Acute Cocoa Supplementation Increases Postprandial HDL Cholesterol and Insulin in Obese Adults with Type 2 Diabetes after Consumption of a High-Fat Breakfast

BACKGROUND: Dietary cocoa is an important source of flavonoids and is associated with favorable cardiovascular disease effects, such as improvements in vascular function and lipid profiles, in nondiabetic adults. Type 2 diabetes (T2D) is associated with adverse effects on postprandial serum glucose, lipids, inflammation, and vascular function.

OBJECTIVE: We examined the hypothesis that cocoa reduces metabolic stress in obese T2D adults after a high-fat fast-food-style meal.

METHODS: Adults with T2D [n = 18; age (means ± SEs): 56 ± 3 y; BMI (in kg/m(2)): 35.3 ± 2.0; 14 women; 4 men) were randomly assigned to receive cocoa beverage (960 mg total polyphenols; 480 mg flavanols) or flavanol-free placebo (110 mg total polyphenols; <0.1 mg flavanols) with a high-fat fast-food-style breakfast [766 kcal, 50 g fat (59% energy)] in a crossover trial. After an overnight fast (10-12 h), participants consumed the breakfast with cocoa or placebo, and blood sample collection [glucose, insulin, lipids, and high-sensitivity C-reactive protein (hsCRP)] and vascular measurements were conducted at 0.5, 1, 2, 4, and 6 h postprandially on each study day. Insulin resistance was evaluated by homeostasis model assessment.

RESULTS: Over the 6-h study, and specifically at 1 and 4 h, cocoa increased HDL cholesterol vs. placebo (overall Δ: 1.5 ± 0.8 mg/dL; P ≤ 0.01) but had no effect on total and LDL cholesterol, triglycerides, glucose, and hsCRP. Cocoa increased serum insulin concentrations overall (Δ: 5.2 ± 3.2 mU/L; P < 0.05) and specifically at 4 h but had no overall effects on insulin resistance (except at 4 h, P < 0.05), systolic or diastolic blood pressure, or small artery elasticity. However, large artery elasticity was overall lower after cocoa vs. placebo (Δ: -1.6 ± 0.7 mL/mm Hg; P < 0.05), with the difference significant only at 2 h.

CONCLUSION: Acute cocoa supplementation showed no clear overall benefit in T2D patients after a high-fat fast-food-style meal challenge. Although HDL cholesterol and insulin remained higher throughout the 6-h postprandial period, an overall decrease in large artery elasticity was found after cocoa consumption. This trial was registered at clinicaltrials.gov as NCT01886989.

The cardiac responses of the scallop Pecten maximus (L.) to respiratory stress

Heart activity of Pecten maximus (L.) has been recorded during various forms of experimentally induced respiratory stress. There was considerable variation in the responses of individual scallops but bradycardia generally occurred in response to all forms of respiratory stress, with the rate of fall in heart rate dependent upon the severity of hypoxia. When oxygen tension declined slowly in a closed respirometer there was regulation of both heart rate and oxygen consumption. The critical tension, Pc, for oxygen consumption lay between 70 and 80 mm Hg, and corresponded with a slight regulatory upswing of the heart rate, whereas the Pc for heart rate was much lower at 20–30 mm Hg. Sudden transfer to deoxygenated water for 3 h resulted in very rapid bradycardia and there was a rapid recovery and initial overshoot of the normal rate on return to well-oxygenated sea water. Aerial exposure for 3 h produced more gradual bradycardia followed by gradual recovery on return to sea water. The results of this work are compared in some detail with previous work on other species of bivalve from different geographical areas and habitats, and the mechanisms controlling cardiac and respiratory regulation are discussed. It is concluded that there are few clear-cut general differences between littoral and sublittoral species in their behavioural and physiological adaptations to hypoxia; the main distinguishing feature of littoral-adapted species is their ability to control air-gaping. Changes in heart activity generally indicate variations in metabolic rate, the speed at which the metabolic rate may be altered reflecting the degree of adaptation to the littoral environment.

Metabolic-activity of pathogenic bacteria during semicontinuous anaerobic-digestion

In natural environments such as anaerobic digesters, bacteria are frequently subjected to the stress of nutrient fluxes because of the continual changes in the flow of nutrients, and to survive, they must be capable of adapting readily to nutrient changes. In this study, the metabolic activities of Escherichia coli, Salmonella typhimurium, Yersinia enterocolitica, Listeria monocytogenes, and Campylobacter jejuni were studied within culture bags (Versapor-200 filters, 0.22-mu m pore size) in laboratory anaerobic digesters. The metabolic activity of these bacteria was indicated by their adenylate energy charge (EC) ratios and their ability to incorporate [H-3]thymidine, which was related to the respective changes in viable numbers within the culture bags during anaerobic digestion. Fluctuations in the adenylate EC ratios, the uptake of [H-3]thymidine, and the viable numbers of E. coli, S. typhimurium, Y. enterocolitica, and L. monocytogenes cells were probably due to constant changes in the amount of available nutrients within the anaerobic digesters. The viability of S. typhimurium increased quickly after a fresh supply of nutrients was added to the system as indicated by the uptake of [H-3]thymidine and an increase in the adenylate EC ratios. The viable numbers of E. coli, S. typhimurium, Y. enterocolitica, and L. monocytogenes organisms declined rapidly from 10(7) to 10(8) CFU/ml to 10(3) to 10(4) CFU/ml and remained at this level for an indefinite period. The decimal reduction time calculated during the period of exponential decline ranged from 0.8 to 1.2 days for these bacteria. C. jejuni had the greatest mean decimal reduction time value (3.6 days). This bacterium had adenylate EC ratios of less than 0.5 during anaerobic digestion, although the adenylate nucleotide concentrations in the cells were much greater than those in the other enteric cells. The results show that the enteric bacteria investigated probably exist in transient states between different stages of growth because of fluctuating nutrient levels during anaerobic digestion.

Use of a lux-marked rhizobacterium as a biosensor to assess changes in rhizosphere C flow due to pollutant stress

The flow of carbon from plant roots into soil supports a range of microbial processes and is therefore critical to ecosystem function and health. Pollution-induced stress, which influences rhizosphere C flow is of considerable potential importance, and therefore needs to be evaluated. This paper reports on a method, based on reporter gene technology, for quantifying pollutant effects on rhizosphere C flow. The method uses the lux-marked rhizobacterium Pseudomonas fluorescens, where bioluminescence output of this biosensor is directly correlated with the metabolic activity and reports on C flow in root exudate. Plantago lanceolata was treated with paraquat (representing a model pollutant stress) in a simple microcosm system. The lux-biosensor response correlated closely with C concentrations in the exudate and demonstrated that the pollutant stress increased the C flow from the plantago roots, 24 h after application of the herbicide. The lux-reporter system therefore potentially offers a technique for use in assessing the impact of pollutant stress on rhizosphere C flow through the soil microbial biomass.

Chronic workplace stress and insufficient physical activity: a cohort study

Objectives To examine whether exposure to workplace stressors predicts changes in physical activity and the risk of insufficient physical activity.

Methods Prospective data from the Finnish Public Sector Study. Repeated exposure to low job control, high job demands, low effort, low rewards and compositions of these (job strain and effort-reward imbalance) were assessed at Time 1 (2000-2002) and Time 2 (2004). Insufficient physical activity (<14 metabolic equivalent task hours per week) was measured at Time 1 and Time 3 (2008). The effect of change in workplace stressors on change in physical activity was examined using fixed-effects (within-subject) logistic regression models (N=6665). In addition, logistic regression analysis was applied to examine the associations between repeated exposure to workplace stressors and insufficient physical activity (N=13 976). In these analyses, coworker assessed workplace stressor scores were used in addition to individual level scores.

Results The proportion of participants with insufficient physical activity was 24% at baseline and 26% at follow-up. 19% of the participants who were sufficiently active at baseline became insufficiently active at follow-up. In the fixed-effect analysis, an increase in workplace stress was weakly related to an increase in physical inactivity within an individual. In between-subjects analysis, employees with repeated exposure to low job control and low rewards were more likely to be insufficiently active at follow-up than those with no reports of these stressors; fully adjusted ORs ranged from 1.11 (95% CI 1.00 to 1.24) to 1.21 (95% CI 1.05 to 1.39).

Conclusions Workplace stress is associated with a slightly increased risk of physical inactivity.

Green tea supplementation affects body weight, lipids, and lipid peroxidation in obese subjects with metabolic syndrome

To compare the effects of supplementation of green tea beverage or green tea extracts with controls on body weight, glucose and lipid profile, biomarkers of oxidative stress, and safety parameters in obese subjects with metabolic syndrome.

Freeze-dried strawberry powder improves lipid profile and lipid peroxidation in women with metabolic syndrome:baseline and post intervention effects

Strawberry flavonoids are potent antioxidants and anti-inflammatory agents that have been shown to reduce cardiovascular disease risk factors in prospective cohort studies. Effects of strawberry supplementation on metabolic risk factors have not been studied in obese populations. We tested the hypothesis that freeze-dried strawberry powder (FSP) will lower fasting lipids and biomarkers of oxidative stress and inflammation at four weeks compared to baseline. We also tested the tolerability and safety of FSP in subjects with metabolic syndrome. FSP is a concentrated source of polyphenolic flavonoids, fiber and phytosterols.

Glycation, carbonyl stress, EAGLEs, and the vascular complications of diabetes

The association between poor metabolic control and the microvascular complications of diabetes is now well established, but the relationship between long-term metabolic control and the accelerated atherosclerosis of diabetes is as yet poorly defined. Hyperglycemia is the standard benchmark by which metabolic control is assessed. One mechanism by which elevated glucose levels may mediate vascular injury is through early and advanced glycation reactions affecting a wide variety of target molecules. The "glycation hypothesis'' has developed over the past 30 years, evolving gradually into a "carbonyl stress hypothesis'' and taking into account not only the modification of proteins by glucose, but also the roles of oxidative stress, a wide range of reactive carbonyl-containing intermediates (derived not only from glucose but also from lipids), and a variety of extra- and intracellular target molecules. The final products of these reactions may now be termed "Either Advanced Glycation or Lipoxidation End-Products'' or "EAGLEs.'' The ubiquity of carbonyl stress within the body, the complexity of the reactions involved, the variety of potential carbonyl intermediates and target molecules and their differing half-lives, and the slow development of the complications of diabetes all pose major challenges in dissecting the significance of these processes. The extent of the reactions tends to correlate with overall metabolic control, creating pitfalls in the interpretation of associative data. Many animal and cell culture studies, while supporting the hypothesis, must be viewed with caution in terms of relevance to human diabetes. In this article, the development of the carbonyl stress hypothesis is reviewed, and implications for present and future treatments to prevent complications are discussed.

Lipoprotein glycation and its metabolic consequences

Glycation of lipoproteins is implicated in the development of the macro- and microvascular complications of diabetes, atherosclerosis in general, and other disease processes including aging. Enhanced glycation may have direct effects, and may also amplify the effects of oxidative stress on lipoproteins. Most studies have examined the effects of glycation of LDL, particularly with respect to its atherogenicity. Other lipoproteins are more difficult to study because their several apolipoproteins, being of varying age, are not uniformly exposed to glucose. Inhibition of the combined stresses of glycation and oxidation towards lipoproteins may have beneficial effects on health.

Ethanol-induced water stress in yeast

This review considers the effect of ethanol-induced water stress on yeast metabolism and integrity. Ethanol causes water stress by lowering water activity (a(w)) and thereby interferes with hydrogen bonding within and between hydrated cell components, ultimately disrupting enzyme and membrane strut and function. The impact of ethanol on the energetic status of water is considered in relation to cell metabolism. Even moderate ethanol concentrations (5 to 10%, w/v) cause a sufficient reduction of a(w) to have metabolic consequences. When exposed to ethanol, cells synthesize compatible solutes such as glycerol and trehalose that protect against water stress and hydrogen-bond disruption. Ethanol affects the control of gene expression by the mechanism that is normally associated with (so-called) osmotic control. Furthermore, ethanol-induced water stress has ecological implications.

Systemic oxidative-nitrosative-inflammatory stress during acute exercise in hypoxia; implications for microvascular oxygenation and aerobic capacity

New Findings

What is the central question of this study?Exercise performance is limited during hypoxia by a critical reduction in cerebral and skeletal tissue oxygenation. To what extent an elevation in systemic free radical accumulation contributes to microvascular deoxygenation and the corresponding reduction in maximal aerobic capacity remains unknown.What is the main finding and its importance?We show that altered free radical metabolism is not a limiting factor for exercise performance in hypoxia, providing important insight into the fundamental mechanisms involved in the control of vascular oxygen transport.

Exercise performance in hypoxia may be limited by a critical reduction in cerebral and skeletal tissue oxygenation, although the underlying mechanisms remain unclear. We examined whether increased systemic free radical accumulation during hypoxia would be associated with elevated microvascular deoxygenation and reduced maximal aerobic capacity (). Eleven healthy men were randomly assigned single-blind to an incremental semi-recumbent cycling test to determine  in both normoxia (21% O_{2) and hypoxia (12% O2) separated by a week. Continuous-wave near-infrared spectroscopy was employed to monitor concentration changes in oxy- and deoxyhaemoglobin in the left vastus lateralis muscle and frontal cerebral cortex. Antecubital venous blood samples were obtained at rest and at  to determine oxidative (ascorbate radical by electron paramagnetic resonance spectroscopy), nitrosative (nitric oxide metabolites by ozone-based chemiluminescence and 3-nitrotyrosine by enzyme-linked immunosorbent assay) and inflammatory stress biomarkers (soluble intercellular/vascular cell adhesion 1 molecules by enzyme-linked immunosorbent assay). Hypoxia was associated with increased cerebral and muscle tissue deoxygenation and lower  (P < 0.05 versus normoxia). Despite an exercise-induced increase in oxidative–nitrosative–inflammatory stress, hypoxia per se did not have an additive effect (P > 0.05 versus normoxia). Consequently, we failed to observe correlations between any metabolic, haemodynamic and cardiorespiratory parameters (P > 0.05). Collectively, these findings suggest that altered free radical metabolism cannot explain the elevated microvascular deoxygenation and corresponding lower  in hypoxia. Further research is required to determine whether free radicals when present in excess do indeed contribute to the premature termination of exercise in hypoxia.}

Myc-dependent purine biosynthesis affects nucleolar stress and therapy response in prostate cancer

The androgen receptor is a key transcription factor contributing to the development of all stages of prostate cancer (PCa). In addition, other transcription factors have been associated with poor prognosis in PCa, amongst which c-Myc (MYC) is a well-established oncogene in many other cancers. We have previously reported that the AR promotes glycolysis and anabolic metabolism; many of these metabolic pathways are also MYC-regulated in other cancers. In this study, we report that in PCa cells de novo purine biosynthesis and the subsequent conversion to XMP is tightly regulated by MYC and independent of AR activity. We characterized two enzymes, PAICS and IMPDH2, within the pathway as PCa biomarkers in tissue samples and report increased efficacy of established anti-androgens in combination with a clinically approved IMPDH inhibitor, mycophenolic acid (MPA). Treatment with MPA led to a significant reduction in cellular guanosine triphosphate (GTP) levels accompanied by nucleolar stress and p53 stabilization. In conclusion, targeting purine biosynthesis provides an opportunity to perturb PCa metabolism and enhance tumour suppressive stress responses.

Protective role of glycerol against benzene stress: insights from the Pseudomonas putida proteome

Chemical activities of hydrophobic substances can determine the windows of environmental conditions over which microbial systems function and the metabolic inhibition of microorganisms by benzene and other hydrophobes can, paradoxically, be reduced by compounds that protect against cellular water stress (Bhaganna et al. in Microb Biotechnol 3:701-716, 2010; Cray et al. in Curr Opin Biotechnol 33:228-259, 2015a). We hypothesized that this protective effect operates at the macromolecule structure-function level and is facilitated, in part at least, by genome-mediated adaptations. Based on proteome profiling of the soil bacterium Pseudomonas putida, we present evidence that (1) benzene induces a chaotrope-stress response, whereas (2) cells cultured in media supplemented with benzene plus glycerol were protected against chaotrope stress. Chaotrope-stress response proteins, such as those involved in lipid and compatible-solute metabolism and removal of reactive oxygen species, were increased by up to 15-fold in benzene-stressed cells relative to those of control cultures (no benzene added). By contrast, cells grown in the presence of benzene + glycerol, even though the latter grew more slowly, exhibited only a weak chaotrope-stress response. These findings provide evidence to support the hypothesis that hydrophobic substances induce a chaotropicity-mediated water stress, that cells respond via genome-mediated adaptations, and that glycerol protects the cell's macromolecular systems. We discuss the possibility of using compatible solutes to mitigate hydrocarbon-induced stresses in lignocellulosic biofuel fermentations and for industrial and environmental applications.