Annals of Nutrition and Metabolism最新文献

Background: The global obesity epidemic necessitates therapies that enhance energy expenditure. Non-shivering thermogenesis (NST) in brown/beige adipose tissue represents a promising target, with fibroblast growth factor 21 (FGF21) emerging as a critical regulator linking environmental stimuli to adipose plasticity and mitochondrial function. However, the precise mechanisms of FGF21 secretion and its specific role in adipose tissue browning and subsequent NST potentiation remain incompletely elucidated.

Summary: FGF21 regulates NST via distinct spatiotemporal mechanisms. Acute cold exposure triggers hepatic FGF21 secretion through a β₃-adrenergic-lipolysis-PPARα axis to provide lipid substrates. In contrast, chronic cold adaptation involves adipose-derived FGF21 signaling via the FGFR1/β-Klotho complex, activating the PLCγ-Ca2+-cAMP response element-binding protein pathway to enhance UCP1 expression and mitochondrial biogenesis. Aging and statins impair NST via mitochondrial dysfunction and CoQ₁₀ depletion, inducing compensatory FGF21 upregulation. Clinically, the efficacy of FGF21-based therapies relies on full activation of adipose FGFR1/β-Klotho signaling, as demonstrated by the superiority of full agonists over partial agonists.

Key messages: FGF21 exhibits dual regulation: hepatic (acute lipid mobilization) and adipose-based (chronic browning); adipose-targeted FGF21 delivery is essential for therapeutic efficacy, and future studies should integrate FGF21 with UCP1-independent pathways (e.g., creatine/succinate cycles) to advance obesity treatment.

Introduction: Observational studies have raised questions regarding the comprehensive metabolomic markers associated with dietary macronutrient intake. This study aimed to identify metabolites that are causally linked to dietary macronutrient consumption using a robust analytical framework.

Methods: This genetic association study employed a two-sample Mendelian randomization (MR) approach. Genetic proxies for metabolites and their summary statistics were sourced from 64 genome-wide association studies, and a meta-analysis provided summary statistics for 3,362 metabolites. Summary statistics for dietary carbohydrate, fat, and protein intakes were obtained from the UK Biobank. MR associations were assessed using inverse-variance weighted, weighted median, and Egger's regression models to enhance robustness. Significant metabolites were subjected to enrichment analysis to identify relevant metabolic pathways. Associations were expressed as odds ratios with 95% confidence intervals, and enrichment analysis was used to identify key KEGG pathways based on p values.

Results: MR analysis identified 540 metabolite-macronutrient associations: 186 for carbohydrate intake, 217 for fat intake, and 137 for protein intake. Metabolites inversely associated with carbohydrate and protein intake, but positively linked to fat intake, were enriched in KEGG pathways, particularly those governing the biosynthesis and metabolism of aromatic amino acids (tryptophan and phenylalanine) and branched-chain amino acids (BCAAs) (tyrosine, valine, leucine, and isoleucine).

Conclusion: This study comprehensively mapped the metabolite associations with dietary macronutrient intake using extensive genetic data. These findings highlight the critical roles of aromatic and BCAA biosynthesis and metabolism as key metabolic pathways in macronutrient regulation.

Introduction: Genetic variations, including rs17782313 (C/T) in the MC4R gene, are associated with lipid levels. Gene-diet interactions contribute to disease development. This study aimed to investigate the effects of interactions between total energy intake, protein intake, and MC4R rs17782313 on lipid parameters in Saudi adults.

Methods: In a cross-sectional study of 268 Saudi adults (aged 20-55 years), dietary data were assessed using a 136-item validated semiquantitative food frequency questionnaire, and MC4R (rs17782313) was genotyped using real-time polymerase chain reaction.

Results: Total energy and protein calorie intake interacted with the MC4R rs17782313 polymorphism to influence total cholesterol (TC) (p_interaction = 0.036 and p_interaction = 0.021, respectively). Low total energy and protein intake was associated with decreased TC levels in all genotypes at rs17782313. The interaction between total energy intake and MC4R rs17782313 affected triglyceride levels (p_interaction = 0.039). Protein calorie intake significantly interacted with MC4R rs17782313 in determining low-density lipoprotein (p_interaction = 0.042). However, none of these interactions remained significant after applying Bonferroni correction (p > 0.01).

Conclusion: Low total energy and protein intake is associated with low lipid levels among all genotypes at rs17782313 in Saudi adults. Further validation in larger cohorts is warranted to confirm these findings and explore their clinical implications.

In the article by Cavdar et al. entitled "Impact of a High-Calorie Diet on Metabolic Health, Carotid Intima-Media Thickness, and Endothelial Function in Individuals with Constitutional Thinness" [Ann Nutr Metab. 2025;81:311-318; https://doi.org/10.1159/000546273], there is an error introduced during production which deleted affiliation 2 (Department of Endocrinology and Metabolic Diseases, Istinye University, Istanbul, Turkey), which belonged to author Bercem Aycicek. The original article has been updated.

Introduction: Efficacy and safety of a novel total parenteral nutrition formula for chronic kidney disease patients, OPF-109, containing multivitamins based on the FDA2000 recommendation were investigated.

Methods: We conducted a phase III clinical trial administering OPF-109 (n = 63) or the control solutions (combination of marketed products including multivitamin based on American Medical Association 1975 guidelines) (n = 61) to the chronic kidney disease patients for 8 days. Blood concentrations of proteins and vitamins and safety were evaluated. The primary efficacy endpoint was protein concentration (serum T-P, ALB, pre-ALB, transferrin) on day 8. Safety endpoints were hematological data, blood biochemistry data, vital signs, and adverse events.

Results: Values of blood protein until day 8 were similar in 2 groups although those of vitamins B1, B6, C, and folic acid (contained more in OPF-109) were higher in the OPF-109 group. For both groups, vitamin C concentration of day 1 was below the normal range, which restored to within the range in the OPF-109 group but decreased in the control group on day 8. Vitamin K concentration (contained less in OPF-109) was over the normal range on day 1 in both groups and decreased to slightly higher than the normal range in the OPF-109 group while increased to higher than day 1 value in the control group on day 8. Safety was similar in 2 groups.

Conclusion: Efficacy and safety of OPF-109 and usefulness of multivitamins based on the FDA2000 recommendation formula were confirmed in chronic kidney disease patients.

Introduction: Creatine is a conditionally essential nutrient central to cellular energy metabolism, with roughly half of daily requirements derived from dietary sources found exclusively in animal-based foods. Insufficient dietary creatine intake has been linked to various adverse health outcomes, yet data on creatine adequacy among individuals following special diets remain limited. This study examined the prevalence of low dietary creatine intake among US individuals adhering to different special diets using cumulative data from the National Health and Nutrition Examination Survey (NHANES).

Methods: Data from NHANES 2003-2023 cycles were merged to identify participants (≥1 year old) reporting adherence to a special diet in the Dietary Data domain. Self-reported diets were categorized into thirteen groups (e.g., weight-loss, diabetic, low-fat, low-carbohydrate, gluten-free). Dietary creatine intake, estimated using established methods and excluding supplements, was classified as adequate (≥1 g/day) or inadequate (<1 g/day). Differences in the prevalence of inadequate creatine intake across diet types were assessed using chi-square tests with Bonferroni-adjusted post hoc comparisons.

Results: Among 8,407 participants (57.8% female; mean age = 45.0 ± 21.5 years) reporting adherence to a single special diet, mean creatine intake was 0.82 ± 0.82 g/day, with 69.5% classified as having inadequate intake. The prevalence of low creatine intake differed significantly across diet types (p < 0.0001), ranging from 83.3% in low-fiber diets to 60.4% in renal diets. Individuals following low-carbohydrate diets exhibited a significantly lower prevalence of inadequate intake (p = 0.00097), while high- and low-fiber, gluten-free, and weight-loss diets were associated with higher prevalence rates. Women showed greater creatine insufficiency than men across several dietary categories.

Conclusion: Inadequate dietary creatine intake is highly prevalent among individuals following a variety of special diets in the US population. Restrictive or plant-forward regimens appear particularly associated with insufficient intake, underscoring the need for nutritional strategies - such as creatine-fortified foods or supplementation - to maintain optimal creatine homeostasis and support metabolic health in at-risk groups.

Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by deficits in social interaction, communication, and the presence of restricted, repetitive behaviors. The rising global prevalence of ASD suggests a multifactorial etiology involving genetic, environmental, and neurodevelopmental factors. This review explores the establishment of the early life microbiome, highlighting rapid microbial colonization from maternal and environmental sources. Emerging evidence indicates that delivery mode and infant feeding practices may influence ASD susceptibility. Although the concept of a sterile intrauterine environment remains debated, its investigation is valuable.

Summary: This review provides a comprehensive analysis of the interplay between diet, gastrointestinal symptoms, and ASD, evaluates the gut-brain axis as a mechanistic framework, and assesses the therapeutic potential of microbial interventions. The bidirectional "microbiota-gut-brain axis" has emerged as a critical pathway linking gut microbiota and brain function, offering potential therapeutic targets for ASD. Dietary patterns in children with ASD are often characterized by selectivity and restriction, which may disrupt gut microbiota composition and exacerbate gastrointestinal symptoms, thereby increasing ASD risk. Nutritional interventions and early behavioral therapies are thus essential.

Key messages: The gluten-free, casein-free diet remains controversial, with inconsistent evidence regarding its efficacy. Probiotic supplementation shows strain-specific effects, necessitating rigorous evaluation before clinical application. Given the heterogeneity of ASD, pharmacological treatments have shown limited universal efficacy. While promising findings have emerged from research on probiotics, prebiotics, and fecal microbiota transplantation, further well-designed clinical studies are needed to elucidate the complex etiology of ASD and validate therapeutic strategies.

Introduction: Despite advances in enhanced recovery after surgery (ERAS), many colorectal cancer (CRC) patients continue to experience sleep disturbance, nutritional decline, pain, and psychological distress. Evidence on integrated psychobehavioral and immunonutritional strategies remains limited.

Methods: In this single-center randomized tcontrolled trial, 260 patients with stage I-III CRC undergoing elective curative resection were randomized (1:1) to receive standard ERAS care or an integrative program. The intervention comprised five structured sessions of resilience-oriented psychological support (two preoperatively, three postoperatively) and prognostic nutritional index (PNI)-guided early enteral nutrition (standard formula for PNI ≥45; ω-3-enriched immunonutrition with prebiotic and lactobacillus-derived postbiotic components for PNI <45, without the assumption of viable probiotic delivery). The primary endpoint was global Pittsburgh Sleep Quality Index (PSQI) score at postoperative day (POD) 15. Secondary endpoints included nutritional biomarkers, pain, anxiety and depression, and health-related quality of life (HRQoL). Exploratory endpoints were C-reactive protein (CRP) and interleukin-6 (IL-6).

Results: Of 298 screened, 260 were randomized and 240 completed per protocol. Adherence exceeded 90% with no serious adverse events. At POD15, the intervention group had lower PSQI scores (adjusted mean difference -2.4; 95% confidence interval: -3.2 to -1.6; p < 0.001), with improvements in latency, disturbance, and daytime dysfunction. Nutritional recovery was enhanced (albumin +2.8 g/L, prealbumin +20.4 mg/L, transferrin +0.3 g/L, PⅢNP +15.2 ng/mL; all p < 0.05). Pain and opioid use were reduced (VAS POD3 -1.5; opioids -30 mg, both p < 0.001). Anxiety and depression scores improved (SAS -5.8, SDS -6.1; p < 0.001), alongside clinically meaningful HRQoL gains in global health (+8.7), physical (+7.2), and emotional functioning (+6.5). Subgroup analyses confirmed consistent benefits, while CRP (-4.8 mg/L) and IL-6 (-3.1 pg/mL) were lower in the intervention group.

Conclusion: Integrative perioperative care combining psychological support with PNI-guided early enteral nutrition is safe, feasible, and effective in improving sleep, nutritional recovery, pain control, psychological well-being, and quality of life after CRC surgery.

Introduction: Whether the consumption of fruits, flavonoid-rich fruits, and 100% fruit juice is associated with the risk of gestational diabetes mellitus (GDM) is unclear. We aimed to examine the association of total fruit, flavonoid-rich fruits, and 100% fruit juice consumption with the risk of GDM.

Methods: A total of 93,759 singleton pregnancies who were enrolled in the Japan Environment and Children's Study remained for the analysis. Total fruit consumption including fruits and 100% fruit juice during the past year in the first trimester was assessed using a validated food frequency questionnaire (FFQ). Odds ratios (ORs) and 95% confidence intervals (CIs) for GDM associated with total fruit, flavonoid-rich fruits, non-flavonoid-rich fruits, and 100% fruit juice consumption were estimated using logistic regression analysis.

Results: GDM occurred in 2,096 (2.2%) of the 93,759 pregnant women. Total fruit consumption was inversely associated with the risk of GDM; the multivariable ORs (95% CI) for the highest vs. lowest quartiles of total fruit consumption were 0.82 (0.71, 0.95) (p for trend = 0.013). An increase in total fruit consumption by each 100 g/day was inversely associated with the risk of GDM (OR = 0.94 [0.91, 0.98], p for trend = 0.001). The multivariable ORs (95% CIs) for the highest versus lowest quartiles of flavonoid-rich fruits consumption was 0.80 (0.70, 0.93) (p for trend = 0.003), whereas that for non-flavonoid-rich fruits consumption was 0.96 (0.83, 1.11) (p for trend = 0.504); 100% fruit juice consumption was inversely associated with the risk of GDM for each 100 mL/day increase (OR = 0.91, 95% CI: 0.87, 0.96).

Conclusion: Total fruit, flavonoid-rich fruits, and 100% fruit juice consumption were inversely associated with risk of GDM.