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Title:
Serum Leptin, Resistin, and Adiponectin Concentrations in Psoriasis: A Meta-Analysis of Observational Studies
Authors:
Kyriakou, Aikaterini; Patsatsi, Aikaterini; Sotiriadis, Dimitrios; Goulis, Dimitrios G.
Abstract:
BACKGROUND: Psoriasis is an immune-mediated, inflammatory disease. Adipokines contribute to the regulation of immune-mediated processes and inflammation. OBJECTIVE: The aim of our study was to systematically review the literature for studies that have evaluated the circulating concentrations of adipokines in patients with psoriasis and controls and to meta-analyze the best evidence available. METHODS: Eligible were studies that have assessed leptin, resistin, or adiponectin concentrations in psoriatic patients and a reference group. The study was conducted in adherence with the PRISMA standards. RESULTS: Psoriatic patients had higher leptin concentrations compared to controls (random effects model, mean difference, MD = 5.64 ng/mL, 95% CI: 3.00-8.29, p < 0.0001). Heterogeneity among studies was high (I2 = 95.9%). Psoriatic patients had higher resistin concentrations compared to controls (MD = 4.66 ng/mL, 95% CI: 2.62-6.69, p < 0.0001). Heterogeneity was high (I2 = 99.2%). Finally, psoriatic patients had lower adiponectin concentrations compared to controls (MD = -1.87 μg/mL, 95% CI: -2.76 to -0.98, p
Published:
2017
Title:
Setting Nutritional Standards: Theory, Policies, Practices
Authors:
Abstract:
Published:
2017
Title:
Sexual Dimorphism, Age, and Fat Mass Are Key Phenotypic Drivers of Proteomic Signatures
Authors:
Curran, Aoife M.; Fogarty Draper, Colleen; Scott-Boyer, Marie-Pier; Valsesia, Armand; Roche, Helen M.; Ryan, Miriam F.; Gibney, Michael J.; Kutmon, Martina; Evelo, Chris T.; Coort, Susan L.; Astrup, Arne; Saris, Wim H.; Brennan, Lorraine; Kaput, Jim
Abstract:
Validated protein biomarkers are needed for assessing health trajectories, predicting and subclassifying disease, and optimizing diagnostic and therapeutic clinical decision-making. The sensitivity, specificity, accuracy, and precision of single or combinations of protein biomarkers may be altered by differences in physiological states limiting the ability to translate research results to clinically useful diagnostic tests. Aptamer based affinity assays were used to test whether low abundant serum proteins differed based on age, sex, and fat mass in a healthy population of 94 males and 102 females from the MECHE cohort. The findings were replicated in 217 healthy male and 377 healthy female participants in the DiOGenes consortium. Of the 1129 proteins in the panel, 141, 51, and 112 proteins (adjusted p
Published:
2017
Title:
Short-term biomarkers of apple consumption
Authors:
Saenger, Theresa; Hübner, Florian; Humpf, Hans-Ulrich
Abstract:
SCOPE: Urinary biomarkers are used to estimate the nutritional intake of humans. The aim of this study was to distinguish between low, medium, and high apple consumption by quantifying possible intake biomarkers in urine samples after apple consumption by HPLC-MS/MS. Apples were chosen as they are the most consumed fruits in Germany. METHODS AND RESULTS: Thirty subjects took part in 7-day study. They abstained from apples and apple products except for one weighed apple portion resembling one, two, or four apples. Before apple consumption and during the following days spot urine samples were collected. These urine samples were incubated with β-glucuronidase, diluted, and directly measured by HPLC-MS/MS. Phloretin, epicatechin, procyanidin B2, and quercetin were detected in urine using Scheduled MRMTM mode. Phloretin was confirmed as a urinary biomarker of apple intake and had the ability to discriminate between low or medium (one or two apples) and high apple consumption (four apples). The groups also differ in the excretion of epicatechin and procyanidin B2. CONCLUSION: Apple consumption can be monitored by urinary biomarkers for a period of at least 12 h after consumption. Furthermore the amount of apples consumed can be estimated by the concentration of certain biomarkers.
Published:
2017
Title:
Specific Features of the Hypothalamic Leptin Signaling Response to Cold Exposure Are Reflected in Peripheral Blood Mononuclear Cells in Rats and Ferrets
Authors:
Reynés, Bàrbara; Klein Hazebroek, Marlou; García-Ruiz, Estefanía; Keijer, Jaap; Oliver, Paula; Palou, Andreu
Abstract:
Objectives: Cold exposure induces hyperphagia to counteract fat loss related to lipid mobilization and thermogenic activation. The aim of this study was investigate on the molecular mechanisms involved in cold-induced compensatory hyperphagia. Methods: We analyzed the effect of cold exposure on gene expression of orexigenic and anorexigenic peptides, and of leptin signaling-related genes in the hypothalamus of rats at different ages (1, 2, 4, and 6 months), as well as in ferrets. We also evaluated the potential of peripheral blood mononuclear cells to reflect hypothalamic molecular responses. Results: As expected, cold exposure induced hypoleptinemia in rats, which could be responsible for the increased ratio of orexigenic/anorexigenic peptides gene expression in the hypothalamus, mainly due to decreased anorexigenic gene expression, especially in young animals. In ferrets, which resemble humans more closely, cold exposure induced greater changes in hypothalamic mRNA levels of orexigenic genes. Despite the key role of leptin in food intake control, the effect of cold exposure on the expression of key hypothalamic leptin signaling cascade genes is not clear. In our study, cold exposure seemed to affect leptin signaling in 4-month-old rats (increased Socs3 and Lepr expression), likely associated with the smaller-increase in food intake and decreased body weight observed at this particular age. Similarly, cold exposed ferrets showed greater hypothalamic Socs3 and Stat3 gene expression. Interestingly, peripheral blood mononuclear cells (PBMC) mimicked the hypothalamic increase in Lepr and Socs3 observed in 4-month-old rats, and the increased Socs3 mRNA expression observed in ferrets in response to cold exposure. Conclusions: The most outstanding result of our study is that PBMC reflected the specific modulation of leptin signaling observed in both animal models, rats and ferrets, which points forwards PBMC as easily obtainable biological material to be considered as a potential surrogate tissue to perform further studies on the regulation of hypothalamic leptin signaling in response to cold exposure.
Published:
2017
Title:
Subclinical diabetes
Authors:
E Lima, Luís Maurício Trambaioli Da Rocha
Abstract:
aBSTRaCT Type 2 diabetes mellitus (T2DM) is increasing in prevalence worldwide, and those non-diagnosed or misdiagnosed comprise a significant group compared to those diagnosed. Accumulated scientific evidence indicate that the current diagnostic markers (fasting glycemia, 2h glycemia after an oral glucose load and HbA1c) are indeed late diagnostic criteria when considering the incidence of diabetes-related complications and comorbidities, which are also at high risk in some groups among normoglycemic individuals. Additionally, the earlier identification of future risk of diabetes is desirable since it would allow better adherence to preventive actions such as lifestyle intervention, ultimately avoiding complications and minimizing the economic impact/burden on health care expenses. Insulin resistance and hyperhormonemia (insulin, amylin, glucagon) are non-disputable hallmarks of T2DM, which already takes place among these normoglycemic, otherwise health subjects, characterizing a state of subclinical diabetes. Insulin resistance and hyperinsulinemia can be computed from fasting plasma insulin as an independent variable in normoglycemia. An overview of the current diagnostic criteria, disease onset, complications, comorbidities and perspectives on lifestyle interventions are presented. A proposal for early detection of subclinical diabetes from routine evaluation of fasting plasma insulin, which is affordable and robust and thus applicable for the general population, is further suggested.
Published:
2017
Title:
System-wide Benefits of Intermeal Fasting by Autophagy
Authors:
Martinez-Lopez, Nuria; Tarabra, Elena; Toledo, Miriam; Garcia-Macia, Marina; Sahu, Srabani; Coletto, Luisa; Batista-Gonzalez, Ana; Barzilai, Nir; Pessin, Jeffrey E.; Schwartz, Gary J.; Kersten, Sander; Singh, Rajat
Abstract:
Autophagy failure is associated with metabolic insufficiency. Although caloric restriction (CR) extends healthspan, its adherence in humans is poor. We established an isocaloric twice-a-day (ITAD) feeding model wherein ITAD-fed mice consume the same food amount as ad libitum controls but at two short windows early and late in the diurnal cycle. We hypothesized that ITAD feeding will provide two intervals of intermeal fasting per circadian period and induce autophagy. We show that ITAD feeding modifies circadian autophagy and glucose/lipid metabolism that correlate with feeding-driven changes in circulating insulin. ITAD feeding decreases adiposity and, unlike CR, enhances muscle mass. ITAD feeding drives energy expenditure, lowers lipid levels, suppresses gluconeogenesis, and prevents age/obesity-associated metabolic defects. Using liver-, adipose-, myogenic-, and proopiomelanocortin neuron-specific autophagy-null mice, we mapped the contribution of tissue-specific autophagy to system-wide benefits of ITAD feeding. Our studies suggest that consuming two meals a day without CR could prevent the metabolic syndrome. Our studies suggest that consuming two meals a day with complete food restriction in between the meals is sufficient to lower blood glucose and lipid levels. This simple dietary approach activates a cell “cleansing system” called autophagy in liver, fat, brain, and muscle that helps prevent obesity and diabetes.
Published:
2017
Title:
Systematic review with meta-analysis: risk factors for non-alcoholic fatty liver disease suggest a shared altered metabolic and cardiovascular profile between lean and obese patients
Authors:
Sookoian, S.; Pirola, C. J.
Abstract:
BACKGROUND: The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is closely associated with the co-occurrence of multiple pathological conditions characterising the metabolic syndrome (MetS), obesity in particular. However, NAFLD also develops in lean subjects, whose risk factors remain poorly defined. METHODS: We performed a meta-analysis of 15 studies, along with the data pertaining to our own population (n=336 patients). Data from lean (n=1966) and obese (n=5938) patients with NAFLD were analysed; lean (n=9946) and obese (n=6027) subjects without NAFLD served as controls. RESULTS: Relative to the lean non-NAFLD controls, lean patients with NAFLD were older (3.79±0.72 years, P=1.36×10-6 ) and exhibited the entire spectrum of the MetS risk factors. Specifically, they had a significant (P=10-10 ) increase in plasma glucose levels (6.44±1.12 mg/dL) and HOMA-IR (0.52±0.094-unit increment), blood lipids (triglycerides: 48.37±3.6, P=10-10 and total cholesterol: 7.04±3.8, mg/dL, P=4.2×10-7 ), systolic (5.64±0.7) and diastolic (3.37±0.9) blood pressure (mm Hg), P=10-10 , and waist circumference (5.88±0.4 cm, P=10-10 ); values denote difference in means±SE. Nevertheless, the overall alterations in the obese group were much more severe when compared to lean subjects, regardless of the presence of NAFLD. Meta-regression suggested that NAFLD is a modifier of the level of blood lipids. CONCLUSION: Lean and obese patients with NAFLD share a common altered metabolic and cardiovascular profile. The former, while having normal body weight, showed excess of abdominal adipose tissue as well as other MetS features.
Published:
2017
Title:
The Anatomical Basis for Dystonia: The Motor Network Model
Authors:
Jinnah, H. A.; Neychev, Vladimir; Hess, Ellen J.
Abstract:
Background The dystonias include a clinically and etiologically very diverse group of disorders. There are both degenerative and non-degenerative subtypes resulting from genetic or acquired causes. Traditionally, all dystonias have been viewed as disorders of the basal ganglia. However, there has been increasing appreciation for involvement of other brain regions including the cerebellum, thalamus, midbrain, and cortex. Much of the early evidence for these other brain regions has come from studies of animals, but multiple recent studies have been done with humans, in an effort to confirm or refute involvement of these other regions. The purpose of this article is to review the new evidence from animals and humans regarding the motor network model, and to address the issues important to translational neuroscience. Methods The English literature was reviewed for articles relating to the neuroanatomical basis for various types of dystonia in both animals and humans. Results There is evidence from both animals and humans that multiple brain regions play an important role in various types of dystonia. The most direct evidence for specific brain regions comes from animal studies using pharmacological, lesion, or genetic methods. In these studies, experimental manipulations of specific brain regions provide direct evidence for involvement of the basal ganglia, cerebellum, thalamus and other regions. Additional evidence also comes from human studies using neuropathological, neuroimaging, non-invasive brain stimulation, and surgical interventions. In these studies, the evidence is less conclusive, because discriminating the regions that cause dystonia from those that reflect secondary responses to abnormal movements is more challenging. Discussion Overall, the evidence from both animals and humans suggests that different regions may play important roles in different subtypes of dystonia. The evidence so far provides strong support for the motor network model. There are obvious challenges, but also advantages, of attempting to translate knowledge gained from animals into a more complete understanding of human dystonia and novel therapeutic strategies.
Published:
2017
Title:
The European Union policy in the field of rare diseases
Authors:
Montserrat Moliner, Antoni; Waligora, Jaroslaw
Abstract:
BACKGROUND: Rare diseases (RDs), including those of genetic origin, are defined by the European Union (EU) as life-threatening or chronically debilitating diseases, which are of low prevalence (fewer than 5 per 10,000). The specificities of RDs - a limited number of patients and scarcity of relevant knowledge and expertise - single them out as a unique domain of a very high European added value.$\backslash$n$\backslash$nMETHODS: Legal instruments at the disposal of the EU, in terms of Article 152 of the Treaties, are very limited. However, a combination of instruments using the research and the pharmaceutical legal regulations, an intensive and creative use of funding from the Second Health Programme, the adoption of the Commission Communication in November 2008, the Council Recommendation in June 2009, and the Directive on cross-border healthcare in 2011 have permitted the creation of a solid basis that Member States have considered as sufficient to place RDs in a privileged position in the health agenda.$\backslash$n$\backslash$nRESULTS: As a result, an operational framework to act in the field of RDs with European coordination in several areas would be possible (orphan medicinal products, national plans on rare diseases, ICD-10 revision, European Reference Networks, European Platform for Rare Diseases registration, IRDiRC, European Committee of Experts, etc.).$\backslash$n$\backslash$nCONCLUSION: RDs is a field with an enormous potential for European cooperation.
Published:
2017
Title:
The Metabolic Phenotype of Prostate Cancer
Authors:
Eidelman, Eric; Twum-Ampofo, Jeffrey; Ansari, Jamal; Siddiqui, Mohummad Minhaj
Abstract:
Prostate cancer is the most common non-cutaneous cancer in men in the United States. Cancer metabolism has emerged as a contemporary topic of great interest for improved mechanistic understanding of tumorigenesis. Prostate cancer is a disease model of great interest from a metabolic perspective. Prostatic tissue exhibits unique metabolic activity under baseline conditions. Benign prostate cells accumulate zinc and this excess zinc inhibits citrate oxidation and metabolism within the citric acid cycle, effectively resulting in citrate production. Malignant cells, however, actively oxidize citrate and resume more typical citric acid cycle function. Of further interest, prostate cancer does not exhibit the Warburg effect, an increase in glucose uptake, seen in many other cancers. These cellular metabolic differences and others are of clinical interest as they present a variety of potential therapeutic targets. Furthermore, understanding of the metabolic profile differences between benign prostate versus low and high-grade prostate cancers also represents an avenue to better understand cancer progression and potentially develop new diagnostic testing. In this paper, we review the current state of knowledge on the metabolic phenotypes of prostate cancer.
Published:
2017
Title:
The Role of Advanced Glycation End-Products in Cancer Disparity
Authors:
Turner, D.P.
Abstract:
While the socioeconomic and environmental factors associated with cancer disparity have been well documented, the contribution of biological factors is an emerging field of research. Established disparity factors such as low income, poor diet, drinking alcohol, smoking, and a sedentary lifestyle may have molecular effects on the inherent biological makeup of the tumor itself, possibly altering cell signaling events and gene expression profiles to profoundly alter tumor development and progression. Our understanding of the molecular and biological consequences of poor lifestyle is lacking, but such information may significantly change how we approach goals to reduce cancer incidence and mortality rates within minority populations. In this review, we will summarize the biological, socioeconomic, and environmental associations between a group of reactive metabolites known as advanced glycation end-products (AGEs) and cancer health disparity. Due to their links with lifestyle and the activation of disease-associated pathways, AGEs may represent both a biological consequence and a bio-behavioral indicator of poor lifestyle which may be targeted within specific populations to reduce disparities in cancer incidence and mortality. © 2017 Elsevier Inc.
Published:
2017
Title:
The androgen receptor plays different roles in macrophage-induced proliferation in prostate stromal cells between transitional and peripheral zones of benign prostatic hypertrophy
Authors:
Xu, Dongliang; Wang, Xingjie; Jiang, Chenyi; Ruan, Yuan; Xia, Shujie; Wang, Xiaohai
Abstract:
Macrophages play a critical role in the process of excessive stromal proliferation of benign prostatic hyperplasia (BPH). In our previous study, we used a BPH mouse model to elucidate a potential mechanism whereby macrophage infiltration promotes stromal cell proliferation in the prostate via the androgen receptor (AR)/inflammatory cytokine CCL3-dependent pathway. In our present study, we used the co-culture system of human macrophages and various prostatic zone stromal cells to further demonstrate that infiltrating macrophages promote prostatic stromal cell proliferation through stromal AR-dependent pathways, and we show that the stroma of TZ and PZ respond to macrophages differently because of differences in stromal AR signaling; this could possibly be one of the key pathways for stromal expansion during BPH development and progression. We hypothesize that AR and different downstream inflammatory mediators between TZ and PZ could serve as potential targets for the future design of therapeutic agents for BPH and our results provide significant insights into the search for targeted therapeutic approaches to battle BPH.
Published:
2017
Title:
The crown joules: energetics, ecology, and evolution in humans and other primates
Authors:
Pontzer, Herman
Abstract:
Biological diversity is metabolic diversity: Differences in anatomy, physiology, life history, and activity reflect differences in energy allocation and expenditure among traits and tasks. Traditional frameworks in primatology, human ecology, public health, and paleoanthropology view daily energy expenditure as being more variable within than between species, changing with activity level but essentially fixed for a given body size. Growing evidence turns this view on its head. Total energy expenditure (kcal/d), varies relatively little within species, despite variation in physical activity; it varies considerably among species even after controlling for the effect of body size. Embracing this emerging paradigm requires rethinking potential trade-offs in energy allocation within and between species, assessing evidence of metabolic acceleration within lineages, and abandoning activity-based estimates of total energy expenditure. Difficult and exciting work lies ahead in the effort to untangle the ecological and evolutionary pressures shaping primate metabolic diversity.
Published:
2017
Title:
The effect of meal frequency in a reduced-energy regimen on the gastrointestinal and appetite hormones in patients with type 2 diabetes: A randomised crossover study
Authors:
Belinova, Lenka; Kahleova, Hana; Malinska, Hana; Topolcan, Ondrej; Windrichova, Jindra; Oliyarnyk, Olena; Kazdova, Ludmila; Hill, Martin; Pelikanova, Terezie
Abstract:
BACKGROUND: Appetite and gastrointestinal hormones (GIHs) participate in energy homeostasis, feeding behavior and regulation of body weight. We demonstrated previously the superior effect of a hypocaloric diet regimen with lower meal frequency (B2) on body weight, hepatic fat content, insulin sensitivity and feelings of hunger compared to the same diet divided into six smaller meals a day (A6). Studies with isoenergetic diet regimens indicate that lower meal frequency should also have an effect on fasting and postprandial responses of GIHs. The aim of this secondary analysis was to explore the effect of two hypocaloric diet regimens on fasting levels of appetite and GIHs and on their postprandial responses after a standard meal. It was hypothesized that lower meal frequency in a reduced-energy regimen leading to greater body weight reduction and reduced hunger would be associated with decreased plasma concentrations of GIHs: gastric inhibitory peptide (GIP), glucagon-like peptide-1(GLP-1), peptide YY(PYY), pancreatic polypeptide (PP) and leptin and increased plasma concentration of ghrelin. The postprandial response of satiety hormones (GLP-1, PYY and PP) and postprandial suppression of ghrelin will be improved. METHODS: In a randomized crossover study, 54 patients suffering from type 2 diabetes (T2D) underwent both regimens. The concentrations of GLP-1, GIP, PP, PYY, amylin, leptin and ghrelin were determined using multiplex immunoanalyses. RESULTS: Fasting leptin and GIP decreased in response to both regimens with no difference between the treatments (p = 0.37 and p = 0.83, respectively). Fasting ghrelin decreased in A6 and increased in B2 (with difference between regimens p = 0.023). Fasting PP increased in B2with no significant difference between regimens (p = 0.17). Neither GLP-1 nor PYY did change in either regimen. The decrease in body weight correlated negatively with changes in fasting ghrelin (r = -0.4, p<0.043) and the postprandial reduction of ghrelin correlated positively with its fasting level (r = 0.9, p
Published:
2017
Title:
The effect of regular intake of dry‐cured ham rich in bioactive peptides on inflammation, platelet and monocyte activation markers in humans
Authors:
Martínez-Sánchez, S.M.; Minguela, A.; Prieto-Merino, D.; Zafrilla-Rentero, M.P.; Abellán-Alemán, J.; Montoro‐García, S.
Abstract:
Background and aims: Dietary studies have shown that active biopeptides provide protective health benefits, although the mediating pathways are somewhat uncertain. To throw light on this situation, we studied the effects of consuming Spanish dry‐cured ham on platelet function, monocyte activation markers and the inflammatory status of healthy humans with pre-hypertension. Methods: Thirty‐eight healthy volunteers with systolic blood pressure of >125 mmHg were enrolled in a two‐arm crossover randomized controlled trial. Participants received 80 g/day dry‐cured pork ham of >11 months proteolysis or 100 g/day cooked ham (control product) for 4 weeks followed by a 2‐week washout before “crossing over” to the other treatment for 4 more weeks. Soluble markers and cytokines were analyzed by ELISA. Platelet function was assessed by measuring P‐selectin expression and PAC‐1 binding after ADP (adenosine diphosphate) stimulation using whole blood flow cytometry. Monocyte markers of the pathological status (adhesion, inflammatory and scavenging receptors) were also measured by flow cytometry in the three monocyte subsets after the interventional period. Results: The mean differences between dry‐cured ham and cooked ham followed by a time period adjustment for plasmatic P‐selectin and interleukin 6 proteins slightly failed (p = 0.062 and p = 0.049, respectively), notably increased for MCP‐1 levels (p = 0.023) while VCAM‐1 was not affected. Platelet function also decreased after ADP stimulation. The expression of adhesion and scavenging markers (ICAM1R, CXCR4 and TLR4) in the three subsets of monocytes was significantly higher (all p
Published:
2017
Title:
The effects of fatty acid composition on cardiac hypertrophy and function in mouse models of diet-induced obesity
Authors:
Nguyen, Son; Shao, Dan; Tomasi, Loreta C.; Braun, Alyssa; de Mattos, Ana Barbosa Marcondes; Choi, Yong Seon; Villet, Outi; Roe, Nathan; Halterman, Carliana R.; Tian, Rong; Kolwicz, Stephen C.
Abstract:
High-fat diets (HFDs) are used frequently to study the development of cardiac dysfunction in animal models of obesity and diabetes. However, impairment in systolic function, often reported as declining ejection fraction, may not consistently occur in a given time frame which could be contributable to a variety of factors within the experimental design. One major factor may be the amounts of saturated and unsaturated fatty acids (FAs) that are present in the diet. To determine whether the FA content and composition were critical determinants in the development of cardiac dysfunction in response to high-fat feeding, we fed adult, male mice Western diet (45% fat, 60% saturated), Surwit diet (60% fat, 90% saturated), milk-fat-based diet (60% fat, 60% saturated) or high-fat Western diet (HFWD, 60% fat, 32% saturated) for 12 weeks. We report that neither the amount of total fat nor the ratio of saturated to unsaturated FAs in the diets differentially affects body weight and adiposity in mice. In addition, no evidence of systolic dysfunction is present after 12 weeks. Interestingly, the HFWD, with equal parts saturated, monounsaturated and polyunsaturated FAs, induces mild cardiac hypertrophy and diastolic dysfunction after 12 weeks, which coincides with elevated serum levels of arachidonic acid. Our results suggest that the dietary FA content and composition may be a primary determinant of diastolic, but not systolic, dysfunction in animal models of diet-induced obesity.
Published:
2017
Title:
The many faces of phosphate in the diet
Authors:
Hahn, K.; Ketteler, M.
Abstract:
Background: Hyperphosphatemia represents one of the central risk factors in patients with advanced stage renal insufficiency. In addition, large epidemiological studies revealed signs that higher serum phosphate levels were especially associated with cardiovascular morbidity. The quantitative phosphate intake in nutrition plays a key role in this context. Objective: This review article deals with the currently available data on phosphate-associated mortality and morbidity in patients with and without chronic kidney disease (CKD). It also discusses the topic of dietary phosphate intake via natural and processed foods and on their potential influence on phosphate balance. Material and methods: Current studies on the influence of different phosphate sources on laboratory values and biomarkers, on clinically relevant surrogate parameters and additional endpoints were screened, summarized and evaluated. Results: There are significant differences concerning phosphate balance with respect to the origin of phosphate in the nutrition. The least uptake is observed with vegetarian sources, uptake of phosphate from meat products is intermediate, while inorganic phosphate additives are resorbed with high efficiency. Conclusion: The quality and amount of phosphate intake have a large influence on phosphate balance, which is especially important for CKD patients at risk for cardiovascular events. For improved management of risk reduction, adequate labeling of food items concerning phosphate contents is required and must be appropriately enforced. © 2017, Springer Medizin Verlag Berlin.
Published:
2017
Title:
The potential of volatile organic compounds for the detection of active disease in patients with ulcerative colitis
Authors:
Smolinska, A.; Bodelier, A. G. L.; Dallinga, J. W.; Masclee, A. a. M.; Jonkers, D. M.; van Schooten, F.-J.; Pierik, M. J.
Abstract:
BACKGROUND: To optimise treatment of ulcerative colitis (UC), patients need repeated assessment of mucosal inflammation. Current non-invasive biomarkers and clinical activity indices do not accurately reflect disease activity in all patients and cannot discriminate UC from non-UC colitis. Volatile organic compounds (VOCs) in exhaled air could be predictive of active disease or remission in Crohn's disease. AIM: To investigate whether VOCs are able to differentiate between active UC, UC in remission and non-UC colitis. METHODS: UC patients participated in a 1-year study. Clinical activity index, blood, faecal and breath samples were collected at each out-patient visit. Patients with clear defined active faecal calprotectin >250 μg/g and inactive disease (Simple Clinical Colitis Activity Index <3, C-reactive protein <5 mg/L and faecal calprotectin
Published:
2017
Title:
The potential role and rationale for treatment of heart failure with sodium–glucose co-transporter 2 inhibitors
Authors:
Butler, Javed; Hamo, Carine E.; Filippatos, Gerasimos; Pocock, Stuart J.; Bernstein, Richard A.; Brueckmann, Martina; Cheung, Alfred K.; George, Jyothis T.; Green, Jennifer B.; Januzzi, James L.; Kaul, Sanjay; Lam, Carolyn S.P.; Lip, Gregory Y.H.; Marx, Nikolaus; McCullough, Peter A.; Mehta, Cyrus R.; Ponikowski, Piotr; Rosenstock, Julio; Sattar, Naveed; Salsali, Afshin; Scirica, Benjamin M.; Shah, Sanjiv J.; Tsutsui, Hiroyuki; Verma, Subodh; Wanner, Christoph; Woerle, Hans Juergan; Zannad, Faiez; Anker, Stefan D.
Abstract:
© 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology Heart failure (HF) and type 2 diabetes mellitus (T2DM) are both growing public health concerns contributing to major medical and economic burdens to society. T2DM increases the risk of HF, frequently occurs concomitantly with HF, and worsens the prognosis of HF. Several anti-hyperglycaemic medications have been associated with a concern for worse HF outcomes. More recently, the results of the EMPA-REG OUTCOME trial showed that the sodium–glucose co-transporter 2 (SGLT2) inhibitor empagliflozin was associated with a pronounced and precocious 38% reduction in cardiovascular mortality in subjects with T2DM and established cardiovascular disease [Correction added on 8 September 2017, after first online publication: “32%” in the previous sentence was corrected to “38%”]. These benefits were more related to a reduction in incident HF events rather than to ischaemic vascular endpoints. Several mechanisms have been put forward to explain these benefits, which also raise the possibility of using these drugs as therapies not only in the prevention of HF, but also for the treatment of patients with established HF regardless of the presence or absence of diabetes. Several large trials are currently exploring this postulate.
Published:
2017
Title:
The role of metabolomics in determination of new dietary biomarkers
Authors:
O'Gorman, A.; Brennan, L.
Abstract:
Traditional methods for the assessment of dietary intake are prone to error; in order to improve and enhance these methods increasing interest in the identification of dietary biomarkers has materialised. Metabolomics has emerged as a key tool in the area of dietary biomarker discovery and to date the use of metabolomics has identified a number of putative biomarkers. Applications to identify novel biomarkers of intake have in general taken three approaches: (1) specific acute intervention studies to identify specific biomarkers of intake; (2) searching for biomarkers in cohort studies by correlating to self-reported intake of a specific food/food group(s); (3) analysing dietary patterns in conjunction with metabolomic profiles to identify biomarkers and nutritypes. A number of analytical technologies are employed in metabolomics as currently there is no single technique capable of measuring the entire metabolome. These approaches each have their own advantages and disadvantages. The present review will provide an overview of current technologies and applications of metabolomics in the determination of new dietary biomarkers. In addition, it will address some of the current challenges in the field and future outlooks.
Published:
2017
Title:
The role of solidarity(-ies) in rare diseases research
Authors:
Mascalzoni, Deborah; Petrini, Carlo; Taruscio, Domenica; Gainotti, Sabina
Abstract:
Solidarity plays a relevant role in rare diseases (RDs) research to create and enable research in the field. In Europe RDs are estimated to affect between 27 and 36 million people even though single RDs can count very few patients, making the contribution of everyone essential to reach solid results. Often RD research is initiated by patient groups devoting substantial time and resources to the scientific enterprise. In RD research solidarity is often evocated and expressed, in different ways and on different levels, so that it is possible to talk about “solidarities{”} played by different stakeholders and sometimes conflicting with each other. In this paper we describe different contexts in which solidarity is expressed and embedded in RD research, in particular the context of tight relationships between individuals and their families or in small communities/ethnic groups; among individuals suffering from different RDs and researchers working on a specific RD or a group of RDs, and within society at large. In all these cases the different types of solidarity should be balanced against each other and also against conflicting values. The request to a patient to share data and samples to increase scientific knowledge on the basis of solidarity values needs to be balanced against the need to protect her privacy and autonomy; the duty for a researcher to allow fair access to RD sample and data collections which were donated in a spirit of solidarity is balanced against the need to be competitive in the research world. In the Report “Solidarity. Reflections on an emerging concept in bioethics{”}, the Nuffield Council of Bioethics defines solidarity as “shared practices reflecting a collective commitment to carry `costs' (financial, social, emotional or otherwise) to assist others{”}. Therefore, if a solidarity framework has to be solid and ethically sound it needs to be framed as a shared value, reflected in the different practices by all the stakeholders and be based on reciprocity ( not one sided). The context of solidarity(ies) provides a solid base for framing the research endeavor as collectively valuable, not only for possible results of the research, but as intrinsic valid societal practice. This paper tries to draw the lessons on solidarity that we can derive from the RD world where “solidarities{”} have been part of the game for long time and are declined on many different levels.
Published:
2017
Title:
Transcriptome analysis in blood cells from children reveals potential early biomarkers of metabolic alterations
Authors:
Sánchez, J.; Picó, C.; Ahrens, W.; Foraita, R.; Fraterman, A.; Moreno, L. A.; Russo, P.; Siani, A.; Palou, A.
Abstract:
OBJECTIVES: The development of effective strategies to prevent childhood obesity and its comorbidities requires new, reliable early biomarkers. Here, we aimed to identify in peripheral blood cells potential transcript-based biomarkers of unhealthy metabolic profile associated to overweight/obesity in children. METHODS: We performed a whole-genome microarray analysis in blood cells to identify genes differentially expressed between overweight and normal weight children to obtain novel transcript-based biomarkers predictive of metabolic complications. RESULTS: The most significant enriched pathway of differentially expressed genes was related to oxidative phosphorylation, for which most of genes were downregulated in overweight versus normal weight children. Other genes were involved in carbohydrate metabolism/glucose homoeostasis or in lipid metabolism (for example, TCF7L2, ADRB3, LIPE, GIPR), revealing plausible mechanisms according to existing biological knowledge. A set of differentially expressed genes was identified to discriminate in overweight children those with high or low triglyceride levels. CONCLUSIONS: Functional microarray analysis has revealed a set of potential blood-cell transcript-based biomarkers that may be a useful approach for early identification of children with higher predisposition to obesity-related metabolic alterations.
Published:
2017
Title:
Tricaprylin Alone Increases Plasma Ketone Response More Than Coconut Oil or Other Medium-Chain Triglycerides: An Acute Crossover Study in Healthy Adults
Authors:
Vandenberghe, Camille; St-Pierre, Valérie; Pierotti, Tyler; Fortier, Mélanie; Castellano, Christian-Alexandre; Cunnane, Stephen C
Abstract:
Background: Ketones are the brain's main alternative fuel to glucose. Dietary medium chain triglyceride (MCT) supplements increase plasma ketones but their ketogenic efficacy relative to coconut oil (CO) is not clear. Objective: To compare the acute ketogenic effect in healthy adults of the following test oils: coconut oil (CO; 3% C8, 5% C10), classical MCT oil (C8/C10; 55% C8, 35% C10), tricaprylin (\textgreater95% C8), tricaprin (\textgreater95% C10), or CO mixed 50:50 with C8/C10 or C8. Design: In a crossover design, 7 men and 2 women of 34±12 y took two 20 mL doses of the test oils prepared as an emulsion in 250 mL of lactose-free skim milk. During the control test (CTL), participants received only the milk vehicle. The first test dose was taken with breakfast and the second at noon but without lunch. Blood was sampled every 30 min over 8 h for plasma acetoacetate and β-hydroxybutyrate analysis. Results: C8 was the most ketogenic test oil with a day-long mean of +295±155 µmol/L above CTL. C8 alone induced the highest plasma ketones expressed as the areas-under-the-curve (AUC) for 0-4 h and 4-8 h; 780±426 µmol·h/L and 1876±772 µmol·h/L, respectively; these values were 813% and 870%, respectively, more than CTL (P\textless0.01). CO plasma ketones peaked at +200 µmol/L, or 25% of the C8 ketone peak. The acetoacetate/β-hydroxybutyrate ratio increased 56% more after CO than after C8 after both doses. There was a significant positive correlation between the amount of C8 consumed and AUCs for net change in plasma ketones (ρ=0.9, P=0.008 for both). Conclusion: In healthy adults, C8 alone had the highest net ketogenic effect over 8 h, but induced only half the increase in acetoacetate/β-hydroxybutyrate ratio compared to CO. Optimising the type of MCT may help in developing ketogenic supplements designed to counteract deteriorating brain glucose uptake associated with aging.
Published:
2017
Title:
Trimethylamine-N-oxide (TMAO) response to animal source foods varies among healthy young men and is influenced by their gut microbiota composition: A randomized controlled trial
Authors:
Cho, Clara E.; Taesuwan, Siraphat; Malysheva, Olga V.; Bender, Erica; Tulchinsky, Nathan F.; Yan, Jian; Sutter, Jessica L.; Caudill, Marie A.
Abstract:
SCOPE: Trimethylamine-N-oxide (TMAO), a metabolite linked to the gut microbiota, is associated with excess risk of heart disease. We hypothesized that (i) TMAO response to animal source foods would vary among healthy men and (ii) this response would be modified by their gut microbiome. METHODS AND RESULTS: A crossover feeding trial in healthy young men (n = 40) was conducted with meals containing TMAO (fish), its dietary precursors, choline (eggs) and carnitine (beef), and a fruit control. Fish yielded higher circulating and urinary concentrations of TMAO (46-62 times; p < 0.0001), trimethylamine (8-14 times; p < 0.0001), and dimethylamine (4-6-times; P
Published:
2017
Title:
Uncovering the embryonic development-related proteome and metabolome signatures in breast muscle and intramuscular fat of fast-and slow-growing chickens
Authors:
Liu, R.; Wang, H.; Liu, J.; Wang, J.; Zheng, M.; Tan, X.; Xing, S.; Cui, H.; Li, Q.; Zhao, G.; Wen, J.
Abstract:
Background: Skeletal muscle development is closely linked to meat production and its quality. This study is the first to quantify the proteomes and metabolomes of breast muscle in two distinct chicken breeds at embryonic day 12 (ED 12), ED 17, post-hatch D 1 and D 14 using mass spectrometry-based approaches. Results: Results found that intramuscular fat (IMF) accumulation increased from ED 17 to D 1 and that was exactly the opposite of when most obvious growth of muscle occurred (ED 12 - ED 17 and D 1 - D 14). For slow-growing Beijing-You chickens, Ingenuity Pathway Analysis of 77-99 differential abundance (DA) proteins and 63-72 metabolites, indicated significant enrichment of molecules and pathways related to protein processing and PPAR signaling. For fast-growing Cobb chickens, analysis of 68-95 DA proteins and 56-59 metabolites demonstrated that molecules and pathways related to ATP production were significantly enriched after ED12. For IMF, several rate-limiting enzymes for beta-oxidation of fatty acid (ACADL, ACAD9, HADHA and HADHB) were identified as candidate biomarkers for IMF deposition in both breeds. Conclusions: This study found that ED 17 - D 1 was the earliest period for IMF accumulation. Pathways related to protein processing and PPAR signaling were enriched to support high capacity of embryonic IMF accumulation in Beijing-You. Pathways related to ATP production were enriched to support the fast muscle growth in Cobb. The beta-oxidation of fatty acid is identified as the key pathway regulating chicken IMF deposition at early stages. © 2017 The Author(s).
Published:
2017
Title:
Understanding the attitudes and perceptions of vegetarian and plant-based diets to shape future health promotion programs
Authors:
Corrin, Tricia; Papadopoulos, Andrew
Abstract:
Vegetarian diets have become a prominent area of interest. However, little research has focused on the attitudes and perceptions on vegetarian diets. The purpose of this scoping review was to methodologically search the literature and summarize public perceptions and attitudes towards a vegetarian diet. Using the information found from this review, the Health Belief Model can be applied to shape future health promotion initiatives to move individuals towards a vegetarian or plant-based diet. The main findings indicate that vegetarian diets are generally perceived in a positive light. There are many barriers to consuming this diet such as health concerns, an unwillingness to make dietary changes, and an enjoyment of eating meat.
Published:
2017
Title:
Undiagnosed diseases: Italy-US collaboration and international efforts to tackle rare and common diseases lacking a diagnosis
Authors:
Taruscio, Domenica; Floridia, Giovanna; Salvatore, Marco; Groft, Stephen C.; Gahl, William A.
Abstract:
© Springer International Publishing AG 2017. Rare diseases (RD), according to European Union criteria, affect 5 per 10,000 persons, or 30 million people, in the EU; in the USA, RD are defined as conditions that affect fewer than 200,000 individuals in the population (320 million). Most known rare disorders are severe and chronic, with many being degenerative and life threatening. There are roughly 5000-8000 rare diseases (European Commission, DG Health and Food Safety, Public Health, Rare Diseases, Policy. http://ec.europa.eu/health/rare_diseases/policy/index_en.htm. Accessed 19 December 2016; NORD-The National Organization for Rare Diseases: https://rarediseases. org/). Patient populations for individual RD are small and scattered; international collaborations are crucial to pool resources fragmented across individual countries for better diagnosis and treatment. Undiagnosed RD (URD) are conditions that elude diagnosis; some patients wait years for a definitive diagnosis. URD may include groups of unnamed disorders with common characteristics, phenotypically well described diseases, diseases with an unknown molecular basis, or those due to unknown, non-genetic factors. The US NIH Undiagnosed Diseases Program arose in 2008 to provide a diagnosis for individuals who had long sought one without success; in 2013 a nationwide Undiagnosed Diseases Network was established in the United States. In 2015, the Undiagnosed Disease Network International (UDNI) was established and includes US, Australia, Canada, Japan, Italy and other European countries. Other national initiatives have also been undertaken and are in progress all over the world.
Published:
2017
Title:
Untargeted metabolomic analysis of human serum samples associated with different levels of red meat consumption: A possible indicator of type 2 diabetes?
Authors:
Carrizo, D.; Chevallier, O.P.; Woodside, J.V.; Brennan, S.F.; Cantwell, M.M.; Cuskelly, G.; Elliott, C.T.
Abstract:
Red meat consumption has been associated with negative health effects. A study to identify biomarkers of meat consumption was undertaken using serum samples collected from combining high resolution mass spectrometry (UPLC-QTof-MS) and chemometrics. Using orthogonal partial last-squares discriminant analysis (OPLS-DA), multivariate models were created for both modes of acquisition (ESI−/ESI+) and red meat intake classes (YES/NO). In the serum samples, a total 3280 and 3225 ions of interest were detected in positive and negative modes, respectively. Of these, 62 were found to be significantly different (p < 0.05) between the two groups. Glycerophospholipids as well as other family lipids, such as lysophospholipids or sphingomyelin, were found significantly (p
Published:
2017
Title:
Untargeted metabolomics of colonic digests reveals kynurenine pathway metabolites, dityrosine and 3-dehydroxycarnitine as red versus white meat discriminating metabolites
Authors:
Rombouts, C.; Hemeryck, L.Y.; Van Hecke, T.; De Smet, S.; De Vos, W.H.; Vanhaecke, L.
Abstract:
Epidemiological research has demonstrated that the consumption of red meat is an important risk factor for the development of colorectal cancer (CRC), diabetes mellitus and cardiovascular diseases. However, there is no holistic insight in the (by-) products of meat digestion that may contribute to disease development. To address this hiatus, an untargeted mass spectrometry (MS)-based metabolomics approach was used to create red versus white meat associated metabolic fingerprints following in vitro colonic digestion using the fecal inocula of ten healthy volunteers. Twenty-two metabolites were unequivocally associated with simulated colonic digestion of red meat. Several of these metabolites could mechanistically be linked to red meat-associated pathways including N'-formylkynurenine, kynurenine and kynurenic acid (all involved in tryptophan metabolism), the oxidative stress marker dityrosine, and 3-dehydroxycarnitine. In conclusion, the used MS-based metabolomics platform proved to be a powerful platform for detection of specific metabolites that improve the understanding of the causal relationship between red meat consumption and associated diseases. © The Author(s) 2017.
Published:
2017
Title:
Urinary 1H Nuclear Magnetic Resonance Metabolomic Fingerprinting Reveals Biomarkers of Pulse Consumption Related to Energy-Metabolism Modulation in a Subcohort from the PREDIMED study
Authors:
Madrid-Gambin, Francisco; Llorach, Rafael; Vázquez-Fresno, Rosa; Urpi-Sarda, Mireia; Almanza-Aguilera, Enrique; Garcia-Aloy, Mar; Estruch, Ramon; Corella, Dolores; Andres-Lacueva, Cristina
Abstract:
Little is known about the metabolome fingerprint of pulse consumption. The study of robust and accurate biomarkers for pulse dietary assessment has great value for nutritional epidemiology regarding health benefits and their mechanisms. To characterize the fingerprinting of dietary pulses (chickpeas, lentils, and beans), spot urine samples from a subcohort from the PREDIMED study were stratified using a validated food frequency questionnaire. Urine samples of nonpulse consumers (≤4 g/day of pulse intake) and habitual pulse consumers (≥25 g/day of pulse intake) were analyzed using a 1H nuclear magnetic resonance (NMR) metabolomics approach combined with multi- and univariate data analysis. Pulse consumption showed differences through 16 metabolites coming from (i) choline metabolism, (ii) protein-related compounds, and (iii) energy metabolism (including lower urinary glucose). Stepwise logistic regression analysis was applied to design a combined model of pulse exposure, which resulted in glutamine, dimethylamine, and 3-methylhistidine. This model was evaluated by a receiver operating characteristic curve (AUC > 90% in both training and validation sets). The application of NMR-based metabolomics to reported pulse exposure highlighted new candidates for biomarkers of pulse consumption and the impact on energy metabolism, generating new hypotheses on energy modulation. Further intervention studies will confirm these findings.
Published:
2017
Title:
Use of biomarkers to assess fruit and vegetable intake
Authors:
Woodside, Jayne V.; Draper, John; Lloyd, Amanda; McKinley, Michelle C.
Abstract:
A high intake of fruit and vegetables (FV) has been associated with reduced risk of a number of chronic diseases, including CVD. The aim of this review is to describe the potential use of biomarkers to assess FV intake. Traditional methods of assessing FV intake have limitations, and this is likely to impact on observed associations with disease outcomes and markers of disease risk. Nutritional biomarkers may offer a more objective and reliable method of assessing dietary FV intake. Some single blood biomarkers, such as plasma vitamin C and serum carotenoids, are well established as indicators of FV intake. Combining potential biomarkers of intake may more accurately predict overall FV intake within intervention studies than the use of any single biomarker. Another promising approach is metabolomic analysis of biological fluids using untargeted approaches to identify potential new biomarkers of FV intake. Using biomarkers to measure FV intake may improve the accuracy of dietary assessment.
Published:
2017
Title:
Using the shared genetics of dystonia and ataxia to unravel their pathogenesis
Authors:
Nibbeling, Esther A.R.; Delnooz, Cathérine C.S.; de Koning, Tom J.; Sinke, Richard J.; Jinnah, Hyder A.; Tijssen, Marina A.J.; Verbeek, Dineke S.
Abstract:
In this review we explore the similarities between spinocerebellar ataxias and dystonias, and suggest potentially shared molecular pathways using a gene co-expression network approach. The spinocerebellar ataxias are a group of neurodegenerative disorders characterized by coordination problems caused mainly by atrophy of the cerebellum. The dystonias are another group of neurological movement disorders linked to basal ganglia dysfunction, although evidence is now pointing to cerebellar involvement as well. Our gene co-expression network approach identified 99 shared genes and showed the involvement of two major pathways: synaptic transmission and neurodevelopment. These pathways overlapped in the two disorders, with a large role for GABAergic signaling in both. The overlapping pathways may provide novel targets for disease therapies. We need to prioritize variants obtained by whole exome sequencing in the genes associated with these pathways in the search for new pathogenic variants, which can than be used to help in the genetic counseling of patients and their families.
Published:
2017
Title:
VDAC-Tubulin, an Anti-Warburg Pro-Oxidant Switch
Authors:
Maldonado, Eduardo N.
Abstract:
Aerobic enhanced glycolysis characterizes the Warburg phenotype. In cancer cells, suppression of mitochondrial metabolism contributes to maintain a low ATP/ADP ratio that favors glycolysis. We propose that the voltage-dependent anion channel (VDAC) located in the mitochondrial outer membrane is a metabolic link between glycolysis and oxidative phosphorylation in the Warburg phenotype. Most metabolites including respiratory substrates, ADP, and Pi enter mitochondria only through VDAC. Oxidation of respiratory substrates in the Krebs cycle generates NADH that enters the electron transport chain (ETC) to generate a proton motive force utilized to generate ATP and to maintain mitochondrial membrane potential (ΔΨ). The ETC is also the major source of mitochondrial reactive oxygen species (ROS) formation. Dimeric α-β tubulin decreases conductance of VDAC inserted in lipid bilayers, and high free tubulin in cancer cells by closing VDAC, limits the ingress of respiratory substrates and ATP decreasing mitochondrial ΔΨ. VDAC opening regulated by free tubulin operates as a "master key" that "seal-unseal" mitochondria to modulate mitochondrial metabolism, ROS formation, and the intracellular flow of energy. Erastin, a small molecule that binds to VDAC and kills cancer cells, and erastin-like compounds antagonize the inhibitory effect of tubulin on VDAC. Blockage of the VDAC-tubulin switch increases mitochondrial metabolism leading to decreased glycolysis and oxidative stress that promotes mitochondrial dysfunction, bioenergetic failure, and cell death. In summary, VDAC opening-dependent cell death follows a "metabolic double-hit model" characterized by oxidative stress and reversion of the pro-proliferative Warburg phenotype.
Published:
2017
Title:
Vegan diets: practical advice for athletes and exercisers
Authors:
Rogerson, David
Abstract:
With the growth of social media as a platform to share information, veganism is becoming more visible, and could be becoming more accepted in sports and in the health and fitness industry. However, to date, there appears to be a lack of literature that discusses how to manage vegan diets for athletic purposes. This article attempted to review literature in order to provide recommendations for how to construct a vegan diet for athletes and exercisers. While little data could be found in the sports nutrition literature specifically, it was revealed elsewhere that veganism creates challenges that need to be accounted for when designing a nutritious diet. This included the sufficiency of energy and protein; the adequacy of vitamin B12, iron, zinc, calcium, iodine and vitamin D; and the lack of the long-chain n-3 fatty acids EPA and DHA in most plant-based sources. However, via the strategic management of food and appropriate supplementation, it is the contention of this article that a nutritive vegan diet can be designed to achieve the dietary needs of most athletes satisfactorily. Further, it was suggested here that creatine and β-alanine supplementation might be of particular use to vegan athletes, owing to vegetarian diets promoting lower muscle creatine and lower muscle carnosine levels in consumers. Empirical research is needed to examine the effects of vegan diets in athletic populations however, especially if this movement grows in popularity, to ensure that the health and performance of athletic vegans is optimised in accordance with developments in sports nutrition knowledge.
Published:
2017
Title:
Voltage-Dependent Anion Channel 1 As an Emerging Drug Target for Novel Anti-Cancer Therapeutics
Authors:
Shoshan-Barmatz, Varda; Krelin, Yakov; Shteinfer-Kuzmine, Anna; Arif, Tasleem
Abstract:
Cancer cells share several properties, high proliferation potential, reprogramed metabolism, and resistance to apoptotic cues. Acquiring these hallmarks involves changes in key oncogenes and non-oncogenes essential for cancer cell survival and prosperity, and is accompanied by the increased energy requirements of proliferating cells. Mitochondria occupy a central position in cell life and death with mitochondrial bioenergetics, biosynthesis, and signaling are critical for tumorigenesis. Voltage-dependent anion channel 1 (VDAC1) is situated in the outer mitochondrial membrane (OMM) and serving as a mitochondrial gatekeeper. VDAC1 allowing the transfer of metabolites, fatty acid ions, Ca2+, reactive oxygen species, and cholesterol across the OMM and is a key player in mitochondrial-mediate apoptosis. Moreover, VDAC1 serves as a hub protein, interacting with diverse sets of proteins from the cytosol, endoplasmic reticulum, and mitochondria that together regulate metabolic and signaling pathways. The observation that VDAC1 is over-expressed in many cancers suggests that the protein may play a pivotal role in cancer cell survival. However, VDAC1 is also important in mitochondria-mediated apoptosis, mediating release of apoptotic proteins and interacting with anti-apoptotic proteins, such as B-cell lymphoma 2 (Bcl-2), Bcl-xL, and hexokinase (HK), which are also highly expressed in many cancers. Strategically located in a "bottleneck" position, controlling metabolic homeostasis and apoptosis, VDAC1 thus represents an emerging target for anti-cancer drugs. This review presents an overview on the multi-functional mitochondrial protein VDAC1 performing several functions and interacting with distinct sets of partners to regulate both cell life and death, and highlights the importance of the protein for cancer cell survival. We address recent results related to the mechanisms of VDAC1-mediated apoptosis and the potential of associated proteins to modulate of VDAC1 activity, with the aim of developing VDAC1-based approaches. The first strategy involves modification of cell metabolism using VDAC1-specific small interfering RNA leading to inhibition of cancer cell and tumor growth and reversed oncogenic properties. The second strategy involves activation of cancer cell death using VDAC1-based peptides that prevent cell death induction by anti-apoptotic proteins. Finally, we discuss the potential therapeutic benefits of treatments and drugs leading to enhanced VDAC1 expression or targeting VDAC1 to induce apoptosis.
Published:
2017
Title:
What is the molecular signature of mind-body interventions? A systematic review of gene expression changes induced by meditation and related practices
Authors:
Buric, Ivana; Farias, Miguel; Jong, Jonathan; Mee, Christopher; Brazil, Inti A.
Abstract:
There is considerable evidence for the effectiveness of mind-body interventions (MBIs) in improving mental and physical health, but the molecular mechanisms of these benefits remain poorly understood. One hypothesis is that MBIs reverse expression of genes involved in inflammatory reactions that are induced by stress. This systematic review was conducted to 25 examine changes in gene expression that occur after MBIs and to explore how these molecular changes are related to health. We searched PubMed throughout September 2016 to look for studies that have used gene expression analysis in MBIs (i.e., mindfulness, yoga, Tai Chi, Qigong, relaxation response, and breath regulation). Due to the limited quantity of studies, we included both clinical and non-clinical samples with any type of research design. Eighteen relevant studies were retrieved and analysed. Overall, the studies indicate that these practices are associated with a downregulation of nuclear factor kappa B (NF-kB) pathway; this is the opposite of the effects of chronic stress on gene expression and suggests that MBI practices may lead to a reduced risk of inflammation-related diseases. However, it is unclear how the effects of MBIs compare to other healthy interventions such as exercise or nutrition due to the small number of available studies. More research is required to be able to understand the effects of MBIs at the molecular level.
Published:
2017
Title:
Wholesome Nutrition: an example for a sustainable diet
Authors:
von Koerber, Karl; Bader, Nadine; Leitzmann, Claus
Abstract:
'Wholesome Nutrition' is a concept of sustainable nutrition that was developed at the University of Giessen in the 1980s. In this concept, health and the ecologic, economic, social and cultural dimensions of nutrition are equally important. In 1992 at the UN-Conference on Environment and Development in Rio de Janeiro the definition of 'Sustainable Development' comprised the dimensions environment, economy and society. Additionally to these three 'classical' dimensions of sustainability, we included 'health' as the fourth dimension because nutrition has far reaching effects on human health. The fifth dimension, 'culture', became part of the sustainability dialogue since many years; the respective cultural background influences food habits. Presently, mankind has to cope with huge global challenges such as poverty and food insecurity in low-income countries as well as climate change. Therefore the objective is to identify prospects for actions to respond to these global challenges. The concept of 'Sustainable Nutrition' analyses the food supply chain at all stages from input-production and primary production to processing, distribution, preparation, consumption and waste disposal. The present analysis leads to the following seven principles: preference of plant-based foods, organic foods, regional and seasonal products, preference of minimally processed foods, Fair Trade products, resource-saving housekeeping and enjoyable eating culture. This concept is based on holistic thinking and has the potential to reduce the global challenges in the field of nutrition. Scientists, stakeholders, multipliers and consumers are asked to consider environmental, economic, social and cultural aspects in addition to the biological (health) aspects.
Published:
2017
Title:
Effects of improved fat meat products consumption on emergent cardiovascular disease markers of male volunteers at cardiovascular risk
Authors:
Celada, Paloma; Sanchez-Muniz, Francisco J.; Delgado-Pando, Gonzalo; Bastida, Sara; Rodilla, Manuel Esparrago; Jimenez-Colmenero, Francisco; Olmedilla-Alonso, Begona
Abstract:
High meat-product consumption has been related to cardiovascular disease (CVD). However, previous results suggest the benefits of consuming improved fat meat products on lipoprotein-cholesterol and anthropometric measurements. Present study aims to assess the effect of consuming different Pate and Frankfurter formulations on emergent CVD biomarkers in male volunteers at increased CVD risk. Eighteen male volunteers with at least two CVD risk factors were enrolled in a sequentially controlled study where different pork-products were tested: reduced-fat (RF), omega-3-enriched-RF (n-3RF), and normal-fat (NF). Pork-products were consumed during 4-week periods separated by 4-week washout. The cardiometabolic index (CI), oxidized low density lipoproteins (oxLDL), apolipoproteins (Apo) A1 and B, homocysteine (tHcys), arylesterase (AE), C-reactive Protein (CRP), tumor necrotic factor-alpha (TNFalpha), and lipoprotein (a) (Lp(a)) were tested and some other related ratios calculated. AE, oxLDL and Lp(a), AE/HDLc, LDLc/Apo B, and AE/oxLDL rate of change were differently affected (P<0.01) by pork-products consumption. RF increased (P < 0.05) AE, AE/HDLc and AE/oxLDL ratios and decreased TNFalpha, tHcys; n-3RF increased (P < 0.001) AE, AE/HDLc and AE/oxLDL ratios and decreased (P < 0.05) Lp(a); while NF increased (P
Published:
2016-12
Title:
Exposure to endocrine disrupting chemicals among residents of a rural vegetarian/vegan community
Authors:
Tordjman, Karen; Grinshpan, Laura; Novack, Lena; Göen, Thomas; Segev, Dar; Beacher, Lisa; Stern, Naftali; Berman, Tamar
Abstract:
BACKGROUND & AIMS: Endocrine-disrupting chemicals (EDCs) are increasingly thought to be involved in the rising prevalence of disorders such as obesity, diabetes, and some hormone-dependent cancers. Several lines of evidence have indicated that vegetarian and vegan diets may offer some protection from such diseases. We hypothesized that exposure to selected EDCs among residents of the unique vegetarian/vegan community of Amirim would be lower than what has recently been reported for the omnivorous population in the first Israel Biomonitoring Study (IBMS). METHODS: We studied 42 Amirim residents (29 vegetarians/13 vegans; 24 women/18men, aged 50.7±13.7y). Subjects answered detailed lifestyle, and multipass, memory-based 24-hr dietary recall questionnaires. Concentrations of bisphenol A (BPA), 11 phthalate metabolites, and the isoflavone phytoestrogens (genistein and daidzein) were determined by GC or LC tandem mass-spectrometry on a spot urine sample. The results were compared to those obtained following the same methodology in the Jewish subgroup of the IBMS (n=184). RESULTS: While a vegetarian/vegan nutritional pattern had no effect on exposure to BPA, it seemed to confer a modest protection (~21%) from exposure to high molecular weight phthalates. Furthermore, the summed metabolites of the high molecular weight phthalate DiNP were 36% lower in vegans compared to vegetarians (P<0.05). In contrast, Amirim residents exhibited a level of exposure to isoflavone phytoestrogens about an order of magnitude higher than in the IBMS (P
Published:
2016-12
Title:
Metabolomics Analysis Revealed Distinct Cyclic Changes of Metabolites Altered by Chronic Ethanol-Plus-Binge and Shp Deficiency
Authors:
Tran, Melanie; Yang, Zhihong; Liangpunsakul, Suthat; Wang, Li
Abstract:
Background Chronic ethanol (EtOH) consumption causes alcoholic liver disease (ALD), and disruption of the circadian system facilitates the development of ALD. Small heterodimer partner (SHP) is a nuclear receptor and critical regulator of hepatic lipid metabolism. This study aimed at depicting circadian metabolomes altered by chronic EtOH-plus-binge and Shp deficiency using high-throughput metabolomics. Methods Wild-type (WT) C57BL/6 and Shp−/− mice were fed the control diet (CD) or Lieber-DeCarli EtOH liquid diet (ED) for 10 days followed by a single bout of maltose (CD + M) or EtOH (ED + E) binge on the 11th day. Serum and liver were collected over a 24-hour light/dark (LD) cycle at Zeitgeber time ZT12, ZT18, ZT0, and ZT6, and metabolomics was performed using gas chromatography-mass spectrometry. Results A total of 110 metabolites were identified in liver and of those 80 were also present in serum from pathways of carbohydrates, lipids, pentose phosphate, amino acids, nucleotides, and tricarboxylic acid cycle. In the liver, 91% of metabolites displayed rhythmicity with ED + E, whereas in the serum, only 87% were rhythmic. Bioinformatics analysis identified unique metabolome patterns altered in WT CD + M, WT ED + E, Shp−/− CD + M, and Shp−/− ED + E groups. Specifically, metabolites from the nucleotide and amino acid pathway (ribose, glucose-6-phosphate, glutamic acid, aspartic acid, and sedoheptulose-7-P) were elevated in Shp−/− CD + M mice during the dark cycle, whereas metabolites including N-methylalanine, 2-hydroxybutyric acid, and 2-hydroxyglutarate were elevated in WT ED + E mice during the light cycle. The rhythmicity and abundance of other individual metabolites were also significantly altered by both control and EtOH diets. Conclusions Metabolomics provides a useful means to identify unique metabolites altered by chronic EtOH-plus-binge.
Published:
2016-12
Title:
Physical Exercise for Treatment of Mood Disorders: A Critical Review
Authors:
Hearing, C. M.; Chang, W. C.; Szuhany, K. L.; Deckersbach, T.; Nierenberg, A. A.; Sylvia, Louisa G.
Abstract:
PURPOSE OF THE REVIEW The purpose of this review is to critically assess the evidence for exercise as an adjunct intervention for major depressive disorder and bipolar disorder, chronic conditions characterized by frequent comorbid conditions as well as interepisodic symptoms with poor quality of life and impaired functioning. Individuals with these mood disorders are at higher risk of cardiovascular disease and premature death in part because of increased rates of obesity, inactivity, and diabetes mellitus compared to the general population. Exercise may not only mitigate the increased risk of cardiovascular disease, but could also potentially improve the long term outcomes of mood disorders. RECENT FINDINGS We conducted a literature review on the impact of exercise on mood disorders and associated comorbid conditions as well as possible biological mechanisms. We found that exercise impacts both the physical health parameters of mood disorders as well as mental health outcomes. Exercise also positively impacts conditions frequently comorbid with mood disorders (i.e. anxiety, pain, and insomnia). There are multiple candidate biomarkers for exercise, with brain-derived neurotrophic factor and oxidative stress as two main promising components of exercise's anti-depressant effect. SUMMARY Exercise appears to be a promising adjunct treatment for mood disorders. We conclude with recommendations for future research of exercise as an adjunct intervention for mood disorders.
Published:
2016-12
Title:
The Safety Limits of An Extended Fast: Lessons from a Non-Model Organism
Authors:
Bertile, Fabrice; Fouillen, Laetitia; Wasselin, Thierry; Maes, Pauline; Le Maho, Yvon; Van Dorsselaer, Alain; Raclot, Thierry
Abstract:
© The Author(s) 2016. While safety of fasting therapy is debated in humans, extended fasting occurs routinely and safely in wild animals. To do so, food deprived animals like breeding penguins anticipate the critical limit of fasting by resuming feeding. To date, however, no molecular indices of the physiological state that links spontaneous refeeding behaviour with fasting limits had been identified. Blood proteomics and physiological data reveal here that fasting-induced body protein depletion is not unsafe "per se". Indeed, incubating penguins only abandon their chick/egg to refeed when this state is associated with metabolic defects in glucose homeostasis/fatty acid utilization, insulin production and action, and possible renal dysfunctions. Our data illustrate how the field investigation of "exotic" models can be a unique source of information, with possible biomedical interest.
Published:
2016-12
Title:
Alzheimer Disease and Its Growing Epidemic: Risk Factors, Biomarkers, and the Urgent Need for Therapeutics.
Authors:
Hickman, Richard A.; Faustin, Arline; Wisniewski, Thomas
Abstract:
Alzheimer disease (AD) represents one of the greatest medical challenges of this century; the condition is becoming increasingly prevalent worldwide and no effective treatments have been developed for this terminal disease. Because the disease manifests at a late stage after a long period of clinically silent neurodegeneration, knowledge of the modifiable risk factors and the implementation of biomarkers is crucial in the primary prevention of the disease and presymptomatic detection of AD, respectively. This article discusses the growing epidemic of AD and antecedent risk factors in the disease process. Disease biomarkers are discussed, and the implications that this may have for the treatment of this currently incurable disease.
Published:
2016-11
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