RESUMO
Kinase suppressor of Ras 2 (KSR2) is an intracellular scaffolding protein involved in multiple signaling pathways. Targeted deletion of Ksr2 leads to obesity in mice, suggesting a role in energy homeostasis. We explored the role of KSR2 in humans by sequencing 2,101 individuals with severe early-onset obesity and 1,536 controls. We identified multiple rare variants in KSR2 that disrupt signaling through the Raf-MEKERK pathway and impair cellular fatty acid oxidation and glucose oxidation in transfected cells; effects that can be ameliorated by the commonly prescribed antidiabetic drug, metformin. Mutation carriers exhibit hyperphagia in childhood, low heart rate, reduced basal metabolic rate and severe insulin resistance. These data establish KSR2 as an important regulator of energy intake, energy expenditure, and substrate utilization in humans. Modulation of KSR2-mediated effects may represent a novel therapeutic strategy for obesity and type 2 diabetes.
Assuntos
Resistência à Insulina , Obesidade/genética , Proteínas Serina-Treonina Quinases/genética , Fatores Etários , Idade de Início , Sequência de Aminoácidos , Animais , Criança , Metabolismo Energético , Ácidos Graxos/metabolismo , Feminino , Glucose/metabolismo , Humanos , Hiperfagia/genética , Hiperfagia/metabolismo , Sistema de Sinalização das MAP Quinases , Masculino , Camundongos , Modelos Moleculares , Dados de Sequência Molecular , Obesidade/epidemiologia , Obesidade/metabolismo , Oxirredução , Proteínas Serina-Treonina Quinases/química , Proteínas Serina-Treonina Quinases/metabolismo , Estrutura Terciária de Proteína , Proteínas Proto-Oncogênicas B-raf/química , Proteínas Proto-Oncogênicas B-raf/metabolismo , Alinhamento de SequênciaRESUMO
Social isolation and loneliness have potent effects on public health1-4. Research in social psychology suggests that compromised sleep quality is a key factor that links persistent loneliness to adverse health conditions5,6. Although experimental manipulations have been widely applied to studying the control of sleep and wakefulness in animal models, how normal sleep is perturbed by social isolation is unknown. Here we report that chronic, but not acute, social isolation reduces sleep in Drosophila. We use quantitative behavioural analysis and transcriptome profiling to differentiate between brain states associated with acute and chronic social isolation. Although the flies had uninterrupted access to food, chronic social isolation altered the expression of metabolic genes and induced a brain state that signals starvation. Chronically isolated animals exhibit sleep loss accompanied by overconsumption of food, which resonates with anecdotal findings of loneliness-associated hyperphagia in humans. Chronic social isolation reduces sleep and promotes feeding through neural activities in the peptidergic fan-shaped body columnar neurons of the fly. Artificial activation of these neurons causes misperception of acute social isolation as chronic social isolation and thereby results in sleep loss and increased feeding. These results present a mechanistic link between chronic social isolation, metabolism, and sleep, addressing a long-standing call for animal models focused on loneliness7.
Assuntos
Encéfalo/metabolismo , Drosophila melanogaster/metabolismo , Comportamento Alimentar , Modelos Animais , Sono , Isolamento Social , Inanição/metabolismo , Animais , Encéfalo/citologia , Drosophila melanogaster/citologia , Drosophila melanogaster/genética , Feminino , Fome , Hiperfagia/genética , Solidão , Masculino , Neurônios/metabolismo , Sono/genética , Privação do Sono/genética , Privação do Sono/metabolismo , Inanição/genética , Fatores de Tempo , TranscriptomaRESUMO
While common obesity accounts for an increasing global health burden, its monogenic forms have taught us underlying mechanisms via more than 20 single-gene disorders. Among these, the most common mechanism is central nervous system dysregulation of food intake and satiety, often accompanied by neurodevelopmental delay (NDD) and autism spectrum disorder. In a family with syndromic obesity, we identified a monoallelic truncating variant in POU3F2 (alias BRN2) encoding a neural transcription factor, which has previously been suggested as a driver of obesity and NDD in individuals with the 6q16.1 deletion. In an international collaboration, we identified ultra-rare truncating and missense variants in another ten individuals sharing autism spectrum disorder, NDD, and adolescent-onset obesity. Affected individuals presented with low-to-normal birth weight and infantile feeding difficulties but developed insulin resistance and hyperphagia during childhood. Except for a variant leading to early truncation of the protein, identified variants showed adequate nuclear translocation but overall disturbed DNA-binding ability and promotor activation. In a cohort with common non-syndromic obesity, we independently observed a negative correlation of POU3F2 gene expression with BMI, suggesting a role beyond monogenic obesity. In summary, we propose deleterious intragenic variants of POU3F2 to cause transcriptional dysregulation associated with hyperphagic obesity of adolescent onset with variable NDD.
Assuntos
Transtorno do Espectro Autista , Transtornos do Neurodesenvolvimento , Síndrome de Prader-Willi , Adolescente , Humanos , Transtorno do Espectro Autista/genética , Hiperfagia/genética , Hiperfagia/complicações , Transtornos do Neurodesenvolvimento/genética , Obesidade/complicações , Síndrome de Prader-Willi/complicações , Síndrome de Prader-Willi/genética , ProteínasRESUMO
Reproduction induces increased food intake across females of many animal species1-4, providing a physiologically relevant paradigm for the exploration of appetite regulation. Here, by examining the diversity of enteric neurons in Drosophila melanogaster, we identify a key role for gut-innervating neurons with sex- and reproductive state-specific activity in sustaining the increased food intake of mothers during reproduction. Steroid and enteroendocrine hormones functionally remodel these neurons, which leads to the release of their neuropeptide onto the muscles of the crop-a stomach-like organ-after mating. Neuropeptide release changes the dynamics of crop enlargement, resulting in increased food intake, and preventing the post-mating remodelling of enteric neurons reduces both reproductive hyperphagia and reproductive fitness. The plasticity of enteric neurons is therefore key to reproductive success. Our findings provide a mechanism to attain the positive energy balance that sustains gestation, dysregulation of which could contribute to infertility or weight gain.
Assuntos
Drosophila melanogaster/citologia , Drosophila melanogaster/fisiologia , Ingestão de Alimentos/fisiologia , Ingestão de Energia/fisiologia , Mães , Neurônios/metabolismo , Reprodução/fisiologia , Estruturas Animais/citologia , Estruturas Animais/inervação , Estruturas Animais/metabolismo , Animais , Regulação do Apetite/fisiologia , Feminino , Hiperfagia/metabolismo , Masculino , Neuropeptídeos/metabolismoRESUMO
The genotype-phenotype relationship in PWS patients is important for a better understanding of the clinical phenotype and clinical characteristics of different genotypes of PWS in children. We aimed to explore the influence of specific gene changes on the clinical symptoms of PWS and the value of early screening and early intervention of the condition. All data in this study were extracted from the database of the XiaoPang Weili Rare Disease Care Center. The collected information included basic demographics, maternal pregnancy information, endocrine abnormalities, growth and development abnormalities, and other clinical phenotypes. The relationships between genotypes and phenotypes in the major categories of PWS were analyzed. A total of 586 PWS cases with confirmed molecular diagnosis and genotyping were included in this study. Among them, 83.8% belonged to the deletion type, 10.9% the uniparental disomy (UPD) type, and 5.3% the imprinting defect (ID) type. Age-wide comparison among the three groups: The rate of hypopigmentation in the deletion group was higher than that in the UPD group (88.8% vs. 60.9%; p < 0.05); A total of 62 patients (14.2%) had epilepsy; and no statistical significance was found among the three groups (p = 0.110). Age-wide comparison between the deletion and non-deletion types: the rate of skin hypopigmentation and epilepsy in the deletion group was significantly higher than that in the non-deletion group (88.8% vs. 68.4%, p < 0.001; 15.9% vs. 7.6%, p = 0.040). The intergroup comparison for the >2-year age group: there were significant intergroup differences in the language development delay among the three groups (p < 0.001). The incidence of delayed language development was the highest in the deletion group, followed by the UPD group, and the lowest in the ID group. The rates of obesity and hyperphagia in the deletion group were also higher than those in the non-deletion group (71.1% vs. 58.9%, p = 0.041; 75.7% vs. 62.0%, p = 0.016). There are significant differences in the rates of skin hypopigmentation and language developmental delay among the deletion, UPD, and ID genotypes. The patients with deletion type had significantly higher rates of lighter skin color, obesity, hyperphagia, language developmental delay, and epilepsy. The results of this study will help clinicians better understand the impact of different PWS molecular etiologies on specific phenotypes.
Assuntos
Epilepsia , Hipopigmentação , Síndrome de Prader-Willi , Criança , Gravidez , Feminino , Humanos , Síndrome de Prader-Willi/epidemiologia , Síndrome de Prader-Willi/genética , Síndrome de Prader-Willi/diagnóstico , Dissomia Uniparental/genética , Fenótipo , Hiperfagia/complicações , Estudos de Associação Genética , China/epidemiologia , Epilepsia/complicações , Cromossomos Humanos Par 15RESUMO
AIMS: The Diabetes Eating Problems Survey - Revised (DEPS-R) is commonly used to assess disordered eating behaviour (DEB) in individuals with type 1 diabetes and has advantages compared to other measures not specifically tailored to diabetes. A score ≥20 on the DEPS-R is used to indicate clinically significant DEB; however, it does not distinguish between eating disorder (ED) phenotypes necessary to guide treatment decisions, limiting clinical utility. METHODS: The current study used latent class analysis to identify distinct person-centred profiles of DEB in adults with type 1 diabetes using the DEPS-R. Analysis of Variance with Games Howell post-hoc comparisons was then conducted to examine the correspondence between the profiles and binge eating, insulin restriction and glycaemic control (HbA1c, mean blood glucose, and percent time spent in hyperglycaemia) during 3 days of assessment in a real-life setting. RESULTS: Latent class analysis indicated a 4-class solution, with patterns of item endorsement suggesting the following profiles: Bulimia, Binge Eating, Overeating and Low Pathology. Differences in binge eating, insulin restriction and glycaemic control were observed between profiles during 3 days of at-home assessment. The Bulimia profile was associated with highest HbA1c and 3-day mean blood glucose. CONCLUSIONS: There are common patterns of responses on the DEPS-R that appear to reflect different ED phenotypes. Profiles based on the DEPS-R corresponded with behaviour in the real-life setting as expected and were associated with different glycaemic outcomes. Results may have implications for the use of the DEPS-R in research and clinical settings.
Assuntos
Diabetes Mellitus Tipo 1 , Transtornos da Alimentação e da Ingestão de Alimentos , Humanos , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/psicologia , Diabetes Mellitus Tipo 1/complicações , Feminino , Masculino , Adulto , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Transtornos da Alimentação e da Ingestão de Alimentos/sangue , Pessoa de Meia-Idade , Bulimia/psicologia , Glicemia/metabolismo , Insulina/uso terapêutico , Controle Glicêmico , Hemoglobinas Glicadas/metabolismo , Hemoglobinas Glicadas/análise , Análise de Classes Latentes , Comportamento Alimentar/psicologia , Hiperglicemia , Hiperfagia/psicologia , Inquéritos e QuestionáriosRESUMO
Overeating is driven by both the hedonic component ('liking') of food, and the motivation ('wanting') to eat it. The nucleus accumbens (NAc) is a key brain center implicated in these processes, but how distinct NAc cell populations encode 'liking' and 'wanting' to shape overconsumption remains unclear. Here, we probed the roles of NAc D1 and D2 cells in these processes using cell-specific recording and optogenetic manipulation in diverse behavioral paradigms that disentangle reward traits of 'liking' and 'wanting' related to food choice and overeating in healthy mice. Medial NAc shell D2 cells encoded experience-dependent development of 'liking', while D1 cells encoded innate 'liking' during the first food taste. Optogenetic control confirmed causal links of D1 and D2 cells to these aspects of 'liking'. In relation to 'wanting', D1 and D2 cells encoded and promoted distinct aspects of food approach: D1 cells interpreted food cues while D2 cells also sustained food-visit-length that facilitates consumption. Finally, at the level of food choice, D1, but not D2, cell activity was sufficient to switch food preference, programming subsequent long-lasting overconsumption. By revealing complementary roles of D1 and D2 cells in consumption, these findings assign neural bases to 'liking' and 'wanting' in a unifying framework of D1 and D2 cell activity.
Assuntos
Preferências Alimentares , Motivação , Animais , Camundongos , Encéfalo , Alimentos , Hiperfagia , Recompensa , Ingestão de AlimentosRESUMO
Antipsychotic (AP) drugs are efficacious treatments for various psychiatric disorders, but excessive weight gain and subsequent development of metabolic disease remain serious side effects of their use. Increased food intake leads to AP-induced weight gain, but the underlying molecular mechanisms remain unknown. In previous studies, we identified the neuropeptide Agrp and the transcription factor nuclear receptor subfamily 5 group A member 2 (Nr5a2) as significantly upregulated genes in the hypothalamus following AP-induced hyperphagia. While Agrp is expressed specifically in the arcuate nucleus of the hypothalamus and plays a critical role in appetite stimulation, Nr5a2 is expressed in both the CNS and periphery, but its role in food intake behaviors remains unknown. In this study, we investigated the role of hypothalamic Nr5a2 in AP-induced hyperphagia and weight gain. In hypothalamic cell lines, olanzapine treatment resulted in a dose-dependent increase in gene expression of Nr5a2 and Agrp. In mice, the pharmacological inhibition of NR5A2 decreased olanzapine-induced hyperphagia and weight gain, while the knockdown of Nr5a2 in the arcuate nucleus partially reversed olanzapine-induced hyperphagia. Chromatin-immunoprecipitation studies showed for the first time that NR5A2 directly binds to the Agrp promoter region. Lastly, the analysis of single-cell RNA seq data confirms that Nr5a2 and Agrp are co-expressed in a subset of neurons in the arcuate nucleus. In summary, we identify Nr5a2 as a key mechanistic driver of AP-induced food intake. These findings can inform future clinical development of APs that do not activate hyperphagia and weight gain.
Assuntos
Hiperfagia , Animais , Humanos , Camundongos , Proteína Relacionada com Agouti/genética , Proteína Relacionada com Agouti/metabolismo , Proteína Relacionada com Agouti/farmacologia , Antipsicóticos/efeitos adversos , Ingestão de Alimentos , Hiperfagia/induzido quimicamente , Hiperfagia/genética , Hiperfagia/metabolismo , Hipotálamo/metabolismo , Olanzapina/efeitos adversos , Receptores Citoplasmáticos e Nucleares/metabolismo , Receptores Citoplasmáticos e Nucleares/farmacologia , Receptores Citoplasmáticos e Nucleares/uso terapêutico , Aumento de PesoRESUMO
Bardet-Biedl syndrome (BBS) is a rare, monogenic, multisystem disorder characterized by retinal dystrophy, renal abnormalities, polydactyly, learning disabilities, as well as metabolic dysfunction, including obesity and an increased risk of type 2 diabetes. It is a primary ciliopathy, and causative mutations in more than 25 different genes have been described. Multiple cellular mechanisms contribute to the development of the metabolic phenotype associated with BBS, including hyperphagia as a consequence of altered hypothalamic appetite signalling as well as alterations in adipocyte biology promoting adipocyte proliferation and adipogenesis. Within this review, we describe in detail the metabolic phenotype associated with BBS and discuss the mechanisms that drive its evolution. In addition, we review current approaches to the metabolic management of patients with BBS, including the use of weight loss medications and bariatric surgery. Finally, we evaluate the potential of targeting hypothalamic appetite signalling to limit hyperphagia and induce clinically significant weight loss.
Assuntos
Síndrome de Bardet-Biedl , Diabetes Mellitus Tipo 2 , Humanos , Síndrome de Bardet-Biedl/complicações , Síndrome de Bardet-Biedl/genética , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Rim , Hiperfagia/complicações , Hiperfagia/genética , Redução de PesoRESUMO
Hypothalamic obesity (HO) is a rare and complex disorder that confers substantial morbidity and excess mortality. HO is a unique subtype of obesity characterized by impairment in the key brain pathways that regulate energy intake and expenditure, autonomic nervous system function, and peripheral hormonal signalling. HO often occurs in the context of hypothalamic syndrome, a constellation of symptoms that follow from disruption of hypothalamic functions, for example, temperature regulation, sleep-wake circadian control, and energy balance. Genetic forms of HO, including the monogenic obesity syndromes, often impact central leptin-melanocortin pathways. Acquired forms of HO occur as a result of tumours impacting the hypothalamus, such as craniopharyngioma, surgery or radiation to treat those tumours, or other forms of hypothalamic damage, such as brain injury impacting the region. Risk for severe obesity following hypothalamic injury is increased with larger extent of hypothalamic damage or lesions that contain the medial and posterior hypothalamic nuclei that support melanocortin signalling pathways. Structural damage in these hypothalamic nuclei often leads to hyperphagia, central insulin and leptin resistance, decreased sympathetic activity, low energy expenditure, and increased energy storage in adipose tissue, the collective effect of which is rapid weight gain. Individuals with hyperphagia are perpetually hungry. They do not experience fullness at the end of a meal, nor do they feel satiated after meals, leading them to consume larger and more frequent meals. To date, most efforts to treat HO have been disappointing and met with limited, if any, long-term success. However, new treatments based on the distinct pathophysiology of disturbed energy homeostasis in acquired HO may hold promise for the future.
Assuntos
Craniofaringioma , Doenças Hipotalâmicas , Neoplasias Hipofisárias , Humanos , Leptina/metabolismo , Doenças Hipotalâmicas/complicações , Doenças Hipotalâmicas/terapia , Doenças Hipotalâmicas/metabolismo , Obesidade/complicações , Obesidade/terapia , Obesidade/genética , Hipotálamo/metabolismo , Craniofaringioma/complicações , Craniofaringioma/terapia , Craniofaringioma/metabolismo , Hiperfagia , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/patologia , Melanocortinas/metabolismo , Metabolismo Energético/fisiologiaRESUMO
Leptin, a hormone produced in white adipose tissue, acts in the brain to communicate fuel status, suppress appetite following a meal, promote energy expenditure and maintain blood glucose stability1,2. Dysregulation of leptin or its receptors (LEPR) results in severe obesity and diabetes3-5. Although intensive studies on leptin have transformed obesity and diabetes research2,6, clinical applications of the molecule are still limited 7 , at least in part owing to the complexity and our incomplete understanding of the underlying neural circuits. The hypothalamic neurons that express agouti-related peptide (AGRP) and pro-opiomelanocortin (POMC) have been hypothesized to be the main first-order, leptin-responsive neurons. Selective deletion of LEPR in these neurons with the Cre-loxP system, however, has previously failed to recapitulate, or only marginally recapitulated, the obesity and diabetes that are seen in LEPR-deficient Lepr db/db mice, suggesting that AGRP or POMC neurons are not directly required for the effects of leptin in vivo8-10. The primary neural targets of leptin are therefore still unclear. Here we conduct a systematic, unbiased survey of leptin-responsive neurons in streptozotocin-induced diabetic mice and exploit CRISPR-Cas9-mediated genetic ablation of LEPR in vivo. Unexpectedly, we find that AGRP neurons but not POMC neurons are required for the primary action of leptin to regulate both energy balance and glucose homeostasis. Leptin deficiency disinhibits AGRP neurons, and chemogenetic inhibition of these neurons reverses both diabetic hyperphagia and hyperglycaemia. In sharp contrast to previous studies, we show that CRISPR-mediated deletion of LEPR in AGRP neurons causes severe obesity and diabetes, faithfully replicating the phenotype of Lepr db/db mice. We also uncover divergent mechanisms of acute and chronic inhibition of AGRP neurons by leptin (presynaptic potentiation of GABA (γ-aminobutyric acid) neurotransmission and postsynaptic activation of ATP-sensitive potassium channels, respectively). Our findings identify the underlying basis of the neurobiological effects of leptin and associated metabolic disorders.
Assuntos
Glicemia/metabolismo , Metabolismo Energético , Homeostase , Leptina/metabolismo , Vias Neurais/fisiologia , Neurônios/metabolismo , Proteína Relacionada com Agouti/metabolismo , Animais , Peso Corporal , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Ingestão de Alimentos , Feminino , Neurônios GABAérgicos/metabolismo , Edição de Genes , Hiperglicemia/metabolismo , Hiperfagia/fisiopatologia , Masculino , Camundongos , Obesidade/genética , Obesidade/metabolismo , Canais de Potássio/metabolismo , Terminações Pré-Sinápticas/metabolismo , Receptores para Leptina/deficiência , Receptores para Leptina/genética , Receptores para Leptina/metabolismo , Resposta de SaciedadeRESUMO
OBJECTIVE: This pilot study aims to investigate the feasibility, acceptability, and potential effectiveness of online Compassion Focused Therapy for overeating (CFT-OE). METHOD: Eighteen Portuguese women seeking treatment for overeating were enrolled in this study, and 15 participants completed the CFT-OE. This was a single-arm study. Participants were assessed at pre- and post-intervention and 3-month follow-up. All participants completed measures assessing binge eating, cognitive restraint, uncontrolled eating, emotional eating, general eating psychopathology, general and body shame, self-criticism, self-compassion, and fears of self-compassion. RESULTS: The treatment attrition rate was 16.7%, which is relatively low compared to other similar online interventions. Participants gave positive feedback on the program and indicated they would recommend it to people with similar difficulties. CFT-OE improved self-compassion and reduced eating psychopathology symptoms, general and body shame, self-criticism, and fears of self-compassion. Clinical significance analysis showed that the majority of participants were classified as in recovery in all measures at post-intervention and 3-month follow-up. DISCUSSION: Preliminary results suggest that the online CFT-OE program is an acceptable and feasible intervention. Results also suggest that CFT-OE is beneficial for the treatment of women with difficulties with overeating. A future randomized controlled trial is necessary to establish the effectiveness of the CFT-OE. PUBLIC SIGNIFICANCE: This study indicates that online CFT-OE is a feasible and adequate intervention for women who struggle with overeating. This therapy showed promising results in reducing eating disorder symptoms, shame, and self-criticism and improving self-compassion. As an online intervention, CFT-OE may be more accessible and offer an alternative to in-person therapy.
Assuntos
Emoções , Empatia , Humanos , Feminino , Projetos Piloto , Estudos de Viabilidade , Hiperfagia/terapiaRESUMO
OBJECTIVE: Theories propose that low self-esteem and problematic eating behaviors (PEBs) negatively impact each other. While previous studies suggested bidirectional associations between self-esteem and PEBs, they did not separate within-person from between-person associations. Therefore, this prospective study investigated the within-person bidirectional associations between self-esteem and four PEBs in adolescence, while accounting for between-person differences. METHOD: We used two independent longitudinal samples of Dutch adolescents, each including three annually collected waves of data. Sample 1 consisted of 1856 adolescents (Baseline: 50.4% males; Mage = 13.79 years, SDage = 0.72), with measures of self-esteem, emotional eating, restrained eating, and loss of control (LOC) while overeating. Sample 2 consisted of 555 adolescents (Baseline: 49.7% males; Mage = 13.13 years, SDage = 0.68), with measures of self-esteem and LOC eating. The data were analyzed using random intercept cross-lagged panel models (CLPMs). RESULTS: Within persons, lower self-esteem was associated with higher emotional and restrained eating (both Sample 1) one year later, and vice versa. Self-esteem did not predict, nor was predicted by, LOC while overeating (Sample 1) or LOC eating (Sample 2). Between persons, self-esteem was negatively correlated with all PEBs (Samples 1 and 2). DISCUSSION: We found within-person bidirectional associations between low self-esteem and emotional and restrained eating (but not LOC while overeating/LOC eating), and between-person correlations between low self-esteem and all PEBs. These results have theoretical and practical implications. Within-person processes clarify underlying mechanisms that explain the occurrence of PEBs; between-person associations are important to identify adolescents at risk of PEBs. PUBLIC SIGNIFICANCE: While theories indicate that low self-esteem and PEBs are inversely associated within individuals, empirical studies have not disentangled within-person processes from between-person differences. This study addressed this disparity, finding that lower self-esteem was bidirectionally associated with higher emotional and restrained eating (but not LOC eating) within persons. These findings suggest that enhancing self-esteem is a viable option for prevention and intervention.
Assuntos
Hiperfagia , Autoimagem , Masculino , Humanos , Adolescente , Lactente , Feminino , Estudos Prospectivos , Hiperfagia/psicologia , Emoções , Comportamento Alimentar/psicologiaRESUMO
BACKGROUND: Children with loss of control (LOC) eating and overweight/obesity have relative deficiencies in trait-level working memory (WM), which may limit adaptive responding to intra- and extra-personal cues related to eating. Understanding of how WM performance relates to eating behavior in real-time is currently limited. METHODS: We studied 32 youth (ages 10-17 years) with LOC eating and overweight/obesity (LOC-OW; n = 9), overweight/obesity only (OW; n = 16), and non-overweight status (NW; n = 7). Youth completed spatial and numerical WM tasks requiring varying degrees of cognitive effort and reported on their eating behavior daily for 14 days via smartphone-based ecological momentary assessment. Linear mixed effects models estimated group-level differences in WM performance, as well as associations between contemporaneously completed measures of WM and dysregulated eating. RESULTS: LOC-OW were less accurate on numerical WM tasks compared to OW and NW (ps < .01); groups did not differ on spatial task accuracy (p = .41). Adjusting for between-subject effects (reflecting differences between individuals in their mean WM performance and its association with eating behavior), within-subject effects (reflecting variations in moment-to-moment associations) revealed that more accurate responding on the less demanding numerical WM task, compared to one's own average, was associated with greater overeating severity across the full sample (p = .013). There were no associations between WM performance and LOC eating severity (ps > .05). CONCLUSIONS: Youth with LOC eating and overweight/obesity demonstrated difficulties mentally retaining and manipulating numerical information in daily life, replicating prior laboratory-based research. Overeating may be related to improved WM, regardless of LOC status, but temporality and causality should be further explored. PUBLIC SIGNIFICANCE STATEMENT: Our findings suggest that youth with loss of control eating and overweight/obesity may experience difficulties mentally retaining and manipulating numerical information in daily life relative to their peers with overweight/obesity and normal-weight status, which may contribute to the maintenance of dysregulated eating and/or elevated body weight. However, it is unclear whether these individual differences are related to eating behavior on a moment-to-moment basis.
Assuntos
Memória de Curto Prazo , Sobrepeso , Criança , Humanos , Adolescente , Sobrepeso/psicologia , Avaliação Momentânea Ecológica , Obesidade/psicologia , Hiperfagia/psicologia , Comportamento Alimentar/psicologia , Ingestão de Alimentos/psicologiaRESUMO
Individuals with Down syndrome (DS) have a higher prevalence of obesity compared to the general population. Conventionally, this has been attributed to endocrine issues and lack of exercise. However, deficits in neural reward responses and dopaminergic disturbances in DS may be contributing factors. To investigate this, we focused on a mouse model (Ts65Dn) bearing some triplicated genes homologous to trisomy 21. Through detailed meal pattern analysis in male Ts65Dn mice, we observed an increased preference for energy-dense food, pointing towards a potential "hedonic" overeating behavior. Moreover, trisomic mice exhibited higher scores in compulsivity and inflexibility tests when limited access to energy-dense food and quinine hydrochloride adulteration were introduced, compared to euploid controls. Interestingly, when we activated prelimbic-to-nucleus accumbens projections in Ts65Dn male mice using a chemogenetic approach, impulsive and compulsive behaviors significantly decreased, shedding light on a promising intervention avenue. Our findings uncover a novel mechanism behind the vulnerability to overeating and offer potential new pathways for tackling obesity through innovative interventions.
Assuntos
Síndrome de Down , Trissomia , Humanos , Masculino , Camundongos , Animais , Síndrome de Down/genética , Modelos Animais de Doenças , Córtex Pré-Frontal , Hiperfagia/genética , Obesidade/genéticaRESUMO
BACKGROUND: About 40% of people respond to stress by consuming more unhealthy foods. This behavior is associated with increased energy intake and the risk of obesity. As mobile health (mHealth) applications (apps) have been shown to be an easy-to-use intervention tool, the characterization of potential app users is necessary to develop target group-specific apps and to increase adherence rates. METHODS: This cross-sectional online survey was conducted in the spring of 2021 in Germany. Sociodemographic data and data on personality (Big Five Inventory, BFI-10), stress-eating (Salzburg Stress Eating Scale, SSES), and technology behavior (Personal Innovativeness in the Domain of Information Technology, PIIT; Technology Acceptance Model 3, TAM 3) were collected. RESULTS: The analysis included 1228 participants (80.6% female, mean age: 31.4 ± 12.8 years, mean body mass index (BMI): 23.4 ± 4.3 kg/m2). Based on the TAM score, 33.3% (409/1228) of the participants had a high intention to use a hypothetical mHealth app to avoid stress-overeating. These persons are characterized by a higher BMI (24.02 ± 4.47 kg/m2, p < 0.001), by being stress-overeaters (217/409, 53.1%), by the personality trait "neuroticism" (p < 0.001), by having specific eating reasons (all p < 0.01), and by showing a higher willingness to adopt new technologies (p < 0.001). CONCLUSION: This study suggests that individuals who are prone to stress-overeating are highly interested in adopting an mHealth app as support. Participants with a high intention to use an mHealth app seem to have a general affinity towards new technology (PIIT) and appear to be more insecure with conflicting motives regarding their diet. TRIAL REGISTRATION: This survey was registered in the German Clinical Trials Register (Registration number: DRKS00023984).
Assuntos
Aplicativos Móveis , Telemedicina , Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto Jovem , Estudos Transversais , Hiperfagia , ObesidadeRESUMO
BACKGROUND: Low-diversity diets and sedentary status are risk factors for depressive symptoms, while knowledge workers were ignored before. The purpose of this current study was to examine the relationship between dietary diversity, sedentary time spent outside of work, and depressive symptoms among knowledge workers. STUDY DESIGN AND METHODS: This was a multicenter and cross-sectional design that included 118,723 knowledge workers. Participants self-reported online between January 2018 and December 2020. Demographic information, the Dietary Diversity Scale, the Patient Health Questionnaire-9, dietary habits (which included eating three meals on time, midnight snacking, overeating, social engagement, coffee consumption, sugary drink consumption, smoking and alcohol use), sedentary time spent outside of work and physical activity were investigated. RESULTS: The relationships between demographic information, dietary habits and dietary diversity, and depressive symptoms were estimated. Compared with the first and second levels of dietary diversity, the third level of dietary diversity (OR: 0.91; 95% CI: 0.84-0.98) reduced the risk of depressive symptoms. Knowledge workers with different degrees of sedentary status (2-4 h (OR: 1.11; 95% CI: 1.07-1.14), 4-6 h (OR: 1.21; 95% CI: 1.17-1.26), and > 6 h (OR: 1.49; 95% CI: 1.43-1.56), presented a progressively higher risk of depressive symptoms. CONCLUSION: High amounts of sedentary time spent after work and low levels of dietary diversity are risk factors for depressive symptoms. In addition, an irregular diet and overeating are also major risk factors for knowledge workers.
Assuntos
Depressão , Comportamento Sedentário , Humanos , Depressão/epidemiologia , Depressão/etiologia , Estudos Transversais , Dieta , HiperfagiaRESUMO
Feeling fat and fear of weight gain are key cognitive-affective symptoms that are theorized to maintain eating disorders (EDs). Little research has examined the dynamic relationships among feeling fat, fear of weight gain, emotions, cognitions, and ED behaviors. Furthermore, it is unknown if these relations vary by ED diagnosis (e.g., anorexia nervosa (AN) vs other ED). The current study (N = 94 ED participants; AN n = 64) utilized ecological momentary assessments collected four times a day for 18 days (72 timepoints) asking about feeling fat, fear of weight gain, emotions (i.e., anxiety, guilt), cognitions (i.e., feelings of having overeaten, thoughts about dieting), and ED behaviors (i.e., vomiting, diuretic/laxative use, excessive exercise, body checking, self-weighing, binge-eating, restriction) at stressful timepoints (contemporaneous [mealtime], and prospective/temporal [next-meal]). Multilevel modeling was used to test for between and within-person associations. Higher feeling fat and fear of weight gain independently predicted higher next-meal emotions (i.e., anxiety, guilt), cognitions (i.e., feelings of having overeaten, thoughts about dieting, fear of weight gain, feeling fat), and ED behaviors (i.e., body checking, self-weighing [feeling fat]). There were relationships in the opposite direction, such that some emotions, cognitions, and ED behaviors prospectively predicted feeling fat and fear of weight gain, suggesting existence of a reciprocal cycle. Some differences were found via diagnosis. Findings pinpoint specific dynamic and cyclical relationships among feeling fat, fear of weight gain, and specific ED symptoms, and suggest the need for more research on how feeling fat, fear of weight gain and cognitive-affective-behavioral aspects of ED operate. Future research can test if treatment interventions targeted at feeling fat and fear of weight gain may disrupt these cycles.
Assuntos
Transtorno da Compulsão Alimentar , Transtornos da Alimentação e da Ingestão de Alimentos , Humanos , Estudos Prospectivos , Emoções , Medo , Aumento de Peso , HiperfagiaRESUMO
During adolescence, processes that control food intake (executive functions [EF]) undergo extensive refinement; underlying differences in EF may explain the inability to resist overeating unhealthy foods. Yet, overeating fat and sugar also causes changes to EF and cognition but disentangling these relationships has been difficult, as previous studies included youth with obesity. Here, amongst youth initially of a healthy weight, we evaluate whether 1) sex-specific underlying variation in EF/cognition at 9/10-years-old predict fat/sugar two-years later (Y2) and 2) if these relationships are moderated by body mass index (BMI), using linear mixed effects models (controlled for puberty, caregiver education; random effect: study site). Data were leveraged from Adolescent Brain Cognitive Development Study (n = 2987; 50.4% male; 15.4% Latino/a/x; 100% healthy weight at baseline; 12.4% overweight/obese by Y2, data release 4.0). EF and cognition (e.g., inhibition, cognition, motor, memory, impulsivity) were assessed with the NIH toolbox, Rey Auditory Verbal Learning Task, Little Man Task, the BIS/BAS, and UPPS-P. A saturated fat/added sugar (kcals) composite score was extracted from the validated Kids Food Block Screener. For males, greater baseline impulsivity (e.g., Positive Urgency, Lack of Planning and Perseverance) and reward (e.g., Fun seeking, Drive) was related to greater Y2 intake. For both sexes, greater baseline Negative Urgency and higher BMI was related to greater Y2 intake. No other relationships were observed. Our findings highlight a phenotype that may be more at risk for weight gain due to overconsumption of fat/sugar. Thus, prevention efforts may wish to focus on impulsive tendencies for these foods.
Assuntos
Função Executiva , Obesidade , Feminino , Humanos , Masculino , Adolescente , Criança , Obesidade/psicologia , Comportamento Impulsivo , Hiperfagia , AçúcaresRESUMO
Distraction during eating contributes to overeating, and when habitually eating with distraction, this may contribute to the development of obesity. One of the proposed mediating mechanisms is the suppression of intensity perception in odor and taste. The effect of distraction on fat intensity perception in flavor, the multisensory combination of odor, taste, and other sensory aspects, is still unknown. In this study, 32 participants (22 women) performed a flavor perception task while also performing a distracting working memory task. In each trial, participants were instructed to observe and memorize a string of 3 (low cognitive load) or 7 (high cognitive load) consonants. Then they received a small quantity of a high- or low-fat chocolate drink, and after that, they were asked to select the string they tried to memorize from three answer options. Last, they rated the intensity and fattiness of the flavor. As intended, in the working memory task, we observed that with a high cognitive load (relative to a low cognitive load), accuracy decreased and response times increased. Regarding perception of the flavors, we observed that overall, high-fat drinks were rated as more intense and fattier. Cognitive load and fat content interacted, such that for the low-fat drink, intensity and fattiness ratings were similar under both cognitive loads; however, under the high cognitive load (relative to the low cognitive load), intensity and fattiness ratings for the high-fat drink were lower. Our results show that distraction can impact the perception of fat in high-fat drinks. If distraction primarily reduces perception of high-fat foods, this may pose a particular risk of overeating high-calorie foods.