1%). The IAS varied with the BMI and was significantly lower among obese subjects (65.1 ± 11.6) as compared to overweight (69.2 ± 13.9) (P < 0.05). Diet during the treatment, significantly improved with an IAS of 91.4 ± 9.8). IAS of the women studied was better (92.3 ± 9.0) than the one of men (86.4 ± 11.8) (P < 0.05). Patients who reached the goal in weight loss acquired better values of IAS (92.1 ± 9.2) during the treatment that those that did not reach it (87.9 ± 11.7) (P < 0.05). CONCLUSION: In this Spanish population, the diet studied, is useful to promote weight loss through the introduction of changes in dietary habits towards the reincorporation of the Mediterranean cultural tradition.

Introducción: El método de pérdida de peso (dieta mediterránea, terapia de comportamiento y educación nutricional) ha mostrado ser efectivo en el tratamiento de la obesidad. Objetivo: El objetivo del presente trabajo es evaluar y comparar la calidad de las dietas ingeridas antes y durante el tratamiento mediante el Índice de Alimentación Saludable (IAS) y su relación con diferentes variables. Materiales y métodos: La muestra fue de 392 pacientes (330 mujeres, 62 hombres), edad 39,3 ± 11,5 años y IMC de 31,2 ± 5,3 kg/m2. A partir del recuerdo-24 h previo al tratamiento y del registro dietético 7 días se estimó el IAS de "antes" y "durante" tratamiento. El IAS consta de 10 variables que representan el cumplimiento de objetivos nutricionales para la población española (SENC, 2004). Resultados: Dieta previa, presentó un IAS "necesita mejorar" (68,6 ± 11,6) con lípidos (%) (43,9 ± 8,4) y AGS (% lípidos) (67,4 ± 20,1) elevados, además el contenido en AGM (% lípidos) (27,8 ± 15,1) fue insuficiente. El IAS varió en función del IMC siendo el de obesos inferior al de personas con sobrepeso (65,1 ± 11,6 vs 69, 2 ± 13,9; P < 0,05). La dieta ingerida durante el tratamiento mejoró notablemente IAS (91,4 ± 9,7). El IAS de las mujeres fue superior (92,3 ± 9,1) al de los hombres (84,4 ± 12,0) (P < 0,05). Aquellos que alcanzaron la meta de pérdida de peso adquirieron mejores valores de IAS durante el tratamiento que los que no la alcanzaron (92,1 ± 9,2 vs 87,9 ± 11,7) (P < 0,05). Conclusiones: Según el IAS, la calidad de la dieta estudiada durante el tratamiento de pérdida de peso mejoró significativamente en relación a la dieta habitual del paciente. El IAS de la dieta durante el tratamiento se asocia con el sexo, el estado ponderal (sobrepeso y obesidad) y con el éxito del tratamiento (> 5% de pérdida del peso inicial).

Effects of resveratrol on changes induced by high-fat feeding on clock genes in rats.

In mammals, the main component of the circadian system is the suprachiasmatic nucleus in the hypothalamus. However, circadian clocks are also present in most peripheral tissues, such as adipose tissue. The aim of the present study was to analyse the potential effects of resveratrol on changes induced by high-fat feeding in the expression of clock genes and clock-controlled genes in the white adipose tissue from rats. For this purpose, rats were divided into three groups: a control group, fed a standard diet, and two other groups, either fed a high-fat diet supplemented with resveratrol (RSV) or no resveratrol (HF). The expression of clock genes and clock-controlled genes was analysed by RT-PCR. Protein expression and fatty acid synthase (FAS) activity were also analysed. When comparing the controls, the RSV group showed similar patterns of response to the HF group, except for reverse erythroblastosis virus α (Rev-Erbα), which was down-regulated. The expression of this gene reached the same levels as in control rats. The response pattern of protein expression for Rev-Erbα was similar to that found for gene expression. High-fat feeding up-regulated all adipogenic genes and resveratrol did not modify them. In the HF group, the activity of FAS tended to increase, while resveratrol decreased. In conclusion, resveratrol reverses the change induced by high-fat feeding in the expression of Rev-Erbα in adipose tissue, which means that clock machinery is a target for this polyphenol. This change seems to be related to reduced lipogenesis, which might be involved in the body fat-lowering effect of this molecule.

[Chronobiological aspects of obesity and metabolic syndrome]. / Aspectos cronobiológicos de la obesidad y el síndrome metabólico.

Circadian rhythms (approximately 24h) are widely characterized at molecular level and their generation is acknowledged to originate from oscillations in expression of several clock genes and from regulation of their protein products. While general entrainment of organisms to environmental light-dark cycles is mainly achieved through the master clock of the suprachiasmatic nucleus in mammals, this molecular clockwork is functional in several organs and tissues. Some studies have suggested that disruption of the circadian system (chronodisruption (CD)) may be causal for manifestations of the metabolic syndrome. This review summarizes (1) how molecular clocks coordinate metabolism and their specific role in the adipocyte; (2) the genetic aspects of and scientific evidence for obesity as a chronobiological illness; and (3) CD and its causes and pathological consequences. Finally, ideas about use of chronobiology for the treatment of obesity are discussed.

Influence of menopause on adipose tissue clock gene genotype and its relationship with metabolic syndrome in morbidly obese women.

Menopausal women exhibit a loss of circadian coordination, a process that runs parallel with a redistribution of adipose tissue. However, the specific genetic mechanisms underlying these alterations have not been studied. Thus, the aim of the present study was to determine whether the development of menopause induces an alteration of the genes that control biological rhythms in human subcutaneous (SAT) and visceral (VAT) adipose tissue, and whether changes in clock gene expression are involved in the increased risk of developing metabolic syndrome (MetS), which is frequently associated with menopause. To this end, VAT and SAT biopsies were taken in pre- (n = 7) and postmenopausal (n = 7) women at similar hours in the morning. RNA was extracted, and a microarray analysis was made. Data were confirmed by quantitative real-time polymerase chain reaction. Western blot and immunohistochemical analysis were also performed. When clock gene expression was compared between both groups of women, data in SAT showed that expression of the core clock gene period3 was significantly higher in postmenopausal women, while casein kinase-1δ, E1A-binding protein and cAMP-responsive element were preferentially expressed in the premenopausal group. In VAT, period2 (PER2) and v-myc myelocytomatosis viral oncogene expressions were significantly higher in the postmenopausal group. Western blot analysis indicated that PER2 and PER3 protein expression was also increased in postmenopausal women. In addition, several genes, including PER2, were differentially expressed depending on whether or not the patient met the MetS criteria. We conclude that menopause transition induces several changes in the genotype of the adipose tissue chronobiological machinery related to an increased risk of developing MetS.

Profile of adipose tissue gene expression in premenopausal and postmenopausal women: site-specific differences.

OBJECTIVES: Menopause increases the risk of several pathologies, probably due to enlarged levels of visceral fat. Apart from morphological and endocrine changes, a cluster of genes, still not fully defined, may be involved in these alterations. The objectives of the present study, therefore, were to analyze differences in adipose tissue gene expression between premenopausal and postmenopausal women and to ascertain whether any differences were depot specific. METHODS: Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) biopsies were taken from 7 premenopausal and 7 postmenopausal women undergoing surgery because of morbid obesity. RNA was extracted, and the overall gene expression profile was analyzed by microarray analysis. RESULTS: In general, SAT genes were overexpressed, whereas VAT genes were down-regulated in premenopausal compared with postmenopausal women. We found 724 differentially expressed genes in SAT and 327 in VAT. These differences suggest that several biological processes, such as the immune system and other metabolic processes, were altered based on menopause status. Regarding individual genes, neurexin 3, metallothionein 1E, and keratyn 7 showed the most pronounced differences. Interestingly, the expression of these genes was related to body fat distribution. CONCLUSIONS: Our results reveal that menopause influences the adipose tissue expression of many genes, especially of neurexin 3, metallothionein 1E, and keratyn 7, which are associated with the alteration of several key biological processes, such as the immune system and cell metabolism. Gene expression in adipose tissue could be used for diagnosis and the development of new therapeutic strategies against obesity and related alterations, depending on menopause status.

Dehydroepiandrosterone-sulfate modifies human fatty acid composition of different adipose tissue depots.

BACKGROUND: Dehydroepiandrosterone-sulfate (DHEA-S) has been described as a protector agent against obesity-related pathologies, although the mechanism of action is still unknown. We have shown that DHEA-S acts on adipose tissue (AT), altering the fatty acid (FA) profile in rodents. Thus, we could hypothesize that some of the beneficial effects shown by DHEA-S in humans are related to a modification of the human AT-FA profile. The present study examines this question and whether this effect is tissue-dependent. METHODS: Paired visceral and subcutaneous AT biopsies were obtained from 20 patients who had undergone bariatric surgery. These samples were subjected to primary adipose culture and incubated for 24 h with 1 µM DHEA-S. The FA profile of both control and treated samples were analyzed by gas chromatography. RESULTS: A reduction in total saturated fatty acids (SFA), the n-6 family of polyunsaturated fatty acids (PUFA) and the n-6/n-3 PUFA ratio was observed after DHEA-S treatment, whereas monounsaturated fatty acids (MUFA) increased. In addition, DHEA-S altered the percentage of several individual FA, decreasing palmitic acid and increasing vaccenic acid in both AT. All estimated desaturase activity ratios slightly increased after DHEA-S treatment, although only the increase of delta-6-desaturase index in both depots reached statistical significance. No depot-specific action of DHEA-S was found between subcutaneous and visceral AT. CONCLUSIONS: In vitro, DHEA-S modifies the AT-FA composition towards a better metabolic profile to a similar extent in the subcutaneous and visceral adipose depots, in both of which a decrease in SFA and increased MUFA are observed after treatment. This effect could help to explain the beneficial effects attributed to DHEA-S. Further studies, however, are required to determine whether the effect of DHEA-S on adipose tissue in vitro is conserved in vivo.

Genetic variants in human CLOCK associate with total energy intake and cytokine sleep factors in overweight subjects (GOLDN population).

Despite the importance of total energy intake in circadian system regulation, no study has related human CLOCK gene polymorphisms and food-intake measures. The aim of this study was to analyze the associations of CLOCK single-nucleotide polymorphisms (SNPs) with food intake and to explore the specific role of the cytokine system. A total of 1100 individual participants in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study were included. Dietary intake was estimated with a validated questionnaire. Interleukin-6 (IL-6), monocyte chemotactic protein 1 (MCP1), tumor necrosis factor-alpha (TNF-alpha), IL-2 soluble receptor-alpha (IL-2sR-alpha) and adiponectin plasma concentrations were measured. Our results showed that four of five CLOCK SNPs selected were significantly associated with total energy intake (P<0.05). For SNP rs3749474, the energy intake and total fat, protein and carbohydrate intakes were significantly higher in minor allele carriers than in non-carriers. Frequency of the minor allele was greater in subjects with high energy intake than in those with low intake. Subjects with the minor allele were 1.33 times more likely to have high energy intake than non-carriers (95% CI 1.09-1.72, P=0.0350). All CLOCK SNPs were associated with plasma cytokine values, in particular with those that were highly correlated with energy intake: MCP1, IL-6 and adiponectin. Interestingly, minor allele carriers with high energy intake showed decreased cytokine values, which could be related with a lower anorectic effect and decreased sleep in these subjects. In conclusion, we show a novel association of genetic variation at CLOCK with total energy intake, which was particularly relevant for SNP rs3749474. Associations could be mediated through the alteration of cytokine levels that may influence energy intake and sleep pattern.

Circadian rhythm of clock genes in human adipose explants.

To analyze in severely obese women the circadian expression of the clock genes hPer2, hBmal1, and hCry1 in explants from subcutaneous (SAT) and visceral (VAT) adipose tissue (AT), in order to elucidate whether this circadian clockwork can oscillate accurately and independently of the suprachiasmatic nucleus (SCN) and if glucocorticoid metabolism-related genes such as glucocorticoid receptor (hGr) and 11beta-hydroxysteroid dehydrogenase 1 (h11 beta Hsd1) and the transcription factor peroxisome proliferator activated receptor gamma (hPPAR gamma) are part of the clock controlled genes. AT biopsies were obtained from morbid obese patients (BMI > or =40 kg/m(2)) (n = 7). Anthropometric variables were measured and fasting plasma lipids and lipoprotein concentrations were analyzed. In order to carry out rhythmic expression analysis, AT explants were cultured during 24 h and gene expression was performed at the following times (T): 0, 6, 12, and 18 h, with quantitative real-time PCR. Clock genes oscillated accurately and independently of the SCN in AT explants. Their intrinsic oscillatory mechanism regulated the timing of other genes such as hPPAR gamma and glucocorticoid-related genes. Circadian patterns differed between VAT and SAT. Correlation analyses between the genetic circadian oscillation and components of the metabolic syndrome (MetS) revealed that subjects with a higher sagittal diameter showed an increased circadian variability in hPer2 expression (r = 0.91; P = 0.031) and hBmal1 (r = 0.90; P = 0.040). Data demonstrate the presence of peripheral circadian oscillators in human AT independently of the central circadian control mechanism. This knowledge paves the way for a better understanding of the circadian contribution to medical conditions such as obesity and MetS.

Adiponectin is involved in the protective effect of DHEA against metabolic risk in aged rats.

The aim of the present work was to analyze the effect of dehydroepiandrosterone (DHEA) on several metabolic risk factors, including cardiovascular health and insulin resistance, in aged rats submitted to a high-fat diet. For that, weaned rats were fed on a high-fat diet until 20 months of age. In the last 13 weeks of life, a group (n=11) received the diet supplemented with DHEA (0.5%, w/w), serving the rest (n=10) as controls. Body weight, body fat, serum lipids (triglycerides, total cholesterol and non-esterified fatty acids (NEFA)), HOMA index, n-6/n-3 polyunsaturated fatty acid (PUFA) ratios, serum adiponectin, leptin, resistin and TNF-alpha, as well as adiponectin expression in adipose tissue, were measured. A stepwise discriminant test was used to analyze these variables, and an index of overall metabolic risk was generated from them. DHEA treatment resulted in a significantly lower overall metabolic risk index, as generated by the discriminant test (P<0.01). The DHEA group had lower body fat and n-6/n-3 polyunsaturated fatty acid (PUFA) ratios than the control group (P<0.01), and the same trends were observed for serum cholesterol, triglycerides and HOMA index; in contrast, adiponectin expression in adipose tissue increased in DHEA-treated rats (P<0.05). The discriminant analysis revealed that adiponectin, both from serum and adipose tissue, was the most influencing factor, followed by n-6/n-3 ratios in adipose tissue, and by body fat. Our results then suggest that adiponectin is involved in the protective effect of DHEA against metabolic risk demonstrated in the present work.

Dehydroepiandrosterone prevents age-associated alterations, increasing insulin sensitivity.

The age decline in DHEA levels has been associated with the appearance of age-related disorders such as obesity and insulin resistance. The aim of this study was to analyse the effect of chronic administration (13 weeks) of DHEA (5 g/kg diet) to old female rats fed on a high-fat diet on body weight and adiposity, and concretely on the expression of the adipokines related to obesity and insulin resistance, such as leptin, adiponectin and resistin. DHEA treatment induced a decrease in body weight, adipose tissue mass and serum insulin, adiponectin and leptin levels. Adiponectin mRNA expression in visceral fat depots decreased with aging, but this reduction was attenuated by DHEA treatment. DHEA treatment also stimulated resistin gene expression in the ovaric and renal adipose depots, which is associated with an increase in its circulating levels. In conclusion, DHEA treatment decreases body weight and adiposity in old female rats fed a high-fat diet, leading to an improvement of the HOMA index for insulin sensitivity, with decreasing circulating insulin levels, and preventing the age-associated decline of visceral-adipose adiponectin expression.

Adiponectin, the controversial hormone.

OBJECTIVE: To discuss present knowledge about adiponectin hormone. DESIGN: Review of existing literature. SETTING AND RESULTS: Adiponectin is one of the most interesting cytokines associated with obesity, although its physiological role remains to be fully clarified. Adiponectin is a 247-amino acid protein that contains four differentiable domains. Contrary to most adipose-related cytokines, adiponectin levels are surprisingly lower in obese than in lean humans. Women have been found to have significantly higher adiponectin plasma concentrations than men. Further research is needed in order to identify new polymorphisms which contribute to explain the potential role of adiponectin in obesity and related pathologies. Considering the anti-inflammatory properties of adiponectin and the fact that it is negatively associated with adiposity, this cytokine could be one of the links between obesity and inflammation. The main mechanisms of action of adiponectin are directed to a protective role against atherogenic and insulin resistance processes. Research has revealed interesting new functions far beyond metabolism, such as immunity, cancer and bone formation. Contrary to all adipose-related proteins, adiponectin decreases with obesity. Most of the contradictory data surrounding adiponectin are related to plasma values and their relationship with body fat, gender differences and insulin resistance. There are important confounding results regarding the mechanisms of action and functions of adiponectin, especially in relation to insulin resistance and inflammation.

Relationship among adiponectin, adiponectin gene expression and fatty acids composition in morbidly obese patients.

BACKGROUND: The aim of this study was to examine the relationship between adiponectin plasma circulating levels and its gene expression in two abdominal fat depots (subcutaneous and visceral) with the fatty acid composition of plasma and adipose tissue in morbidly obese subjects. METHODS: 20 patients (10 women and 10 men) were selected. All were morbidly obese (BMI > or =40 kg/m2) and admitted for gastric surgery. Plasma samples and adipose tissue from both subcutaneous and visceral regions were obtained. Plasma adiponectin and adipose adiponectin expression were analyzed. RESULTS: Adiponectin mRNA expression in the subcutaneous tissue was significantly higher (P=0.048) than in visceral tissue. Circulating adiponectin values, were positively associated with the proportion of n-3 polyunsaturated fatty acids in plasma (r=0.62, P=0.002). The visceral depot showed greater statistical associations between adiponectin gene expression and fatty acids profile, being saturated fatty acids associated with a decrease (r=-0.68, P=0.015), whereas monounsaturated were related to an increase in this adipose region (r=0.67, P=0.017). CONCLUSIONS: We demonstrated significant associations between adipose tissue adiponectin gene expression and fatty acid composition. These associations were more evident in relation to the visceral depot, an adipose tissue region highly implicated in the metabolic syndrome.

[Comparative study of the type of obesity in pre- and postmenopausal women: Relationship with fat cell data, fatty acid composition and endocrine, metabolic, nutritional and psychological variables]. / Estudio comparativo del tipo de obesidad en mujeres pre y posmenopáusicas: relación con el tamaño adipocitario, la composición de la grasa y diferentes variables endocrinas, metabólicas, nutricionales y psicológicas.

BACKGROUND: The weight increase that many women experience during menopause may be the result of ageing. However, the precise factors inducing obesity during this period remain to be identified. The object of this study was to determine the type of obesity in a group of women along with its distinctive features, if any, as a function of the menopause stage. PATIENTS AND METHOD: The sample consisted of 55 women (22 premenopausal and 33 postmenopausal) with grade I and II obesity. Distribution of body fat, composition of the adipose tissue, size and number of adipocytes, lipidic and hormonal profile as well as nutritional and psychological aspects were all taken into account. RESULTS: Postmenopausal women had an android distribution of fat, whereas it was gynoid in premenopausal women. The adipose tissue showed different cell characteristics, the number of fat cells and content of saturated fatty acids (myristic and palmitic) being significantly lower in the postmenopausal group. Menopause was associated with an increase in plasmatic lipids and a decrease in the levels of certain hormones (dehydroepiandrosterone-sulphate and insulin). Postmenopausal women tended to have healthier eating habits than premenopausal women, with a significantly lower fat intake but higher carbohydrate and fibre intakes. However, the degree of physical activity was lower than in premenopausal women. CONCLUSIONS: The type of obesity differs as a function of the menopausal status, a finding that should be taken into account when establishing a dietetic treatment.