Acid accumulation is associated with metabolic alterations; higher energy, fat, and protein intake; and energy expenditure.

OBJECTIVE: The objective of this study was to study how acid accumulation (lower plasma bicarbonate and higher anion gap [AG] and corrected anion gap [CAG]) correlates with metabolic parameters, food intake, and 24-h energy expenditure (EE). METHODS: Acid accumulation was measured in 286 healthy adults with estimated glomerular filtration rate > 60 mL/min/1.73 m2. Measurements included body composition by dual-energy x-ray absorptiometry scan, ad libitum energy intake by a vending machine paradigm over 3 days, and 24-h EE in a whole-room indirect calorimeter. RESULTS: Lower bicarbonate, higher AG, and higher CAG were correlated with higher waist and thigh circumferences, body fat (percentage), fat mass, triglycerides, and lower high-density lipoprotein cholesterol. Acid accumulation markers were correlated with higher total energy (CAG partial r = 0.17; p = 0.02), fat (CAG partial r = 0.17; p = 0.02), protein intake (CAG partial r = 0.20; p = 0.006), and 24-h EE (CAG partial r = 0.24; p = 0.0007). A mediation analysis of CAG and total energy intake found that 24-h EE was a partial mediator (40%), but the association remained significant (ß = 0.15; p < 0.0001). CONCLUSIONS: In healthy individuals, acid accumulation was associated with an unfavorable metabolic phenotype; higher 24-h EE; and increased total energy, fat, and protein intake. Acid accumulation markers, as putative markers of higher dietary acid load (e.g., from protein), may affect energy balance physiology promoting weight gain.

Dietary Adherence Is Associated with Perceived Stress, Anhedonia, and Food Insecurity Independent of Adiposity.

We examined whether perceived stress, anhedonia, and food insecurity were associated with dietary adherence during a 6-week intervention. Sixty participants (23 m; 53 ± 14 y) completed psychosocial measures and were provided with full meals. Individuals with obesity were randomized to a weight-maintaining energy needs (WMENs) (n = 18; BMI 33 ± 4) or a 35% calorie-reduced diet (n = 19; BMI 38 ± 9); normal-weight individuals (n = 23; BMI 23 ± 2) were assigned to a WMENs diet. Adherence scores were determined via weekly assessments and daily ecological momentary assessments (EMAs) of real-time behavior in a natural environment. Perceived stress and anhedonia were associated with % body fat (all r-values > 0.25, all p-values < 0.05), but food insecurity and adherence were not. Higher perceived stress (r = -0.31, p = 0.02), anhedonia (r = -0.34, p = 0.01), and food insecurity (r = -0.27, p = 0.04) were associated with lower adherence scores, even after adjusting for age, sex, and % body fat. In all adjusted models, % body fat was not associated with adherence. Higher measures of stress, anhedonia, and food insecurity predicted lower adherence independently of body fat, indicating that psychosocial factors are important targets for successful adherence to dietary interventions, regardless of body size.

Greater anhedonia scores in healthy individuals are associated with less decline in 24-hour energy expenditure with fasting: Evidence for a link between behavioral traits and spendthrift phenotype.

Obesity rates are increasing and affecting mental health. It is important to understand how behavioral traits such as anhedonia are associated with physiologic traits that may predict weight-change in clinical and non-clinical populations. We studied whether 24-hour energy expenditure (24hEE) changes with fasting and overfeeding are associated with anhedonia in a healthy cohort. We performed behavioral assessments (physical anhedonia scale (PAS) and inventory for depressive symptoms (IDS)) followed by measures of 24hEE and urinary catecholamines in a whole-room indirect calorimeter (respiratory chamber) during energy balance, and then randomly during fasting and 2 different overfeeding diets. Participants (n=98) were medically healthy, between 18 and 55 years of age, with normal glucose regulation and weight-stable 6 months before admission. Women were premenopausal and not pregnant. Higher PAS was significantly associated with lesser decrease in 24hEE with fasting and higher urinary catecholamine excretion rates - consistent with spendthrift metabolism. As IDS increased, the association between anhedonia and the change in 24hEE from energy balance to fasting decreased (B-values were lower for change in EE). Here, higher PAS scores may reflect the ability to respond with appropriate homeostatic reactions which balance energy needs. IDS scores blunting this response may explain how anhedonia and depression can lead to weight gain.

The Neurobiology of Eating Behavior in Obesity: Mechanisms and Therapeutic Targets: A Report from the 23rd Annual Harvard Nutrition Obesity Symposium.

Obesity is increasing at an alarming rate. The effectiveness of currently available strategies for the treatment of obesity (including pharmacologic, surgical, and behavioral interventions) is limited. Understanding the neurobiology of appetite and the important drivers of energy intake (EI) can lead to the development of more effective strategies for the prevention and treatment of obesity. Appetite regulation is complex and is influenced by genetic, social, and environmental factors. It is intricately regulated by a complex interplay of endocrine, gastrointestinal, and neural systems. Hormonal and neural signals generated in response to the energy state of the organism and the quality of food eaten are communicated by paracrine, endocrine, and gastrointestinal signals to the nervous system. The central nervous system integrates homeostatic and hedonic signals to regulate appetite. Although there has been an enormous amount of research over many decades regarding the regulation of EI and body weight, research is only now yielding potentially effective treatment strategies for obesity. The purpose of this article is to summarize the key findings presented in June 2022 at the 23rd annual Harvard Nutrition Obesity Symposium entitled "The Neurobiology of Eating Behavior in Obesity: Mechanisms and Therapeutic Targets." Findings presented at the symposium, sponsored by NIH P30 Nutrition Obesity Research Center at Harvard, enhance our current understanding of appetite biology, including innovative techniques used to assess and systematically manipulate critical hedonic processes, which will shape future research and the development of therapeutics for obesity prevention and treatment.

Disinhibition augments thirst perception from two dehydrating stimuli in men.

Physiological systems controlling water and energy ingestion are coordinated. Whether maladaptive eating behavior and appetite for water are linked is unknown. Thus, we sought to investigate the association between maladaptive eating and both thirst and water drinking behavior with two dehydrating conditions. Twenty-two lean men and 20 men with obesity (mean age 32.3 ± 8.4 years and 30.0 ± 11.1 years, respectively) completed the Three-Factor Eating Questionnaire (TFEQ) and Gormally Binge Eating Scale. On separate days, volunteers were dehydrated by a 2-h hypertonic saline infusion and a 24-h water deprivation, and thirst was measured on a 100-mm visual analogue scale (VAS) during each procedure. After each dehydrating condition, ad libitum water intake was measured. In the saline infusion, higher Disinhibition on the TFEQ was associated with thirst in the lean group (ß = 4.2 mm VAS, p = 0.03) but not in the group with obesity (p = 0.51). In the water-deprivation condition, higher Disinhibition was also associated with thirst in the lean group (ß = 5.6 mm VAS, p = 0.01) with the strength of relationship being 3.5-fold stronger than that observed in the group with obesity (ß = 1.6 mm VAS, p = 0.0003). Hunger, Restraint, and binge-eating scores were not associated with thirst in either dehydrating condition (all p > 0.05). Maladaptive eating behaviors were not associated with ad libitum water intake (all p > 0.05). Disinhibition is associated with higher thirst perception in healthy weight individuals and may be attenuated in obesity. The characteristics of disinhibition which typically includes a heightened readiness to eat, may reflect a more general phenotype that also reflects a readiness to drink.

Improved food Go/No-Go scores after transcranial direct current stimulation (tDCS) to prefrontal cortex in a randomized trial.

OBJECTIVE: Reduced dorsolateral prefrontal cortex (dlPFC) activity and inhibitory control may contribute to obesity. The study objective was to assess effects of repeated transcranial direct current stimulation (tDCS) on food Go/No-Go (GNG), food Stroop performance, and snack food intake. METHODS: Twenty-nine individuals with obesity (12 male; mean [SD], age 42 [11] years; BMI 39 [8]) participated in a combined inpatient/outpatient randomized parallel-design trial and received 15 sessions of anodal or sham tDCS to the left dlPFC. Food-related inhibitory control (GNG), attentional bias (Stroop), and snack food intake were assessed at baseline, completion of inpatient sessions (day 7), and follow-up (day 31). RESULTS: GNG performance improved in the anodal group by day 31, compared with sham (p = 0.01), but Stroop scores did not differ by intervention. Greater snack food intake was associated with lower GNG scores (p = 0.01), driven by the sham group (p < 0.001) and higher food and palatable bias scores on the Stroop (all p = 0.02) across both groups. Changes on tasks were not associated with changes in intake. CONCLUSIONS: Anodal tDCS to the left dlPFC improved performance on a food-related inhibitory control task, providing evidence of potential for therapeutic benefit of neuromodulation in areas controlling executive function. Results showed that tDCS to the dlPFC reduced snack food intake and hunger; however, underlying neurocognitive mechanisms remain uncertain.

Water intake, thirst, and copeptin responses to two dehydrating stimuli in lean men and men with obesity.

OBJECTIVE: Physiological systems responsible for water homeostasis and energy metabolism are interconnected. This study hypothesized altered responses to dehydration including thirst, ad libitum water intake, and copeptin in men with obesity. METHODS: Forty-two men (22 lean and 20 with obesity) were stimulated by a 2-hour hypertonic saline infusion and a 24-hour water deprivation. In each dehydrating condition, thirst, ad libitum water intake after dehydration, and urinary and hormonal responses including copeptin were assessed. RESULTS: After each dehydration condition, ad libitum water intake was similar between both groups (p > 0.05); however, those with obesity reported feeling less thirsty (p < 0.05) and had decreased copeptin response and higher urinary sodium concentrations when stressed (p < 0.05). Angiotensin II, aldosterone, atrial and brain natriuretic peptides, and apelin concentrations did not differ by adiposity group and did not explain the different thirst or copeptin responses in men with obesity. However, leptin was associated with copeptin response in lean individuals during the hypertonic saline infusion (p < 0.05), but the relationship was diminished in those with obesity. CONCLUSIONS: Diminished thirst and copeptin responses are part of the obesity phenotype and may be influenced by leptin. Adiposity may impact pathways regulating thirst and vasopressin release, warranting further investigation.

Food insecurity is associated with higher respiratory quotient and lower glucagon-like peptide 1.

OBJECTIVE: Food insecurity is known to be associated with obesity, but its association with physiological measures is unclear. Therefore, it was hypothesized that, compared with food-secure individuals, those with food insecurity would have higher 24-hour energy expenditure (EE [kilocalories per day]) and 24-hour respiratory quotient (RQ [ratio]). Subsequently, hormones involved in appetite regulation, substrate oxidation, and EE were explored. METHODS: A total of 113 healthy participants without diabetes (75 men; mean [SD], age 40 [12] years; BMI 30 [8] kg/m2 ) were included in this analysis. Participants completed the Food Security Short Form, underwent a dual-energy x-ray absorptiometry scan, and spent 24 hours in a human respiratory chamber following a weight-maintaining diet. RESULTS: Compared with individuals with food security, participants with food insecurity had no difference in 24-hour EE. However, they had higher carbohydrate oxidation rates (p = 0.03) and lower lipid oxidation rates (p = 0.02), resulting in higher 24-hour RQ (p < 0.01). They also had lower fasting glucagon-like peptide 1 (p = 0.03) concentrations. CONCLUSIONS: Food insecurity is associated with higher 24-hour RQ and lower fasting glucagon-like peptide 1 concentrations, metabolic and hormonal differences previously shown to drive greater calorie intake in the setting of unrestricted food availability. These findings therefore provide new insight into the paradoxical link between restricted food access and increased adiposity.

Trends in spontaneous physical activity and energy expenditure among adults in a respiratory chamber, 1985 to 2005.

OBJECTIVE: Fidgeting, a type of spontaneous physical activity (SPA), has substantial thermogenic potential. This research aims to examine secular trends in SPA and energy expenditure (EE) inside a respiratory chamber. METHODS: From 1985 to 2005, healthy adults (n = 678; mean age: 28.8 years; men: 60%; 522 Indigenous American, 129 White, and 27 Black) had a 24-hour stay in the respiratory chamber equipped with radar sensors. Body composition, glucose tolerance, fasting insulin, insulin action (hyperinsulinemic-euglycemic clamp), and insulin secretion (intravenous glucose tolerance test) were measured as covariates. RESULTS: SPA, adjusted for age, sex, race, and body composition, declined (r = -0.30, p < 0.0001), with a concomitant rise in the energy cost of SPA (r = 0.30, p < 0.0001). The 24-hour EE adjusted for covariates increased (r = 0.31, p < 0.0001), which was reflected in increases in EE during sleep (r = 0.18, p < 0.0001) and during the awake, fed condition (r = 0.28, p < 0.0001). The secular trends in SPA or 24-hour EE were unchanged with adjustment for measures related to glucose metabolism. CONCLUSIONS: Secular trend analyses showed a decline in fidgeting. However, this decline in SPA was partially counterbalanced by an increase in energy cost of this activity and a rise in EE. Nevertheless, our results support public health efforts to promote small but sustained changes in these behaviors.

Meal-to-meal and day-to-day macronutrient variation in an ad libitum vending food paradigm.

BACKGROUND: Theory posits that macronutrient intake is regulated by protein consumption and adequate intake of protein results in consumption of less carbohydrates and fat. The current study investigates the effect of protein intake on calorie and macronutrient content using an ad libitum vending machine paradigm. METHODS: Healthy volunteers (n = 287; 177 m; Age = 36 ± 11; BMI = 32 ± 8) were admitted to our clinical research unit. Macronutrient meal content (grams) and energy intake (Kcal) were quantified by specialized food processing software and collected on an hourly basis over a three-day period using a validated ad libitum vending machine paradigm. Body composition was assessed by DXA. Lagged multi-level models accounting for age, sex, race/ethnicity, fat and fat free mass indices were fitted to examine the impact of prior macronutrient content on subsequent meals. RESULTS: Protein intake was associated with decreased energy intake (Kcal; B = -1.67 kcal, p = 0.0048), lower protein and carbohydrate intake (B = -0.08 g, p = 0.0006; B = -0.21 g, p = 0.0003, respectively) at subsequent meals. Daily Macronutrient intake and subsequent intake were positively associated. CONCLUSIONS: Dietary protein exhibits a negative regulatory effect on a short-term meal-to-meal rather than day-to-day basis. In the setting of readily available food, protein intake impacts energy intake only over very short time courses.

Food insecurity moderates the relationship between momentary affect and adherence in a dietary intervention study.

OBJECTIVE: Negative affect and food insecurity have been proposed to impede adherence to weight loss interventions. Therefore, this study examined the role of these variables on dietary adherence using Ecological Momentary Assessment. METHODS: A total of 50 participants (19 male participants; age = 49 [SD 14] years) participated in an outpatient dietary study. Lean participants (n = 22; BMI ≤ 25 kg/m2 ) received a weight-maintaining energy needs (WMEN) diet, and participants with obesity (BMI ≥ 30) were randomized to receive either a WMEN diet (n = 14) or a 35% calorie-reduced diet (n = 14). Food insecurity was measured, and, twice daily, Ecological Momentary Assessment captured real-time affect ratings and adherence. Between-person (trait-level) and lagged within-person (state-level) scores were calculated. RESULTS: Greater food insecurity and trait-level negative affect were associated with reduced adherence (p = 0.0015, p = 0.0002, respectively), whereas higher trait-level positive affect was associated with greater adherence (p < 0.0001). Significant interactions between affect and food insecurity revealed an association between higher trait positive affect and increased adherence at lower levels of food insecurity. Higher trait negative affect was more strongly associated with decreased adherence in participants with greater levels of food insecurity (-1 SD: B = -0.21, p = 0.22; mean: B = -0.46, SE = 0.13, p = 0.0004; +1 SD: B = -0.71, SE = 0.17, p < 0.0001). CONCLUSIONS: Trait-level affect may be crucial in predicting dietary adherence, especially in those with greater food insecurity.

Is Dietary Nonadherence Unique to Obesity and Weight Loss? Results From a Randomized Clinical Trial.

OBJECTIVE: Weight stigma is associated with poor dietary adherence, yet adherence is essential for weight loss and maintenance. This study aimed to determine differences in dietary adherence and perceived hunger between lean individuals and two groups of individuals with obesity. METHODS: In a 6-week outpatient dietary intervention (23 males; aged 48 [SD 14] years), lean participants (n = 23; BMI 23 [SD 2] kg/m2 ) received a weight-maintaining energy needs (WMEN) diet, and participants with obesity (BMI 36 [SD 7]) were randomized to either WMEN (n = 18) or a 35% calorie-reduced (CR) diet (n = 19). All food was provided, and multiple adherence and hunger ratings were assessed daily and weekly on an outpatient basis and in person at twice-weekly visits (e.g., 24-hour recall, diaries). RESULTS: Weight decreased more in the group of CR individuals with obesity (ß = -0.301 kg/wk, P = 0.02) compared with the group of lean individuals and the group of WMEN individuals with obesity. However, total percent adherence did not differ between groups (P = 0.60), and hunger scores did not change across groups over time (P = 0.08). CONCLUSIONS: Results indicate that there are no differences in dietary adherence between lean individuals and individuals with obesity and adherence is not associated with adiposity or hunger. Thus, the belief that nonadherence (e.g., lack of willpower) is unique to obesity is untrue and may perpetuate weight bias and stigma.

Assessing established BMI variants for a role in nighttime eating behavior in robustly phenotyped Southwestern American Indians.

BACKGROUND/OBJECTIVES: Nighttime eating (NE) behavior has a genetic component and predicts weight gain. We hypothesized that some genetic variants, which affect NE would also show an effect on body mass index (BMI). We aimed to determine which known BMI variants associate with NE in Southwestern American Indians (SWAIs), who are at elevated risk for obesity. METHODS: Known BMI variants from the GIANT-UK Biobank meta-analysis (N = 700,000) were analysed in SWAIs characterized for NE during an inpatient 3-day protocol. Variants were analysed for association with NE using whole-genome sequence data from 50 SWAIs (23 cases and 27 controls) and selected variants were genotyped in an additional 32 SWAIs (13 NE cases and 19 controls). Variants associated with NE in a meta-analysis of the two SWAI samples were further analysed for association with nightly caloric intake and functionality in hypothalamus, pituitary, and adrenal tissues. RESULTS: Variants were identified where the allele that associated with increased BMI in the GIANT-UK Biobank meta-analysis (P ≤ 1 × 10-8) also had a P < 0.01 for increased NE in the SWAI meta-analysis. These variants were captured by six tagSNPs. Comparison of the nightly calorie intake by genotype and eQTL data from relevant tissues highlighted rs3753612 upstream of HCRTR1. CONCLUSIONS: Our strategy led to the HCRTR1 locus, which has previously been linked to sleep regulation and feeding. Although this is an intriguing candidate gene for NE, further studies in larger samples and different populations are required to validate the role of HCRTR1 in NE.

Brain Stimulation to Modulate Food Intake and Eating Behavior.

PURPOSE OF REVIEW: Appetitive behaviors are mediated through homeostatic and reward signaling of brain circuits. There has been increasing interest in the use of neuromodulation techniques aimed at targeting brain regions such as the lateral prefrontal and subcortical regions associated with dysregulation of eating behaviors. RECENT FINDINGS: Invasive brain stimulation techniques have demonstrated promising results in treating severe and enduring anorexia nervosa and morbid obesity. In addition, non-invasive techniques have been shown to successfully reduce food craving, hunger ratings, and calorie intake as well as binge/purge symptoms in eating disorders. Brain stimulation offers promising results for treating symptoms associated with eating disorders and modifying appetitive behaviors including craving and caloric consumption. Future research should focus on identifying optimal frequency and duration of stimulation and employ longitudinal studies to assess long-term effectiveness on clinical outcomes such as eating disorder symptomatology, weight loss, and sustained improvements in eating behaviors over time.

Cognitive dietary restraint, disinhibition, and hunger are associated with 24-h energy expenditure.

BACKGROUND: Higher energy expenditure (EE) is associated with greater food intake, possibly because the human body senses EE and modifies eating behaviors to regulate food intake and ultimately achieve energy balance. As eating behaviors are also influenced by social and cultural factors, any association between EE and eating behavior may differ between ethnicities and sexes. OBJECTIVE: To assess relationships between EE and eating behavior constructs of the Three-Factor Eating Questionnaire (TFEQ). SUBJECTS/METHODS: In all, 307 healthy adults (201 M/106 F, 160 Native Americans) completed the TFEQ and had measures of 24-h EE in a whole-room calorimeter during energy balance. Body composition was assessed by DXA. RESULTS: On average, adjusted 24-h EE was lower (ß = -229 kcal/day, CI: -309 to -148, p < 0.001) but cognitive restraint (Δ = + 1.5; CI: 0.5 to 2.5, p = 0.003) and disinhibition (Δ = + 2.1, CI: 1.3 to 2.8, p < 0.001) scores were higher in women compared with men. In Native Americans, adjusted 24-h EE (ß = + 94 kcal/day, CI: 48 to 139, p < 0.001) and disinhibition scores (Δ = + 1.0, CI: 0.1 to 2.0, p = 0.003) were higher compared with other ethnicities. Higher 24-h EE associated with lower cognitive restraint in women (ρ = -0.20, p = 0.04), but not men (p = 0.71; interaction term p = 0.01) with no ethnic differences. Greater 24-h EE associated with higher disinhibition (ρ = 0.20, p = 0.001) and hunger cues (ρ = 0.16, p = 0.004) with no gender differences. These associations were primarily present in non-Native Americans (ρ = 0.23, p = 0.006 and ρ = 0.25, p = 0.003) but not observed in Native Americans (both p > 0.40). CONCLUSIONS: Higher EE is associated with psychological constructs of eating behaviors that favors overeating including lower cognitive restraint, higher dietary disinhibition, and greater susceptibility to hungers cues, supporting the existence of energy-sensing mechanisms influencing human eating behavior. These associations were observed in ethnicities other than Native Americans, possibly explaining the contradictory relationships reported between EE and weight change in different ethnic groups. We propose that increased EE may alter eating behaviors, potentially leading to uncontrolled overeating and weight gain.

Food Insecurity is Associated with Maladaptive Eating Behaviors and Objectively Measured Overeating.

OBJECTIVE: The association between food insecurity and obesity may be partially explained by overeating in response to unpredictable food availability cycles. The aim of this study was to measure objective food intake in food-insecure individuals. METHODS: Eighty-two volunteers (53 m; BMI 29 ± 7; 38 ± 12 years) were admitted to our inpatient Clinical Research Unit and completed the Food Security Short Form, Three-Factor Eating Questionnaire, Gormally Binge Eating Scale, and body composition assessment (dual-energy x-ray absorptiometry). After 5 days of a weight-maintaining diet, participants self-selected food from an ad libitum vending machine paradigm for 3 days. Mean daily intake (kilocalories), macronutrient intake, and percentage of weight-maintaining energy needs (%WMEN) were calculated. RESULTS: Based on Food Security Short Form cutoffs, food-insecure participants (n = 46; 56%) had higher body weight (P = 0.04), fat-free mass (P = 0.05), disinhibition (P = 0.008), hunger (P = 0.02), and binge-eating scores (P = 0.02) but not cognitive restraint (P = 0.37) compared with food-secure individuals. They overate more kilocalories (P = 0.001), %WMEN (P = 0.003), fat (P = 0.003), and carbohydrates (P = 0.004) during the vending machine paradigm, continued to increase their hourly rate of kilocalories (group × time; ß = 37.7 cumulative kcal/h; P < 0.0001), and ate more total kilocalories across the 72 hours (ß = 47.09 kcal/h; P = 0.003). CONCLUSIONS: Food insecurity may amplify susceptibility to weight gain via overeating during times of unlimited food access.

Depressive symptoms and poorer performance on the Stroop Task are associated with weight gain.

OBJECTIVE: Executive function impairments and depression are associated with obesity but whether they predict weight gain is unclear. METHODS: Forty-six individuals (35m, 37±10y) completed the Stroop Task, Iowa Gambling Task (IGT), Wisconsin Card Sorting Task (WCST), Inventory for Depressive Symptomatology (IDS-SR), Physical Anhedonia Scale (PAS), and Perceived Stress Scale (PSS). Body composition (DXA) and fasting glucose were also measured. Data from return visits were used to assess changes in weight. RESULTS: Poorer Stroop and WCST performance associated with higher BMI whereas poorer IGT and WCST performance associated with higher body fat (%; all p's≤0.05). Stroop interference (p=0.04; p=0.05) and IDS-SR (p=0.06; p=0.02) associated with increased BMI and weight gain (%/yr). In a multivariate linear model Stroop interference (ß=0.40, p<0.01; ß=0.35, p<0.01) and IDS-SR (ß=0.38, p<0.01; ß=0.37, p<0.01) independently predicted increased BMI and weight gain (%/yr) even after controlling for baseline weight and glucose levels. CONCLUSIONS: Poorer response inhibition and depressive symptoms, but not glucose levels, predicted weight gain. Evaluating neurocognitive and mood deficits could improve current treatment strategies for weight loss. Clinical Trial Registration Numbers NCT00523627, NCT00342732, NCT01224704. clinicaltrials.gov.

Obesity, Appetite, and the Prefrontal Cortex.

PURPOSE OF REVIEW: Obesity is a chronic illness and its prevalence is growing worldwide and numerous factors play a role in the regulation of food intake. The prefrontal cortex (PFC) is involved in high-order executive function, regulation of limbic reward regions, and the inhibition of impulsive behaviors. Understanding the role of the PFC in the control of appetite regulation may contribute to a greater understanding of the etiology of obesity and could improve weight loss outcomes. RECENT FINDINGS: Neuroimaging studies have identified lower activation in the left dorsolateral PFC (DLPFC) in obese compared to lean individuals and others have focused on efforts to improve cognitive control in this area of the brain. The DLPFC is a critical brain area associated with appetitive control, food craving, and executive functioning, indicating a candidate target area for treatment. Further studies are needed to advance our understanding of the relationship between obesity, appetite, and the DLPFC and provide validation for the effectiveness of novel treatments in clinical populations.

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.