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Title:
MERRF
Authors:
Cohen, Bruce H.
Abstract:
The acronym, MERRF, or myoclonus epilepsy and ragged red fiber disease, represents one of the early mitochondrial syndromes, whose molecular genetic basis was first established in 1990 by Shoffner and coworkers. Pathogenic mutations in the mitochondrial tRNALys may cause the MERRF syndrome. Myoclonus and epilepsy, most often medically intractable epilepsy, are hallmarks of the illness. Other features of the illness may include retinitis pigmentosa, progressive external ophthalmoplegia, sensorineural hearing loss, dementia, ataxia, cervical lipomatosis, cardiac conduction defects (Wolff-Parkinson-White syndrome and others), lipomatosis, neuropathy, cardiomyopathy, and a myopathy. MERRF cases may have features that overlap other mitochondrial disorders. The diagnostic evaluation requires recognizing the clinical phenotype and performing confirmatory genetic testing. Although the name of this disorder includes the words ragged red fibers, a microscopic description of the appearance of the muscle fibers in many cases is currently not part of the case's evaluation, as the illness can be confirmed by genetic testing without the need for a muscle biopsy. Treatment is symptomatic, with myoclonus best treated with benzodiazepines and the seizures treated with medications best for myoclonic epilepsy and generalized epilepsy, such as lamotrigine, zonisamide, levetiracetam, and lacosamide. The use of electroencephalography (EEG) is often important to distinguish between myoclonus and myoclonic seizures, as the treatment for myoclonus would be aimed at symptom relief, whereas the treatment for seizures would be to prevent or lessen their frequency. The EEG can also distinguish subclinical seizures from the neuropsychological effects of medication use and dementia. There are no curative therapies at this time.
Published:
2016
Title:
Mechanisms and significance of brain glucose signaling in energy balance, glucose homeostasis, and food-induced reward
Authors:
Devarakonda, Kavya; Mobbs, Charles V.
Abstract:
The concept that hypothalamic glucose signaling plays an important role in regulating energy balance, e.g., as instantiated in the so-called "glucostat" hypothesis, is one of the oldest in the field of metabolism. However the mechanisms by which neurons in the hypothalamus sense glucose, and the function of glucose signaling in the brain, has been difficult to establish. Nevertheless recent studies probing mechanisms of glucose signaling have also strongly supported a role for glucose signaling in regulating energy balance, glucose homeostasis, and food-induced reward.
Published:
2016
Title:
Mechanisms of Action of Antiseizure Drugs and the Ketogenic Diet
Authors:
Rogawski, Michael A.; Löscher, Wolfgang; Rho, Jong M.
Abstract:
Antiseizure drugs (ASDs), also termed antiepileptic drugs, are the main form of symptomatic treatment for people with epilepsy, but not all patients become free of seizures. The ketogenic diet is one treatment option for drug-resistant patients. Both types of therapy exert their clinical effects through interactions with one or more of a diverse set of molecular targets in the brain. ASDs act by modulation of voltage-gated ion channels, including sodium, calcium, and potassium channels; by enhancement of γ-aminobutyric acid (GABA)-mediated inhibition through effects on GABAA receptors, the GABA transporter 1 (GAT1) GABA uptake transporter, or GABA transaminase; through interactions with elements of the synaptic release machinery, including synaptic vesicle 2A (SV2A) and α2δ; or by blockade of ionotropic glutamate receptors, including α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) receptors. The ketogenic diet leads to increases in circulating ketones, which may contribute to the efficacy in treating pharmacoresistant seizures. Production in the brain of inhibitory mediators, such as adenosine, or ion channel modulators, such as polyunsaturated fatty acids, may also play a role. Metabolic effects, including diversion from glycolysis, are a further postulated mechanism. For some ASDs and the ketogenic diet, effects on multiple targets may contribute to activity. Better understanding of the ketogenic diet will inform the development of improved drug therapies to treat refractory seizures.
Published:
2016
Title:
Medication and creativity in Attention Deficit Hyperactivity Disorder (ADHD)
Authors:
González-Carpio Hernández, Gracia; Serrano Selva, Juan P.
Abstract:
BACKGROUND: The aim of this study was to determine the effect of methylphenidate (MPH) on creative potential in a group of children with attention deficit disorder with hyperactivity (ADHD). METHOD: A randomized single blind crossover study was performed with 24 children with ADHD, aged between 18 and 96 (M = 10.0, SD = 1.3), evaluating each child’s creativity with and without MPH, using the Torrance Tests of Creative Thinking-Figural (TTCT). RESULTS: Children under treatment with MPH showed a lower global Creative Index and lower scores on Fluency, Originality and Creative Strengths, compared to when not under treatment. The capacities for Elaboration, Abstractness of Titles, and Resistance to Closure did not differ whether on or off pharmacological treatment. CONCLUSION: Our finding suggests that is important to take into account the impact that MPH might have on the creative potential of a child with ADHD to develop a more accurate evaluation and to develop better treatment plans.
Published:
2016
Title:
Medicines and Vegetable Oils as Hidden Causes of Cardiovascular Disease and Diabetes. [Review]
Authors:
Okuyama, Harumi; Langsjoen, Peter H.; Ohara, Naoki; Hashimoto, Yoko; Hamazaki, Tomohito; Yoshida, Satoshi; Kobayashi, Tetsuyuki; Langsjoen, Alena M.
Abstract:
KEY MESSAGES: To date, no randomized controlled trials (RCTs) have been performed to prove the above interpretation. However, the opposite types of RCT trials have been performed by increasing the intake of high-linoleic vegetable oils and reducing that of animal fats, which resulted in increased CVD and all-cause mortality. The amounts of these vegetable oils to exhibit adverse effects in animal studies are not huge (
Published:
2016
Title:
Metabolic Markers to Predict Incident Diabetes Mellitus in Statin-Treated Patients (from the Treating to New Targets and the Stroke Prevention by Aggressive Reduction in Cholesterol Levels Trials)
Authors:
Kohli, Payal; Knowles, Joshua W.; Sarraju, Ashish; Waters, David D.; Reaven, Gerald
Abstract:
The goal of this analysis was to evaluate the ability of insulin resistance, identified by the presence of prediabetes mellitus (PreDM) combined with either an elevated triglyceride (TG \textgreater1.7 mmol/l) or body mass index (BMI ≥27.0 kg/m2), to identify increased risk of statin-associated type 2 diabetes mellitus (T2DM). Consequently, a retrospective analysis of data from subjects without diabetes in the Treating to New Targets and the Stroke Prevention by Aggressive Reduction in Cholesterol Levels randomized controlled trials was performed, subdividing participants into 4 experimental groups: (1) normal fasting glucose (NFG) and TG ≤1.7 mmol/l (42%); (2) NFG and TG \textgreater1.7 mmol/l (22%); (3) PreDM and TG ≤1.7 mmol/l (20%); and (4) PreDM and TG \textgreater1.7 mmol/l (15%). Comparable groupings were created substituting BMI values (kg/m2\textless27.0 and ≥27.0) for TG concentrations. Patients received atorvastatin or placebo for a median duration of 4.9 years. Incident T2DM, defined by developing at least 2 fasting plasma glucose (FPG) concentrations ≥126 mg/dl, an increase in FPG ≥37 mg/dl, or a clinical diagnosis of T2DM, was observed in 8.2% of the total population. T2DM event rates (statin or placebo) varied from a low of 2.8%/3.2% (NFG and TG ≤1.7 mmol/l) to a high of 22.8%/7.6% (PreDM and TG \textgreater1.7 mmol/l) with intermediate values for only an elevated TG \textgreater1.7 mmol/l (5.2%/4.3%) or only PreDM (12.8%/7.6%). Comparable differences were observed when BMI values were substituted for TG concentrations. In conclusion, these data suggest that (1) the diabetogenic impact of statin treatment is relatively modest in general; (2) the diabetogenic impact is accentuated relatively dramatically as FPG and TG concentrations and BMI increase; and (3) PreDM, TG concentrations, and BMI identify people at highest risk of statin-associated T2DM.
Published:
2016
Title:
Metabolic parameters linked by phenotype microarray to acid resistance profiles of poultry-associated Salmonella enterica
Authors:
Guard, J.; Rothrock, M.J.; Shah, D.H.; Jones, D.R.; Gast, R.K.; Sanchez-Ingunza, R.; Madsen, M.; El-Attrache, J.; Lungu, B.
Abstract:
Phenotype microarrays were analyzed for 51 datasets derived from Salmonella enterica. The top 4 serotypes associated with poultry products and one associated with turkey, respectively Typhimurium, Enteritidis, Heidelberg, Infantis and Senftenberg, were represented. Datasets were partitioned initially into two clusters based on ranking by values at pH 4.5 (PM10 A03). Negative control wells were used to establish 90 respiratory units as the point differentiating acid resistance from sensitive strains. Thus, 24 isolates that appeared most acid-resistant were compared initially to 27 that appeared most acid-sensitive (24 × 27 format). Paired cluster analysis was also done and it included the 7 most acid-resistant and -sensitive datasets (7 × 7 format). Statistical analyses of ranked data were then calculated in order of standard deviation, probability value by the Student's t-test and a measure of the magnitude of difference called effect size. Data were reported as significant if, by order of filtering, the following parameters were calculated: i) a standard deviation of 24 respiratory units or greater from all datasets for each chemical, ii) a probability value of less than or equal to 0.03 between clusters and iii) an effect size of at least 0.50 or greater between clusters. Results suggest that between 7.89% and 23.16% of 950 chemicals differentiated acid-resistant isolates from sensitive ones, depending on the format applied. Differences were more evident at the extremes of phenotype using the subset of data in the paired 7 × 7 format. Results thus provide a strategy for selecting compounds for additional research, which may impede the emergence of acid-resistant Salmonella enterica in food. © 2016
Published:
2016
Title:
Methods for mitochondria and mitophagy flux analyses in stem cells of resting and regenerating skeletal muscle
Authors:
García-Prat, Laura; Martínez-Vicente, Marta; Muñoz-Cánoves, Pura
Abstract:
Mitochondria generate most of the cell's supply of ATP as a source of energy. They are also implicated in the control of cell's growth and death. Because of these critical functions, mitochondrial fitness is key for cellular homeostasis. Often, however, mitochondria become defective following damage or stress. To prevent accumulation of damaged mitochondria, the cells clear them through mitophagy, which is defined as the selective degradation of mitochondria by autophagy (the process for degradation of long-lived proteins and damaged organelles in lysosomes). Recently, constitutive mitophagic activity has been reported in quiescent muscle stem cells (satellite cells), which sustain regeneration of skeletal muscle. In response to muscle damage, these cells activate, expand, and differentiate to repair damaged myofibers. Mitophagy was shown to be required for maintenance of satellite cells in their healthy quiescent state. Conversely, damaged mitochondria accumulated in satellite cells with aging and this was attributed to defective mitophagy. This caused increased levels of reactive oxygen species (ROS) and loss of muscle stem cell regenerative capacity at old age. In this chapter, we describe different experimental strategies to evaluate mitochondria status and mitophagy in muscle stem cells from mice. They should improve our ability to study muscle stem homeostasis in adult life, and their loss of function in aging and disease.
Published:
2016
Title:
Methylglyoxal and carboxyethyllysine reduce glutamate uptake and S100B secretion in the hippocampus independently of RAGE activation
Authors:
Hansen, F.; Battú, C.E.; Dutra, M.F.; Galland, F.; Lirio, F.; Broetto, N.; Nardin, P.; Goncąlves, C.-A.
Abstract:
Diabetes is a metabolic disease characterized by high fasting-glucose levels. Diabetic complications have been associated with hyperglycemia and high levels of reactive compounds, such as methylglyoxal (MG) and advanced glycation endproducts (AGEs) formation derived from glucose. Diabetic patients have a higher risk of developing neurodegenerative diseases, such as Alzheimer's disease or Parkinson's disease. Herein, we examined the effect of high glucose, MG and carboxyethyllysine (CEL), a MG-derived AGE of lysine, on oxidative, metabolic and astrocyte-specific parameters in acute hippocampal slices, and investigated some of the mechanisms that could mediate these effects. Glucose, MG and CEL did not alter reactive oxygen species (ROS) formation, glucose uptake or glutamine synthetase activity. However, glutamate uptake and S100B secretion were decreased after MG and CEL exposure. RAGE activation and glycation reactions, examined by aminoguanidine and l-lysine co-incubation, did not mediate these changes. Acute MG and CEL exposure, but not glucose, were able to induce similar effects on hippocampal slices, suggesting that conditions of high glucose concentrations are primarily toxic by elevating the rates of these glycation compounds, such as MG, and by generation of protein cross-links. Alterations in the secretion of S100B and the glutamatergic activity mediated by MG and AGEs can contribute to the brain dysfunction observed in diabetic patients. © 2015 Springer-Verlag Wien.
Published:
2016
Title:
Mice Fed a High-Fat Diet Supplemented with Resistant Starch Display Marked Shifts in the Liver Metabolome Concurrent with Altered Gut Bacteria
Authors:
Kieffer, Dorothy A.; Piccolo, Brian D.; Marco, Maria L.; Eun Bae Kim; Goodson, Michael L.; Keenan, Michael J.; Dunn, Tamara N.; Bach Knudsen, Knud Erik; Martin, Roy J.; Adams, Sean H.; Kim, Eun Bae; Knudsen, Knud Erik Bach
Abstract:
Background: High-amylose-maize resistant starch type 2 (HAMRS2) is a fermentable dietary fiber known to alter the gut milieu, including the gut microbiota, which may explain the reported effects of resistant starch to ameliorate obesity-associated metabolic dysfunction.Objective: Our working hypothesis was that HAMRS2-induced microbiome changes alter gut-derived signals (i.e., xenometabolites) reaching the liver via the portal circulation, in turn altering liver metabolism by regulating gene expression and other pathways.Methods: We used a multi-omics systems biology approach to characterize HAMRS2-driven shifts to the cecal microbiome, liver metabolome, and transcriptome, identifying correlates between microbial changes and liver metabolites under obesogenic conditions that, to our knowledge, have not previously been recognized. Five-week-old male C57BL/6J mice were fed an energy-dense 45% lard-based-fat diet for 10 wk supplemented with either 20% HAMRS2 by weight (n = 14) or rapidly digestible starch (control diet; n = 15).Results: Despite no differences in food intake, body weight, glucose tolerance, fasting plasma insulin, or liver triglycerides, the HAMRS2 mice showed a 15-58% reduction in all measured liver amino acids, except for Gln, compared with control mice. These metabolites were equivalent in the plasma of HAMRS2 mice compared with controls, and transcripts encoding key amino acid transporters were not different in the small intestine or liver, suggesting that HAMRS2 effects were not simply due to lower hepatocyte exposure to systemic amino acids. Instead, alterations in gut microbial metabolism could have affected host nitrogen and amino acid homeostasis: HAMRS2 mice showed a 62% increase (P < 0.0001) in 48-h fecal output and a 41% increase (P
Published:
2016
Title:
Microbiota-dependent metabolite trimethylamine n-oxide and coronary artery calcium in the coronary artery risk development in young adults study (CARDIA)
Authors:
Meyer, K.A.; Benton, T.Z.; Bennett, B.J.; Jacobs, D.R., Jr.; Lloyd-Jones, D.M.; Gross, M.D.; Carr, J.J.; Gordon-Larsen, P.; Zeisel, S.H.
Abstract:
Background-Clinical studies implicate trimethylamine N-oxide (TMAO; a gut microbiota-dependent nutrient metabolite) in cardiovascular disease risk. There is a lack of population-based data on the role of TMAO in advancing early atherosclerotic disease. We tested the prospective associations between TMAO and coronary artery calcium (CAC) and carotid intima-media thickness (cIMT). Methods and Results-Data were from the Coronary Artery Risk Development in Young Adults Study (CARDIA), a biracial cohort of US adults recruited in 1985-1986 (n=5115). We randomly sampled 817 participants (aged 33-55 years) who attended examinations in 2000-2001, 2005-2006, and 2010-2011, at which CAC was measured by computed tomography and cIMT (2005-2006) by ultrasound. TMAO was quantified using liquid chromotography mass spectrometry on plasma collected in 2000- 2001. Outcomes were incident CAC, defined as Agatston units=0 in 2000-2001 and > 0 over 10-year follow-up, CAC progression (any increase over 10-year follow-up), and continuous cIMT. Over the study period, 25% (n=184) of those free of CAC in 2000- 2001 (n=746) developed detectable CAC. In 2000-2001, median (interquartile range) TMAO was 2.6 (1.8-4.2) lmol/L. In multivariable-adjusted models, TMAO was not associated with 10-year CAC incidence (rate ratio=1.03; 95% CI: 0.71-1.52) or CAC progression (0.97; 0.68-1.38) in Poisson regression, or cIMT (beta coefficient: -0.009; -0.03 to 0.01) in linear regression, comparing the fourth to the first quartiles of TMAO. Conclusions-In this population-based study, TMAO was not associated with measures of atherosclerosis: CAC incidence, CAC progression, or cIMT. These data indicate that TMAO may not contribute significantly to advancing early atherosclerotic disease risk among healthy early-middle-aged adults. © 2016 The Authors.
Published:
2016
Title:
Mindfulness meditation and the immune system: a systematic review of randomized controlled trials
Authors:
Black, David S.; Slavich, George M.
Abstract:
© 2016 New York Academy of Sciences. Mindfulness meditation represents a mental training framework for cultivating the state of mindful awareness in daily life. Recently, there has been a surge of interest in how mindfulness meditation improves human health and well-being. Although studies have shown that mindfulness meditation can improve self-reported measures of disease symptomatology, the effect that mindfulness meditation has on biological mechanisms underlying human aging and disease is less clear. To address this issue, we conducted the first comprehensive review of randomized controlled trials examining the effects of mindfulness meditation on immune system parameters, with a specific focus on five outcomes: (1) circulating and stimulated inflammatory proteins, (2) cellular transcription factors and gene expression, (3) immune cell count, (4) immune cell aging, and (5) antibody response. This analysis revealed substantial heterogeneity across studies with respect to patient population, study design, and assay procedures. The findings suggest possible effects of mindfulness meditation on specific markers of inflammation, cell-mediated immunity, and biological aging, but these results are tentative and require further replication. On the basis of this analysis, we describe the limitations of existing work and suggest possible avenues for future research. Mindfulness meditation may be salutogenic for immune system dynamics, but additional work is needed to examine these effects.
Published:
2016
Title:
Mitochondrial dysfunction-mediated apoptosis resistance associates with defective heat shock protein response in African-American men with prostate cancer
Authors:
Chaudhary, Ajay K.; Bhat, Tariq A.; Kumar, Sandeep; Kumar, Anil; Kumar, Rahul; Underwood, Willie; Koochekpour, Shahriar; Shourideh, Mojgan; Yadav, Neelu; Dhar, Shanta; Chandra, Dhyan
Abstract:
BACKGROUND: African-American (AA) patients with prostate cancer (PCa) respond poorly to current therapy compared with Caucasian American (CA) PCa patients. Although underlying mechanisms are not defined, mitochondrial dysfunction is a key reason for this disparity. METHODS: Cell death, cell cycle, and mitochondrial function/stress were analysed by flow cytometry or by Seahorse XF24 analyzer. Expression of cellular proteins was determined using immunoblotting and real-time PCR analyses. Cell survival/motility was evaluated by clonogenic, cell migration, and gelatin zymography assays. RESULTS: Glycolytic pathway inhibitor dichloroacetate (DCA) inhibited cell proliferation in both AA PCa cells (AA cells) and CA PCa cells (CA cells). AA cells possess reduced endogenous reactive oxygen species, mitochondrial membrane potential (mtMP), and mitochondrial mass compared with CA cells. DCA upregulated mtMP in both cell types, whereas mitochondrial mass was significantly increased in CA cells. DCA enhanced taxol-induced cell death in CA cells while sensitising AA cells to doxorubicin. Reduced expression of heat shock proteins (HSPs) was observed in AA cells, whereas DCA induced expression of CHOP, C/EBP, HSP60, and HSP90 in CA cells. AA cells are more aggressive and metastatic than CA cells. CONCLUSIONS: Restoration of mitochondrial function may provide new option for reducing PCa health disparity among American men.
Published:
2016
Title:
Mitophagy programs: Mechanisms and physiological implications of mitochondrial targeting by autophagy
Authors:
Hamacher-Brady, Anne; Brady, Nathan Ryan
Abstract:
Mitochondria are an essential source of ATP for cellular function, but when damaged, mitochondria generate a plethora of stress signals, which lead to cellular dysfunction and eventually programmed cell death. Thus, a major component of maintaining cellular homeostasis is the recognition and removal of dysfunctional mitochondria through autophagy-mediated degradation, i.e., mitophagy. Mitophagy further constitutes a developmental program, and undergoes a high degree of crosstalk with apoptosis. Reduced mitochondrial quality control is linked to disease pathogenesis, suggesting the importance of process elucidation as a clinical target. Recent work has revealed multiple mitophagy programs that operate independently or undergo crosstalk, and require modulated autophagy receptor activities at outer membranes of mitochondria. Here, we review these mitophagy programs, focusing on pathway mechanisms which recognize and target mitochondria for sequestration by autophagosomes, as well as mechanisms controlling pathway activities. Furthermore, we provide an introduction to the currently available methods for detecting mitophagy.
Published:
2016
Title:
Modulating mitochondrial quality in disease transmission: towards enabling mitochondrial DNA disease carriers to have healthy children.
Authors:
Diot, Alan; Dombi, Eszter; Lodge, Tiffany; Liao, Chunyan; Morten, Karl; Carver, Janet; Wells, Dagan; Child, Tim; Johnston, Iain G; Williams, Suzannah; Poulton, Joanna
Abstract:
One in 400 people has a maternally inherited mutation in mtDNA potentially causing incurable disease. In so-called heteroplasmic disease, mutant and normal mtDNA co-exist in the cells of carrier women. Disease severity depends on the proportion of inherited abnormal mtDNA molecules. Families who have had a child die of severe, maternally inherited mtDNA disease need reliable information on the risk of recurrence in future pregnancies. However, prenatal diagnosis and even estimates of risk are fraught with uncertainty because of the complex and stochastic dynamics of heteroplasmy. These complications include an mtDNA bottleneck, whereby hard-to-predict fluctuations in the proportions of mutant and normal mtDNA may arise between generations. In 'mitochondrial replacement therapy' (MRT), damaged mitochondria are replaced with healthy ones in early human development, using nuclear transfer. We are developing non-invasive alternatives, notably activating autophagy, a cellular quality control mechanism, in which damaged cellular components are engulfed by autophagosomes. This approach could be used in combination with MRT or with the regular management, pre-implantation genetic diagnosis (PGD). Mathematical theory, supported by recent experiments, suggests that this strategy may be fruitful in controlling heteroplasmy. Using mice that are transgenic for fluorescent LC3 (the hallmark of autophagy) we quantified autophagosomes in cleavage stage embryos. We confirmed that the autophagosome count peaks in four-cell embryos and this correlates with a drop in the mtDNA content of the whole embryo. This suggests removal by mitophagy (mitochondria-specific autophagy). We suggest that modulating heteroplasmy by activating mitophagy may be a useful complement to mitochondrial replacement therapy.
Published:
2016
Title:
Molecular nutrition: Interaction of nutrients, gene regulations and performances
Authors:
Sato, K.
Abstract:
Nutrition deals with ingestion of foods, digestion, absorption, transport of nutrients, intermediary metabolism, underlying anabolism and catabolism, and excretion of unabsorbed nutrients and metabolites. In addition, nutrition interacts with gene expressions, which are involved in the regulation of animal performances. Our laboratory is concerned with the improvement of animal productions, such as milks, meats and eggs, with molecular nutritional aspects. The present review shows overviews on the nutritional regulation of metabolism, physiological functions and gene expressions to improve animal production in chickens and dairy cows. © 2016 The Authors. Animal Science Journal published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Animal Science.
Published:
2016
Title:
Monocarboxylate transporters in the brain and in cancer
Authors:
Pérez-Escuredo, Jhudit; Van Hée, Vincent F.; Sboarina, Martina; Falces, Jorge; Payen, Valéry L.; Pellerin, Luc; Sonveaux, Pierre
Abstract:
Monocarboxylate transporters (MCTs) constitute a family of 14 members among which MCT1–4 facilitate the passive transport of monocarboxylates such as lactate, pyruvate and ketone bodies together with protons across cell membranes. Their anchorage and activity at the plasma membrane requires interaction with chaperon protein such as basigin/CD147 and embigin/gp70. MCT1–4 are expressed in different tissues where they play important roles in physiological and pathological processes. This review focuses on the brain and on cancer. In the brain, MCTs control the delivery of lactate, produced by astrocytes, to neurons, where it is used as an oxidative fuel. Consequently, MCT dysfunctions are associated with pathologies of the central nervous system encompassing neurodegeneration and cognitive defects, epilepsy and metabolic disorders. In tumors, MCTs control the exchange of lactate and other monocarboxylates between glycolytic and oxidative cancer cells, between stromal and cancer cells and between glycolytic cells and endothelial cells. Lactate is not only a metabolic waste for glycolytic cells and a metabolic fuel for oxidative cells, but it also behaves as a signaling agent that promotes angiogenesis and as an immunosuppressive metabolite. Because MCTs gate the activities of lactate, drugs targeting these transporters have been developed that could constitute new anticancer treatments. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and Jean-Claude Martinou.
Published:
2016
Title:
Motives of consumers following a vegan diet and their attitudes towards animal agriculture
Authors:
Janssen, Meike; Busch, Claudia; Rödiger, Manika; Hamm, Ulrich
Abstract:
The number of consumers following a vegan diet has notably increased in many industrialised countries and it is likely that their influence on the food sector will continue to grow. The aim of the present study was to identify different segments of consumers according to their motivation for following a vegan diet. Another objective was to analyse the attitudes of these consumers towards animal agriculture. The main focus was to determine whether all consumers following a vegan diet oppose animal agriculture in general or if some of these consumers accept certain forms of animal agriculture. The 2014 study, conducted at seven vegan supermarkets in Germany, was based on face-to-face interviews with 329 consumers following a vegan diet. The open question on consumer motivations for adopting a vegan diet revealed three main motives: Animal-related motives (mentioned by 89.7% of the respondents), motives related to personal well-being and/or health (69.3%), and environment-related motives (46.8%). The two-step cluster analysis identified five consumer segments with different motivations for following a vegan diet. The vast majority of respondents (81.8%) mentioned more than one motive. We conclude that making a dichotomous segmentation into ethical versus self-oriented consumers, as previous authors have done, disregards the fact that many consumers following a vegan diet are driven by more than one motive. The consumer segments had significantly different attitudes towards animal agriculture. We identified consumers following a vegan diet (about one third of the sample) who might be open to forms of animal agriculture guaranteeing animal welfare standards going beyond current practices. The present study has interesting implications for the food sector and the agricultural sector.
Published:
2016
Title:
N-Acetyl Cysteine Attenuated the Deleterious Effects of Advanced Glycation End-Products on the Kidney of Non-Diabetic Rats
Authors:
Thieme, K.; Da Silva, K.S.; Fabre, N.T.; Catanozi, S.; Monteiro, M.B.; Santos-Bezerra, D.P.; Costa-Pessoa, J.M.; Oliveira-Souza, M.; Machado, U.F.; Passarelli, M.; Correa-Giannella, M.L.
Abstract:
Aim: To assess the renal effects of chronic exposure to advanced glycation end-products (AGEs) in the absence of diabetes and the potential impact of concomitant treatment with the antioxidant N-acetyl cysteine (NAC). Methods: Wistar rats received intraperitoneally 20 mg/kg/day of albumin modified (AlbAGE) or not (AlbC) by advanced glycation for 12 weeks and oral NAC (600mg/L; AlbAGE+NAC and AlbC+NAC, respectively). Biochemical, urinary and renal morphological analyses; carboxymethyl-lysine (CML, an AGE), CD68 (macrophage infiltration), and 4-hydroxynonenal (4-HNE, marker of oxidative stress) immunostaining; intrarenal mRNA expression of genes belonging to pathways related to AGEs (Ager, Ddost, Nfkb1), renin-angiotensin system (Agt, Ren, Ace), fibrosis (Tgfb1, Col4a1), oxidative stress (Nox4, Txnip), and apoptosis (Bax, Bcl2); and reactive oxidative species (ROS) content were performed. Results: AlbAGE significantly increased urine protein-to-creatinine ratio; glomerular area; renal CML content and macrophage infiltration; expression of Ager, Nfkb1, Agt, Ren, Tgfb1, Col4a1, Txnip, Bax/Bcl2 ratio; and 4-HNE and ROS contents. Some of these effects were attenuated by NAC concomitant treatment. Conclusion: Because AGEs are highly consumed in modern diets and implicated in the progression of different kidney diseases, NAC could be a therapeutic intervention to decrease renal damage, considering that long-term restriction of dietary AGEs is difficult to achieve in practice. © 2016 The Author(s) Published by S. Karger AG, Basel.
Published:
2016
Title:
NMR-based metabolic characterization of chicken tissues and biofluids: a model for avian research
Authors:
Le Roy, C.I.; Mappley, L.J.; La Ragione, R.M.; Woodward, M.J.; Claus, S.P.
Abstract:
Introduction: Poultry is one of the most consumed meat in the world and its related industry is always looking for ways to improve animal welfare and productivity. It is therefore essential to understand the metabolic response of the chicken to new feed formulas, various supplements, infections and treatments. Objectives: As a basis for future research investigating the impact of diet and infections on chicken’s metabolism, we established a high-resolution proton nuclear magnetic resonance (NMR)-based metabolic atlas of the healthy chicken (Gallus gallus). Methods: Metabolic extractions were performed prior to 1 H-NMR and 2D NMR spectra acquisition on twelve biological matrices: liver, kidney, spleen, plasma, egg yolk and white, colon, caecum, faecal water, ileum, pectoral muscle and brain of 6 chickens. Metabolic profiles were then exhaustively characterized. Results: Nearly 80 metabolites were identified. A cross-comparison of these matrices was performed to determine metabolic variations between and within each section and highlighted that only eight core metabolites were systematically found in every matrice. Conclusion: This work constitutes a database for future NMR-based metabolomic investigations in relation to avian production and health. © 2016, The Author(s).
Published:
2016
Title:
Natural Selection in the Great Apes
Authors:
Cagan, Alexander; Theunert, Christoph; Laayouni, Hafid; Santpere, Gabriel; Pybus, Marc; Casals, Ferran; Prüfer, Kay; Navarro, Arcadi; Marques-Bonet, Tomas; Bertranpetit, Jaume; Andrés, Aida M.
Abstract:
Natural selection is crucial for the adaptation of populations to their environments. Here, we present the first global study of natural selection in the Hominidae (humans and great apes) based on genome-wide information from population samples representing all extant species (including most subspecies). Combining several neutrality tests we create a multi-species map of signatures of natural selection covering all major types of natural selection. We find that the estimated efficiency of both purifying and positive selection varies between species and is significantly correlated with their long-term effective population size. Thus, even the modest differences in population size among the closely related Hominidae lineages have resulted in differences in their ability to remove deleterious alleles and to adapt to changing environments. Most signatures of balancing and positive selection are species-specific, with signatures of balancing selection more often being shared among species. We also identify loci with evidence of positive selection across several lineages. Notably, we detect signatures of positive selection in several genes related to brain function, anatomy, diet and immune processes. Our results contribute to a better understanding of human evolution by putting the evidence of natural selection in humans within its larger evolutionary context. The global map of natural selection in our closest living relatives is available as an interactive browser at http://tinyurl.com/nf8qmzh.
Published:
2016
Title:
Neoliberal science, Chinese style: Making and managing the ‘obesity epidemic’
Authors:
Greenhalgh, Susan
Abstract:
Published:
2016
Title:
New 3D-Culture Approaches to Study Interactions of Bone Marrow Adipocytes with Metastatic Prostate Cancer Cells
Authors:
Herroon, Mackenzie Katheryn; Diedrich, Jonathan Driscoll; Podgorski, Izabela
Abstract:
Adipocytes are a major component of the bone marrow that can critically affect metastatic progression in bone. Understanding how the marrow fat cells influence growth, behavior, and survival of tumor cells requires utilization of in vitro cell systems that can closely mimic the physiological microenvironment. Herein, we present two new three-dimensional (3D) culture approaches to study adipocyte-tumor cell interactions in vitro. The first is a transwell-based system composed of the marrow-derived adipocytes in 3D collagen I gels and reconstituted basement membrane-overlayed prostate tumor cell spheroids. Tumor cells cultured under these 3D conditions are continuously exposed to adipocyte-derived factors, and their response can be evaluated by morphological and immunohistochemical analyses. We show via immunofluorescence analysis of metabolism-associated proteins that under 3D conditions tumor cells have significantly different metabolic response to adipocytes than tumor cells grown in 2D culture. We also demonstrate that this model allows for incorporation of other cell types, such as bone marrow macrophages, and utilization of dye-quenched collagen substrates for examination of proteolysis-driven responses to adipocyte- and macrophage-derived factors. Our second 3D culture system is designed to study tumor cell invasion toward the adipocytes and the consequent interaction between the two cell types. In this model, marrow adipocytes are separated from the fluorescently labeled tumor cells by a layer of collagen I. At designated time points, adipocytes are stained with BODIPY and confocal z-stacks are taken through the depth of the entire culture to determine the distance traveled between the two cell types over time. We demonstrate that this system can be utilized to study effects of candidate factors on tumor invasion toward the adipocytes. We also show that immunohistochemical analyses can be performed to evaluate the impact of direct interaction of prostate tumor cells with adipocytes. Our models underline the importance of using the appropriate culture conditions to mimic physiological interactions between marrow adipocytes and metastatic tumor cells. These systems have a potential to be utilized for analyses of various factors that may be regulated by the adipocytes in bone. Their application likely extends beyond metastatic prostate cancer to other tumors that colonize the bone marrow microenvironment.
Published:
2016
Title:
New Nordic Diet versus Average Danish Diet: A Randomized Controlled Trial Revealed Healthy Long-Term Effects of the New Nordic Diet by GC-MS Blood Plasma Metabolomics
Authors:
Khakimov, Bekzod; Poulsen, Sanne Kellebjerg; Savorani, Francesco; Acar, Evrim; Gürdeniz, Gözde; Larsen, Thomas M.; Astrup, Arne; Dragsted, Lars O.; Engelsen, Søren Balling
Abstract:
A previous study has shown effects of the New Nordic Diet (NND) to stimulate weight loss and lower systolic and diastolic blood pressure in obese Danish women and men in a randomized, controlled dietary intervention study. This work demonstrates long-term metabolic effects of the NND as compared with an Average Danish Diet (ADD) in blood plasma and reveals associations between metabolic changes and health beneficial effects of the NND including weight loss. A total of 145 individuals completed the intervention and blood samples were taken along with clinical examinations before the intervention started (week 0) and after 12 and 26 weeks. The plasma metabolome was measured using GC-MS, and the final metabolite table contained 144 variables. Significant and novel metabolic effects of the diet, resulting weight loss, gender, and intervention study season were revealed using PLS-DA and ASCA. Several metabolites reflecting specific differences in the diets, especially intake of plant foods and seafood, and in energy metabolism related to ketone bodies and gluconeogenesis formed the predominant metabolite pattern discriminating the intervention groups. Among NND subjects, higher levels of vaccenic acid and 3-hydroxybutanoic acid were related to a higher weight loss, while higher concentrations of salicylic, lactic, and N-aspartic acids and 1,5-anhydro-d-sorbitol were related to a lower weight loss. Specific gender and seasonal differences were also observed. The study strongly indicates that healthy diets high in fish, vegetables, fruit, and whole grain facilitated weight loss and improved insulin sensitivity by increasing ketosis and gluconeogenesis in the fasting state.
Published:
2016
Title:
New perspectives on dairy and cardiovascular health
Authors:
Lovegrove, Julie A.; Hobbs, Ditte A.
Abstract:
CVD are the leading cause of mortality and morbidity worldwide. One of the key dietary recommendations for CVD prevention is reduction of saturated fat intake. Yet, despite milk and dairy foods contributing on average 27 % of saturated fat intake in the UK diet, evidence from prospective cohort studies does not support a detrimental effect of milk and dairy foods on risk of CVD. The present paper provides a brief overview of the role of milk and dairy products in the diets of UK adults, and will summarise the evidence in relation to the effects of milk and dairy consumption on CVD risk factors and mortality. The majority of prospective studies and meta-analyses examining the relationship between milk and dairy product consumption and risk of CVD show that milk and dairy products, excluding butter, are not associated with detrimental effects on CVD mortality or risk biomarkers that include serum LDL-cholesterol. In addition, there is increasing evidence that milk and dairy products are associated with lower blood pressure and arterial stiffness. These apparent benefits of milk and dairy foods have been attributed to their unique nutritional composition, and suggest that the elimination of milk and dairy may not be the optimum strategy for CVD risk reduction.
Published:
2016
Title:
Novel ketone diet enhances physical and cognitive performance
Authors:
Murray, Andrew J.; Knight, Nicholas S.; Cole, Mark A.; Cochlin, Lowri E.; Carter, Emma; Tchabanenko, Kirill; Pichulik, Tica; Gulston, Melanie K.; Atherton, Helen J.; Schroeder, Marie A.; Deacon, Robert M.J.; Kashiwaya, Yoshihiro; King, M. Todd; Pawlosky, Robert; Rawlins, J. Nicholas P.; Tyler, Damian J.; Griffin, Julian L.; Robertson, Jeremy; Veech, Richard L.; Clarke, Kieran
Abstract:
© 2016 The Author(s). Ketone bodies are themost energy-efficient fuel and yieldmoreATP permole of substrate than pyruvate and increase the free energy released from ATP hydrolysis. Elevation of circulating ketones via high-fat, lowcarbohydrate diets has been used for the treatment of drug-refractory epilepsy and for neurodegenerative diseases, such as Parkinson's disease. Ketones may also be beneficial for muscle and brain in times of stress, such as endurance exercise. The challenge has been to raise circulating ketone levels by using a palatable diet without altering lipid levels. We found that blood ketone levels can be increased and cholesterol and triglycerides decreased by feeding rats a novel ketone ester diet: chow that is supplemented with (R)-3-hydroxybutyl (R)-3-hydroxybutyrate as 30% of calories. For 5 d, rats on the ketone diet ran 32% further on a treadmill than did control rats that ate an isocaloric diet that was supplemented with either corn starch or palmoil (P \textless 0.05). Ketone-fed rats completed an 8-arm radial maze test 38% faster than did those on the other diets, making more correct decisions before making a mistake (P \textless 0.05). Isolated, perfused hearts fromrats thatwere fed the ketone diet had greater free energy available from ATP hydrolysis during increased work than did hearts from rats on the other diets as shown by using [31P]- NMR spectroscopy. The novelketone diet, therefore, improved physical performance and cognitive function in rats, and its energy-sparing properties suggest that it may help to treat a range of human conditions with metabolic abnormalities.
Published:
2016
Title:
Nutrition and dietary Vitamin D in chronic kidney disease
Authors:
Souberbielle, J.-C.
Abstract:
Although the main source of vitamin D is not nutritional, some foods contain significant amounts of vitamin D. Fatty fish liver oil such as cod liver and fatty fish are the main natural source of dietary vitamin D3. White fish, offal (liver, kidney), egg yolk, and to a lesser extent meat (muscle) also contain significant amounts of vitamin D3, while dairy products (non fortified) contain very small amounts of vitamin D3 with the exception of butter that has significant amounts of vitamin D3 due to its high fat content. Mushrooms seem to be the only significant source of vitamin D2, and are the only non-animal-based foods containing vitamin D. As it has been demonstrated that some animal foods (meat, offal, egg yolk) contain 25(OH)D, and that 25(OH)D is better and more quickly absorbed than native vitamin D, it is now accepted that this metabolite contributes significantly to the vitamin D status. Food fortification is a good way to eradicate severe vitamin D deficiency (i.e. 25(OH)D
Published:
2016
Title:
Nutritional Ketosis Alters Fuel Preference and Thereby Endurance Performance in Athletes
Authors:
Cox, Pete J.; Kirk, Tom; Ashmore, Tom; Willerton, Kristof; Evans, Rhys; Smith, Alan; Murray, Andrew J.; Stubbs, Brianna; West, James; McLure, Stewart W.; King, M. Todd; Dodd, Michael S.; Holloway, Cameron; Neubauer, Stefan; Drawer, Scott; Veech, Richard L.; Griffin, Julian L.; Clarke, Kieran
Abstract:
Ketosis, the metabolic response to energy crisis, is a mechanism to sustain life by altering oxidative fuel selection. Often overlooked for its metabolic potential, ketosis is poorly understood outside of starvation or diabetic crisis. Thus, we studied the biochemical advantages of ketosis in humans using a ketone ester-based form of nutrition without the unwanted milieu of endogenous ketone body production by caloric or carbohydrate restriction. In five separate studies of 39 high-performance athletes, we show how this unique metabolic state improves physical endurance by altering fuel competition for oxidative respiration. Ketosis decreased muscle glycolysis and plasma lactate concentrations, while providing an alternative substrate for oxidative phosphorylation. Ketosis increased intramuscular triacylglycerol oxidation during exercise, even in the presence of normal muscle glycogen, co-ingested carbohydrate and elevated insulin. These findings may hold clues to greater human potential and a better understanding of fuel metabolism in health and disease.
Published:
2016
Title:
Nutritional interventions for Alzheimer's prevention: A clinical precision medicine approach
Authors:
Schelke, Matthew W.; Hackett, Katherine; Chen, Jaclyn L.; Shih, Chiashin; Shum, Jessica; Montgomery, Mary E.; Chiang, Gloria C.; Berkowitz, Cara; Seifan, Alon; Krikorian, Robert; Isaacson, Richard Scott
Abstract:
Alzheimer's disease (AD) is a major source of morbidity and mortality, with the disease burden expected to rise as the population ages. No disease-modifying agent is currently available, but recent research suggests that nutritional and lifestyle modifications can delay or prevent the onset of AD. However, preventive nutritional interventions are not universally applicable and depend on the clinical profile of the individual patient. This article reviews existing nutritional modalities for AD prevention that act through improvement of insulin resistance, correction of dyslipidemia, and reduction of oxidative stress, and discusses how they may be modified on the basis of individual biomarkers, genetics, and behavior. In addition, we report preliminary results of clinical application of these personalized interventions at the first AD prevention clinic in the United States. The use of these personalized interventions represents an important application of precision medicine techniques for the prevention of AD that can be adopted by clinicians across disciplines.
Published:
2016
Title:
O-GlcNAcylation in Cancer Biology: Linking Metabolism and Signaling
Authors:
Ferrer, Christina M.; Sodi, Valerie L.; Reginato, Mauricio J.
Abstract:
The hexosamine biosynthetic pathway (HBP) is highly dependent on multiple metabolic nutrients including glucose, glutamine, and acetyl-CoA. Increased flux through HBP leads to elevated post-translational addition of β-D-N-acetylglucosamine sugars to nuclear and cytoplasmic proteins. Increased total O-GlcNAcylation is emerging as a general characteristic of cancer cells, and recent studies suggest that O-GlcNAcylation is a central communicator of nutritional status to control key signaling and metabolic pathways that regulate multiple cancer cell phenotypes. This review summarizes our current understanding of changes of O-GlcNAc cycling enzymes in cancer, the role of O-GlcNAcylation in tumorigenesis, and the current challenges in targeting this pathway therapeutically.
Published:
2016
Title:
Obese Mice Fed a Diet Supplemented with Enzyme-Treated Wheat Bran Display Marked Shifts in the Liver Metabolome Concurrent with Altered Gut Bacteria
Authors:
Kieffer, Dorothy A.; Piccolo, Brian D.; Marco, Maria L.; Eun Bae Kim; Goodson, Michael L.; Keenan, Michael J.; Dunn, Tamara N.; Bach Knudsen, Knud Erik; Adams, Sean H.; Martin, Roy J.; Kim, Eun Bae; Knudsen, Knud Erik Bach
Abstract:
Background: Enzyme-treated wheat bran (ETWB) contains a fermentable dietary fiber previously shown to decrease liver triglycerides (TGs) and modify the gut microbiome in mice. It is not clear which mechanisms explain how ETWB feeding affects hepatic metabolism, but factors (i.e., xenometabolites) associated with specific microbes may be involved.Objective: The objective of this study was to characterize ETWB-driven shifts in the cecal microbiome and to identify correlates between microbial changes and diet-related differences in liver metabolism in diet-induced obese mice that typically display steatosis.Methods: Five-week-old male C57BL/6J mice fed a 45%-lard-based fat diet supplemented with ETWB (20% wt:wt) or rapidly digestible starch (control) (n = 15/group) for 10 wk were characterized by using a multi-omics approach. Multivariate statistical analysis was used to identify variables that were strong discriminators between the ETWB and control groups.Results: Body weight and liver TGs were decreased by ETWB feeding (by 10% and 25%, respectively; P < 0.001), and an index of liver reactive oxygen species was increased (by 29%; P < 0.01). The cecal microbiome showed an increase in Bacteroidetes (by 42%; P < 0.05) and a decrease in Firmicutes (by 16%; P
Published:
2016
Title:
Obesity and tumor growth: inflammation, immunity, and the role of a ketogenic diet. [Review]
Authors:
Wright, Christopher; Simone, Nicole L.
Abstract:
SUMMARY: Obesity is becoming more prevalent and its link to cancer is clearly established providing a rationale for the implementation of dietary interventions as an adjuvant therapeutic strategy for malignancy.
Published:
2016
Title:
Oral AGE restriction ameliorates insulin resistance in obese individuals with the metabolic syndrome: a randomised controlled trial
Authors:
Vlassara, Helen; Cai, Weijing; Tripp, Elizabeth; Pyzik, Renata; Yee, Kalle; Goldberg, Laurie; Tansman, Laurie; Chen, Xue; Mani, Venkatesh; Fayad, Zahi A.; Nadkarni, Girish N.; Striker, Gary E.; He, John C.; Uribarri, Jaime
Abstract:
AIMS/HYPOTHESIS: We previously reported that obese individuals with the metabolic syndrome (at risk), compared with obese individuals without the metabolic syndrome (healthy obese), have elevated serum AGEs that strongly correlate with insulin resistance, oxidative stress and inflammation. We hypothesised that a diet low in AGEs (L-AGE) would improve components of the metabolic syndrome in obese individuals, confirming high AGEs as a new risk factor for the metabolic syndrome. METHODS: A randomised 1 year trial was conducted in obese individuals with the metabolic syndrome in two parallel groups: L-AGE diet vs a regular diet, habitually high in AGEs (Reg-AGE). Participants were allocated to each group by randomisation using random permuted blocks. At baseline and at the end of the trial, we obtained anthropometric variables, blood and urine samples, and performed OGTTs and MRI measurements of visceral and subcutaneous abdominal tissue and carotid artery. Only investigators involved in laboratory determinations were blinded to dietary assignment. Effects on insulin resistance (HOMA-IR) were the primary outcome. RESULTS: Sixty-one individuals were randomised to a Reg-AGE diet and 77 to an L-AGE diet; the data of 49 and 51, respectively, were analysed at the study end in 2014. The L-AGE diet markedly improved insulin resistance; modestly decreased body weight; lowered AGEs, oxidative stress and inflammation; and enhanced the protective factors sirtuin 1, AGE receptor 1 and glyoxalase I. The Reg-AGE diet raised AGEs and markers of insulin resistance, oxidative stress and inflammation. There were no effects on MRI-assessed measurements. No side effects from the intervention were identified. HOMA-IR came down from 3.1 ± 1.8 to 1.9 ± 1.3 (p < 0.001) in the L-AGE group, while it increased from 2.9 ± 1.2 to 3.6 ± 1.7 (p
Published:
2016
Title:
Passive heat therapy improves endothelial function, arterial stiffness and blood pressure in sedentary humans
Authors:
Brunt, Vienna E.; Howard, Matthew J.; Francisco, Michael A.; Ely, Brett R.; Minson, Christopher T.
Abstract:
The majority of cardiovascular diseases are characterized by disorders of the arteries, predominantly caused by endothelial dysfunction and arterial stiffening. Intermittent hot water immersion ("heat therapy") results in elevations in core temperature and changes in cardiovascular hemodynamics, such as cardiac output and vascular shear stress, that are similar to exercise, and thus, may provide an alternative means of improving health which could be utilized by patients with low exercise tolerance and/or capabilities. We sought to comprehensively assess the effects of 8 weeks of heat therapy biomarkers of vascular function in young, sedentary subjects. Methods: Twenty young, sedentary subjects were assigned to participate in 8 weeks (4-5x/week) of heat therapy (N = 10; immersion in a 40.5°C bath sufficient to maintain rectal temperature ≥ 38.5°C for 60 min per session) or thermoneutral water immersion (N = 10; sham). Results: Eight weeks of heat therapy increased flow-mediated dilation from 5.6 ± 0.3{%} to 10.9 ± 1.0{%} (P {\textless} 0.01) and superficial femoral dynamic arterial compliance from 0.06 ± 0.01 to 0.09 ±0.01 mm2 mmHg-1 (P = 0.03), and reduced (i.e., improved) aortic pulse wave velocity from 7.1 ± 0.3 to 6.1 ± 0.3 m sec-1 (P = 0.03), carotid intima media thickness from 0.43 ± 0.01 to 0.37 ± 0.01 mm (P {\textless} 0.001), and mean arterial blood pressure from 83 ± 1 to 78 ± 2 mmHg (P = 0.02). No changes were observed in the sham group or for carotid arterial compliance, superficial femoral intima media thickness or endothelium-independent dilation. Conclusions: Heat therapy improved endothelium-dependent dilation, arterial stiffness, intima media thickness, and blood pressure, indicating improved cardiovascular health. These data suggest heat therapy may provide a simple and effective tool for improving cardiovascular health in various populations.
Published:
2016
Title:
Position of the Academy of Nutrition and Dietetics: Vegetarian Diets
Authors:
Melina, Vesanto; Craig, Winston; Levin, Susan
Abstract:
It is the position of the Academy of Nutrition and Dietetics that appropriately planned vegetarian, including vegan, diets are healthful, nutritionally adequate, and may provide health benefits for the prevention and treatment of certain diseases. These diets are appropriate for all stages of the life cycle, including pregnancy, lactation, infancy, childhood, adolescence, older adulthood, and for athletes. Plant-based diets are more environmentally sustainable than diets rich in animal products because they use fewer natural resources and are associated with much less environmental damage. Vegetarians and vegans are at reduced risk of certain health conditions, including ischemic heart disease, type 2 diabetes, hypertension, certain types of cancer, and obesity. Low intake of saturated fat and high intakes of vegetables, fruits, whole grains, legumes, soy products, nuts, and seeds (all rich in fiber and phytochemicals) are characteristics of vegetarian and vegan diets that produce lower total and low-density lipoprotein cholesterol levels and better serum glucose control. These factors contribute to reduction of chronic disease. Vegans need reliable sources of vitamin B-12, such as fortified foods or supplements.
Published:
2016
Title:
Preliminary evaluation of a differential effect of an α-linolenate-rich supplement on ketogenesis and plasma $ømega$-3 fatty acids in young and older adults
Authors:
Hennebelle, Marie; Courchesne-Loyer, Alexandre; St-Pierre, Valérie; Vandenberghe, Camille; Castellano, Christian Alexandre; Fortier, Mélanie; Tessier, Daniel; Cunnane, Stephen C.
Abstract:
Objectives The aim of the present study was to compare the effects of an α-linolenic acid-rich supplement (ALA-RS) on the ketogenic response and plasma long-chain $ømega$-3 polyunsaturated fatty acid in healthy young adults and older individuals. Methods Ten young (25 ± 0.9 y) and 10 older adults (73.1 ± 2.2 y) consumed a flaxseed oil supplement providing 2 g/d of ALA for 4 wk. Plasma ketones, nonesterified fatty acids (NEFA), triacylglycerols, glucose, and insulin were measured over 6 h, before and after supplementation. Total body fat mass was assessed before and after the ALA-RS. Results The ALA-RS did not significantly modify fasting ketones but postprandial production of β-hydroxybutyrate was increased by 26% (P = 0.037) only in the young adult group. Fasting plasma ketones were positively correlated to fasting plasma NEFA (P \textless 0.01) in both groups. However, the relation was shifted to the right in the older group, suggesting that older adults needed higher plasma NEFA levels to achieve the same ketone amounts as young adults. At baseline, the older group had 47% higher total plasma fatty acids than the young group (P = 0.007). After the ALA-RS, plasma ALA doubled in both groups (P \textless 0.01), an effect that was associated in the older group with a 40% higher eicosapentaenoic acid (EPA; P = 0.004), but no difference in docosahexaenoic acid. The postsupplementation increase in plasma ALA correlated positively with percent total body fat, especially in the older group (r2 = 0.77; P = 0.0016). Conclusion In young adults, ALA-RS mildly stimulated postprandial ketogenesis, whereas in the older group, it favored increased plasma ALA and EPA.
Published:
2016
Title:
Processed Meat, but Not Unprocessed Red Meat, Is Inversely Associated with Leukocyte Telomere Length in the Strong Heart Family Study
Authors:
Fretts, Amanda M.; Howard, Barbara V.; Siscovick, David S.; Best, Lyle G.; Beresford, Shirley A. A.; Mete, Mihriye; Eilat-Adar, Sigal; Sotoodehnia, Nona; Jinying Zhao; Beresford, Shirley Aa; Zhao, Jinying
Abstract:
Background: Telomeres are repetitive nucleotide sequences (TTAGGG) and their associated proteins at the end of eukaryote chromosomes. Telomere length shortens throughout the lifespan with each cell division, and leukocyte telomere length (LTL) is often used as a biomarker of cellular aging. LTL is related to many chronic diseases, including cardiovascular disease and diabetes. However, to our knowledge, the relation between LTL and risk factors for cardiovascular disease and diabetes, such as dietary intake of processed meat and unprocessed red meat, is largely unknown.Objective: We examined the associations of processed meat intake and unprocessed red meat intake with LTL.Methods: This cross-sectional study comprised 2846 American Indians from the Strong Heart Family Study who participated in the 2001-2003 examination. Dietary factors, including past-year consumption of processed meat and unprocessed red meat, were assessed with the use of a 119-item Block Food-Frequency Questionnaire. LTL was measured with the use of quantitative polymerase chain reaction. Generalized estimating equations were used to examine the associations of intake of processed meat and unprocessed red meat with LTL.Results: Consumption of processed meat was negatively associated with LTL after adjustment for age, sex, site, education, smoking, alcohol use, physical activity, and other dietary factors. For every additional daily serving of processed meat, LTL was 0.021 units (telomeric product-to-single-copy gene ratio) shorter (β ± SE = -0.021 ± 0.008, P = 0.009). No association was observed between the intake of unprocessed red meat and LTL (β ± SE = 0.008 ± 0.011, P = 0.46).Conclusions: In the Strong Heart Family Study, consumption of processed meat, but not unprocessed red meat, was associated with shorter LTL, a potential mediator for several age-related diseases. Further studies are needed to better understand the biological mechanism by which processed meat intake influences cellular aging.
Published:
2016
Title:
Progressing Insights into the Role of Dietary Fats in the Prevention of Cardiovascular Disease. [Review]
Authors:
Zock, Peter L.; Blom, Wendy A. M.; Nettleton, Joyce A.; Hornstra, Gerard
Abstract:
Dietary fats have important effects on the risk of cardiovascular disease (CVD). Abundant evidence shows that partial replacement of saturated fatty acids (SAFA) with unsaturated fatty acids improves the blood lipid and lipoprotein profile and reduces the risk of coronary heart disease (CHD). Low-fat diets high in refined carbohydrates and sugar are not effective. Very long-chain polyunsaturated n-3 or omega-3 fatty acids (n-3 VLCPUFA) present in fish have multiple beneficial metabolic effects, and regular intake of fatty fish is associated with lower risks of fatal CHD and stroke. Food-based guidelines on dietary fats recommend limiting the consumption of animal fats high in SAFA, using vegetable oils high in monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA), and eating fatty fish. These recommendations are part of a healthy eating pattern that also includes ample intake of plant-based foods rich in fiber and limited sugar and salt.
Published:
2016
Title:
Proscribing Deception: The Gould Net Weight Amendment and the Origins of Mandatory Nutrition Labeling
Authors:
Junod, Suzanne
Abstract:
Published:
2016
Title:
Rational prescribing: the principles of drug selection
Authors:
Maxwell, Simon RJ
Abstract:
Published:
2016
Title:
Recent fast food consumption and bisphenol A and phthalates exposures among the U.S. population in NHANES, 2003–2010
Authors:
Zota, A.R.; Phillips, C.A.; Mitro, S.D.
Abstract:
Background: Phthalates and bisphenol A (BPA) are widely used industrial chemicals that may adversely impact human health. Human exposure is ubiquitous and can occur through diet, including consumption of processed or packaged food. Objective: To examine associations between recent fast food intake and BPA and urinary metabolites of di(2-ethylhexyl) phthalate (ΣDEHPm) and diisononyl phthalate (DiNPm) among the U.S. population. Methods: We combined data on 8,877 participants from the National Health and Nutrition Examination Survey (NHANES 2003–2010). Using 24-hr dietary recall data, we quantified: a) fast food intake [percent of total energy intake (TEI) from fast food]; b) fast food-derived fat intake (percent of TEI from fat in fast food); and c) fast food intake by food group (dairy, eggs, grains, meat, and other). We examined associations between dietary exposures and urinary chemical concentrations using multivariate linear regression. Results: We observed evidence of a positive, dose–response relationship between fast food intake and exposure to phthalates (p-trend < 0.0001) but not BPA; participants with high consumption (≥ 34.9% TEI from fast food) had 23.8% (95% CI: 11.9%, 36.9%) and 39.0% (95% CI: 21.9%, 58.5%) higher levels of ΣDEHPm and DiNPm, respectively, than nonconsumers. Fast food-derived fat intake was also positively associated with ΣDEHPm and DiNPm (p-trend
Published:
2016
Title:
Recipes for thought: knowledge and taste in the early modern English kitchen
Authors:
Wall, Wendy
Abstract:
Published:
2016
Title:
Recurrent nightly ketosis after prolonged exercise in type 1 diabetes - the need for glycogen replacement strategies. Case report and review of literature
Authors:
van Albada, M. E.; Bakker-van Waarde, W. M.
Abstract:
Exercise in diabetes patients has many benefits but also several risks, of which hypoglycemia is most often discussed. We present a case with recurrent keto-acidosis post-exercise, in which we hypothesize that glycogen replacement strategies were insufficient. Our experience in this case and review of the literature emphasize the importance of discussing glycogen replacement strategies with your diabetic athletes.
Published:
2016
Title:
Red blood cell oleic acid levels reflect olive oil intake while omega-3 levels reflect fish intake and the use of omega-3 acid ethyl esters: The Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Heart Failure trial
Authors:
Harris, William S.; Masson, Serge; Barlera, Simona; Milani, Valentina; Pileggi, Silvana; Franzosi, Maria Grazia; Marchioli, Roberto; Tognoni, Gianni; Tavazzi, Luigi; Latini, Roberto; GISSI-HF Investigators
Abstract:
The Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Heart Failure (GISSI-HF) study reported benefits of n-3 fatty acid (FA) treatment on cardiovascular (CV) events, but the effects of treatment on a putative CV disease risk factor, the red blood cell (RBC) n-3 FA level (the omega-3 index), have not been examined in this context. We hypothesized that treatment with prescription omega-3 acid ethyl esters (O3AEE) would increase the omega-3 index to the proposed cardioprotective value of 8%. RBCs were collected from a subset of patients participating in the GISSI-HF study (n=461 out of 6975 randomized), at baseline and after 3 months of treatment with either an olive oil placebo or O3AEE (1 g/d). RBC FA levels were expressed as a percentage of total FA. Patients also reported their typical olive oil and fish intakes. RBC oleic acid levels were directly correlated with reported frequency of olive oil consumption, and the omega-3 index was correlated with reported fish intake (P for trends <0.001 for both). After treatment, the omega-3 index increased from 4.8±1.7% to 6.7±1.9% but was unchanged in the placebo group (4.7±1.7 to 4.8±1.5%) (P<.0001 for changes between groups). At 3 months, more patients reached the proposed target omega-3 index level of 8%-12% in the treated vs placebo group (22.6% vs. 1.3%, P
Published:
2016
Title:
Reduced or modified dietary fat for preventing cardiovascular disease
Authors:
Hooper, Lee; Summerbell, Carolyn D.; Thompson, Rachel; Sills, Deirdre; Roberts, Felicia G.; Moore, Helen J.; Smith, George Davey
Abstract:
AUTHORS' CONCLUSIONS: The findings are suggestive of a small but potentially important reduction in cardiovascular risk on modification of dietary fat, but not reduction of total fat, in longer trials. Lifestyle advice to all those at risk of cardiovascular disease and to lower risk population groups, should continue to include permanent reduction of dietary saturated fat and partial replacement by unsaturates. The ideal type of unsaturated fat is unclear.
Published:
2016
Title:
Remission of pre-diabetes to normal glucose tolerance in obese adults with high protein versus high carbohydrate diet: Randomized control trial
Authors:
Stentz, Frankie B.; Brewer, Amy; Wan, Jim; Garber, Channing; Daniels, Blake; Sands, Chris; Kitabchi, Abbas E.
Abstract:
© 2016, BMJ Publishing Group. All rights reserved. Objective: Remission of pre-diabetes to normal is an important health concern which has had little success in the past. This study objective was to determine the effect on remission of pre-diabetes with a high protein (HP) versus high carbohydrate (HC) diet and effects on metabolic parameters, lean and fat body mass in prediabetic, obese subjects after 6 months of dietary intervention. Research design and methods: We recruited and randomized 24 pre-diabetes women and men to either a HP (30% protein, 30% fat, 40% carbohydrate; n=12) or HC (15% protein, 30% fat, 55% carbohydrate; n=12) diet feeding study for 6 months in this randomized controlled trial. All meals were provided to subjects for 6 months with daily food menus for HP or HC compliance with weekly food pick-up and weight measurements. At baseline and after 6 months on the respective diets oral glucose tolerance and meal tolerance tests were performed with glucose and insulin measurements and dual energy X-ray absorptiometry scans. Results: After 6 months on the HP diet, 100% of the subjects had remission of their pre-diabetes to normal glucose tolerance, whereas only 33.3% of subjects on the HC diet had remission of their pre-diabetes. The HP diet group exhibited significant improvement in (1) insulin sensitivity (p=0.001), (2) cardiovascular risk factors (p=0.04), (3) inflammatory cytokines (p=0.001), (4) oxidative stress (p=0.001), (5) increased percent lean body mass (p=0.001) compared with the HC diet at 6 months. Conclusions: This is the first dietary intervention feeding study, to the best of our knowledge, to report 100% remission of pre-diabetes with a HP diet and significant improvement in metabolic parameters and anti-inflammatory effects compared with a HC diet at 6 months.
Published:
2016
Title:
Role of diet in development of (colon) cancer
Authors:
Roelandt, P.; Van Hootegem, A.; Tejpar, S.; Prenen, H.; Van Cutsem, E.
Abstract:
Diet and lifestyle have a great impact on our overall health, including the development of cancer. Despite the fact that most of the data come from epidemiological studies, wherein cause and consequence are sometimes difficult to unravel, there are some clear links between diet and colon cancer. A diet low in fibres, calcium and vitamin D on the one hand and rich in red/processed meat and fat on the other hand is associated with a higher incidence of colon cancer. Not only diet is related to carcinogenesis, also obesity and/or lack of physical activity increase the risk of cancer. While the role of dietary supplements is still questionable, the preventive role of acetylsalicylic acid is clear, although this effect is also most pronounced in high-risk patients. In recent years, there has been more and more interest in the gut microbiome. Every day, the gut bacteria metabolize dietary constituents through which toxic metabolites are formed, influencing the underlying intestinal cells in turn. The exact correlation between diet, gut microbiome and colon cancer has been formulated in several hypotheses, but additional research is needed before the gut microbiome will become relevant to clinical practice.
Published:
2016
Title:
SGLT2 Inhibition and cardiovascular events: why did EMPA-REG Outcomes surprise and what were the likely mechanisms?
Authors:
Sattar, Naveed; McLaren, James; Kristensen, Søren L.; Preiss, David; McMurray, John J.
Abstract:
© 2016, The Author(s).While the modest reduction in the primary composite outcome of myocardial infarction, stroke or cardiovascular death in the EMPA-REG Outcomes trial was welcome, the 30–40% reductions in heart failure hospitalisation (HFH) and cardiovascular and all-cause deaths in patients treated with empagliflozin were highly impressive and unexpected. In this review, we discuss briefly why cardiovascular endpoint trials for new diabetes agents are required and describe the results of the first four such trials to have reported, as a precursor to understanding why the EMPA-REG Outcomes results came as a surprise. Thereafter, we discuss potential mechanisms that could explain the EMPA-REG Outcomes results, concentrating on non-atherothrombotic effects. We suggest that the main driver of benefit may derive from the specific effects of sodium-glucose linked transporter-2 (SGLT2) inhibition on renal sodium and glucose handling, leading to both diuresis and improvements in diabetes-related maladaptive renal arteriolar responses. These haemodynamic and renal effects are likely to be beneficial in patients with clinical or subclinical cardiac dysfunction. The net result of these processes, we argue, is an improvement in cardiac systolic and diastolic function and, thereby, a lower risk of HFH and sudden cardiac death. We also discuss whether other drugs in this class are likely to show similar cardiovascular benefits. Finally, areas for future research are suggested to better understand the relevant mechanisms and to identify other groups who may benefit from SGLT2 inhibitor therapy.
Published:
2016
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