Affect Food Intake Research Articles

The role of apelinergic system in metabolism and reproductive system in normal and pathological conditions: an overview.

Lifestyle changes have made metabolic disorders as one of the major threats to life. Growing evidence demonstrates that obesity and diabetes disrupt the reproductive system by affecting the gonads and the hypothalamus-pituitary-gonadal (HPG) axis. Apelin, an adipocytokine, and its receptor (APJ) are broadly expressed in the hypothalamus nuclei, such as paraventricular and supraoptic, where gonadotropin-releasing hormone (GnRH) is released, and all three lobes of the pituitary, indicating that apelin is involved in the control of reproductive function. Moreover, apelin affects food intake, insulin sensitivity, fluid homeostasis, and glucose and lipid metabolisms. This review outlined the physiological effects of the apelinergic system, the relationship between apelin and metabolic disorders such as diabetes and obesity, as well as the effect of apelin on the reproductive system in both gender. The apelin-APJ system can be considered a potential therapeutic target in the management of obesity-associated metabolic dysfunction and reproductive disorders.

POLA MAKAN DAN STATUS GIZI REMAJA DI DESA ADAT BUNGAYA KABUPATEN KARANGASEM

Nutrition is one of the most important factors and major development determinants of teenager growth, as in adolescence, the hormonal changes that cause the rapid growth of other phases in life except the first year of life. This research aimed to investigate the dietary habit and teenager's nutritional status at Bungaya Traditional Village, Karangasem Regency. This research method used cross sectional method. The samples of research were 41 teenager with an age range of 13-18 years old who are living at Dusun Beji in Bungaya Village, Karangasem Regency. Dietary habbit was umeasured by the Food Recall 1x24 hours and nutritional status of BMI. Data analysis describe according to the purpose. The results showed as much of 41 total samples of 34 samples (82.9%) had dietary habit in the good diet pattern categories with a tendency to have a normal nutritional status were 20 people (58.8%) of the total sample with a good diet habbt. Obeses was 7 samples (20.6%), overweight was 6 samples (17.6%) and thinness was 1 sample (2.9%). While the sample with enough dietary habbit as many as 7 people consisted of 5 samples (71.4%) with normlal nutritional status and 2 samples (28.6% ) of the total sampelts with enough dietary habbit included in thinness. Food frequency, type and amount of food will affect food intake which will have an impact on nutritional status. Then there needs to be improvements in food consumption both in quantity and quality and variety of food menus. Meal frequency, type and amount of food would affect food intake that have an impact on nutritional status. So it needed for improvements in dietary habit both in quantity and quality and variety of the food menu.Keywords : Dietary habbit, Nutritional status, Teenagers

Adipocyte-Derived PXR Signaling Is Dispensable for Diet-Induced Obesity and Metabolic Disorders in Mice.

Pregnane X receptor (PXR) is a xenobiotic receptor that can be activated by numerous chemicals including endogenous hormones, dietary steroids, pharmaceutical agents, and environmental chemicals. PXR has been established to function as a xenobiotic sensor to coordinately regulate xenobiotic metabolism by regulating the expression of many enzymes and transporters required for xenobiotic metabolism. Recent studies have implicated a potentially important role for PXR in obesity and metabolic disease beyond xenobiotic metabolism, but how PXR action in different tissues or cell types contributes to obesity and metabolic disorders remains elusive. To investigate the role of adipocyte PXR in obesity, we generated a novel adipocyte-specific PXR deficient mouse model (PXRΔAd). Notably, we found that loss of adipocyte PXR did not affect food intake, energy expenditure, and obesity in high-fat diet-fed male mice. PXRΔAd mice also had similar obesity-associated metabolic disorders including insulin resistance and hepatic steatosis as control littermates. PXR deficiency in adipocytes did not affect expression of key adipose genes in PXRΔAd mice. Our findings suggest that adipocyte PXR signaling may be dispensable in diet-induced obesity and metabolic disorders in mice. Further studies are needed to understand the role of PXR signaling in obesity and metabolic disorders in the future. SIGNIFICANCE STATEMENT: The authors demonstrate that deficiency of adipocyte pregnane X receptor (PXR) does not affect diet-induced obesity or metabolic disorders in mice and infers that adipocyte PXR signaling may not play a key role in diet-induced obesity. More studies are needed to understand the tissue-specific role of PXR in obesity.

Renal function is a major predictor of circulating acyl-CoA-binding protein/diazepam-binding inhibitor.

Acyl-CoA-binding protein (ACBP)/diazepam-binding inhibitor has lately been described as an endocrine factor affecting food intake and lipid metabolism. ACBP is dysregulated in catabolic/malnutrition states like sepsis or systemic inflammation. However, regulation of ACBP has not been investigated in conditions with impaired kidney function, so far. Serum ACBP concentrations were investigated by enzyme-linked immunosorbent assay i) in a cohort of 60 individuals with kidney failure (KF) on chronic haemodialysis and compared to 60 individuals with a preserved kidney function; and ii) in a human model of acute kidney dysfunction (AKD). In addition, mACBP mRNA expression was assessed in two CKD mouse models and in two distinct groups of non-CKD mice. Further, mRNA expression of mACBP was measured in vitro in isolated, differentiated mouse adipocytes - brown and white - after exposure to the uremic agent indoxyl sulfate. Median [interquartile range] serum ACBP was almost 20-fold increased in KF (514.0 [339.3] µg/l) compared to subjects without KF (26.1 [39.1] µg/l) (p<0.001). eGFR was the most important, inverse predictor of circulating ACBP in multivariate analysis (standardized β=-0.839; p<0.001). Furthermore, AKD increased ACBP concentrations almost 3-fold (p<0.001). Increased ACBP levels were not caused by augmented mACBP mRNA expression in different tissues of CKD mice in vivo or in indoxyl sulfate-treated adipocytes in vitro. Circulating ACBP inversely associates with renal function, most likely through renal retention of the cytokine. Future studies need to investigate ACBP physiology in malnutrition-related disease states, such as CKD, and to adjust for markers of renal function.

Nutritional Status and Factors affecting Food Intake among Hospitalised Patients in Hospital Al-Sultan Abdullah

Hospital food intake can impact patients' nutritional status, resulting in a lengthier hospital stay or a higher mortality rate. This study aimed to investigate the nutritional status and the factors influencing the food intake of patients at Hospital Al-Sultan Abdullah (HASA). Malnutrition risk was assessed using Nutritional Risk Screening 2002, and factors affecting food intake were investigated using a questionnaire. Participants' weight and height were estimated using the anthropometry assessment formula. The body mass index was 25.3 ± 8.1 kg/m2 and 70.6% (113) posed no risk of malnutrition. Food tasting differently (48.8%) was the highest affecting factor in food intake.

Association of Protein Intake with Recurrence and Survival Following Primary Treatment of Ovarian Cancer

BackgroundMalnutrition is common during treatment of ovarian cancer, and 1 in 3 patients report multiple symptoms affecting food intake after primary treatment. Little is known about diet posttreatment in relation to ovarian cancer survival; however, general recommendations for cancer survivors are to maintain a higher level of protein intake to support recovery and minimize nutritional deficits. ObjectivesTo investigate whether intake of protein and protein food sources following primary treatment of ovarian cancer is associated with recurrence and survival. MethodsIntake levels of protein and protein food groups were calculated from dietary data collected ∼12 mo postdiagnosis using a validated FFQ in an Australian cohort of women with invasive epithelial ovarian cancer. Disease recurrence and survival status were abstracted from medical records (median 4.9 y follow-up). Cox proportional hazards regression was used to calculate adjusted HRs and 95% CIs for protein intake and progression-free and overall survival. ResultsAmong 591 women who were progression-free at 12 mo follow-up, 329 (56%) subsequently experienced cancer recurrence and 231 (39%) died. A higher level of protein intake was associated with better progression-free survival (>1–1.5 compared with ≤1 g/kg body weight, HRadjusted: 0.69, 95% CI: 0.48, 1.00; >1.5 compared with ≤1 g/kg, HRadjusted: 0.61, 95% CI: 0.41, 0.90; >20% compared with ≤20% total EI from protein, HRadjusted: 0.77, 95% CI: 0.61, 0.96). There was no evidence for better progression-free survival with any particular protein food sources. There was a suggestion of better overall survival among those with higher total intakes of animal-based protein foods, particularly dairy products (HR: 0.71; 95% CI: 0.51, 0.99 for highest compared with lowest tertiles of total dairy intake). ConclusionsAfter primary treatment of ovarian cancer, a higher level of protein intake may benefit progression-free survival. Ovarian cancer survivors should avoid dietary practices that limit intake of protein-rich foods.

The administration of Exendin-4 and CCK affects food intake differentially in female and male rats tested on an alternate day fasting paradigm

Alternate day fasting (ADF) which involves the repetition of a 2-day cycle of a day of free access to food followed by a day of limited or no access to food, is an effective dietary intervention for weight loss in both humans and rats. We have previously reported that when presented with a high energy (HE) and standard chow diet, rats maintained on an ADF schedule displayed decreased HE diet preference compared to controls. Both male and female ADF rats increased overall intake of chow. However, this increase was driven by both meal size and meal number for males and only number of meals for females. Administration of cholecystokinin (CCK) or the glucagon-like peptide 1 (GLP-1) receptor agonist Exendin-4 (Ex-4) reduces food intake. It appears that CCK decreases food intake primarily through satiety signals whereas GLP-1 signaling may reduce intake by satiety and reward cues. Here, female and male rats were administered (i.p.) saline, 3.0 µg/kg Ex-4 (3 h before test), 3.0 µg/kg CCK (15 min before test) or a combination of both. Next, all rats were presented 23-h access to both HE diet and chow following food-restriction (ADF) or free access to chow (CON). Compared to saline-control sessions, administration of the combination of Ex-4 and CCK, but not Ex-4 or CCK alone, resulted in a decrease in both HE and chow intake early in the session for male ADF rats but the combination primarily decreased chow diet intake early in the session for female ADF rats. Thus, it appears that under these energy homeostatic conditions, administration of Ex-4 or CCK alone does not affect intake in ADF rats, but the combination produces decreases in feeding that are more than the sum of their individual effects. These findings support a role for the combination of GLP-1 and CCK signaling in the changes in diet preference induced by an alternate day fasting paradigm differentially in female and male rats.

The traditional herbal medicines mixture, Banhasasim-tang, relieves the symptoms of irritable bowel syndrome via modulation of TRPA1, NaV1.5 and NaV1.7 channels

Ethnopharmacological relevance: The cause of irritable bowel syndrome (IBS), a functional gastrointestinal (GI) disorder, remains unclear. Banhasasim-tang (BHSST), a traditional herbal medicines mixture, mainly used to treat GI-related diseases, may have a potential in IBS treatment. IBS is characterized by abdominal pain as the main clinical symptom, which seriously affects the quality of life. Aim of the study: We conducted a study to evaluate the effectiveness of BHSST and its mechanisms of action in treating IBS. Materials and methods: We evaluated the efficacy of BHSST in a zymosan-induced diarrhea-predominant animal model of IBS. Electrophysiological methods were used to confirm modulation of transient receptor potential (TRP) and voltage-gated Na+ (NaV) ion channels, which are associated mechanisms of action. Results: Oral administration of BHSST decreased colon length, increased stool scores, and increased colon weight. Weight loss was also minimized without affecting food intake. In mice administered with BHSST, the mucosal thickness was suppressed, making it similar to that of normal mice, and the degree of tumor necrosis factor-α was severely reduced. These effects were similar to those of the anti-inflammatory drug—sulfasalazine—and antidepressant—amitriptyline. Moreover, pain-related behaviors were substantially reduced. Additionally, BHSST inhibited TRPA1, NaV1.5, and NaV1.7 ion channels associated with IBS-mediated visceral hypersensitivity. Conclusions: In summary, the findings suggest that BHSST has potential beneficial effects on IBS and diarrhea through the modulation of ion channels.

Daily intranasal insulin at 40IU does not affect food intake and body composition: A placebo-controlled trial in older adults over a 24-week period with 24-weeks of follow-up

Centrally administered insulin stimulates the reward system to reduce appetite in response to food intake in animal studies. In humans, studies have shown conflicting results, with some studies suggesting that intranasal insulin (INI) in relatively high doses may decrease appetite, body fat, and weight in various populations. These hypotheses have not been tested in a large longitudinal placebo-controlled study. Participants in the Memory Advancement with Intranasal Insulin in Type 2 Diabetes (MemAID) trial were enrolled in this study. This study on energy homeostasis enrolled 89 participants who completed baseline and at least 1 intervention visit (42 women; age 65±9 years; 46 INI, 38 with type 2 diabetes) and 76 completed treatment (16 women, age 64±9; 38 INI, 34 with type 2 diabetes). The primary outcome was the INI effect on food intake. Secondary outcomes included the effect of INI on appetite and anthropometric measures, including body weight and body composition. In exploratory analyses, we tested the interaction of treatment with gender, body mass index (BMI), and diagnosis of type 2 diabetes. There was no INI effect on food intake or any of the secondary outcomes. INI also showed no differential effect on primary and secondary outcomes when considering gender, BMI, and type 2 diabetes. INI did not alter appetite or hunger nor cause weight loss when used at 40 I.U. intranasally daily for 24 weeks in older adults with and without type 2 diabetes.

Upregulation of Tribbles decreases body weight and increases sleep duration.

Eukaryotic Tribbles proteins are pseudoenzymes that regulate multiple aspects of intracellular signalling. Both Drosophila melanogaster and mammalian members of this family of pseudokinases act as negative regulators of insulin signalling. Mammalian tribbles pseudokinase (TRIB) genes have also been linked to insulin resistance and type 2 diabetes mellitus. Type 2 diabetes mellitus is associated with increased body weight, sleep problems and increased long-term mortality. Here, we investigated how manipulating the expression of Tribbles impacts body weight, sleep and mortality. We showed that the overexpression of Drosophila tribbles (trbl) in the fly fat body reduces both body weight and lifespan in adult flies without affecting food intake. Furthermore, it decreases the levels of Drosophila insulin-like peptide 2 (DILP2; ILP2) and increases night-time sleep. The three genes encoding TRIBs of mammals, TRIB1, TRIB2 and TRIB3, show both common and unique features. As the three human TRIB genes share features with Drosophila trbl, we further explored the links between TRIB genetic variants and both body weight and sleep in the human population. We identified associations between the polymorphisms and expression levels of the pseudokinases and markers of body weight and sleep duration. We conclude that Tribbles pseudokinases are involved in the control of body weight, lifespan and sleep.

Chronic environmental circadian disruption increases atherosclerosis and dyslipidemia in female, but not male, ApolipoproteinE-deficient mice.

Shift work chronically disrupts circadian rhythms and increases the risk of developing cardiovascular disease. However, the mechanisms linking shift work and cardiovascular disease are largely unknown. The goal of this study was to investigate the effects of chronically shifting the light-dark (LD) cycle, which models the disordered exposure to light that may occur during shift work, on atherosclerosis. Atherosclerosis is the progressive accumulation of lipid-filled lesions within the artery wall and is the leading cause of cardiovascular disease. We studied ApolipoproteinE-deficient (ApoE -/- ) mice that are a well-established model of atherosclerosis. Male and female ApoE -/- mice were housed in control 12L:12D or chronic LD shift conditions for 12weeks and fed low-fat diet. In the chronic LD shift condition, the light-dark cycle was advanced by 6h every week. We found that chronic LD shifts exacerbated atherosclerosis in female, but not male, ApoE -/- mice. In females, chronic LD shifts increased total serum cholesterol concentrations with increased atherogenic VLDL/LDL particles. Chronic LD shifts did not affect food intake, activity, or body weight in male or female ApoE -/- mice. We also examined eating behavior in female ApoE -/- mice since aberrant meal timing has been linked to atherosclerosis. The phases of eating behavior rhythms, like locomotor activity rhythms, gradually shifted to the new LD cycle each week in the chronic LD shift group, but there was no effect of the LD shift on the amplitudes of the eating rhythms. Moreover, the duration of fasting intervals was not different in control 12L:12D compared to chronic LD shift conditions. Together these data demonstrate that female ApoE -/- mice have increased atherosclerosis when exposed to chronic LD shifts due to increased VLDL/LDL cholesterol, independent of changes in energy balance or feeding-fasting cycles.

Orexin induces the production of an endocannabinoid-derived lysophosphatidic acid eliciting hypothalamic synaptic loss in obesity

ObjectiveOrexin-A (OX-A) is a neuropeptide produced selectively by neurons of the lateral hypothalamus. It exerts powerful control over brain function and physiology by regulating energy homeostasis and complex behaviors linked to arousal. Under conditions of chronic or acute brain leptin signaling deficiency, such as in obesity or short-term food deprivation, respectively, OX-A neurons become hyperactive and promote hyperarousal and food seeking. However, this leptin-dependent mechanism is still mostly unexplored. The endocannabinoid 2-arachidonoyl-glycerol (2-AG) is known to be implicated in food consumption by promoting hyperphagia and obesity, and we and others demonstrated that OX-A is a strong inducer of 2-AG biosynthesis. Here, we investigated the hypothesis that, under acute (6 h fasting in wt mice) or chronic (in ob/ob mice) hypothalamic leptin signaling reduction, OX-A-induced enhancement of 2-AG levels leads to the production of the 2-AG-derived 2-arachidonoyl-sn-glycerol-3-phosphate (2-AGP), a bioactive lipid belonging to the class of lysophosphatidic acids (LPAs), which then regulates hypothalamic synaptic plasticity by disassembling α-MSH anorexigenic inputs via GSK-3β-mediated Tau phosphorylation, ultimately affecting food intake. MethodsWe combined cell-type-specific morphological (CLEM and confocal microscopy), biochemical, pharmacological, and electrophysiological techniques to dissect the leptin- and OX-A/2-AGP-mediated molecular pathways regulating GSK-3β-controlled pT231-Tau production at POMC neurons of obese ob/ob and wild-type (wt) lean littermate mice and in an in vitro model of POMC neurons such as mHypoN41 neurons (N41). Results2-AGP is overproduced in the hypothalamus of obese leptin-deficient, or lean 6 h food-deprived mice, and promotes food intake by reducing α-MSH-expressing synaptic inputs to OX-A neurons via lysophosphatidic acid type-1 receptor (LPA1-R) activation, and pT231-Tau accumulation in α-MSH projections. This effect is due to the activation of the Pyk2-mediated pTyr216-GSK3β pathway and contributes to further elevating OX-A release in obesity. Accordingly, we found a strong correlation between OX-A and 2-AGP levels in the serum of obese mice and of human subjects. ConclusionsHypothalamic feeding pathways are endowed with 2-AGP-mediated synaptic plasticity according to their inherent functional activities and the necessity to adapt to changes in the nutritional status. These findings reveal a new molecular pathway involved in energy homeostasis regulation, which could be targeted to treat obesity and related disturbances.

Maternal overnutrition is associated with altered synaptic input to lateral hypothalamic area

ObjectiveMaternal overnutrition is associated with adverse outcomes in offspring, including increased risk for obesity and diabetes. Here, we aim to test the effects of maternal obesity on lateral hypothalamic feeding circuit function and determine the relationship with body weight regulation. MethodsUsing a mouse model of maternal obesity, we assessed how perinatal overnutrition affected food intake and body weight regulation in adult offspring. We then used channelrhodopsin-assisted circuit mapping and electrophysiological recordings to assess the synaptic connectivity within an extended amygdala-lateral hypothalamic pathway. ResultsWe show that maternal overnutrition during gestation and throughout lactation produces offspring that are heavier than controls prior to weaning. When weaned onto chow, the body weights of over-nourished offspring normalize to control levels. However, when presented with highly palatable food as adults, both male and female maternally over-nourished offspring are highly susceptible to diet-induced obesity. This is associated with altered synaptic strength in an extended amygdala-lateral hypothalamic pathway, which is predicted by developmental growth rate. Additionally, lateral hypothalamic neurons receiving synaptic input from the bed nucleus of the stria terminalis have enhanced excitatory input following maternal overnutrition which is predicted by early life growth rate. ConclusionsTogether, these results demonstrate one way in which maternal obesity rewires hypothalamic feeding circuits to predispose offspring to metabolic dysfunction.

Do categorically distinct stressors alter the attention to visual food cues?

Stressor exposure affects food intake as well as the preference for high or low palatability foods, but little is known about how stressor types impact the visual attention to food images. We used eye tracking methodology in humans to determine if activation of the hypothalamus–pituitary-adrenal (HPA) axis and sympathetic nervous system is associated with changes in attention to food images as determined by measuring changes in oculomotor activity. Specifically, we tested two questions: 1) Do categorically distinct stressors alter aspects of visual attention to food images as determined by oculomotor activity (i.e., saccade latency, gaze duration, and saccade bouts)? 2) Do categorically distinct stressors differentially affect visual attention to food images of high or low palatability? A total of sixty participants were randomly divided into one of three test groups: controls, an anticipatory stressor group, or a reactive stressor group. We measured salivary cortisol and salivary alpha-amylase (sAA) before and after stressor exposure to confirm activation of the HPA axis and sympathetic nervous system, respectively. Following stressor exposure participants performed an eye-tracking test using a standardized food picture database (Food-pics). We analyzed saccade latency, gaze duration, and saccade bouts in balanced pairs of food and non-food images. Salivary cortisol was elevated by both stressors, although the elevation in salivary cortisol to the reactive stressor was driven by women only. sAA was elevated only by the anticipatory stressor. There were main effects of image type for all three eye-tracking variables, with initial saccades of shorter latency to food images and longer gaze duration and more saccade bouts with food images. Participants exposed to the reactive stressor reduced gaze duration on food images relative to controls, and this affect was not linked to palatability or salivary cortisol levels. We conclude that the reactive stressor decreased time spent looking at food, but not non-food, images. These data are partly consistent with the idea that reactive stressors reduce attention to non-critical visual signals.

Long-term exposure to low-dose Di(2-ethylhexyl) phthalate aggravated high fat diet-induced obesity in female mice

The potential obesogenic roles of di(2-ethylhexyl) phthalate (DEHP) have attracted great attention. The current study aimed to evaluate the combined effects of chronic low-dose DEHP (0.05 mg/kg BW) and a high-fat diet (HFD) on obesity in female mice and explore the underlying mechanisms. We found that low-dose DEHP challenge for 29 weeks increased fat accumulation both in CD- and HFD-fed mice and significantly accelerated the weight gain without affecting food intake in HFD-fed mice. DEHP exposure reduced the energy metabolism, down-regulated the uncoupling protein 1 (UCP1) and total oxidative phosphorylation (OXPHOS) proteins expression in the brown adipose tissue, and up-regulated the PPARγ expression and its phosphorylation at Ser273 in white adipose tissue (WAT). Besides, the combination of DEHP and HFD drove the remodeling of gut microbiota of mice, characterized by the reduced richness and diversity and the elevated Firmicutes to Bacteroidetes (F/B) ratio. Short-chain fatty acids (SCFAs) analysis revealed that DEHP and HFD cotreatment led to a decrease in levels of acetic acid, butyric acid, and pentanoic acid. Interestingly, sodium butyrate (NaB) significantly inhibited the adipogenesis and lipid accumulation of NIH/3T3 mouse embryonic fibroblasts (PPARγ2 overexpression) and the PPARγ phosphorylation at Ser273 induced by DEHP or MEHP. These findings demonstrate that chronic low-dose DEHP challenge could prompt fat accumulation by increasing PPARγ phosphorylation at Ser273 and decreasing thermogenesis in BAT, which might be associated with the SCFAs reduction.

Blood-Based Biomarkers for Eosinophilic Esophagitis and Concomitant Atopic Diseases: A Look into the Potential of Extracellular Vesicles

Eosinophilic esophagitis (EoE) is a chronic, Th2-inflammatory disease of the esophagus that can severely affect food intake. Currently, diagnosis and assessing response to treatment of EoE is highly invasive and requires endoscopy with esophageal biopsies. Finding non-invasive and accurate biomarkers is important for improving patient well-being. Unfortunately, EoE is usually accompanied by other atopies, which make it difficult to identify specific biomarkers. Providing an update of circulating EoE biomarkers and concomitant atopies is therefore timely. This review summarizes the current knowledge in EoE blood biomarkers and two of its most common comorbidities, bronchial asthma (BA) and atopic dermatitis (AD), focusing on dysregulated proteins, metabolites, and RNAs. It also revises the current knowledge on extracellular vesicles (EVs) as non-invasive biomarkers for BA and AD, and concludes with the potential use of EVs as biomarkers in EoE.

A novel davunetide (NAPVSIPQQ to NAPVSIPQE) point mutation in activity-dependent neuroprotective protein (ADNP) causes a mild developmental syndrome.

NAP (NAPVSIPQ, drug candidate name, davunetide) is the neuroprotective fragment of activity-dependent neuroprotective protein (ADNP). Recent studies identified NAPVSIP as a Src homology 3 (SH3) domain-ligand association site, responsible for controlling signalling pathways regulating the cytoskeleton. Furthermore, the SIP motif in NAP/ADNP was identified as crucial for direct microtubule end-binding protein interaction facilitating microtubule dynamics and Tau microtubule interaction, at the microtubule end-binding protein site EB1 and EB3. Most de novo ADNP mutations reveal heterozygous STOP or frameshift STOP aberrations, driving the autistic/intellectual disability-related ADNP syndrome. Here, we report for the first time on a de novo missense mutation, resulting in ADNP containing NAPVISPQE instead of NAPVSIPQQ, in a child presenting developmental hypotonia, possibly associated with inflammation affecting food intake in early life coupled with fear of peer interactions and suggestive of a novel case of the ADNP syndrome. In silico modelling showed that the mutation Q (polar side chain) to E (negative side chain) affected the electrostatic characteristics of ADNP (reducing, while scattering the electrostatic positive patch). Comparison with the most prevalent pathogenic ADNP mutation, p.Tyr719*, indicated a further reduction in the electrostatic patch. Previously, exogenous NAP partially ameliorated deficits associated with ADNP p.Tyr719* mutations in transfected cells and in CRISPR/Cas9 genome edited cell and mouse models. These findings stress the importance of the NAP sequence in ADNP and as a future putative therapy for the ADNP syndrome.

The effect of unit number and inter-unit distance on perceived food portion size

Previous studies have demonstrated that perceived portion size of food influences consumption, so modifying perceived portion size may affect food intake. The present study evaluated the effects of unit number and inter-unit distance on perceived food portion size through eye-tracking and behavioral experiments. After observing one reference portion size picture, 34 participants in Experiment 1 and 29 participants in Experiment 2 evaluated 60 chocolate pictures with 10 different total portion sizes, with a unit number of 9 or 16 and an inter-unit distance of 100%, 120%, or 130%. The results demonstrated that unit number and inter-unit distance independently influenced the perception of overall portion size, while only the unit number could influence the perception of unit portion size. Making estimations about unit portion size requires more cognitive resources than that of overall portion size. These findings imply that we can adjust people's perceived portion sizes by varying the inter-unit distance or unit number of foods, thus nudging individuals to make more rational portion size decisions.

Taste and smell abnormalities in advanced cancer: Negative impact on subjective food intake.

Taste and smell abnormalities (TSAs) are present in all cancer stages and may contribute to malnutrition. Despite this, they are rarely screened for. This study examined the prevalence and characteristics of TSAs and their influence on subjective food intake in advanced cancer. Consecutive patients with advanced cancer were recruited. A modified Taste and Smell Survey assessed subjective TSAs. Objective TSAs were assessed with validated taste strips and "Sniffin Sticks." A six-item food intake questionnaire identified any effect TSAs had on food preferences/aversions. Nutrition status was evaluated with the abridged Patient-Generated Subjective Global Assessment. All 30 participants had either subjective or objective TSAs. The prevalence of TSAs varied based on the assessment tool used. Participants were more aware of taste changes (TCs) than smell changes (SCs). TCs caused reduced food intake in 13 participants. Six reported SCs affected food intake. Food choices caused by TSAs were inconsistent. Some foods preferred because of TSAs were avoided by other participants. None received nutrition counseling on TSA management. Almost all were at malnutrition risk (97%). Almost half (47%) felt TSAs reduced quality of life (QoL). Participants reported "not looking forward to meals" and "can't sit down and eat anything" because of TSAs. TSAs were highly prevalent and impactful on food intake. Both TCs and SCs were complex and varied on an individual basis. Despite the effect on health and QoL, no patients received any nutrition counseling on TSA management. Individualized screening and advice are needed for TSAs in advanced cancer.

Acute and developmental toxicity of embelin isolated from Embelia schimperi Vatke fruit: In vivo and in silico studies.

Embelin is a hydroxybenzoquinone constituent of the Embelia species that has anti-disease properties. However, its toxicity, particularly the in silico, acute, and developmental toxicity profiles, has yet to be thoroughly investigated. Hence, this study aims to assess these toxicity profiles. In silico and in vivo experimental studies were conducted on embelin isolated from the fruits of Embelia schimperi Vatke. In silico toxicity predictions were computed using the ProTox model. The in vivo experiment was done by administering 5000mg/kg of embelin to a single female albino Wistar rat, followed by three female rats in the absence of death, to determine the mean lethal dose (LD50). Afterwards, three groups of pregnant rats were treated with embelin at doses of 250mg/kg, 500mg/kg, and 1000mg/kg for the developmental toxicity test. Vehicle and ad libitum control groups were used to compare the acute and developmental toxicity variables. In silico toxicity predicted that embelin is free from hepatotoxic, carcinogenic, mutagenic, and cytotoxic effects. No inhibitory effect on hERG channels was observed. It has an immunotoxic property and an inhibitory effect on the CYP2D6 enzyme. Since mortality and signs of toxicities were not observed after treatment with 5000mg/kg, the mean lethal dose (LD50) is determined to be >5000mg/kg. There was no significant difference in the morphological scores or number of somites among experimental animals. None of the embryonic systems possessed developmental delays. Nevertheless, the crown-rump length of the high-dose group became significantly shorter. Maternal food intake and weight gain exhibited significant dose-dependent differences between embelin-treated animals and controls. The number of implantations was significantly low in the treatment group, accompanied by a higher frequency of prior resorption. Embelin is predicted to have a high probability of immunotoxicity potential and affect drug metabolism by inhibiting CYP2D6. In addition, it affects food intake, weight gain, and the number of implantations in pregnant rats. Therefore, it is highly recommended not to take embelin and embelin-rich plants during pregnancy. Further in vitro and in vivo studies need to be conducted to understand the mechanism behind the toxicity of embelin.