Nutrition & Metabolism最新文献

Vitamin D (VD) is a pleiotropic secosteroid hormone with well-established roles in calcium homeostasis, bone metabolism, and emerging functions in immune regulation, inflammation, and chronic disease modulation. In this paper, we provide a comprehensive summary of the current research on the significance of VD for bone health, with emphasis on its mechanism of action and its clinical significance in bone health. This review starts with an overview of VD metabolism, with emphasis on the enzyme transformation of vitamin D3 (VD3) and vitamin D2 (VD2) into the active 1,25-dihydroxyvitamin D (1α,25(OH)₂D) and their genomic and non-genomic signaling pathways through the Vitamin D receptor (VDR). Then, we discuss how VDR polymorphisms affect disease susceptibility and the dual role of VD in promoting innate immunity as well as inhibiting over-adaptive immunity. Our main focus is placed on VD's involvement in bone destruction diseases, including osteoarthritis (OA), osteoporosis (OP), rheumatoid arthritis (RA), and bone tuberculosis. For OA, there is conflicting evidence on whether VD supplementation reduces cartilage degradation or pain. In OP, vitamin D deficiency aggravates bone loss, but the effectiveness of supplementation is dependent on baseline and calcium supplementation. For RA, the immunomodulatory effects of VD may decrease the activity of the disease, whereas in tuberculosis, VD increases the clearance of macrophage-mediated mycobacterial clearance, although the clinical study data are still inconclusive. This review underscores VD as a critical mediator of bone-immune crosstalk while calling for rigorous translational research to clarify its therapeutic potential across diverse diseases.

Background: Increased liver fat increases the risk of chronic metabolic diseases. This study is an exploratory secondary analysis aimed at (1) investigating whether transcriptomic responses of abdominal subcutaneous adipose tissue (SAT) to a high-fat-high-glucose meal challenge differ according to varying levels of liver fat accumulation and (2) identifying pathways in abdominal SAT metabolism that may be related to liver fat accumulation. We examined differences in abdominal SAT gene expression and pathway activity both at fasting and in response to a mixed-meal challenge, comparing individuals with varying levels of liver fat.

Method: From the subset of 66 of 110 middle-aged participants of a previous intervention study, we grouped participants by tertiles of intrahepatic lipids (IHL) into high liver fat group (n = 22, IHL: 8.0%-32.6%), middle liver fat group (n = 22, IHL: 2.5%-8.0%) and low liver fat group (n = 22, IHL: 0.1%-2.5%). Participants received a high-fat-high-glucose mixed-meal challenge (3833 kJ). Abdominal SAT samples were collected before and 4 h after the challenge for microarray gene expression analysis.

Results: At fasting, 87 gene sets were differently expressed (FDR < 0.25) between the high and the low liver fat group, and 66 gene sets were differently expressed between the high and middle liver fat group, pathways related to energy metabolism were lower expressed in the high compared to the low liver fat group. Postprandially, 17 gene sets responded differently to the mixed meal challenge, of which 7 changed within the high liver fat group, 2 changed within the middle liver fat group and 4 within the low liver fat group. The challenge increased the expression of genes involved in oxidative phosphorylation more in the high compared to the low liver fat group.

Conclusions: Compared to individuals with low liver fat, individuals with high liver fat have lower gene expression but a higher response of energy-related pathways in abdominal SAT at fasting and after a high-fat-high-glucose challenge. Whether this is the cause or consequence of increased liver fat storage or an early stage of insulin resistance needs to be investigated.

Trial registration: This trial was registered at clinicaltrials.gov as NCT02194504.

Background: Although mechanistic studies suggest protective roles for carotenoids against breast cancer (BC), human studies yield inconsistent findings. Few have comprehensively evaluated dietary intake of individual and grouped carotenoids in relation to BC risk.

Methods: This population-based case-control study recruited 600 patients with newly diagnosed BC and 600 healthy controls. Dietary carotenoid intake was assessed using a validated 168-item food frequency questionnaire. The intake levels of α-carotene, β-carotene, β-cryptoxanthin, lutein/zeaxanthin, lycopene, astaxanthin, phytoene, phytofluene, neoxanthin, violaxanthin, and total carotenoids were categorized into quartiles. Logistic regression models were employed to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for BC risk, controlling for potential confounders.

Results: Higher intake of lycopene, phytoene, phytofluene, total non-provitamin A and provitamin A, β-carotene, lutein/zeaxanthin, as well as total carotenoids was significantly associated with reduced BC risk Lycopene showed the strongest inverse association (Q4 vs. Q1: OR = 0.23; 95% CI: 0.14-0.37). Total provitamin A (Q4 OR = 0.46; 95% CI: 0.29-0.75) and total non-provitamin A carotenoids (Q4 OR = 0.25; 95% CI: 0.15-0.41) also showed strong protective associations. Total carotenoid (Q4 OR = 0.34, 95% CI: 0.20-0.56, p < 0.001) intake also showed inverse associations across all quartiles. Conversely, α-carotene, β-cryptoxanthin, astaxanthin, neoxanthin, and violaxanthin displayed weaker or inconsistent associations.

Conclusion: These findings support an inverse association between dietary intake of specific carotenoids, particularly lycopene, lutein/zeaxanthin, and colorless carotenoids (phytoene and phytofluene) and BC risk. Promoting a carotenoid-rich diet may represent a feasible strategy for BC prevention.

Background: Chronic obstructive pulmonary disease (COPD) patients face increased mortality risk, particularly from cardiovascular causes. While polyunsaturated fatty acids (PUFAs) have shown cardiovascular benefits in general populations, their impact on COPD mortality remains unexplored.

Methods: This prospective cohort study analyzed 2,102 COPD patients from NHANES (1999-2018). PUFA intake was assessed through 24-hour dietary recalls and categorized into tertiles. Associations with all-cause and cardiovascular mortality were evaluated using Cox regression models, restricted cubic splines (RCS), and weighted quantile sum (WQS) regression. Comprehensive subgroup and sensitivity analyses confirmed result robustness.

Results: During 9.08 years of follow-up, 603 deaths (28.7%) occurred, including 190 (9.0%) from cardiovascular disease. Compared to the lowest tertile, the highest tertile of total PUFA (HR: 0.70, 95% CI: 0.53-0.91), N-3 PUFA (HR: 0.67, 95% CI: 0.52-0.87), and N-6 PUFA (HR: 0.74, 95% CI: 0.57-0.97) intake was associated with lower all-cause mortality. For cardiovascular mortality, higher intake of total PUFA (HR: 0.55, 95% CI: 0.33-0.90), N-3 PUFA (HR: 0.56, 95% CI: 0.36-0.89), and N-6 PUFA (HR: 0.57, 95% CI: 0.34-0.93) showed significant protective effects. RCS analyses revealed non-linear associations with significant threshold effects. WQS analysis identified two plant-derived PUFA-α-linolenic acid (ALA) and linoleic acid (LA) as the primary contributors to mortality reduction. All sensitivity analyses confirmed the stability and consistency of our main findings.

Conclusions: Higher dietary PUFA intake is associated with lower all-cause and cardiovascular mortality among COPD patients, suggesting that increasing dietary PUFA, particularly from plant sources, may help reduce COPD-related mortality risk.

Intermittent fasting (IF) as a dietary intervention with potential health benefits has garnered significant attention in recent years. This study investigated the effects of varying fasting intensities on skeletal muscle growth using mouse models. Compared to the normal-diet (ND) control group, short-term fasting induced feeding amount-dependent alterations in skeletal muscle autophagy markers, characterized by elevated LC3B expression, reduced p62 levels, and decreased p-mTOR/mTOR ratio. Notably, short-term mild fasting (sMF) significantly upregulated myogenic (MYH, MyoD) and adipogenic (LPL, PPARγ) differentiation markers, whereas short-term severe fasting (sSF) suppressed myogenic markers without significantly affecting adipogenic factors. Pharmacological modulation using 3-methyladenine (3-MA) and rapamycin (RAPA) confirmed the critical role of autophagy in myogenic and adipogenic processes. Multi-cycle IF studies revealed that intermittent mild fasting (IMF) enhanced metabolic efficiency (evidenced by increased feed conversion ratio), elevated organ indices of gastrocnemius and quadriceps femoris muscles, and reduced groin fat. IMF also promoted intramuscular adipogenesis and myofiber remodeling. In contrast, intermittent severe fasting (ISF) impaired glucose tolerance, decreased triglyceride levels and aspartate aminotransferase (AST) activity, inhibited myofiber growth, and exhibited no significant effect on intramuscular adipogenesis. Our findings demonstrate that IMF enhances skeletal muscle mass and reduces visceral adiposity through mTOR-autophagy axis, providing an optimized fasting regimen for metabolic health and body composition regulation.

Background: Inflammatory Bowel Diseases (IBD) encompass chronic inflammatory conditions such as ulcerative colitis and Crohn's disease. This umbrella meta-analysis investigates the efficacy of probiotic supplementation in reducing relapse, recurrence, and maintaining remission in IBD patients.

Methods: We systematically searched PubMed, Scopus, and Web of Science up to November 2024 for meta-analyses evaluating probiotics in IBD. A random-effects model calculated pooled effect sizes. The methodological quality of included reviews was assessed using AMSTAR 2. Publication bias was evaluated through funnel plots, Egger's and Begg's tests, and corrected by trim-and-fill when appropriate.

Results: Twenty meta-analyses including 46 datasets were analyzed. Probiotics significantly reduced relapse risk compared to placebo (RR = 0.55; 95% CI, 0.22-0.88), but showed no significant effect compared to mesalazine. No consistent benefit was found for remission or recurrence; however, recurrence risk was reduced after correction for publication bias (RR:0.74;95%CI:0.51-0.97, P < 0.05). Subgroup analyses suggested greater benefit with lower probiotic doses (≤ 10¹⁰ Colony-Forming Units/day) and longer supplementation durations (≥ 8 weeks) regarding to relapse rate, although strain-specific effects could not be clarified.

Conclusion: Probiotic supplementation appears effective in reducing relapse compared to placebo, but shows no advantage over mesalazine and demonstrates benefit for recurrence only after adjusting for publication bias. These findings highlight a potential role for probiotics in IBD management, but interpretation should be cautious given the high heterogeneity and substantial overlap among included meta-analyses. Further high-quality, non-overlapping meta-analyses and randomized controlled trials are needed to determine the most effective probiotic regimens.

Background: The role of nutritional status in predicting prognosis in patients with sarcopenia has not been fully elucidated. This investigation sought to evaluate the link between prognostic nutritional index (PNI) and sarcopenia, as well as its influence on overall and cardiovascular death rates in adults diagnosed with sarcopenia.

Methods: This retrospective observational study utilized data from individuals aged 18 years and older extracted from the National Health and Nutrition Examination Survey (NHANES) during 1999-2004 and 2011-2018. The PNI calculation incorporated initial serum albumin measurements and complete lymphocyte numbers. To investigate the link between PNI and sarcopenia, researchers employed multiple analytical approaches, including multivariate logistic regression, stratified group evaluation, restricted cubic spline, and threshold and saturation effect analysis. The investigation utilized Cox regression modeling and Kaplan-Meier survival analysis to examine the link between PNI and both overall and cardiovascular-related mortality among subjects with sarcopenia.

Results: Among the 24,661 patients examined, sarcopenia was detected in 2760 individuals (11.19%). Throughout a median monitoring duration of 132.01 months, all-cause mortality claimed 959 (34.75%) subjects with sarcopenia, while cardiovascular-related fatalities accounted for 321 (33.47%) cases. Subjects in the uppermost PNI quartile (Q4) exhibited markedly decreased likelihood of sarcopenia (odds ratio [OR] 0.43, 95% confidence interval [CI] 0.37-0.49) and lower risks of both all-cause and cardiovascular mortality (hazard ratio [HR] 0.64, 95% CI 0.53-0.78; and 0.60, 95% CI 0.43-0.84, respectively) versus those in the lowermost quartile (Q1). These findings were consistent across subgroup analyses, restricted cubic spline, and threshold and saturation effect analysis.

Conclusions: The PNI is an independent predictor of sarcopenia, all-cause mortality, and cardiovascular mortality in U.S. adults. It can be a valuable tool for identifying individuals at elevated risk of unfavorable health outcomes.

Background: Parasitic infections possess comparable risk factors to obesity. In addition, obesity impairs innate and adaptive immunity subsequently increasing vulnerability to infectious diseases.

Aim: The study investigated the leptin/leptin receptors, obesity-parasites mutual relationship and the effect of parasitic infections on immune metabolism, microbiota, and tumorigenesis in the context of obesity.

Methodology: To implement the current review, articles were gathered using the Egyptian Knowledge Bank (EKB), Web of Science, PubMed, and Google Scholar.

Conclusion: Leptin enhances anti-parasitic immunity. Obesity favors intestinal colonization of Blastocystis sp., Dientamoeba fragilis, Entamoeba coli, and Giardia intestinalis. Adipocytes act as a niche and a food source for Trypanosoma cruzi, Trypanosoma brucei, and Plasmodium. In addition, Toxoplasma gondii relies on the circulatory cholesterol to thrive. Obesity provokes low-grade chronic inflammation and metabolic syndrome. Yet, Nippostrongylus brasiliensis and Fasciola hepatica attempted to alleviate inflammation and metabolic syndrome. Hookworm improves insulin resistance. However, parasites such as Schistosoma mansoni, Trichuris suis, Taenia pisiformis, Entamoeba histolytica, Trypanosoma cruzi, and Trypanosoma brucei, and Toxoplasma aggravated metabolic immune metabolic syndrome. Obesity hampered immunity against Leishmania sp.. and Plasmodium sp. is diabetogenic. Giardia infection and Heligmosoides polygyrus infections induce dysbiosis in obesity. Obesity and parasites like Trichomonas vaginalis, S. haematobium, S. mansoni, Clonorchis sinensis, Opishorchis viverrini showed similar cancer types. Yet, Toxoplasma gondii and Echinococcus granulosus have anti-tumorigenic effects. Obesity/high-fat diet hinders Schistosoma mansoni, Trichuris muris, and Entamoeba histolytica infections. Also, Blastocystis sp., Dientamoeba fragilis, Giardia intestinalis, Trichinella spiralis, and Schistosoma appeared to have ameliorative effects in obesity.

Background: Untargeted metabolomic analysis provides novel insights into the relationship between sodium intake and cardiometabolic risk. This study examined cross-sectional associations between estimated sodium intake and plasma metabolite profiles in a large Swedish cohort.

Methods: This cross-sectional analysis was conducted in the in the SCAPIS cohort (mean age 50-64 years, n = 8,957). Sodium intake was estimated using the Kawasaki formula (est24hNa) from urine samples. Plasma metabolites were measured using ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) (Metabolon Inc^®), identifying 713 metabolites grouped into eight biochemical classes (CC). Principal component analysis (PCA) was conducted for each CC, and the first principal component (PC1) was used as the response variable, with est24hNa, age, sex, and cardiovascular risk factors as predictors in restricted cubic spline models. ANOVA and pathway enrichment analyses were performed to explore associations.

Results: Est24hNa was significantly associated with the lipid and energy CC. Lower est24hNa was linked to higher concentrations of free fatty acids and citric acid cycle intermediates, suggesting enhanced beta-oxidation. Bonferroni-adjusted analyses revealed 231 metabolites significantly associated with est24hNa, with 2 S,3R-dihydroxybutyrate (β = -0.13, p = 2.28 × 10^- 37) showing the strongest association. Lipid subgroups including phosphatidylcholines, lysophospholipids, bile acids, and plasmalogens were positively associated with est24hNa. Pathway enrichment suggested links to branched-chain amino acid metabolism and biosynthesis of unsaturated fatty acids.

Conclusions: Lower salt intake was associated with a metabolic profile indicative of increased beta-oxidation, while higher salt intake was linked to lipid species previously implicated in atherosclerosis. These findings highlight potential metabolic pathways through which salt intake may influence cardiovascular health and merit further evaluation in longitudinal studies.