Journal of Nutrition最新文献

Background: Diet is an important determinant of health and may moderate genetic susceptibility to obesity, but meta-analyses of available evidence are lacking.

Objectives: This study aimed to systematically review and meta-analyze evidence on the moderating effect of diet on genetic susceptibility to obesity, assessed with polygenic risk scores (PRS).

Methods: A systematic search was conducted using MEDLINE, EMBASE, Web of Science, and the Cochrane Library to retrieve observational studies that examined PRS-diet interactions on obesity-related outcomes. Dietary exposures of interest included diet quality/dietary patterns and consumption of specific food and beverage groups. Random-effects meta-analyses were performed for pooled PRS- healthy eating index (HEI) interaction coefficients on body mass index (BMI) (on the basis of data from 4 cohort studies) and waist circumference (WC) (on the basis of data from 3 cohort studies).

Results: Out of 36 retrieved studies, 78% were conducted among European samples. Twelve out of 21 articles examining dietary indices/patterns, and 16 out of 21 articles examining food/beverage groups observed some significant PRS-diet interactions. However, within many articles, findings are inconsistent when testing different combinations of obesity PRS-dietary factors and outcomes. Nevertheless, higher HEI scores and adherence to plant-based dietary patterns emerged as the more prominent diet quality/patterns that moderated genetic susceptibility to obesity, whereas higher consumption of fruits and vegetables, and lower consumption of fried foods and sugar-sweetened beverages emerged as individual food/beverage moderators. Results from the meta-analysis suggest that a higher HEI attenuates genetic susceptibility on BMI (pooled PRS∗HEI coefficient: -0.08; 95% confidence interval (CI): -0.15, 0.00; P = 0.0392) and WC (-0.37; 95% CI: -0.60, -0.15; P = 0.0013).

Conclusions: Current observational evidence suggests a moderating role of overall diet quality in polygenic risk of obesity. Future research should aim to identify genetic loci that interact with dietary exposures on anthropometric outcomes and conduct analyses among diverse ethnic groups.

Trial registration number: This study was registered at the International Prospective Register of Systematic Reviews as CRD42022312289.

Background: Mycotoxin exposure during pregnancy has been associated with adverse birth outcomes and poor infant growth. We assessed multiple biomarkers and metabolites of exposure to mycotoxins at birth and their associations with birth outcomes and infant growth in 274 newborns in rural Burkina Faso.

Methods: Whole-blood microsamples were analyzed for mycotoxin concentrations in newborns in the Biospecimen substudy nested in the MIcronutriments pour la SAnté de la Mère et de l'Enfant-III trial using ultra-performance liquid chromatography coupled with tandem mass spectrometry. Unadjusted and adjusted associations between mycotoxin exposure, and birth outcomes and infant growth at 6 mo were estimated using linear regression models for continuous outcomes and linear probability models with robust variance estimation for binary outcomes. Infant growth trajectories from birth to 6 mo were compared by exposure status using mixed-effects models with a random intercept for the individual infant and a random slope for the infant's age.

Results: Ochratoxin A (OTA) exposure was detected in 38.3% of newborns, with other mycotoxins being detected in the range of 0.36% and 4.01%. OTA exposure was significantly associated with adverse birth outcomes, such as lower birth weight [β (95% CI): -0.11 kg (-0.21, 0.00); P = 0.042] and ponderal index [β (95% CI): -0.62 gm/cm³ (-1.19, -0.05); P = 0.034], and a marginally significant lower length growth trajectories during the first 6 mo [β (95% CI): -0.08 cm/mo (-0.15, 0.0); P = 0.057].

Conclusions: OTA exposure was prevalent among newborns and also associated with lower growth at birth and during the first 6 mo. The results emphasize the importance of nutrition-sensitive strategies to mitigate dietary OTA, as well as adopting food safety measures in Burkina Faso during the fetal period of development.

Background: Increased dietary protein at breakfast promotes cardiometabolic health; however, whether these improvements occur at the molecular level is unknown.

Objectives: The objective was to examine whether long-term consumption of breakfast, varying in protein quantity, alters the expression of circulating microRNAs (miRNAs) associated with cardiometabolic health in "breakfast-skipping" adolescents.

Methods: Thirty adolescents (age: 19 ± 1 y; body mass index: 25.4 ± 3 kg/m²) completed a 6-mo tightly controlled breakfast trial in which participants consumed 350 kcal normal-protein (NP, 10 g protein) or higher-protein (HP, 30 g protein) breakfasts or continued to BS for 6 mo. Fasting blood samples were collected at baseline (PRE) and 6 mo (POST) for assessment of 12 a priori circulating plasma miRNA expression levels (real-time quantitative polymerase chain reaction), glucose, insulin, IL-6, and C-reactive protein.

Results: No main effects of group were observed for any miRNAs; however, a time-by-group interaction was detected for the expression of miR-126-3p (P = 0.05). HP breakfast tended to increase miR-126-3p expression throughout the study (POST-PRE, P = 0.09) leading to greater expression at POST compared with BS (P = 0.03), whereas NP breakfast did not. Additionally, several miRNAs predicted fasting concentrations of IL-6: miR-320a-3p, -146a-5p, -150-5p, -423-5p, -122-5p, glucose: miR-24-3p, -126-3p; insulin: miR-24-3p, -126-3p, -15b-5p; insulin sensitivity: miR-24-3p, -126-3p, -199a-5p, -15b-5p; and β-cell function: miR-15b-5p (R² between 0.2 and 0.39; P < 0.05) from PRE and POST samples across groups.

Conclusions: These data support the daily consumption of a HP breakfast to promote cardiometabolic health, potentially through changes in miRNA expression, in a sensitive life-stage where early intervention strategies are critical to reduce the risk of adult-onset chronic disease.

Trial registration number: NCT03146442.

Background: Consumption of tomatoes and tomato carotenoids is associated with a reduced risk of prostate cancer. Prostate tissue accumulates tomato carotenoids, including lycopene, β-carotene, and phytoene. Phytoene accumulation is relatively greater in the prostate than that of lycopene, but the metabolic determinants of tissue carotenoid profiles are poorly understood.

Objectives: The purpose of this study was to determine if differences in stability, cellular uptake, and clearance of phytoene compared with lycopene or β-carotene by prostate and intestinal cells may explain differences in observed tissue carotenoid profiles.

Methods: Gene and protein expression for carotenoid metabolism in prostate cell lines were analyzed by qRT-PCR and Western blot, respectively. Uptake, efflux, and clearance of phytoene, lycopene, or β-carotene by prostate cell (LNCaP, RWPE-1, and PC-3) and absorptive enterocyte (Caco-2) cultures were compared. The effect of scavenger receptor class B member 1 (SCARB1) inhibition on carotenoid uptake by LNCaP, RWPE-1, and Caco-2 cells was tested.

Results: SCARB1 was expressed across prostate cell lines. Lycopene, phytoene, and β-carotene uptakes were similar in LNCaP and PC-3 cells, whereas RWPE-1 cells absorbed a smaller portion of the phytoene dose than lycopene or β-carotene doses. The clearance rates of carotenoids from LNCaP cells did not differ. Intestinal cell uptake of phytoene was greatest, followed by β-carotene and lycopene. SR-BI inhibitor treatment did not significantly reduce the uptake or efflux of carotenoids by LNCaP or Caco-2 cells at the dose concentration provided.

Conclusions: Overall, this study suggests that greater bioavailability at the point of the intestine and greater stability of phytoene are determinants of the relative enrichment of phytoene in prostate tissue.

Background: Accumulating evidence reveals that inappropriate meal timing contributes to the development of lifestyle-related diseases. An underlying mechanism is thought to be the disruption of the intracellular circadian clock in various tissues based on observations in both systemic and tissue-specific clock gene-deficient mice. However, whether the effects of conditional clock gene knockout are comparable to those of inappropriate meal timing remains unclear.

Objectives: This study aimed to compare the effects of a recently developed 28-h feeding cycle model with those of a core clock gene Bmal1 uterine conditional knockout (Bmal1 cKO) model on uterine mRNA expression profiles.

Methods: The models were generated by subjecting C57BL/6J mice to an 8-h/20-h feeding/fasting cycle for 2 wk and crossing Bmal1-floxed mice with PR-Cre mice. Microarray analyses were conducted using uterine samples obtained at the beginning of the dark and light periods.

Results: The analyses identified 516 and 346, significantly 4-fold and 2-fold, up- or downregulated genes in the 28-h feeding cycle and Bmal1 cKO groups, respectively, compared with each control group. Among these genes, only 7 (1.4%) and 63 (18.2%) were significantly up- or downregulated in the other model. Moreover, most (n = 44, 62.9%) of these genes were oppositely regulated. These findings were confirmed by gene set enrichment analyses.

Conclusions: This study reveals that a 28-h feeding cycle and Bmal1 cKO differently affect gene expression profiles and highlights the need for considering this difference to assess the pathophysiology of diseases associated with inappropriate meal timing.

Background: Our previous work has shown that senescent B cells accumulate in the human adipose tissue (AT) from people with obesity, where they express transcripts for markers associated with the senescence-associated secretory phenotype (SASP) and secrete multiple inflammatory mediators. These functions of AT-derived B cells are metabolically supported.

Objectives: To show that Metformin (MET), a widely used hypoglycemic and antidiabetic drug, is able at least in vitro to decrease frequencies, secretory profile, and metabolic requirements of senescent B cells isolated from the AT from people with obesity.

Methods: We recruited adult females with obesity (n = 8, age 40 ± 2 y, BMI range: 33-42) undergoing breast reduction surgery, who donated their discarded subcutaneous AT. B cells from stromal vascular fractions isolated after collagenase digestion of the AT were evaluated after in vitro incubation with MET (1 mM × 10⁶ B cells) or with a medium for the following measures. The expression of transcripts for SASP-associated markers (p16^INK4a and p21^CIP1/WAF1) measured by quantitative polymerase chain reaction (qPCR); secretion of inflammatory cytokines (TNF-α, IL-6, IFN-γ and IL-17A) measured by a Cytometric Bead Array); metabolic characteristics as identified by a glycolytic test and Seahorse technology, and by the expression of transcripts for glucose transporters and metabolic enzymes involved in glucose metabolic pathways, measured by qPCR. To examine differences between MET-treated compared with untreated groups, paired Student's t tests (two-tailed) were employed.

Results: MET in vitro was able to reduce frequencies and numbers of senescent B cells, as identified by staining with β-galactosidase, as well as the secretion of inflammatory cytokines, the expression of transcripts for SASP, and metabolic markers that support intrinsic B cell inflammation.

Conclusions: Our results provide evidence to support the beneficial effects of MET in reducing AT-related inflammation through its effects on senescent B cells.

Background: Single-nucleotide polymorphism (SNP) allele frequencies, dietary habits, and folate status and their associations vary across ethnic populations. Little is known about the SNPs accounting for variations of folate-related biomarkers for Chinese preparing-for-pregnant females.

Objectives: We aimed to identify SNPs contributing to RBC and serum folate, vitamin B-12, and homocysteine concentrations in Chinese female preconception population.

Methods: A genome-wide association study was conducted on 1000 randomly selected preconception Chinese women from the Shanghai Preconception Cohort. SNPs were genotyped using Illumina chips, and associations with biomarkers were assessed using simple linear regression models under the assumption of an additive genetic model. Genome-wide significance was considered at P < 10^-7.

Results: The MTHFR rs1801133 was the major genetic coding variant contributing to RBC folate, serum folate, and homocysteine concentrations (P = 2.28 × 10^-16; P = 8.85 × 10^-8, and P = 2.46 × 10^-13, repsectively). It is associated with increased RBC folate (β: 0.154 per additional risk allele after log transform), decreased serum folate (β: -0.951 per additional risk allele), and increased serum homocysteine concentrations (β: 1.153 per additional risk allele). The predominant SNP associated with serum folate was rs147162222 in NTRK2 (P = 2.55 × 10^-8), although that associated with homocysteine was rs77025184 located between PDE7B and LINC00271 (P = 4.91 × 10^-17). For vitamin B-12, FUT2 rs1047781 was the dominant genetic variant (P = 1.59 × 10^-10). The numbers of signals with a P value of <10^-7 for RBC folate, serum folate, vitamin B-12, and homocysteine were 12, 18, 8, and 614, respectively.

Conclusions: This study represents the first genome-wide association study focusing on folate-related biomarkers in a Chinese preparing-for-pregnant female population. The contributions of dominent SNPs to each biomarker are partly different from other populations. The rs1801133 (C677T) in MTHFR is the predominant genetic variant contributing to RBC folate and rs1047781 (A385T) in FUT2 as the primary one explaining vitamin B-12. Notably, the intronic rs147162222 and noncoding rs77025184 are the predominant SNPs for serum folate and homocysteine, respectively.

Background: Intravenous lipids are critical to the care of extremely premature and other high-risk infants.

Objectives: This study evaluated safety and efficacy of parenteral nutrition (PN) with composite intravenous lipid emulsion (CO-ILE) with fish oil compared with pure soybean oil lipid emulsion (SOLE).

Methods: Randomized, controlled, double-blind, multicenter study (NCT02579265) in neonates/infants anticipated to require ≥28 d of PN due to gastrointestinal malformations or injury. Duration of the initial and extended treatment phase was 28 d and 84 d, respectively (for patients with PN indication after day 28).

Results: Eighty-three patients (mean postnatal age 11.4 d, 54 preterm) received CO-ILE and 78 patients received SOLE (mean postnatal age 8.3 d, 59 preterm). Thirty-three patients per group completed 28 d of treatment. Risk of having conjugated bilirubin values >2 mg/dL confirmed by a second sample 7 d after the first during the initial treatment phase (primary outcome) was 2.4% (2 of 83) with CO-ILE and 3.8% (3 of 78) with SOLE (risk ratio: 0.59; 95% confidence interval [CI]: 0.09, 3.76). Between days 29 and 84, the number of patients with confirmed conjugated bilirubin values >2 mg/dL did not increase in the CO-ILE group (n = 2) and increased in the SOLE group (n = 9). At the end of the initial treatment phase, conjugated bilirubin concentrations were 45.6% lower under CO-ILE than under SOLE (P = 0.006). There was no clinical or laboratory evidence of essential fatty acid deficiency in patients in the CO-ILE group. Median time to discharge alive was 56.7 d and 66.4 d with CO-ILE and SOLE, respectively (hazard ratio: 1.16; 95% CI: 0.81, 1.68).

Conclusions: CO-ILE was associated with a possible lower risk of cholestasis and significantly lower conjugated bilirubin concentration at the end of the initial treatment phase in high-risk neonates and infants as compared with patients treated with SOLE. In summary, these data indicate that CO-ILE can be considered safe and may be preferable over SOLE in high-risk neonates. This trial was registered at clinicaltrials.gov as NCT02579265.

Background: Circulating dietary biomarkers are not direct proxies for intake, as the biomarkers reflect not only food and supplement consumption but also nutrient absorption, metabolism, and tissue distribution. Therefore, along with nutrient intake, several other upstream factors can impact dietary biomarker concentrations, including demographic, medical history, and genetic factors.

Objectives: The aim of this study was to explore the dietary and nondietary determinants of circulating levels of vitamins A, C, D, and E among children aged 6 mo-4 y.

Methods: Plasma retinol, β-carotene, ascorbic acid, 25(OH)D, α-tocopherol, and γ-tocopherol were measured in 2887 samples from 1490 children enrolled in The Environmental Determinants of Diabetes in the Young study. Dietary intake was assessed with 3-d food records. Associations of genetic and environmental factors with biomarker concentrations were examined using multivariable linear regression models with random intercepts.

Results: All biomarkers except retinol were positively associated with intake of the same nutrient. Inverse associations were identified between recent gastrointestinal infection and β-carotene, ascorbic acid, and α-tocopherol, whereas recent respiratory infection was associated inversely with plasma retinol. Several genetic determinants of biomarker status were identified, validating previously reported findings. For some genetic and environmental exposures, we found evidence of statistical interaction with same-nutrient intake, indicating that the association between intake and biomarker concentration is dependent on the level or status of these other exposures. For example, the association between β-carotene intake and concentration is weaker among children with a recent respiratory infection.

Conclusions: Our findings suggest that nondietary exposures including childhood infections can alter micronutrient metabolism. This summary of micronutrient determinants will facilitate improved design of future analyses exploring the role of diet in childhood chronic disease etiology through a better understanding of relevant potential confounders and mediators of the diet-outcome relationships.

Background: Multiple sclerosis (MS) is an inflammatory neuroimmune disease with a multifaceted etiology and long-lasting adverse effects. Several studies have explored the role of 25-hydroxyvitamin D (25(OH)D) serum levels, vitamin D receptor (VDR) gene polymorphisms, and vitamin D supplementation (VDS) in individuals with MS.

Objectives: The aim of this study was to evaluate the relationship of MS with 25(OH)D serum levels, VDR gene polymorphisms, and VDS.

Methods: We assessed relevant articles published in PubMed, Scopus, and Web of Science from the inception up to 24 February, 2024. Meta-analyses that investigated the link of 25(OH)D serum levels, VDR gene polymorphisms including Apal (rs7975232), BsmI (rs1544410), Taql (rs731236), and Fokl (rs10735810), and VDS with the risk and clinical manifestations of MS were included. The methodological quality of selected articles was assessed by the Assessment of Multiple Systematic Reviews version 2. The statistical analysis of this umbrella review was carried out using RStudio version 2023.03.1 and R version 4.3.2, simultaneously.

Results: A total of 23 of 304 records were entered into this umbrella review with a pooled sample size of 37,567 participants. Eleven articles were rated as high quality, 1 was moderate quality, 1 was low quality, and 10 were critically low quality. The homozygote model of FokI (FF+ff compared with Ff) was significantly associated with an 8% reduction of MS risk (odds ratio: 0.92, 95% confidence interval: 0.86, 0.98; I² = 0%, P > 0.99).

Conclusion: According to existing clinical evidence, the risk of MS may be associated with VDR gene polymorphism. Further studies are needed to explore the association of MS and vitamin D.

Trial registration number: This trial was registered at International Prospective Register of Systematic Reviews (PROSPERO) as registration number CRD42024521541.