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Prediction of metabolic syndrome using machine learning approaches based on genetic and nutritional factors: a 14-year prospective-based cohort study.

INTRODUCTION: Metabolic syndrome is a chronic disease associated with multiple comorbidities. Over the last few years, machine learning techniques have been used to predict metabolic syndrome. However, studies incorporating demographic, clinical, laboratory, dietary, and genetic factors to predict the incidence of metabolic syndrome in Koreans are limited. In the present study, we propose a genome-wide polygenic risk score for the prediction of metabolic syndrome, along with other factors, to improve the prediction accuracy of metabolic syndrome. METHODS: We developed 7 machine learning-based models and used Cox multivariable regression, deep neural network (DNN), support vector machine (SVM), stochastic gradient descent (SGD), random forest (RAF), Na&#xef;ve Bayes (NBA) classifier,&#xa0;and AdaBoost (ADB) to predict the incidence of metabolic syndrome at year 14 using the dataset from the Korean Genome and Epidemiology Study (KoGES) Ansan and Ansung. RESULTS: Of the 5440 patients, 2,120 were considered to have new-onset metabolic syndrome. The AUC values of model, which included sex, age, alcohol intake, energy intake, marital status, education status, income status, smoking status, dried laver intake, and genome-wide polygenic risk score (gPRS)&#xa0;Z-score based on 344,447 SNPs (p-value&#x2009;<&#x2009;1.0), were the highest for RAF (0.994 [95% CI 0.985, 1.000]) and ADB (0.994 [95% CI 0.986, 1.000]). CONCLUSIONS: Incorporating both gPRS and demographic, clinical, laboratory, and seaweed data led to enhanced metabolic syndrome risk prediction by capturing the distinct etiologies of metabolic syndrome development. The RAF- and ADB-based models predicted metabolic syndrome more accurately than the NBA-based model for the Korean population.

Humans

Robust human genetic evidence supporting causal effects of FGF21 on reducing alcohol consuming behaviours.

BACKGROUND: Alcohol use disorder (AUD) represents a tremendous societal burden, yet few efficacious therapies are available and widely used. Pre-clinical and human observational data support fibroblast growth factor 21 (FGF21) as a promising therapeutic target for the treatment of AUD. The objective of this study is to identify a robust genetic instrument for FGF21 agonism and leverage it to explore the effects of FGF21 agonism on AUD and related traits, as well as metabolic outcomes more widely. METHODS: We first compared associations with the positive control outcomes of liver fat and liver cirrhosis risk for the FGF21 cis-protein quantitative trait locus (cis-pQTL) (rs838131) to those for the common allele FGF21 L174P missense variant (rs739320). Having identified the L174P missense variant as a plausible genetic instrument, we subsequently performed association analyses investigating effects on AUD, related traits, and metabolic outcomes more widely. Finally, we performed colocalisation analyses to test whether observed association results reflect a causal mechanism that overlaps with the clinical effects of FGF21 on liver fat and liver cirrhosis. RESULTS: Consistent association and colocalisation evidence support a protective association between genetically predicted FGF21 agonism and alcohol consumption (association p&#x2009;=&#x2009;1&#x2009;&#xd7;&#x2009;10-18, colocalisation posterior probability&#x2009;=&#x2009;0.90), problematic alcohol use (association p&#x2009;=&#x2009;0.02, posterior probability&#x2009;=&#x2009;0.64), and AUD (association p&#x2009;=&#x2009;9&#x2009;&#xd7;&#x2009;10-8, posterior probability&#x2009;=&#x2009;0.97). Similar evidence was also observed for favourable effects of FGF21 on improving kidney function, lowering triglyceride levels, lowering proportional energy intake from carbohydrates, increasing proportional energy intake from protein and fat, increasing body weight and lowering waist-to-hip ratio. CONCLUSIONS: This study identifies a genetic instrument for FGF21 effects to provide causal human evidence supporting favourable effects of FGF21 analogues for the treatment of AUD and related traits, as well as on metabolic outcomes more broadly. Further clinical study is duly warranted.

Humans

Risk factors for loss of skeletal muscle mass in patients with chronic kidney disease on a low-protein diet.

OBJECTIVES: A low-protein diet (LPD) is recommended for patients with chronic kidney disease (CKD) to prevent a further decline in renal function. However, its impact on muscle mass in these patients remains unclear. This study investigated the risk factors for loss of muscle mass in patients with CKD on an LPD. METHODS: Eighty-four patients with predialysis CKD (59 men, mean age 61.9 &#xb1; 11.5 y) who participated in a multicenter randomized controlled trial initiated in 2014 were retrospectively reviewed. We collected data on baseline blood and urine tests, body composition, and dietary records at the start and end of the observation period. We evaluated muscle mass using the skeletal muscle index (SMI) and analyzed risk factors for a decrease in SMI during the 24-wk observation period, using logistic regression analysis. Variables with an association (P < 0.1) in univariate analysis, as well as age, sex, use of low-protein rice, and changes in protein intake, were subjected to multivariate analysis. RESULTS: SMI decreased in 50 patients (59.5%) during the observation period. Multivariate analysis identified significant associations of the SMI with serum albumin at baseline (odds ratio 0.11, 95% confidence interval 0.02-0.52, P = 0.004) and changes in energy intake while on the LPD (odds ratio 3.39, 95% confidence interval 1.00-11.43, P = 0.049). CONCLUSIONS: Risk factors for reduced SMI in patients with CKD on an LPD were malnutrition when initiating the LPD and reduced energy intake during its implementation. Clinicians should optimize nutritional status before initiation of an LPD and ensure adequate energy intake throughout treatment.

Humans

Trends in the Prevalence of Foods High in Saturated Fats, Sodium, and Added Sugars among U.S. adults, NHANES 2007-2018.

BACKGROUND: Foods and beverages high in saturated fats, sodium, and added sugars (HFSS) are often ultra-processed and linked to poor health outcomes, but few studies have investigated their intake. OBJECTIVE: To describe the trends in the intake of HFSS foods and beverages between 2007 and 2018 in a nationally representative sample of U.S. adults, by sociodemographic characteristics and What We Eat in America food groups. DESIGN: This is a secondary, cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2018. PARTICIPANTS/SETTING: The final sample included 27,984 adults 19 years of age or older from NHANES with at least one complete dietary recall. MAIN OUTCOME MEASURES: The primary outcomes are the percentage of total energy intake from foods classified as HFSS according to the Pan American Health Organization (PAHO) Nutrient Profile Model. STATISTICAL ANALYSES PERFORMED: To estimate the percentage of energy intake from foods and beverages HFSS, linear regression models with interaction terms between cycles and covariates were used. RESULTS: The overall intake of foods and beverages HFSS did not change, representing over 60% of the total energy intake between 2007-2010 and 2015-2018. The intake of foods and beverages high in sodium increased by 2.0 percentage points (95% CI: 0.5, 3.5) and 3.5 percentage points (95% CI: 1.1, 5.8), respectively. The intake of foods and beverages high in saturated fats increased by 6.1 percentage points (95% CI: 4.5, 7.6) and 6.1 percentage points (95% CI: 3.9, 8.2), respectively. The intake of foods and beverages high in added sugars did not change. CONCLUSION: In the U.S., intake of HFSS foods and beverages is high. Future research should focus on whether public health interventions and policies might reduce the intake of foods high in nutrients of concern.

Added sugars

Deletion of neurosecretory proteins GL and GM drives dual anti-obesity effects via appetite suppression and enhanced energy expenditure.

Obesity results from an imbalance between energy intake and expenditure and is regulated by hypothalamic neuropeptide systems. The neurosecretory proteins GL (NPGL) and GM (NPGM) are expressed in the hypothalamus and promote feeding in gain-of-function studies; however, their endogenous physiological roles remain unclear. Here, we show that mice lacking both NPGL and NPGM display a lean phenotype driven by reduced food intake and increased energy expenditure. This anti-obesity phenotype is associated with increased expression of anorexigenic pro-opiomelanocortin in the hypothalamus and enhanced thermogenic activity in brown adipose tissue, marked by elevated uncoupling protein 1. Consistent with these findings, suppression of NPGL/NPGM signaling reduces feeding and alters sympathetic nerve activity. In addition, genome-wide association analysis identifies an obesity-associated variant near the human NPGM locus, suggesting relevance to human energy balance. Together, these findings identify NPGL and NPGM as endogenous regulators of energy homeostasis with potential relevance to obesity.

Animals

Water intake, switching between bites and sips, and drinking behavior are associated with food intake across meals varying in spiciness: A secondary analysis of two randomized crossover studies.

Widespread nutrition advice instructs consumers to drink water with meals to increase fullness and reduce energy intake. However, recent data indicates greater water intake is associated with more food intake at a meal, not less. Switching between meal components (e.g., alternating between food and water), has also been associated with increased food intake at a pasta meal, but it remains unclear whether this applies to other foods. In a secondary analysis, we pooled existing data from 2 crossover experiments (total n&#xa0;=&#xa0;86) where adults ate an ad libitum lunch consisting of 650&#xa0;g of beef chili (n&#xa0;=&#xa0;52) or chicken tikka masala (n&#xa0;=&#xa0;34) with 450&#xa0;g of water twice in the laboratory while being video-recorded. For both experiments, the spiciness of the lunch was varied by adding different ratios of hot:sweet paprika. Videos were coded to measure sip number, sip size (g/sip), drinking rate (g/min), and number of switches between bites of food and sips of water. As we previously reported, increasing spiciness slowed eating rate and reduced food intake; in secondary analyses described here, the reduction in food intake was not moderated by water intake, switching, or drinking behaviors (all p&#xa0;>&#xa0;0.73). Notably, across all meals, greater water intake (p&#xa0;<&#xa0;0.001) and switching (p&#xa0;=&#xa0;0.02) associated with greater food intake. Overall, individuals ate more when they drank more and switched between bites and sips more often, highlighting the potential influence of water and drinking behaviors on food consumption. This finding challenges the widespread dietary advice to drink water with meals to reduce food intake.

Humans

Development and evaluation of a machine learning model for osteoporosis risk prediction in Korean women.

BACKGROUND: The aim of this study was to develop a machine learning (ML) model for classifying osteoporosis in Korean women based on a large-scale population cohort study. This study also aimed to assess ML model performance compared with traditional osteoporosis screening tools. Furthermore, this study aimed to examine the factors influencing the risk of osteoporosis through variable importance. METHODS: Data was collected from 4199 women aged 40-69 years in the baseline survey of the Ansan and Ansung cohort of the Korean Genome and Epidemiology Study. Osteoporosis was set as the dependent variable to develop ML classification models. Independent variables included 122 factors related to osteoporosis risk, such as socio-demographic characteristics, anthropometric parameters, lifestyle factors, reproductive factors, nutrient intakes, diet quality indices, medical history, medication history, family history, biochemical parameters, and genetic factors. The six classification models were developed using ML techniques, including decision tree, random forest, multilayer perceptron, support vector machine, light gradient boosting machine, and extreme gradient boosting (XGBoost). The six ML classification models were compared with two traditional osteoporosis screening tools, including the osteoporosis risk assessment instrument (ORAI) and the osteoporosis self-assessment tool (OST). The ML model performances were evaluated and compared using the confusion matrix and area under the curve (AUC) metrics. Variable importance was assessed using the XGBoost technique to investigate osteoporosis risk factors. RESULTS: The XGBoost model showed the highest performance out of the six ML classification models, with an accuracy of 0.705, precision of 0.664, recall of 0.830, and F1 score of 0.738. Moreover, the XGBoost model showed a higher performance on AUC than ORAI and OST. Variable importance scores were identified for 69 out of the 122 variables associated with osteoporosis risk factors. Age at menopause ranked first in variable importance. Variables of arthritis, physical activities, hypertension, education level, income level; alcohol intake, potassium intake, homeostatic model assessment for insulin resistance; energy intake, vitamin C intake, gout; and dietary inflammatory index ranked in the top 20 out of the 69 variables, using the XGBoost technique. CONCLUSIONS: This study found that an XGBoost model can be utilized to classify osteoporosis in Korean women. Age at menopause is a significant factor in osteoporosis risk, followed by arthritis, physical activities, hypertension, and education level.

Humans

Acute Stevia Consumption does not Alter Endocrine Responses in Individuals with Normal Weight, Overweight, and Type 2 Diabetes Mellitus.

BACKGROUND: Stevia is a plant-based non-nutritive sweetener. Acute effects of stevia ingestion on glycemia and hormonal responses have not been fully investigated. OBJECTIVE: This objective of this study was to evaluate the acute effects of beverages containing stevia alone and in combination with glucose on glycemic, hormonal, and appetite responses. METHODS: This study evaluated three cohorts of n=23 individuals with either normal weight (NW), overweight (OW), or type 2 diabetes mellitus (T2DM) for which each individual completed four test conditions in a randomized sequence crossover study design. The four test conditions were beverages containing stevia (75.6 mg steviol equivalents), water, glucose (30 g), and stevia+glucose (30 g glucose+75.6 mg steviol equivalents). Blood samples were collected before and for 180 min after beverage consumption. Assessments included net area under the curve (niAUC) and incremental maximal concentration values for plasma glucose, insulin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1, glucagon, and PYY. Appetite was assessed with visual-analog scale questions and energy consumption during an ad libitum meal. RESULTS: Responses to the stevia beverage did not differ significantly from those for water alone, and stevia + glucose did not differ significantly from glucose alone for any of the three groups. CONCLUSION: Acute stevia consumption did not materially alter responses for glycemia or hormones involved in glucose and appetite regulation, appetite ratings, or energy intake at a subsequent meal. Clinical Trial Registry number and website where it was obtained: Clinical Trials.gov Identifier: NCT05287906. Study Details | NCT05287906 | A Trial to Assess Steviol Glycosides on Acute Appetite Hormone Release | ClinicalTrials.gov.

Appetite

Effect of a 6-month low-carbohydrate diet on the circulating fatty acid composition in patients with type 2 diabetes: a secondary analysis of an open-label randomized controlled trial.

BACKGROUND: Circulating fatty acid profiles are linked to cardiovascular disease risk and mortality. Short-term interventions suggest that low-carbohydrate diets (LCDs) promote cardioprotective shifts in circulating fatty acids in obesity. OBJECTIVES: We examined whether a 6-mo, non-calorie-restricted, LCD high in fat similarly improves circulating fatty acid composition in adults with type 2 diabetes. METHODS: In an open-label, randomized, controlled trial, 71 individuals with type 2 diabetes were randomly assigned 2:1 to an LCD [maximum of 20 E% (energy per cent) carbohydrates] or a control diet (50-60 E% carbohydrates) for 6 mo with no restriction in energy intake. The prespecified secondary outcomes were the mean difference in change between groups in serum phospholipid fatty acids in weight percentage (wt%) measured by gas chromatography and reported as 95% confidence intervals (CIs) and significance adjusted for multiple comparisons (q value). RESULTS: LCD reduced total saturated [-0.6 (CI: -0.9, -0.2)] and monounsaturated fatty acids [-0.9 (CI: -1.4, -0.3)] and increased total polyunsaturated fatty acids [1.3 (CI: 0.6, 2.0)] compared with the control diet (all q < 0.05). Importantly, LCD reduced palmitoleic acid (16:1n-7) [-0.13 (CI: -0.21, -0.06)], a marker of de novo lipogenesis, by 23% and dihomo-&#x3b3;-linolenic acid (20:3n-6) [-0.38 (CI: -0.67, -0.09)] by 12%, whereas it increased arachidonic acid (20:4n-6) [1.1 (CI: 0.3, 2.0)] by 9% compared with the control diet (all q < 0.05). Moreover, the LCD improved estimated desaturase activities by lowering stearoyl-coenzyme A desaturase 1 [-0.5 (CI: -0.7, -0.2)] and &#x394;6 desaturase [-0.6 (CI: -0.9, -0.2)] and increasing &#x394;5 desaturase [1.05 (CI: 0.3, 1.79)] activities, respectively (all q < 0.01). These changes occurred despite a 2.6-fold higher intake of saturated fatty acids in the LCD group. CONCLUSIONS: A 6-mo, non-calorie-restricted LCD modified the circulating composition of fatty acids in adults with type 2 diabetes in a manner consistent with a potentially favorable cardioprotective profile. This trial was registered at www. CLINICALTRIALS: gov as NCT03068078.

Humans

A consensus guide to preclinical indirect calorimetry experiments.

Understanding the complex factors influencing mammalian metabolism and body weight homeostasis is a long-standing challenge requiring knowledge of energy intake, absorption and expenditure. Using measurements of respiratory gas exchange, indirect calorimetry can provide non-invasive estimates of whole-body energy expenditure. However, inconsistent measurement units and flawed data normalization methods have slowed progress in this field. This guide aims to establish consensus standards to unify indirect calorimetry experiments and their analysis for more consistent, meaningful and reproducible results. By establishing community-driven standards, we hope to facilitate data comparison across research datasets. This advance will allow the creation of an in-depth, machine-readable data repository built on shared standards. This overdue initiative stands to markedly improve the accuracy and depth of efforts to interrogate mammalian metabolism. Data sharing according to established best practices will also accelerate the translation of basic findings into clinical applications for metabolic diseases afflicting global populations.

Calorimetry, Indirect

An expanded breakfast buffet increases daily energy and protein intakes in hospitalised patients: A prospective crossover quality improvement study.

BACKGROUND & AIMS: Inadequate dietary intake remains common during hospitalisation. Ordinary hospital meals are central to nutritional intake, but their contribution depends on what is offered and what patients are able and willing to eat. We evaluated whether a preference-informed, limited expansion of the hospital breakfast buffet could increase total daily energy and protein intakes. METHODS: This prospectively structured, ward-based crossover quality-improvement study was conducted in seven inpatient wards at a tertiary university hospital. Each ward was observed for four consecutive days and randomly allocated to begin with standard or expanded breakfast, after which conditions alternated daily. The expanded buffet consisted of standard breakfast supplemented with familiar energy- and protein-rich foods selected from previous patient-choice data. Twenty-four-hour intake was registered using component-level weighed food records during the day and nursing registration overnight. Primary outcomes were total daily energy and protein intakes. Linear mixed-effects models adjusted for observation day and ward-level starting sequence and accounted for repeated patient observations and ward-level clustering. Analyses used data from patients who consumed breakfast and contributed analysable observations under both breakfast conditions. RESULTS: The primary crossover population included 71 patients contributing 188 analysable patient-days. Compared with standard breakfast, the expanded breakfast increased total daily energy intake by +198 kcal/day (95% CI 44 to 352) and protein intake by +6.8 g/day (95% CI 1.0 to 12.5), without a statistically significant increase in total food weight. Daily energy and protein adequacy increased by +8.7 and + 6.8 percentage points, respectively. The increase was driven mainly by breakfast intake, with no measurable reduction in non-breakfast intake. CONCLUSIONS: A limited expansion of the ordinary hospital breakfast buffet increased total daily energy and protein intakes in the primary crossover population of hospitalised adults who consumed breakfast. This increase occurred without a statistically significant increase in total food weight or a measurable reduction in non-breakfast intake. Small, preference-informed additions of familiar energy- and protein-rich foods at breakfast may improve daily intake by increasing the nutrient yield of foods patients are able or willing to eat.

Humans

The relationship between food intake and outdoor temperature in a longitudinal study: a public health perspective in the context of global warming.

BACKGROUND: Climate change affects human health and nutrition. Rising temperatures may significantly impact diets, but research on their influence on dietary habits in large populations remains limited. OBJECTIVES: We aimed to study the link between outdoor temperature and energy-adjusted food consumption across profiles in a longitudinal study. METHODS: This study included 100,851 participants from the NutriNet-Sant&#xe9; study (2009-2023) with 1,716,046 24-h dietary records linked to daily maximum outdoor temperature at the residence, from the nearest M&#xe9;t&#xe9;o-France station. Associations were analyzed using linear mixed models with interactions tested for sex and 6 socioeconomic profiles (employees, privileged, intermediate, young, disadvantaged, and retirees) derived from clustering. RESULTS: Across all subgroups, higher outdoor temperature was associated with higher consumption of fruits, vegetables, processed meats, sweet products, water, alcoholic beverages, and sugar-sweetened beverages, whereas consumption of red meat, pulses, and dairy products decreased. From 25&#xb0;C to 35&#xb0;C, the increase in alcohol consumption with temperature was more pronounced in males {150 g/d [95% confidence interval (CI): 147 g/d, 153 g/d] to 166 g/d [95% CI: 162 g/d, 171 g/d], +11%} than in females [101 g/d (95% CI: 98 g/d, 103 g/d) to 107 g/d (95% CI: 104 g/d, 109 g/d), +6%]. Across socioeconomic profiles, changes shared similar directions, but some trends were more marked, notably for alcoholic beverages among employees (95% CI: 114 g/d, 130 g/d; +14%) and sugar-sweetened beverages in young (95% CI: 56 g/d, 72 g/d; +29%). Consumption of fruits increased more modestly in the young (95% CI: 227 g/d, 248 g/d; +9%) than in employees (95% CI: 194 g/d, 227 g/d; +17%). These changes, although variable in magnitude, were not accompanied by substantial modifications in energy intake or overall diet quality scores. CONCLUSIONS: These results emphasize the importance of targeted prevention messages when temperatures exceed 25&#xb0;C, especially concerning alcoholic and sugar-sweetened beverages, and offer insight into potential long-term food consumption patterns (beyond seasonal changes) in the context of global warming.

Humans

Proteomic Profile in Retinopathy of Prematurity: A Secondary Analysis of the Mega Donna Mega Randomized Clinical Trial.

IMPORTANCE: Identifying early proteomic profiles in infants who develop severe retinopathy of prematurity (ROP) may reveal targets for preventive interventions to reduce retinal vessel loss and the subsequent risk of severe ROP. OBJECTIVE: To assess early longitudinal profiles of blood protein levels in preterm infants with or without severe ROP and the effect of arachidonic acid (AA) and docosahexaenoic acid (DHA) supplementation. DESIGN, SETTING, AND PARTICIPANTS: This was an exploratory, post hoc analysis of serum proteome profiles in preterm infants in the double-masked Mega Donna Mega (MDM) randomized clinical trial using targeted Olink Proximity Extension Assay proteomics covering 538 analytes. The setting was 3 university hospitals in Sweden and included extremely preterm infants born before 28 weeks of gestational age (GA), from 2016 to 2019. Data were analyzed from January to March 2025. EXPOSURES: All infants received standard nutrition; additionally, half received enteral lipid supplementation with AA/DHA (100/50 mg/kg per day) from birth to term equivalent age. MAIN OUTCOMES AND MEASURES: Longitudinal protein profiles during the first month of life were examined using mixed models for repeated measures, adjusted for GA, study center, and AA/DHA supplementation, and tested for the interaction between severe ROP (stage &#x2265;3 and/or treated) and postnatal age. RESULTS: A total of 177 extremely preterm infants (mean [SD] GA, 25.6 [1.4] weeks; 100 male [56.5%]) were included, of whom 50 (28.2%) developed severe ROP. Of 538 longitudinal analyzed proteins, 109 protein profiles in the first month of life associated with severe ROP, proteins related to immune response, apoptotic processes, blood coagulation, and lipid metabolism. The most pronounced association with severe ROP was a fast rise in fibroblast growth factor 21 (FGF-21; &#x3b2;&#x2009;=&#x2009;0.68; 95% CI,&#x2009;0.39-0.97; Q =.002) and tissue plasminogen activator (tPA; &#x3b2;&#x2009;=&#x2009;0.21; 95% CI,&#x2009;0.13-0.29; Q <.001) during the first postnatal days. The increase in serum FGF-21 level in the first week of life was associated with lower GA, lower birth weight, low enteral energy intake, and more days receiving mechanical ventilation. No association was observed between AA/DHA supplementation and the proteome. CONCLUSIONS AND RELEVANCE: In this post hoc exploratory analysis of data from the MDM randomized clinical trial, a fast rise in FGF-21 levels, a metabolic stress-induced hormone, during the first postnatal days was strongly associated with the development of severe ROP in extremely preterm infants. These findings suggest that early interventions improving bioenergetic status may help prevent severe ROP. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03201588.

Humans

Association of urinary levels of trace metals with type 2 diabetes and obesity in postmenopausal women in Korea: A community-based cohort study.

Several toxic metals have been associated with metabolic diseases like obesity and diabetes mellitus (DM) in humans. However, knowledge regarding the influence of many trace elements, especially in combination with essential elements is limited. This study aims to address this research gap by investigating the associations of both non-essential and essential inorganic trace elements in urine with DM and obesity, employing a group of postmenopausal women (n&#xa0;=&#xa0;851) from the Korean Genome and Epidemiology Study (KoGES) cohort. Urine samples were collected during 2017-2018, and were analyzed for 19 trace elements using inductively coupled plasma-mass spectrometry and an automatic mercury analyzer. Outcomes of interest were metabolic diseases (DM and obesity) and DM-related traits (insulin resistance and &#x3b2;-cell function). After adjustment of covariates, such as age, alcohol consumption, smoking status, educational level, and daily energy intake, urinary Zn, Ni, Tl, and U levels were associated with the prevalence of DM and homeostatic model assessment (HOMA) for insulin resistance (IR) in the postmenopausal women. In the whole mixture model, however, no significant association was observed for the prevalence of DM. Urinary levels of Zn were negatively associated with HOMA of &#x3b2;-cell function (HOMA-&#x3b2;), positively correlated with HbA1c levels, HOMA-IR, and prevalent DM. In addition, urinary Zn, Co, Tl, and Cs were positively associated with obesity (body mass index &#x2265;25&#xa0;kg/m2). The present observation shows that several individual elements and their mixtures may be associated with the prevalence of DM, IR, or obesity.

Humans

lncRNA TUG1 transcript levels and psychological disorders: insights into interplay of glycemic index and glycemic load.

BACKGROUND: There is an association between obesity and psychological disorders such as depression, anxiety, and stress. Environmental factors and genetics play a crucial role in this regard. Several long non-coding RNAs (lncRNAs) are involved in the pathophysiology of the nervous system. Additionally, we intend to investigate how dietary glycemic index and load relate to psychological disorders in women with obesity and overweight by identifying the possible interaction with metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and taurine upregulated gene 1 (TUG1). METHODS: 267 overweight or obese women between the ages of 18 and 48 were recruited for the current study. A reliable and validated food frequency questionnaire (FFQ) consisting of 147 items assessed food consumption, glycemic load (GL), and glycemic index (GI). Depression-Anxiety-Stress Scales (DASS-21) were used to assess mental well-being. A real-time polymerase chain reaction (PCR) was used to assess transcript levels for lncRNAs MALAT1 and TUG1. RESULTS: In obese and overweight women, a positive correlation was found between anxiety and MALAT1 mRNA levels (P&#x2009;=&#x2009;0.007, CC&#x2009;=&#x2009;0.178). Age, energy intake, physical activity, total fat, income, marriage, thyroid, and BMI were adjusted, and GI and TUG1 were positively correlated on DASS-21 (&#x3b2;&#x2009;=&#x2009;0.006, CI&#x2009;=&#x2009;0.001, 0.01, P&#x2009;=&#x2009;0.031), depression (&#x3b2;&#x2009;=&#x2009;0.002, CI&#x2009;=&#x2009;0.001, 0.004, P&#x2009;=&#x2009;0.019), Stress (&#x3b2;&#x2009;=&#x2009;0.003, CI&#x2009;=&#x2009;0.001, 0.005, P&#x2009;=&#x2009;0.027). The interaction of GL and TUG1 on stress was also observed (&#x3b2;&#x2009;=&#x2009;0.03, CI&#x2009;=&#x2009;0.001, 0.07, P&#x2009;=&#x2009;0.048). CONCLUSIONS: The lncRNA TUG1 appears to be associated with depression and stress through interaction with GI and correlated with stress by interaction with GL. To establish this concept, further research is required.

RNA, Long Noncoding

Enteral Nutrition Is Associated with a Distinct Gut Microbiome Composition and Fermentation Capacity Profile After Acute Colonic Injury in Rats.

Enteral nutrition (EN) is known to promote mucosal healing in inflammatory bowel disease, and multi-omics data suggest that the gut microbiome mediates its therapeutic effects. However, the impact of EN and its components on the gut community during recovery from acute epithelial injury remains incompletely understood. We used whole-genome metagenomic sequencing to investigate the effect of an EN formula based on extruded amaranth flour and pea protein on the gut microbiome in a dextran sulfate sodium (DSS) rat model of acute colonic injury. Three groups were compared, as follows: an unchallenged control (n = 9) with standard chow, a colonic injury (5% DSS; n = 9) group with standard chow, and a colonic injury (5% DSS; n = 9) group with EN. Injury was confirmed histologically (median MCHI score was 2, indicating epithelial damage without inflammation). DSS caused significant weight loss. Animals receiving EN regained baseline weight faster, by day 14, whereas animals on standard chow achieved recovery only by day 21. Differences in energy intake should be further investigated to validate the effect of EN on body weight recovery. At day 21, both injury groups demonstrated higher relative abundances of Bacteroidaceae and Erysipelotrichaceae, including the mucin-degrader Allobaculum mucilyticum, compared with the control group. Conversely, Lactobacillus abundance, notably Lactobacillus acidophilus, was higher in the EN group than in both other groups, as was the inferred capacity for lactate-producing fermentation. These findings suggest that EN is associated with a distinct microbial composition and inferred metabolic profile during the post-injury period, with lactobacilli as one of the potential mediators of its effects.

Animals

The combined and independent influence of food texture and a 'mindful eating' instruction on eating rate and food intake among Dutch primary schoolchildren.

Eating rate (ER), the amount of food consumed per unit of time, is a key determinant of food intake, with faster ER associated with larger meal size. Research in adults has shown that both sensory properties like texture, and instructions can influence ER and intake. However, their independent and combined effect on ER and intake in children remain poorly understood. This study examined the effects of food texture and a 'mindful eating' instruction on ER and food intake in children. Children (N&#xa0;=&#xa0;73), 38 boys, aged 4-12 years, participated in a 4-week cluster-randomized incomplete cross-over study conducted during regular school lunches. Using a 2&#xd7;3 factorial design, children were exposed to two levels of food texture (softer vs. harder whole-grain buns) and three types of instructions (none, control, 'mindful'). Linear mixed models with repeated measures were used, adjusting for sex and group. As the interaction between food-texture and type of instructions was non-significant, it was excluded from the final models. Results revealed a strong main effect of food texture on ER and food intake (all p&#xa0;<&#xa0;0.001), where compared with softer buns, harder buns were associated with a slower eating rate (&#x394;&#xa0;=&#xa0;-6.67&#xa0;g/min, SE&#xa0;=&#xa0;0.59) and reduced food intake (&#x394;&#xa0;=&#xa0;-70&#xa0;g, SE&#xa0;=&#xa0;8). In contrast, type of instruction had no significant effect on ER or intake (p&#xa0;=&#xa0;0.85). Our findings demonstrate that food texture exerts a dominant influence on children's eating rate and food intake, highlighting texture modification as a potential leverage point for influencing ER and intake in children.

Humans

A mammalian tripartite enhancer cluster controls hypothalamic Pomc expression, food intake, and body weight.

Food intake and energy balance are tightly regulated by a group of hypothalamic arcuate neurons expressing the proopiomelanocortin (POMC) gene. In mammals, arcuate-specific POMC expression is driven by two cis-acting transcriptional enhancers known as nPE1 and nPE2. Because mutant mice lacking these two enhancers still showed hypothalamic Pomc mRNA, we searched for additional elements contributing to arcuate Pomc expression. By combining molecular evolution with reporter gene expression in transgenic zebrafish and mice, here, we identified a mammalian arcuate-specific Pomc enhancer that we named nPE3, carrying several binding sites also present in nPE1 and nPE2 for transcription factors known to activate neuronal Pomc expression, such as ISL1, NKX2.1, and ER&#x3b1;. We found that nPE3 originated in the lineage leading to placental mammals and remained under purifying selection in all mammalian orders, although it was lost in Simiiformes (monkeys, apes, and humans) following a unique segmental deletion event. Interestingly, ablation of nPE3 from the mouse genome led to a drastic reduction (>70%) in hypothalamic Pomc mRNA during development and only moderate (<33%) in adult mice. Comparison between double (nPE1 and nPE2) and triple (nPE1, nPE2, and nPE3) enhancer mutants revealed the relative contribution of nPE3 to hypothalamic Pomc expression and its importance in the control of food intake and adiposity in male and female mice. Altogether, these results demonstrate that nPE3 integrates a tripartite cluster of partially redundant enhancers that originated upon a triple convergent evolutionary process in mammals and that is critical for hypothalamic Pomc expression and body weight homeostasis.

Animals