Creation and validation of a NOVA scored picture set to evaluate ultra-processed foods.

There has been a rapid shift in the modern food environment towards increased processing in foods consumed in the United States (US) and globally. The NOVA system (not an acronym) for classifying food on degree of processing currently has the most empirical support. Consumption of foods in the NOVA 4 category, ultra-processed foods (UPF), is a risk factor for a host of poor health outcomes including heart disease, stroke, and cancer. Despite these poor health outcomes, UPF make up 58% of calories consumed in the US. Methodologies for assessing the reinforcing and rewarding properties of these foods are necessary tools. The Becker-DeGroot-Marschak auction paradigm (BDM) is a well validated tool for measuring value and is amenable to neuromonitoring environments. To allow for the testing of hypotheses based on level of food processing, we present a picture set of 14 UPF and 14 minimally-processed foods (MPF) matched on visual properties, food characteristics (fat, carbohydrate, cost, etc.), and rated perceptual properties. Further, we report our scoring of these foods using the NOVA classification system and provide additional data from credentialed nutrition professionals and on inter-rater reliability using NOVA, a critique of the system. Finally, we provide all pictures, data, and code used to create this picture set as a tool for researchers.

The Impact of Weight Bias and Stigma on the 24 h Dietary Recall Process in Adults with Overweight and Obesity: A Pilot Study.

People with overweight and obesity tend to both underreport dietary energy intake and experience weight stigma. This exploratory pilot study aimed to determine the relationship between weight bias and weight stigma and energy intake reporting accuracy. Thirty-nine weight-stable adults with BMI ≥ 25 completed three 24 h dietary recalls; indirect calorimetry to measure resting metabolic rate; a survey measuring weight stigma, psychosocial constructs, and physical activity; and a semi-structured qualitative interview. Multiple linear regression was used to determine if weight bias internalization, weight bias toward others, and experiences of weight stigma were predictive of the accuracy of energy reporting. A thematic analysis was conducted for the qualitative interviews. Weight stigma was reported by 64.1% of the sample. Weight stigma constructs did not predict the accuracy of energy intake reporting. People with obesity underreported by a mean of 477 kcals (p = 0.02). People classified as overweight overreported by a mean of 144 kcals, but this was not significant (p = 0.18). Participants reported a desire to report accurate data despite concerns about reporting socially undesirable foods. Future research should quantify the impact of weight stigma on energy reporting in 24 h recalls using a larger, more diverse sample size and objective measures like doubly labeled water for validation.

Semaglutide and Tirzepatide reduce alcohol consumption in individuals with obesity.

Alcohol Use Disorder (AUD) contributes significantly to global mortality. GLP-1 (Glucagon-like peptide-1) and GLP-1/GIP (Glucose-dependent Insulinotropic Polypeptide) agonists, FDA-approved for managing type 2 diabetes and obesity, where the former has shown to effectively reduce the consumption of alcohol in animal models but no reports exist on the latter. In this report, we conducted two studies. In the first study, we conducted an analysis of abundant social media texts. Specifically, a machine-learning based attribution mapping of ~ 68,250 posts related to GLP-1 or GLP-1/GIP agonists on the Reddit platform. Secondly, we recruited participants (n = 153; current alcohol drinkers; BMI ≥ 30) who self-reported either taking Semaglutide (GLP-1 agonist), Tirzepatide (the GLP-1/GIP combination) for ≥ 30 days or, as a control group; no medication to manage diabetes or weight loss for a within and between subject remote study. In the social media study, we report 8 major themes including effects of medications (30%); diabetes (21%); and Weight loss and obesity (19%). Among the alcohol-related posts (n = 1580), 71% were identified as craving reduction, decreased desire to drink, and other negative effects. In the remote study, we observe a significantly lower self-reported intake of alcohol, drinks per drinking episode, binge drinking odds, Alcohol Use Disorders Identification Test (AUDIT) scores, and stimulating, and sedative effects in the Semaglutide or Tirzepatide group when compared to prior to starting medication timepoint (within-subjects) and the control group (between-subjects). In summary, we provide initial real-world evidence of reduced alcohol consumption in people with obesity taking Semaglutide or Tirzepatide medications, suggesting potential efficacy for treatment in AUD comorbid with obesity.

The influence of ultra-processed food consumption on reward processing and energy intake: Background, design, and methods of a controlled feeding trial in adolescents and young adults.

BACKGROUND: The greatest age-related weight gain occurs in the early/mid-20s. Overall dietary quality among adolescents and emerging adults (age 18-25) is poor, with ultra-processed foods (UPF) representing more than two-thirds of adolescents' total energy intake (i.e., 68%). UPF consumption may impact cognitive and neurobiological factors that influence dietary decision-making and energy intake (EI). To date, no research has addressed this in this population. METHODS: Participants aged 18-25 will undergo two 14-day controlled feeding periods (81% UPF, 0% UPF) using a randomly assigned crossover design, with a 4-week washout between conditions. Brain response to a UPF-rich milkshake, as well as behavioral measures of executive function, will be evaluated before and after each diet. Following each diet, measurements include ad libitum buffet meal EI, food selection, eating rate, and eating in the absence of hunger (EAH). Prior to initiating recruitment, controlled diet menus, buffet, and EAH snacks were developed and evaluated for palatability. Sensory and texture attributes of buffet and EAH snack foods were also evaluated. RESULTS: Overall diet palatability was rated "like very much" (8)/"like moderately"(7) (UPF: 7.6 ± 1.0; Non-UPF: 6.8 ± 1.5). Subjective hardness rating (range = 1-9 [1 = soft, 9 = hard] was similar between UPF and Non-UPF buffet and snack items (UPF:4.22 ± 2.19, Non-UPF: 4.70 ± 2.03), as was the objective measure of hardness (UPF: 2874.33 ± 2497.06 g, Non-UPF: 2243.32 ± 1700.51 g). CONCLUSIONS: Findings could contribute to an emerging neurobiological understanding of the effects of UPF consumption including energy overconsumption and weight gain among individuals at a critical developmental stage.

Validity and reliability of a new whole room indirect calorimeter to assess metabolic response to small-calorie loads.

Objective: To provide an overview of our whole room indirect calorimeter (WRIC), demonstrate validity and reliability of our WRIC, and explore a novel application of Bayesian hierarchical modeling to assess responses to small carbohydrate loads. Methods: Seven gas infusion studies were performed using a gas blender and profiles designed to mimic resting and postprandial metabolic events to assess WRIC validity. In a crossover design, 16 participants underwent fasting and postprandial measurements, during which they consumed a 75-kcal drink containing sucrose, dextrose, or fructose. Linear mixed effects models were used to compare resting and postprandial metabolic rate (MR) and CO (CO). Bayesian Hierarchical Modeling was also used to model postprandial CO trajectories for each participant and condition. Results: Mean total error in infusions were 1.27 ± 1.16% and 0.42 ± 1.21% for VO2 and VCO2 respectively, indicating a high level of validity. Mean resting MR was similar across conditions (x¯=1.05±0.03 kcal/min, p=0.82, ICC: 0.91). While MR increased similarly among all conditions (~13%, p=0.29), postprandial CO parameters were significantly lower for dextrose compared with sucrose or fructose. Conclusions: Our WRIC validation and novel application of statistical methods presented here provide important foundations for new research directions using WRIC.

Habitual daily intake of a sweet and fatty snack modulates reward processing in humans.

Western diets rich in fat and sugar promote excess calorie intake and weight gain; however, the underlying mechanisms are unclear. Despite a well-documented association between obesity and altered brain dopamine function, it remains elusive whether these alterations are (1) pre-existing, increasing the individual susceptibility to weight gain, (2) secondary to obesity, or (3) directly attributable to repeated exposure to western diet. To close this gap, we performed a randomized, controlled study (NCT05574660) with normal-weight participants exposed to a high-fat/high-sugar snack or a low-fat/low-sugar snack for 8 weeks in addition to their regular diet. The high-fat/high-sugar intervention decreased the preference for low-fat food while increasing brain response to food and associative learning independent of food cues or reward. These alterations were independent of changes in body weight and metabolic parameters, indicating a direct effect of high-fat, high-sugar foods on neurobehavioral adaptations that may increase the risk for overeating and weight gain.

Highly processed foods can be considered addictive substances based on established scientific criteria.

BACKGROUND: There is growing evidence that an addictive-eating phenotype may exist. There is significant debate regarding whether highly processed foods (HPFs; foods with refined carbohydrates and/or added fats) are addictive. The lack of scientifically grounded criteria to evaluate the addictive nature of HPFs has hindered the resolution of this debate. ANALYSIS: The most recent scientific debate regarding a substance's addictive potential centered around tobacco. In 1988, the Surgeon General issued a report identifying tobacco products as addictive based on three primary scientific criteria: their ability to (1) cause highly controlled or compulsive use, (2) cause psychoactive (i.e. mood-altering) effects via their effect on the brain and (3) reinforce behavior. Scientific advances have now identified the ability of tobacco products to (4) trigger strong urges or craving as another important indicator of addictive potential. Here, we propose that these four criteria provide scientifically valid benchmarks that can be used to evaluate the addictiveness of HPFs. Then, we review the evidence regarding whether HPFs meet each criterion. Finally, we consider the implications of labeling HPFs as addictive. CONCLUSION: Highly processed foods (HPFs) can meet the criteria to be labeled as addictive substances using the standards set for tobacco products. The addictive potential of HPFs may be a key factor contributing to the high public health costs associated with a food environment dominated by cheap, accessible and heavily marketed HPFs.

Hedgehog-interacting protein acts in the habenula to regulate nicotine intake.

Hedgehog-interacting protein (HHIP) sequesters Hedgehog ligands to repress Smoothened (SMO)-mediated recruitment of the GLI family of transcription factors. Allelic variation in HHIP confers risk of chronic obstructive pulmonary disease and other smoking-related lung diseases, but underlying mechanisms are unclear. Using single-cell and cell-type-specific translational profiling, we show that HHIP expression is highly enriched in medial habenula (MHb) neurons, particularly MHb cholinergic neurons that regulate aversive behavioral responses to nicotine. HHIP deficiency dysregulated the expression of genes involved in cholinergic signaling in the MHb and disrupted the function of nicotinic acetylcholine receptors (nAChRs) through a PTCH-1/cholesterol-dependent mechanism. Further, CRISPR/Cas9-mediated genomic cleavage of the Hhip gene in MHb neurons enhanced the motivational properties of nicotine in mice. These findings suggest that HHIP influences vulnerability to smoking-related lung diseases in part by regulating the actions of nicotine on habenular aversion circuits.

The impact of caloric availability on eating behavior and ultra-processed food reward.

The food environment has changed rapidly and dramatically in the last 50 years. While industrial food processing has increased the safety and stability of the food supply, a rapid expansion in the scope and scale of food processing in the 1980's has resulted in a market dominated by ultra-processed foods. Here, we use the NOVA definition of category 4 ultra-processed foods (UPFs) as they make up around 58% of total calories consumed in the US and 66% of calories in US children. UPFs are formulated from ingredients with no or infrequent culinary use, contain additives, and have a long shelf-life, spending long periods in contact with packaging materials, allowing for the absorption of compounds from those materials. The full implications of this dietary shift to UPFs on human health and disease outcomes are difficult, if not impossible, to quantify. However, UPF consumption is linked with various forms of cancer, increased cardiovascular disease, and increased all-cause mortality. Understanding food choice is, therefore, a critical problem in health research. Although many factors influence food choice, here we focus on the properties of the foods themselves. UPFs are generally treated as food, not as the highly refined, industrialized substances that they are, whose properties and components must be studied. Here, we examine one property of UPFs, that they deliver useable calories rapidly as a potential factor driving UPF overconsumption. First, we explore evidence that UPFs deliver calories more rapidly. Next, we examine the role of the gut-brain axis and its interplay with canonical reward systems, and last, we describe how speed affects both basic learning processes and drugs of abuse.

Opposing roles for striatonigral and striatopallidal neurons in dorsolateral striatum in consolidating new instrumental actions.

Comparatively little is known about how new instrumental actions are encoded in the brain. Using whole-brain c-Fos mapping, we show that neural activity is increased in the anterior dorsolateral striatum (aDLS) of mice that successfully learn a new lever-press response to earn food rewards. Post-learning chemogenetic inhibition of aDLS disrupts consolidation of the new instrumental response. Similarly, post-learning infusion of the protein synthesis inhibitor anisomycin into the aDLS disrupts consolidation of the new response. Activity of D1 receptor-expressing medium spiny neurons (D1-MSNs) increases and D2-MSNs activity decreases in the aDLS during consolidation. Chemogenetic inhibition of D1-MSNs in aDLS disrupts the consolidation process whereas D2-MSN inhibition strengthens consolidation but blocks the expression of previously learned habit-like responses. These findings suggest that D1-MSNs in the aDLS encode new instrumental actions whereas D2-MSNs oppose this new learning and instead promote expression of habitual actions.

Fat and Carbohydrate Interact to Potentiate Food Reward in Healthy Weight but Not in Overweight or Obesity.

Prior work suggests that actual, but not estimated, energy density drives the reinforcing value of food and that energy from fat and carbohydrate can interact to potentiate reward. Here we sought to replicate these findings in an American sample and to determine if the effects are influenced by body mass index (BMI). Thirty participants with healthy weight (HW; BMI 21.92 ± 1.77; M ± SD) and 30 participants with overweight/obesity (OW/OB; BMI 29.42 ± 4.44) rated pictures of common American snacks in 120-kcal portions for liking, familiarity, frequency of consumption, expected satiety, healthiness, energy content, energy density, and price. Participants then completed an auction task where they bid for the opportunity to consume each food. Snacks contained either primarily carbohydrate, primarily fat, or roughly equal portions of fat and carbohydrate (combo). Replicating prior work, we found that participants with HW bid the most for combo foods in linear mixed model analyses. This effect was not observed among individuals with OW/OB. Additionally, in contrast with previous reports, our linear regression analyses revealed a negative relationship between the actual energy density of the snacks and bid amount that was mediated by food price. Our findings support altered macronutrient reinforcement in obesity and highlight potential influences of the food environment on the regulation of food reward.

Development of MacroPics: A novel food picture set to dissociate the effects of carbohydrate and fat on eating behaviors.

Emerging evidence suggests that fat and carbohydrate interact to potentiate the reward value of food (DiFeliceantonio et al., 2018). The primary goal of the current study was to develop a novel picture set to facilitate research into the effects of macronutrient composition on food choice and eating behavior. Toward this aim, we developed "MacroPics." In Experiment 1, we photographed 120-kcal portions of 60 snack foods falling into one of the three macronutrient categories: (1) mostly carbohydrate, (2) mostly fat, or (3) a combination of fat and carbohydrate. Sixty-one participants rated the images for liking, familiarity, frequency of consumption, healthiness, estimated energy content (in kcal), and expected satiation. A subset of these images consisting of 36 items was then selected in an iterative process to minimize differences in ratings between the macronutrient categories while simultaneously ensuring similar within-category variability on a number of food characteristics (e.g., energy density, portion size, retail price) and visual properties (e.g., color, complexity, visual area). In Experiment 2, an independent sample of 67 participants rated the pictures of the final 36-item MacroPics. Both experiments reveal similar participant ratings across categories for item liking, familiarity, frequency, healthiness, and estimated energy content. Protein content was higher in the fat compared to the carbohydrate and combination categories, leading to higher ratings of estimated satiety and energy density for fatty foods. Item and macronutrient category characteristics of the final MacroPics set are reported.

No evidence for an association between obesity and milkshake liking.

BACKGROUND: Prevailing models of obesity posit that hedonic signals override homeostatic mechanisms to promote overeating in today's food environment. What researchers mean by "hedonic" varies considerably, but most frequently refers to an aggregate of appetitive events including incentive salience, motivation, reinforcement, and perceived pleasantness. Here we define hedonic as orosensory pleasure experienced during eating and set out to test whether there is a relationship between adiposity and the perceived pleasure of a palatable and energy-dense milkshake. METHODS: The perceived liking, wanting, and intensity of two palatable and energy-dense milkshakes were assessed using the Labeled Hedonic Scale (1), visual analog scale (VAS), and Generalized Labeled Magnitude Scale (2) in 110 individuals ranging in body mass index (BMI) from 19.3 to 52.1 kg/m2. Waist circumference, waist-hip ratio, and percent body fat were also measured. Importantly, unlike the majority of prior studies, we attempted to standardize internal state by instructing participants to arrive to the laboratory neither hungry nor full and at least 1-h fasted. Data were analyzed with general linear and linear mixed effects models (GLMs). Hunger ratings were also examined prior to hedonic measurement and included as covariates in our analyses. RESULTS: We identified a significant association between ratings of hunger and milkshake liking and wanting. By contrast, we found no evidence for a relationship between any measure of adiposity and ratings of milkshake liking, wanting, or intensity. CONCLUSIONS: We conclude that adiposity is not associated with the pleasure experienced during consumption of our energy-dense and palatable milkshakes. Our results provide further evidence against the hypothesis that heightened hedonic signals drive weight gain.

Unique contributions of parvalbumin and cholinergic interneurons in organizing striatal networks during movement.

Striatal parvalbumin (PV) and cholinergic interneurons (CHIs) are poised to play major roles in behavior by coordinating the networks of medium spiny cells that relay motor output. However, the small numbers and scattered distribution of these cells have hindered direct assessment of their contribution to activity in networks of medium spiny neurons (MSNs) during behavior. Here, we build on recent improvements in single-cell calcium imaging combined with optogenetics to test the capacity of PVs and CHIs to affect MSN activity and behavior in mice engaged in voluntary locomotion. We find that PVs and CHIs have unique effects on MSN activity and dissociable roles in supporting movement. PV cells facilitate movement by refining the activation of MSN networks responsible for movement execution. CHIs, in contrast, synchronize activity within MSN networks to signal the end of a movement bout. These results provide new insights into the striatal network activity that supports movement.

Food Intake Recruits Orosensory and Post-ingestive Dopaminergic Circuits to Affect Eating Desire in Humans.

Pleasant taste and nutritional value guide food selection behavior. Here, orosensory features of food may be secondary to its nutritional value in underlying reinforcement, but it is unclear how the brain encodes the reward value of food. Orosensory and peripheral physiological signals may act together on dopaminergic circuits to drive food intake. We combined fMRI and a novel [11C]raclopride PET method to assess systems-level activation and dopamine release in response to palatable food intake in humans. We identified immediate orosensory and delayed post-ingestive dopamine release. Both responses recruit segregated brain regions: specialized integrative pathways and higher cognitive centers. Furthermore, we identified brain areas where dopamine release reflected the subjective desire to eat. Immediate dopamine release in these wanting-related regions was inversely correlated with, and presumably inhibited, post-ingestive release in the dorsal striatum. Our results highlight the role of brain and periphery in interacting to reinforce food intake in humans.