Metabolic Inhibitors Block ABA-Induced Stomatal Closure

Closure of stomata of Commelina communis L. leaf epidermis causedby abscisic acid (ABA) was inhibited by sodium azide, potassiumcyanide and hypoxic conditions. Azide was more effective thancyanide at low concentrations, but the cyanide effect couldbe enhanced by addition of salicylhydroxamic acid, providingindirect evidence for cyanide-resistant respiration in epidermaltissue. Azide also inhibited ABA-induced closure of ‘isolated’ stomata and shrinkage of guard cell protoplasts.The results indicate that metabolic energy is required for ABAaction involving solute loss from the guard cells. Possiblemechanisms of action are discussed.     

Early Life Stress Interacts with the Diet Deficiency of Omega-3 Fatty Acids during the Life Course Increasing the Metabolic Vulnerability in Adult Rats

Early stress can cause metabolic disorders in adulthood. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) deficiency has also been linked to the development of metabolic disorders. The aim of this study was to assess whether an early stressful event such as maternal separation interacts with the nutritional availability of n-3 PUFAs during the life course on metabolic aspects. Litters were randomized into: maternal separated (MS) and non-handled (NH). The MS group was removed from their dam for 3 hours per day and put in an incubator at 32°C on days 1° to 10° postnatal (PND). On PND 35, males were subdivided into diets that were adequate or deficient in n-3 PUFAs, and this intervention was applied during the subsequent 15 weeks. Animal''s body weight and food consumption were measured weekly, and at the end of the treatment tissues were collected. MS was associated with increased food intake (p = 0.047) and weight gain (p = 0.012), but no differences were found in the NPY hypothalamic content between the groups. MS rats had also increased deposition of abdominal fat (p<0.001) and plasma triglycerides (p = 0.018) when compared to the NH group. Interactions between early life stress and n-3 PUFAs deficiency were found in plasma insulin (p = 0.033), HOMA index (p = 0.049), leptin (p = 0.010) and liver PEPCK expression (p = 0.050), in which the metabolic vulnerability in the MS group was aggravated by the n-3 PUFAs deficient diet exposure. This was associated with specific alterations in the peripheral fatty acid profile. Variations in the neonatal environment interact with nutritional aspects during the life course, such as n-3 PUFAs diet content, and persistently alter the metabolic vulnerability in adulthood.     

Effects of a 12-Week Hatha Yoga Intervention on Metabolic Risk and Quality of Life in Hong Kong Chinese Adults with and without Metabolic Syndrome

Objective

To determine the efficacy of a 12-week Hatha yoga intervention to improve metabolic risk profiles and health-related quality of life (HRQoL) in Chinese adults with and without metabolic syndrome (MetS).

Methods

We conducted a controlled trial within an university-affiliated hospital. 173 Chinese men and women aged 18 or above were assigned to either the yoga intervention group (n = 87) or the control group (n = 86). Primary outcomes included 12-week change in metabolic risk factors and MetS z score. Secondary outcome was HRQoL (Medical Outcomes Short Form Survey at 12 weeks).

Results

The mean age of participants was 52.0 (SD 7.4, range 31-71) years. Analysis involving the entire study population revealed that the yoga group achieved greater decline in waist circumference (p<0.001), fasting glucose (p<0.01), triglycerides (p<0.05), and MetS z score (p<0.01). Yoga training also improved general health perceptions (p<0.01), physical component score (p<0.01), and social functioning (p<0.01) domains score of HRQoL. However, no significant differences between groups were observed in the mean change of systolic/diastolic blood pressures or high-density lipid protein cholesterol (all p>0.05). There were no significant differences in the intervention effects on waist circumference and MetS z score between the MetS subgroups (both p>0.05).

Conclusion

A 12-week Hatha yoga intervention improves metabolic risk profiles and HRQoL in Chinese adults with and without MetS.

Trial Registration

Australian New Zealand Clinical Trials Registry ACTRN12613000816752     

Effect of Pregnancy for Females Born Small on Later Life Metabolic Disease Risk

There is a strong inverse relationship between a females own birth weight and her subsequent risk for gestational diabetes with increased risk of developing diabetes later in life. We have shown that growth restricted females develop loss of glucose tolerance during late pregnancy with normal pancreatic function. The aim of this study was to determine whether growth restricted females develop long-term impairment of metabolic control after an adverse pregnancy adaptation. Uteroplacental insufficiency was induced by bilateral uterine vessel ligation (Restricted) or sham surgery (Control) in late pregnancy (E18) in F0 female rats. F1 Control and Restricted female offspring were mated with normal males and allowed to deliver (termed Ex-Pregnant). Age-matched Control and Restricted Virgins were also studied and glucose tolerance and insulin secretion were determined. Pancreatic morphology and hepatic glycogen and triacylglycerol content were quantified respectively. Restricted females were born lighter than Control and remained lighter at all time points studied (p<0.05). Glucose tolerance, first phase insulin secretion and liver glycogen and triacylglycerol content were not different across groups, with no changes in β-cell mass. Second phase insulin secretion was reduced in Restricted Virgins (−34%, p<0.05) compared to Control Virgins, suggestive of enhanced peripheral insulin sensitivity but this was lost after pregnancy. Growth restriction was associated with enhanced basal hepatic insulin sensitivity, which may provide compensatory benefits to prevent adverse metabolic outcomes often associated with being born small. A prior pregnancy was associated with reduced hepatic insulin sensitivity with effects more pronounced in Controls than Restricted. Our data suggests that pregnancy ameliorates the enhanced peripheral insulin sensitivity in growth restricted females and has deleterious effects for hepatic insulin sensitivity, regardless of maternal birth weight.     

A Mathematical Model of the Human Metabolic System and Metabolic Flexibility

In healthy subjects some tissues in the human body display metabolic flexibility, by this we mean the ability for the tissue to switch its fuel source between predominantly carbohydrates in the postprandial state and predominantly fats in the fasted state. Many of the pathways involved with human metabolism are controlled by insulin and insulin-resistant states such as obesity and type-2 diabetes are characterised by a loss or impairment of metabolic flexibility. In this paper we derive a system of 12 first-order coupled differential equations that describe the transport between and storage in different tissues of the human body. We find steady state solutions to these equations and use these results to nondimensionalise the model. We then solve the model numerically to simulate a healthy balanced meal and a high fat meal and we discuss and compare these results. Our numerical results show good agreement with experimental data where we have data available to us and the results show behaviour that agrees with intuition where we currently have no data with which to compare.     

Life Cycle Analysis of Mammalian Cells: I. A Method for Localizing Metabolic Events within the Life Cycle, and Its Application to the Action of Colcemide and Sublethal Doses of X-Irradiation

Equations are presented describing the accumulation of cells at any part of the life cycle as a result of addition of specific blocking agents. An experimental methodology using these relationships is described which makes possible analysis with relatively high resolution of the distribution of cells throughout the life cycle in normal cultures or those treated with various agents. The action of colcemide on S3 HeLa cells studied by this method revealed that colcemide has no effect on the G1, S, or G2 stages; it blocks cells quantitatively at the metaphase-anaphase region; but it accumulates mitotic figures only from the cells which have not yet entered mitosis at the time of its addition. The technique was also applied to study the efficiency of x-irradiation in delaying the entrance of G2 cells into mitosis. A definite lag was found at the lowest dose studied which was 9 rads. Only the cells confined to a central region of G2 at the time of irradiation are affected by this dose.     

Global Metabolic Reconstruction and Metabolic Gene Evolution in the Cattle Genome

The sequence of cattle genome provided a valuable opportunity to systematically link genetic and metabolic traits of cattle. The objectives of this study were 1) to reconstruct genome-scale cattle-specific metabolic pathways based on the most recent and updated cattle genome build and 2) to identify duplicated metabolic genes in the cattle genome for better understanding of metabolic adaptations in cattle. A bioinformatic pipeline of an organism for amalgamating genomic annotations from multiple sources was updated. Using this, an amalgamated cattle genome database based on UMD_3.1, was created. The amalgamated cattle genome database is composed of a total of 33,292 genes: 19,123 consensus genes between NCBI and Ensembl databases, 8,410 and 5,493 genes only found in NCBI or Ensembl, respectively, and 266 genes from NCBI scaffolds. A metabolic reconstruction of the cattle genome and cattle pathway genome database (PGDB) was also developed using Pathway Tools, followed by an intensive manual curation. The manual curation filled or revised 68 pathway holes, deleted 36 metabolic pathways, and added 23 metabolic pathways. Consequently, the curated cattle PGDB contains 304 metabolic pathways, 2,460 reactions including 2,371 enzymatic reactions, and 4,012 enzymes. Furthermore, this study identified eight duplicated genes in 12 metabolic pathways in the cattle genome compared to human and mouse. Some of these duplicated genes are related with specific hormone biosynthesis and detoxifications. The updated genome-scale metabolic reconstruction is a useful tool for understanding biology and metabolic characteristics in cattle. There has been significant improvements in the quality of cattle genome annotations and the MetaCyc database. The duplicated metabolic genes in the cattle genome compared to human and mouse implies evolutionary changes in the cattle genome and provides a useful information for further research on understanding metabolic adaptations of cattle.     

Factors Affecting Gender Differences in the Association between Health-Related Quality of Life and Metabolic Syndrome Components: Tehran Lipid and Glucose Study

Objective

Using structural equation modeling, this study is one of the first efforts aimed at assessing influential factors causing gender differences in the association between health-related quality of life (HRQoL) and metabolic syndrome.

Methods

A sample of 950 adults, from Tehran Lipid and Glucose Study were recruited for this cross sectional study in 2005–2007. Health-related quality of life was assessed using the Iranian version of SF-36. Metabolic syndrome components (MetSCs) and physical and mental HRQoL were considered as continuous latent constructs explaining the variances of their observed components. Structural equation modeling was performed to examine the association between the constructs of MetSCs and the physical and mental HRQoL within the two gender groups.

Results

Based on the primary hypothesis, MetSCs and HRQoL were fitted in a model. The negative effect of MetSCs on HRQoL was found to be significant only in the physical domain and only in women. The proportion of all the cardio-metabolic risk factors as well as subscales of physical HRQoL that have been explained via the two constructs of MetSCs and HRQoL, respectively, were significantly higher in women. Physical activity in both men (β = 3.19, p<0.05) and women (β = 3.94, p<0.05), age (β = -3.28, p<0.05), education (β = 2.63, p<0.05) only in women and smoking (β = 2.28, p<0.05) just in men, directly affected physical HRQoL. Regarding the mental domain, physical activity (β = 3.37, p<0.05) and marital status (β = 3.44, p<0.05) in women and age (β = 2.01, p<0.05) in men were direct effective factors. Age and education in women as well as smoking in men indirectly affected physical HRQoL via MetSCs.

Conclusion

Gender differences in the association between MetSCs and physical HRQoL could mostly be attributed to the different structures of both MetSCs and physical HRQoL constructs in men and women. Age and smoking are the most important socio-behavioral factors which could affect this gender-specific association in the mental domain.     

Health-Related Quality of Life in Relation to Obesity Grade,Type 2 Diabetes,Metabolic Syndrome and Inflammation

Background

Health-related quality of life (HR-QoL) may be compromised in obese individuals, depending on the presence of other complications. The aim of this study is to assess the effect of obesity-related conditions on HR-QoL. These conditions are i) grade of obesity with and without type 2 diabetes (T2D), ii) metabolic syndrome (MetS), and iii) level of inflammation.

Methods

From the Dutch LifeLines Cohort Study we included 13,686 obese individuals, aged 18–80 years. HR-QoL was measured with the RAND 36-Item Health Survey which encompasses eight health domains. We calculated the percentage of obese individuals with poor HR-QoL, i.e. those scoring below the domain and sex specific cut-off value derived from the normal weight population. Logistic regression analysis was used to calculate the probability of having poor domain scores according to the conditions under study.

Results

Higher grades of obesity and the additional presence of T2D were associated with lower HR-QoL, particularly in the domains physical functioning (men: odds ratios (ORs) 1.48–11.34, P<0.005, and women: ORs 1.66–5.05, P<0.001) and general health (men: ORs 1.44–3.07, P<0.005, and women: ORs 1.36–3.73, P<0.001). A higher percentage of obese individuals with MetS had a poor HR-QoL than those without MetS. Furthermore, we observed a linear trend between inflammation and the percentage of obese individuals with poor scores on the HR-QoL domains. Individuals with MetS were more likely to have poor scores in the domains general health, vitality, social functioning and role limitations due to emotional problems. Obese women with increased inflammation levels were more likely to have poor scores on all domains except role limitations due to emotional problems and mental health.

Conclusions

The impact of obesity on an individual’s quality of life is enhanced by grade of obesity, T2D, MetS and inflammation and are mainly related to reduced physical health. The mental well-being is less often impaired.     

Conception and pharmacodynamic profile of drospirenone

Progesterone is more than a progestin. Beyond functions in cycle and pregnancy, progesterone binds with high affinity to the mineralocorticoid receptor (MR) acting as an antagonist, with obvious significance for electrolyte homeostasis, an array of MR-related functions in the circulation as well as in the CNS. Progesterone induces natriuresis at physiological concentrations. Lack of antimineralocorticoid activity with conventional progestins may account for sodium and water retention, minor elevation of blood pressure and "pill hypertension" in susceptible women on oral contraceptives. Ethinylestradiol (EE) contributes to this problem by distinct activation of the renin-angiotensin-aldosterone (RAAS) system. Drospirenone (DRSP: 6beta,7beta,15beta,16beta-dimethylene-3-oxo 17alpha-pregn-4-ene-21,17 carbolactone) is the first synthetic progestin with antialdosterone activity. DRSP and progesterone bind to PR in uterine (affinity of both is about 30% of R5020) and MR in kidney cytosol (affinity about 230 and 100% of aldosterone, respectively). Intrauterine administration of DRSP in silastic tubes induced maximum local progestational effects in rabbits. At systemic subcutaneous (s.c.) administration (McPhail-assay) full endometrial transformation was obtained at 1mg per animal per day. At 1-3mg DRSP per animal per day subcutaneously, pregnancy maintenance after ovariectomy, antiovulatory activity, and antimineralocorticoid activity were seen in the respective assays in rats. The latter activity indicates about eight-fold higher potency than spironolactone. DRSP decreased blood pressure in male hypertensive rats, whereas an increase was noted under conventional progestins. DRSP also prevented hypertension and fetal growth retardation in pregnant rats after L-NAME, an inhibitor of nitric oxide synthase. DRSP has antiandrogenic activity. Feminizing effects were recorded during sexual differentiation in male fetuses at high doses. Powerful antiandrogenic effects were also seen in gonad intact and testosterone substituted castrated male rats. The antiandrogenic potency of DRSP is superior to that of spironolactone but below that of cyproterone acetate. Endometrial transformation, inhibition of ovulation, and antimineralocorticoid, i.e. natriuretic effects and mild antiandrogenic effects were recorded at the same range of oral doses (0.5-4 mg per day) in humans. Combined with EE (3 mg DRSP+30 microg EE), DRSP provides effective inhibition of ovulation and cycle control. Body weight compared to conventional oral contraceptives was reduced. DRSP (3 mg per day+15, 20, or 30 microg ethinyl estradiol per day) prevented the mild increase of blood pressure seen under a conventional levonorgestrel-containing contraceptive and even tended to reduce pretreatment blood pressure. Studies on modulation (i.e. inhibition) of glucocorticoid effects at the MR in the CNS remain an unexplored and interesting area for research.