Effect of consuming hi-oleic peanuts on adiposity and cardiometabolic health

Inflammation markers predict zinc transporter gene expression in women with type 2 diabetes mellitus

Research suggests a role for inflammation and oxidative stress in mild cognitive impairment (MCI) and its progression. Evidence suggests anthocyanin-rich foods may reduce inflammation and oxidative stress and improve cognition but benefits in MCI are unclear. Therefore, it was hypothesized that daily consumption of anthocyanin-rich Queen Garnet Plum (QGP) juice would improve cognition, mood and blood pressure in people with MCI. Participants diagnosed with MCI (N = 42) participated in a double-blind, randomized controlled trial. Participants were administered either QGP juice or apricot juice (comparator) daily for 8-weeks and participated in a 6-week group-based memory program. Cognitive function was assessed using a battery of cognitive tests, including the Rey Auditory Verbal Learning Test (RAVLT), Complex Figure Test (CFT), Royal Prince Alfred-Prospective Memory Test (RPA-ProMem), and Comprehensive Assessment of Prospective Memory self-report (CAPM-self). Mood and blood pressure were also measured pre- and post-intervention. There was a significant effect of TIME for total RAVLT (P = .028, η2 = .12), CFT-recall (P = .036, η2 = .11), RPA-ProMem (P < .001, η2 = .28), and CAPM-self (P = .007, η2 = .22) scores. There was a non-significant trend towards an interaction for CFT-recall (p = .063, η2 = .09), where Bonferroni adjusted pairwise comparisons showed that the QGP group, but not comparators, had significantly improved CFT-recall scores (QGP: +13.93%, P = .007; comparators: +0.84%, P = .855). Overall, QGP consumption during a group-based memory rehabilitation program did not result in additional cognitive benefits in older adults with MCI. This trial was registered at the Australian New Zealand Clinical Trials Registry as ACTRN12618001184268.

The usefulness of zinc transporter and metallothionein (MT) gene expressions to detect changes in zinc intake remains unclear. This pilot study aimed to determine the effects of zinc supplementation on zinc transporter and MT gene expressions in humans. Healthy adults (n=39) were randomised to zinc treatment (ZT), receiving 22mg Zn/day (n=19), or no treatment (NT) (n=20). Blood samples were collected on Days 0, 2, 7, 14, and 21. Plasma zinc and serum C-reactive protein concentrations were analysed. Gene expression of zinc transporters and MT in peripheral blood mononuclear cells was analysed using real-time PCR. Using repeated-measures ANOVA, MT-2A gene expression and fold change were found to be higher in the ZT group (P=0.025 and P=0.016, respectively) compared to the NT group, specifically at Day 2 (40±18% increase from baseline, P=0.011), despite no significant increase in plasma zinc concentration. In a multiple regression model exploring the changes in gene expressions between Days 0 and 21, the change in MT-2A gene expression was correlated with changes in all zinc transporter expressions (r (2)=0.54, P=0.029); the change in ZIP1 expression emerged as a univariate predictor (P=0.003). Dietary zinc intake was predictive of zinc transporter and MT expressions (P=0.030). Physical activity level was positively correlated with baseline ZIP7 expression (r=0.36, P=0.029). The present study shows that MT-2A expression is related to changing expression of zinc transporter genes, specifically ZIP1, in response to zinc supplementation. The current report adds to our understanding of MT in the coordinated nature of cellular zinc homeostasis.

We measured fractional absorption of zinc (FAZ) in children with environmental enteropathy (EE) and carried out transcriptomic analysis of biopsies from these children in order to compare FAZ to histology of intestinal biopsies, expression of zinc transporter genes, and biomarkers of enteropathy. Fractional absorption of a standardized aqueous dose of zinc was measured by a dual isotope ratio technique in a cohort of children ages between 9 and 24 months in Lusaka, Zambia, who all had non-responsive stunting. Gene expression analysis was carried out on biopsies through RNA sequencing using an Illumina HiSeq2000 platform. All 33 children had histological features of environmental enteropathy and plasma zinc concentrations below the lower limit of normal. Measured FAZ ranged from 0.18 to 0.93; all values >0.55 were observed in girls. FAZ was negatively correlated with faecal myeloperoxidase (MPO) (ρ = -0.51, n = 17; P = 0.04) and faecal calprotectin (ρ = -0.50, n = 16; P = 0.05), but not blood biomarkers. Of 41 genes with known roles in zinc metabolism, only three metallothionein genes were significantly correlated with FAZ. Zinc homeostasis is impaired in children with environmental enteropathy, and was inversely correlated with mucosal inflammation. Reduced FAZ without specific changes in expression of most zinc transporter genes could be explained by reduced absorptive surface area due to villus/microvillus atrophy.

Anthocyanins are plant pigments and dietary phytochemicals, and may have potential health benefits. There is emerging evidence from epidemiological and experimental studies that suggests a higher consumption of anthocyanin-rich foods is associated with a reduced risk of heart disease and diabetes. To better understand the observed beneficial effects of anthocyanins and their underlying mode of action, bioavailability and metabolic fate needs to be studied in more detail. Healthy human subjects (10–12 in two different studies) received red grape pomace (700 mg anthocyanins/mainly as malvidin-3-glucoside) or Queen Garnet plum (QGP) juice (426 mg anthocyanins/mainly as cyanidin-3-glucoside) and an anthocyanin-free control in a randomised crossover design. Malvidin- and cyanidin-glycosides are common in many fruits and beverages such as red grapes, red grape juice, red wine, blueberry, cherry, elderberry, (Japanese) plum and are therefore of dietary significance. 24-hr urine samples were collected and analysed for anthocyanins and metabolites by UHPLC-PDA-MS. Methylated, glucuronidated and sulphated anthocyanins could be identified as characteristic metabolites in both studies. Furthermore, the increase in urinary hippuric acid (microbial/hepatic metabolite) was considerable in both studies after the consumption of red grape pomace or QGP juice (1.8–4.5-fold vs. control; p &lt; 0.05). These findings suggest that structurally different anthocyanins are exposed to a similar extensive metabolism by enzymes and the gut microbiome and that the generated metabolites are most likely the bioactive compounds in vivo. Therefore, more human studies are warranted to investigate the metabolic fate of dietary anthocyanins and the bioactivity of generated metabolites.

Obesity is associated with an alteration in zinc metabolism. This alteration may be associated with changes in gene expression of zinc transporters. In this study, we examined the leukocyte expression of zinc transporter ZnTs in response to zinc supplementation in young obese women. Thirty-five young obese women (BMI ≥ 25 kg/m(2)), aged 18-28 years, were randomly assigned to two groups: a placebo group or a zinc group (30 mg zinc/day for 8 weeks). Usual dietary zinc intake was estimated from 3-day diet records. Serum zinc and urinary zinc concentrations were measured by atomic absorption spectrometry. Messenger RNA (mRNA) levels of leukocyte ZnT transporters were examined using quantitative real-time PCR. Expression levels of two ZnT transporters, ZnT1 and ZnT5, in obese women, increased significantly after zinc supplementation. At the end of the study, mRNA levels of ZnT1 and ZnT5 showed no correlation with serum zinc or urinary zinc concentration in obese women. In addition, a further study was conducted to identify whether the association between the gene expression levels of leukocyte ZnT1 and ZnT5 and dietary zinc intake remained consistent in 216 healthy young adults aged 20-29 years. A positive correlation between ZnT1 and dietary zinc intake (r = 0.181, P = 0.089) was also observed in healthy men although the significance was marginal. Taken together, these results show that the gene expression levels of ZnT1 and ZnT5 may be changed by zinc intake, suggesting that zinc supplementation could potentially restore ZnT transporter expression in obese women with altered zinc metabolism.

Zinc nutritional status influences ZnT1 and ZIP4 gene expression in children with a high risk of zinc deficiency

Zinc plays an essential role in various fundamental biological processes. The focus of this research was to investigate the dosage effect of zinc glycine chelate (Zn-Gly) on zinc metabolism and the gene expression of zinc transporters in intestinal segments. A total of 30 4-week-old SD rats were randomized into five treatment groups. The basal diets for each group were supplemented with gradient levels of Zn (0, 30, 60, 90, and 180mg/kg) from Zn-Gly. After 1-week experiment, the results showed that serum and hepatic zinc concentration were elevated linearly with supplemental Zn levels from 0 to 180mg Zn/kg. Serum Cu-Zn SOD activities resulted in a significant (P<0.01) quadratic response and reached the peak when fed 60mg Zn/kg. There were linear responses to the addition of Zn-Gly from 0 to 180mg Zn/kg on Cu-Zn SOD and AKP activities in the liver. In the duodenum, MT1 mRNA was upregulated with the increasing dietary Zn-Gly levels and reached the peak of 180mg Zn/kg (P<0.05). Zip4 mRNA expression was downregulated with the increasing zinc levels (P<0.05) in both duodenum and jejunum. In the jejunum, Zip5 mRNA expression in 60mg Zn/kg was higher compared with other groups (P<0.05). ZnT1 mRNA in duodenum was numerically increased with the rising levels of zinc content and was significantly higher (P<0.05) with 180mg Zn/kg. In the duodenum, adding 60 or 90mg Zn/kg increased PepT1 expression, but in the jejunum, 60mg Zn/kg did not differ from 0 added Zn. In summary, there is a dose-dependent effect of dietary Zn-Gly on serum and hepatic zinc levels and the activities of Cu-Zn SOD and AKP on rats. Dietary Zn-Gly has a certain effect on MT1, Zip4, Zip5, and ZnT1 expression, which expressed differently in intestinal segments with different levels of Zn-Gly load. Besides, Zn-Gly also could regulate PepT1 expression in intestinal segments.

In recent years, there has been intense interest in the potential health benefits of dietary derived plant polyphenols and antioxidants. A new variety of Prunus salicina, Queen Garnet plum (QGP), was developed as a high anthocyanin, high antioxidant plum, in a Queensland Government breeding program. Following consumption of 400 mL QGP juice (QGPJ; 1,117 mg anthocyanins) by two healthy male subjects, QGP anthocyanins (cyanidin-3-glucoside and cyanidin-3-rutinoside) were excreted mainly as methylated and glucuronidated metabolites in urine (0.5% of the ingested dose within 24 h). Furthermore, QGPJ intake resulted in a threefold increase in hippuric acid excretion (potential biomarker for total polyphenols intake and metabolite), an increased urinary antioxidant capacity and a decreased malondialdehyde excretion (biomarker for oxidative stress) within 24 h as compared with the polyphenol-/antioxidant-free control. Results from this pilot study suggest that metabolites, and not the native QGP anthocyanins/polyphenols, are most likely the bioactive compounds in vivo.

Tudents’ experiences and perceptions of clinical prediction rules

Backgroundβ-cells are extremely rich in zinc and zinc homeostasis is regulated by zinc transporter proteins. β-cells are sensitive to cytokines, interleukin-1β (IL-1β) has been associated with β-cell dysfunction and -death in both type 1 and type 2 diabetes. This study explores the regulation of zinc transporters following cytokine exposure.MethodsThe effects of cytokines IL-1β, interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) on zinc transporter gene expression were measured in INS-1-cells and rat pancreatic islets. Being the more sensitive transporter, we further explored ZnT8 (Slc30A8): the effect of ZnT8 over expression on cytokine induced apoptosis was investigated as well as expression of the insulin gene and two apoptosis associated genes, BAX and BCL2.ResultsOur results showed a dynamic response of genes responsible for β-cell zinc homeostasis to cytokines: IL-1β down regulated a number of zinc-transporters, most strikingly ZnT8 in both islets and INS-1 cells. The effect was even more pronounced when mixing the cytokines. TNF-α had little effect on zinc transporter expression. IFN-γ down regulated a number of zinc transporters. Insulin expression was down regulated by all cytokines. ZnT8 over expressing cells were more sensitive to IL-1β induced apoptosis whereas no differences were observed with IFN-γ, TNF-α, or a mixture of cytokines.ConclusionThe zinc transporting system in β-cells is influenced by the exposure to cytokines. Particularly ZnT8, which has been associated with the development of diabetes, seems to be cytokine sensitive.

Macro and micronutrient differences of AD—libitum palaeolithic vs Australian guide to healthy eating diets

The effects of anthocyanins on body weight and expression of adipocyte’s hormones: Leptin and adiponectin

A new variety of Prunus salicina, Queen Garnet plum (QGP), was developed as a high anthocyanin, high antioxidant plum, in a Queensland, Australia, Government breeding program. In this manuscript, we are presenting for the first time data about the urinary pharmacokinetics of QGP anthocyanins and derived metabolites in healthy humans. Following consumption of 400 mL QGP juice (QGPJ; 2.49 mmol anthocyanins) by two male subjects, QGP anthocyanins (cyanidin-3-glucoside and cyanidin-3-rutinoside) were excreted mainly as methylated glycosides, glucuronides, and sulfoconjugated metabolites in urine. The cumulative excretion of anthocyanins could be fitted to a one-compartment pharmacokinetic model with instantaneous, parallel excretion of anthocyanin metabolites. The usefulness of this non-linear modeling statistical technique for characterizing the urine excretion-time profiles and estimating relevant PK parameters is demonstrated. Results from this pilot study indicate that methylation and glucuronidation are significant metabolic routes when cyanidin-based anthocyanins are consumed in QGPJ. Future studies investigating the benefits of the consumption of anthocyanin-rich Queen Garnet plums and/or derived products should therefore focus on identifying anthocyanin metabolites and include their putative colonic degradation products. This will assist in evaluating the biological relevance of these compounds to health and disease prevention.

A coordinated network of zinc transporters and binding proteins tightly regulate cellular zinc levels. Canonical responses to zinc availability are thought to be mediated by changes in gene expression of key zinc transporters. We investigated the temporal relationships of actual zinc uptake with patterns of gene expression in membrane-bound zinc transporters in the human immortalized T lymphocyte Jurkat cell line. Cellular zinc levels were elevated or reduced with exogenous zinc sulfate or N,N,N',N-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), respectively. Excess zinc resulted in a rapid 44 % decrease in the rate of zinc uptake within 10 min. After 120 min, the expression of metallothionein (positive control) increased, as well as the zinc exporter, ZnT1; however, the expression of zinc importers did not change during this time period. Zinc chelation with TPEN resulted in a rapid twofold increase in the rate of zinc uptake within 10 min. After 120 min, the expression of ZnT1 decreased, while again the expression of zinc importers did not change. Overall, zinc transporter gene expression kinetics did not match actual changes in cellular zinc uptake with exogenous zinc or TPEN treatments. This suggests zinc transporter regulation may be the initial response to changes in zinc within Jurkat cells.