Eating disorders and obesity: bridging clinical, neurobiological, and therapeutic perspectives.

Eating disorders (EDs) and obesity are complex health conditions sharing various risk and maintenance factors, intensified in cases of comorbidity. This review explores the similarities and connections between these conditions, examining different facets from a multidisciplinary perspective, among them comorbidities, metabolic and psychological factors, neurobiological aspects, and management and therapy implications. We aim to investigate the common characteristics and complexities of weight and EDs and explore their interrelationships in individuals who experience both. The rising prevalence of EDs in people with obesity necessitates integrated approaches to study this comorbidity and to identify and analyze both common and distinct features of these conditions. This review may offer new opportunities for simultaneous prevention and management approaches, as well as future lines of research.

Probiotic and prebiotic interventions in eating disorders: A narrative review.

AIMS: The review aimed to summarise and discuss findings focused on therapeutic probiotic and prebiotic interventions in eating disorders (ED). METHODS: Using PubMed/MEDLINE, Cochrane Library, and Web of Science all published studies were retrieved until February 2023, following PRISMA guidelines. From the 111 initial studies, 5 met the inclusion criteria for this review. RESULTS: All studies included in this narrative review were focused on anorexia nervosa (AN). Three longitudinal, randomised, controlled trials aimed to evaluate interventions with probiotics (Lactobacillus reuteri, yoghurt with Lactobacillus, and Streptococcus) in children and adolescents. These studies primarily emphasised medical outcomes and anthropometric measures following the administration of probiotics. However, the findings yielded mixed results in terms of short-term weight gain or alterations in specific immunological parameters. With a lower level of evidence, supplementation with synbiotics (probiotic + prebiotic) has been associated with improvements in microbiota diversity and attenuation of inflammatory responses. CONCLUSIONS: Research on probiotics and prebiotics in ED is limited, primarily focussing on anorexia nervosa (AN). Their use in AN regarding medical and anthropometric outcomes needs further confirmation and future research should be warranted to assess their impact on psychological and ED symptomatology, where there is a notable gap in the existing literature.

Actualización sobre los aspectos neurobiológicos, clínicos y de tratamiento sobre el juego patológico / Update on the neurobiological, clinical and treatment aspects of gambling disorder

El juego es una actividad cada vez más común en nuestra sociedad, especialmente con la aparición de nuevas modalidades de juego, que lo hacen más fácilmente accesible. A pesar de que para la mayoría de individuos jugar es solo un entretenimiento, algunas personas pueden desarrollar un trastorno de juego (TJ). En los últimos años, el interés por dicho trastorno ha ido aumentado tanto en la comunidad clínica como científica, y el número de estudios sobre etiopatogenia y factores de riesgo ha crecido significativamente. Entre los distintos factores hormonales en el desarrollo y mantenimiento del TJ destacan: la edad, el sexo masculino, tener un nivel socioeconómico bajo, niveles altos de impulsividad y baja regulación emocional. A nivel neurobiológico, se han descrito anomalías en los sistemas de neurotransmisión que regulan las conductas de recompensa. Asimismo, algunos estudios han demostrado la implicación de factores hormonales y en el desarrollo y mantenimiento del TJ. Todo esto ha contribuido notablemente en la mejora de las acciones de prevención y tratamiento. No obstante, aún quedan muchas cuestiones por resolver y es necesario seguir avanzando en la exploración de este trastorno. La presente revisión ofrece una actualización sobre los aspectos clínicos, neurobiológicos y de tratamiento del TJ. (AU)

Gambling is an increasingly more common activity in our society, especially with the advent of new gambling modalities, such as online gambling. Although many people gamble without undergoing health problems, some individuals develop gambling disorder (GD). In recent years, the concern about this disorder has growth substantially among researchers and clinicians, and the number of studies exploring its etiopathogenesis and risk factors has increased significantly. Indeed, certain groups of individuals may have an elevated risk for GD; for example, being male, young, people with low socioeconomic, high impulsivity and emotional instability. From a neurobiological perspective, GD has been associated with alterations in neurotransmitter systems involved in motivation and reward processing. Likewise, some studies have reported that hormonal factors may play an important role in the development and maintenance of GD. Taken together, all these findings have contributed to the improvement of preventive and treatment interventions of gambling disorder. However, further studies are needed to better understand the mechanisms involved in the development and maintenance of this disorder. The present review offers an update on the main clinical, neurobiological and treatment aspects of gambling disorder. (AU)

Athletes with Eating Disorders: Analysis of Their Clinical Characteristics, Psychopathology and Response to Treatment.

Eating disorders (ED) have frequently been described among athletes. However, their specific features and therapy responses are lacking in the literature. The aims of this article were to compare clinical, psychopathological and personality traits between ED patients who were professional athletes (ED-A) with those who were not (ED-NA) and to explore differences in response to treatment. The sample comprised n = 104 patients with ED (n = 52 ED-A and n = 52 matched ED-NA) diagnosed according to DSM-5 criteria. Evaluation consisted of a semi-structured face-to-face clinical interview conducted by expert clinicians and a psychometric battery. Treatment outcome was evaluated when the treatment program ended. ED-A patients showed less body dissatisfaction and psychological distress. No differences were found in treatment outcome among the groups. Within the ED-A group, those participants who performed individual sport activities and aesthetic sports presented higher eating psychopathology, more general psychopathology, differential personality traits and poor therapy outcome. Individual and aesthetic sports presented more severity and worse prognosis. Although usual treatment for ED might be similarly effective in ED-A and ED-NA, it might be important to develop preventive and early detection programs involving sports physicians and psychologists, coaches and family throughout the entire athletic career and afterwards.

Applying psycho-behavioural phenotyping in obesity characterization.

Individual differences in obesity, beyond being explained by metabolic and medical complications, are understood by alterations in eating behaviour which underlie psychological processes. From this psychological perspective, studies have identified several potential characteristic features at the psycho-behavioural level that could additionally explain the maintenance of chronic excess weight or the unsuccessful results of current treatments. To date, despite the growing evidence, the heterogeneity of the psychological evidence associated with obesity has made it challenging to generate consensus on whether these psycho-behavioural phenotypes can be a complement to improve outcomes of existing interventions. For this reason, this narrative review is an overview focused on summarizing studies describing the psycho-behavioural phenotypes associated with obesity. Based on the literature, three psychological constructs have emerged: reward dependence, cognitive control, and mood and emotion. We discuss the clinical implications of stratifying and identifying these psycho-behavioural profiles as potential target for interventions which may ensure a better response to treatment in individuals with obesity. Our conclusions pointed out a considerable overlap between these psycho-behavioural phenotypes suggesting bidirectional interactions between them. These findings endorse the complexity of the psycho-behavioural features associated with obesity and reinforce the need to consider them in order to improve treatment outcomes.

Insulin and disorders of behavioural flexibility.

Behavioural inflexibility is a symptom of neuropsychiatric and neurodegenerative disorders such as Obsessive-Compulsive Disorder, Autism Spectrum Disorder and Alzheimer's Disease, encompassing the maintenance of a behaviour even when no longer appropriate. Recent evidence suggests that insulin signalling has roles apart from its regulation of peripheral metabolism and mediates behaviourally-relevant central nervous system (CNS) functions including behavioural flexibility. Indeed, insulin resistance is reported to generate anxious, perseverative phenotypes in animal models, with the Type 2 diabetes medication metformin proving to be beneficial for disorders including Alzheimer's Disease. Structural and functional neuroimaging studies of Type 2 diabetes patients have highlighted aberrant connectivity in regions governing salience detection, attention, inhibition and memory. As currently available therapeutic strategies feature high rates of resistance, there is an urgent need to better understand the complex aetiology of behaviour and develop improved therapeutics. In this review, we explore the circuitry underlying behavioural flexibility, changes in Type 2 diabetes, the role of insulin in CNS outcomes and mechanisms of insulin involvement across disorders of behavioural inflexibility.

The link between cognition and somatic conditions related to insulin resistance in the UK Biobank study cohort: a systematic review.

Clinical and genomic studies have shown an overlap between neuropsychiatric disorders and insulin resistance (IR)-related somatic conditions, including obesity, type 2 diabetes, and cardiovascular diseases. Impaired cognition is often observed among neuropsychiatric disorders, where multiple cognitive domains may be affected. In this review, we aimed to summarise previous evidence on the relationship between IR-related diseases/traits and cognitive performance in the large UK Biobank study cohort. Electronic searches were conducted on PubMed, Scopus, and Web of Science until April 2022. Eighteen articles met the inclusion criteria and were qualitatively reviewed. Overall, there is substantial evidence for an association between IR-related cardio-metabolic diseases/traits and worse performance on various cognitive domains, which is largely independent of possible confoundings. The most consistent findings referred to IR-related associations with poorer verbal and numerical reasoning ability, as well as slower processing speed. The observed associations might be mediated by alterations in immune-inflammation, brain integrity/connectivity, and/or comorbid somatic or psychiatric diseases/traits. Our findings provide impetus for further research into the underlying neurobiology and possible new therapeutic targets.

Food addiction in Bulimia Nervosa: Analysis of body composition, psychological and problematic foods profile.

Introduction: Food Addiction (FA) has been related with eating disorders (ED), especially Bulimia Nervosa (BN). BN + FA may have different physical characteristics than patients with BN without the comorbidity, such as body mass index (BMI) or body composition, and psychological as emotion regulation. However, the relationship between psychological and physical aspects, connected by problematic food and its influence on body composition, has been barely studied. Therefore, the aims of the present study are. Aims: (a) To explore the differences in body composition between FA positive (FA+) and negative (FA-) in women with BN; (b) to identify problematic relationship with certain food types, according with the foods mentioned in the YFAS scale questionnaire, between FA+ and FA- patients; (c) to know the psychological characteristic differences between FA+ and FA- patients, considering emotion regulation, personality traits and general psychopathological state; (d) to identify the relationship between physical and psychological traits, and the identified problematic foods, in patients with BN and FA. Methodology: N = 81 BN women patients, with a mean age of 29.73 years ± 9.80 SD, who completed the questionnaires: Yale Food Addiction Scale V 1.0 (YFAS 1.0), Eating Disorder Inventory-2 (EDI-2), Symptom Checklist-90 Items-Revised (SCL-90-R), and Difficulties in Emotion Regulation Strategies (DERS). YFAS problematic foods were grouped considering their principal nutrients sources. Body composition and difference in metabolic age was determined using bioimpedance analyzer. Results: The 88% of patients with BN presented FA+. Patients with BN who were FA+ self-reported more problematic relationships with sweets and starches. Also presented higher emotion regulation difficulties, general psychopathology and eating symptomatology severity, than those without FA. Finally, emotional regulation difficulties were positively associated with higher eating disorder symptomatology and more types of foods self-reported as problematic, which increased indirectly fat mass. Conclusion: The results suggest that BN + FA presented more eating and psychopathology symptomatology and higher problems with specific food types. As well, the path analysis emphasized that emotion regulation difficulties might be related with problematic food relationship in BN, impacting over the ED severity. Implications: The results may impact the development of precise therapies for patients with BN + FA.

Temporally ordered associations between type 2 diabetes and brain disorders - a Danish register-based cohort study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is linked with several neurodegenerative and psychiatric disorders, either as a comorbid condition or as a risk factor. We aimed to expand the evidence by examining associations with a broad range of brain disorders (psychiatric and neurological disorders, excluding late-onset neurodegenerative disorders), while also accounting for the temporal order of T2DM and these brain disorders. METHODS: In a population-based cohort-study of 1,883,198 Danish citizens, born 1955-1984 and followed until end of 2016, we estimated associations between T2DM and 16 brain disorders first diagnosed between childhood and mid-adulthood. We calculated odds ratios (OR) and hazard ratios (HR) with 95% confidence intervals (CI) in temporally ordered analyses (brain disorder diagnosis after T2DM and vice versa), adjusted for sex, age, follow-up, birth year, and parental factors. RESULTS: A total of 67,660 (3.6%) of the study population were identified as T2DM cases after age 30 and by a mean age of 45 years (SD of 8 years). T2DM was associated with most psychiatric disorders. Strongest associations were seen with other (i.e. non-anorectic) eating disorders (OR [95% CI]: 2.64 [2.36-2.94]) and schizophrenia spectrum disorder (2.73 [2.63-2.84]). Among neurological disorders especially inflammatory brain diseases (1.73 [1.57-1.91]) and epilepsy (1.67 [1.60-1.75]) were associated with T2DM. Most associations remained in both directions in the temporally ordered analyses. For most psychiatric disorders, associations were strongest in females. CONCLUSIONS: T2DM was associated with several psychiatric and neurological disorders, and most associations were consistently found for both temporal order of disorders. This suggests a shared etiology of T2DM and those brain disorders. This study can form the starting point for studies directed at further elucidating potential causal links between disorders and shared biological mechanisms.

Motherhood and Treatment Outcome in Female Patients with Compulsive Buying-Shopping Disorder.

Motherhood has been proposed as an internal facilitating factor for the recovery of women with mental disorders. However, at the same time, there are significant barriers that may be interfering with the access and adherence to treatment for these women. The present longitudinal study aimed to deepen the sociodemographic and clinical profile of women with children and compulsive buying-shopping disorder (CBSD), and to explore the association between motherhood and response to treatment. The total sample included 77 women with a diagnosis of CBSD (n = 49 mothers) who received cognitive behavioral therapy (CBT) for 12 weeks. No association between psychopathology and motherhood was observed. The group of mothers reported an older age of onset of the CBSD, a lower amount of money spent per compulsive-buying episode, and a higher likelihood of family support for the CBSD. Moreover, this group showed lower risk of relapse. The findings support the theoretical proposal that considers motherhood as an internal facilitating factor for recovery and treatment adherence of mothers with addictions.

Impulsive Personality Traits Predicted Weight Loss in Individuals with Type 2 Diabetes after 3 Years of Lifestyle Interventions.

Impulsivity has been associated with type 2 diabetes (T2D) and may negatively impact its management. This study aimed to investigate impulsive personality traits in an older adult population with T2D and their predicting role in long-term weight control and glycemic management, through glycated hemoglobin (HbA1c), following 3 years of intervention with a Mediterranean diet. The Impulsive Behavior Scale (UPPS-P) was administered as a measure of impulsive traits at baseline. Results showed higher total baseline scores of UPPS-P, and higher positive urgency in individuals with T2D, compared with those without T2D. The regression analysis in patients with T2D showed that sensation seeking and lack of perseverance predicted weight loss at follow-up. By contrast, impulsive traits did not predict follow-up levels of HbA1c. In conclusion, the present findings suggest that higher impulsive traits in individuals with T2D seem to affect long-term weight control, but not glycemic control.

Food addiction in anorexia nervosa: Implications for the understanding of crossover diagnosis.

OBJECTIVE: Food addiction (FA) construct was introduced to reflect abnormal eating patterns that resemble behavioural ones found in substance use disorders. FA has been barely explored in anorexia nervosa (AN). This study evaluated FA occurrence and associated factors in a sample of patients with AN, distinguishing between restrictive and binge-purging subtypes and focussing on the influence of FA in the crossover diagnosis between them. METHOD: A sample of 116 patients with AN admitted for treatment seeking at an Bellvitge Hospital Eating Disorders Unit were included (72 restrictive [AN-R]; 44 binge-purge AN [AN-BP]), and eating-related, personality and psychopathological variables were assessed. Most participants were women (92.2%), mean age 27.1 years old (SD = 10.5). RESULTS: FA was more prevalent in patients with AN-BP compared to the AN-R group (75.0% and 54.2%, respectively). The patients with AN-R FA+, presented more similar ED symptomatology, general psychopathology and personality traits, with the AN-BP patients, than with the AN-R FA-. CONCLUSIONS: Patients with AN-R FA+, exhibit more similarities with the AN-BP subgroup than with the AN-R FA-. Thus, it is possible to hypothesise that the presence of FA might be an indicator of the possible crossover from AN-R to AN-BP.

Vitamin K dietary intake is associated with cognitive function in an older adult Mediterranean population.

BACKGROUND: In the last years, evidence that dietary vitamin K could have a role in the cognitive domain has increased. However, data from large trials are limited. The objective of this study was to assess the association of 2 year changes in the dietary intake of vitamin K with cognitive function measured through neuropsychological performance tests. METHODS: In 5,533 participants of the multicentre PREDIMED-Plus study (48.1% women, age 65.1 ± 4.9 years with overweight/obesity and metabolic syndrome), we assessed the adjusted odds ratios of cognitive function decline according to 2 year changes in vitamin K intake. Participants answered a battery of cognitive function tests and Food Frequency Questionnaires (FFQs) in order to estimate the vitamin K dietary intake. RESULTS: After adjusting for potential cofounders, the highest tertile of change of dietary vitamin K intake (median [IQR]; 194.4 µg/d [120.9, 373.1]) was inversely associated with a Mini-Mental State Examination (MMSE) score ≤24 (OR [95% CI]; 0.53 [0.35, 0.79] P for trend = 0.002) compared with a decrease in the intake of vitamin K (median [IQR]; -97.8 µg/d [-292.8, -51.5]). A significant positive association between changes in dietary vitamin K intake and the semantic verbal fluency test scores (OR [95% CI]; 0.69 [0.51, 0.94] P for trend = 0.019) was found. CONCLUSIONS: An increase of the intake of dietary vitamin K was associated with better cognitive function scores, independently of recognised risk factors for cognitive decline, in an older adult Mediterranean population with high cardiovascular risk.

Transdiagnostic Perspective of Impulsivity and Compulsivity in Obesity: From Cognitive Profile to Self-Reported Dimensions in Clinical Samples with and without Diabetes.

Impulsive and compulsive behaviors have both been observed in individuals with obesity. The co-occurrence of obesity and type 2 diabetes (T2D) is more strongly associated with impulsivity, although there are no conclusive results yet. A multidimensional assessment of impulsivity and compulsivity was conducted in individuals with obesity in the absence or presence of T2D, compared with healthy, normal-weight individuals, with highly impulsive patients (gambling disorders), and with highly compulsive patients (anorexia nervosa). Decision making and novelty seeking were used to measure impulsivity, and cognitive flexibility and harm avoidance were used for compulsivity. For impulsivity, patients with obesity and T2D showed poorer decision-making ability compared with healthy individuals. For compulsivity, individuals with only obesity presented less cognitive flexibility and high harm avoidance; these dimensions were not associated with obesity with T2D. This study contributes to the knowledge of the mechanisms associated with diabetes and its association with impulsive-compulsive behaviors, confirming the hypothesis that patients with obesity and T2D would be characterized by higher levels of impulsivity.

Metabolic, Affective and Neurocognitive Characterization of Metabolic Syndrome Patients with and without Food Addiction. Implications for Weight Progression.

According to the food addiction (FA) model, the consumption of certain types of food could be potentially addictive and can lead to changes in intake regulation. We aimed to describe metabolic parameters, dietary characteristics, and affective and neurocognitive vulnerabilities of individuals with and without FA, and to explore its influences on weight loss progression. The sample included 448 adults (55-75 years) with overweight/obesity and metabolic syndrome from the PREDIMED-Plus cognition sub-study. Cognitive and psychopathological assessments, as well as dietary, biochemical, and metabolic measurements, were assessed at baseline. Weight progression was evaluated after a 3-year follow up. The presence of FA was associated with higher depressive symptomatology, neurocognitive decline, low quality of life, high body mass index (BMI), and high waist circumference, but not with metabolic comorbidities. No differences were observed in the dietary characteristics except for the saturated and monounsaturated fatty acids consumption. After three years, the presence of FA at baseline resulted in a significantly higher weight regain. FA is associated with worse psychological and neurocognitive state and higher weight regain in adults with metabolic syndrome. This condition could be an indicator of bad prognosis in the search for a successful weight loss process.

Effects of the Mediterranean Diet or Nut Consumption on Gut Microbiota Composition and Fecal Metabolites and their Relationship with Cardiometabolic Risk Factors.

SCOPE: To examine whether a Mediterranean Diet (MedDiet) compared to the consumption of nuts in the context of a habitual non-MedDiet exerts a greater beneficial effect on gut microbiota and fecal metabolites; thus, contributing to explain major benefits on cardiometabolic risk factors. METHODS AND RESULTS: Fifty adults with Metabolic Syndrome are randomized to a controlled, crossover 2-months dietary-intervention trial with a 1-month wash-out period, following a MedDiet or consuming nuts (50 g day-1 ). Microbiota composition is assessed by 16S rRNA gene sequencing and metabolites are measured using Nuclear Magnetic Resonance (NMR) and liquid chromatography coupled to triple quadrupole mass spectrometry (LC-qTOF) platforms in a targeted metabolomics approach. Decreased glucose, insulin and the homeostatic model assessment of insulin resistance (HOMA-IR) is observed after the MedDiet compared to the nuts intervention. Relative abundances of Lachnospiraceae NK4A136 and an uncultured genera of Ruminococcaceae are significantly increased after the MedDiet compared to nuts supplementation. Changes in Lachnospiraceae NK4A136 are inversely associated with insulin levels and HOMA-IR, while positively and negatively with changes in cholate and cadaverine, respectively. CONCLUSIONS: Following a MedDiet, rather than nuts, induces a significant increase in Lachnospiraceae NK4A136 and improves the metabolic risk. This genera seems to affect the bile acid metabolism and cadaverine which may account for the improvement in insulin levels.

Changes in Circulating Metabolites During Weight Loss are Associated with Adiposity Improvement, and Body Weight and Adiposity Regain During Weight Loss Maintenance: The SATIN Study.

SCOPE: To examine the relationship between changes in circulating metabolites during diet-induced weight loss and changes of adiposity. This study also investigates changes in these metabolites in relation to body weight and adiposity regain during a weight loss maintenance period. METHODS AND RESULTS: This cohort study is nested within the Satiety Innovation (SATIN) study. Participants (n = 162) achieving ≥8% weight loss during an initial 8-week low-calorie formula diet (LCD) are included in a 12-week weight loss maintenance period. A targeted metabolite profiling (123 metabolites) approach is applied using three different platforms (proton nuclear magnetic resonance, liquid chromatography mass spectrometry, gas chromatography mass spectrometry). Changes in several lipid species and citric acid are significantly associated with greater reduction of body weight, total fat, and abdominal adiposity distribution during the LCD. Decreases in the concentrations of lysophosphatidylcholines (LPCs) 14:0, LPC 20:3, phosphatidylcholine (PC) 32:2, PC 38:3, sphingomyelin (SM) 32:2, and increases in citric acid concentrations during the LCD are associated with adiposity regain and loss, respectively, during the weight loss maintenance period. CONCLUSIONS: The results show that weight loss is associated with changes in lipid species and citric acid. These changes are related to subsequent weight and adiposity regain identifying the adipose lipid metabolism as an important factor for the maintenance of lost weight and adiposity.

Circulating Metabolites Associated with Body Fat and Lean Mass in Adults with Overweight/Obesity.

The interplay between fat mass and lean mass within human metabolism is not completely understood. We aimed to identify specific circulating metabolomic profiles associated with these body composition compartments. Cross-sectional analyses were conducted over 236 adults with overweight/obesity from the Satiety Innovation (SATIN) study. Body composition was assessed by dual-energy X-ray absorptiometry. A targeted multiplatform metabolite profiling approach was applied. Associations between 168 circulating metabolites and the body composition measures were assessed using elastic net regression analyses. The accuracy of the multimetabolite weighted models was evaluated using a 10-fold cross-validation approach and the Pearson's correlation coefficients between metabolomic profiles and body compartments were estimated. Two different profiles including 86 and 65 metabolites were selected for % body fat and lean mass. These metabolites mainly consisted of lipids (sphingomyelins, phosphatidylcholines, lysophosphatidylcholines), acylcarnitines, and amino acids. Several metabolites overlapped between these body composition measures but none of them towards the same direction. The Pearson correlation coefficients between the metabolomic profiles and % body fat or lean mass were 0.80 and 0.79, respectively. Our findings suggest alterations in lipid metabolism, fatty acid oxidation, and protein degradation with increased adiposity and decreased lean body mass. These findings could help us to better understand the interplay between body composition compartments with human metabolic processes.

Effects of Mediterranean Diet on plasma metabolites and their relationship with insulin resistance and gut microbiota composition in a crossover randomized clinical trial.

BACKGROUND & AIMS: The Mediterranean Diet (MedDiet) may decrease the cardiometabolic risk through modulation of metabolic pathways. Furthermore, the interplay between MedDiet, metabolites and microbial metabolism may improve our understanding on the metabolic effects of this diet. We aimed to evaluate the effect of the MedDiet compared to nuts supplementation on circulating metabolites and their relationship with cardiometabolic health. We further examined whether changes in the metabolomic profiles were associated with changes in gut microbiota composition in a multi-omics integrative approach. METHODS: Forty-four adults with Metabolic Syndrome (MetS), (aged 37-65) participated in a randomized controlled, crossover 2-months dietary-intervention trial with a 1-month wash-out period, consuming a MedDiet or a non MedDiet plus nuts (50 g/day). Nutritional data were collected at the beginning and the end of each intervention period using 3-day dietary records, as well as fasting blood and fecal samples. Plasma metabolites (m = 378) were profiled using targeted metabolomics. Associations of these metabolites with the interventions were assessed with elastic net regression analyses. Gut microbiota composition was assessed by 16S rRNA sequencing. A sparse least regression analysis combined with a canonical correlation analysis was conducted between the plasma selected metabolites and genera in order to identify the relevant dual-omics signatures discriminating the dietary interventions. RESULTS: Changes in 65 circulating metabolites were significantly associated with the MedDiet (mainly lipids, acylcarnitines, amino acids, steroids and TCA intermediates). Importantly, these changes were associated with decreases in glucose, insulin and HOMA-IR. The network analysis identified two main clusters of genera with an opposite behaviour towards selected metabolites, mainly PC species, ChoE(20:5), TGs and medium/long-chain acylcarnitines. CONCLUSION: Following a MedDiet, rather than consuming nuts in the context of a non-MedDiet was associated with a specific plasma metabolomic profile, which was also related to metabolic improvements in adults with MetS. The identified correlated network between specific bacteria and metabolites suggests interplay between diet, circulating metabolites and gut microbiota. The trial was registered in the ISRCTN with identifier ISRCTN88780852, https://doi.org/10.1186/ISRCTN88780852.

Circulating Metabolites Associated with Postprandial Satiety in Overweight/Obese Participants: The SATIN Study.

Scope: To identify a metabolomic profile related to postprandial satiety sensations involved in appetite control would help for a better understanding of the regulation of food intake. Methods and Results: A cross-sectional analysis of plasma metabolites was conducted over 151 overweight/obese adults from the "Satiety Innovation"-SATIN study, a randomized clinical trial of a 12-week weight-loss maintenance period. Postprandial satiety sensations (3 h-iAUC) were assessed by visual analogue scale (VAS) at the beginning and at the end of the study. Fasting plasma metabolites were profiled using a targeted multiplatform metabolomics approach before each appetite test meal. Associations between 124 metabolites and iAUC-satiety were assessed using elastic net linear regression analyses. The accuracy of the multimetabolite weighted models for iAUC-VAS was evaluated using a 10-fold cross-validation (CV) approach and the Pearson's correlation coefficients were estimated. Five and three metabolites were selected in the first and the second assessments, respectively. Circulating glycine and linoleic acid concentrations were consistently and positively associated with higher iAUC-satiety in both visits. Sucrose and sphingomyelins (C32:2, C38:1) were negatively associated with iAUC-satiety in the first visit. The Pearson correlations coefficients between the metabolomic profiles and iAUC-satiety in the first and the second appetite assessments were 0.37 and 0.27, respectively. Conclusion: Higher glycine and linoleic acid were moderately but consistently associated with higher postprandial satiety in two different appetite assessments in overweight and obese subjects.