Effect of a chronotype-adjusted diet on weight loss effectiveness: A randomized clinical trial.

BACKGROUND & AIMS: The alteration of normal biological rhythms, also known as chronodisruption, may be associated with obesity development. For instance, those subject with preference for vespertinity seem to be prone to develop obesity. However, the current hypocaloric dietary treatment of obesity does not take into account these aspects. Therefore, the objective of this trial was to evaluate whether a diet adjusted to patient's chronotype is more effective that the current dietary recommendations. METHODS: 209 subjects take part on a 3 month randomized, double-blind trial. 104 subjects followed a typical hypocaloric dietary treatment and the other 105 subjects undergone a diet with a daily caloric distribution adjusted to their chronotype. There were no sex or age differences between groups. RESULTS: Baseline characteristics were similar in both groups. Dropout rate was also similar in both interventions (p = 0.683). Although both groups improved their anthropometrical parameters, the chronotype-adjusted diet group achieved a statistically significant greater reduction in percentage of total body weight loss (%TWL), BMI and waist circumference than the control group (p < 0.010 in all contrasts). The effect on clinical parameters was less pronounced. CONCLUSIONS: This randomized trial has demonstrated for the first time that in overweight/obese subjects, a chronotype-adjusted diet is more effective than the traditional hypocaloric dietary treatment, at least regarding the anthropometrical parameters. Further research will confirm if this intervention is also more effective in the long term. TRIAL REGISTRATION: NCT-ID: #NCT03755674, (available at: http://www.clinicaltrials.gov).

Altered Eating Attitudes in Nursing Home Residents and Its Relationship with their Cognitive and Nutritional Status.

BACKGROUND: although eating disorders are usually linked to young adolescents, these mental disorders can also appear in the elderly, especially in those living in nursing homes, which might be associated or not with the cognitive decline; however, there are few data regarding elderly subjects. OBJECTIVES: the objective of the present work was to evaluate the presence of abnormal eating attitudes in nursing home residents and its relation with several cognitive, nutritional and psychological factors that could be influencing their nutritional state. DESIGN AND SETTING: a observational experimental study was carried out at several nursing homes of Murcia, Spain. SUBJECTS: 139 nursing home residents. METHODS: EAT-26 test was used to screen classic eating disorders (anorexia and bulimia). Blandford's scale was employed to determine aversive eating attitudes. Moreover, subjective appetite sensations, body image perception, nutritional (MNA and diet composition) and biochemical data were also evaluated. RESULTS: 33% of the subjects had malnutrition. No subject showed symptoms of anorexia or bulimia; however, subjects with cognitive decline frequently showed aversive feeding behaviours (21.6%). Albumin values were significantly lower in subjects with cognitive impairment. CONCLUSIONS: our data showed a clear relation between cognitive impairment and altered eating attitudes, which was reflected by both biochemical (albumin) and nutritional parameters, while no classic eating disorder was observed in residents with normal cognitive-status. These data confirm the need to strengthen our efforts towards maintaining the nutritional status of the subjects with cognitive impairment.

Dehydroepiandrosterone-sulphate replacement improves the human plasma fatty acid profile in plasma of obese women.

DHEA-S treatment is used as an anti-aging and anti-obesity hormone therapy in adults; however, it mechanisms of action are not clearly elucidated. The objective of the present work was to analyze the effect of a replacement therapy, which included a daily single oral dose of DHEA-S for three months, on the composition of human plasma fatty acids (FAs) in obese women. In the first study, a randomized, double-blind, placebo-controlled trial was conducted involving 61 postmenopausal women, who were assigned to receive 100mg/day of DHEA-S (n = 41) or placebo (n = 20) orally for 3 months. In a second study, the effect of DHEA-S treatment on postmenopausal obese women (n = 41) was compared to that in premenopausal obese women (n = 20). Blood samples were collected at the beginning and at the end of the treatment. Plasma FAs were analyzed by gas chromatography. DHEA-S treatment produced significant changes in plasma FAs of both post- and premenopausal women with a reduction of total saturated FAs (SFA) as well as an increase in n-6 polyunsaturated FA (PUFA). Particularly, in premenopausal women the DHEA-S treatment also increased the plasma n-3 PUFA percentage. Regarding estimation of desaturase activity, our data showed that Δ6-desaturase was significantly decreased in postmenopausal women after DHEA-S treatment, whereas Δ5-desaturase was increased in the premenopausal group. In conclusion, DHEA-S treatment in obese women modifies plasma FA composition towards a potentially better metabolic profile, mainly by decreasing SFA and increasing n-6 PUFA in both postmenopausal and premenopausal women.

Differences in AMPK expression between subcutaneous and visceral adipose tissue in morbid obesity.

Adenine monophosphate (AMP) activated protein kinase (AMPK) is an important regulator of obesity. The objective of the present work was to study and compare AMPK protein expression in visceral vs. subcutaneous adipose tissue of morbid obese subjects and to correlate it with adipose tissue characteristics. We selected a total population of 17 extreme obese (BMI>or=40 kg/m2) aged 42.8+/-10.2 years were included in this study. We measured anthropometric and body composition parameters. Adiponectin expression by qRT-PCR, isoproterenol-stimulated lipolytic rates, and AMPK alpha subunits expression by Western blot in adipose tissue explants were determined. Finally plasma concentrations of glucose, triacylglycerols, total cholesterol, HDL-c, LDL-c and insulin were also measured. Our results showed that AMPK alpha expression was higher in subcutaneous than in visceral tissue. A positive correlation between AMPK expression and adiponectin expression in human subcutaneous adipose tissue was observed. Furthermore, a positive correlation between AMPK expression and isoproterenol evoked upregulation of lipolysis rate was also observed. In conclusion, AMPK alpha expression differed according to adipose tissue location. The positive correlation between subcutaneous adipose tissue AMPK and adiponectin or the evoked lipolysis rate could indicate a protective role of AMPK in this tissue, counteracting insulin resistance in morbid obese patients.

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.

New computed tomography-derived indices to predict cardiovascular and insulin-resistance risks in overweight/obese patients.

OBJECTIVE: To determine whether a series of new computed tomography (CT)-derived indices are better diagnostic criteria than the classical CT-derived measurements. A second objective is to propose specific or sensitive threshold values of the most accurate criteria for the occurrence of metabolic disturbances. SUBJECTS/METHODS: Anthropometric measurements and CT scans were performed in 74 obese subjects. Fat thicknesses, diameters, diagonals and areas were determined. Plasma lipids, insulin, glucose and fat cell size were analyzed. A multivariate regression analysis was performed to determine the most accurate predictor index for metabolic alterations explaining the highest percentage of variance. RESULTS: All the new indices were highly correlated with body mass index, percentage of fat and fat cell size. Subcutaneous thicknesses were greater in women, while internal-coronal and sagittal diameters, visceral adipose tissue (VAT) and internal circumference area were greater in men (P<0.001). Those observations were reinforced by the adipocyte size in both fat depots. Subcutaneous parameters showed the strongest correlation with metabolic alterations, being positively associated with metabolic risk in women and negatively in men. Multivariate regression analysis showed that the best predictor index was the superficial subcutaneous adipose tissue (SSAT) and its relation to visceral area (SSAT/VAT), explaining 42% of total variance for high-density lipoprotein-cholesterol in men and 26% for homeostasis model assessment in women. After receiver operating characteristic-curves analysis, three threshold values for both sexes were proposed to select the most appropriate depending on the clinical situation. CONCLUSION: For the first time, we have described SSAT and the SSAT/VAT ratio as important indices in obesity-related 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.

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.

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 subject's 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 significantly 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.

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.