Associations of dietary sugars with liver stiffness in Latino adolescents with obesity differ on PNPLA3 and liver disease severity.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common paediatric liver disease. Latinos have high MASLD risk due to 50% prevalence of GG genotype of PNPLA3. Our primary aim was to evaluate associations between dietary carbohydrates/sugars and liver stiffness in Latino adolescents with obesity. Our secondary aim was to examine effect modification by (a) PNPLA3 genotype or (b) liver disease severity. Data were obtained from 114 Latino adolescents with obesity involved in two prior studies. No associations were seen between dietary carbohydrates/sugars and liver stiffness in the group as a whole. In subjects with GG genotype of PNPLA3, total sugar, fructose, sucrose, and glucose were associated with liver stiffness. Positive relationships between carbohydrate, total sugar, and sucrose and liver stiffness were stronger in those with MASLD and fibrosis compared to those with healthy livers and MASLD without fibrosis.

Pre-pregnancy maternal obesity and infant neurodevelopmental outcomes in Latino infants.

OBJECTIVE: This study explores the impact of maternal pre-pregnancy BMI on infant neurodevelopment at 24 months in low-income Latino families. It also investigates whether infant diet mediates this relationship. METHODS: Latino mother-infant pairs (n = 163) were enrolled at 1 month post partum and were followed for 2 years, with assessments at 6-month intervals. Maternal pre-pregnancy anthropometrics were self-reported at baseline, and child neurodevelopment was assessed at 24 months using the Bayley Scales of Infant Development. Diet quality of infants was measured using the Healthy Eating Index (HEI)-2015 and HEI-Toddlers-2020 scores at multiple time points. Mediation and regression models that adjust for maternal factors were used to examine the associations. RESULTS: Pre-pregnancy BMI showed significant negative associations with child cognitive scores (ß = -0.1, 95% CI: -0.2 to -0.06, p < 0.001) and language scores (ß = -0.1, 95% CI: -0.2 to -0.03, p = 0.01) at 24 months. Infant HEI-2015 scores at 24 months partly mediated these associations, explaining 23% and 30% of the total effect on cognitive and language subscales, respectively. No specific dietary components in infants mediated the relationship, except for the total HEI-2015 score. CONCLUSIONS: Managing maternal obesity pre-pregnancy is crucial for improving infant neurodevelopmental outcomes, especially in low-income Latino families. Promoting healthy weight and enhancing infant diet quality can enhance neurodevelopment in these populations.

Air pollution exposure may impact the composition of human milk oligosaccharides.

Human milk oligosaccharides (HMOs) impact neonate immunity and health outcomes. However, the environmental factors influencing HMO composition remain understudied. This study examined the associations between ambient air pollutant (AAP) exposure and HMOs at 1-month postpartum. Human milk samples were collected at 1-month postpartum (n = 185). AAP (PM2.5, PM10, NO2) exposure included the 9-month pregnancy period through 1-month postpartum. Associations between AAP with (1) HMO diversity, (2) the sum of sialylated and fucosylated HMOs, (3) 6 a priori HMOs linked with infant health, and (4) all HMOs were examined using multivariable linear regression and principal component analysis (PCA). Exposure to AAP was associated with lower HMO diversity. PM2.5 and PM10 exposure was positively associated with the HMO 3-fucosyllactose (3FL); PM2.5 exposure was positively associated with the sum of total HMOs, sum of fucosylated HMOs, and the HMO 2'-fucosyllactose (2'FL). PCA indicated the PM2.5, PM10, and NO2 exposures were associated with HMO profiles. Individual models indicated that AAP exposure was associated with five additional HMOs (LNFP I, LNFP II, DFLNT, LNH). This is the first study to demonstrate associations between AAP and breast milk HMOs. Future longitudinal studies will help determine the long-term impact of AAP on human milk composition.

Associations of dietary intake and longitudinal measures of per- and polyfluoroalkyl substances (PFAS) in predominantly Hispanic young Adults: A multicohort study.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are pollutants linked to adverse health effects. Diet is an important source of PFAS exposure, yet it is unknown how diet impacts longitudinal PFAS levels. OBJECTIVE: To determine if dietary intake and food sources were associated with changes in blood PFAS concentrations among Hispanic young adults at risk of metabolic diseases. METHODS: Predominantly Hispanic young adults from the Children's Health Study who underwent two visits (CHS; n = 123) and young adults from NHANES 2013-2018 who underwent one visit (n = 604) were included. Dietary data at baseline was collected using two 24-hour dietary recalls to measure individual foods and where foods were prepared/consumed (home/restaurant/fast-food). PFAS were measured in blood at both visits in CHS and cross-sectionally in NHANES. In CHS, multiple linear regression assessed associations of baseline diet with longitudinal PFAS; in NHANES, linear regression was used. RESULTS: In CHS, all PFAS except PFDA decreased across visits (all p < 0.05). In CHS, A 1-serving higher tea intake was associated with 24.8 %, 16.17 %, and 12.6 % higher PFHxS, PFHpS, and PFNA at follow-up, respectively (all p < 0.05). A 1-serving higher pork intake was associated with 13.4 % higher PFOA at follow-up (p < 0.05). Associations were similar in NHANES, including unsweetened tea, hot dogs, and processed meats. For food sources, in CHS each 200-gram increase in home-prepared food was associated with 0.90 % and 1.6 % lower PFOS at baseline and follow-up, respectively, and in NHANES was associated with 0.9 % lower PFDA (all p < 0.05). CONCLUSION: Results suggest that beverage consumption habits and food preparation are associated with differences in PFAS levels in young adults. This highlights the importance of diet in determining PFAS exposure and the necessity of public monitoring of foods and beverages for PFAS contamination.

Any Infant Formula Amount, but Not Infant Formula Type, Is Associated with Less Healthful Subsequent Beverage Intake among Special Supplemental Nutrition Program for Women, Infants, and Children-Participating Children.

Background: The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) provides nutrition assistance to low-income households, including infant formula for infants not fully breastfeeding. Issuance of lactose-reduced infant formula made with corn syrup solids (CSSF) is associated with elevated risk of obesity in early life, but associations between formula type and dietary intake have not been examined. Objectives: To evaluate associations between infant formula (amount and type) issued by WIC with subsequent child diet at ages 12-59 mo. Methods: Dietary data from 2014, 2017, and 2020 Los Angeles County WIC Survey respondents (n = 1339 children, 12-59 mo of age) were merged with WIC administrative data on infant feeding (amount and type of infant formula at ages 0-12 mo). Intake frequencies were available for sweetened beverages, sweets, juice, fast food, water, fruit, vegetables, and milk. Infant feeding was categorized by amount of WIC-issued formula (descending: fully formula fed, mostly formula fed, mostly breastfed, fully breastfed) and issuance of a CSSF (any, none). Associations between infant feeding (infant formula amount and type) and child diet were evaluated in multivariable generalized estimating equation negative binomial regression models, stratified by child age (12 to <24 mo, 24 to <60 mo). Results: Any infant formula issuance in the first year of life was adversely associated with subsequent dietary intake. This included 21%-23% higher 100% juice intake at 24 to <60 mo and 11%-13% (at 24 to <60 mo) or 20%-22% (at 12 to <24 mo) lower water intake. CSSF receipt compared with only other infant formula was not consistently associated with subsequent child diet. Conclusions: Any infant formula amount, but not CSSF receipt compared with other formula types, was associated with less healthful beverage intake patterns among WIC-participating children. WIC nutrition education may have a stronger impact if tailored based on infant feeding practices.

Proteomic and Metabolomic Signatures of Diet Quality in Young Adults.

The assessment of "omics" signatures may contribute to personalized medicine and precision nutrition. However, the existing literature is still limited in the homogeneity of participants' characteristics and in limited assessments of integrated omics layers. Our objective was to use post-prandial metabolomics and fasting proteomics to identify biological pathways and functions associated with diet quality in a population of primarily Hispanic young adults. We conducted protein and metabolite-wide association studies and functional pathway analyses to assess the relationships between a priori diet indices, Healthy Eating Index-2015 (HEI) and Dietary Approaches to Stop Hypertension (DASH) diets, and proteins (n = 346) and untargeted metabolites (n = 23,173), using data from the MetaAIR study (n = 154, 61% Hispanic). Analyses were performed for each diet quality index separately, adjusting for demographics and BMI. Five proteins (ACY1, ADH4, AGXT, GSTA1, F7) and six metabolites (undecylenic acid, betaine, hyodeoxycholic acid, stearidonic acid, iprovalicarb, pyracarbolid) were associated with both diets (p < 0.05), though none were significant after adjustment for multiple comparisons. Overlapping proteins are involved in lipid and amino acid metabolism and in hemostasis, while overlapping metabolites include amino acid derivatives, bile acids, fatty acids, and pesticides. Enriched biological pathways were involved in macronutrient metabolism, immune function, and oxidative stress. These findings in young Hispanic adults contribute to efforts to develop precision nutrition and medicine for diverse populations.

Altered Nutrient Composition of Lactose-Reduced Infant Formula.

This research comprehensively examines 88 infant formulas available in the US market, with an emphasis on their diverging nutritional attributes based on lactose content. We stratified formulas into three categories: lactose-free, lactose-reduced, and entirely lactose-based. The formulas' nutritional content for 58 nutrients was obtained from the Nutrition Data System for Research (NDSR). Nutritional analysis revealed significant differences in nutrient composition across formula categories. For example, the results showed significant associations between the lactose content and glycemic index (GI) of the formula as well as 25 other nutrients. Specifically, we showed that for every gram of lactose per 100 g of formula that is removed, there was a 10.1% increase in GI (ß = -10.12, p ≤ 0.000), a 19%,5%, and a 2% increase in added sugar (ß = -0.19, p < 0.01), protein (ß = -0.05, p < 0.001), and polyunsaturated fatty acids (ß = -0.01, p < 0.01). The substitution of lactose in infant formulas significantly alters their nutritional profile, inducing changes in GI, added sugar, protein, and polyunsaturated fatty acids. These modifications have potential consequences for infant growth and metabolic responses and could influence long-term health trajectories. The clinical relevance of the composition differences between formulas should be further explored.

Exposure to perfluoroalkyl substances and longitudinal changes in bone mineral density in adolescents and young adults: A multi-cohort study.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) may impair bone development in adolescence, which impacts life-long bone health. No previous studies have examined prospective associations of individual PFAS and their mixture with bone mineral density (BMD) changes in Hispanic young persons, a population at high risk of osteoporosis in adulthood. OBJECTIVES: To examine associations of individual PFAS and PFAS mixtures with longitudinal changes in BMD in an adolescent Hispanic cohort and examine generalizability of findings in a mixed-ethnicity young adult cohort (58.4% Hispanic). METHODS: Overweight/obese adolescents from the Study of Latino Adolescents at Risk of Type 2 Diabetes (SOLAR; n = 304; mean follow-up = 1.4 years) and young adults from the Southern California Children's Health Study (CHS; n = 137; mean follow-up = 4.1 years) were included in this study. Plasma PFAS were measured at baseline and dual x-ray absorptiometry scans were performed at baseline and follow-up to measure BMD. We estimated longitudinal associations between BMD and five PFAS via separate covariate-adjusted linear mixed effects models, and between BMD and the PFAS mixture via quantile g-computation. RESULTS: In SOLAR adolescents, baseline plasma perfluorooctanesulfonic acid (PFOS) was associated with longitudinal changes in BMD. Each doubling of PFOS was associated with an average -0.003 g/cm2 difference in change in trunk BMD per year over follow-up (95% CI: -0.005, -0.0002). Associations with PFOS persisted in CHS young adults, where each doubling of plasma PFOS was associated with an average -0.032 g/cm2 difference in total BMD at baseline (95% CI -0.062, -0.003), though longitudinal associations were non-significant. We did not find associations of other PFAS with BMD; associations of the PFAS mixture with BMD outcomes were primarily negative though non-significant. DISCUSSION: PFOS exposure was associated with lower BMD in adolescence and young adulthood, important periods for bone development, which may have implications on future bone health and risk of osteoporosis in adulthood.

Postprandial Metabolite Profiles and Risk of Prediabetes in Young People: A Longitudinal Multicohort Study.

OBJECTIVE: Prediabetes in young people is an emerging epidemic that disproportionately impacts Hispanic populations. We aimed to develop a metabolite-based prediction model for prediabetes in young people with overweight/obesity at risk for type 2 diabetes. RESEARCH DESIGN AND METHODS: In independent, prospective cohorts of Hispanic youth (discovery; n = 143 without baseline prediabetes) and predominately Hispanic young adults (validation; n = 56 without baseline prediabetes), we assessed prediabetes via 2-h oral glucose tolerance tests. Baseline metabolite levels were measured in plasma from a 2-h postglucose challenge. In the discovery cohort, least absolute shrinkage and selection operator regression with a stability selection procedure was used to identify robust predictive metabolites for prediabetes. Predictive performance was evaluated in the discovery and validation cohorts using logistic regression. RESULTS: Two metabolites (allylphenol sulfate and caprylic acid) were found to predict prediabetes beyond known risk factors, including sex, BMI, age, ethnicity, fasting/2-h glucose, total cholesterol, and triglycerides. In the discovery cohort, the area under the receiver operator characteristic curve (AUC) of the model with metabolites and known risk factors was 0.80 (95% CI 0.72-0.87), which was higher than the risk factor-only model (AUC 0.63 [0.53-0.73]; P = 0.001). When the predictive models developed in the discovery cohort were applied to the replication cohort, the model with metabolites and risk factors predicted prediabetes more accurately (AUC 0.70 [95% CI 40.55-0.86]) than the same model without metabolites (AUC 0.62 [0.46-0.79]). CONCLUSIONS: Metabolite profiles may help improve prediabetes prediction compared with traditional risk factors. Findings suggest that medium-chain fatty acids and phytochemicals are early indicators of prediabetes in high-risk youth.

Associations between Dietary Sugar and Fiber with Infant Gut Microbiome Colonization at 6 Mo of Age.

BACKGROUND: The taxonomic composition of the gut microbiome undergoes rapid development during the first 2-3 y of life. Poor diet during complementary feeding has been associated with alterations in infant growth and compromised bone, immune system, and neurodevelopment, but how it may affect gut microbial composition is unknown. OBJECTIVES: This cross-sectional study aimed to examine the associations between early-life nutrition and the developing infant gut microbiota at 6 mo of age. METHODS: Latino mother-infant pairs from the Mother's Milk Study (n = 105) were included. Infant gut microbiota and dietary intake were analyzed at 6 mo of age using 16S ribosomal RNA amplicon sequencing and 24-h dietary recalls, respectively. Poisson generalized linear regression analysis was performed to examine associations between dietary nutrients and microbial community abundance while adjusting for infants' mode of delivery, antibiotics, infant feeding type, time of introduction of solid foods, energy intake, and body weight. A P value of <0.05 was used to determine the statistical significance in the study. RESULTS: Infants with higher consumption of total sugar exhibited a lower relative abundance of the genera Bacteroides (ß = -0.01; 95% CI: -0.02, -0.00; P = 0.03) and genus Clostridium belonging to the Lachnospiraceae family (ß = -0.02; 95% CI: -0.03, -0.00; P = 0.01). In addition, a higher intake of free sugar (which excludes sugar from milk, dairy, and whole fruit) was associated with several bacteria at the genus level, including Parabacteroides genus (ß = 0.03; 95% CI: 0.01, 0.05; P = 0.001). Total insoluble fiber intake was associated with favorable bacteria at the genus level such as Faecalibacterium (ß = 0.28; 95% CI: 0.03, 0.52; P = 0.02) and Coprococcus (ß = 0.28; 95% CI: 0.02, 0.52; P = 0.03). CONCLUSION: These findings demonstrate that early-life dietary intake at 6 mo impacts the developing gut microbiome associated with the presence of both unfavorable gut microbes and dietary fiber-associated commensal microbes.

Endotoxin biomarkers, hepatic fat fraction, liver volume and liver stiffness among adolescents at high-risk for non-alcoholic fatty liver disease: The HEROES study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is on the rise among youth. Identifying biomarkers of NAFLD progression/risk can aid in prevention efforts. AIMS: This pilot study investigated associations of two endotoxin biomarkers-lipopolysaccharide-binding protein (LBP) and anti-endotoxin core immunoglobulin G (EndoCab)-with markers of NAFLD among 99 Latino/Latina adolescents (11-19 years) with obesity. MATERIALS & METHODS: We used linear regression to examine associations of each endotoxin biomarker (per 1-SD) with hepatic fat fraction (HFF), liver volume, and liver stiffness. RESULTS: We found positive associations of LBP with HFF and liver volume. Each 1-SD increment in LBP corresponded with 2.35% (95% CI: 0.46%, 4.23%) higher HFF and 0.14 (0.06, 0.23) L greater liver volume after adjusting for age, sex, and maternal education. Accounting for abdominal adiposity and Tanner stage did not change results. Excluding 72 participants with NAFLD attenuated associations of LBP with HFF but associations with liver volume persisted (0.11 [0.01, 0.21] L). EndoCab was not associated with any liver outcomes. Neither endotoxin biomarker predicted liver stiffness. DISCUSSION/CONCLUSION: While additional research is warranted, our results support LBP as a biomarker of NAFLD risk/progression in high-risk youth.

Sex-specific impulsivity, but not other facets of executive function, predicts fat and sugar intake two-years later amongst adolescents with a healthy weight: Findings from the ABCD study.

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.

Characterizing alterations in the gut microbiota following postpartum weight change.

IMPORTANCE: Previous research has reported differences in the gut microbiome associated with varying body compositions. More specifically, within populations of mothers, the focus has been on the impact of gestational weight gain. This is the first study to examine postpartum weight change and its association with changes in the gut microbiome, similarly, it is the first to use a Latina cohort to do so. The results support the idea that weight gain may be an important factor in reducing gut microbiome network connectivity, diversity, and changing abundances of specific microbial taxa, all measures thought to impact host health. These results suggest that weight gain dynamically alters mothers' gut microbial communities in the first 6 months postpartum, with comparatively little change in mothers who lost weight; further research is needed to examine the health consequences of such changes.

Human milk EV-miRNAs: a novel biomarker for air pollution exposure during pregnancy.

Exposure to ambient and near-roadway air pollution during pregnancy has been linked with several adverse health outcomes for pregnant women and their babies. Emerging research indicates that microRNA (miRNA) expression can be altered by exposure to air pollutants in a variety of tissues. Additionally, miRNAs from breast tissue and circulating miRNAs have previously been proposed as a biomarker for breast cancer diagnosis and prognosis. Therefore, this study sought to evaluate the associations between pregnancy exposures to ambient (PM10, PM2.5, NO2, O3) and near-roadway air pollution (total NOx, freeway NOx, non-freeway NOx) with breast milk extracellular vesicle miRNA (EV-miRNA), measured at 1-month postpartum, in a cohort of 108 Latina women living in Southern California. We found that PM10 exposure during pregnancy was positively associated with hsa-miR-200c-3p, hsa-miR-200b-3p, and hsa-let-7c-5p, and was negatively associated with hsa-miR-378d. We also found that pregnancy PM2.5 exposure was positively associated with hsa-miR-200c-3p and hsa-miR-200b-3p. First and second trimester exposure to PM10 and PM2.5 was associated with several EV-miRNAs with putative messenger RNA targets related to cancer. This study provides preliminary evidence that air pollution exposure during pregnancy is associated with human milk EV-miRNA expression.

Variation in executive function relates to BMI increases in youth who were initially of a healthy weight in the ABCD Study.

OBJECTIVE: The study aim was to determine whether (A) differences in executive function (EF) and cognition precede weight gain or (B) weight gain causes changes to EF and cognition. METHODS: Data were gathered from the Adolescent Brain Cognitive Development (ABCD) Study (release 4.0; ages 9-12 years old [N = 2794]; 100% had healthy weight at baseline [i.e., 9/10 years old], 12.4% had unhealthy weight by ages 11/12 years). EF and cognition were assessed across several domains (e.g., impulsivity, inhibitory control, processing speed, memory); BMI was calculated from height and weight. Nested random-effects mixed models examined (A) BMI ~ EF × Time (i.e., variation in EF/cognition precedes weight gain) and (B) EF ~ BMI × Time (weight gain causes changes to EF/cognition) and controlled for sex, puberty, and caregiver education; random effects were site and subject. RESULTS: Variation in impulsivity, memory, learning, and processing speed was associated with greater increases in BMI trajectories from 9 to 12 years old. Weight gain was associated with a decrease in inhibitory control, but no other associations were observed. CONCLUSIONS: Underlying variation in EF and cognition may be important for weight gain, but 2 years of weight gain may not be enough to have clinical implications for EF and cognition beyond inhibitory control. These findings suggest that more attention should be paid to the inclusion of EF programs in obesity prevention efforts.

Effects of Low-Calorie Sweetener Restriction on Glycemic Variability and Cardiometabolic Health in Children with Type 1 Diabetes: Findings of a Pilot and Feasibility Study.

Low-calorie sweeteners (LCS) are commonly consumed by children with type 1 diabetes (T1D), yet their role in cardiometabolic health is unclear. This study examined the feasibility, acceptability, and preliminary effects of 12 weeks of LCS restriction among children with T1D. Children (n = 31) with T1D completed a two-week run-in (n = 28) and were randomly assigned to avoid LCS (LCS restriction, n = 15) or continue their usual LCS intake (n = 13). Feasibility was assessed using recruitment, retention, and adherence rates percentages. Acceptability was assessed through parents completing a qualitative interview (subset, n = 15) and a satisfaction survey at follow-up. Preliminary outcomes were between-group differences in change in average daily time-in-range (TIR) over 12 weeks (primary), and other measures of glycemic variability, lipids, inflammatory biomarkers, visceral adiposity, and dietary intake (secondary). Linear regression, unadjusted and adjusted for age, sex, race, and change in BMI, was used to compare mean changes in all outcomes between groups. LCS restriction was feasible and acceptable. No between-group differences in change in TIR or other measures of glycemic variability were observed. However, significant decreases in TNF-alpha (-0.23 ± 0.08 pg/mL) and improvements in cholesterol (-0.31 ± 0.18 mmol/L) and LDL (-0.60 ± 0.39 mmol/L) were observed with usual LCS intake, compared with LCS restriction. Those randomized to LCS restriction did not report increases in total or added sugar intake, and lower energy intake was reported in both groups (-190.8 ± 106.40 kcal LCS restriction, -245.3 ± 112.90 kcal usual LCS intake group). Decreases in percent energy from carbohydrates (-8.5 ± 2.61) and increases in percent energy from protein (3.2 ± 1.16) and fat (5.2 ± 2.02) were reported with usual LCS intake compared with LCS restriction. Twelve weeks of LCS restriction did not compromise glycemic variability or cardiometabolic outcomes in this small sample of youth with T1D. Further examination of LCS restriction among children with T1D is warranted.

Effects of Dietary Sugar Reduction on Biomarkers of Cardiometabolic Health in Latino Youth: Secondary Analyses from a Randomized Controlled Trial.

Pediatric obesity and cardiometabolic disease disproportionately impact minority communities. Sugar reduction is a promising prevention strategy with consistent cross-sectional associations of increased sugar consumption with unfavorable biomarkers of cardiometabolic disease. Few trials have tested the efficacy of pediatric sugar reduction interventions. Therefore, in a parallel-design trial, we randomized Latino youth with obesity (BMI ≥ 95th percentile) [n = 105; 14.8 years] to control (standard diet advice) or sugar reduction (clinical intervention with a goal of ≤10% of calories from free sugar) for 12-weeks. Outcomes included changes in glucose tolerance and its determinants as assessed by a 2-h frequently sample oral glucose tolerance test, fasting serum lipid profile (total cholesterol, HDL, LDL, triglycerides, cholesterol:HDL), and inflammatory markers (CRP, IL-6, TNF-α). Free sugar intake decreased in the intervention group compared to the control group [11.5% to 7.3% vs. 13.9% to 10.7% (% Energy), respectively, p = 0.02], but there were no effects on any outcome of interest (pall > 0.07). However, an exploratory analysis revealed that sugar reduction, independent of randomization, was associated with an improved Oral-disposition index (p < 0.001), triglycerides (p = 0.049), and TNF-α (p = 0.02). Dietary sugar reduction may have the potential to reduce chronic disease risks through improvements in beta-cell function, serum triglycerides, and inflammatory markers in Latino adolescents with obesity.

Influence of technical and maternal-infant factors on the measurement and expression of extracellular miRNA in human milk.

Breast milk contains thousands of bioactive compounds including extracellular vesicle microRNAs (EV-miRNAs), which may regulate pathways such as infant immune system development and metabolism. We examined the associations between the expression of EV-miRNAs and laboratory variables (i.e., batch effects, sample characteristics), sequencing quality indicators, and maternal-infant characteristics. The study included 109 Latino mother-infant dyads from the Southern California Mother's Milk Study. Mothers were age 28.0 ± 5.6 and 23-46 days postpartum. We used principal components analysis to evaluate whether EV-miRNA expression was associated with factors of interest. Then, we used linear models to estimate relationships between these factors and specific EV-miRNA counts and analyzed functional pathways associated with those EV-miRNAs. Finally, we explored which maternal-infant characteristics predicted sequencing quality indicators. Sequencing quality indicators, predominant breastfeeding, and breastfeedings/day were associated with EV-miRNA principal components. Maternal body mass index and breast milk collection timing predicted proportion of unmapped reads. Expression of 2 EV-miRNAs were associated with days postpartum, 23 EV-miRNAs were associated with breast milk collection time, 23 EV-miRNAs were associated with predominant breastfeeding, and 38 EV-miRNAs were associated with breastfeedings/day. These EV-miRNAs were associated with pathways including Hippo signaling pathway and ECM-receptor interaction, among others. This study identifies several important factors that may contribute to breast milk EV-miRNA expression. Future studies should consider these findings in the design and analysis of breast milk miRNA research.

Obesogens and Obesity: State-of-the-Science and Future Directions Summary from a Healthy Environment and Endocrine Disruptors Strategies Workshop.

On September 7 and 8, 2022, Healthy Environment and Endocrine Disruptors Strategies, an Environmental Health Sciences program, convened a scientific workshop of relevant stakeholders involved in obesity, toxicology, or obesogen research to review the state of the science regarding the role of obesogenic chemicals that might be contributing to the obesity pandemic. The workshop's objectives were to examine the evidence supporting the hypothesis that obesogens contribute to the etiology of human obesity; to discuss opportunities for improved understanding, acceptance, and dissemination of obesogens as contributors to the obesity pandemic; and to consider the need for future research and potential mitigation strategies. This report details the discussions, key areas of agreement, and future opportunities to prevent obesity. The attendees agreed that environmental obesogens are real, significant, and a contributor at some degree to weight gain at the individual level and to the global obesity and metabolic disease pandemic at a societal level; moreover, it is at least, in theory, remediable.

Maternal low-calorie sweetener consumption rewires hypothalamic melanocortin circuits via a gut microbial co-metabolite pathway.

The prevalence of obesity and type 2 diabetes is growing at an alarming rate, including among pregnant women. Low-calorie sweeteners (LCSs) have increasingly been used as an alternative to sugar to deliver a sweet taste without the excessive caloric load. However, there is little evidence regarding their biological effects, particularly during development. Here, we used a mouse model of maternal LCS consumption to explore the impact of perinatal LCS exposure on the development of neural systems involved in metabolic regulation. We report that adult male, but not female, offspring from both aspartame- and rebaudioside A-exposed dams displayed increased adiposity and developed glucose intolerance. Moreover, maternal LCS consumption reorganized hypothalamic melanocortin circuits and disrupted parasympathetic innervation of pancreatic islets in male offspring. We then identified phenylacetylglycine (PAG) as a unique metabolite that was upregulated in the milk of LCS-fed dams and the serum of their pups. Furthermore, maternal PAG treatment recapitulated some of the key metabolic and neurodevelopmental abnormalities associated with maternal LCS consumption. Together, our data indicate that maternal LCS consumption has enduring consequences on the offspring's metabolism and neural development and that these effects are likely to be mediated through the gut microbial co-metabolite PAG.