Nutrition & Metabolism最新文献

Background: The influence of life-course body size on the progression of cardio-renal-metabolic multimorbidity (CRMM) is insufficiently understood.

Methods: We included 398,491 UK Biobank participants. Childhood-to-adulthood body size trajectories were defined using recalled childhood somatotype and adult body mass index (BMI). Multi-state models evaluated transition-specific hazards, state-occupation probabilities, and expected length of stay (ELOS) across body size trajectories. Progression was represented as a comorbidity-count pathway (healthy, first/double/triple CRMM, and death) and a comorbidity-pattern pathway specifying the entry disease and comorbidities among cardiovascular disease (CVD), type 2 diabetes (T2D), and chronic kidney disease (CKD). Subgroup and interaction analyses evaluated joint effects of trajectory and Life's Essential 4 (LE4). Mediation by the C-reactive protein-triglyceride-glucose index (CTI) was assessed.

Results: Trajectories culminating in obesity were associated with higher hazards along the comorbidity-count pathway and shorter healthy time (ELOS 13.08 vs. 10.59 years for Average-to-normal vs Thinner-to-obesity). Comorbidity-pattern analyses identified T2D-containing comorbidities (T2D-CKD, T2D-CVD) as hubs toward CRMM. Compared with the Average-to-normal group, hazard ratios (HRs) were highest when the destination included T2D: CVD to T2D-CVD, 3.24 (Plumper-to-obesity), and 3.85 (Thinner-to-obesity); CKD to T2D-CKD, 2.66 (Plumper-to-obesity) and 4.03 (Thinner-to-obesity). Moving from LE4-low to LE4-high attenuated the risks of CRMM associated with progressive or persistent obesity trajectories by 26.8-37.8%. CTI mediated approximately 42-54% of the associations between sustained or progressive obesity trajectories and CRMM comorbidity outcomes.

Conclusions: Progressive or persistent obesity trajectories were associated with higher CRMM progression hazards. Early adiposity prevention and sustained lifestyle improvement may slow this progression. Integrating body size trajectory and lifestyle factors with metabolic inflammation indicators may strengthen risk stratification.

Background: Insulin resistance (IR) is considered a key pathogenic mechanism of peripheral artery disease (PAD). The estimated glucose disposal rate (eGDR) serves as a practical surrogate marker of IR. The study aimed to investigate the association between eGDR and incident PAD risk in the general population.

Methods: A total of 456,743 participants free of PAD at baseline were included from the prospective UK Biobank cohort. In addition, we examined the cross-sectional association between eGDR and prevalent PAD among 7,208 participants from the National Health and Nutrition Examination Survey (NHANES) as a supplementary analysis.

Results: Multivariable Cox regression analysis showed that participants in the highest eGDR quartile (Q4) experienced the greatest reduction in the risk of developing PAD compared with the reference group [Q4 vs. Q1; fully adjusted hazard ratio (HR) = 0.67, 95% confidence interval (CI): 0.63-0.72, P < 0.001]. Restricted cubic spline (RCS) curve and threshold effect analysis also suggested a significant nonlinear inverse relationship between eGDR and PAD risk, with an inflection point at 7.829 (P for overall < 0.001; P for nonlinearity < 0.001). Two-piecewise Cox regression further indicated that below the threshold, an increase in eGDR was associated with a greater reduction in PAD risk (HR = 0.85, 95% CI: 0.84-0.87, P < 0.001). A similar inverse association between eGDR and prevalent PAD was observed in the NHANES analysis.

Conclusions: eGDR was inversely associated with PAD. Further studies are needed to explore the clinical utility of this association.

Background: Purple sweet potato leaves are a rich source of caffeoylquinic acids (CQA) and related compounds with potential metabolic benefits. Our previous research demonstrated that 5-CQA and 3,4-diCQA increase mitochondrial respiration in primary hepatocytes. To explore the translational relevance of purple sweet potato leaves extract (PSPLE) in the management and treatment of obesity, we evaluated the effect of PSPLE in C57BL/6 mice fed a high-fat (HF) diet supplemented with either 1% or 3% PSPLE (w/w) and assessed insulin secretion in INS-1E cells.

Methods: PSPLE phenolic compounds were identified by LC-MS. Male C57BL/6J mice were fed (1) a Control, (2) high-fat (HF) diet, (3) HF diet supplemented with 1% and (4) HF diet supplemented with 3% of PSPLE for 15 weeks. Body composition, energy expenditure, glucose and insulin tolerance, serum metabolites, and tissue morphology were evaluated. AMPK activation was analyzed in the liver and skeletal muscle. Complementary, β-cell function was assessed in vitro.

Results: LC-MS revealed that PSPLE contained abundant CQA derivatives (5-CQA, caffeic acid, 3,4-di-CQA, 3,5-di-CQA, 4,5-di-CQA, 4 F-5CQA, and 3,4,5-tri-CQA). The HF + 1% PSPLE diet attenuated weight gain and adipocyte hypertrophy, increased brown adipose UCP-1 expression, and prevented hepatic steatosis. AMPK phosphorylation was enhanced in the liver and muscle, paralleling higher oxygen consumption and energy expenditure. Although PSPLE stimulated β-cell metabolism and insulin secretion in vitro, in vivo glucose tolerance showed only modest improvement, likely reflecting the multiple regulatory inputs on insulin secretion under physiological conditions.

Conclusions: PSPLE enhanced metabolic flexibility and oxidative capacity in HF-fed mice by activating AMPK-dependent pathways in muscle, liver, and adipose tissue. The higher efficacy of the 1% PSPLE indicates a hormetic response, where low polyphenol exposure triggers adaptive mitochondrial and metabolic activation, on the contrary, higher doses offer no further benefits. These results present PSPLE as a sustainable, polyphenol-rich food ingredient with potential to combat obesity-related metabolic dysfunction.

Background: We investigated the serial mediating roles of insulin re-sistance (IR) and abdominal obesity in the association between the Dietary Inflamma-tory Index (DII) and hyperuricemia (HUA), and whether abdominal obesity moder-ated this pathway.

Methods: We analyzed data from 8,232 adults in the National Health and Nutrition Examination Survey (2007-2016). The triglyceride-glucose (TyG) index served as a surrogate for IR. We employed serial mediation and moderated me-diation models.

Results: Higher DII was associated with increased HUA risk. This re-lationship was serially mediated through the pathway: DII → TyG index → abdominal obesity → HUA. This indirect pathway accounted for 52.3% of the total effect, with abdominal obesity being the most potent mediator (contribution: 31.0%). Importantly, the mediating effect of the TyG index was significant only in individuals with a normal waist circumference (β = 0.0016, 95% CI: 0.0006, 0.0026) but was attenuated to non-significance in those with abdominal obesity.

Conclusion: Our findings suggest that IR and abdominal obesity may serially mediate the link between a pro-inflammatory diet and HUA. The me-diating role of IR appears to be prominent in individuals without abdominal obesity, whereas in those with obesity, obesity itself becomes the dominant factor. However, given the cross-sectional design, causal inferences cannot be drawn. These findings support developing stage-specific HUA prevention strategies, targeting insulin sensitivity or weight control based on an individual's obesity status.

Background: Exercise-induced immunosuppression poses significant health risks for adolescent athletes during intensive training. This study investigated whether high-polyphenol dietary intervention could maintain immune homeostasis through immunometabolic reprogramming.

Methods: Eighty adolescent athletes (aged 15-17) were randomized to receive either high-polyphenol supplementation (1200 mg/day: quercetin, EGCG, resveratrol, curcumin) or placebo during a 12-week high-intensity training period. Multi-omics profiling (transcriptomics, proteomics, metabolomics, microbiomics) was performed at baseline, weeks 4, 8, and 12.

Results: The high-polyphenol group maintained CD4 + /CD8 + ratios above clinical thresholds (1.65 ± 0.29 vs. 1.38 ± 0.42, p < 0.001) at peak training. Regulatory T cells increased 17.2% while Th17 cells remained stable, yielding favorable Treg/Th17 ratios (3.09 ± 0.82 vs. 1.58 ± 0.54, p < 0.001). Multi-omics integration revealed 1,847 differentially expressed genes converging on NF-κB suppression, AMPK-mTOR activation, and Nrf2-mediated antioxidant responses. Gut microbiome analysis showed doubled butyrate-producing bacteria and twofold increased short-chain fatty acid production. Salivary IgA declined only 6.5% versus 29.3% in placebo (p < 0.001).

Conclusions: High-polyphenol dietary intervention effectively prevents exercise-induced immunosuppression through coordinated immunometabolic reprogramming, establishing a practical strategy for maintaining immune resilience in adolescent athletes.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic disease, but it remains unclear whether it is related to dietary folate. This research sought to investigate the association between dietary folate and MASLD.

Methods: This cohort study utilized the UK Biobank (UKB) database (N = 58,047). Dietary folate intake was assessed using an online dietary questionnaire, and MASLD was ascertained through International Classification of Diseases, Tenth Revision (ICD-10). Cox proportional hazard regression, mediation analysis and restricted cubic splines (RCS) were employed to investigate the association and dose-response relationship between dietary and MASLD. The stability of findings was verified by stratified analyses and sensitivity analyses.

Results: Dietary folate intake was observed to be negatively associated with MASLD in cohort studies. During a median follow-up of 12.18 years, 691 cases of MASLD occurred. The risk of MASLD decreased by 24% (HR = 0.76, 95% CI: 0.59-0.97) among the participants in the highest dietary folate intake relative to lowest quartile. The protective effect was more pronounced in participants aged < 60 years (HR = 0.63, 95% CI: 0.45-0.89), male (HR = 0.63, 95% CI: 0.44-0.89), and obese participants (HR = 0.68, 95% CI: 0.48-0.95). The research results remained robust in the sensitivity analyses that excluded participants with ≤ 2 years of follow-up time, extremely folate intake, and other conditions. C-reactive protein (CRP) explained 6.56% of the association between dietary folate and MASLD. The dietary folate intake had an L-shaped relationship with the risk of MASLD (P for nonlinearity = 0.003).

Conclusions: Moderate folate intake (approximately 300 µg) may reduce the risk of MASLD, suggesting that promoting folate-rich diets may be a viable and cost-effective strategy for MASLD prevention.

Background: Amino acid metabolism plays a critical role in cardiovascular disease, yet its prognostic value in ST-elevation acute myocardial infarction (STEMI) remains underexplored. Therefore, we investigated whether specific plasma amino acid concentrations at admission for STEMI are associated with 28-day mortality.

Methods: This analysis was based on data from 724 patients with STEMI aged 29 to 98 years who were admitted to the University Hospital Augsburg between May 2009 and July 2013. Immediately after admission arterial blood samples were taken from these patients and a panel of amino acids was measured by a high-throughput nuclear magnetic resonance spectroscopy platform (Nightingale Health, Finland). Multivariable logistic regression models were conducted to examine the associations between the amino acids phenylalanine, tyrosine, glycine, alanine, histidine, glutamine, as well as branched-chain amino acids (BCAAs; a group that includes valine, isoleucine, and leucine) and 28-day mortality. P values were False discovery rate (FDR) adjusted.

Results: Altogether, 47 patients died within 28 days after admission. There were significant positive associations found between plasma levels of phenylalanine, glycine, tyrosine, valine, and alanine and 28-day mortality. Phenylalanine showed the highest effect estimate (OR: 1.84; 95% CI 1.34-2.53). No significant associations were observed for the remaining amino acids.

Conclusions: The acute phase of STEMI is associated with changes in plasma amino acid levels that may reflect alterations in energy metabolism and metabolic stress. The associations between amino acid fluctuations and 28-day mortality highlight the potential of metabolomic profiling to refine early risk stratification.

Background and aims: Oxidative stress plays a crucial role in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD). While antioxidant-rich diets may help reduce this stress and possibly reduce MASLD risk, there is little long-term evidence. This prospective study examined the link between the Composite Dietary Antioxidant Index (CDAI) and MASLD risk.

Methods: This study followed 5,988 participants (49.3% male) without MASLD at baseline from the Monitoring of Metabolic Diseases Risk Factors in Tehran (MMRT) cohort. Dietary intake was assessed using a validated 125-item food frequency questionnaire to determine the CDAI. Cases of MASLD were identified using transient elastography and at least one cardiometabolic risk factor. The association between CDAI and MASLD risk was analyzed through multivariable logistic regression.

Results: Following a five-year follow-up, 550 new cases of MASLD were identified. After adjusting for multiple confounders, individuals in the highest quartile of CDAI exhibited a 40% reduction in the risk of developing MASLD compared to those in the lowest quartile (OR: 0.60, 95% CI: 0.40-0.89; p-trend = 0.002). Additionally, each one-unit increment in CDAI significantly corresponded to an 8% decrease in MASLD risk. An inverse dose-response relationship was also observed between CDAI and incident MASLD, with C-reactive protein (CRP) mediating 48% of this association. Among CDAI components, increased consumption of Vitamin C and Vitamin E was independently associated with a significantly reduced risk of MASLD.

Conclusion: A higher intake of dietary antioxidants was significantly associated with a reduced risk of developing MASLD. These results indicate that encouraging antioxidant-rich dietary patterns may serve as a lifestyle modification approach for the primary prevention of MASLD.

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) poses a growing public health challenge, but traditional metabolic markers may not fully capture individual risk, especially in individuals with normal metabolic phenotypes. Phenotypic age acceleration (PhenoAgeAccel), a composite biomarker reflecting systemic aging burden, may offer additional value for risk stratification.

Methods: We conducted a two-stage study involving a case-control analysis (6,343 MAFLD cases vs. 6,343 chronological age- and sex-matched controls) and a prospective cohort analysis (7,997 participants initially free of fatty liver disease). PhenoAgeAccel was derived from chronological age and nine clinical biomarkers. Associations between PhenoAgeAccel and MAFLD were assessed using conditional logistic regression and competing risk models, with adjustments for lifestyle factors, comorbidities and medication histories.

Results: In the case-control analysis, each 5-year increase in PhenoAgeAccel was associated with 66% higher odds of MAFLD after multivariable adjustment (OR = 1.66, 95% CI: 1.56-1.77). In the prospective cohort, PhenoAgeAccel remained significantly associated with incident MAFLD (HR = 1.45, 95% CI: 1.32-1.59). While the main analyses estimated the overall association, subgroup analyses examined whether this association varied across different populations. These suggested stronger associations in females (vs. males), individuals with younger chronological age (vs. older age), and those without hypertension or diabetes (vs. those with hypertension or diabetes, respectively). PhenoAgeAccel demonstrated better discriminative ability (AUC = 0.622) than traditional fibrosis scores (FIB-4, NFS, BARD), with a high negative predictive value (88.8%).

Conclusions: PhenoAgeAccel was associated with MAFLD risk in a Chinese health examination population, providing information beyond chronological age and common metabolic factors. It may serve as a useful indicator for identifying individuals with normal metabolic phenotypes but accelerated biological aging, particularly in those without overt metabolic risk factors.