Appetite

Background Emerging evidence highlights the gut-brain axis as a key pathway linking diet and anxiety, yet the key determinants remain unclear. Most studies have focused on single components of diet and rarely integrate long- and short-term intake. Furthermore, prior gut-brain work has focused on microbiome composition, while functional features remain underexplored. In this study, we investigated associations between long- and short-term dietary intake, gut microbiome composition and functions, and anxiety in a subclinical cohort of 46 females (18-24 years) from the United Kingdom. Results Long-term diet quality was assessed using the Healthy Eating Index (HEI-2020) derived from a food frequency questionnaire, stratifying participants into lower and higher diet quality clusters. Short-term dietary intake was assessed via 24-hour recalls. Shotgun metagenomics of stool samples was used to assess differences in alpha and beta diversity indices, species abundances, and bacterial pathways putatively metabolizing gut-brain-axis-relevant molecules. Anxiety was measured using the State-Trait Anxiety Inventory (state subscale STAI-s). Regression models identified diet quality (HEI cluster) as the primary dietary feature of anxiety variation. The presence of Ruminococcus gnavus and Flavonifractor plautii and the abundances of Bilophila wadsworthia and Bacteroides thetaiotaomicron were positively associated with anxiety. The presence of Feacalibacterium prausnitzii and greater abundances of butyrate, propionate, and GABA synthesis pathways were inversely associated with anxiety. Non-linear models revealed a U-shaped relationship between inositol synthesis and STAI-s. Finally, we found that habitual diet quality may modulate anxiety-related responses to short-term dietary variation. Conclusions These findings reveal widespread links between long-term diet quality, microbiota composition and function, and anxiety symptoms. These results point towards several promising targets for prebiotic, probiotic, postbiotic, and dietary interventions aimed at reducing anxiety.

Obesity is a growing public health concern with more than 40% of adults meeting criteria for obesity in the United States. Although many treatments seek to lower individuals weight, few treatments have focused on cognitive strategies to change the way individuals think about food, therefore, decreasing consumption of non-nutrient-dense foods. Cognitive reappraisal is one strategy that involves changing the way one thinks about a situation and can be used to downregulate responses to those stimuli. Leveraging this intuitive, cost-effective strategy to decrease ones desire to eat unhealthy food and therefore, decrease overeating, could improve physical and mental health. The present study identified brain regions that are differentially activated when using cognitive reappraisal to downregulate responses to food (FR) versus when using the same strategy to downregulate negative emotions (ER). We collected functional magnetic resonance imaging (fMRI) data in 63 undergraduate students while participants completed both tasks. There was increased reappraisal-related activation in widespread regions across both tasks, including in expected subcortical (i.e., striatum) and cortical areas (i.e., visual, frontoparietal). We also found domain-specific activity, with greater insula activation in the FR than the ER task and greater hippocampal activation in the ER than the FR task. These results reveal domain-general and domain-specific effects of cognitive reappraisal in FR and ER tasks that inform future work examining eating behavior. Taken together, a better explication of the overlapping and discrete processes of food regulation, as it compares to other applications of this regulatory strategy can inform new intervention targets.

Unpredictable and insufficient access to food, known as food insecurity, is associated with the development of obesity. However, causal mechanisms underlying this paradoxical relationship remain poorly understood. Using a rat model of food insecurity, this study investigated whether food insecurity causes dysregulated feeding behaviours, specifically impaired gut signal sensitivity and enhanced cue-driven appetitive responses. Adolescent female rats were assigned to receive either ad libitum chow access (Food secure), 90% caloric restriction (Food restricted) or unpredictable quantity and timing of food access (Food insecure), for 4 weeks. After which, rats were returned to an ad libitum chow diet for the remainder of the study. To examine gut signal sensitivity, we measured the effects of cholecystokinin (CCK) on 10% sucrose intake. To examine cue-driven feeding behaviours, we used Pavlovian appetitive conditioning and measured appetitive responses towards a food-predictive cue. Results showed that prior food insecure rats were less sensitive to the intake inhibitory effects of CCK and exhibited enhanced cue-induced appetitive behaviours, when compared to food secure and food restricted groups. Anxiety-like behaviours or learning and memory was not different between groups. At the end of the study, adolescent caloric restriction resulted in reduced fat mass, plasma leptin levels and body weight when compared to food secure, but not food insecure rats, suggesting that adolescent food insecurity somewhat overcame these metabolic effects. Taken together, our findings suggest that adolescent food insecurity impaired gut signal sensitivity and heightened food cue sensitivity, which may cause enduring metabolic and behavioural adaptations that promote overeating and weight gain.

Although dietary intake is a leading risk factor for many common diseases, adherence to dietary recommendations remains low. This may partly reflect limited consideration of individual differences in eating behavior that arise from both environmental and genetic factors. While genome-wide association studies (GWAS) of dietary intake have identified hundreds of associated loci, the X chromosome has largely been ignored. To address this gap, we applied multiple X-chromosome-wide association study (X-WAS) models on dietary intake phenotypes to identify novel associations. We performed X-WAS of 46 dietary intake traits from food frequency questionnaires in up to 424,758 European participants from the UK Biobank. Phenotypes included quantitative measures (e.g., fruit intake), binary traits (e.g., decaffeinated vs caffeinated coffee), and principal component-derived food groups. We tested for genetic associations using several models: a traditional sex-combined additive GWAS, additive models stratified by sex, and two joint models accounting for sex-interaction effects and non-additivity. We also conducted X-WAS in five additional genetic ancestry groups and performed a sex-combined multi-ancestry additive GWAS meta-analysis with up to 445,773 individuals. We identified 18 loci associated with 20 dietary intake traits (P < 5x10-8), including 17 variants without prior associations in the GWAS Catalog. Among these loci, 10 were significant across multiple X-WAS models, and 5 were strongest in a model other than the traditional sex-combined additive GWAS, highlighting the value of approaches that address known complexities of the X chromosome. These results demonstrate that incorporating the X chromosome in GWAS can reveal novel loci, even for complex behavioral traits such as dietary intake. Applying multiple association models further improves discovery by accounting for unique features of the X chromosome. Author SummaryAlthough diet is a major risk factor for many common diseases, adherence to healthy eating guidelines remains low. One reason is that current recommendations do not account for individual differences in food choice that arise from environmental or genetic factors. Previous genetic studies have identified hundreds of genetic variants associated with dietary behaviors, but most have excluded the X chromosome due to its analytical complexity and differences between males and females. However, accumulating evidence suggests that the X chromosome contains important genetic variation that impacts complex traits. We analyzed data from hundreds of thousands of individuals to identify genetic variants on the X chromosome associated with dietary intake. To address the unique features of the X chromosome, we applied multiple different models that account for sex-differences and non-additive genetic effects. We identified 18 regions in the genome associated with at least one dietary intake trait. These results reveal new insights into the genetics underlying eating behavior and highlight the importance of incorporating the X chromosome in genetic studies of complex traits.

BackgroundObesogenic diets (ODs) are known to trigger metabolic and inflammatory disturbances. However, the effects of short-term OD withdrawal on systemic and neuroinflammatory parameters remain unclear. ObjectivesThis study investigated the short-term effects of OD withdrawal on metabolic, inflammatory, and anxiety-like behaviours in young male Wistar rats. MethodsThree-week-old male Wistar rats were fed either a control (Ct, n=5) or high-sugar/high-fat (HSHF) diet for 14 days. Animals in the HSHF group were further divided into no-withdrawal (NWt, n=5) and withdrawal (Wt, n=5) groups, where Wt received a control diet for 48 hours. Food intake, body mass, adiposity, serum metabolic parameters, hepatic energy stores, inflammatory markers (serum, liver, hypothalamus, hippocampus, mesenteric fat), and oxidative stress markers in the hippocampus were measured. Anxiety-like behaviour was assessed using the elevated plus maze. ResultsOD intake significantly increased caloric intake, visceral adiposity, hepatic glycogen, and TAG levels. The 48-hour withdrawal reduced TAG, induced hyperinsulinemia and hypoglycaemia, and heightened inflammation in mesenteric fat, serum, and the hippocampus. Oxidative stress markers (SOD and MDA) increased in the hippocampus, correlating with elevated serum corticosterone and heightened anxiety-like behaviour in the Wt group compared to the other groups. ConclusionShort-term withdrawal after only two weeks of OD intake exacerbates systemic and neuroinflammation, hippocampal oxidative stress, and anxiety-like behaviours, indicating rapid negative responses to dietary transition. These findings highlight the metabolic and behavioural challenges associated with short-term OD withdrawal and highlight the need for adjunct interventions to mitigate its adverse effects.

Genetic variation contributes to individual differences in food liking and dietary behaviour. Genome-wide association studies (GWAS) have identified genetic variants associated with these traits, but most evidence comes from middle-aged and older populations. Young adulthood is a key life stage during which long-term dietary habits develop, yet the genetic basis of food liking during this period remains largely unexplored. We conducted GWAS of 97 food liking traits and two derived principal components (PCs) in 2,784 young adults (age 25) from the Avon Longitudinal Study of Parents and Children. The PCs captured broader food preference patterns reflecting preferences for diverse plant-based and seafood foods (PC1) and meat-based foods (PC2). GWAS identified 32 genome-wide significant associations across 24 traits. Cross-trait analyses indicated that several variants influenced liking across groups of related foods. For example, the lentil-associated variant rs76659918 showed associations with multiple foods, including honey, plain yogurt, chilli peppers, aubergines, avocado, and black olives, as well as PC1, whereas variants associated with bacon, burgers, and steak were linked to multiple meat-based foods and PC2. Exploratory analyses showed that TAS2R38 bitter-sensitive alleles were associated with lower liking for Brussels sprouts, with limited evidence for associations with other traits. Comparison with GWAS of food liking in the UK Biobank cohort (age 37-73) showed limited replication, with robust evidence only for the grapefruit-associated locus. This study identifies genetic variants associated with food liking in young adulthood and suggests that genetic influences operate at both the level of individual foods and broader food preference patterns.

BackgroundFood-related gastrointestinal (GI) symptoms are highly prevalent in patients with IBS. Although dietary components may trigger symptoms through luminal mechanisms, cognitive expectations may also shape symptom perception within the gut-brain axis. No validated instrument currently exists to measure food-related symptom expectations. Hence, we developed and validated the Food Expectation Questionnaire (FEX-Q). MethodsThe FEX-Q was developed using a stepwise process including focus group interviews and face-to-face validation to ensure content validity. The finalized digital questionnaire presents 44 food images with six items rated on a visual analogue scale (VAS; 0-100), including the core item assessing food-related symptom expectation ("How severe GI symptoms do you expect after eating this food?"). Additional domains assess taste preference, willingness to eat, perceived healthiness, and perceived fat and carbohydrate content. The finalized FEX-Q was administered in a nationwide online validation survey of adults with IBS and non-IBS controls in Sweden. Participants also completed validated questionnaires including GI symptom severity (combined GSRS), psychological distress (HADS), food-related quality of life (FR-QOL), and a screening tool for food avoidance (NIAS). ResultsTwenty adults with IBS and non-IBS controls participated in the face-to-face validation, resulting in a final version of the FEX-Q comprising 44 food images, which were properly identified and provided a range of macronutrient distributions and trigger foods. In the nationwide online study including 134 patients with IBS and 126 non-IBS controls, the FEX-Q demonstrated strong known-groups validity (mean symptom expectation 18.4 in controls vs 50.1 in IBS), strong construct validity (perceived vs actual fat content r=0.78, p<0.001 and carbohydrate content r=0.59, p<0.001), significant convergent validity with GI symptom severity and food-related quality of life, and high internal consistency (split-half reliability Spearman-Brown corrected r=0.88). ConclusionThe FEX-Q can capture individual food-related symptom expectations to distinct food images. This reliable measurement can be useful to reveal the mechanism of food-related symptom expectations and provide clinically relevant insights for personalized dietary management

Understanding how nutritional interventions alter food evaluations may help clarify mechanisms of dietary behavior change; however, most studies focus on intake outcomes and rarely assess within-person changes in subjective food evaluation. We developed a brief, image-based rating tool that measures two core dimensions of food evaluation, liking and perceived healthiness, using standardized food images. The tool was piloted in adults with type 2 diabetes participating in a medically supervised intervention that included structured glucose monitoring and professional dietary guidance. Ratings were collected at baseline, post-monitoring, and follow-up. In line with the methodological aim of this study, we examined whether the tool demonstrates internal coherence, sensitivity to change, and external validity against expert ratings and physiological measures, and whether it can capture item-level patterns relevant to eating behavior. Results provide preliminary evidence that the tool is feasible, it is low-burden, and capable of detecting coherent relationships between food liking and health perceptions, including coordinated within-person changes over time and meaningful associations with external benchmarks. To support scalability and self-administration, we also developed an online smartphone-based demonstration version to exemplify the task structure and user experience. Overall, this pilot study suggests that a short, flexible rating task can serve as a practical measurement tool for tracking intervention-relevant changes in food evaluation and for informing the design of future nutritional interventions.

Dietary choice plays a critical role in metabolic and neurological health, yet the biological factors that shape macronutrient preference remain poorly understood. Evidence from both humans and rodents suggests potential sex differences in the attractiveness of specific nutrients, though findings have been inconsistent and often rely on self-report or diets with mixed macronutrient composition. The present study examined sex differences in macronutrient preference and food-directed behavior in mice using a controlled three-food choice paradigm. Adult male (n = 12) and female (n = 11) C57BL/6J mice were given simultaneous access to foods consisting of fat, sucrose, or a fat-carbohydrate combination across 14 days. Intake, latency to approach, and time spent near each food source were quantified, and estrous cycle stage was monitored in females. Female mice consumed significantly more food than males overall, driven by a selective increase in fat intake. Behavioral measures paralleled these results, with females spending more time in proximity to fat-associated food zones. In contrast, males preferentially consumed the fat-carbohydrate combination and showed weaker nutrient-specific engagement. Estrous cycle stage modestly influenced feeding behavior, with estrus associated with increased overall intake and greater consumption of combination diets, reflecting elevated carbohydrate intake. These findings demonstrate robust sex differences in macronutrient preference and suggest that hormonal state may selectively modulate nutrient-specific feeding behavior.

Dietary patterns worldwide have shifted toward increased consumption of ultraprocessed foods (UPFs), which has been linked to higher disease burden. One mechanism proposed to impact both their consumption and contribution to metabolic disease is altered post-ingestive metabolic response in comparison to nutritionally similar foods. Here, we recruited 57 healthy-weight 18-45-year-old adults to examine the effects of food processing on postprandial metabolism and brain response. Despite nutritional matching, UPF meals evoked a greater insulinemic and energetic response with attenuated carbohydrate oxidation relative to non-UPF meals. Next, between-condition differences in peak carbohydrate oxidation were associated with mesolimbic and superior temporal gyrus activation in response to food cues. Finally, although food value did not differ between conditions, brain responses correlated with food valuation were positive for non-UPF but negative for UPF in visual cortex and striatum. These findings demonstrate that food processing influences post-ingestive metabolism in a way that could help explain long term health effects and differences in food reward through mechanisms beyond calories and macronutrient composition alone.

ObjectiveThe average American consumes 55% of their daily energy from ultraprocessed foods (UPF) created through industrial processes and additives not used at home. We investigated if a high-UPF diet alters brain response to milkshake compared with a diet free-from UPF (NonUPF) in emerging adults, who are in a critical period for brain development and typically consume high amounts of UPF. MethodsIn a randomized controlled crossover trial participants aged 18-25 completed two, 2-week controlled feeding periods including a UPF (81% UPF) and nonUPF (0% UPF) diet. Before and after each diet intervention participants consumed milkshake concomitant with functional magnetic resonance imaging. ResultsIn the entire cohort, there were no differences between diet conditions in brain response. An exploratory analysis revealed orbitofrontal cortex (OFC) response to milkshake decreased after the UPF diet and increased following the NonUPF diet in adolescents (18-21 years) but not young adults (22-25 years). Habitual UPF intake (gs) was positively associated with OFC response to milkshake independent of diet intervention in all participants. ConclusionsAn acute UPF dietary intervention may only alter brain response in adolescents. Further work is needed to determine potential vulnerability of adolescents to changes in dietary UPF on brain response to rewards.

Of the three dietary macronutrients, protein plays an especially pivotal role in physiological functions. Nevertheless, the behavioural control of protein intake is poorly understood. In this study, we used Feeding Experimentation Devices (FED3s) to examine the structure of ingestive behaviour in mice given access to diets varying in protein content. Adult C57BL/6NRj mice were contact-housed in pairs in custom-made cages with perforated dividers, each having access to an individual FED3 unit. Mice were given ad libitum access to either 20 mg control, non-restricted (NR) pellets (20% casein) or 20 mg protein-restricted (PR) pellets (5% casein) from FED3s on free-feeding mode. Each pellet retrieval event was timestamped ~24 h/day. All mice experienced both diets for 7 days with order of diet presentation counterbalanced (i.e., NR[-&gt;]PR and PR[-&gt;]NR). Analysis of dynamics of pellet intake per day revealed that mice that were initially protein-restricted first showed a decrease in pellet intake before increasing on later days and exhibiting a persistent high level of intake once non-restricted diet was available. The group that was initially non-restricted exhibited a blunted response to the same diet manipulation. In addition, we clustered pellet retrieval data into discrete clusters of feeding events and used a mathematical approach to determine the boundary of meals (2-5 pellets), separated from "snacks" (1 pellet) and "feasts" (>5 pellets). We identified alterations in meal patterning in response to diet manipulation with protein restriction increasing "snacking" and leading to increased meal number, and reduced meal size. Moreover, restored access to NR diet, elicited "feasting". These effects depended on the sequence of diets the mice experienced, such that the effects were stronger in initially protein restricted mice compared to those initially non-restricted. In summary, our findings show that manipulation of dietary protein levels affects meal patterning in adult mice.

BackgroundPsychiatric conditions, eating disorders (EDs), and exposure to violence are highly prevalent in patients with severe obesity. However, their association with postoperative weight trajectories following bariatric surgery remains unclear. ObjectiveTo assess the associations between eating disorders, psychiatric conditions, and history of violence with multiple dimensions of weight trajectory after bariatric surgery. MethodsThis retrospective study included 414 patients with severe obesity from the OBESEPI cohort who underwent bariatric surgery at Nancy University Hospital (France). Psychological factors were assessed using a standardized preoperative psychiatric interview. Weight outcomes included preoperative BMI change, maximal BMI loss ({Delta}BMImax), final BMI change (dBMIdf), weight regain (BMIR), and magnitude of weight regain (dBMIR). Multivariable linear and logistic regression models were adjusted for age and sex. ResultsPsychological factors were not associated with baseline BMI or preoperative BMI variation. A history of violence was significantly associated with greater maximal BMI loss ({beta} = 1.99, 95% CI [0.73-3.26]; p = 0.002) and greater final BMI reduction ({beta} = 1.81, 95% CI [0.47- 3.14]; p = 0.009). Eating disorders and psychiatric conditions were not associated with weight loss outcomes. No association was observed between overall exposure to violence and weight regain. However, subtype analyses showed that physical violence was associated with a higher risk of weight regain, whereas psychological violence was associated with a lower risk. No significant associations were found for the magnitude of weight regain. ConclusionsEating disorders and psychiatric conditions were not associated with postoperative weight outcomes in this cohort. In contrast, exposure to violence--particularly when differentiated by subtype--was associated with distinct patterns of weight loss and regain. These findings highlight the relevance of trauma-informed assessment in bariatric care and support a more individualized approach to obesity management.

Despite growing availability of plant-based meat, limited data exist on how these products perform relative to animal-based options in real-world consumption settings. This study compares consumer sensory perceptions of two plant-based meatballs (soy, soy-wheat) and two animal-based meatballs (beef, beef-mushroom) among university dining hall patrons (n = 128), complemented by instrumental Texture Profile Analysis. Animal-based meatballs received significantly higher ratings for moistness, meatiness, fattiness, and tastiness (all p < 0.001), with the meatiness gap being the largest ({Delta} = 1.40 on a 5-point scale). Texture analysis found that animal-based samples were significantly harder, more cohesive, and chewier than plant-based samples. In contrast, consumers perceived no difference in chewiness or hardness between categories, revealing a disconnect between instrumental and sensory measures. Just-About-Right penalty analysis identified insufficient savoriness as a universal improvement target across all products, including beef. Flavor and texture were the dominant drivers of dining choice, while sustainability and animal welfare ranked lowest in importance. These findings indicate that achieving sensory parity--particularly in moistness, meatiness, and savoriness--rather than emphasizing sustainability messaging, may be critical for increasing acceptance of plant-based meat in institutional food service. Data and code are available at https://github.com/LivingMatterLab/AI4Food

Binge eating disorder (BED) is characterized by episodic overconsumption of palatable food and involves dysregulated motivational and arousal processes. The orexin (hypocretin) system, through its widespread projections to mesolimbic circuits, has been implicated in cue-driven reward seeking and escalated intake, raising the possibility that orexin receptor antagonists may modulate binge-like behavior. Here we evaluated the effects of a dual orexin receptor antagonist (DORA-22) and an OX1R-selective antagonist (1-SORA-51) in a cyclic intermittent high-fat access model that generates robust and reproducible binge-like intake in male and female mice. DORA-22 produced no detectable effect on consumption at either early (2 h) or extended (24 h) binge timepoints. In contrast, 1-SORA-51 significantly reduced high-fat intake during the initial 2 hours of access in both sexes, with no effect on 24-hour consumption, indicating a selective attenuation of the early phase of binge intake. Fiber photometry recordings of GRABDA2m fluorescence in the nucleus accumbens revealed that 1-SORA-51 did not alter baseline dopamine signals or the dopamine increase triggered by high-fat pellet delivery, demonstrating that its behavioral effects occur without detectable modulation of mesolimbic dopamine dynamics. Together, these findings identify OX1R antagonism as a strategy for suppressing the initiation of binge-like feeding and highlight the receptor-level specificity of orexin contributions to maladaptive overconsumption.

Introduction High consumption of ultra-processed foods (UPF) is associated with adverse health outcomes and weight gain. Despite increasing calls for behavioural strategies to reduce UPF intake, no theory-informed intervention targeting UPF reduction has been evaluated in UK adults in alignment with national dietary guidance. We assessed the feasibility, acceptability, and preliminary behavioural and clinical outcomes of a multi-component intervention designed to reduce UPF consumption (and increase physical activity (PA)/minimally processed food (MPF) intake). Methods In this exploratory single-arm pre-post study, adults (N=45) living with overweight or obesity and habitual UPF intake [&ge;]50% of total energy were offered a 6-month behavioural intervention following a controlled feeding phase (UPDATE trial, stage 1). The intervention was developed using the Behaviour Change Wheel and Capability, Opportunity, Motivation-Behaviour (COM-B) model and included one-to-one sessions with a behavioural scientist, tailored print and digital materials, peer-support meetings, and a moderated group chat. Feasibility outcomes included uptake, retention, and intervention fidelity. Secondary outcomes included COM-B constructs, dietary intake, PA, clinical and self-reported outcomes, and qualitative feedback. Results Uptake was 91% (41/45). Retention at 6 months was 68% (28/41), with 83% (34/41) providing follow-up data (intention-to-treat). Median attendance at one-to-one sessions was 86% (interquartile range (IQR): 57-100) with 56% (23/41) attending all sessions (per-protocol). Fidelity to core behaviour change techniques was high. At 6 months, COM-B scores improved for healthy eating (+7%, standard deviation (SD): 8; p<0.001) and physical activity (+5%, SD: 9; p=0.013). UPF intake decreased by 25% of total energy (95% confidence interval (95%CI): -32, -17), with a corresponding increase in minimally processed foods (+23%; 95%CI: 17, 29). Vigorous physical activity increased (+60 min/week, IQR: 0-180), weekday sitting time decreased (-61 min/day, SD: 110), and weight reduced by 3.8 kg (IQR: -8.5-1.0; p=0.001). Findings were similar in per-protocol analyses. Qualitative data indicated perceived improvements in wellbeing and habit formation. Conclusion This theory-informed intervention demonstrated good feasibility and acceptability and was associated with improvements in targeted behavioural mechanisms and health-related outcomes. A randomised controlled pilot trial is warranted to evaluate effectiveness and refine implementation.

Background: 39M children worldwide are overweight or have obesity, accelerating risk for adult non-communicable diseases. Presently, interventions to prevent obesity have had limited success due to poor timing and lack of personalisation. Objective: We aimed to identify early-life predictors of childhood obesity (ChOB) that could aid targeting specific population subsets for obesity prevention interventional studies. Methods: Data were from the Raine Study Gen2 participants (n=1494). Anthropometric and genetic predictors evaluated included birthweight (BW), early-life BMI (1-3 years), and three polygenic scores (PGS) [two BW-PGSs (BW-PGS2016 and BW-PGS2019) and a ChOB-PGS], developed from BW and ChOB genome-wide-association-studies, respectively. Multivariate analyses were performed to investigate associations between predictors and child-BMI (5-, 8-, 10-years). Results: BW-PGS2019 associate with child-BMI at 5-years. BW-PGS2016 was not associated with child-BMI. Remaining predictors positively associate with child-BMI at 5-, 8- and 10-years (p<0.001). Early-life BMI, ChOB-PGS and BW accounted for up to 38.7%, 5.8% and 3.4% of the variability in child-BMI, respectively. Conclusions: Our data suggest early-life BMI is a better predictor of child-BMI than ChOB-PGS, and BW, accounting for up to ten-fold more variance in child-BMI. Future interventional studies to mitigate obesity could target early-life BMI as a marker to identify children at the highest risk.

While standard high fat diets cause hyperphagia and obesity in mice, high fat-low carbohydrate ketogenic diets (KDs) reduce food intake and body weight. Because the basis for this difference is still unclear, we systematically altered the macronutrient content of a standard KD and found that feeding C57BL/6J (B6J) mice a KD with 5% protein resulted in hypophagia, weight loss, and hypoglycemia, whereas the same diet with 10% protein led to increased adiposity and glucose intolerance. However, these effects were strain-dependent as C57BL/6NJ (B6NJ) weighed similar amounts on the two diets leading us to investigate the molecular mechanisms. When fed the KD-5% diet, B6J but not B6NJ mice showed increased levels of two anorexigenic factors, GDF15 and LCN2, and loss of function of either blunted the weight loss of B6J mice fed the diet. B6J mice harbor mutations in Nnt (Nicotinamide nucleotide transhydrogenase) and Nlrp12 (NLR family pyrin domain containing 12), both of which are wildtype in B6NJ mice. B6J mice fed the KD-5% diet showed the RNA signature of oxidative and integrated stress responses (ISR) and restoring NNT function in liver reduced the levels of GDF15. RNA-seq also revealed that B6J but not B6NJ mice had the RNA signature for hepatic inflammation and a knockout of Nlrp12 led B6NJ mice to lose weight on the KD-5% diet with increased levels of LCN2. Suppression of oxidative stress with N-acetylcysteine (NAC) reduced expression of both GDF15 and LCN2 and prevented the weight loss associated with the KD-5% protein diet in B6J mice, whereas inhibition of the integrated stress response with ISRIB only attenuated the GDF15 axis. Collectively, these findings explain why B6J mice lose weight on a ketogenic diet and reveal a critical interplay between macronutrient composition and genetic background leading to increased levels of GDF15 and LCN2 to induce hypophagia. Finally, these data suggest that the response to different diets among humans might be similarly variable based on genetic variation and macronutrient composition, suggesting the possible need for personalized dietary interventions.

IntroductionEating behaviors are consistently associated with weight-related traits, yet the biological factors contributing to individual differences in these behaviors remain poorly characterized. Plasma proteomics offers an opportunity to investigate the biological processes underlying eating behaviors. MethodsParticipants were 730 young adult twins from the FinnTwin12 cohort. Eating behaviors were measured through self-report questionnaires, including the Three-Factor Eating Questionnaire-R18 and four additional items on eating styles. Associations between plasma proteins and eating behaviors were examined using generalized estimating equation models adjusted for age and sex, with additional analyses adjusting for body mass index (BMI). Within-pair analyses were conducted in both monozygotic (MZ) and dizygotic twin pairs to assess whether associations were influenced by genetic or environmental factors. ResultsWe identified 51 significant protein-eating behavior associations involving 35 unique proteins (FDR <0.05). We observed 19 associations for the item "overeating when feeling down" and 12 for the TFEQ factor of emotional eating. The identified proteins were predominantly enriched in immune system pathways, including the complement cascade and adaptive immune signaling. After further adjustment for BMI, 12 associations persisted, most of which were associated with eating-style items, suggesting that BMI had a substantial influence on protein-eating behavior associations. Within-pair analyses of MZ pairs indicated that several associations persist after accounting for genetic effects. ConclusionOur study identifies plasma proteins associated with eating behaviors, largely involving immune-related pathways. While some associations attenuated in twin analyses, several persisted, suggesting environmental influences. These results highlight potential biomarker candidates and indicate that modifiable environmental factors may contribute to the proteomic profiles associated with eating behaviors, with possible implications for weight-related traits.

Introduction. Ultra-processed foods (UPFs), defined as foods in group 4 of the NOVA classification system, are a key contributor to chronic disease in the United States. Front-of-package warning labels ('warnings') offer a promising strategy to help Americans reduce consumption of UPFs. Requiring warning labels on UPFs could help reduce consumption of these foods. However, the effects of UPF warnings are largely unknown. The impact of warning labels on UPFs among Latino adults was examined. Study design. Online randomized trial. Setting/participants. 4,107 Latino adults (49% limited English proficiency) in the US. Intervention. Participants viewed one of three labels: control labels displaying barcodes; identity warnings stating 'WARNING: Ultra-processed food'; or health warnings stating 'WARNING: Consuming ultra-processed food and drinks can cause weight gain, which increases the risk of obesity and type 2 diabetes'. Main outcome measures. Participants viewed four UPF products displaying their randomly assigned labels. Participants indicated whether the product was UPF (primary outcome) and rated perceived healthfulness of the product, intentions to purchase the product, and perceived message effectiveness (secondary outcomes). Results. Identity warnings (70% correct) and health warnings (67% correct) both led to higher correct identification of UPF compared to control labels (54%, p<.001), with the identity warning having a larger impact than the health warning (p=.007). Compared to the control label, the identity warning and health warning both elicited higher perceived message effectiveness and lower perceptions of healthfulness and purchase intentions (p<.001 for all outcomes) with no significant differences between UPF labels. The impact of the health warning label (vs. the control label) on correct identification of UPF was greater for participants with high education (p=0.012) compared to those with low education, and participants with limited English proficiency (p=0.001). Conclusions: UPF warnings may help consumers identify UPFs and influence product perceptions and intentions.