Mixed Nutrient Research Articles

Produksi selada (Lactuca sativa l.) dengan penyinaran lampu led merah dan biru di malam hari pada teknologi hidroponik sistem terapung termodifikasi

This research has an aim to observe the production of lettuce (Lactuca sativa L.) on hydroponic technology of floating system with red and blue LED (Light Emitting Diode) at night. This research was conducted inside the Screenhouse in which located on the top of Griya Kads House building, Bulusan Village, Tembalang Sub-district from May to June 2017. The research was conducted by 3x3 factorial experiments in Nested Design with 3 replications. The first factor was 0, 1.5 and 3 hours irradiation of red and blue LED lights at night. The second factor was 3, 5 and 7 ml/liter of AB mix nutrient concentration which was nested in the first factor. The data collected were fresh weight, dry weight and root canopy ratio. The results of the study showed that the treatment of AB mix nutrient concentration had no significant effect on all parameters. The production of lettuce with level of 5 ml concentration of AB mix was quite good, yet 3 ml and 7 ml levels didn’t improve lettuce production. The duration of red and blue LED irradiation only resulted in an increase in the production of canopy fresh weight. This research can be concluded that 3 hours was sufficient to give the good results to improve the results of lettuce plants production. Keywords : Lettuce Production, AB Mix Nutrition, Red and Blue LED.

GROWTH OF SPINACH (AMARANTHUS TRICOLOR L.) UNDER VARIOUS APPLICATIONS OF NUTRIENT CONCENTRATIONS IN HYDROPONIC SYSTEM OF NUTRIENT FILM TECHNIQUE

The research aimed to discover the response of the growth of two spinach species on Nutrient Film Technique (NFT) hydroponic system and the concentration of the appropriate AB Mix solution on each species. The research was conducted in January to February 2016, at Green House, Faculty of Agriculture, Tadulako University by using Split Plot Design method. The main plot was red and green spinach, while the subplot was the concentration of AB Mix nutrient solution, namely 4 ml/L of water, 5 ml/L of water, 6 ml/L of water and 7 ml/L of water. The research findings reveal that AB Mix nutrient solution was generally very good to support the growth of spinach on NFT hydroponic. The green spinach had better response rather than the red one. There was no interaction between species and the concentration of nutrient solution. The good concentration of nutrient solution for green spinach is 6 ml/L. It was showed by the better growth of plant height on all age of plant, the more number of leaves, the canopy and the root (wet and dry) were heavier, while on the red spinach, 5 ml/L of concentration of nutrient solution resulted in the best growth, yet it was not significantly different from other concentration except on the parameter of plant height and the dry weight of plant canopy.

Efektivitas Perendaman Serat Aren dan Endosperm Kelapa Terhadap Pertumbuhan dan Hasil Tomat Pada Hidroponik Substrat

<p>This study was conducted to determine the effect of soaking period of arenga fibers and the addition of coconut endosperm to growth and yield of tomatoe. The observations were analyzed by using the 5% F test and if significant continued by the 5% DMRT. The experiment was conducted using a completely randomized factorial design with two factors, factors substrate consists of 5 levels, fiber arenga without soaking (S0), fiber soaking for 1 month (S1), fiber soaking for 2 months (S2), fiber soaking for 3 months(S3), and substrate husk as control. The second factor is a nutrient with two levels ie. AB mix nutrient (N1), AB mix nutrient plus 50% coconut endosperm (N2). The results showed that treatment of arenga fiber substrate by immersion of one month, 2 month, and 3 month not significantly influenced on all growth variable and yield of tomato. Treatment spraying coconut endosperm with a concentration of 50% could be low variable root length, root volume and fresh weight of the plant. There was no interaction between the two factors of all the observed variables.<strong></strong></p>

The Effects of a Normal Rate versus a Slow Intervalled Rate of Oral Nutrient Intake and Intravenous Low Rate Macronutrient Application on Psychophysical Function - Two Pilot Studies.

Stomach distension and energy per time are factors influencing satiety. Moreover, different rates of nutrient intake induce different stomach distension. The goal of our studies was to elucidate the influence of different oral rates of nutrient intake (normal rate versus slow intervalled rate; study I) and intravenous low rate macronutrient application (protein, carbohydrate, fat) or placebo (study II) on psychophysical function. The pilot studies investigated the effects of 1) study I: a mixed nutrient solution (1/3 protein, 1/3 fat, 1/3 carbohydrates) 2) study II: intravenous macronutrient infusions (protein, carbohydrate, fat) or placebo on psychophysical function (mood, hunger, food craving, alertness, smell intensity ratings and hedonic ratings) in human subjects. In study I 10 male subjects (age range: 21–30 years) completed the study protocol participating in both test conditions and in study II 20 male subjects (age range: 19–41 years) completed the study protocol participating in all test conditions. Additionally, metabolic function was analyzed and cognitive and olfactory tests were conducted twice starting 100 min before the beginning of the intervention and 240 min after. Psychophysical (mood, hunger, fat-, protein-, carbohydrate-, sweets- and vegetable-craving), alertness and metabolic function tests were performed seven times on each examination day. Greater effects on hunger and food cravings were observed for normal rate of intake compared to slow intervalled rate of intake and intravenous low rate macronutrient application. Our findings potentially confirm that volume of the food ingested and a higher rate of energy per time contribute to satiety during normal rate of food intake, while slow intervalled rate of food intake and intravenous low rate macronutrient application showed no effects on satiation. Our results motivate the view that a certain amount of volume of the food ingested and a certain energy per time ratio are necessary to reduce hunger and food craving.

Extension of ASM2d to Model the Fate of 17α-Ethinylestradiol in Activated Sludge Systems

The discharge of the synthetic estrogen, 17α-ethinylestradiol (EE2), in wastewater treatment plant (WWTP) effluents is an environmental concern as this compound can alter the reproductive system of aquatic wildlife at low ng L-1 concentrations. The impact of EE2 at such low concentrations indicates the need to identify activated sludge (AS) process designs that minimize WWTP effluent EE2 concentrations. An EE2 fate and transformation model was developed based on the following mechanism: (1) EE2 production from deconjugation of EE2-3-sulfate, a conjugated form excreted from humans, (2) EE2 removal from biodegradation by heterotrophic biomass growing on other substrates, and (3) EE2 removal from sorption to activated sludge. These mechanisms were incorporated into the International Water Association (IWA) Activated Sludge Model No. 2d (ASM2d) to model the fate of EE2 across aerobic and biological nutrient removal (BNR) AS systems. The model was calibrated and evaluated for mixed liquor solids, nutrients, and EE2 using lab-scale aerobic and BNR AS reactors fed primary effluent and amended with ng.L-1 estrogen concentrations. A sensitivity analysis predicted effluent EE2 concentrations were most sensitive to the biodegradation rate coefficient (kbio,H), the influent biodegradable chemical oxygen demand to EE2 ratio, and the aerobic solids retention time and were least sensitive to the deconjugation rate coefficient (kcle,H) and the solidliquid partitioning coefficient. Predicted effluent EE2 concentrations were more sensitive to the kcle,H/kbio,H ratio for AS systems with low kbio,H values.

Significantly greater triglyceridemia in Black African compared to White European men following high added fructose and glucose feeding: a randomized crossover trial.

BackgroundBlack African (BA) populations are losing the cardio-protective lipid profile they historically exhibited, which may be linked with increasing fructose intakes. The metabolic effects of high fructose diets and how they relate to blood lipids are documented for Caucasians, but have not been described in BA individuals.ObjectiveThe principle objective of this pilot study was to assess the independent impacts of high glucose and fructose feeding in men of BA ancestry compared to men of White European (WE) ancestry on circulating triglyceride (TG) concentrations.MethodsHealthy males, aged 25–60 years, of BA (n = 9) and WE (n = 11) ethnicity were randomly assigned to 2 feeding days in a crossover design, providing mixed nutrient meals with 20 % total daily caloric requirements from either added glucose or fructose. Circulating TG, non-esterified fatty acids (NEFA), glucose, insulin and C-peptide were measured over two 24-h periods.ResultsFasting TGs were lower in BAs than WEs on the fructose feeding day (p < 0.05). There was a trend for fasting TG concentrations 24 h following fructose feeding to increase in both BA (baseline median fasting: 0.80, IQR 0.6–1.1 vs 24-h median post-fructose: 1.09, 0.8–1.4 mmol/L; p = 0.06) and WE (baseline median fasting 1.10, IQR 0.9–1.5 vs 24-h median post-fructose: 1.16, IQR 0.96–1.73 mmol/L; p = 0.06). Analysis within ethnic group demonstrated that in TG iAUC was significantly higher in BA compared to WE on both glucose (35, IQR 11–56 vs −4, IQR −10–1 mmol/L/min; p = 0.004) and fructose (48, IQR 15–68 vs 13, IQR −7–38 mmol/L/min; p = 0.04). Greater suppression of postprandial NEFA was evident in WE than BA after glucose feeding (−73, IQR −81– −52 vs −26, IQR −48– −3 nmol/L/min; p = 0.001) but there was no ethnic difference following fructose feeding.ConclusionsUnderstanding the metabolic effects of dietary acculturation and Westernisation that occurs in Black communities is important for developing prevention strategies for chronic disease development. These data show postprandial hypertriglyceridemia following acute feeding of high added fructose and glucose in BA men, compared to WE men, may contribute to metabolic changes observed during dietary acculturation and Westernisation.Trial registrationThe study was retrospectively registered on clinicaltrials.gov: NCT02533817.Electronic supplementary materialThe online version of this article (doi:10.1186/s12944-016-0315-3) contains supplementary material, which is available to authorized users.

Effects of fertiliser applications after thinning of Pinus radiata on a high-elevation site in south-eastern Australia

ABSTRACTA trial to assess the effects of fertiliser applied after thinning was established in a ten-year-old Pinus radiata stand growing on a high elevation site in south-eastern Australia. The trial had two components. The first studied the effects of fertilisers applied in a factorial design with two levels of phosphorus (0 and 50 kg P ha–1) and three of nitrogen (0, 150 and 300 kg N ha–1) plus a mixed nutrient treatment to areas thinned to a routine intensity. In the second part, levels of thinning intensity were assessed with and without a fertiliser (N1P1) application. Over the seven years of the study, growth was affected by below average rainfall in four of the years. Significant responses to fertiliser were achieved with all treatments; the best was 150 kg N ha–1 + 50 kg P ha–1 plus trace elements. The volume increment was increased by 28%, however this was not significantly different from the N1P1 alone. The N1P1 fertiliser increased productivity at all thinning levels including the unthinned treatment. Models predicting relative growth response based on foliage nutrient levels gave reasonable predictions, that is, 29% increase in volume periodic increment and this was slightly higher than that achieved. On such low rainfall sites, rather than having multiple thinnings, one option is a relatively heavy thinning at a young age with fertiliser application and then leaving the stand until final harvest. Estate optimisation models provide forest managers with the means to evaluate fertiliser-thinning treatment options against objectives such as maximising the present value of expected future cash flow within production and budget constraints.

Hypoxia-Inducible Factor-1: A Critical Player in the Survival Strategy of Stressed Cells.

HIF-1 activation has been well known as an adaptive strategy to hypoxia. Recently it became clear that hypoxia was often accompanied by insufficient supply of glucose or amino acids as a common result of poor circulation that frequently occurs in solid tumors and ischemic lesions, creating a mixed nutrient insufficiency. In response to nutrient insufficiency, stressed cells elicit survival strategies including activation of AMPK and HIF-1 to cope with the stress. Particularly, in solid tumors, HIF-1 promotes cell survival and migration, stimulates angiogenesis, and induces resistance to radiation and chemotherapy. Interestingly, radiation and some chemotherapeutics are reported to trigger the activation of AMPK. Here we discuss the recent advances that may potentially link the stress responsive mechanisms including AMPK activation, ATF4 activation and the enhancement of Hsp70/Hsp90 function to HIF-1 activation. Potential implication and application of the stress-facilitated HIF-1 activation in solid tumors and ischemic disorders will be discussed. A better understanding of HIF-1 activation in cells exposed to stresses is expected to facilitate the design of therapeutic approaches that specifically modulate cell survival strategy.

FACS for Fungi: revealing population heterogeneity among fungal pathogens via flow cytometry

Although we often consider pathogens as presenting a single face to the immune system, it is clear that this “golf ball” model of pathogen-host interaction limits our understanding of population dynamics in the host. For example, others have shown that population heterogeneity in surface antigen presentation by Trypanosoma brucei and heterogeneity in the expression of pathogenicity factors by Vibrio harveyi and the human fungal pathogen Candida albicans are required for full virulence of these organisms [1, 2, 3]. This is perhaps counter-intuitive, given a working model in which virulence factor expression is correlated to degree of pathogenicity of a given organism. In this work, we discuss the application of flow cytometry techniques to the analysis of fungal pathogens. Specifically, we examine the impact of environmental fluctuations in nutrient availability on the presentation of cell wall components on the surface of fungal cells and use these features as markers for population heterogeneity. We demonstrate that population heterogeneity can be modulated by environmental conditions such as carbon source availability. We show that heterogeneity is rapidly lost when cells grown in a mixed nutrient environment representative of in vivo conditions are transitioned to the single nutrient conditions more typical of in vitro laboratory culture, and is slow to re-emerge when cells are transitioned back. Moreover, we show that heterogeneity in the presentation of pathogenassociated molecular patterns is similarly modulated by environmental conditions. Together, our observations underscore the potential for population-based analyses in investigating host-pathogen dynamics.

A randomized, double-blind, placebo-controlled, multiple-dose, parallel-group clinical trial to assess the effects of teduglutide on gastric emptying of liquids in healthy subjects

BackgroundTeduglutide, a recombinant analog of human glucagon-like peptide (GLP)-2, is a novel therapy recently approved for the treatment of adult patients with short bowel syndrome who are dependent on parenteral support. Previous studies assessing the effect of GLP-2 on gastric emptying in humans have yielded inconsistent results, with some studies showing no effect and others documenting a GLP-2–dependent delay in gastric emptying. The primary objective of this study was to assess the effect of teduglutide on gastric emptying of liquids in healthy subjects, as measured by the pharmacokinetics of acetaminophen.MethodsThis double-blind, parallel-group, single-center study enrolled and randomized 36 healthy subjects (22 men, 14 women) to receive subcutaneous doses of teduglutide 4 mg or placebo (2:1 ratio; 23:13) once daily on Days 1 through 10 in the morning. Gastric emptying of a mixed nutrient liquid meal was assessed by measuring acetaminophen levels predose and at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 3.5, 4, 5, 6, 8, 10, 12, and 14 hours after administration of 1000 mg acetaminophen on Days 0 and 10. The primary study endpoint was a pharmacokinetic analysis of acetaminophen absorption in subjects receiving teduglutide or placebo.ResultsNo significant differences in gastric emptying of liquids (acetaminophen area under the concentration [AUC] vs time curve from time 0 to the last measurable concentration, AUC extrapolated to infinity, maximum concentration [Cmax], and time to Cmax) were observed on Day 10 in subjects receiving teduglutide 4 mg versus subjects receiving placebo. There were no serious adverse events (AEs), deaths, or discontinuations due to an AE reported during the study.ConclusionsTeduglutide 4 mg/day for 10 days does not affect gastric emptying of liquids in healthy subjects as measured by acetaminophen pharmacokinetics. No unexpected safety signals were observed.Trial registrationThis study was registered at ClinicalTrials.gov, identifier NCT01209351.

Protein Supplements: Do They Alter Dietary Intakes?

Effects of protein versus mixed macronutrient supplementation on total energy intake (TEI) and protein intake during an ad libitum diet were examined. Trained males undertook two, 2-week dietary interventions which were randomized, double blinded, and separated by 2 weeks. These were high-protein supplementation (HP: 1034.5 kJ energy, 29.6 g protein, 8.7 g fat and 12.3 g CHO) and standard meal supplementation (SM: 1039 kJ energy, 9.9 g protein, 9.5 g fat, and 29.4 g CHO) consumed daily following a week of baseline measures. Eighteen participants finished both interventions and one only completed HP. TEI (mean ± SD) was not different between baseline (11148 ± 3347 kJ) and HP (10705 ± 3143 kJ) nor between baseline and SM (12381 ± 3877 kJ), however, TEI was greater with SM than HP (923 ± 4015 kJ p = .043). Protein intake (%TEI) was greater with HP (22.4 ± 6.2%) than baseline (19.4 ± 5.4%; p = .008) but not SM (20.0 ± 5.0%). No differences in absolute daily protein intake were found. Absolute CHO intake was greater with SM than HP (52.0 ± 89.5 g, p = .006). No differences in fat intake were found. Body mass did not change between baseline (82.7 ± 11.2 kg) and either HP (83.1 ± 11.7 kg) or SM (82.9 ± 11.0 kg). Protein supplementation increases the relative proportion of protein in the diet, but doesn't increase the absolute amount of total protein or energy consumed. Thus some compensation by a reduction in other foods occurs. This is in contrast to a mixed nutrient supplement, which does not alter the proportion of protein consumed but does increase TEI.

Differential response of microbial plankton to nutrient inputs in oligotrophic versus mesotrophic waters of the North Atlantic

The effects of inorganic and/or organic (glucose+AAs) inputs on phytoplankton and heterotrophic bacteria were assessed, using a microcosm approach, in two contrasting marine environments: an open ocean oligotrophic site (North Atlantic Subtropical Gyre) and a highly productive coastal embayment (Ría de Vigo, NW Spain). Overall, changes in microbial plankton biomass were smaller than those of metabolic rates. The largest increases in primary production, bacterial production and community respiration were measured in response to mixed () nutrient additions in both sites. Primary production responded to additions only in oligotrophic waters. The distinct autotrophic responses to nutrient additions measured in these environments were related to the different initial composition of phytoplankton populations and, presumably, also to differences in grazing pressures in both marine ecosystems. Heterotrophic bacteria were limited by organic substrates in both ecosystems, although mixed additions further enhanced bacterial growth in the subtropical gyre. The differences detected in bacterial responses to nutrient additions may be related to differences in nutrient limitations and to the prevalence of different relationships between components of the microbial food web (e.g. coupling between heterotrophic bacteria and phytoplankton and predation pressure) in both environments. We found a more relevant role of inorganic nutrients in controlling the efficiency of bacterial growth in oligotrophic regions as compared with highly productive systems. Our results suggest that organic matter inputs into both ecosystems might result in a tendency towards heterotrophy and in increases in bacterial growth efficiency.

Spatial and Temporal Variations of Nutrient Loads in Overland Flow and Subsurface Drainage from A Marginal Land Site in South-East Ireland

In Ireland, Food Harvest 2020 focuses on increasing productivity while enhancing environmental sustainability of agricultural land. On underutilised or marginal land, drainage systems may be installed to expand agricultural enterprises. Mixed nutrient losses are inevitable from any drainage system, but assessing processes leading to differences in nutrient speciation, fractionation and losses in grasslands between locations or flow paths is important to achieve sustainability. This study investigates these processes in overland flow and subsurface drains over three rainfall events from four non-grazed plots recently converted from marginal land in the south-east of Ireland. A shallower water table and smaller plot size resulted in greater water and nutrient losses in overland flow per unit of land area. Nutrient losses were less in subsurface drains. Dissolved organic nitrogen (DON) dominated, but dissolved inorganic nitrogen (DIN) was more abundant in the drains. Particulate phosphorus generally dominated in drains, except in plots with a shallow water table where dissolved unreactive phosphorus (DUP) was more abundant. In overland flow, a shallower water table resulted in a switch from dissolved reactive phosphorus (DRP) to DUP. Fertilisation increased phosphorus losses in overland flow, with DRP dominating. These results highlight the importance of an integrated assessment of the controls on flow and nutrient losses to design drainage systems in marginal lands.

Crohn's disease affecting the small bowel is associated with reduced appetite and elevated levels of circulating gut peptides

Appetite disturbance is an important nutritional issue in Crohn's disease (CD), but the biological basis is unclear. Satiety signals such as polypeptide YY (PYY) and glucagon-like peptide-1 (GLP-1) are produced by enteroendocrine cells (EEC). In animal models, upregulation of EEC plays a mechanistic role in feeding disturbance and weight loss. We recently showed increased EEC activity in tissue from active small bowel CD. This study investigated EEC products in plasma in CD, and appetite-related symptoms. Active CD patients and a healthy reference group were studied. Gut peptide responses to a mixed nutrient test meal were measured by ELISA. Symptoms were assessed by visual analogue score. A patient subset was re-studied in remission. CD subjects displayed reduced appetite (p<0.0001) before and after eating. Total PYY was increased 2.2-fold (p=0.04) and correlated with nausea (p=0.036) and bloating (p=0.037) scores only in small bowel CD. Postprandial plasma ghrelin levels were also elevated. Leptin correlated with body mass index (p=0.0001) and weight loss (p=0.01). GLP-1 and GIP were not elevated. In remission, postprandial PYY and ghrelin reverted to control levels. Enhanced EEC responses may directly and adversely affect appetite in CD patients through increased gut-brain signalling.

Effects of Mixed Dietary Supplements on Total Plasma Homocysteine Concentrations (tHcy): A Randomized, Double-Blind, Placebo-Controlled Trial

Although a number of studies have reported raised total plasma homocysteine (tHcy) concentrations in free-living older people, there are no data on homocysteine response to a mixed nutrient supplement in older patients. A raised plasma homocysteine concentration in older patients is partly a reflection of their co-morbidity, including impaired renal function, and there is uncertainty about the extent to which dietary interventions can improve plasma tHcy. To determine the plasma tHcy response to dietary supplements during acute illness. Two-hundred and thirty-six hospitalized, acutely ill older patients, who were part of a randomized double-blind placebo-controlled trial, were assigned to receive a daily oral nutritional supplement drink containing 1.3 mg of vitamin B2, 1.4 mg of vitamin B6, 1.5 μg of B12, 200 μg of folic acid, or a placebo, for 6 weeks. Outcome measures were plasma tHcy concentration at baseline, 6 weeks, and 6 months. The mean plasma tHcy concentration fell among patients given the supplements (mean difference 4.1 µmol/L [95 % C.I, 0.14 to 8.03), p = 0.043], but tHcy concentration increased between 6 weeks and 6 months, after patients stopped taking the supplements [mean difference -2.0 µmol/L (95 % C.I, -03.9 to -0.18), p = 0.033]. About 46 % of patients in the placebo group and 55 % of patients in the supplement group had hyperhomocysteinemia (>14 µmol/L) at baseline compared with 45 % and 29 % at the end of the treatment period. A mixed nutrient supplement containing physiological amounts of B vitamins significantly reduced plasma tHcy concentrations in older patients recovering from acute illness.

A moderate acute increase in physical activity enhances nutritive flow and the muscle protein anabolic response to mixed nutrient intake in older adults

Nutrient stimulation of muscle protein anabolism is blunted with aging and may contribute to the development and progression of sarcopenia in older adults. This is likely due to insulin resistance of protein metabolism and/or endothelial dysfunction with a reduction in nutritive flow, both of which can be improved by aerobic exercise. Our objective was to determine whether increasing physical activity can enhance the muscle protein anabolic effect of essential amino acid (EAA) + sucrose intake in older subjects by improving nutritive flow and/or insulin signaling. Using a randomized crossover design, we measured in older subjects [n = 6, 70 ± 3 y of age, BMI (in kg/m2) of 25 ± 1] the acute effects of increasing physical activity with aerobic exercise, as compared with normal sedentary lifestyle, on the response of blood flow, microvascular perfusion, insulin signaling, and muscle protein kinetics to EAA+sucrose intake. No differences between treatment groups were found in the basal state. The change from the basal state in blood flow, muscle perfusion, phenylalanine delivery, net balance, and muscle protein synthesis during the consumption of EAA+sucrose was significantly higher after the exercise than after the control treatment (P < 0.05). Insulin signaling increased during EAA+sucrose ingestion in both groups (P < 0.05). Our data indicate that a prior bout of aerobic exercise increases the anabolic effect of nutrient intake in older adults. This effect appears to be mediated by an exercise-induced improvement in nutrient-stimulated vasodilation and nutrient delivery to muscle rather than to improved insulin signaling. This trial was registered at clinicaltrials.gov as NCT00690534.

Quantitative imaging of electron transfer flavoprotein autofluorescence reveals the dynamics of lipid partitioning in living pancreatic islets

Pancreatic islet β-cells metabolically sense nutrients to maintain blood glucose homeostasis through the regulated secretion of insulin. Long-term exposure to a mixed supply of excess glucose and fatty acids induces β-cell dysfunction and type II diabetes in a process termed glucolipotoxicity. Despite a number of documented mechanisms for glucolipotoxicity, the interplay between glucose and fatty acid oxidation in islets remains debated. Here, we develop confocal imaging of electron transfer flavoprotein (ETF) autofluorescence to reveal the dynamics of fatty acid oxidation in living pancreatic islets. This method further integrates microfluidic devices to hold the islets stationary in flow, and thus achieve ETF imaging in the β-cells with high spatial and temporal resolution. Our data first confirm that ETF autofluorescence reflects electron transport chain (ETC) activity downstream of Complex I, consistent with a response directly related to fatty acid metabolism. Together with two-photon imaging of NAD(P)H and confocal imaging of lipoamide dehydrogenase (LipDH) autofluorescence, we show that the ETC predominantly draws electrons from LipDH/NADH-dependent Complex I rather than from ETF/FADH(2)-dependent ETF:CoQ oxidoreductase (ETF-QO). Islets stimulated with palmitate also show increased ETF redox state that is dose-dependently diminished by glucose (>10 mM). Furthermore, stimulation with a glucose bolus causes a two-tier drop in the ETF redox state at ∼5 and ∼20 min, suggesting glucose metabolism immediately increases ETC activity and later decreases fatty acid oxidation. Our results demonstrate the utility of ETF imaging in characterizing fatty acid-induced redox responses with high subcellular and temporal resolution. Our results further demonstrate a dominant role of glucose metabolism over fatty acid oxidation in β-cells even when presented with a mixed nutrient condition associated with glucolipotoxicity.

Contributions of fat and protein to the incretin effect of a mixed meal

The relative contributions of fat and protein to the incretin effect are still largely unknown. This study assessed the incretin effects elicited by a mixed meal, and by its fat and protein components alone, with the use of a hyperglycemic clamp combined with oral nutrients. Eight healthy volunteers were studied over 6 h after ingestion of a sandwich containing 1) dried meat, butter, and white bread; 2) dried meat alone; 3) butter alone; or 4) no meal (fasting control). Meals were ingested during a hyperglycemic clamp, and the incretin effect was calculated as the increment in plasma insulin after food intake relative to the concentrations observed during the control study. A significant augmentation of postprandial insulin secretion, independent of plasma glycemia, occurred after ingestion of the mixed nutrients and the lipid component of the mixed meal (203 ± 20.7% and 167.4 ± 22.9% of control, respectively; both P < 0.05), whereas the protein component did not induce a significant incretin effect (129.0 ± 7.9% of control; P = 0.6) Fat ingestion, in an amount typical of a standard meal, increases insulin secretion during physiologic hyperglycemia and thus contributes to the incretin effect. In contrast, ingestion of protein typical of normal meals does not contribute to the augmentation of postprandial insulin secretion. This trial was registered at clinicaltrials.gov as NCT00869453.

Changes in Differential Functional Magnetic Resonance Signals in the Rodent Brain Elicited by Mixed-Nutrient or Protein-Enriched Meals

The hypothalamus and brain stem have important roles in regulating food intake; the roles of other nonhomeostatic centers in detecting nutrient content of ingested food have been poorly characterized. We used blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) to map brain regions that are responsive to intragastric infusion of isocaloric amounts of a mixed nutrient or protein, and assessed the role of blood glucose in the observed BOLD signal changes. Brain images were acquired, using a 9.4 T MRI system, from anesthetized rats during intragastric infusion of saline (n = 7), or 12 kcal of a mixed nutrient (n = 13) or protein (n = 6). Nutrient-induced changes in blood parameters and the effects of intravenous infusion of saline or glucose (n = 5/treatment) on BOLD fMRI signal changes were also evaluated. Intragastric nutrient infusion reduced the BOLD fMRI signal intensity in homeostatic (hypothalamus, nucleus tractus solitarius) and nonhomeostatic (thalamus, hippocampus, caudate putamen, cerebral cortex, cerebellum) centers; these effects were mimicked qualitatively by intravenous glucose. In contrast to a mixed meal, protein load reduced the BOLD fMRI signal in the amygdala. BOLD fMRI signal changes were inversely correlated with circulating concentrations of amylin, insulin, peptide YY, and glucagon-like peptide-1. The caloric content of a meal is signaled from the gut to the brain and affects activity in homeostatic and non-homeostatic centers; blood glucose concentrations have an important role. The satiety effects of protein are associated with activity changes specifically in the amygdala.

Methionine and protein metabolism in non-alcoholic steatohepatitis: evidence for lower rate of transmethylation of methionine

Hepatic metabolism of methionine is the source of cysteine, the precursor of glutathione, the major intracellular antioxidant in the body. Methionine also is the immediate precursor of SAM (S-adenosylmethionine) the key methyl donor for phosphatidylcholine synthesis required for the export of VLDL (very-low-density lipoprotein) triacylglycerols (triglycerides) from the liver. We have examined the kinetics of methionine, its transmethylation and trans-sulfuration with estimates of whole body rate of protein turnover and urea synthesis in clinically stable biopsy-confirmed subjects with NASH (non-alcoholic steatohepatitis). Subjects with NASH were more insulin-resistant and had significantly higher plasma concentrations of usCRP (ultrasensitive C-reactive protein), TNFα (tumour necrosis factor α) and other inflammatory cytokines. There was no significant effect of insulin resistance and NASH on whole body rate of protein turnover [phenylalanine Ra (rate of appearance)] and on the rate of urea synthesis. The rates of methylation of homocysteine and transmethylation of methionine were significantly lower in NASH compared with controls. There was no difference in the rate of trans-sulfuration of methionine between the two groups. Enteric mixed nutrient load resulted in a significant increase in all the measured parameters of methionine kinetics. Heterozygosity for MTHFR (5,10-methylene-tetrahydrofolate reductase) (677C→T) did not have an impact on methionine metabolism. We speculate that, as a result of oxidant stress possibly due to high fatty acid oxidation, the activity of methionine adenosyltransferase is attenuated resulting in a lower rate of transmethylation of methionine and of SAM synthesis. These results are the first evidence for perturbed metabolism of methionine in NASH in humans and provide a rationale for the development of targeted intervention strategies.