Examining nutrition strategies to influence DNA methylation and epigenetic clocks: a systematic review of clinical trials.

Nutrition has powerful impacts on our health and longevity. One of the mechanisms by which nutrition might influence our health is by inducing epigenetic modifications, modulating the molecular mechanisms that regulate aging. Observational studies have provided evidence of a relationship between nutrition and differences in DNA methylation. However, these studies are limited in that they might not provide an accurate control of the interactions between different nutrients, or between nutrition and other lifestyle behaviors. Here we systematically reviewed clinical studies examining the impact of nutrition strategies on DNA methylation. We examined clinical studies in community-dwelling adults testing the effects of nutrition interventions on i) global DNA methylation and its proxies, and ii) epigenetic clocks. We included 21 intervention studies that focused on the effects of healthy nutrition patterns, specific foods or nutrients, as well as the effect of multivitamin or multimineral supplements. In four studies on the methylation effects of healthy dietary patterns, as defined by being rich in vegetables, fruits, whole-grains, and nuts and reduced in the intake of added sugars, saturated fat, and alcohol, two of them suggested that a healthy diet, is associated with lower epigenetic age acceleration, one of them reported increases in global DNA methylation, while another one found no diet effects. Studies examining epigenetic effects of specific foods, nutrients, or mixtures of nutrients were scarce. For both folic acid and polyunsaturated fatty acids, the available independent studies produced conflicting findings. Although more evidence is still needed to draw firm conclusions, results begin to suggest that healthy dietary patterns have positive effects on DNA methylation. Additional evidence from large randomized-controlled clinical trials is needed to support the effects of healthy nutrition on the DNA methylome.

Plasma levels of adipokines and insulin are associated with markers of brain atrophy and cognitive decline in the spectrum of Alzheimer's Disease.

The discovery that metabolic alterations often coexist with neurodegenerative conditions has sparked interest in the examination of metabolic regulatory factors as potential modulators of brain health. Here, we examined the role of adipokines (leptin, adiponectin, resistin, and IL6) and insulin on different markers of brain atrophy in participants on the spectrum of Alzheimer's Disease. We included 566 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset with 1063 follow-up time points (average follow-up: one year); and examined the association between metabolic regulatory factors and volumetric MRI values, white matter hyperintensities, and measures of cognitive impairment. Higher leptin, resistin, IL6, and insulin were associated with markers of cerebral atrophy, such as lower total brain volume, or higher ventricular volume. Higher leptin and resistin were also associated with greater impairment in daily life activities. Higher adiponectin was associated with lower ventricle volume. There was no association between adipokines or insulin with white matter hyperintensities. Our findings indicate a co-occurrence between alterations in metabolic regulatory factors and in brain volume along the preclinical to clinical spectrum of Alzheimer's Disease. These results suggest that strategies aimed at promoting metabolic health may positively impact brain health.

Comprehensive immune profiling reveals that Orbivirus infection activates immune checkpoints during acute T cell immunosuppression.

Bluetongue virus (BTV) is an arbovirus transmitted by the bite of infected Culicoides midges that affects domestic and wild ruminants producing great economic losses. The infection induces an IFN response, followed by an adaptive immune response that is essential in disease clearance. BTV can nonetheless impair IFN and humoral responses. The main goal of this study was to gain a more detailed understanding of BTV pathogenesis and its effects on immune cell populations. To this end, we combined flow cytometry and transcriptomic analyses of several immune cells at different times post-infection (pi). Four sheep were infected with BTV serotype 8 and blood samples collected at days 0, 3, 7 and 15pi to perform transcriptomic analysis of B-cell marker+, CD4+, CD8+, and CD14+ sorted peripheral mononuclear cells. The maximum number of differentially expressed genes occurred at day 7pi, which coincided with the peak of infection. KEGG pathway enrichment analysis indicated that genes belonging to virus sensing and immune response initiation pathways were enriched at day 3 and 7 pi in all 4 cell population analyzed. Transcriptomic analysis also showed that at day 7pi T cell exhaustion pathway was enriched in CD4+ cells, while CD8+ cells downregulated immune response initiation pathways. T cell functional studies demonstrated that BTV produced an acute inhibition of CD4+ and CD8+ T cell activation at the peak of replication. This coincided with PD-L1 upregulation on the surface of CD4+ and CD8+ T cells as well as monocytes. Taken together, these data indicate that BTV could exploit the PD1/PD-L1 immune checkpoint to impair T cell responses. These findings identify several mechanisms in the interaction between host and BTV, which could help develop better tools to combat the disease.

Maintaining brain health across the lifespan.

Across the lifespan, the human body and brain endure the impact of a plethora of exogenous and endogenous factors that determine the health outcome in old age. The overwhelming inter-individual variance spans between progressive frailty with loss of autonomy to largely preserved physical, cognitive, and social functions. Understanding the mechanisms underlying the diverse aging trajectories can inform future strategies to maintain a healthy body and brain. Here we provide a comprehensive overview of the current literature on lifetime factors governing brain health. We present the growing body of evidence that unhealthy alimentary regime, sedentary behaviour, sleep pathologies, cardio-vascular risk factors, and chronic inflammation exert their harmful effects in a cumulative and gradual manner, and that timely and efficient intervention could promote healthy and successful aging. We discuss the main effects and interactions between these risk factors and the resulting brain health outcomes to follow with a description of current strategies aiming to eliminate, treat, or counteract the risk factors. We conclude that the detailed insights about modifiable risk factors could inform personalized multi-domain strategies for brain health maintenance on the background of increased longevity.

Warming appears as the main risk of non-adaptedness for western Mediterranean relict fir forests under expected climate change scenarios.

Circum-Mediterranean firs are considered among the most drought-sensitive species to climate change. Understanding the genetic basis of trees' adaptive capacity and intra-specific variability to drought avoidance is mandatory to define conservation measures, thus potentially preventing their extinction. We focus here on Abies pinsapo and Abies marocana, both relict tree species, endemic from south Spain and north Morocco, respectively. A total of 607 samples were collected from eight nuclei: six from Spanish fir and two from Moroccan fir. A genotyping by sequencing technique called double digestion restriction site-associated DNA sequencing (ddRAD-seq) was performed to obtain a genetic matrix based on single-nucleotide polymorphisms (SNPs). This matrix was utilized to study the genetic structure of A. pinsapo populations and to carry out selection signature studies. In order to understand how Spanish fir and Moroccan fir cope with climate change, genotype-environment associations (GEAs) were identified. Further, the vulnerability of these species to climate variations was estimated by the risk of non-adaptedness (RONA). The filtering of the de novo assembly of A. pinsapo provided 3,982 SNPs from 504 out of 509 trees sequenced. Principal component analysis (PCA) genetically separated Grazalema from the rest of the Spanish populations. However, FST values showed significant differences among the sampling points. We found 51 loci potentially under selection. Homolog sequences were found for some proteins related to abiotic stress response, such as dehydration-responsive element binding transcription factor, regulation of abscisic acid signaling, and methylation pathway. A total of 15 associations with 11 different loci were observed in the GEA studies, with the maximum temperature of the warmest month being the variable with the highest number of associated loci. This temperature sensitivity was also supported by the risk of non-adaptedness, which yielded a higher risk for both A. pinsapo and A. marocana under the high emission scenario (Representative Concentration Pathway (RCP) 8.5). This study sheds light on the response to climate change of these two endemic species.

Climate and Soil Microsite Conditions Determine Local Adaptation in Declining Silver Fir Forests.

Ongoing climatic change is threatening the survival of drought-sensitive tree species, such as silver fir (Abies alba). Drought-induced dieback had been previously explored in this conifer, although the role played by tree-level genetic diversity and its relationship with growth patterns and soil microsite conditions remained elusive. We used double digest restriction-site-associated DNA sequencing (ddRADseq) to describe different genetic characteristics of five silver fir forests in the Spanish Pyrenees, including declining and non-declining trees. Single nucleotide polymorphisms (SNPs) were used to investigate the relationships between genetics, dieback, intraspecific trait variation (functional dendrophenotypic traits and leaf traits), local bioclimatic conditions, and rhizosphere soil properties. While there were no noticeable genetic differences between declining and non-declining trees, genome-environment associations with selection signatures were abundant, suggesting a strong influence of climate, soil physicochemical properties, and soil microbial diversity on local adaptation. These results provide novel insights into how genetics and diverse environmental factors are interrelated and highlight the need to incorporate genetic data into silver fir forest dieback studies to gain a better understanding of local adaptation.

Body mass index, systemic inflammation and cognitive performance in adolescents: A cross-sectional study.

BACKGROUND: Excessive body weight has been related to lower cognitive performance. One of the mechanisms through which excess body weight may affect cognition is inflammation. HYPOTHESIS: Our hypothesis is that both body mass index (BMI) and circulating levels of inflammatory biomarkers will be negatively related to cognitive performance. DESIGN: Cross-sectional study. SETTING: Users of the public health centres of the Consorci Sanitari de Terrassa (Terrassa, Spain) between 2010 and 2017 aged 12-21 years. PARTICIPANTS: One hundred and five adolescents (46 normoweight, 18 overweight, 41 obese). MEASUREMENTS: Levels of high sensitivity C-reactive protein, interleukin 6, tumour necrosis factor α (TNFα) and fibrinogen were determined from blood samples. Cognitive performance was evaluated and six cognitive composites were obtained: working memory, cognitive flexibility, inhibitory control, decision-making, verbal memory, and fine motor speed. A single multivariate general lineal model was used to assess the influence of the four inflammatory biomarkers, as well as participants' BMI, sex, and age on the 6 cognitive indexes. RESULTS: An inverse relationship between BMI and inhibitory control (F = 5.688, p = .019; ß = -0.212, p = .031), verbal memory (F = 5.404, p = .022; ß = -0.255, p = .009) and fine motor speed (F = 9.038, p = .003; ß = -0.319, p = .001) was observed. Levels of TNFα and fibrinogen were inversely related to inhibitory control (F = 5.055, p = .027; ß = -0.226, p = .021) and verbal memory (F = 4.732, p = .032; ß = -0.274, p = .005), respectively. LIMITATIONS: The cross-sectional nature of the study, the use of cognitive tests designed for clinical purposes, and the use of BMI as a proxy for adiposity are limitations of our study that must be taken into account when interpreting results. CONCLUSIONS: Our data indicate that some components of executive functions, together with verbal memory, are sensitive to specific obesity-related inflammatory agents at early ages.

Assessing adipokines as potential biomarkers of dementia, Alzheimer's disease, and mild cognitive impairment: A systematic review and meta-analysis.

Midlife obesity and late-life weight loss confer a greater risk for developing dementia and Alzheimer's disease (AD), but the exact mechanisms behind this phenomenon are currently unknown. The answer could lie on the involvement of gastrointestinal factors, such as adipokines (e.g., leptin, adiponectin, and resistin) and ghrelin. In this context, we conducted a pre-registered systematic review and meta-analysis of 42 cross-sectional and 13 longitudinal studies targeting the associations between leptin, adiponectin, resistin, and ghrelin and the prevalence of general dementia, AD, and mild cognitive impairment (MCI). We also examined the relationship between the four gastrointestinal factors and neurocognitive outcomes and AD-related cerebrospinal fluid biomarkers. Patients with AD had lower blood leptin and higher resistin levels than cognitively normal participants. Lower leptin and higher resistin were associated with higher degree of cognitive impairment. Additionally, lower late-life leptin levels might be associated with higher prospective risk of dementia and AD, although more studies are needed to corroborate this. Results in ghrelin and adiponectin were not conclusive, with age, sex distribution, obesity, and severity of dementia seemingly acting as moderators across several analyses. Our work might contribute to the identification of new preclinical blood markers of MCI and AD.

Tree-Level Growth Patterns and Genetic Associations Depict Drought Legacies in the Relict Forests of Abies marocana.

The frequency and intensity of drought events are increasing worldwide, challenging the adaptive capacity of several tree species. Here, we evaluate tree growth patterns and climate sensitivity to precipitation, temperature, and drought in the relict Moroccan fir Abies marocana. We selected two study sites, formerly stated as harboring contrasting A. marocana taxa (A. marocana and A. tazaotana, respectively). For each tree, dendrochronological methods were applied to quantify growth patterns and climate-growth sensitivity. Further, ddRAD-seq was performed on the same trees and close saplings to obtain single nucleotide polymorphisms (SNPs) and related genotype-phenotype associations. Genetic differentiation between the two studied remnant populations of A. marocana was weak. Growth patterns and climate-growth relationships were almost similar at the two sites studied, supporting a negative effect of warming. Growth trends and tree size showed associations with SNPs, although there were no relationships with phenotypes related to climatic sensitivity. We found significant differences in the SNPs subjected to selection in the saplings compared to the old trees, suggesting that relict tree populations might be subjected to genetic differentiation and local adaptation to climate dryness. Our results illustrate the potential of tree rings and genome-wide analysis to improve our understanding of the adaptive capacity of drought-sensitive forests to cope with ongoing climate change.

Beyond BMI: cardiometabolic measures as predictors of impulsivity and white matter changes in adolescents.

Obesity is characterized by cardiometabolic and neurocognitive changes. However, how these two factors relate to each other in this population is unknown. We tested the association that cardiometabolic measures may have with impulse behaviors and white matter microstructure in adolescents with and without an excess weight. One hundred and eight adolescents (43 normal-weight and 65 overweight/obesity; 11-19 years old) were medically and psychologically (Temperament Character Inventory Revised, Three-Factor Eating Questionnaire-R18, Conners' Continuous Performance Test-II, Stroop Color and Word Test, Wisconsin Card Sorting Test, Kirby Delay Discounting Task) evaluated. A subsample of participants (n = 56) underwent a brain magnetic resonance imaging acquisition. In adolescents, higher triglycerides and having a body mass index indicative of overweight/obesity predicted a more impulsive performance in Conners' Continuous Performance Test-II (higher commission errors). In addition, higher glucose and diastolic blood pressure values predicted increments in the Three-Factor Eating Questionnaire-R18 emotional eating scale. Neuroanatomically, cingulum fractional anisotropy showed a negative relationship with glycated hemoglobin. The evaluation of the neurocognitive differences associated with obesity, usually based on body mass index, should be complemented with cardiometabolic measures.

Weak genetic differentiation but strong climate-induced selective pressure toward the rear edge of mountain pine in north-eastern Spain.

Local differentiation at distribution limits may influence species' adaptive capacity to environmental changes. However, drivers, such gene flow and local selection, are still poorly understood. We focus on the role played by range limits in mountain forests to test the hypothesis that relict tree populations are subjected to genetic differentiation and local adaptation. Two alpine treelines of mountain pine (Pinus uncinata Ram. ex DC) were investigated in the Spanish Pyrenees. Further, an isolated relict population forming the species' southernmost distribution limit in north-eastern Spain was also investigated. Using genotyping by sequencing, a genetic matrix conformed by single nucleotide polymorphisms (SNPs) was obtained. This matrix was used to perform genotype-environment and genotype-phenotype associations, as well as to model risk of non-adaptedness. Increasing climate seasonality appears as an essential element in the interpretation of SNPs subjected to selective pressures. Genetic differentiations were overall weak. The differences in leaf mass area and radial growth rate, as well as the identification of several SNPs subjected to selective pressures, exceeded neutral predictions of differentiation among populations. Despite genetic drift might prevail in the isolated population, the Fst values (0.060 and 0.066) showed a moderate genetic drift and Nm values (3.939 and 3.555) indicate the presence of gene flow between the relict population and both treelines. Nonetheless, the SNPs subjected to selection pressures provide evidences of possible selection in treeline ecotones. Persistence in range boundaries seems to involve several selective pressures in species' traits, which were significantly related to enhanced drought seasonality at the limit of P. uncinata distribution range. We conclude that gene flow is unlikely to constrain adaptation in the P. uncinata rear edge, although this species shows vulnerability to future climate change scenarios involving warmer and drier conditions.

Contrasting transcriptomic patterns reveal a genomic basis for drought resilience in the relict fir Abies pinsapo Boiss.

Climate change challenges the adaptive capacity of several forest tree species in the face of increasing drought and rising temperatures. Therefore, understanding the mechanistic connections between genetic diversity and drought resilience is highly valuable for conserving drought-sensitive forests. Nonetheless, the post-drought recovery in trees from a transcriptomic perspective has not yet been studied by comparing contrasting phenotypes. Here, experimental drought treatments, gas-exchange dynamics and transcriptomic analysis (RNA-seq) were performed in the relict and drought-sensitive fir Abies pinsapo Boiss. to identify gene expression differences over immediate (24 h) and extended drought (20 days). Post-drought responses were investigated to define resilient and sensitive phenotypes. Single nucleotide polymorphisms (SNPs) were also studied to characterize the genomic basis of A. pinsapo drought resilience. Weighted gene co-expression network analysis showed an activation of stomatal closing and an inhibition of plant growth-related genes during the immediate drought, consistent with an isohydric dynamic. During the extended drought, transcription factors, as well as cellular damage and homeostasis protection-related genes prevailed. Resilient individuals activate photosynthesis-related genes and inhibit aerial growth-related genes, suggesting a shifting shoot/root biomass allocation to improve water uptake and whole-plant carbon balance. About, 152 fixed SNPs were found between resilient and sensitive seedlings, which were mostly located in RNA-activity-related genes, including epigenetic regulation. Contrasting gene expression and SNPs were found between different post-drought resilience phenotypes for the first time in a forest tree, suggesting a transcriptomic and genomic basis for drought resilience. The obtained drought-related transcriptomic profile and drought-resilience candidate genes may guide conservation programs for this threatened tree species.

A Morbillivirus Infection Shifts DC Maturation Toward a Tolerogenic Phenotype to Suppress T Cell Activation.

Viruses have evolved numerous strategies to impair immunity so that they can replicate more efficiently. Among those, the immunosuppressive effects of morbillivirus infection can be particularly problematic, as they allow secondary infections to take hold in the host, worsening disease prognosis. In the present work, we hypothesized that the highly contagious morbillivirus peste des petits ruminants virus (PPRV) could target monocytes and dendritic cells (DC) to contribute to the immunosuppressive effects produced by the infection. Monocytes isolated from healthy sheep, a natural host of the disease, were able be infected by PPRV and this impaired the differentiation and phagocytic ability of immature monocyte-derived DC (MoDC). We also assessed PPRV capacity to infect differentiated MoDC. Ovine MoDC could be productively infected by PPRV, and this drastically reduced MoDC capacity to activate allogeneic T cell responses. Transcriptomic analysis of infected MoDC indicated that several tolerogenic DC signature genes were upregulated upon PPRV infection. Furthermore, PPRV-infected MoDC could impair the proliferative response of autologous CD4+ and CD8+ T cell to the mitogen concanavalin A (ConA), which indicated that DC targeting by the virus could promote immunosuppression. These results shed new light on the mechanisms employed by morbillivirus to suppress the host immune responses. IMPORTANCE Morbilliviruses pose a threat to global health given their high infectivity. The morbillivirus peste des petits ruminants virus (PPRV) severely affects small-ruminant-productivity and leads to important economic losses in communities that rely on these animals for subsistence. PPRV produces in the infected host a period of severe immunosuppression that opportunistic pathogens exploit, which worsens the course of the infection. The mechanisms of PPRV immunosuppression are not fully understood. In the present work, we demonstrate that PPRV can infect professional antigen-presenting cells called dendritic cells (DC) and disrupt their capacity to elicit an immune response. PPRV infection promoted a DC activation profile that favored the induction of tolerance instead of the activation of an antiviral immune response. These results shed new light on the mechanisms employed by morbilliviruses to suppress the immune responses.

Mechanisms linking obesity and its metabolic comorbidities with cerebral grey and white matter changes.

Obesity is a preventable risk factor for cerebrovascular disorders and it is associated with cerebral grey and white matter changes. Specifically, individuals with obesity show diminished grey matter volume and thickness, which seems to be more prominent among fronto-temporal regions in the brain. At the same time, obesity is associated with lower microstructural white matter integrity, and it has been found to precede increases in white matter hyperintensity load. To date, however, it is unclear whether these findings can be attributed solely to obesity or whether they are a consequence of cardiometabolic complications that often co-exist with obesity, such as low-grade systemic inflammation, hypertension, insulin resistance, or dyslipidemia. In this narrative review we aim to provide a comprehensive overview of the potential impact of obesity and a number of its cardiometabolic consequences on brain integrity, both separately and in synergy with each other. We also identify current gaps in knowledge and outline recommendations for future research.

Relationship between impulsivity, uncontrolled eating and body mass index: a hierarchical model.

BACKGROUND: Impulsivity increases the risk for obesity and weight gain. However, the precise role of impulsivity in the aetiology of overeating behavior and obesity is currently unknown. Here we examined the relationships between personality-related measures of impulsivity, Uncontrolled Eating, body mass index (BMI), and longitudinal weight changes. In addition, we analyzed the associations between general impulsivity domains and cortical thickness to elucidate brain vulnerability factors related to weight gain. METHODS: Students (N = 2318) in their first year of university-a risky period for weight gain-completed questionnaire measures of impulsivity and eating behavior at the beginning of the school year. We also collected their weight at the end of the term (N = 1177). Impulsivity was divided into three factors: stress reactivity, reward sensitivity and lack of self-control. Using structural equation models, we tested a hierarchical relationship, in which impulsivity traits were associated with Uncontrolled Eating, which in turn predicted BMI and weight change. Seventy-one participants underwent T1-weighted MRI to investigate the correlation between impulsivity and cortical thickness. RESULTS: Impulsivity traits showed positive correlations with Uncontrolled Eating. Higher scores in Uncontrolled Eating were in turn associated with higher BMI. None of the impulsivity-related measurements nor Uncontrolled Eating were correlated with longitudinal weight gain. Higher stress sensitivity was associated with increased cortical thickness in the superior temporal gyrus. Lack of self-control was positively associated with increased thickness in the superior medial frontal gyrus. Finally, higher reward sensitivity was associated with lower thickness in the inferior frontal gyrus. CONCLUSION: The present study provides a comprehensive characterization of the relationships between different facets of impulsivity and obesity. We show that differences in impulsivity domains might be associated with BMI via Uncontrolled Eating. Our results might inform future clinical strategies aimed at fostering self-control abilities to prevent and/or treat unhealthy weight gain.

Restrained Eating Is Associated with Lower Cortical Thickness in the Inferior Frontal Gyrus in Adolescents.

Some eating patterns, such as restrained eating and uncontrolled eating, are risk factors for eating disorders. However, it is not yet clear whether they are associated with neurocognitive differences. In the current study, we analyzed whether eating patterns can be used to classify participants into meaningful clusters, and we examined whether there are neurocognitive differences between the clusters. Adolescents (n = 108; 12 to 17 years old) and adults (n = 175, 18 to 40 years old) completed the Three Factor Eating Questionnaire, which was used to classify participants according to their eating profile using k means clustering. Participants also completed personality questionnaires and a neuropsychological examination. A subsample of participants underwent a brain MRI acquisition. In both samples, we obtained a cluster characterized by high uncontrolled eating patterns, a cluster with high scores in restrictive eating, and a cluster with low scores in problematic eating behaviors. The clusters were equivalent with regards to personality and performance in executive functions. In adolescents, the cluster with high restrictive eating showed lower cortical thickness in the inferior frontal gyrus compared to the other two clusters. We hypothesize that this difference in cortical thickness represents an adaptive neural mechanism that facilitates inhibition processes.

The Impact of Restrictive and Non-restrictive Dietary Weight Loss Interventions on Neurobehavioral Factors Related to Body Weight Control: the Gaps and Challenges.

PURPOSE OF REVIEW: Restrictive diets, such as low-calorie diets, are difficult to maintain in the long term. For this reason, their popularity has decreased compared to non-restrictive approaches, which instead promote healthy eating strategies. Since both strategies may entail different neurobiological mechanisms, this review will examine the current evidence on the effects of restrictive and non-restrictive interventions on neurobehavioral factors. RECENT FINDINGS: Restrictive diets appear to improve eating behaviors, and the evidence reviewed argues against the notion that they may worsen the severity of binge eating. Moreover, they may lead to short-term changes in brain structure and improvements in cerebrovascular markers which, in turn, could impact eating behaviors. Non-restrictive interventions may have a positive effect on weight management and eating behaviors. However, evidence of their neural effects is scarce. Small sample sizes, short follow-ups, and the absence of control groups are limitations of the studies targeting both interventions. Rigorous long-term randomized studies are needed to examine the neurobehavioral effects of restrictive and non-restrictive approaches.

White matter integrity differences in obesity: A meta-analysis of diffusion tensor imaging studies.

Some Diffusion Tensor Imaging studies have shown a loss of white matter (WM) integrity linked to impaired cognitive function in obese individuals. However, inconsistent WM integrity changes have been reported. We aimed to identify which WM tracts show consistent changes with obesity. We conducted a systematic search to find studies examining the association between obesity-related measures and Fractional Anisotropy (FA) or Mean Diffusivity. We performed a meta-analysis with FA datasets using Anisotropic Effect Size-Signed Differential Mapping software. The meta-analysis showed that increased obesity measurements were related to reduced FA in the genu of the corpus callosum. We validated our findings using an independent sample from the Human Connectome Project dataset, which supports lower FA in this region in individuals with obesity compared to those with normal weight (p = 0.028). Our findings provide evidence that obesity is associated with reduced WM integrity in the genu of the corpus callosum, a tract linking frontal areas involved in executive function. Future studies are needed on the mechanisms linking obesity with loss of WM integrity.

Alterations in Brain Network Organization in Adults With Obesity as Compared With Healthy-Weight Individuals and Seniors.

OBJECTIVE: Life expectancy and obesity rates have drastically increased in recent years. An unhealthy weight is related to long-lasting medical disorders that might compromise the normal course of aging. The aim of the current study of brain connectivity patterns was to examine whether adults with obesity would show signs of premature aging, such as lower segregation, in large-scale networks. METHODS: Participants with obesity (n = 30, mean age = 32.8 ± 5.68 years) were compared with healthy-weight controls (n = 33, mean age = 30.9 ± 6.24 years) and senior participants who were stroke-free and without dementia (n = 30, mean age = 67.1 ± 6.65 years) using resting-state magnetic resonance imaging and graph theory metrics (i.e., small-world index, clustering coefficient, characteristic path length, and degree). RESULTS: Contrary to our hypothesis, participants with obesity exhibited a higher clustering coefficient compared with senior participants (t = 5.06, p < .001, d = 1.23, 95% CIbca = 0.64 to 1.88). Participants with obesity also showed lower global degree relative to seniors (t = -2.98, p = .014, d = -0.77, 95% CIbca = -1.26 to -0.26) and healthy-weight controls (t = -2.92, p = .019, d = -0.72, 95% CIbca = -1.19 to -0.25). Regional degree alterations in this group were present in several functional networks. CONCLUSIONS: Participants with obesity displayed greater network clustering than did seniors and also had lower degree compared with seniors and individuals with normal weight, which is not consistent with the notion that obesity is associated with premature aging of the brain. Although the cross-sectional nature of the study precludes causal inference, the overly clustered network patterns in obese participants could be relevant to age-related changes in brain function because regular networks might be less resilient and metabolically inefficient.

Clinical binge eating, but not uncontrolled eating, is associated with differences in executive functions: Evidence from meta-analytic findings.

INTRODUCTION: Binge eating disorder (BED) is a common psychiatric diagnosis characterized by the presence of episodes of loss of control over food consumption. Understanding the neurocognitive factors associated with binge eating pathology might help to design clinical strategies aimed at preventing or treating BED. However, results in the field are notably heterogeneous. In the current study, we aimed to establish whether binge eating behaviors (both at a clinical and at a non-clinical level) are associated with executive functions. METHODS: We performed a pre-registered meta-analysis to examine the link between executive functions, BED, and uncontrolled eating, a psychobiological construct closely associated with binge eating behaviors. Articles were searched on PubMed and the main exclusion criteria were lack of information about participants' age or sex distribution or adiposity measurements, studies performed in older populations (age > 65 years old) or studies including participants with purging symptoms. RESULTS: Relative to healthy controls, patients with BED showed lower performance in executive functions, with a small effect size. At the same time, uncontrolled eating patterns were not associated with differences in executive functions. Neither age nor body mass index (BMI) influenced these results. CONCLUSIONS: Our findings suggest that there is no association between performance in executive functions and variations along the non-clinical spectrum of binge eating behaviors. Small deficits in executive functions, however, seem to appear in individuals showing severe binge eating symptoms, that is, individuals meeting diagnostic criteria for BED. We speculate that the close links between BED and emotional distress could partly explain these results.