Journal of Nutrition最新文献

Background: Intake of added sugars, such as sucrose, is high globally. In rats, a maternal high-sucrose diet (HSD) from 10 wk before pregnancy to embryonic day (E)19.5 has widespread impacts on maternal, placental, and fetal blood and brain steroid levels, including glucocorticoids, androgens, and aldosterone.

Objective: This study examined whether maternal HSD during pregnancy alone is sufficient to alter maternal, placental, and fetal steroids.

Methods: Pregnant rats received either a control diet (1% kcal sucrose) or an isocaloric, nutrient-matched HSD (26% kcal sucrose) between E0.5-19.5. On E19.5, we collected maternal serum, placenta, fetal blood and brain, and amniotic fluid. We microdissected the placenta and fetal brain and measured 14 steroids using liquid chromatography tandem mass spectrometry (n=12-15/diet/sex).

Results: Maternal HSD during pregnancy alone did not alter maternal food intake, maternal body mass, and litter size (all p values ≥ 0.29, Student's t-test) but increased the percentage of males in a litter (p = 0.03, Student's t-test). Maternal HSD did not alter steroids in the maternal serum (all p values ≥ 0.21, Student's t-test), placenta (all p values ≥ 0.07, 2-way ANOVA), and fetal blood (all p values ≥ 0.13, 2-way ANOVA). Nonetheless, maternal HSD increased testosterone in the fetal nucleus accumbens (p = 0.04, 2-way ANOVA), decreased allopregnanolone in the fetal amygdala (p = 0.01, 2-way ANOVA), and decreased 11-dehydrocorticosterone in the amniotic fluid (p = 0.05, 2-way ANOVA).

Conclusions: Maternal HSD during pregnancy alone does not affect steroid levels in the maternal serum, placenta, or fetal blood of rats, but disrupts testosterone and allopregnanolone levels in critical regions of the fetal brain that regulate reward-seeking and emotion. Thus, while a long-term maternal HSD is necessary for widespread endocrine effects, the fetal brain is sensitive to short-term increases in maternal sucrose consumption during pregnancy.

Background: Although plant proteins have less environmental impact than animal proteins, it remains unclear whether they can adequately support physical functioning in old age.

Objective: This prospective study aimed to investigate the association of the dietary plant-to-animal protein intake ratio with the incidence of slow gait speed among older adults.

Methods: Data from 997 adults (50.7% male, mean age 65.5 (SD6.9) years) with a baseline gait speed ≥0.8 m/s were derived from the Longitudinal Aging Study Amsterdam. The dietary plant-to-animal protein intake ratio was calculated from a 238-item food frequency questionnaire completed in 2014-15. Gait speed was measured at baseline and at three 3-year follow-up waves using a 6-meter walk test. Cox proportional hazards models estimated the association between protein ratio quintiles and incident slow gait speed (<0.8 m/s), while adjusting for demographic and lifestyle factors and testing for interaction by sex, overall diet quality, protein intake and baseline gait speed.

Results: The median dietary plant-to-animal protein intake ratio was 0.67 (IQR 0.52-0.86). During follow-up, slow gait speed (<0.8 m/s) developed in 415 participants (41.6%). No significant association was found between the protein ratio and incident slow gait speed. The adjusted hazard ratio of the highest (ratio>0.91) vs. lowest (ratio≤0.49) quintile was 0.98 (95% confidence interval 0.68-1.42, trend across quintiles p=0.89). No significant interactions were observed with sex, overall diet quality, or total protein intake. A higher plant-to-animal protein ratio was suggested to be associated with a lower risk of incident slow gait speed in those with relatively faster baseline gait speed, although associations were not statistically significant.

Conclusions: Among Dutch older adults, the dietary plant-to-animal protein intake ratio was not associated with the risk of developing slow gait speed, suggesting that a more sustainable diet including higher plant protein intake may not compromise physical functioning in older adults.

Background: Despite the effectiveness of conventional antidiabetic agents, limitations still remain, necessitating the use of alternative treatment options in the management of diabetes. Some preliminary studies report the antidiabetic effects of Cyanidin-3-glucoside (C3G). However, there is a paucity of comprehensive evidence on this.

Objective: To systematically analyze the results of animal studies investigating C3G as an antidiabetic agent.

Method: A comprehensive literature search was conducted across databases, including PubMed, Scopus, Web of Science, and Google Scholar, using appropriate keywords and Boolean operators. Articles were screened for eligibility, ensuring that only animal studies reporting diabetes-related outcomes were included.

Results: Of the 6,067 articles generated from the database search, 16 met the inclusion criteria and were included in the study. All studies used diabetic mice or rat models. Due to the variability in animal models, intervention protocols, and measured outcomes across the included studies, meta-analysis was not feasible. Across the studies, C3G administration significantly reduced serum glucose levels in 14 studies (87.5%) and improved glucose tolerance test in the other 2 studies compared to the untreated diabetic groups. Serum insulin decreased from ∼25-35 ng/mL to 15-17 ng/mL, and in a few cases increased modestly in insulin-deficient models, reflecting improved sensitivity C3G. Also, C3G decreased HbA1c by 30-40% compared to diabetic controls.

Conclusion: C3G shows considerable promise as an anti-diabetic agent as it improved glucose, insulin, and HbA1c levels in animal models of diabetes. Given these encouraging findings, there is a need for more robust clinical trials to validate its anti-diabetic effect and assess its superiority, inferiority, or otherwise to standard anti-diabetic agents.

Prospero registration number: CRD420251078672.

Background: With the increasing use of HFD, fatty liver has become prevalent in farmed fish. Leucine regulates lipid metabolism via multiple pathways, but its role in hepatic lipotoxic injury remains unclear. This study aimed to determine the molecular mechanism responsible for alleviation of HFD-induced liver injury by dietary supplementation with leucine in black seabream (Acanthopagrus schlegelii).

Methods: In vivo, juvenile black seabream (male; 1.25 ± 0.01 g) were fed one of five diets in triplicate (30 fish/replicate, n=3) for 8-weeks. The diets consisted of Control (11% lipid) and HFD (18% lipid) diets with the HFD supplemented with 0.5%, 1.0%, or 2.0% leucine. Fish were hand-fed a fixed ration twice daily. Growth, hepatic lipid deposition, and lipotoxic injury were assessed by biochemical, histological, and molecular (flow cytometry, qPCR, Western blot) methods. In vitro, primary hepatocytes were treated with OA alone or with 2 mM leucine (n = 3). To explore the mechanism, OA was combined with leucine, Ampk, Sar1b, and Sestrin2 overexpression. Oil Red O staining, immunofluorescence, qPCR, and Western blot assessed lipid accumulation, and signaling pathways. Data were means ± SEM and analyzed by t-test or one-way ANOVA, with p < 0.05 considered significant.

Results: In vivo, leucine supplementation activated Sar1b/Sestrin2 and Ampkα1/Sirt1 pathways, reducing HFD-induced hepatic lipid deposition (36% - 54%) by enhancing lipolysis (75%-309%) and suppressing lipogenesis (24%-87%). Leucine downregulated ER stress markers (p-Ire1α, 54%-67%) and inhibited p-P65 and p-Jnk (23%-33%, 23%-32%), attenuating inflammation and apoptosis. Similar patterns in vitro confirmed leucine's consistent alleviation of HFD-induced hepatic lipid deposition and lipotoxic injury across models. Overexpression of Ampkα1, Sar1b, or Sestrin2 mimicked leucine's effects, alleviating OA-induced lipid accumulation, inflammation, and apoptosis.

Conclusion: Leucine alleviated HFD-induced liver lipotoxic injury in black seabream by activating Sar1b/Sestrin2 and Ampk1/Sirt1 pathways, providing novel insights for developing nutritional strategies against diet-induced liver injury.

Background: Skeletal muscle fatigue reflects the interaction of metabolic demand, contractile efficiency, and oxygen delivery, processes highly dependent on microvascular function. Prolonged ischemia induces transient microvascular dysfunction that can impair fatigue resistance. Dietary nitrate, abundant in beetroot juice, enhances nitric oxide (NO) bioavailability and vascular function, but whether it mitigates ischemia-induced decrements in microvascular reactivity and fatigue resistance remains unclear.

Objective: To determine whether a single oral dose of nitrate-rich beetroot juice protects against prolonged ischemia-induced impairments in microvascular function and fatigue resistance in a sex-dependent manner.

Methods: Sixteen healthy adults (8 males, 8 females; 20-40 y) completed a randomized, double-blind, crossover trial with nitrate-rich (∼10 mmol nitrate, NR-BJ) or nitrate-depleted (∼0.34 mmol nitrate, ND-BJ) beetroot juice. Two hours post-ingestion, participants underwent 20 min of forearm arterial occlusion to induce microvascular dysfunction. Microvascular reactivity was assessed by near-infrared spectroscopy (StO₂ resaturation slope), and fatigue resistance was determined during 50 maximal isokinetic wrist flexion-extension contractions. Serum nitrate and nitrite were measured by high-performance liquid chromatography.

Results: Circulating nitrate and nitrite increased significantly after NR-BJ in both males and females. Prolonged ischemia reduced the StO₂ resaturation slope in both sexes under ND-BJ condition. NR-BJ attenuated this decline in females but not in males. In males, ischemia reduced total work and early-phase work (the first one-third of repetitions) under ND-BJ, effects that were prevented by NR-BJ. Fatigue resistance was preserved in females across conditions.

Conclusion: Acute dietary nitrate supplementation preserves fatigue resistance in males despite persistent microvascular dysfunction, whereas in females it attenuates ischemia-induced microvascular impairment without affecting fatigue resistance. These findings support sex-specific protective effects of dietary nitrate against transient vascular stress.

Background: Porcine epidemic diarrhea virus (PEDV) poses a significant threat to the global pig industry. Niacin (NA) may play an important role in improving intestinal health in piglets.

Objective: The present study aimed to investigate the effects of NA supplementation on growth performance and intestinal health in young piglets infected with PEDV.

Methods: Forty 7-day-old healthy piglets were randomly assigned to four groups: Control, NA, PEDV, and PEDV+NA. After three days of adaptation, piglets in the NA and PEDV+NA groups were orally administered NA at 30 mg/kg body weight from days 4 to 11. On day 9, piglets in the PEDV and PEDV+NA groups were orally inoculated with PEDV at a dose of 10^4.5 TCID₅₀. On day 12, tissue samples were collected following euthanasia and exsanguination. Intestinal injury was confirmed by the determination of intestinal villus height (VH), crypt depth (CD), as well as plasma diamine oxidase (DAO) and d-xylose concentration. qPCR was performed to evaluate the viral load. Western blot analysis was employed to investigate the intestinal immune response. Data were analyzed by two-way analysis of variance, with PEDV and NA as factors.

Results: NA administration improved average daily gain and mitigated intestinal injury in PEDV-infected piglets, as indicated by reduced CD and increased VH/CD ratios in the duodenum, jejunum, and colon, along with decreased plasma DAO levels (P < 0.05). NA significantly inhibited the expression of PEDV M and N genes in both the jejunum and ileum (P < 0.01). Moreover, NA reduced the protein abundance of interferon-stimulated genes, including interferon-stimulated gene 15 (ISG15), 2'-5'-oligoadenylate synthetase-like protein (OASL), and myxovirus resistance 1 (MX1), in the intestines of PEDV-infected piglets (P < 0.05).

Conclusion: The results suggest that NA could inhibit viral replication and alleviate the intestinal injury in PEDV-infected piglets by regulating host immune responses.

Background: Unhealthy diet and microbiota dysbiosis are known risk factors of type 2 diabetes (T2D), but the value of microbial metabolites as indicators of diet quality and T2D risk has rarely been explored.

Objective: In this prospective study, we examined the correlations of dietary intake and circulating microbial metabolism-associated metabolites with T2D parameters in adults enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study.

Methods: A cohort of 2296 non-diabetic participants were examined on their diet quality, plasma metabolome, fasting glucose, and insulin in year 7 of the CARDIA study, and the occurrence of incident T2D afterwards. Dietary intake was assessed by an interviewer-administered diet history. Diet quality was characterized by the healthy eating index 2020 (HEI) score. Spearman correlation analysis assessed the associations of plasma metabolites with HEI, fasting glucose, insulin, and homeostatic model assessment (HOMA) indexes. Subsequent propensity matching 131 incident T2D cases with controls yielded a paired dataset for logistic and multivariate regression analyses, resulting in the predictive markers that were further validated by Cox proportional hazard models on three random cohorts selected from the full cohort.

Results: Among 611 circulating plasma metabolites, 41 were classified as microbial metabolites or their dietary precursors. Cinnamoylglycine, a metabolite produced jointly by microbial phenylalanine fermentation and hepatic glycine conjugation, was positively correlated with diet quality and inversely associated with incident T2D risk (odds ratio [OR] =0.66; 95% C.I. 0.49, 0.87). Isoleucine was inversely correlated with diet quality and positively associated with T2D risk (OR=1.98; 95% C.I. 1.36, 2.87). This contrast between cinnamoylglycine and isoleucine provided a cinnamoylglycine/isoleucine (C/I) ratio as a predictive indicator of diet quality and incident T2D risk (OR=0.61; 95% C.I. 0.46, 0.82), which was validated from the three randomly selected samples (hazard ratio [HR]=0.75; 95% C.I. 0.59, 0.96; p=0.02).

Conclusions: The C/I ratio may be an effective indicator linking diet quality, microbial metabolism, and T2D risk. CLINICAL TRIAL REGISTRY NUMBER AND WEBSITE WHERE IT WAS OBTAINED: not applicable.

Background: The source of dietary protein with different tryptophan concentrations can influence brain tryptophan and its metabolite concentrations. However, little is known about changes in tryptophan metabolites after a single meal.

Objective: To determine how fasting and postprandial brain concentrations of tryptophan and its metabolites vary in the growing pig fed different dietary proteins.

Methods: After seven days of meal adaptation, nine-week-old fasted male pigs (n=180) consumed an isocaloric meal without protein or with protein sources (45 g) differing in their tryptophan content (0.1, 3.7, 6.6, and 10 mg/g diet for zein, casein, whey protein isolate, and alpha-lactalbumin, respectively) before being euthanized at 0 (fasted values, 12 h from previous meal), 1, 2, 3, 4, and 6 h postprandially (n=6/dietary and time point combination). Blood plasma tryptophan, and tryptophan, serotonin, melatonin, kynurenine, and 3-hydroxykynurenine concentrations in hippocampus, striatum, prefrontal cortex, and pineal gland were determined. ANOVA and ANCOVA models were used to analyze the baseline values (0 h) and the complete dataset (0 to 6 h), respectively. Light intensity in the crates (23-256 lux) was included in the models as a covariate.

Results: In all brain regions, fasting concentrations of tryptophan and its metabolites (except serotonin), generally mirrored (P ≤ 0.05 or tended to follow P < 0.1) the tryptophan content of the protein sources consumed during the adaptation period. Postprandially, the pigs given alpha-lactalbumin had the highest (P < 0.001) increase in plasma and brain tryptophan concentrations compared to the other meals. Conversely, postprandial brain serotonin increased (or tended to increase) for all dietary treatments (P ≤ 0.05), whereas brain kynurenine and 3-hydroxykynurenine did not increase over time. Postprandial pineal gland melatonin varied (P < 0.001) across dietary treatments.

Conclusions: Fasting and postprandial brain tryptophan concentrations and tryptophan metabolite concentrations can be modulated through dietary intervention.

Background: The amino acids, L-leucine and L-isoleucine, and the bitter substance, quinine, reduce postprandial glucose, stimulate insulin and/or slow gastric emptying. Whether combining these stimuli can enhance these effects is not known.

Objective: We investigated whether combined intragastric administration of quinine with L-leucine or L-isoleucine, each in submaximal dose, would reduce the plasma glucose response to a mixed-nutrient drink more than each compound individually, associated with greater insulin stimulation and/or slowing of gastric emptying.

Methods: Fifteen healthy, lean males were recruited for each of two study parts. They received on 4 separate occasions, i) 300mg quinine-hydrochloride ('QHCl'), ii) 5g L-leucine ('Leu'; part A) or 5g L-isoleucine ('Ile'; part B), iii) combination of (i)+(ii) ('QHCl+Leu' or 'QHCl+Ile'), or iv) control intragastrically, in randomized, double-blind fashion. At t=-60 min, either QHCl or control was administered, and 30 min later (at t=-30 min), amino acid or control. At t=-1 min, participants consumed a mixed-nutrient drink labeled with sodium acetate-1-¹³C for measurement of gastric emptying by breath-test. Plasma glucose and insulin were measured at baseline (i.e. t=-60 min), for 60 min before the drink, and for 180 min post-drink. Breath samples were collected at baseline and post-drink, for subsequent analysis of ¹³CO₂.

Results: QHCl, QHCl+Leu and QHCl+Ile delayed the early rise in plasma glucose compared with control, Leu and Ile (all P<0.05). QHCl+Leu and QHCl+Ile stimulated insulin compared with QHCl, Leu and control (all P<0.05), but did not affect gastric emptying. The early glucose response (area under the curve, t=0-30 min (AUC_0-30min)) was related directly to early gastric emptying (AUC_0-30min) (R>0.41, P<0.01).

Conclusions: In healthy males, while combining QHCl with Leu or Ile, in the doses used, did not enhance their glucose-lowering effects, even small changes in the early gastric-emptying rate and insulin stimulation appear to contribute to postprandial glucose-lowering.

Clinical trial registry number: The study was registered as a clinical trial (https://clinicaltrials.gov/; part A: NCT05720390, date of registration: February 09, 2023; part B: NCT05682339, date of registration: January 12, 2023).