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.

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.

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.

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.

Introduction: Eating 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. Methods: Participants 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. Results: We 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. Conclusion: Our 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.

Objective To examine group differences and continuity in caregiving environments of infants born preterm from Spanish- and English-speaking families. Study Design We conducted a prospective cohort study of Spanish- (n = 17) and English-speaking (n = 23) families of infants born preterm (< 32 weeks gestation). Caregiver-infant engagement was assessed neonatally via hospital visitation and skin-to-skin (STS) care, and at home via child-directed adult word counts/hour (CD-AWC/hour) from all-day audio recordings. Result No significant group differences were observed in family visitation, neonatal STS care, or in-home verbal engagement, although STS care rates varied considerably, especially within Spanish-speaking families. Across both groups, greater STS care was associated with higher CD-AWC/hour at home. Conclusion Spanish- and English-speaking families showed comparable patterns of caregiver-infant engagement, as a group, however, many Spanish-speaking families engaged in less STS than English-speaking families. STS care predicted caregiver-infant verbal engagement at home, highlighting continuity from hospital to home.

Selectively bred diet-induced obesity-prone (DIO-P) rats have defective nutrient sensing prior to obesity onset. We hypothesized that glial inflammation in the arcuate nucleus (ARC) impairs hypothalamic responses to dietary clues, thereby promoting obesity development in genetically susceptible animals. This study established a timeline of inflammatory events in male and female DIO-P and diet-resistant (DR) rats fed either a low fat chow or exposed to a high energy diet (HED; 32% fat, 25% sucrose) for three days or four weeks. On chow diet, DIO-P rats of both sexes displayed elevated astrocyte density and increased expression of pro-inflammatory markers in the ARC, alongside reduced microglial content, compared to DR rats. Three days of HED transiently amplified most MBH pro-inflammatory markers in DIO-P rats. Four weeks of HED decreased GFAP expression in DIO-P rats while Iba1 density remained unchanged, whereas, DR rats showed a reduction in Iba1with no change in GFAP or cytokine expression. To determine whether mediobasal hypothalamus (MBH) astrocyte inflammation contributes to the development and maintenance of an obesity, astrocytic IKK{beta} was depleted before or after HED exposure. Prophylactic MBH astrocyte-specific IKK{beta} knockdown prevented subsequent body weight gain, improved glucose tolerance and decreased leptin levels in DIO-P rats to levels comparable to DR rats, with no effect in the latter. In contrast, MBH IKK{beta} astrocytic depletion in already obese DIO-P rats had no effect on energy homeostasis. Together, these findings validate the DIO-P rat as a polygenic model of obesity predisposition and demonstrate that preventing ARC astrogliosis is sufficient to HED-induced body weight gain and obesity development in genetically susceptible animals, highlighting MBH inflammation as a marker and driver of obesity predisposition. HighlightsO_LIChow-fed DIO-P rats present heightened ARC astrogliosis and cytokine expression preceding HED-induced obesity. C_LIO_LIInhibition of IKK{beta} in MBH astrocytes prevents DIO-P rats from becoming obese. C_LIO_LIOnce obese, inhibition of IKK{beta} in MBH astrocytes is not sufficient to reverse the obese phenotype. C_LI

Importance: Parent/caregiver-infant early relational health (ERH) is known to play a critical role in the promotion of socio-emotional functioning and wellbeing across the life course. The negative impact of the COVID-19 pandemic on maternal mental health and secondarily on ERH and child socio-emotional functioning is clear. However, the direct impact of maternal viral exposure during pregnancy on ERH has not been investigated. Objective: The goal of this study was to determine the impact of prenatal SARS-CoV-2 exposure on ERH and infant socio-emotional functioning in the first 6 months of life. Design: Mothers with and without SARS-CoV-2 exposure during pregnancy who gave birth from 02/2020 to 09/2021 were enrolled from 05/2020 to 09/2021 in one of two parallel prospective studies (the COVID-19 Mother Baby Outcomes [COMBO] Initiative or the Respiratory Syndrome Coronavirus 2 in Pregnancy and Infancy [ESPI] COMBO sub-study). Mothers reported on their health and the socio-emotional functioning of their infant via online surveys (REDCap) at enrollment, 1, 2, 4, and 6 months. At 4 to 6 months, dyads were invited to participate in a video-based, remote assessment of ERH. Participants: 884 mother-infant dyads from three U.S. States (Alabama, New York, and Utah). Exposure: Prenatal SARS-CoV-2. Main Outcomes and Measures: Maternal-reported ERH (parental stress, parenting confidence and bonding) and observer-based ERH (video-coded quality of maternal caregiving behaviors and mother-infant emotional connection). Infant socio-emotional development assessed using the 6-month Ages and Stages Questionnaire: Socio-Emotional 2nd Edition (ASQ:SE-2). Results: 316 (36%) mothers had a positive prenatal SARS-CoV-2 exposure. Prenatal SARS-CoV-2 exposure was associated with an adjusted estimate of ~5% reduction (incidence rate ratio=0.95, 95% confidence interval [0.90, 1.00], p=0.03) in observed maternal caregiving quality, after accounting for postnatal maternal mental health and sociodemographic factors. We found no evidence of effect on other ERH constructs or infant socio-emotional functioning. Conclusions and Relevance: In this large prospective cohort study, prenatal SARS-CoV-2 was associated with a small decrement in caregiving quality, but not other ERH constructs or infant socio-emotional functioning. These findings should be interpreted as hypothesis generating and will require replication in independent studies.

Wellbeing is commonly defined as the combination of feeling good and functioning well and typically conceptualized as two related but distinct components. Hedonic wellbeing emphasizes pleasure, happiness, and life satisfaction, while eudaimonic wellbeing focuses on meaning, personal growth, flourishing, and the realization of ones potential. The Mental Health Continuum-Short Form was developed as a comprehensive measure of wellbeing and includes three subscales assessing emotional, social, and psychological wellbeing. Although the Mental Health Continuum total score is often interpreted as an indicator of overall wellbeing, the underlying genetic structure of its three subscales and its genetic overlap with other commonly used wellbeing measures remains unclear. Using data from 5,212 individuals from the Netherlands Twin Register (72% female, mean age 36.4), we fitted multivariate twin models to examine the genetic architecture of the Mental Health Continuum and its associations with other wellbeing measures (quality of life, life satisfaction, subjective happiness, and flourishing). Results indicate that, at the genetic level, the Mental Health Continuum is best explained by its three distinct subscales rather than by a latent factor. When considering the Mental Health Continuum together with the other wellbeing measures, we found moderate to high genetic correlations (r = 0.52 - 0.83), indicating substantial overlap in the genetics underlying the wellbeing constructs. However, we did not find evidence for a single common genetic factor underlying all constructs. These findings highlight the multidimensional structure of wellbeing, but the moderate to high genetic correlations across measures suggest that it is important to align the level of measurement (phenotypic vs genetic) with the research question.

BackgroundPrimary care practitioners are well-positioned to support people of reproductive age in preparing for pregnancy and parenthood. Such "preconception care" is ideally delivered opportunistically during routine consultations, although limited time presents a barrier. AimTo achieve consensus on priority topics for opportunistic preconception care in general practice. Design and settingA three-step consensus study involving UK-based primary care practitioners and people of reproductive age. MethodThe consensus process involved: 1) identifying potential topics through literature and guideline reviews, workshops with people of reproductive age (n=15), and interviews with primary care practitioners who work in general practice (n=14); 2) prioritising topics using a Delphi survey (n=85 participants completing round one, n=63 completing all three rounds); and 3) agreeing on priority topics during an online consensus workshop (n=21 participants). Participants were recruited through a Public Advisory Group, charities, and professional organisations. ResultsReviews and workshops/interviews with people of reproductive age and practitioners identified 37 potential topics. The Delphi survey and consensus workshop identified 16 priority topics. These were combined into four overarching topic areas for discussion during relevant consultations: O_LIPatient knowledge of preconception health and pregnancy C_LIO_LIIdeas, concerns and expectations (e.g. pregnancy intention, prior pregnancy experiences) C_LIO_LIHealth conditions (e.g. medication use, mental/physical health, immunisation) C_LIO_LIHealth behaviours (e.g. folic acid supplement use, smoking, alcohol consumption). C_LI ConclusionThe agreed priority topic areas offer a structured foundation for delivering patient-centred, opportunistic preconception care in primary care. The findings support future co-development of practical tools and resources to enable routine implementation. How this fits inPreconception care improves pregnancy outcomes, but in UK general practice it is inconsistently delivered, partly due to limited time and guidance that offers little prioritisation for opportunistic consultations. This study identifies four overarching topic areas for preconception care, based on consensus among people of reproductive age and primary care practitioners. The resulting priority list offers clinicians a practical, flexible way to initiate patient-centred preconception care discussions within routine consultations.

Oxytocin is a hypothalamic hormone and neuromodulator that has been linked to a variety of different functions, including parturition, social behavior, and cognitive processing. More recently, oxytocin has also been associated with metabolism and energy balance. However, evidence to date in this field has been inconsistent, especially in human research. To address this, we performed a preregistered systematic review and meta-analysis, which synthesized existing literature on the effect of exogenous oxytocin administration compared to a placebo on caloric intake and appetite in humans, using a living meta-analysis approach. Results indicated a significant, reductive effect of oxytocin administration on appetite in participants belonging to certain patient groups (e.g., obesity or type II diabetes; Hedges' g = -0.21). A separate moderator analysis evaluating oxytocin's effect on caloric intake revealed a conditional effect depending on the patient group, with the obesity group showing a significant effect. We did not find any statistically significant effects in healthy participants. However, further analyses revealed that these effects were also not equivalent, indicating that the data are currently too insensitive to draw clear conclusions. Taken together, the results provide some evidence for the role of oxytocin in regulating appetite in an anorexigenic, possibly homeostatic fashion. Future updates in this living meta-analysis may lead to more definitive conclusions.

Background Parenting practices shape children's emotional, social, and cognitive developmental wellbeing. Yet, many families face complex challenges that increase the risk of poor outcomes and demand on social care. The Sutton Parenting Offer (SPO) is a universal, peer-led parenting offer that provides early, non-stigmatising support to families with children aged 0-25 years. It combines evidence-based programmes with informal workshops and peer networks delivered through Family Hubs. This present study is an evaluation protocol of the parenting offer. Aim This evaluation aims to explore how, why, and in what contexts SPO supports families in engaging, sustaining positive change, and generating wider system value. Methods A mixed-methods realist evaluation approach will be used to evaluate SPO across four work packages: engagement pathways, early changes and peer-led ecosystems, long-term change, and system value for money. Data sources will include attendance data (anonymised service records), survey data (entry and exit), and qualitative data (dyad interviews, story circles, and stakeholder-value mapping workshops). The COM-B and the Theoretical Domains Framework (TDF) will guide the analysis of behavioural data. Quantitative data will be analysed descriptively and using paired parametric and non-parametric tests, while qualitative data will be analysed thematically following a realist-informed approach to refine context-mechanism-outcome (CMO) configurations. Discussion This protocol presents the first realist informed evaluation of a universal parenting program in a local authority setting. The evaluation will generate evidence on how, when and why a universal, community-based, and peer-led model such as the Sutton Parenting Offer engages families and generates change. The findings will be useful to inform future parenting service design and implementation in local contexts in England.

Objectives: Acute gastroenteritis is a leading cause of pediatric emergency department (ED) visits. While ondansetron reduces vomiting, intravenous rehydration, and hospital admissions, its efficacy when initiated at triage remains unclear. We aimed to evaluate whether triage nurse-initiated administration of ondansetron in children with suspected gastroenteritis reduces the proportion of patients requiring observation following initial physician assessment. Methods: We conducted a randomized, double-blind, placebo-controlled trial in a tertiary pediatric ED in Canada. Children aged 6 months to 17 years presenting with morae than 3 episodes of vomiting in the preceding 24 hours (including 1 within 2 hours of arrival), were eligible. At triage, we randomized participants to receive liquid ondansetron or a color- and taste-matched placebo. The primary outcome was the proportion of patients requiring observation after the first physician evaluation. Secondary outcomes included post-intervention vomiting, ED length of stay, patient comfort, and 48-hour return visits. The trial was registered at ClinicalTrials.gov (NCT03052361). Results: Recruitment was stopped prematurely due to the COVID-19 pandemic. Ninety-one participants were randomized to ondansetron (n= 44) or placebo (n= 47). Overall, 40 patients (45%) were discharged immediately after the initial physician assessment, with no difference between the ondansetron and placebo groups (44% vs. 45%; absolute difference -1%, 95% CI: -20% to 19%). No significant differences were observed in all secondary outcomes. Conclusion: In this trial, triage nurse-initiated ondansetron administration did not reduce the need for ED observation in children with presumed gastroenteritis. While being underpowered, this study could inform researchers planning larger clinical trials.

Background and aimsPerseverative behaviours are commonly assessed using operant paradigms in which rodents work for drugs or food under physiological deprivation, limiting translational relevance to some behavioural addictions. Here we validated an operant paradigm in which the acquired behaviour is driven neither by physiological needs nor hedonic responses. MethodsMice were trained to lever-press for green light. Exp.1 used a within-subjects design to examine lever discrimination and whether responding could be "satiated" by light preexposure. Exp.2 examined instrumental contingency using a between-subjects design, with light delivery equated between contingent and non-contingent groups. Exp.3 replaced green light with dim red light producing less retinal photoreceptor excitation but comparable heat to assess non-photic cues. Exp.4 examined whether green light could affect food seeking different motivational states. ResultsIn Exp.1, green light supported lever discrimination. Among high responders, the satiation effect was modest (<15% reduction) and did not deter lever pressing. In Exp.2, instrumental contingency promoted response acquisition whereas random light delivery did not. In Exp.3, dim red light failed to sustain behaviour, producing [~]50% response decrement. In Exp.4, light potentiated food seeking under ad libitum feeding. Discussion and conclusionsResponse-contingent light serves as a reward to establish operant responding, which cannot be explained by alerting effects or thermal cues. Our study bridges the gap between animal models and findings from humans that coloured light may exacerbate smartphone use and that light therapy may reshape reward circuits in individuals with Internet gaming disorder symptoms [Li et al. (2026) Advanced Science 13:e14044].

We assessed whether pigs provide consolation, referring to targeted affiliation that attenuates a partners stress, under experimental conditions that manipulated exposure to stressed partners. Using a within-subject design, 74 pigs were tested in three contexts: a helping task in which group members could observe and help a trapped focal pig to return to the group, a direct-reunion, in which group members were naive to the experience of a separated focal pig until reunion, and an undisturbed control. We measured affiliative and non-affiliative interactions, anxiety behaviours and changes in salivary cortisol. Only the helping context satisfied most consolation criteria: there were selective increases in unidirectional affiliative contacts from the observer to the focal pig, non-affiliative interactions remained at baseline, and focal pigs showed fewer anxiety behaviours. In contrast, direct-reunions triggered increases in affiliative and non-affiliative interactions and higher anxiety. Cortisol increased during both direct-reunions and helping, but its level was not linked to affiliation. Results add to growing evidence for consolation behaviour in pigs and suggest best practices for reintegrating pigs into groups. Graded reintroductions that allow observers to assess the emotional state of targets may promote social buffering, whereas abrupt regrouping may trigger more generalized arousal or personal distress.

Childhood weight development, especially overweight and obesity, has been associated with mental health, but their dynamic, causal relationships, and whether these differ by sex, remain unclear. We applied causal discovery to data from the Danish National Birth Cohort (n=67,593) spanning six periods from pregnancy to late adolescence and considering 67 variables related to child and parental weight, mental health, lifestyle, and socio-economic factors. We found no statistically significant difference between the causal graphs for boys and girls (P=0.079). The data-driven models found causal influence of childhood weight on subsequent weight status. Mental health pathways were exclusively within or across adjacent periods and centered on early adolescent stress. We examined the interplay between a subset of mental health variables, containing information on externalizing and internalizing problems, and weight, and found no direct causal pathway between the two processes. These findings suggest that observed links between weight and these mental health measures may be attributable to confounding. Our findings demonstrate the value of data-driven causal discovery in large cohort studies and how to test for differences in causal mechanisms across subgroups. Results are available in an interactive application, enabling future research to further explore the interplay between weight and mental health.

Nuclei within the limbic system like the central amygdala (CeA) play a critical role in mediating fear, motivation, reward, and appetitive behavior. Although previous reports demonstrate the presence of the glucagon-like peptide-1 receptor (GLP-1R) in limbic nuclei, how limbic neurons mediate the actions of systemically administrated GLP-1R agonists is unclear. In this study, we investigated the CeAs response to peripherally administered GLP-1R agonist Exendin-4 (Ex-4) in vivo, and determined the functional requirement of select CeA neuron populations in acute Ex-4 induced hypophagia. Using fiber photometry, we observed that Ex-4 promoted a rapid and lasting activation of CeA neurons that was blocked by pretreatment with the GLP-1R antagonist Exendin-9. We then tested the functional requirement of CeA neuron activation in mediating Ex-4 induced hypophagia of standard grain chow using inhibitory chemogenetics. Chemogenetic inhibition of all CeA neurons significantly suppressed the hypophagic actions of Ex-4. Then using selective mouse Cre-drivers, we found that chemogenetic inhibition of protein kinase c delta (Prk-cd CeA) and GLP-1R (Glp1r CeA), but not somatostatin (SstCeA), neurons also attenuates the full hypophagic effect of Ex-4. Having observed that inhibition of Glp1rCeA modestly attenuated Ex-4 induced hypophagia of standard chow, we then tested whether these neurons might mediate Ex-4 suppression of energy-dense, palatable diet. We used intermittent high-fat diet (HFD) access and found that inhibition of Glp1rCeA neurons significantly rescued the reduction of HFD consumption by Ex-4. Collectively, these data demonstrate that the CeA responds to peripherally administered GLP-1R agonists and that multiple CeA neuron mediate GLP-1R agonist-mediated hypophagia.

Background: The European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines on nutrition for cancer patients provides evidence based dietary recommendations that is routinely deployed by dieticians in oncology settings. Although these can be culturally adapted, they do not adequately address inter individual variability in treatment related gastrointestinal symptoms and appetite, issues that increase malnutrition risk in cancer patients. Ayurveda, on the other hand, lacks nutrient based guidelines but offers a well grounded dietary framework to assess digestive function and personalise diets. This study investigated the feasibility of combining the two approaches in a clinical setting. Methods: Consenting adult cancer patients diagnosed with any type and stage of cancer were recruited. At baseline, digestive strength, dietary intake, quality and frequency and Patient Generated Subjective Global Assessment (PGSGA) score were recorded. Based on this, personalised meal plans (MPs) that combine nutrient guidelines from ESPEN and traditional food concepts to support digestive strength were provided to participants. Follow ups ranged from 4 weeks to 6 months, at which digestive strength and PGSGA was noted. To evaluate against a benchmark, meal plans were theoretically constructed using Ayurveda concepts (traditional MP) or ESPEN guidelines (Standard MP) alone. Results: Data is presented for 33 participants, of which 52% had weak digestive strength. Baseline intake averaged 879 kcal/day, well below the recommended 1400 to 1600 kcal/ day level. Traditional MPs improved energy intake but were protein insufficient, aspects that were addressed in the standard MPs. Diet quantity (1417 kcal/day), quality and frequency improved on the integrated MP, with 3 patients achieving optimal digestive strength. Personalised counselling reduced malnutrition risk, as reported by PGSGA score. Conclusion: Customising dietary advice by overlaying nutrient guidelines with Ayurveda dietary concepts is feasible. The evaluation of digestive strength holds promise for personalising nutrition therapy. Trial Registration: CTRI/2023/07/055657