Reduced metabolic efficiency in sedentary eucaloric conditions predicts greater weight regain in adults with obesity following sustained weight loss.

BACKGROUND: Successful long-term weight loss maintenance after caloric restriction (CR) is rarely achieved. Besides known metabolic, behavioural, and cognitive factors, 24-hour energy expenditure (24hEE) relative to body size (i.e., metabolic efficiency) might influence subsequent weight loss maintenance. METHODS: Eleven participants with obesity (BMI = 39.0 ± 8.7 kg/m2, body fat = 36.1 ± 6.4%) had 24hEE measured in a whole-room indirect calorimeter during eucaloric conditions and weight stability prior to starting a 6-week inpatient CR study (50% of daily energy needs). Twenty-four-hour energy expenditure was adjusted via regression analysis for fat free mass (FFM) and fat mass (FM) by DXA. Body composition was reassessed at the end of CR and after 1-year follow-up. Free-living weight was assessed by monthly weight measurements during 12 months. RESULTS: After 6-week CR, participants lost 8.5 ± 2.7% weight (FFM: -6.3 ± 3.6 kg, FM: -3.4 ± 1.2 kg) but regained 5.1 ± 8.0% 1 year following CR, which was mostly due to FFM regain (+5.7 ± 5.5 kg) and unchanged FM. A relatively higher 24hEE by 100 kcal/day prior to CR was associated with an average greater rate of weight regain by +0.3 kg/month during follow-up and a greater final weight regain by +5.1 kg after 1 year of follow-up. CONCLUSION: These results suggest that reduced metabolic efficiency in 24hEE during eucaloric, sedentary conditions may predict greater weight regain after CR-induced weight loss.

[Typhoid and paratyphoid fever]. / Typhus abdominalis und Paratyphus.

Typhoid fever and paratyphoid fever are systemic infectious diseases of global significance caused by Salmonella enterica subspecies enterica Serovar Typhi (short name: Salmonella Typhi) or Serovar Paratyphi (short name: Salmonella Paratyphi). The course of these fecal-orally transmitted diseases is mainly characterized by a high fever. Left untreated, the course of typhoid fever can be severe and lethal. The infection is almost always acquired outside of Europe (mainly in India) and is notifiable in Germany, Austria and Switzerland. Paratyphoid is an attenuated disease of typhoid fever caused by Salmonella Paratyphi. Available vaccines only protect against Salmonella Typhi. Antibiotic resistance reflects the situation in endemic countries and shows a worrying increase of multi-drug resistant isolates. Currently, third-generation cephalosporins such as ceftriaxone are recommended as first-line therapy; if sensitive to quinolones, fluoroquinolones such as ciprofloxacin may continue to be administered. Crucial preventive measures for travelers to endemic regions include consistent water and food hygiene as well as vaccination, whereby only protection rates of 50-70 % are achieved by currently available vaccines. In the light of increasing multi-drug resistance, a more effective conjugate vaccine against Salmonella Typhi with cross-reactivity against Salmonella Paratyphi is needed more than ever.

Response of skeletal muscle UCP2-expression during metabolic adaptation to caloric restriction.

BACKGROUND/OBJECTIVES: Spendthrift vs. thrifty individuals expend more energy and experience greater weight loss during caloric restriction (CR). Adaptive mechanisms in skeletal muscle, adipose tissue, and on hormone level modulate energy expenditure (EE) during weight loss. Metabolic mechanisms underlying the variability in EE during CR are unclear. The present study explored whether during long-term CR (i) gene expression changes in skeletal muscle and adipose tissue relate with the individual EE response and weight loss, and (ii) altered catecholamine and FGF21-concentrations are associated with measures of metabolic adaptation. SUBJECTS/METHODS: In a 10-week inpatient study, 24-h EE was measured before and after 6 weeks of 50% CR in 12 subjects using whole-room indirect calorimetry. Weight loss was assessed and repeated hormone measurements performed. Muscle and adipose tissue biopsies were taken before and after CR, and gene expression was assessed (RNA-Seq). Genes showing the most significant changes after CR were tested for association with EE and followed-up for further association with metabolic measures in a separate phenotyping study (n = 103). RESULTS: Muscle UCP2 showed the strongest change after CR (log2-fold change = -1.57, false discovery rate = 0.10) and was considered the best gene for exploration of metabolic adaptive processes. A greater decrease in UCP2-expression was associated with less weight loss (P = 0.03, r = 0.77) and relatively lower 24-h EE after CR (P = 0.001, r = -0.96). Post-CR changes in FGF21-plasma concentrations correlated with UCP2-expression change (P = 0.02, r = -0.89) and weight loss (P = 0.003, r = -0.83). In a separate metabolic phenotyping study, muscle UCP2-expression correlated with respiratory quotient and macronutrient oxidation. In adipose tissue, no candidate genes for metabolic exploration were found. CONCLUSIONS: Changes in muscle UCP2-expression reflect an inter-individual metabolic response to long-term CR and may influence EE and weight loss via modulation of substrate oxidation.

Decline in the acute insulin response in relationship to plasma glucose concentrations.

BACKGROUND: To investigate (1) whether the decline in acute insulin response (AIR) precedes or coincides with defined glucose regulation categories and whether acute insulin response decline varies by race and adiposity, (2) linearity of the relationship between acute insulin response and increasing plasma glucose concentrations, (3) longitudinal changes in acute insulin response accounting for changes in insulin action across categories of glucose tolerance. METHODS: Clinical cross-sectional and longitudinal study of nondiabetic subjects. Inpatient assessment of oral glucose tolerance (2-h PG, fasting PG), and acute insulin response (intravenous glucose tolerance test) in 326 and 84 Native Americans of full and ≤6/8th Southwestern heritage, respectively, and 115 Whites. Linearity of acute insulin response vs plasma glucose concentrations investigated using spline analyses. Follow-up (average = 2.07 years) glucose tolerance, acute insulin response, and insulin action (hyperinsulinemic-euglycemic clamp) assessed in 230 full Native Americans. RESULTS: In certain groups, the relationship between acute insulin response and increasing plasma glucose levels was non-linear. In all groups, acute insulin response decline preceded the cut-offs for traditional glucose regulation categories, although the timing with respect to increasing plasma glucose varied by race and adiposity. Longitudinal data indicated that improvement in insulin action is the key factor to preserve insulin secretion, underlying the reversion of glucose tolerance in prediabetic individuals. CONCLUSIONS: With worsening insulin action, the decline in insulin secretion occurred prior to current diagnostic guidelines for impaired glucose regulation. However, the relationship between acute insulin response and increasing plasma glucose varies and was not always non-linear. Understanding the dynamics of this relationship may determine when to initiate preventive pharmacotherapy directed at the preservation of ß-cell failure.

An E115A Missense Variant in CERS2 Is Associated With Increased Sleeping Energy Expenditure and Hepatic Insulin Resistance in American Indians.

Genetic determinants of interindividual differences in energy expenditure (EE) are largely unknown. Sphingolipids, such as ceramides, have been implicated in the regulation of human EE via mitochondrial uncoupling. In this study, we investigated whether genetic variants within enzymes involved in sphingolipid synthesis and degradation affect EE and insulin-related traits in a cohort of American Indians informative for 24-h EE and glucose disposal rates during a hyperinsulinemic-euglycemic clamp. Association analysis of 10,084 genetic variants within 28 genes involved in sphingolipid pathways identified a missense variant (rs267738, A>C, E115A) in exon 4 of CERS2 that was associated with higher sleeping EE (116 kcal/day) and increased rates of endogenous glucose production during basal (5%) and insulin-stimulated (43%) conditions, both indicators of hepatic insulin resistance. The rs267738 variant did not affect ceramide synthesis in HepG2 cells but resulted in a 30% decrease in basal mitochondrial respiration. In conclusion, we provide evidence that the CERS2 rs267738 missense variant may influence hepatic glucose production and postabsorptive sleeping metabolic rate.

X-linked Dystonia-Parkinsonism manifesting in a female patient due to atypical turner syndrome.

BACKGROUND: Recessive X-linked dystonia-parkinsonism almost exclusively affects men. We investigated the genetic mechanisms causing this disorder in a female patient. METHODS: We confirmed the presence of an X-linked dystonia-parkinsonism-specific change in our patient by sequencing. In addition, we employed quantitative real-time PCR and array comparative genomic hybridization to determine the patient's X-chromosome copy number. RESULTS: The patient's sequence electropherogram suggested a higher amount of the mutated allele compared with the wild-type allele. Subsequently, extensive gene dosage analyses revealed a copy number of the X chromosomes between 1 and 2, indicating loss of 1 X chromosome in a subset of cells. Phenotypic reevaluation of the patient showed several clinical features of Turner syndrome. CONCLUSIONS: Our female X-linked dystonia-parkinsonism patient suffered from an undiagnosed X-chromosome monosomy in a subset of cells (45,X/46,XX), suggesting an atypical Turner syndrome and contributing the first molecular explanation for the manifestation of an X-linked dystonia-parkinsonism phenotype in women. © 2013 Movement Disorder Society.

The application of high-performance ultrasound probes increases anatomic depiction in obese patients.

This study evaluated the impact of obesity on abdominal ultrasound diagnostics and assessed effect of high-performance ultrasound probes increased imaging quality. Lean and obese subjects (n = 40; 58% female) were categorized according to body mass index (BMI, 21 to 48 kg/m2). A highly standardized ultrasound examination of the abdomen was performed by trained examiners using three different probes in randomized order (standard probe versus two high-performance probes). Quality of B-mode and duplex ultrasound were assessed using a custom scoring approach for depiction of liver and kidney anatomy and vascularization. Across probes, imaging quality of hepatic and kidney anatomy was inversely related with BMI (P < 0.03, r < - 0.35). Age, sex, and BMI explained 51% of the variance within the ultrasound quality score, with ß = - 0.35, P < 0.0001 for BMI. Compared to the standard probe, high-performance probes allowed for a better depiction of kidney and liver anatomy in subjects above BMI 35 kg/m2 (n = 20, all P < 0.05), resulting in a less pronounced deterioration of imaging quality with increased BMI (all P < 0.05). In conclusion the study shows that obesity impairs ultrasound imaging quality of abdominal anatomy. The application of high-performance probes can increase anatomic depiction in obese patients.Registration number of the German Registry of Clinical Studies: DRKS00023498.

Metabolic Responses to 24-Hour Fasting and Mild Cold Exposure in Overweight Individuals Are Correlated and Accompanied by Changes in FGF21 Concentration.

A greater decrease in 24-h energy expenditure (24 EE) during 24-h fasting defines a "thriftier" metabolic phenotype prone to weight gain during overfeeding and resistant to weight loss during caloric restriction. As the thermogenic response to mild cold exposure (COLD) may similarly characterize this human phenotype identified by acute fasting conditions, we analyzed changes in 24 EE and sleeping metabolic rate (SLEEP) in a whole-room indirect calorimeter during 24-h fasting at thermoneutrality (24°C) and during energy balance both at thermoneutrality (24°C) and mild cold (19°C) in 20 healthy volunteers (80% male; aged 36.6 ± 11.4 years; percentage body fat 34.8 ± 10.5%). Greater decrease in 24 EE during fasting (thriftier phenotype) was associated with less increase in 24 EE during COLD (i.e., less cold-induced thermogenesis). Greater decreases in plasma fibroblast growth factor 21 (FGF21) after 24-h fasting and after COLD were highly correlated and associated with greater decreases in SLEEP in both conditions. We conclude that the metabolic responses to short-term fasting and COLD are associated with and mediated by the liver-derived hormone FGF21. Thus, the 24 EE response to COLD further identifies the "thrifty" versus "spendthrift" phenotype, providing an additional setting to investigate the physiological mechanisms underlying the human metabolic phenotype and characterizing the individual susceptibility to weight change.

Early adaptive thermogenesis is a determinant of weight loss after six weeks of caloric restriction in overweight subjects.

BACKGROUND: Adaptive thermogenesis during prolonged energy deficit refers to the greater than expected reduction in energy expenditure (EE) independent of concomitant loss of metabolically active body mass. OBJECTIVE: As inter-individual variability in the magnitude of adaptive thermogenesis may influence the extent of energy deficit thereby predicting the amount of weight reduction, we investigated whether early adaptive thermogenesis is a determinant of weight loss after 6 weeks of daily 50% caloric restriction in an inpatient setting. DESIGN AND METHODS: The current study reports the results of an exploratory, secondary analysis in overweight but otherwise healthy subjects (n = 11, 7 men, 35 ±â€¯9y, BMI = 40 ±â€¯7 kg/m2, body fat = 63.3 ±â€¯5.3%). Body composition and 24-h EE (24hEE) measurement in a whole-room indirect calorimeter were used to calculate the magnitude of adaptive thermogenesis while on caloric restriction after 1, 3 and 6 weeks. Energy deficit during caloric restriction was quantified via food, stool, and urine bomb calorimetry. Fasting hormonal concentrations (FT4, FT3, FGF21, leptin) were obtained at baseline and at weeks 3 and 6 during caloric restriction. RESULTS: The magnitude of adaptive thermogenesis in 24hEE after 1 week of caloric restriction was -178 ±â€¯137 kcal/day (mean ±â€¯SD), was overall stable during and following caloric restriction, and demonstrated remarkable intra-individual consistency. A relatively greater decrease in 24hEE of 100 kcal/d after 1 week of caloric restriction was associated on average with reduced energy deficit by 8195 kcal over 6 weeks and predicted 2.0 kg less weight loss, of which 0.5 kg was fat mass, after 6 weeks. No correlations were found between hormonal concentrations and weight loss. CONCLUSIONS: The extent of weight loss is influenced by the magnitude of adaptive thermogenesis in the early stage of caloric restriction. Although these results need replication in larger study groups with adequate statistical power, targeting adaptive thermogenesis may help to optimize long-term interventions in obesity therapy.

Effects of underfeeding and oral vancomycin on gut microbiome and nutrient absorption in humans.

Direct evidence in humans for the impact of the microbiome on nutrient absorption is lacking. We conducted an extended inpatient study using two interventions that we hypothesized would alter the gut microbiome and nutrient absorption. In each, stool calorie loss, a direct proxy of nutrient absorption, was measured. The first phase was a randomized cross-over dietary intervention in which all participants underwent in random order 3 d of over- and underfeeding. The second was a randomized, double-blind, placebo-controlled pharmacologic intervention using oral vancomycin or matching placebo (NCT02037295). Twenty-seven volunteers (17 men and 10 women, age 35.1 ± 7.3, BMI 32.3 ± 8.0), who were healthy other than having impaired glucose tolerance and obesity, were enrolled and 25 completed the entire trial. The primary endpoints were the effects of dietary and pharmacological intervention on stool calorie loss. We hypothesized that stool calories expressed as percentage of caloric intake would increase with underfeeding compared with overfeeding and increase during oral vancomycin treatment. Both primary endpoints were met. Greater stool calorie loss was observed during underfeeding relative to overfeeding and during vancomycin treatment compared with placebo. Key secondary endpoints were to evaluate the changes in gut microbial community structure as evidenced by amplicon sequencing and metagenomics. We observed only a modest perturbation of gut microbial community structure with under- versus overfeeding but a more widespread change in community structure with reduced diversity with oral vancomycin. Increase in Akkermansia muciniphila was common to both interventions that resulted in greater stool calorie loss. These results indicate that nutrient absorption is sensitive to environmental perturbations and support the translational relevance of preclinical models demonstrating a possible causal role for the gut microbiome in dietary energy harvest.

Atg7 Knockdown Reduces Chemerin Secretion in Murine Adipocytes.

CONTEXT: In individuals with obesity, adipocyte endocrine function is affected by altered autophagy. Genetic variants in autophagy-related gene 7 (ATG7) correlated with serum chemerin (RARRES2) concentrations. OBJECTIVES: To investigate a functional interplay between chemerin and ATG7, how it may relate to autophagy-mediated adipocyte dysfunction in obesity, and the relevance of genetic ATG7 variants in chemerin physiology. DESIGN: Adipose ATG7 mRNA expression and adiposity measures were available in two human study cohorts. The effect of a high-calorie diet on adipose Rarres2 and Atg7 expression was investigated in mice. In 3T3-L1 adipocytes, the effect of Atg7 knockdown on chemerin expression and secretion was studied. The influence of single nucleotide polymorphisms on ATG7 transcription and chemerin physiology was investigated using a luciferase assay. SETTING: Mouse model, clinical trials, in vitro studies. PARTICIPANTS: Native American (n = 83) and white (n = 100) cohorts. MAIN OUTCOME MEASURE: Adipocyte chemerin expression and secretion. RESULTS: In mice fed a high-calorie diet, adipose Atg7 mRNA expression did not parallel an increase in Rarres2 mRNA expression. ATG7 mRNA expression in human subcutaneous adipose tissue correlated with body mass index, fat mass (r > 0.27; P < 0.01), and adipocyte cell size (r > 0.24; P < 0.02). Atg7 knockdown in 3T3-L1 adipocytes decreased chemerin secretion by 22% (P < 0.04). Rs2606729 in ATG7 was predicted to alter ATG7 transcription and induced higher luciferase activity in vitro (P < 0.0001). CONCLUSIONS: Human adipose ATG7 mRNA expression relates to measures of adiposity. Atg7 knockdown reduces chemerin secretion from adipocytes in vitro, supportive of a functional interplay between ATG7 and chemerin in autophagy-mediated adipocyte dysfunction.

Deviations in energy sensing predict long-term weight change in overweight Native Americans.

BACKGROUND/OBJECTIVES: Energy expenditure (EE), as reflective of body energy demand, has been proposed to be the key driver of food intake, possibly influencing weight change in humans. Variation in this energy-sensing link (overeating relative to weight-maintaining energy requirements) may lead to weight gain over time. SUBJECTS/METHODS: Sixty-one overweight otherwise healthy Native Americans (age: 34.0 ±â€¯7.9 years, body fat: 39.7 ±â€¯9.5%, 36 males) were admitted to our clinical research unit for measurements of body composition by dual-energy X-ray absorptiometry, and 24-h EE and respiratory quotient (RQ) in a whole-room indirect calorimeter during energy balance and weight stability. Following this, ad libitum food intake was assessed for three days using computerized vending machines. Body weight change under unrestricted free-living conditions was assessed at an outpatient follow-up visit (median follow-up time = 1.7 years). RESULTS: Total ad libitum food intake (3-day average) was positively associated with 24-h EE (r = 0.44, p < 0.001), RQ (r = 0.34, p = 0.007), and fat free mass (r = 0.38, p = 0.002). A relatively greater food intake after accounting for 24-h EE, but not for RQ (p = 0.30) or for fat free mass (p = 0.23) nor total food intake (p = 0.16), predicted weight gain at the outpatient follow-up visit (r = 0.26, p = 0.04), such that overeating 100 Kcal/d above the food intake predicted by 24-h EE at baseline was associated with an average weight gain of 0.22 Kg over the follow-up period (95% CI: 0.01 to 0.42 Kg). This was due to relatively greater dietary fat intake (r = 0.32, p = 0.01), but not carbohydrate (p = 0.27) or protein (p = 0.06) intake. CONCLUSION: The individual propensity to overeating, particularly fat, in excess of the weight-maintaining energy requirements can be assessed and predicts long-term weight gain, suggesting that variation in energy sensing may influence appetite by favoring overeating thus promoting obesity development.

Endocannabinoid Anandamide Mediates the Effect of Skeletal Muscle Sphingomyelins on Human Energy Expenditure.

Context: Skeletal muscle endocannabinoids and sphingolipids (particularly sphingomyelins) are inversely associated with sleeping energy expenditure (SLEEP) in humans. The endocannabinoid system may increase sphingolipid synthesis via cannabinoid receptor-1. Objective: To investigate in human skeletal muscle whether endocannabinoids are responsible for the effect of sphingomyelins on SLEEP. Design: Muscle endocannabinoid [anandamide (AEA), 2-arachidonoylglycerol (2-AG)], endocannabinoid congeners [oleoylethanolamide (OEA), palmitoylethanolamide (PEA)], and sphingomyelin content were measured with liquid chromatography/mass spectrometry. SLEEP was assessed in a whole-room indirect calorimeter. Mediation analyses tested whether the inverse associations between sphingomyelins and SLEEP depended on endocannabinoids and endocannabinoid-related OEA and PEA. Setting: Inpatient study. Participants: Fifty-three Native Americans who are overweight. Main Outcome Measure: SLEEP. Results: AEA (r = 0.45, P = 0.001), 2-AG (r = 0.47, P = 0.0004), OEA (r = 0.27, P = 0.05), and PEA (r = 0.53, P < 0.0001) concentrations were associated with the total sphingomyelin content. AEA, OEA, and PEA correlated with specific sphingomyelins (SM18:1/23:0, SM18:1/23:1, and SM18:1/26:1) previously reported to be determinants of SLEEP in Native Americans (all r > 0.31, all P < 0.03). Up to half of the negative effect of these specific sphingomyelins on SLEEP was accounted for by AEA (all P < 0.04), rendering the direct effect by sphingomyelins per se on SLEEP negligible (P > 0.05). Conclusions: In skeletal muscle, AEA is responsible for the sphingomyelin effect on SLEEP, indicating that endocannabinoids and sphingomyelins may jointly reduce human whole-body energy metabolism.

Peripheral Endocannabinoids Associated With Energy Expenditure in Native Americans of Southwestern Heritage.

Context: The endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG), as well as the related acylethanolamide oleoylethanolamide (OEA), have been implicated in energy expenditure (EE) regulation and metabolic diseases. Muscle (fat-free mass) and fat (fat mass) are metabolically active compartments and main determinants of EE. Objective: To assess whether human muscle, adipose, and plasma endocannabinoids correlate with EE. Design: Muscle, adipose, and plasma AEA, 2-AG, and OEA concentrations were measured via liquid chromatography-mass spectrometry. EE was assessed by indirect whole-room calorimetry. Setting: Clinical trial. Participants: Obese/overweight Native Americans of full (n = 35) and at least half (n = 21) Southwestern heritage. Main Outcome Measures: Twenty-four-hour EE, sleeping EE (SLEEP), resting EE (REE), respiratory quotient (RQ), and macronutrient oxidation. Results: In full Natives, muscle AEA concentration correlated with SLEEP (r = -0.65, P = 0.004) and REE (r = -0.53, P = 0.02). Muscle 2-AG was associated with SLEEP (r = -0.75, P = 0.0003). Adipose OEA concentration correlated with RQ (r = -0.47, P = 0.04) and lipid oxidation (r = 0.51, P = 0.03). Plasma OEA concentration was associated with SLEEP (r = -0.52, P = 0.04). After adjustment for major determinants, these lipids explained nearly 20% of the additional variance of the respective measure. Similarly, in Native Americans of at least half Southwestern heritage, investigated lipids correlated with EE measures. Conclusion: Endocannabinoids in metabolically relevant peripheral tissues explained a large part of EE variation and may be involved in regulating EE. Dysregulation of peripheral endocannabinoids may predispose people to metabolic diseases via an effect on EE and lipid oxidation.

Neuromodulation directed at the prefrontal cortex of subjects with obesity reduces snack food intake and hunger in a randomized trial.

Background: Obesity is associated with reduced activation in the left dorsolateral prefrontal cortex (DLPFC), a region of the brain that plays a key role in the support of self-regulatory aspects of eating behavior and inhibitory control. Transcranial direct current stimulation (tDCS) is a noninvasive technique used to modulate brain activity.Objectives: We tested whether repeated anodal tDCS targeted at the left DLPFC (compared with sham tDCS) has an immediate effect on eating behavior during ad libitum food intake, resulting in weight change, and whether it might influence longer-term food intake-related appetite ratings in individuals with obesity.Design: In a randomized parallel-design study combining inpatient and outpatient assessments over 31 d, 23 individuals with obesity [12 men; mean ± SD body mass index (BMI; in kg/m2): 39.3 ± 8.42] received 15 sessions of anodal (i.e., enhancing cortical activity) or sham tDCS aimed at the left DLPFC. Ad libitum food intake was assessed through the use of a vending machine paradigm and snack food taste tests (SFTTs). Appetite was evaluated with a visual analog scale (VAS). Body weight was measured. We examined the effect of short-term (i.e., 3 sessions) and long-term (i.e., 15 sessions) tDCS on these variables.Results: Relative to sham tDCS, short-term anodal tDCS did not influence ad libitum intake of food from the vending machines. Accordingly, no effect on short-term or 4-wk weight change was observed. In the anodal tDCS group, compared with the sham group, VAS ratings for hunger and the urge to eat declined significantly more (P = 0.01 and P = 0.05, respectively), and total energy intake during an SFTT was relatively lower in satiated individuals (P = 0.01), after long-term tDCS.Conclusions: Short-term anodal tDCS of the left DLPFC did not have an immediate effect on ad libitum food intake or thereby weight change, relative to sham tDCS. Hunger and snack food intake were reduced only after a longer period of anodal tDCS in individuals with obesity. This trial was registered at clinicaltrials.gov as NCT00739362.