Short communication: Relationship between lysine/methionine ratios and glucose levels and their effects on casein synthesis via activation of the mechanistic target of rapamycin signaling pathway in bovine mammary epithelial cells
Wang, F. ; Baal, J. van; Ma, L. ; Loor, J.J. ; Wu, Z.L. ; Dijkstra, J. ; Bu, D.P. - \ 2019
Journal of Dairy Science 102 (2019)9. - ISSN 0022-0302 - p. 8127 - 8133.
amino acid - casein - glucose - mammary cell signaling
The synthesis of protein requires the availability of specific AA and a large supply of energy in bovine mammary epithelial cells (BMEC). Whether an interaction exists between Lys/Met ratio and glucose level on milk protein synthesis and its potential regulatory mechanism is unclear. We investigated the effects of different Lys/Met ratios and glucose levels on casein synthesis-related gene expression in BMEC to elucidate the underlying molecular mechanisms. Primary BMEC were subjected to 4 treatments for 36 h, arranged in a 2 × 2 factorial design with Lys/Met ratios of 3:1 (1.2:0.4 mM, LM3.0; total AA = 8.24 mM) and 2.3:1 (1.4:0.6 mM, LM2.3; total AA = 8.64 mM) and glucose levels of 17.5 mM (high glucose level) and 2.5 mM (low glucose level). No interactions between Lys/Met ratio and glucose level on cell viability, cell cycle progression, mRNA, or protein expression levels were found. High glucose level increased cell proliferation and promoted cell cycle transition from intermediate phase (G1 phase) to synthesis (S phase) by approximately 50%, whereas Lys/Met ratio had no effect. Both mRNA and protein abundance of αS1-casein and β-casein were positively affected by LM3.0, whereas a high glucose level increased protein abundance of αS1-casein and β-casein and increased gene expression of CSN1S1 but not of CSN2. Furthermore, high glucose increased the mRNA abundance of ELF5 and decreased that of GLUT8, enhanced protein expression of total and phosphorylated mechanistic target of rapamycin (mTOR), and decreased phosphorylated AMP-activated protein kinase (AMPK) levels. Treatment LM3.0 had a stimulatory effect on total and phosphorylated mTOR but did not affect AMPK phosphorylation. The mRNA levels of JAK2, ELF5, and RPS6KB1 were upregulated and mRNA levels of EIF4EBP1 were downregulated with LM3.0 compared with LM2.3. Our results indicate that casein synthesis was regulated by Lys/Met ratio via JAK2/ELF5, mTOR, and its downstream RPS6KB1 and EIF4EBP1 signaling. In contrast, glucose regulated casein synthesis through promoting cell proliferation, accelerating cell cycle progression, and activating the ELF5 and AMPK/mTOR signaling pathways. Within the range of substrate levels in the present study, a change in Lys/Met ratio had a stronger effect on abundance of αS1-casein and β-casein than a change in glucose level.
A Medicago truncatula SWEET transporter implicated in arbuscule maintenance during arbuscular mycorrhizal symbiosis
An, Jianyong ; Zeng, Tian ; Ji, Chuanya ; Graaf, Sanne de; Zheng, Zijun ; Xiao, Ting Ting ; Deng, Xiuxin ; Xiao, Shunyuan ; Bisseling, Ton ; Limpens, Erik ; Pan, Zhiyong - \ 2019
New Phytologist 224 (2019)1. - ISSN 0028-646X - p. 396 - 408.
arbuscular mycorrhiza (AM) - glucose - Medicago truncatula - sugar export - SWEET - symbiosis
Plants form a mutualistic symbiosis with arbuscular mycorrhizal (AM) fungi, which facilitates the acquisition of scarce minerals from the soil. In return, the host plants provide sugars and lipids to its fungal partner. However, the mechanism by which the AM fungi obtain sugars from the plant has remained elusive. In this study we investigated the role of potential SWEET family sugar exporters in AM symbiosis in Medicago truncatula. We show that M. truncatula SWEET1b transporter is strongly upregulated in arbuscule-containing cells compared to roots and localizes to the peri-arbuscular membrane, across which nutrient exchange takes place. Heterologous expression of MtSWEET1b in a yeast hexose transport mutant showed that it mainly transports glucose. Overexpression of MtSWEET1b in M. truncatula roots promoted the growth of intraradical mycelium during AM symbiosis. Surprisingly, two independent Mtsweet1b mutants, which are predicted to produce truncated protein variants impaired in glucose transport, exhibited no significant defects in AM symbiosis. However, arbuscule-specific overexpression of MtSWEET1bY57A/G58D, which are considered to act in a dominant-negative manner, resulted in enhanced collapse of arbuscules. Taken together, our results reveal a (redundant) role for MtSWEET1b in the transport of glucose across the peri-arbuscular membrane to maintain arbuscules for a healthy mutually beneficial symbiosis.
The uptake of carbon sources by Aspergillus niger
Sloothaak, Jasper - \ 2017
Wageningen University. Promotor(en): Vitor Martins dos Santos, co-promotor(en): P.J. Schaap; J.A. Tamayo-Ramos. - Wageningen : Wageningen University - ISBN 9789463432085 - 179
aspergillus niger - carbon - proteomes - glucose - cell membranes - markov processes - organic acids - aspergillus niger - koolstof - proteomen - glucose - celmembranen - markov-processen - organische zuren
Fungi have been used as food and in food fermentations long before written accounts were created and they have been used in folk medicine in ancient cultures. For centuries, species of the genus Aspergillus have been used for the preparation of traditional Asian foodstuffs or together with baker’s yeast in preparation of alcoholic beverages and have therefore been of great economical value. Later, Aspergillus niger has been used for large-scale production of organic acids, enzymes and other food-additives. Today, we aim to harness its saprophytic nature and extraordinary ability to degrade and utilize plant material that is naturally recalcitrant to degradation. To facilitate that ability, the range of sugar transporters employed by this fungus is large even among fungi. This makes it an excellent choice for the identification and characterization of a variety of proteins with different substrate specificities, with potential application in the design of newly engineered cell factories. This thesis was focused on the identification and characterization of previously unknown sugar uptake transporters. Aspergillus niger transporter proteins for the uptake of glucose, xylose, galacturonic acid and rhamnose were identified and characterized.
Biobased itaconzuur en methacrylzuur : Chemische bouwstenen van de toekomst
Es, D.S. van - \ 2016
Fluids Processing Benelux (2016)4. - ISSN 1874-7914 - p. 46 - 47.
biobased economy - chemie op basis van biologische grondstoffen - chemicaliën uit biologische grondstoffen - zuren - biomassa - glucose - biochemie - biobased economy - biobased chemistry - biobased chemicals - acids - biomass - glucose - biochemistry
Wageningen UR Food & Biobased Research is van plan een flinke stap te zetten in de productie van biobased itaconzuur en methacrylzuur. Deze zuren kunnen bouwstenen zijn voor hoogwaardige materialen, zoals biobased verf en drukinkt. De stoffen worden geproduceerd uit biomassa (glucose) en vormen alternatieven voor fossiele grondstoffen. Voor verdere ontwikkeling wordt samengewerkt met de Amerikaanse agrifoodproducent Archer Daniels Midland, leverancier voor de verfindustrie EOC Belgium en de Nederlandse verfproducent Van Wijhe Verf. Daan van Es, is senioronderzoeker bij Wageningen UR en treedt op als projectleider.
Programming effects of glucose, fructose or galactose in post-weaning diet on adiposity and serum adipokines in adult mice
Bouwman, L.M.S. ; Fernández Calleja, J.M.S. ; Keijer, J. ; Oosting, A. ; Schothorst, E.M. van - \ 2016
programming effects - glucose - fructose - post-weaning diet - adiposity - serum adipokines
Replacing lactose from calf milk replacers : effects on digestion and post-absorptive metabolism
Gilbert, M.S. - \ 2015
Wageningen University. Promotor(en): Wouter Hendriks, co-promotor(en): Walter Gerrits; Henk Schols. - Wageningen : Wageningen University - ISBN 9789462576032 - 171
vleeskalveren - lactose - kunstmelk - polysacchariden - glucose - fructose - glycerol - zetmeelvertering - metabolisme - fermentatie - kalvervoeding - diervoeding - voedingsfysiologie - veal calves - lactose - filled milk - polysaccharides - glucose - fructose - glycerol - starch digestion - metabolism - fermentation - calf feeding - animal nutrition - nutrition physiology
Summary PhD thesis Myrthe S. Gilbert
Replacing lactose from calf milk replacers – Effects on digestion and post-absorptive metabolism
Veal calves are fed milk replacer (MR) and solid feed. The largest part of the energy provided to veal calves originates from the MR. Calf MR contains 40 to 50% lactose, originating from whey, a by-product from cheese production. High and strongly fluctuating dairy prices are a major economic incentive to replace lactose from the calf MR by alternative energy sources. The objective of this thesis was to study the effects of replacing lactose from calf MR on nutrient digestion and fermentation and post-absorptive metabolism.
In Chapter 2 and 3, four starch products (SP) were evaluated for replacing lactose. The four SP differed in size and branching, and consequently required different ratios of starch-degrading enzymes for their complete hydrolysis to glucose. Gelatinized starch required α-amylase and (iso)maltase; maltodextrin required (iso)maltase and α-amylase; maltodextrin with α-1,6-branching required isomaltase, maltase and α-amylase and maltose required maltase. In Chapter 2, adaptation to these SP was assessed during 14 weeks, using a within-animal titration study. Forty male Holstein-Friesian calves (n = 8 per treatment) were assigned to either a lactose control MR or one of four titration strategies, each testing the stepwise exchange of lactose for one of the SP. For control calves, fecal dry matter (DM) content and fecal pH did not change over time. The response in fecal DM content and fecal pH in time did not differ between SP treatments and decreased linearly with 0.57% and 0.32 per week, respectively, where one week corresponded to an increase in SP inclusion of 3%. This indicates that the capacity for starch digestion was already exceeded at low inclusion levels, resulting in SP fermentation. All SP required maltase to achieve complete hydrolysis to glucose and it was, therefore, suggested that maltase is the rate-limiting enzyme in starch digestion in milk-fed calves.
Following the titration, a fixed inclusion level of 18% of the SP in the MR was applied. Effects on starch-degrading enzyme activity, nutrient disappearance, SP fermentation and jugular glucose appearance were measured (Chapter 3). Lactase activity in the brush border was high in the proximal small intestine of all calves, resulting in a high apparent ileal disappearance of lactose (≥ 99% of intake). Maltase and isomaltase activities in the brush border were not increased for any of the SP treatments. Luminal α-amylase activity was lower in the proximal small intestine but greater in the distal small intestine of SP-fed calves compared to control calves. This amylase activity in the distal small intestine of SP-fed calves might have been of microbial origin. Apparent SP disappearance did not differ between SP treatments. The difference between apparent ileal (62%) and total tract (99%) SP disappearance indicated substantial SP fermentation in the large intestine (37% of intake). In addition, total tract SP fermentation was quantified using fecal 13C excretion which originated from the naturally 13C-enriched corn SP. Total tract SP fermentation averaged 89% of intake, regardless of SP treatment. MR leaking into the reticulorumen was measured as the recovery of Cr in the reticulorumen at slaughter after feeding MR pulse-dosed with Cr 4h prior to slaughter. MR leaking into the reticulorumen averaged 11% for SP-fed calves. By difference, this leaves 41% of the SP intake fermented in the small intestine. This coincided with increased fecal nitrogen (N) and DM losses for SP-fed calves. However, apparent total tract crude fat disappearance tended to increase when replacing lactose with SP. The substantial SP fermentation indicates that only 10% of the SP intake was enzymatically hydrolyzed and absorbed as glucose. This was in agreement with the marginal increase in 13C enrichment in peripheral plasma glucose after feeding naturally 13C-enriched gelatinized starch and maltose, compared to a clear increase after feeding naturally 13C-enriched lactose to control calves. It was concluded that fermentation, rather than enzymatic digestion, is the main reason for small intestinal starch disappearance in milk-fed calves. The expected decrease in growth performance with such extensive SP fermentation is partially compensated by the greater crude fat digestion and possibly by a reduced urinary glucose excretion when replacing lactose with SP.
Glucose, fructose and glycerol do not require enzymatic hydrolysis and can be absorbed directly from the small intestine. However, these lactose replacers might differentially affect glucose and insulin metabolism and with that energy partitioning. The effects of partly replacing lactose with glucose, fructose or glycerol on energy and N partitioning and glucose homeostasis and insulin sensitivity were, therefore, studied in Chapter 4 and 5. Forty male Holstein-Friesian calves either received a lactose control MR or a MR in which one third of the lactose was replaced with glucose, fructose or glycerol (n = 10 per treatment). Energy and N retention were not affected by MR composition. Fructose absorption from the small intestine was incomplete resulting in fructose fermentation. This resulted in fecal losses of DM, energy and N and the lowest numerical energy and N retention for fructose-fed calves. Postprandial plasma concentrations of glucose exceeded the renal threshold for glucose in glucose-fed calves and control calves, which resulted in urinary glucose excretion. Glycerol was likely excreted with the urine of glycerol-fed calves. Oxidation of glucose, fructose and glycerol was quantified by feeding a single dose of [U-13C]glucose, [U-13C]fructose or [U-13C]glycerol with the MR and subsequently measuring 13CO2 production. Oxidation of lactose replacers did not differ between lactose replacers and averaged 72% of intake. However, the time at which the maximum rate of oxidation was reached was delayed for fructose-fed compared to glucose-fed and glycerol-fed calves, indicating that fructose was converted into other substrates before being oxidized. Conversion of fructose and glycerol into glucose was confirmed by an increase in 13C enrichment of peripheral plasma glucose after feeding [U-13C]fructose and [U-13C]glycerol, respectively. Insulin sensitivity did not differ between MR treatments, but was already low at the start of the experiment at 15 weeks of age and remained low throughout the experiment. It was concluded that glucose and glycerol can replace one third of the lactose from the calf MR, but that inclusion of fructose should be lower to prevent incomplete absorption from the small intestine.
In literature and the studies in this thesis, high inter-individual variation in growth performance was found in veal calves. The experiment described in Chapter 6 was, therefore, designed to assess the predictability of later life growth performance by charactering calves in early life. In addition, it was examined whether the ability of calves to cope with MR in which lactose is partially replaced by alternative energy sources can be predicted. From 2 to 11 weeks of age, male Holstein-Friesian calves were fed a lactose control MR and solid feed according to a practical feeding scheme and were characterized individually using targeted challenges related to feeding motivation, digestion, post-absorptive metabolism, immunology, behavior and stress. Based on the results in Chapter 4, a combination of glucose, fructose and glycerol in a 2:1:2 ratio was used to replace half of the lactose from the MR (GFG). From 11 to 27 weeks of age, calves received a lactose control MR or the GFG MR (n = 65 per treatment). Growth performance from 11 to 27 weeks of age tended to be lower for GFG-fed than for control calves (-25 g/d). Measurements in early life explained 12% of the variation in growth performance in later life. However, this was mainly related to variation in solid feed refusals. When growth performance was adjusted to equal solid feed intake, only 4% of the variation in standardized growth performance in later life, reflecting feed efficiency, could be explained by early life measurements. This indicates that > 95% of the variation in feed efficiency in later life could not be explained by early life characterization. It is hypothesized that variation in health status explains substantial variation in feed efficiency in veal calves. Significant relations between fasting plasma glucose concentrations, fecal dry matter and fecal pH in early life and feed efficiency in later life depended on MR composition. These measurements are, therefore, potential tools for screening calves in early life on their ability to cope with a MR in which half of the lactose is replaced by glucose, fructose and glycerol (in a 2:1:2 ratio).
The studies reported in this thesis demonstrate that glycerol, glucose and a combination of glucose, fructose and glycerol in a 2:1:2 ratio are promising lactose replacers. The effects of replacing lactose by other carbohydrate or energy sources described in this thesis are required to evaluate the potential of lactose replacers for inclusion in calf milk replacers and provide input for feed evaluation for calves and ruminants.
Effect of dietary protein on lipid and glucose metabolism: implications for metabolic health
Rietman, A. - \ 2015
Wageningen University. Promotor(en): Frans Kok; D. Tomé, co-promotor(en): Marco Mensink. - Wageningen : Wageningen University - ISBN 9789462573482 - 160
voeding en gezondheid - stofwisselingsstoornissen - eiwitinname - dieet - metabolisme - lipiden - glucose - macronutriënten - nutrition and health - metabolic disorders - protein intake - diet - metabolism - lipids - glucose - macronutrients
Background: Diet is an important factor in the development of the Metabolic Syndrome (Mets) and type 2 Diabetes Mellitus. Accumulation of intra hepatic lipid (IHL) can result in non-alcoholic fatty liver disease (NAFLD), which is sometimes considered the hepatic manifestation of Mets. Manipulation of the dietary macronutrient composition – altering either fat or simple carbohydrates – has the potential to change lipid storage in the liver. Protein also has this ability, however human data is scarce. Moreover, high dietary protein intake is linked with an increased type 2 Diabetes risk. Therefore, it is essential to study the metabolic consequences of changes in macronutrient composition focussing on altering dietary protein quantity.
Objective: In this thesis the effects of dietary protein on metabolic health focusing on lipid and glucose metabolism were investigated in both observational studies as well as in a human dietary intervention trial.
Methods: In an observational study (n=1283), Fatty Liver Index (FLI) was calculated and related to macronutrient consumption from dietary assessment data. In a controlled dietary intervention, participants (n=27) were assigned to either a control-diet for 4 weeks, or a high-fat, hypercaloric diet, with either a high-protein or a normal-protein content for two weeks, and vice versa. Measurements of IHL (1H-MRS) and blood plasma glucose and lipid concentrations were performed, both in the fasting state and following a meal.
Results: In the observational study, the prevalence of fatty liver as indicated by an FLI>60, was 22.0%. Compared to persons with a normal FLI score of <30, protein intake was positively related with high FLI score >60 (OR: 1.26 per 1 en%, 95%CI 1.16-1.37). This was in particular the case for protein intake from animal sources. In the dietary intervention study, the high-protein diet compared to the normal-protein diet resulted in lower IHL and plasma TG concentrations (IHL: 0.35 ± 0.04 % vs. 0.51 ± 0.08 %; p=0.08; TG: 0.65 ± 0.03 vs. 0.77 ± 0.05 mmol/L; p=0.07). Furthermore, after the meal challenge the free fatty acids (FFA) response was significant different between all three intervention diets (p=0.03). Moreover, the postprandial glucose response was significantly lower after adaptation to NP compared with HP (p=0.03), without differences in the postprandial insulin responses (p=0.37).
Conclusions: From data of the intervention study and observational studies reported in this thesis, it can be concluded that dietary protein intake is associated with alterations in metabolic profile, with both favourable and potential unfavorable health outcomes. On the short term increasing dietary protein in healthy subjects improved lipid metabolism, as seen by lower TG and IHL levels, but not glucose metabolism. On the long term, however, a high-protein intake was related to a fatty liver, and associated to insulin resistance.
Using bioconductor package BiGGR for metabolic flux estimation based on gene expression changes in brain
Gavai, A.K. ; Supandi, F. ; Hettling, H. ; Murrell, P. ; Leunissen, J.A.M. ; Beek, J.H.G.M. van - \ 2015
PLoS ONE 10 (2015)3. - ISSN 1932-6203 - 21 p.
alzheimers-disease - energy-metabolism - balance analysis - in-silico - models - glucose - biology - networks - neurons - oxygen
Predicting the distribution of metabolic fluxes in biochemical networks is of major interest in systems biology. Several databases provide metabolic reconstructions for different organisms. Software to analyze flux distributions exists, among others for the proprietary MATLAB environment. Given the large user community for the R computing environment, a simple implementation of flux analysis in R appears desirable and will facilitate easy interaction with computational tools to handle gene expression data. We extended the R software package BiGGR, an implementation of metabolic flux analysis in R. BiGGR makes use of public metabolic reconstruction databases, and contains the BiGG database and the reconstruction of human metabolism Recon2 as Systems Biology Markup Language (SBML) objects. Models can be assembled by querying the databases for pathways, genes or reactions of interest. Fluxes can then be estimated by maximization or minimization of an objective function using linear inverse modeling algorithms. Furthermore, BiGGR provides functionality to quantify the uncertainty in flux estimates by sampling the constrained multidimensional flux space. As a result, ensembles of possible flux configurations are constructed that agree with measured data within precision limits. BiGGR also features automatic visualization of selected parts of metabolic networks using hypergraphs, with hyperedge widths proportional to estimated flux values. BiGGR supports import and export of models encoded in SBML and is therefore interoperable with different modeling and analysis tools. As an application example, we calculated the flux distribution in healthy human brain using a model of central carbon metabolism. We introduce a new algorithm termed Least-squares with equalities and inequalities Flux Balance Analysis (Lsei-FBA) to predict flux changes from gene expression changes, for instance during disease. Our estimates of brain metabolic flux pattern with Lsei-FBA for Alzheimer’s disease agree with independent measurements of cerebral metabolism in patients. This second version of BiGGR is available from Bioconductor
Analysis of by-product formation and sugar monomerization in sugarcane bagasse pretreated at pilot plant scale: Differences between autohydrolysis, alkaline and acid pretreatment
Pol, E.C. van der; Bakker, R. ; Zeeland, A.N.T. van; Sanchez Garcia, D. ; Punt, A.M. ; Eggink, G. - \ 2015
Bioresource Technology 181 (2015). - ISSN 0960-8524 - p. 114 - 123.
saccharomyces-cerevisiae - degradation-products - wet oxidation - hydrolysis - ethanol - fermentations - cellulose - glucose - biomass
Sugarcane bagasse is an interesting feedstock for the biobased economy since a large fraction is polymerized sugars. Autohydrolysis, alkaline and acid pretreatment conditions combined with enzyme hydrolysis were used on lignocellulose rich bagasse to acquire monomeric. By-products found after pretreatment included acetic, glycolic and coumaric acid in concentrations up to 40, 21 and 2.5 g/kg dry weight bagasse respectively. Alkaline pretreated material contained up to 45 g/kg bagasse DW of sodium. Acid and autohydrolysis pretreatment results in a furan formation of 14 g/kg and 25 g/kg DW bagasse respectively. Enzyme monomerization efficiencies of pretreated solid material after 72 h were 81% for acid pretreatment, 77% for autohydrolysis and 57% for alkaline pretreatment. Solid material was washed with superheated water to decrease the amount of by-products. Washing decreased organic acid, phenol and furan concentrations in solid material by at least 60%, without a major sugar loss.
Inulin-type fructans modulate intestinal Bifidobacterium species populations and decrease fecal short-chain fatty acids in obese women
Salazar, N. ; Dewulf, E.M. ; Neyrinck, A.M. ; Bindels, L.B. ; Cani, P.D. ; Mahillon, J. ; Vos, W.M. de; Thissen, J.P. ; Gueimonde, M. ; Reyes-Gavilán, C.G. de los; Delzenne, N.M. - \ 2015
Clinical Nutrition 34 (2015)3. - ISSN 0261-5614 - p. 501 - 507.
gradient gel-electrophoresis - protein-coupled receptor - gut microbiota - mice - prebiotics - increases - glucose - diet - pcr - fermentation
Background & aims : Inulin-type fructans (ITF) prebiotics promote changes in the composition and activity of the gut microbiota. The aim of this study was to determine variations on fecal short chain fatty acids (SCFA) concentration in obese women treated with ITF and to explore associations between Bifidobacterium species, SCFA and host biological markers of metabolism. Methods Samples were obtained in a randomized, double blind, parallel, placebo-controlled trial, with 30 obese women randomly assigned to groups that received either 16 g/day ITF (n = 15) or maltodextrin (n = 15) for 3 months. The qualitative and quantitative analysis of Bifidobacterium spp. was performed in feces by PCR-DGGE and q-PCR, and SCFA profile was analyzed by gas chromatography. Spearman correlation analysis was performed between the different variables analyzed. Results The species Bifidobacterium longum, Bifidobacterium pseudocatenulatum and Bifidobacterium adolescentis were significantly increased at the end of the treatment in the prebiotic group (p <0.01) with being B. longum negatively correlated with serum lipopolysaccharide (LPS) endotoxin (p <0.01). Total SCFA, acetate and propionate, that positively correlated with BMI, fasting insulinemia and homeostasis model assessment (HOMA) (p <0.05), were significantly lower in prebiotic than in placebo group after the treatment period. Conclusions ITF consumption selectively modulates Bifidobacterium spp. and decreases fecal SCFA concentration in obese women. ITF could lessen metabolic risk factors associated with higher fecal SCFA concentration in obese individuals.
The effects of functional fiber on postprandial glycemia, energy intake, satiety, palatability and gastrointestinal wellbeing: a randomized crossover trial
Yuan, J.Y.F. ; Smeele, R.J.M. ; Harington, K.D. ; Loon, F.M. van; Wanders, A.J. ; Venn, B.J. - \ 2014
Nutrition Journal 13 (2014). - ISSN 1475-2891
type-2 diabetes-mellitus - desk-top guide - dietary fiber - digestive tolerance - insulin - foods - metaanalysis - glucose - index
Background: Fiber intakes in developed countries are generally below those recommended by relevant authorities. Given that many people consume fiber-depleted refined-grain products, adding functional fiber will help to increase fiber intakes. The objective of the study was to determine metabolic and sensory effects of adding fiber to bread. Methods: A double-blind pair of randomized crossover trials with a two-week washout in which two fiber-containing breads were compared with control bread. The functional fiber (fruit fiber and FibreMax (TM)) was added to yield 10 g fiber per serve (two slices). Eighty participants (n = 37 fruit fiber and n = 43 FibreMax (TM)) consumed one serve of bread (fiber or control) followed three hours later by a pasta meal consumed ad libitum. Outcome measures included glycemia, satiety, palatability, gastrointestinal wellbeing, visual appeal and subsequent energy intake of the pasta meal. Multivariate regression was undertaken to test for differences between treatment and control for blood glucose, satiety, and cumulative energy intake. Satiety responses were also compared by splitting the data into an immediate response after eating (0-30 min) and a return to hunger analysis (30-180 min). A Wilcoxon sign rank test was used for the first component (0-30 min) and Wilcoxon matched-pairs signed-rank test for the second component (30-180 min). Between treatment differences for gastrointestinal wellbeing were tested using Pearson's chi-square test or Fisher's exact test. Results: Consumption of the fruit fiber bread reduced postprandial glycemia by 35% (95% CI 13 to 51; P = 0.004) and cumulative energy intake by 368 kJ (95% CI 163 to 531; P = 0.001). There was little influence on satiety and the bread was rated as having poor taste and smell whilst generating feelings of nausea in some participants. FibreMax (TM) enriched bread reduced glycemia by 43% (95% CI 17 to 61; P = 0.004) without influence on energy intake or satiety. Apart from a lower visual appeal, the FibreMax (TM) bread was palatable. Neither bread caused gastrointestinal discomfort related to flatulence or bloating. Conclusions: Enriching bread with 10 g of functional fiber per serve is feasible although reformulation is needed to create not only an acceptable bread, but a desirable product.
Differential effects of proteins and carbohydrates on postprandial blood pressure-related responses
Teunissen-Beekman, K.F.M. ; Dopheide, J. ; Geleijnse, J.M. ; Bakker, S.J.L. ; Brink, E.J. ; Leeuw, P.W. de; Serroyen, J. ; Baak, M.A. van - \ 2014
The British journal of nutrition 112 (2014)4. - ISSN 0007-1145 - p. 600 - 608.
randomized controlled-trials - plasma amino-acids - healthy-subjects - insulin responses - dietary-protein - overweight adults - energy-intake - whey-protein - glucose - fructose
Diet composition may affect blood pressure (BP), but the mechanisms are unclear. The aim of the present study was to compare postprandial BP-related responses to the ingestion of pea protein, milk protein and egg-white protein. In addition, postprandial BP-related responses to the ingestion of maltodextrin were compared with those to the ingestion of sucrose and a protein mix. We hypothesised that lower postprandial total peripheral resistance (TPR) and BP levels would be accompanied by higher plasma concentrations of nitric oxide, insulin, glucagon-like peptide 1 (GLP-1) and glucagon. On separate occasions, six meals were tested in a randomised order in forty-eight overweight or obese adults with untreated elevated BP. Postprandial responses of TPR, BP and plasma concentrations of insulin, glucagon, GLP-1 and nitrite, nitroso compounds (RXNO) and S-nitrosothiols (NOx) were measured for 4 h. No differences were observed in TPR responses. Postprandial BP levels were higher after the ingestion of the egg-white-protein meal than after that of meals containing the other two proteins (P
Autophagy in adipose tissue and the beta cell: implications for obesity and diabetes
Stienstra, R. ; Haim, Y. ; Riahi, Y. ; Netea, M.G. ; Rudich, A. ; Leibowitz, G. - \ 2014
Diabetologia 57 (2014)8. - ISSN 0012-186X - p. 1505 - 1516.
endoplasmic-reticulum stress - unfolded protein response - pancreatic b-cell - insulin-secretion - proinflammatory response - protective role - kappa-b - pathway - metabolism - glucose
Autophagy is a lysosomal degradation pathway recycling intracellular long-lived proteins and damaged organelles, thereby maintaining cellular homeostasis. In addition to inflammatory processes, autophagy has been implicated in the regulation of adipose tissue and beta cell functions. In obesity and type 2 diabetes autophagic activity is modulated in a tissue-dependent manner. In this review we discuss the regulation of autophagy in adipose tissue and beta cells, exemplifying tissue-specific dysregulation of autophagy and its implications for the pathophysiology of obesity and type 2 diabetes. We will highlight common themes and outstanding gaps in our understanding, which need to be addressed before autophagy could be envisioned as a therapeutic target for the treatment of obesity and diabetes.
Colorectal cancer risk and dyslipidemia: a case-cohort study nested in an Italian multicentre cohort
Agnoli, C. ; Grioni, S. ; Sieri, S. ; Sacerdote, C. ; Vineis, P. ; Tumino, R. ; Giurdanella, M.C. ; Pala, V. ; Mattiello, A. ; Chiodini, P. ; Iacoviello, L. ; Curtis, A. de; Cattaneo, L. ; Duijnhoven, F.J.B. van - \ 2014
Cancer Epidemiology 38 (2014)2. - ISSN 1877-7821 - p. 144 - 151.
metabolic syndrome - serum-cholesterol - colon-cancer - lipoprotein levels - blood-cholesterol - glucose - triglyceride - association - nutrition - lipids
Background: Dyslipidemia is an established risk factor for many diseases, but its effect on colorectal cancer risk is less clear. We investigated the association of colorectal cancer risk with plasma triglycerides, total, HDL, and LDL cholesterol in four Italian EPIC centers. Methods: We conducted a case-cohort study on participants recruited to four Italian EPIC centers (Turin, Varese, Naples, and Ragusa; 34,148 subjects). A random subcohort of 850 subjects was obtained and 286 colorectal cancer cases were diagnosed. Triglycerides, total and HDL cholesterol were determined in plasma samples obtained at baseline and stored at -196 degrees C; LDL cholesterol was calculated. Hazard ratios (HR) with 95% confidence intervals (CI), adjusted for potential confounders, were estimated by Cox regression models using the Prentice method. Results: The highest tertiles of total (HR 1.66, 95% CI 1.12-2.45) and LDL cholesterol (HR 1.87, 95% CI 1.27-2.76) were associated with increased colorectal cancer risk compared to lowest tertiles. Risks were greater for men than women, and for postmenopausal than premenopausal women. Highest tertiles of total and LDL cholesterol were also significantly associated with increased risks of colon cancer, distal colon cancer, and rectal cancer, but not proximal colon cancer. Conclusions: Our findings suggest that high levels of total and LDL cholesterol increase colorectal cancer risk, particularly in men and postmenopausal women. However additional studies are needed to clarify the role of plasma lipids in these cancers, particularly in view of the conflicting findings of previous studies. (C) 2014 Elsevier Ltd. All rights reserved.
Adipose tissue metabolism and inflammation are differently affected by weight loss in obese mice due to either a high-fat diet restriction or change to a low-fat diet
Hoevenaars, F.P.M. ; Keijer, J. ; Herreman, L. ; Palm, I.F. ; Hegeman, M.A. ; Swarts, J.J.M. ; Schothorst, E.M. van - \ 2014
Genes & Nutrition 9 (2014). - ISSN 1555-8932 - 11 p.
nicotinamide nucleotide transhydrogenase - c57bl/6j mice - mitochondrial biogenesis - energy restriction - insulin-resistance - glucose - acid - expression - health - gene
Restriction of a high-fat diet (HFD) and a change to a low-fat diet (LFD) are two interventions that were shown to promote weight loss and improve parameters of metabolic health in obesity. Examination of the biochemical and molecular responses of white adipose tissue (WAT) to these interventions has not been performed so far. Here, male C57BL/6JOlaHsd mice, harboring an intact nicotinamide nucleotide transhydrogenase gene, were fed a purified 40 energy% HFD for 14 weeks to induce obesity. Afterward, mice were divided into three dietary groups: HFD (maintained on HFD), LFD (changed to LFD with identical ingredients), and HFD-CR (restricted to 70 % of the HFD). The effects of the interventions were examined after 5 weeks. Beneficial effects were seen for both HFD-CR and LFD (compared to HFD) regarding physiological parameters (body weight and fat mass) and metabolic parameters, including circulating insulin and leptin levels. Macrophage infiltration in WAT was reduced by both interventions, although more effectively by HFDCR. Strikingly, molecular parameters in WAT differed between HFD-CR and LFD, with increased activation of mitochondrial carbohydrate and fat metabolism in HFDCR mice. Our results confirm that restriction of the amount of dietary intake and reduction in the dietary energy content are both effective in inducing weight loss. The larger decrease in WAT inflammation and increase in mitochondrial carbohydrate metabolism may be due to a larger degree of energy restriction in HFD-CR, but could also be due to superior effectiveness of dietary restriction in weight loss strategies.
Smoking and long-term risk of type 2 Diabetes: The EPIC-InterAct Study in European populations
The InterAct Consortium, A. ; Spijkerman, A.M.W. ; A, D.L. van der; Nilsson, P. ; Balkau, B. ; Beulens, J.W.J. ; Boeing, H. ; Feskens, E.J.M. ; Kaaks, R. - \ 2014
Diabetes Care 37 (2014)12. - ISSN 0149-5992 - p. 3164 - 3171.
kora s4/f4 cohort - middle-aged men - cigarette-smoking - insulin-resistance - physical-activity - fat distribution - active smoking - mellitus - women - glucose
OBJECTIVE The aims of this study were to investigate the association between smoking and incident type 2 diabetes, accounting for a large number of potential confounding factors, and to explore potential effect modifiers and intermediate factors. RESEARCH DESIGN AND METHODS The European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct is a prospective case-cohort study within eight European countries, including 12,403 cases of incident type 2 diabetes and a random subcohort of 16,835 individuals. After exclusion of individuals with missing data, the analyses included 10,327 cases and 13,863 subcohort individuals. Smoking status was used (never, former, current), with never smokers as the reference. Country-specific Prentice-weighted Cox regression models and random-effects meta-analysis were used to estimate hazard ratios (HRs) for type 2 diabetes. RESULTS In men, the HRs (95% CI) of type 2 diabetes were 1.40 (1.26, 1.55) for former smokers and 1.43 (1.27, 1.61) for current smokers, independent of age, education, center, physical activity, and alcohol, coffee, and meat consumption. In women, associations were weaker, with HRs (95% CI) of 1.18 (1.07, 1.30) and 1.13 (1.03, 1.25) for former and current smokers, respectively. There was some evidence of effect modification by BMI. The association tended to be slightly stronger in normal weight men compared with those with overall adiposity. CONCLUSIONS Former and current smoking was associated with a higher risk of incident type 2 diabetes compared with never smoking in men and women, independent of educational level, physical activity, alcohol consumption, and diet. Smoking may be regarded as a modifiable risk factor for type 2 diabetes, and smoking cessation should be encouraged for diabetes prevention.
Nutrition and cognition in older adults : studies on the role of glucose, sucrose, protein, vitamin B12 and folic acid
Zwaluw, N.L. van der - \ 2014
Wageningen University. Promotor(en): Lisette de Groot, co-promotor(en): Ondine van de Rest; Rosalie Dhonukshe-Rutten. - Wageningen : Wageningen University - ISBN 9789462571075 - 184
ouderenvoeding - voeding - ouderen - kenvermogen - glucose - sucrose - eiwittoevoegingen - vitamine b12 - dementie - elderly nutrition - nutrition - elderly - cognition - glucose - sucrose - protein supplements - vitamin b12 - dementia
The age-related cognitive decline and the increase in dementia patients are large problems in societies with growing ageing populations. No cure is present for dementia, while the available medication only focuses on alleviating symptoms. It is therefore of major importance to find risk factors that can modify the development of cognitive decline and dementia. Pre-clinical and observational studies suggest a role for nutrients. Evidence derived from randomized controlled trials (RCTs) is, however, limited and equivocal with most studies showing no effect and only a few studies showing a beneficial effect of a nutritional intervention. In the current thesis, we investigated the acute and longer-term effects of different nutrients, i.e. glucose and sucrose, protein, resistance-type exercise training with or without protein, and vitamin B12 and folic acid in order to optimize and preserve cognitive functions in non-demented elderly people.
A comprehensive literature review was performed on the acute effects of glucose and sucrose on cognitive performance (Chapter 2). Glucose is the most important fuel for the brain, and as such, manipulation of the supply of glucose may affect cognitive functions. The main conclusion of our review was that a glucose load may have a short-term beneficial effect on episodic memory. Enhancing effects on other cognitive domains were less clear, partly due to the small number of studies examining these effects. Limited research was also done on the possible effects of sucrose on cognitive functions. Therefore, we investigated the acute effects of 50 g of glucose and 100 g of sucrose on a broad spectrum of cognitive functions reflecting performance on episodic memory, working memory, attention and information processing speed, and executive functions (Chapter 3). This was done by a cross-over study in 43 elderly participants who had self-reported memory complaints. In contrast to the conclusion of our review, we did not observe an effect of glucose or sucrose on episodic memory, though we showed a beneficial effect of sucrose on attention and information processing speed.
Protein supplementation was the next nutritional intervention that was investigated. Several amino acids are precursors for neurotransmitters, and their supply may affect the synthesis and release of these neurotransmitters, and may consequently affect cognitive performance. A 24-week randomized placebo-controlled trial was carried out in 65 frail and pre-frail elderly people (Chapter 4). The protein supplementation included twice a day 15 grams of protein in the form of a drink. Reaction time improved more in the protein group compared to the placebo group, but the scores on the cognitive domains, i.e. episodic memory, attention and working memory, information processing speed, and executive functions, or the other single test scores, did not differ between treatment groups. In addition, we investigated the effects of 24 weeks resistance-type exercise training with and without protein supplementation in pre-frail and frail elderly people (Chapter 5). Exercise training without extra protein (n=62) improved performance on the domain attention and working memory. Exercise training together with protein supplementation (n=65) improved performance on information processing speed.
Last, the role of vitamin B12 and folate on cognitive health was investigated. Low levels of these nutrients can increase homocysteine levels, which is a suggested risk factor for cognitive decline. The effect of daily supplementation with 500 µg vitamin B12 and 400 µg folic acid was investigated in 2,919 participants for two years (Chapter 6). Global cognitive function and episodic memory were assessed in the total study population, whereas extensive neuropsychological testing was done in a subpopulation (n=856). B-vitamin supplementation did not improve cognitive domain scores. Only a small, though significant, effect was observed on global cognitive performance, measured by the Mini-Mental State Examination, but this was suggested to be due to chance. Brain MRI scans were made in a subgroup (n=218) after two years of intervention to obtain volumetric measures of grey and white matter, and total brain volume (Chapter 7). We investigated the cross-sectional associations between follow-up levels of folate, homocysteine and three vitamin B12 status biomarkers, e.g. methylmalonic acid, holotranscobalamin and serum vitamin B12, and brain volumes. Fully adjusted regression models showed a borderline significant association between plasma homocysteine and total brain volume, with a stronger association in the group that received B-vitamin supplementation. Serum B12 and holotranscobalamin were not associated with brain volumes, whereas high methylmalonic acid levels were associated with lower brain volumes in the group that received B-vitamins. In contrast, higher folate levels were associated with lower total brain volumes. In addition, when comparing the group that received two years of B-vitamin supplementation and those who did not, we observed lower brain volumes in the B-vitamin group, which might be a result of a difference in age between the two groups.
To conclude, the nutritional intervention studies showed little evidence for a beneficial effect on cognitive performance in relatively healthy older adults. Given the large problem of dementia, research on modifiable risk factors, including nutrition, should continue, with well thought out research methods, including large and long-term observational and intervention studies with high-sensitive study populations and early biomarkers (e.g. imaging techniques) for cognitive decline in combination with neuropsychological tests. In this way, nutrition can be added to the list of lifestyle factors that can fight dementia.
Vitamin D-tour : cognition and depression: the role of vitamin D and its interplay with glucose homeostasis
Brouwer-Brolsma, E.M. - \ 2014
Wageningen University. Promotor(en): Lisette de Groot; Edith Feskens, co-promotor(en): Teun Schuurman; Wilma Steegenga. - Wageningen : Wageningen University - ISBN 9789462571082 - 215
vitamine d - depressie - glucose - homeostase - gezondheid - hersenen - vitaminetekorten - vitamin d - depression - glucose - homeostasis - health - brain - vitamin deficiencies
According to recent estimations approximately 35.6 million people have dementia worldwide. Globally, 350 million people experience one or more depressive episodes during their life. As the therapeutic options for dementia and depression are limited, these conditions form a major challenge for public health and society. More and more researchers have initiated research on potential preventive factors for dementia and depression, including the potential effects of nutritional factors. The aim of this PhD-thesis was to study the role of vitamin D and its potential interplay with glucose homeostasis, in the development of cognitive decline and depression, using epidemiological data as well experimental animal data.
Chapter 2 recapitulates a debate between vitamin D experts that was organized to make a step towards the harmonization on the formulation of optimal vitamin D intake levels and serum 25(OH)D concentrations across Europe. It was concluded that based on the current evidence-base 25(OH)D concentrations ≥50 nmol/L are sufficient with respect to optimal bone health. For health outcomes beyond bone health evidence was considered insufficient to formulate optimal levels. In order to achieve and maintain a 25(OH)D concentration ≥50 nmol/L, older adults aged ≥65 years were recommended to adhere to a vitamin D intake of 20 μg/day.
Chapter 3 shows that there is a high prevalence of 25(OH)D inadequacy in a population of Dutch older adults that participated in the B-PROOF study (n=2857), namely 45% had 25(OH)D concentrations <50 nmol/L. Mean vitamin D intake was 4.9±2.9 µg/day and only 20% of the participants reported to use vitamin D containing supplements. Exploration of the determinants of 25(OH)D status showed significant associations between vitamin D ‘raising’ SNPs (n=2530), higher sun exposure (n=1012), vitamin D intake (n=596) and higher 25(OH)D concentrations. Including all the potential relevant predictors in one model explained 35% of the variance in 25(OH)D status (R2=0.35).
In chapter 4 the associations between 25(OH)D status and global cognitive performance (n=116), depressive symptoms (n=118), and surrogate markers of glucose intolerance (n=593) were evaluated using data of European adults aged 70-75 years. None of the associations reached significance.
Studying the potential role of vitamin D in domain-specific cognitive performance and depression in 127 Dutch pre-frail and frail older adults aged ≥65 years (chapter 5), showed an association between 25(OH)D concentration and executive functioning, and a tendency towards an association with information processing speed. Stratification for ‘low’ and ‘high’ fasting glucose concentrations did not suggest an interaction between vitamin D and glucose homeostasis in the association with domain-specific cognitive performance. Moreover, adding fasting glucose or insulin did not substantially influence the associations between 25(OH)D status and domain-specific cognitive performance, and hence a mediation effect of glucose homeostasis was considered unlikely.
We furthermore observed associations of 25(OH)D status with attention and working memory (n=787) (chapter 6), depression (n=2839) (chapter 7) and grey matter volume of the brain (n=217) (chapter 8) in a population community-dwelling Dutch older adults aged ≥65 years. Again, these studies did not provide evidence that the associations were modified or mediated by glucose intolerance. However, it should be emphasized that glucose intolerance in these three chapters was defined sub-optimally, specifically using blood samples that may have been collected in a non-fasting state, or by using self-reported diabetes data. Hence, the mediation and interaction effects should be interpreted cautiously.
Finally, chapter 9 shows the results of a proof of principle study on the effect of a long-term vitamin D deficiency on cognitive decline and emotional reactivity in old C57BL/6j mice. Modest tendencies were shown for a relation between vitamin D and spatial learning, but these tendencies did not reach significance. Vitamin D deficiency did not affect recognition memory, spatial memory or emotional reactivity. Mice that received a higher dietary fat load, which was given to induce an impaired glucose tolerance, did not respond differently to a vitamin D deficiency than mice that received a low fat diet did.
Overall, it is concluded that the evidence for an effect of vitamin D on cognitive performance/decline, depression or brain volume is insufficient to formulate disease specific cut-off values for vitamin D intake or 25(OH)D status. However, given the high prevalence of 25(OH)D concentrations <50 nmol/L we do call for a more active promotion of the current vitamin D intake recommendations.
Acrylamide and 5-hydroxymethylfurfural formation during baking of biscuits: NaCl and temperature-time profile effects and kinetics
Fels, H.J. van der; Capuano, E. ; Nguyen, H.T. ; Mogol, B.A. ; Kocadagli, T. ; Goncuoglu Tas, N. ; Hamzalioglu, A. ; Boekel, M.A.J.S. van; Gokmen, V. - \ 2014
Food Research International 57 (2014). - ISSN 0963-9969 - p. 210 - 217.
aberrant crypt foci - maillard reaction - mass-spectrometry - model system - food - glucose - cookies - asparagine - sucrose - cancer
The present study aimed to investigate the effect of recipe and temperature–time on the formation of acrylamide and 5-hydroxymethylfurfural (HMF) during biscuit baking. Baking experiments were performed with biscuits of two different recipes, with and without NaCl, at 180 °C, 190 °C and 200 °C. Acrylamide and HMF reached highest concentrations at 200 °C for both recipes. The presence of NaCl in the biscuit formulation lowered acrylamide concentrations at 180 °C and 190 °C but not at 200 °C, and led to higher concentrations of HMF at all the tested temperatures. Sucrose hydrolysis was a key step in acrylamide and HMF formation during biscuit baking, even though a significant amount of acrylamide already had formed before the onset of sucrose hydrolysis. A lag phase was observed before sucrose hydrolysis occurred, which might depend on the melting of crystalline sucrose occurring at approximately 180 °C. A mathematical model based on the chemical reaction pathways was developed for the recipe with NaCl baked at 200 °C. The model described the chemical evolution during the last part of biscuit baking, and accurately predicted acrylamide and HMF content at the end of baking. The model showed the significant contribution of the reducing sugars to the formation of both acrylamide and HMF. The model could not be extended to the entire baking period because it was not possible to incorporate the lag phase observed before sucrose hydrolysis. The results reported in this study confirm that the kinetics of acrylamide and HMF formation in real food and dry systems may depend on the physical state of their precursors.
Glycated hemoglobin measurement and prediction of cardiovascular disease
Angelantonio, E. Di; Gao, P. ; Khan, H. ; Feskens, E.J.M. - \ 2014
JAMA: The Journal of the American Medical Association 311 (2014)12. - ISSN 0098-7484 - p. 1225 - 1233.
statistical-methods - diabetes-mellitus - risk score - task-force - glucose - guidelines - metaanalysis - mortality - adults
(For a complete list of authors see The Emerging Risk Factors Collaboration in the Article Information) Importance The value of measuring levels of glycated hemoglobin (HbA1c) for the prediction of first cardiovascular events is uncertain. Objective To determine whether adding information on HbA1c values to conventional cardiovascular risk factors is associated with improvement in prediction of cardiovascular disease (CVD) risk. Design, Setting, and Participants Analysis of individual-participant data available from 73 prospective studies involving 294¿998 participants without a known history of diabetes mellitus or CVD at the baseline assessment. Main Outcomes and Measures Measures of risk discrimination for CVD outcomes (eg, C-index) and reclassification (eg, net reclassification improvement) of participants across predicted 10-year risk categories of low (