Transcriptomic Differences Between Monozygotic Adolescent Twins Discordant For Metabolic Syndrome Following Weight Loss: A Case Study.

This case reports peripheral blood mononuclear cell (PBMC) transcriptomic changes in a pair of male monozygotic pediatric twins with metabolic syndrome (MetS) undertaking assisted weight loss. These 14-year-old boys presented with similar baseline biochemistry and body composition. After a 16-week weight-loss intervention, percent body weight loss was similar (Twin A 12%, and Twin B 13%). MetS resolved in Twin A but Twin B maintained elevated triglycerides after weight loss. Analysis of the PBMC transcriptome before and after weight loss revealed very different changes in gene expression including differences in the direction of expression of genes related to immune cell activation. 48.7% of genes that were downregulated in Twin A were upregulated in Twin B. This case highlights a novel approach to report the influence of chronic low-grade inflammation and metabolic dysfunction on the PBMC transcriptome. It explores whether expression of genes related to immune functions may underlie the differences in response to weight loss or whether transcriptomic alterations in immune cells may precede more traditional biomarkers of chronic pro-inflammation. These monozygotic twins present an example of divergence of phenotypic outcomes despite identical genetic background and similar treatment response.

Zinc-rich inhibitor of apoptosis proteins (IAPs) as regulatory factors in the epithelium of normal and inflamed airways.

Integrity of the airway epithelium (AE) is important in the context of inhaled allergens and noxious substances, particularly during asthma-related airway inflammation where there is increased vulnerability of the AE to cell death. Apoptosis involves a number of signaling pathways which activate procaspases leading to cleavage of critical substrates. Understanding the factors which regulate AE caspases is important for development of strategies to minimize AE damage and airway inflammation, and therefore to better control asthma. One such factor is the essential dietary metal zinc. Zinc deficiency results in enhanced AE apoptosis, and worsened airway inflammation. This has implications for asthma, where abnormalities in zinc homeostasis have been observed. Zinc is thought to suppress the steps involved in caspase-3 activation. One target of zinc is the family of inhibitor of apoptosis proteins (IAPs) which are endogenous regulators of caspases. More studies are needed to identify the roles of IAPs in regulating apoptosis in normal and inflamed airways and to study their interaction with labile zinc ions. This new information will provide a framework for future clinical studies aimed at monitoring and management of airway zinc levels as well as minimising airway damage and inflammation in asthma.

New insights into the nutritional genomics of adult-onset riboflavin-responsive diseases.

Riboflavin, or vitamin B2, is an essential nutrient that serves as a precursor to flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN). The binding of the FAD and/or FMN cofactors to flavoproteins is critical for regulating their assembly and activity. There are over 90 proteins in the human flavoproteome that regulate a diverse array of biochemical pathways including mitochondrial metabolism, riboflavin transport, ubiquinone and FAD synthesis, antioxidant signalling, one-carbon metabolism, nitric oxide signalling and peroxisome oxidative metabolism. The identification of patients with genetic variants in flavoprotein genes that lead to adult-onset pathologies remains a major diagnostic challenge. However, once identified, many patients with adult-onset inborn errors of metabolism demonstrate remarkable responses to riboflavin therapy. We review the structure:function relationships of mutant flavoproteins and propose new mechanistic insights into adult-onset riboflavin-responsive pathologies and metabolic dysregulations that apply to multiple biochemical pathways. We further address the vexing issue of how the inheritance of genetic variants in flavoprotein genes leads to an adult-onset disease with complex symptomologies and varying severities. We also propose a broad clinical framework that may not only improve the current diagnostic rates, but also facilitate a personalized approach to riboflavin therapy that is low cost, safe and lead to transformative outcomes in many patients.

A 12-month weight loss intervention in adults with obstructive sleep apnoea: is timing important? A step wedge randomised trial.

BACKGROUND/OBJECTIVES: Continuous positive airway pressure (CPAP) concomitant with weight loss is a recommended treatment approach for adults with moderate-severe obstructive sleep apnoea (OSA) and obesity. This requires multiple synchronous behaviour changes. The aim of this study was to examine the effectiveness of a 6-month lifestyle intervention and to determine whether the timing of starting a weight loss attempt affects weight change and trajectory after 12 months in adults newly diagnosed with moderate-severe OSA and treated at home with overnight CPAP. METHODS: Using a stepped-wedge design, participants were randomised to commence a six-month lifestyle intervention between one and six-months post-enrolment, with a 12-month overall follow-up. Adults (n = 60, 75% males, mean age 49.4 SD 10.74 years) newly diagnosed with moderate-severe OSA and above a healthy weight (mean BMI 34.1 SD 4.8) were recruited. RESULTS: After 12 months, exposure to the intervention (CPAP and lifestyle) resulted in a 3.7 (95% CI: 2.6 to 4.8, p < 0.001) kg loss of weight compared to the control condition (CPAP alone). Timing of the weight loss attempt made no difference to outcomes at 12 months. When exposed to CPAP only (control period) there was no change in body weight (Coef, [95% CI] 0.03, [-0.3 to 0.36], p = 0.86). CONCLUSIONS: The lifestyle intervention resulted in a modest reduction in body weight, while timing of commencement did not impact the degree of weight loss at 12 months. These findings support the recommendation of adjunctive weight-loss interventions within six-months of starting CPAP.

Dietary zinc mediates inflammation and protects against wasting and metabolic derangement caused by sustained cigarette smoke exposure in mice.

In mouse asthma models, inflammation can be modulated by zinc (Zn). Given that appetite loss, muscle wasting and poor nutrition are features of chronic obstructive pulmonary disease (COPD) and that poor dietary Zn intake is in itself accompanied by growth retardation and appetite loss, we hypothesised that dietary Zn limitation would not only worsen airway inflammation but also exaggerate metabolic effects of cigarette smoke (CS) exposure in mice. Conversely, Zn supplementation would lessen inflammation. Mice were exposed to CS [2× 2RF, 3×/day; 15 min/cigarette] and fed diets containing 2, 20 or 140 mg/kg Zn ad libitum. Airway cells were collected by bronchoalveolar lavage (BAL). Plasma Zn was measured by fluorometric assay. Inflammatory, metabolic and Zn transport markers were measured by real-time RT-PCR. Mice fed low Zn diets had less plasma labile zinc (0-0.18 µM) than mice fed moderate (0.61-0.98 µM) or high (0.77-1.1 µM) Zn diets (SDs 0.1-0.4, n = 8-10). Smoke exposure increased plasma and BAL labile Zn (1.5-2.5 fold, P < 0.001), bronchoalveolar macrophages (2.0 fold, P < 0.0001) and MT-1 (1.5 fold), MIP-2 (2.3 fold) and MMP-12 (3.5 fold) mRNA. Zn supplementation reduced alveolar macrophage numbers by 62 and 52% in sham and smoke-exposed mice, respectively (Zn effect: P = 0.011). Gastrocnemius, soleus and tibialis anterior muscle mass were affected by both smoke and dietary Zn in the order of 3-7%. The 50-60% reduction in alveolar macrophages in Zn-supplemented mice supports our evolving hypothesis that Zn is an important anti-inflammatory mediator of airway inflammation. Restoring airway Zn levels through dietary supplementation may lessen the severity of lung inflammation when Zn intake is low.

Ultrastructural analysis, zinc transporters, glucose transporters and hormones expression in New world primate (Callithrix jacchus) and human pancreatic islets.

The New world primates (NWP) Callithrix jacchus separated from man approximately 50 million years ago and is a potential alternative small non-human primate model for diabetes research. Ultrastructure, and gene expression of pancreatic islets and the recently described diabetes auto antigenic zinc transporters families in human, NWP and pig pancreas were studied. Morphologically NWP islets were larger than pig islets and similar in size to human islets. NWP islets alpha cells had high dense core surrounded by a limiting membrane, beta cells by the mixed morphology of the granule core, and delta cells by moderate opaque core. Antibody staining for insulin, glucagon, somatostatin and Glucagon-like peptide-1 (GLP-1) showed that the distribution pattern of the different cell types within islets was comparable to pig and human islets. In all three species protein expression of zinc transporter ZnT8 was detected in most of the insulin producing beta cells whereas Zip14 expression was widely expressed in alpha and beta cells. In both human and NWP little or no expression of Glut2 was observed compared to Glut1 and glucokinase at the protein level, however the messenger RNA level of Glut2 was greater than Glut1 and glucokinase. In contrast all three glucose transporters were expressed in pig islets at the protein level. The expression of Zip14 in islets is reported for the first time. In conclusion NWP pancreatic islets express comparable islet cell types and distribution to humans and pigs. Importantly, marmosets have a similar glucose transporter profile to humans, making this non-endangered primate species a useful animal model for pancreatic biology.

Transcriptomic changes in peripheral blood mononuclear cells with weight loss: systematic literature review and primary data synthesis.

BACKGROUND AND OBJECTIVES: Peripheral blood mononuclear cells (PBMCs) have shown promise as a tissue sensitive to subtle and possibly systemic transcriptomic changes, and as such may be useful in identifying responses to weight loss interventions. The primary aim was to comprehensively evaluate the transcriptomic changes that may occur during weight loss and to determine if there is a consistent response across intervention types in human populations of all ages. METHODS: Included studies were randomised control trials or cohort studies that administered an intervention primarily designed to decrease weight in any overweight or obese human population. A systematic search of the literature was conducted to obtain studies and gene expression databases were interrogated to locate corresponding transcriptomic datasets. Datasets were normalised using the ArrayAnalysis online tool and differential gene expression was determined using the limma package in R. Over-represented pathways were explored using the PathVisio software. Heatmaps and hierarchical clustering were utilised to visualise gene expression. RESULTS: Seven papers met the inclusion criteria, five of which had raw gene expression data available. Of these, three could be grouped into high responders (HR, ≥ 5% body weight loss) and low responders (LR). No genes were consistently differentially expressed between high and low responders across studies. Adolescents had the largest transcriptomic response to weight loss followed by adults who underwent bariatric surgery. Seven pathways were altered in two out of four studies following the intervention and the pathway 'cytoplasmic ribosomal proteins' (WikiPathways: WP477) was altered between HR and LR at baseline in the two datasets with both groups. Pathways related to 'toll-like receptor signalling' were altered in HR response to the weight loss intervention in two out of three datasets. CONCLUSIONS: Transcriptomic changes in PBMCs do occur in response to weight change. Transparent and standardised data reporting is needed to realise the potential of transcriptomics for investigating phenotypic features. REGISTRATION NUMBER: PROSPERO: CRD42019106582.

Diurnal variation in gene expression of human peripheral blood mononuclear cells after eating a standard meal compared with a high protein meal: A cross-over study.

BACKGROUND & AIMS: Eating at night has been linked to impaired glucose metabolism and dyslipidaemia that is likely a consequence of an underlying disrupted circadian rhythm in metabolic processes. The aim of this study was to explore the gene expression differences after eating a standard test meal or high protein test meal at night compared with the same meal in the morning. METHODS: In a cross over design, 10 healthy adults fasted for >10 h and then completed four acute meal challenges at 8am and 8pm on non-consecutive days separated by a wash out, consuming either a high protein low carbohydrate test meal or an isocaloric standard protein and carbohydrate test meal. Fasting and two-hour postprandial blood samples were collected to measure gene expression. For a subset of five participants RNA sequencing was completed on the Illumina NextSeq500. RESULTS: The time of day a meal is consumed had an effect on which genes were differentially regulated in the acute postprandial period, with only 6.5% of differentially expressed genes the same both morning and night. More genes were involved in lipid metabolic pathways in the morning and immune pathways at night. RTqPCR analysis of target genes suggested that key regulatory genes responsible for nutrient sensing and lipid and glucose metabolism are differentially expressed at night. These may play a role in improved blood glucose control in peripheral tissues that is observed after eating in the morning but to a lesser extent or not at all at night. Modulation of the macronutrient composition of a meal led to changes in expression of genes involved in the circadian clock and metabolism. CONCLUSIONS: Investigating the differences in the transcriptomic response to food at night provides a greater understanding of the mechanisms underlying the changing metabolic phenotypes, characterised by circulating metabolic biomarkers, according to the time of day.

Blunted nutrient-response pathways in adipose tissue following high fat meals in men with metabolic syndrome: A randomized postprandial transcriptomic study.

BACKGROUND: Excessive adipose tissue is central to disease burden posed by the Metabolic Syndrome (MetS). Whilst much is known of the altered transcriptomic regulation of adipose tissue under fasting conditions, little is known of the responses to high-fat meals. METHODS: Nineteen middle-aged males (mean ± SD 52.0 ± 4.6 years), consumed two isocaloric high-fat, predominately dairy-based or soy-based, breakfast meals. Abdominal subcutaneous adipose biopsies were collected after overnight fast (0 h) and 4 h following each meal. Global gene expression profiling was performed by microarray (Illumina Human WG-6 v3). RESULTS: In the fasted state, 13 genes were differently expressed between control and MetS adipose tissue (≥1.2 fold-difference, p < 0.05). In response to the meals, the control participants had widespread increases in genes related to cellular nutrient responses (≥1.2 fold-change, p < 0.05; 2444 & 2367 genes; dairy & soy, respectively). There was blunted response in the MetS group (≥1.2 fold-change, p < 0.05; 332 & 336 genes; dairy & soy, respectively). CONCLUSIONS: In middle-aged males with MetS, a widespread suppression of the subcutaneous adipose tissue nutrient responsive gene expression suggests an inflexibility in the transcriptomic responsiveness to both high-fat meals.

Promoting Evidence Based Nutrition Education Across the World in a Competitive Space: Delivering a Massive Open Online Course.

The internet is the fastest growing source of nutrition information for consumers. Massive Open Online Courses (MOOCs) provide and avenue for nutrition professionals' urgent need to respond to consumer demand for low-cost, accessible and engaging information. This research aimed to evaluate learner participation and perceptions in an evidence-based nutrition MOOC and provide recommendations for engaging international online lay audiences. Learners completed pre and post course surveys including quantitative and open-ended questions. Pre-course surveys collected demographic data, prior nutrition knowledge and motivations for doing the course. Post-course surveys evaluated their preferred learning modes and learners' opinions of the course. Quantitative were analyzed using descriptive statistics. Conventional content analysis was conducted on learners' responses to open-ended survey questions using an inductive approach. Learners represented 158 countries from a range of educational backgrounds. There were 3799 qualitative comments related to learners' learning and course content preferences. Qualitative analysis identified key themes related to (1) online interaction, the (2) value of the evidence presented by nutrition experts and (3) the course structure and practical aspects. Divergent opinions were expressed within these themes. Satisfying the needs of large international audiences with diverse backgrounds is challenging in promoting sound evidence-based nutrition messages. MOOCs provide a means for delivering evidence based global nutrition education in the online space crowded with food advertising and nutrition conjecture. Recommendations are made as to how to construct and engage diverse on-line audiences.

Effects of macronutrient manipulation on postprandial metabolic responses in overweight males with high fasting lipids during simulated shift work: A randomized crossover trial.

BACKGROUND & AIMS: Meals consumed out of synchronisation with normal circadian rhythms are associated with metabolic dysregulation. Changes in macronutrient composition of meals can improve metabolic responses during the day. Therefore, we aimed to investigate whether macronutrient manipulation of meals alters postprandial glucose and lipid responses and the expression of circadian genes during the night. METHODS: In a randomised crossover trial, 16 overweight males with high fasting lipids were fed isocaloric meals (2.7 MJ) at 0000 h. The meals differed primarily in total fat and total sugars content (control (8% total sugar, 5% saturated fat) vs test (16% total sugar, 26% saturated fat)). Postprandial blood samples were collected for glucose, insulin (3 h) and triglycerides (6 h) and analysed as incremental area under the curve (iAUC). RNA was extracted at 0 h, 2 h and 4 h and changes in expressions of the circadian genes clock and Per 1-3 analysed. RESULTS: Postprandial glucose (p = 0.04) and insulin iAUC (p = 0.02) were significantly higher after consumption of the test meal compared to the control meal. Postprandial triglyceride iAUC was not statistically different between the two meal types (p = 0.72). No change in circadian gene expression was observed after the two meals. CONCLUSIONS: Our results showed that macronutrient composition affects postprandial metabolic response at night. It emphasizes the need to consider the role and effects of night time eating, when developing metabolic disease prevention strategies for shift workers. STUDY ID NUMBER: ACTRN12618001115224. WEBSITE OF TRIAL REGISTRY: http://www.anzctr.org.au/. Retrospectively registered after data collection.

Sleeping Well Trial: Increasing the effectiveness of treatment with continuous positive airway pressure using a weight management program in overweight adults with obstructive sleep apnoea-A stepped wedge randomised trial protocol.

BACKGROUND: The majority of adults diagnosed with obstructive sleep apnoea (OSA) are overweight or obese. Continuous positive airway pressure (CPAP) is the most common effective therapy for OSA. However, adherence declines over time with only 50% of patients prescribed CPAP continuing to use it long term. Furthermore, a recent prospective analysis indicated that those more adherent with CPAP therapy have enhanced weight gain trajectories which in turn may negatively impact their OSA. AIM: The Sleeping Well Trial aims to establish whether the timing of starting a lifestyle weight loss intervention impacts on weight trajectory in those with moderate-severe OSA treated at home with CPAP, while testing the potential for smart phone technology to improve adherence with lifestyle interventions. METHODS: A stepped wedge design with randomisation of individuals from 1 to 6 months post-enrolment, with 5 months of additional prospective follow up after completion of the stepped wedge. This design will investigate the effect of the 6-month lifestyle intervention on people undergoing CPAP on body weight, body composition and health-related quality of life. DISCUSSION: This trial tests whether the timing of supporting the patient through a weight loss intervention is important in obtaining the maximum benefit of a lifestyle change and CPAP usage, and identify how best to support patients through this critical period. TRIAL REGISTRATION: The protocol (v1) is registered prospectively with the International Clinical Trials Registry (CTR) ACTRN12616000203459 (public access). Any amendments to protocol will be documented via the CTR. Recruitment commenced in March 2016 with data collection scheduled to finish by May 2018.

Opportunities for training for nutritional professionals in nutritional genomics: What is out there?

AIM: To identify and profile training courses available to dietitians and nutritionists in the area of nutritional genomics. Genetic technology is progressing quickly, leading to increased public interest and requests from the public for personalised nutrition advice based on genetic background. Tertiary courses often lack specific curriculum in nutritional genomics, preventing graduates from discussing confidently with their clients the relationships between genetics, nutrition and health. This has increased the demand for professional development in this field. METHODS: The search strategy was intended to replicate real-life practice. Google and snowball searches were conducted using terms related to education and nutritional genomics. Results included online or face-to-face courses in any country providing content on nutritional genomics. One-off courses and those courses no longer accessible were excluded. A descriptive analysis of characteristics of courses was undertaken, reporting on mode of delivery, cost, duration, content, qualification awarded, target audience and affiliations. RESULTS: In total, 37 courses varying in duration, content and cost were identified: 4 postgraduate university degrees, 5 university course units, 4 recurring face-to-face workshops, 15 online short courses, 8 pre-recorded presentations and 1 service offering regular live webinars. Affiliations with food and pharmaceutical industry (e.g. genetic testing companies), professional organisations and research/education institutes were observed. CONCLUSIONS: Training courses identified were predominantly delivered online, enabling nutrition professionals worldwide to upskill in nutritional genomics and personalised nutrition. Additional courses exist. Those seeking training should scrutinise and compare cost, duration, mode, content and affiliations of course providers to ensure learning needs are met.

Proteomic Analysis of Zn Depletion/Repletion in the Hormone-Secreting Thyroid Follicular Cell Line FRTL-5.

Zinc deficiency predisposes to a wide spectrum of chronic diseases. The human Zn proteome was predicted to represent about 10% of the total human proteome, reflecting the broad array of metabolic functions in which this micronutrient is known to participate. In the thyroid, Zn was reported to regulate cellular homeostasis, with a yet elusive mechanism. The Fischer Rat Thyroid Cell Line FRTL-5 cell model, derived from a Fischer rat thyroid and displaying a follicular cell phenotype, was used to investigate a possible causal relationship between intracellular Zn levels and thyroid function. A proteomic approach was applied to compare proteins expressed in Zn deficiency, obtained by treating cells with the Zn-specific chelator N,N,N',N'-tetrakis (2-pyridylmethyl) ethylene-diamine (TPEN), with Zn repleted cells. Quantitative proteomic analysis of whole cell protein extracts was performed using stable isotope dimethyl labelling coupled to nano-ultra performance liquid chromatography-mass spectrometry (UPLC-MS). TPEN treatment led to almost undetectable intracellular Zn, while decreasing thyroglobulin secretion. Subsequent addition of ZnSO4 fully reversed these phenotypes. Comparative proteomic analysis of Zn depleted/repleted cells identified 108 proteins modulated by either treatment. Biological process enrichment analysis identified functions involved in calcium release and the regulation of translation as the most strongly regulated processes in Zn depleted cells.

Does modifying the timing of meal intake improve cardiovascular risk factors? Protocol of an Australian pilot intervention in night shift workers with abdominal obesity.

INTRODUCTION: Shift work is an independent risk factor for cardiovascular disease (CVD). Shift workers who are awake overnight and sleep during the day are misaligned with their body's endogenous circadian rhythm. Eating at night contributes to this increased risk of CVD by forcing the body to actively break down and process nutrients at night. This pilot study aims to determine whether altering meal timing overnight, in a shift working population, will impact favourably on modifiable risk factors for CVD (postprandial bplasma lipids and glucose concentration). METHODS AND ANALYSIS: A randomised cross-over study with two 4-week test periods, separated by a minimum of a 2-week washout will be undertaken. The effectiveness of redistributing energy intake overnight versus ad libitum eating patterns on CVD risk factors will be examined in night shift workers (n=20), using a standard acute test meal challenge protocol. Primary outcomes (postprandial lipids and glucose) will be compared between the two conditions: post-intervention and post-control period using analysis of variance. Potential effect size estimates to inform sample size calculations for a main trial will also be generated. ETHICS AND DISSEMINATION: Ethics approval has been granted by the Monash University Human Research Ethics Committee (2017-8619-10329). Outcomes from this study will determine whether eliminating food intake for a defined period at night (1-6 am) impacts favourably on metabolic risk factors for CVD in night shift workers. Collective results from this novel trial will be disseminated through peer-reviewed journals, and national and international presentations. The results are essential to inform health promotion policies and guidelines for shift workers, especially those who aim to improve their metabolic health. TRIAL REGISTRATION NUMBER: ACTRN12617000791336; Pre-results.

Zinc fluxes and zinc transporter genes in chronic diseases.

The group IIb metal zinc (Zn) is an essential dietary component that can be found in protein rich foods such as meat, seafood and legumes. Thousands of genes encoding Zn binding proteins were identified, especially after the completion of genome projects, an indication that a great number of biological processes are Zn dependent. Imbalance in Zn homeostasis was found to be associated with several chronic diseases such as asthma, diabetes and Alzheimer's disease. As it is now evident for most nutrients, body Zn status results from the interaction between diet and genotype. Zn ions cross biological membranes with the aid of specialized membrane proteins, belonging to the ZRT/IRT-related Proteins (ZIP) and zinc transporters (ZnT) families. The ZIPs are encoded by the Slc39A gene family and are responsible for uptake of the metal, ZnTs are encoded by the Slc30A genes and are involved in intracellular traffic and/or excretion. Both ZnTs and Zips exhibit unique tissue-specific expression, differential responsiveness to dietary Zn deficiency and excess, as well as to physiological stimuli via hormones and cytokines. Intracellular Zn concentration is buffered by metallothioneins (MTs), a class of cytosolic protein with high affinity for metals. Scattered information is available on the role of proteins responsible for regulating Zn fluxes in the onset and progression of chronic diseases. This paper reviews reports that link Zn transporter genes, their allelic variants and/or expression profiles in the context of specific diseases. Further investigation in this direction is very important, since Zn imbalance can result not only from insufficient dietary intake, but also from impaired activity of proteins that regulate Zn metabolism, thus contributing to multifactorial diseases.

Translation of Nutritional Genomics into Nutrition Practice: The Next Step.

Genetics is an important piece of every individual health puzzle. The completion of the Human Genome Project sequence has deeply changed the research of life sciences including nutrition. The analysis of the genome is already part of clinical care in oncology, pharmacology, infectious disease and, rare and undiagnosed diseases. The implications of genetic variations in shaping individual nutritional requirements have been recognised and conclusively proven, yet routine use of genetic information in nutrition and dietetics practice is still far from being implemented. This article sets out the path that needs to be taken to build a framework to translate gene-nutrient interaction studies into best-practice guidelines, providing tools that health professionals can use to understand whether genetic variation affects nutritional requirements in their daily clinical practice.

Genetic Variations as Modifying Factors to Dietary Zinc Requirements-A Systematic Review.

Due to reduced cost and accessibility, the use of genetic testing has appealed to health professionals for personalising nutrition advice. However, translation of the evidence linking polymorphisms, dietary requirements, and pathology risk proves to be challenging for nutrition and dietetic practitioners. Zinc status and polymorphisms of genes coding for zinc-transporters have been associated with chronic diseases. The present study aimed to systematically review the literature to assess whether recommendations for zinc intake could be made according to genotype. Eighteen studies investigating 31 Single Nucleotide Polymorphisms (SNPs) in relation to zinc intake and/or status were identified. Five studies examined type 2 diabetes; zinc intake was found to interact independently with two polymorphisms in the zinc-transporter gene SLC30A8 to affect glucose metabolism indicators. While the outcomes were statistically significant, the small size of the effect and lack of replication raises issues regarding translation into nutrition and dietetic practice. Two studies assessed the relationship of polymorphisms and cognitive performance; seven studies assessed the association between a range of outcomes linked to chronic conditions in aging population; two papers described the analysis of the genetic contribution in determining zinc concentration in human milk; and two papers assessed zinc concentration in plasma without linking to clinical outcomes. The data extracted confirmed a connection between genetics and zinc requirements, although the direction and magnitude of the dietary modification for carriers of specific genotypes could not be defined. This study highlights the need to summarise nutrigenetics studies to enable health professionals to translate scientific evidence into dietary recommendations.

Zinc metabolism in airway epithelium and airway inflammation: basic mechanisms and clinical targets. A review.

In addition to basic housekeeping roles in metalloenzymes and transcription factors, dietary zinc (Zn) is an important immunoregulatory agent, growth cofactor, and cytoprotectant with anti-oxidant, anti-apoptotic, and anti-inflammatory roles. These properties of Zn are of particular importance in maintaining homeostasis of epithelial tissues which are at the front line of defense. This review is about the role of Zn in airway epithelium (AE). The first part focuses on the cellular biology of Zn, and what is known about its distribution and function in AE. The second part of the review considers evidence for altered Zn metabolism in asthma and other chronic diseases of airway inflammation. Important issues arise from a potential therapeutic perspective as to the optimal ways to monitor circulating and epithelial Zn levels in patients and the most effective means of supplementing these levels.

Use of a zinc fluorophore to measure labile pools of zinc in body fluids and cell-conditioned media.

Here we describe a rapid and sensitive zinquin-based fluorometric assay that enables one to monitor levels of labile Zn(II) in body fluids, buffers, and cell-conditioned culture media as well as changes in these pools in disease. Labile pools of Zn(II) are free or loosely bound pools and more tightly bound but zinquin-accessible pools in contrast to the fixed pools of Zn(II) within metalloproteins. In human plasma, mean labile Zn(II) was 8.1 microM (SEM 0.53; n = 81) and constituted about 70% of the total plasma Zn(II) and >90% of human plasma albumin Zn(II). Plasma labile Zn(II) was significantly depleted after 7 days of Zn(II) deprivation in mice, despite only small changes in body weight. Labile Zn(II) concentrations were also measured in the induced sputum plugs, saliva, and urine of normal adults and were 1.30 microM (SEM 0.27; n = 73), 0.11 microM (SEM 0.11; n = 6), and 0.23 microM (SEM 0.08; n = 8), respectively. Urinary labile Zn(II) concentration was significantly increased in some patients with type II diabetes mellitus (overall mean was 0.90 microM, SEM 0.30; n = 12). The technique may be particularly useful in assessing extracellular Zn(II) levels in diseases associated with altered Zn(II) homeostasis, identifying those subjects most in need of Zn(II) supplementation, and defining the optimum concentrations of available Zn(II) in buffers and culture media.