Genetic Parameter Estimates for Metabolizing Two Common Pharmaceuticals in Swine

PubMed Central

Howard, Jeremy T.; Ashwell, Melissa S.; Baynes, Ronald E.; Brooks, James D.; Yeatts, James L.; Maltecca, Christian

2018-01-01

In livestock, the regulation of drugs used to treat livestock has received increased attention and it is currently unknown how much of the phenotypic variation in drug metabolism is due to the genetics of an animal. Therefore, the objective of the study was to determine the amount of phenotypic variation in fenbendazole and flunixin meglumine drug metabolism due to genetics. The population consisted of crossbred female and castrated male nursery pigs (n = 198) that were sired by boars represented by four breeds. The animals were spread across nine batches. Drugs were administered intravenously and blood collected a minimum of 10 times over a 48 h period. Genetic parameters for the parent drug and metabolite concentration within each drug were estimated based on pharmacokinetics (PK) parameters or concentrations across time utilizing a random regression model. The PK parameters were estimated using a non-compartmental analysis. The PK model included fixed effects of sex and breed of sire along with random sire and batch effects. The random regression model utilized Legendre polynomials and included a fixed population concentration curve, sex, and breed of sire effects along with a random sire deviation from the population curve and batch effect. The sire effect included the intercept for all models except for the fenbendazole metabolite (i.e., intercept and slope). The mean heritability across PK parameters for the fenbendazole and flunixin meglumine parent drug (metabolite) was 0.15 (0.18) and 0.31 (0.40), respectively. For the parent drug (metabolite), the mean heritability across time was 0.27 (0.60) and 0.14 (0.44) for fenbendazole and flunixin meglumine, respectively. The errors surrounding the heritability estimates for the random regression model were smaller compared to estimates obtained from PK parameters. Across both the PK and plasma drug concentration across model, a moderate heritability was estimated. The model that utilized the plasma drug

Relationship between primary lesion metabolic parameters and clinical stage in lung cancer.

PubMed

Sahiner, I; Atasever, T; Akdemir, U O; Ozturk, C; Memis, L

2013-01-01

The relation of PET-derived parameters as maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG), metabolic tumor volume (MTV) with clinical stage in lung cancer and correlation of SUVmax of primary tumor and that of metastatic lesion was studied in lung cancer patients. Patients with lung cancer who were referred for FDG PET/CT were included in the study. PET/CT scans and pathology reports of 168 patients were assessed. A total of 146 (86.9%) of these patients had a diagnosis of non-small cell lung cancer (NSCLC) and 22 (13.1%) had small cell lung cancer (SCLC). Metabolic parameters such as SUVmax, TLG and MTV showed significant differences in all the stages in NSCLC patients (p<0.001). However, after tumors sizes <25 mm were excluded, no significant differences in SUVmax between stages were observed. No significant differences were found between these metabolic parameters and limited or extended disease SCLC. Tumor diameter correlated with primary tumor SUVmax and significant correlations between primary lesion SUVmax and metastatic lesion SUVmax were found. Although differences were found regarding indices between stages of NSCLC cases, SUVmax differences between stages seem to be caused by underestimation of SUVmax in small lesions. Other glucose metabolism indexes such as MTV and TLG show promising results in terms of prognostic stratification. Future studies are needed for better understanding of their contribution to clinical cases. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

The association between hematological parameters and metabolic syndrome in Iranian men: A single center large-scale study.

PubMed

Ahmadzadeh, Jamal; Mansorian, Behnam; Attari, Mohammad Mirza-Aghazadeh; Mohebbi, Ira; Naz-Avar, Raha; Moghadam, Karaim; Ghareh-Bagh, Seyyed Adel Khoshbou

Some studies have demonstrated that metabolic syndrome is associated with hematological parameters. The present study explores the relationship between hematological parameters and numbers of metabolic syndrome conditions in Iranian men. This cross-sectional study included 11,114 participants who were professional drivers of commercial motor vehicles, and were enrolled in the Iranian Health Surveys between 2014 and 2016. Diagnosis of metabolic syndrome was made according to International Diabetes Federation criteria. Clinical data, including anthropometric measurements and serum parameters, were collected. Odds ratios for hematological parameters and metabolic syndrome were calculated using binary logistic regression models. We found that hemoglobin; platelet, and white blood cell counts increased with increasing numbers of metabolic syndrome components (p<0.05 for all). The odds ratio of metabolic syndrome significantly increased across successive quartiles of platelet (1.00, 1.25, 1.29, and 1.51) and white blood cell counts (1.00, 1.51, 1.79, and 2.11) with the lowest quartile as the referent group. Similar associations for hemoglobin and hematocrit in the top quartile were also observed. We did not observe any significant difference in the mean of neutrophil count, mean platelet volume (MPV), red cell distribution width, or platelet distribution width among participants with or without metabolic syndrome. Our findings indicate that high levels of major hematological parameters such as hemoglobin, hematocrit, as well as platelet and white blood cell counts could be novel indicators for the development of metabolic syndrome. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Evaluation of oxidative stress parameters and metabolic activities of nurses working day and night shifts.

PubMed

Ulas, Turgay; Buyukhatipoglu, Hakan; Kirhan, Idris; Dal, Mehmet Sinan; Ulas, Sevilay; Demir, Mehmet Emin; Eren, Mehmet Ali; Ucar, Mehmet; Hazar, Abdussamet; Kurkcuoglu, Ibrahim Can; Aksoy, Nurten

2013-04-01

The aim of this study was to evaluate the oxidative stress and metabolic activities of nurses working day and night shifts. Intensive care unit (ICU) (n=70) and ordinary service (OS) nurses (n=70) were enrolled in the study. Just before and the end of the shifts, blood samples were obtained to measure the participants' oxidative stress parameters. Metabolic activities were analyzed using the SenseWear Armband. Oxidative stress parameters were increased at the end of the shifts for all OS and ICU nurses compared to the beginning of the shifts. Compared to the OS nurses, the ICU nurses' TAS, TOS, and OSI levels were not significantly different at the end of the day and night shifts. The metabolic activities of the OS and ICU nurses were found to be similar. As a result, the OS and ICU nurses' oxidative stress parameters and metabolic activities were not different, and all of the nurses experienced similar effects from both the day and night shifts.

Vibration parameters affecting vibration-induced reflex muscle activity.

PubMed

Cidem, Muharrem; Karacan, Ilhan; Cakar, Halil Ibrahim; Cidem, Mehmet; Sebik, Oguz; Yilmaz, Gizem; Turker, Kemal Sitki; Karamehmetoglu, Safak Sahir

2017-03-01

To determine vibration parameters affecting the amplitude of the reflex activity of soleus muscle during low-amplitude whole-body vibration (WBV). This study was conducted on 19 participants. Vibration frequencies of 25, 30, 35, 40, 45, and 50 Hz were used. Surface electromyography, collision force between vibration platform and participant's heel measured using a force sensor, and acceleration measured using an accelerometer fixed to the vibration platform were simultaneously recorded. The collision force was the main independent predictor of electromyographic amplitude. The essential parameter of vibration affecting the amplitude of the reflex muscle activity is the collision force.

Branched-chain Amino Acids are associated with Metabolic Parameters in Bipolar Disorder.

PubMed

Fellendorf, F T; Platzer, M; Pilz, R; Rieger, A; Kapfhammer, H P; Mangge, H; Dalkner, N; Zelzer, S; Meinitzer, A; Birner, A; Bengesser, S A; Queissner, R; Hamm, C; Hartleb, R; Reininghaus, E Z

2018-06-14

An important aspect of bipolar disorder (BD) research is the identification of biomarkers pertaining to the somatic health state. The branched-chain essential amino acids (BCAAs), viz valine, leucine and isoleucine, have been proposed as biomarkers of an individual's health state, given their influence on protein synthesis and gluconeogenesis inhibition. BCAA levels of 141 euthymic/subsyndromal individuals with BD and 141 matched healthy controls (HC) were analyzed by high-pressure lipid chromatography and correlated with clinical psychiatric, anthropometric and metabolic parameters. BD and HC did not differ in valine and isoleucine, whereas leucine was significantly lower in BD. Furthermore, correlations were found between BCAAs and anthropometric and glucose metabolism data. All BCAAs correlated with lipid metabolism parameters in females. There were no associations between BCAAs and long-term clinical parameters of BD. A negative correlation was found between valine and Hamilton-Depression-Scale, and Beck-Depression-Inventory-II, in male individuals. Our results indicate the utility of BCAAs as biomarkers for the current state of health, also in BD. As BD individuals have a high risk for overweight/obesity, in association with comorbid medical conditions (e.g. cardiovascular diseases, insulin resistance), health-state markers are urgently required. However, no illness-specific associations were found in this euthymic/subsyndromal BD group.

Cardiac metabolic pathways affected in the mouse model of barth syndrome.

PubMed

Huang, Yan; Powers, Corey; Madala, Satish K; Greis, Kenneth D; Haffey, Wendy D; Towbin, Jeffrey A; Purevjav, Enkhsaikhan; Javadov, Sabzali; Strauss, Arnold W; Khuchua, Zaza

2015-01-01

Cardiolipin (CL) is a mitochondrial phospholipid essential for electron transport chain (ETC) integrity. CL-deficiency in humans is caused by mutations in the tafazzin (Taz) gene and results in a multisystem pediatric disorder, Barth syndrome (BTHS). It has been reported that tafazzin deficiency destabilizes mitochondrial respiratory chain complexes and affects supercomplex assembly. The aim of this study was to investigate the impact of Taz-knockdown on the mitochondrial proteomic landscape and metabolic processes, such as stability of respiratory chain supercomplexes and their interactions with fatty acid oxidation enzymes in cardiac muscle. Proteomic analysis demonstrated reduction of several polypeptides of the mitochondrial respiratory chain, including Rieske and cytochrome c1 subunits of complex III, NADH dehydrogenase alpha subunit 5 of complex I and the catalytic core-forming subunit of F0F1-ATP synthase. Taz gene knockdown resulted in upregulation of enzymes of folate and amino acid metabolic pathways in heart mitochondria, demonstrating that Taz-deficiency causes substantive metabolic remodeling in cardiac muscle. Mitochondrial respiratory chain supercomplexes are destabilized in CL-depleted mitochondria from Taz knockdown hearts resulting in disruption of the interactions between ETC and the fatty acid oxidation enzymes, very long-chain acyl-CoA dehydrogenase and long-chain 3-hydroxyacyl-CoA dehydrogenase, potentially affecting the metabolic channeling of reducing equivalents between these two metabolic pathways. Mitochondria-bound myoglobin was significantly reduced in Taz-knockdown hearts, potentially disrupting intracellular oxygen delivery to the oxidative phosphorylation system. Our results identify the critical pathways affected by the Taz-deficiency in mitochondria and establish a future framework for development of therapeutic options for BTHS.

Four-year stability of anthropometric and cardio-metabolic parameters in a prospective cohort of older adults.

PubMed

Jackson, Sarah E; van Jaarsveld, Cornelia Hm; Beeken, Rebecca J; Gunter, Marc J; Steptoe, Andrew; Wardle, Jane

2015-01-01

To examine the medium-term stability of anthropometric and cardio-metabolic parameters in the general population. Participants were 5160 men and women from the English Longitudinal Study of Ageing (age ≥50 years) assessed in 2004 and 2008. Anthropometric data included height, weight, BMI and waist circumference. Cardio-metabolic parameters included blood pressure, serum lipids (total cholesterol, HDL, LDL, triglycerides), hemoglobin, fasting glucose, fibrinogen and C-reactive protein. Stability of anthropometric variables was high (all intraclass correlations >0.92), although mean values changed slightly (-0.01 kg weight, +1.33 cm waist). Cardio-metabolic parameters showed more variation: correlations ranged from 0.43 (glucose) to 0.81 (HDL). The majority of participants (71-97%) remained in the same grouping relative to established clinical cut-offs. Over a 4-year period, anthropometric and cardio-metabolic parameters showed good stability. These findings suggest that when no means to obtain more recent data exist, a one-time sample will give a reasonable approximation to average levels over the medium-term, although reliability is reduced.

Nutritional Ketosis Affects Metabolism and Behavior in Sprague-Dawley Rats in Both Control and Chronic Stress Environments

PubMed Central

Brownlow, Milene L.; Jung, Seung H.; Moore, Raquel J.; Bechmann, Naomi; Jankord, Ryan

2017-01-01

Nutritional ketosis may enhance cerebral energy metabolism and has received increased interest as a way to improve or preserve performance and resilience. Most studies to date have focused on metabolic or neurological disorders while anecdotal evidence suggests that ketosis may enhance performance in the absence of underlying dysfunction. Moreover, decreased availability of glucose in the brain following stressful events is associated with impaired cognition, suggesting the need for more efficient energy sources. We tested the hypotheses that ketosis induced by endogenous or exogenous ketones could: (a) augment cognitive outcomes in healthy subjects; and (b) prevent stress-induced detriments in cognitive parameters. Adult, male, Sprague Dawley rats were used to investigate metabolic and behavioral outcomes in 3 dietary conditions: ketogenic (KD), ketone supplemented (KS), or NIH-31 control diet in both control or chronic stress conditions. Acute administration of exogenous ketones resulted in reduction in blood glucose and sustained ketosis. Chronic experiments showed that in control conditions, only KD resulted in pronounced metabolic alterations and improved performance in the novel object recognition test. The hypothalamic-pituitary-adrenal (HPA) axis response revealed that KD-fed rats maintained peripheral ketosis despite increases in glucose whereas no diet effects were observed in ACTH or CORT levels. Both KD and KS-fed rats decreased escape latencies on the third day of water maze, whereas only KD prevented stress-induced deficits on the last testing day and improved probe test performance. Stress-induced decrease in hippocampal levels of β-hydroxybutyrate was attenuated in KD group while both KD and KS prevented stress effects on BDNF levels. Mitochondrial enzymes associated with ketogenesis were increased in both KD and KS hippocampal samples and both endothelial and neuronal glucose transporters were affected by stress but only in the control diet group

Morningness-eveningness questionnaire score and metabolic parameters in patients with type 2 diabetes mellitus.

PubMed

Osonoi, Yusuke; Mita, Tomoya; Osonoi, Takeshi; Saito, Miyoko; Tamasawa, Atsuko; Nakayama, Shiho; Someya, Yuki; Ishida, Hidenori; Kanazawa, Akio; Gosho, Masahiko; Fujitani, Yoshio; Watada, Hirotaka

2014-11-01

"Morningness" and "Eveningness" represent lifestyle patterns including sleep-wake patterns. Although previous studies described a relationship between the morningness-eveningness trait and glycemic control in patients with type 2 diabetes mellitus (T2DM), the mechanism underlying this association remains unknown. The study participants comprised 725 Japanese T2DM outpatients free of history of cardiovascular diseases. Various lifestyles were analyzed using self-reported questionnaires, including morningness-eveningness questionnaire (MEQ). The relationships between morningness-eveningness trait and various biochemical parameters were investigated by linear regression analysis and logistic regression analysis. We classified the study patients into three groups, morning type (n=117), neither type (n=424) and evening type (n=184). Subjects of the evening type had high levels of alanine aminotransferase, triglyceride, fasting blood glucose and HbA1c and low high-density lipoprotein-cholesterol level in a model adjusted for age and gender. Furthermore, multivariate analysis showed that the evening type was associated with high HbA1c and estimated glomerular filtration rate even after adjustment for other lifestyle factors known to affect metabolic control. The results suggest that T2DM patients with eveningness trait are under inadequate metabolic control independent of other lifestyle factors. Thus, the evening trait of T2DM patients represents an important target for intervention to ensure appropriate metabolic function.

Relationship of metabolic and endocrine parameters to brain glucose metabolism in older adults: do cognitively-normal older adults have a particular metabolic phenotype?

PubMed

Nugent, S; Castellano, C A; Bocti, C; Dionne, I; Fulop, T; Cunnane, S C

2016-02-01

Our primary objective in this study was to quantify whole brain and regional cerebral metabolic rates of glucose (CMRg) in young and older adults in order to determine age-normalized reference CMRg values for healthy older adults with normal cognition for age. Our secondary objectives were to--(i) report a broader range of metabolic and endocrine parameters including body fat composition that could form the basis for the concept of a 'metabolic phenotype' in cognitively normal, older adults, and (ii) to assess whether medications commonly used to control blood lipids, blood pressure or thyroxine affect CMRg values in older adults. Cognition assessed by a battery of tests was normal for age and education in both groups. Compared to the young group (25 years old; n = 34), the older group (72 years old; n = 41) had ~14% lower CMRg (μmol/100 g/min) specifically in the frontal cortex, and 18% lower CMRg in the caudate. Lower grey matter volume and cortical thickness was widespread in the older group. These differences in CMRg, grey matter volume and cortical thickness were present in the absence of any known evidence for prodromal Alzheimer's disease (AD). Percent total body fat was positively correlated with CMRg in many brain regions but only in the older group. Before and after controlling for body fat, HOMA2-IR was significantly positively correlated to CMRg in several brain regions in the older group. These data show that compared to a healthy younger adult, the metabolic phenotype of a cognitively-normal 72 year old person includes similar plasma glucose, insulin, cholesterol, triglycerides and TSH, higher hemoglobin A1c and percent body fat, lower CMRg in the superior frontal cortex and caudate, but the same CMRg in the hippocampus and white matter. Age-normalization of cognitive test results is standard practice and we would suggest that regional CMRg in cognitively healthy older adults should also be age-normalized.

Exposure to gemfibrozil and atorvastatin affects cholesterol metabolism and steroid production in zebrafish (Danio rerio).

PubMed

Al-Habsi, Aziz A; Massarsky, Andrey; Moon, Thomas W

2016-09-01

The commonly used lipid-lowering pharmaceuticals gemfibrozil (GEM) and atorvastatin (ATV) are detected in the aquatic environment; however, their potential effects on non-target fish species are yet to be fully understood. This study examined the effects of GEM and/or ATV on female and male adult zebrafish after a 30d dietary exposure. The exposure led to changes in several biochemical parameters, including reduction in cholesterol, triglycerides, cortisol, testosterone, and estradiol. Changes in cholesterol and triglycerides were also associated with changes in transcript levels of key genes involved with cholesterol and lipid regulation, including SREBP2, HMGCR1, PPARα, and SREBP1. We also noted higher CYP3A65 and atrogin1 mRNA levels in drug-treated male fish. Sex differences were apparent in some of the examined parameters at both biochemical and molecular levels. This study supports these drugs affecting cholesterol metabolism and steroid production in adult zebrafish. We conclude that the reduction in cortisol may impair the ability of these fish to mount a suitable stress response, whereas the reduction of sex steroids may negatively affect reproduction. Copyright © 2015 Elsevier Inc. All rights reserved.

Novel effects of the cannabinoid inverse agonist AM 251 on parameters related to metabolic syndrome in obese Zucker rats.

PubMed

Merroun, Ikram; Sánchez-González, Cristina; Martínez, Rosario; López-Chaves, Carlos; Porres, Jesús M; Aranda, Pilar; Llopis, Juan; Galisteo, Milagros; Zarzuelo, Antonio; Errami, Mohammed; López-Jurado, María

2013-11-01

Recent research suggests that cannabinoid receptor CB1 antagonists can affect appetite and body weight gain, although their influence on other parameters related to metabolic syndrome is not well documented. The present study was designed to assess the effects of chronic treatment with the CB1 receptor inverse agonist AM 251 (3 mg/kg for 3 weeks) in obese and lean Zucker rats on parameters related to metabolic syndrome. Four groups of rats were used: lean Zucker rats, untreated obese Zucker rats, AM 251-treated obese Zucker rats and a pair-fed obese Zucker rat experimental group which received the same amount of food as that consumed by the animals treated with AM251. Food intake, body weight gain, energy expenditure, plasma biochemical parameters, leptin, insulin and hepatic status markers were analysed. Daily injection of AM 251 in obese Zucker rats produced a marked and sustained decrease in daily food intake and body weight and a considerable increase in energy expenditure in comparison with untreated obese Zucker rats. AM 251 administration to obese rats significantly reduced plasma levels of glucose, leptin, AST, ALT, Gamma GT, total bilirubin and LDL cholesterol whereas HDL cholesterol plasma levels increased. The results also showed a decrease in liver/weight body ratio and total fat content in the liver. The main effects of AM251 (3 mg/kg) found in this study were not observed in pair-fed obese animals, highlighting the additional beneficial effects of treatment with AM 251. The results obtained in obese rats can be interpreted as a decrease in leptin and insulin resistance, thereby improving glucose and lipid metabolism, alleviating the steatosis present in the metabolic syndrome and thus favourably modifying plasma levels of hepatic biomarkers. Our results indicate that the cannabinoid CB1 inverse agonist AM 251 represents a promising therapeutic strategy for the treatment of obesity and metabolic syndrome. © 2013.

Flavanol plasma bioavailability is affected by metabolic syndrome in rats.

PubMed

Margalef, Maria; Pons, Zara; Iglesias-Carres, Lisard; Bravo, Francisca Isabel; Muguerza, Begoña; Arola-Arnal, Anna

2017-09-15

Flavanols, which exert several health benefits, are metabolized after ingestion. Factors such as the host physiological condition could affect the metabolism and bioavailability of flavanols, influencing their bioactivities. This study aimed to qualitatively evaluate whether a pathological state influenced flavanol plasma bioavailability. Standard and cafeteria (CAF) diet fed rats, a robust model of metabolic syndrome (MeS), were administered 1000mg/kg of flavanol enriched grape seed polyphenol extract (GSPE). Flavanols and their metabolites were quantified by HPLC-MS/MS in plasma before and at 2, 4, 7, 24, and 48h after GSPE ingestion. Results showed that in CAF administered rats the maximum time of plasma flavanol concentration was delayed and these animals presented higher levels of plasma phase-II metabolites as well as altered microbial metabolites. In conclusion, this study demonstrated that MeS pathological state modified flavanol bioavailability, supporting the hypothesis that flavanol metabolism, and therefore flavanol functionality, depend on the organism's state of health. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of Slow Wave Sleep Disruption on Metabolic Parameters in Adolescents

PubMed Central

Shaw, Natalie D.; McHill, Andrew W.; Schiavon, Michele; Kangarloo, Tairmae; Mankowski, Piotr W.; Cobelli, Claudio; Klerman, Elizabeth B.; Hall, Janet E.

2016-01-01

Study Objectives: Cross-sectional studies report a correlation between slow wave sleep (SWS) duration and insulin sensitivity (SI) in children and adults. Suppression of SWS causes insulin resistance in adults but effects in children are unknown. This study was designed to determine the effect of SWS fragmentation on SI in children. Methods: Fourteen pubertal children (11.3–14.1 y, body mass index 29th to 97th percentile) were randomized to sleep studies and mixed meal (MM) tolerance tests with and without SWS disruption. Beta-cell responsiveness (Φ) and SI were determined using oral minimal modeling. Results: During the disruption night, auditory stimuli (68.1 ± 10.7/night; mean ± standard error) decreased SWS by 40.0 ± 8.0%. SWS fragmentation did not affect fasting glucose (non-disrupted 76.9 ± 2.3 versus disrupted 80.6 ± 2.1 mg/dL), insulin (9.2 ± 1.6 versus 10.4 ± 2.0 μIU/mL), or C-peptide (1.9 ± 0.2 versus 1.9 ± 0.1 ng/mL) levels and did not impair SI (12.9 ± 2.3 versus 10.1 ± 1.6 10−4 dL/kg/min per μIU/mL) or Φ (73.4 ± 7.8 versus 74.4 ± 8.4 10−9 min−1) to a MM challenge. Only the subjects in the most insulin-sensitive tertile demonstrated a consistent decrease in SI after SWS disruption. Conclusion: Pubertal children across a range of body mass indices may be resistant to the adverse metabolic effects of acute SWS disruption. Only those subjects with high SI (i.e., having the greatest “metabolic reserve”) demonstrated a consistent decrease in SI. These results suggest that adolescents may have a unique ability to adapt to metabolic stressors, such as acute SWS disruption, to maintain euglycemia. Additional studies are necessary to confirm that this resiliency is maintained in settings of chronic SWS disruption. Citation: Shaw ND, McHill AW, Schiavon M, Kangarloo T, Mankowski PW, Cobelli C, Klerman EB, Hall JE. Effect of slow wave sleep disruption on metabolic parameters in adolescents. SLEEP 2016;39(8):1591–1599. PMID:27166229

Parameter estimation of kinetic models from metabolic profiles: two-phase dynamic decoupling method.

PubMed

Jia, Gengjie; Stephanopoulos, Gregory N; Gunawan, Rudiyanto

2011-07-15

Time-series measurements of metabolite concentration have become increasingly more common, providing data for building kinetic models of metabolic networks using ordinary differential equations (ODEs). In practice, however, such time-course data are usually incomplete and noisy, and the estimation of kinetic parameters from these data is challenging. Practical limitations due to data and computational aspects, such as solving stiff ODEs and finding global optimal solution to the estimation problem, give motivations to develop a new estimation procedure that can circumvent some of these constraints. In this work, an incremental and iterative parameter estimation method is proposed that combines and iterates between two estimation phases. One phase involves a decoupling method, in which a subset of model parameters that are associated with measured metabolites, are estimated using the minimization of slope errors. Another phase follows, in which the ODE model is solved one equation at a time and the remaining model parameters are obtained by minimizing concentration errors. The performance of this two-phase method was tested on a generic branched metabolic pathway and the glycolytic pathway of Lactococcus lactis. The results showed that the method is efficient in getting accurate parameter estimates, even when some information is missing.

Metabolic and endocrine profiles and reproductive parameters in dairy cows under grazing conditions: effect of polymorphisms in somatotropic axis genes

PubMed Central

2011-01-01

Background The present study hypothesized that GH-AluI and IGF-I-SnabI polymorphisms do change the metabolic/endocrine profiles in Holstein cows during the transition period, which in turn are associated with productive and reproductive parameters. Methods Holstein cows (Farm 1, primiparous cows, n = 110, and Farm 2, multiparous cows, n = 76) under grazing conditions were selected and GH and IGF-I genotypes were determined. Blood samples for metabolic/endocrine determinations were taken during the transition period and early lactation in both farms. Data was analyzed by farm using a repeated measures analyses including GH and IGF-I genotypes, days and interactions as fixed effects, sire and cow as random effects and calving date as covariate. Results and Discussion Frequencies of GH and IGF-I alleles were L:0.84, V:0.16 and A:0.60, B:0.40, respectively. The GH genotype was not associated with productive or reproductive variables, but interaction with days affected FCM yield in multiparous (farm 2) cows (LL yielded more than LV cows) in early lactation. The GH genotype affected NEFA and IGF-I concentrations in farm 1 (LV had higher NEFA and lower IGF-I than LL cows) suggesting a better energy status of LL cows. There was no effect of IGF-I genotype on productive variables, but a trend was found for FCM in farm 2 (AB cows yielded more than AA cows). IGF-I genotype affected calving first service interval in farm 1, and the interaction with days tended to affect FCM yield (AB cows had a shorter interval and yielded more FCM than BB cows). IGF-I genotype affected BHB, NEFA, and insulin concentrations in farm 1: primiparous BB cows had lower NEFA and BHB and higher insulin concentrations. In farm 2, there was no effect of IGF-I genotype, but there was an interaction with days on IGF-I concentration, suggesting a greater uncoupling somatropic axis in AB and BB than AA cows, being in accordance with greater FCM yield in AB cows. Conclusion The GH and IGF-I genotypes had no

Loss or Mislocalization of Aquaporin-4 Affects Diffusion Properties and Intermediary Metabolism in Gray Matter of Mice.

PubMed

Pavlin, T; Nagelhus, E A; Brekken, C; Eyjolfsson, E M; Thoren, A; Haraldseth, O; Sonnewald, U; Ottersen, O P; Håberg, A K

2017-01-01

The first aim of this study was to determine how complete or perivascular loss of aquaporin-4 (AQP4) water channels affects membrane permeability for water in the mouse brain grey matter in the steady state. Time-dependent diffusion magnetic resonance imaging was performed on global Aqp4 knock out (KO) and α-syntrophin (α-syn) KO mice, in the latter perivascular AQP4 are mislocalized, but still functioning. Control animals were corresponding wild type (WT) mice. By combining in vivo diffusion measurements with the effective medium theory and previously measured extra-cellular volume fractions, the effects of membrane permeability and extracellular volume fraction were uncoupled for Aqp4 and α-syn KO. The second aim was to assess the effect of α-syn KO on cortical intermediary metabolism combining in vivo [1- 13 C]glucose and [1,2- 13 C]acetate injection with ex vivo 13 C MR spectroscopy. Aqp4 KO increased the effective diffusion coefficient at long diffusion times by 5%, and a 14% decrease in membrane water permeability was estimated for Aqp4 KO compared with WT mice. α-syn KO did not affect the measured diffusion parameters. In the metabolic analyses, significantly lower amounts of [4- 13 C]glutamate and [4- 13 C]glutamine, and percent enrichment in [4- 13 C]glutamate were detected in the α-syn KO mice. [1,2- 13 C]acetate metabolism was unaffected in α-syn KO, but the contribution of astrocyte derived metabolites to GABA synthesis was significantly increased. Taken together, α-syn KO mice appeared to have decreased neuronal glucose metabolism, partly compensated for by utilization of astrocyte derived metabolites.

Mechanistic analysis of multi-omics datasets to generate kinetic parameters for constraint-based metabolic models.

PubMed

Cotten, Cameron; Reed, Jennifer L

2013-01-30

Constraint-based modeling uses mass balances, flux capacity, and reaction directionality constraints to predict fluxes through metabolism. Although transcriptional regulation and thermodynamic constraints have been integrated into constraint-based modeling, kinetic rate laws have not been extensively used. In this study, an in vivo kinetic parameter estimation problem was formulated and solved using multi-omic data sets for Escherichia coli. To narrow the confidence intervals for kinetic parameters, a series of kinetic model simplifications were made, resulting in fewer kinetic parameters than the full kinetic model. These new parameter values are able to account for flux and concentration data from 20 different experimental conditions used in our training dataset. Concentration estimates from the simplified kinetic model were within one standard deviation for 92.7% of the 790 experimental measurements in the training set. Gibbs free energy changes of reaction were calculated to identify reactions that were often operating close to or far from equilibrium. In addition, enzymes whose activities were positively or negatively influenced by metabolite concentrations were also identified. The kinetic model was then used to calculate the maximum and minimum possible flux values for individual reactions from independent metabolite and enzyme concentration data that were not used to estimate parameter values. Incorporating these kinetically-derived flux limits into the constraint-based metabolic model improved predictions for uptake and secretion rates and intracellular fluxes in constraint-based models of central metabolism. This study has produced a method for in vivo kinetic parameter estimation and identified strategies and outcomes of kinetic model simplification. We also have illustrated how kinetic constraints can be used to improve constraint-based model predictions for intracellular fluxes and biomass yield and identify potential metabolic limitations through the

Mechanistic analysis of multi-omics datasets to generate kinetic parameters for constraint-based metabolic models

PubMed Central

2013-01-01

Background Constraint-based modeling uses mass balances, flux capacity, and reaction directionality constraints to predict fluxes through metabolism. Although transcriptional regulation and thermodynamic constraints have been integrated into constraint-based modeling, kinetic rate laws have not been extensively used. Results In this study, an in vivo kinetic parameter estimation problem was formulated and solved using multi-omic data sets for Escherichia coli. To narrow the confidence intervals for kinetic parameters, a series of kinetic model simplifications were made, resulting in fewer kinetic parameters than the full kinetic model. These new parameter values are able to account for flux and concentration data from 20 different experimental conditions used in our training dataset. Concentration estimates from the simplified kinetic model were within one standard deviation for 92.7% of the 790 experimental measurements in the training set. Gibbs free energy changes of reaction were calculated to identify reactions that were often operating close to or far from equilibrium. In addition, enzymes whose activities were positively or negatively influenced by metabolite concentrations were also identified. The kinetic model was then used to calculate the maximum and minimum possible flux values for individual reactions from independent metabolite and enzyme concentration data that were not used to estimate parameter values. Incorporating these kinetically-derived flux limits into the constraint-based metabolic model improved predictions for uptake and secretion rates and intracellular fluxes in constraint-based models of central metabolism. Conclusions This study has produced a method for in vivo kinetic parameter estimation and identified strategies and outcomes of kinetic model simplification. We also have illustrated how kinetic constraints can be used to improve constraint-based model predictions for intracellular fluxes and biomass yield and identify potential

Coping, affect, and the metabolic syndrome in older men: how does coping get under the skin?

PubMed

Yancura, Loriena A; Aldwin, Carolyn M; Levenson, Michael R; Spiro, Avron

2006-09-01

The metabolic syndrome is a complex construct with interrelated factors of obesity, blood pressure, lipids, and glucose. It is a risk factor for a number of chronic diseases in late life. This study tested a model in which the relationship between stress and the metabolic syndrome was mediated by appraisal, coping, and affect. Data were collected from 518 male participants in the Normative Aging Study (X(age) = 68.17 years). The model was partially confirmed. Relationships among stress, appraisal, coping, and affect were valenced along positive and negative pathways. However, affect was not directly related to the metabolic syndrome. The metabolic syndrome was related to positive coping as operationalized by self-regulatory strategies. The results of this study suggest that the influence of coping on physical health may occur through emotional regulation.

Antioxidant metabolism in Xenopus laevis embryos is affected by stratospheric balloon flight.

PubMed

Rizzo, Angela M; Rossi, Federica; Zava, Stefania; Montorfano, Gigliola; Adorni, Laura; Cotronei, Vittorio; Zanini, Alba; Berra, Bruno

2007-07-01

To test the effects of low levels of radiation from space on living organisms, we flew Xenopus laevis embryos at different stages of development on a stratospheric balloon (BI.R.BA mission). After recovery, different parameters were analyzed to assess the effects of flight, with particular regard to oxidative stress damage. Because of failed temperature control during flight, the flight shielded embryos (FC) could not be used for biochemical or morphological comparisons. In contrast, the incubation conditions (i.e. temperature, containers, volumes) for the flight embryos (F) were parallel to those for the ground controls. Mortality data show that younger embryos (16 h) flown on the balloon (F) are more sensitive to radiation exposure than older ones (40 h and 6 days). Exposure during flight lowered the antioxidant potential in all embryos, particularly older ones. These preliminary data demonstrate that flight on a stratospheric balloon might affect antioxidant metabolism, though it is not yet possible to correlate these results with low radiation exposure during flight.

Select nutrients, progesterone, and interferon tau affect conceptus metabolism and development

PubMed Central

Bazer, Fuller W; Kim, Jingyoung; Song, Gwonhwa; Ka, Hakhyun; Tekwe, Carmen D; Wu, Guoyao

2012-01-01

Interferon tau (IFNT), a novel multifunctional type I interferon secreted by trophectoderm, is the pregnancy recognition signal in ruminants that also has antiviral, antiproliferative, and immunomodulatory bioactivities. IFNT, with progesterone, affects availability of the metabolic substrate in the uterine lumen by inducing expression of genes for transport of select nutrients into the uterine lumen that activate mammalian target of rapamycin (mTOR) cell signaling responsible for proliferation, migration, and protein synthesis by conceptus trophectoderm. As an immunomodulatory protein, IFNT induces an anti-inflammatory state affecting metabolic events that decrease adiposity and glutamine:fructose-6-phosphate amidotransferase 1 activity, while increasing insulin sensitivity, nitric oxide production by endothelial cells, and brown adipose tissue in rats. This short review focuses on effects of IFNT and progesterone affecting transport of select nutrients into the uterine lumen to stimulate mTOR cell signaling required for conceptus development, as well as effects of IFNT on the immune system and adiposity in rats with respect to its potential therapeutic value in reducing obesity. PMID:23050969

Xylitol affects the intestinal microbiota and metabolism of daidzein in adult male mice.

PubMed

Tamura, Motoi; Hoshi, Chigusa; Hori, Sachiko

2013-12-10

This study examined the effects of xylitol on mouse intestinal microbiota and urinary isoflavonoids. Xylitol is classified as a sugar alcohol and used as a food additive. The intestinal microbiota seems to play an important role in isoflavone metabolism. Xylitol feeding appears to affect the gut microbiota. We hypothesized that dietary xylitol changes intestinal microbiota and, therefore, the metabolism of isoflavonoids in mice. Male mice were randomly divided into two groups: those fed a 0.05% daidzein with 5% xylitol diet (XD group) and those fed a 0.05% daidzein-containing control diet (CD group) for 28 days. Plasma total cholesterol concentrations were significantly lower in the XD group than in the CD group (p < 0.05). Urinary amounts of equol were significantly higher in the XD group than in the CD group (p < 0.05). The fecal lipid contents (% dry weight) were significantly greater in the XD group than in the CD group (p < 0.01). The cecal microbiota differed between the two dietary groups. The occupation ratios of Bacteroides were significantly greater in the CD than in the XD group (p < 0.05). This study suggests that xylitol has the potential to affect the metabolism of daidzein by altering the metabolic activity of the intestinal microbiota and/or gut environment. Given that equol affects bone health, dietary xylitol plus isoflavonoids may exert a favorable effect on bone health.

Exploring natural variation of photosynthetic, primary metabolism and growth parameters in a large panel of Capsicum chinense accessions.

PubMed

Rosado-Souza, Laise; Scossa, Federico; Chaves, Izabel S; Kleessen, Sabrina; Salvador, Luiz F D; Milagre, Jocimar C; Finger, Fernando; Bhering, Leonardo L; Sulpice, Ronan; Araújo, Wagner L; Nikoloski, Zoran; Fernie, Alisdair R; Nunes-Nesi, Adriano

2015-09-01

Collectively, the results presented improve upon the utility of an important genetic resource and attest to a complex genetic basis for differences in both leaf metabolism and fruit morphology between natural populations. Diversity of accessions within the same species provides an alternative method to identify physiological and metabolic traits that have large effects on growth regulation, biomass and fruit production. Here, we investigated physiological and metabolic traits as well as parameters related to plant growth and fruit production of 49 phenotypically diverse pepper accessions of Capsicum chinense grown ex situ under controlled conditions. Although single-trait analysis identified up to seven distinct groups of accessions, working with the whole data set by multivariate analyses allowed the separation of the 49 accessions in three clusters. Using all 23 measured parameters and data from the geographic origin for these accessions, positive correlations between the combined phenotypes and geographic origin were observed, supporting a robust pattern of isolation-by-distance. In addition, we found that fruit set was positively correlated with photosynthesis-related parameters, which, however, do not explain alone the differences in accession susceptibility to fruit abortion. Our results demonstrated that, although the accessions belong to the same species, they exhibit considerable natural intraspecific variation with respect to physiological and metabolic parameters, presenting diverse adaptation mechanisms and being a highly interesting source of information for plant breeders. This study also represents the first study combining photosynthetic, primary metabolism and growth parameters for Capsicum to date.

Dexmedetomidine metabolic clearance is not affected by fat mass in obese patients.

PubMed

Rolle, A; Paredes, S; Cortínez, L I; Anderson, B J; Quezada, N; Solari, S; Allende, F; Torres, J; Cabrera, D; Contreras, V; Carmona, J; Ramírez, C; Oliveros, A M; Ibacache, M

2018-05-01

Obesity has been associated with reduced dexmedetomidine clearance, suggesting impaired hepatic function or reduced hepatic blood flow. The aim of this study was to clarify the effect of obesity in dexmedetomidine metabolic clearance. Forty patients, ASA I-III, 18-60 yr old, weighing 47-126 kg, scheduled for abdominal laparoscopic surgery, were enrolled. Anaesthetic agents (propofol, remifentanil, and dexmedetomidine) were dosed based on lean body weight measured by dual X-ray absorptiometry. Serial venous samples were drawn during and after dexmedetomidine infusion. A pharmacokinetic analysis was undertaken using non-linear mixed-effect models. In the modelling approach, the total body weight, lean body weight, and adjusted body weight were first tested as size descriptors for volumes and clearances. Hepatic blood flow, liver histopathology, liver enzymes, and gene expression of metabolic enzymes (UGT2B10 and UGT1A4) were tested as covariates of dexmedetomidine metabolic clearance. A decrease in NONMEM objective function value (ΔOFV) of 3.84 points, for an added parameter, was considered significant at the 0.05 level. A total of 637 dexmedetomidine serum samples were obtained. A two-compartmental model scaled to measured lean weight adequately described the dexmedetomidine pharmacokinetics. Liver blood flow was a covariate for dexmedetomidine clearance (ΔOFV=-5.878). Other factors, including fat mass, histopathological damage, and differential expression of enzymes, did not affect the dexmedetomidine clearance in the population studied (ΔOFV<3.84). We did not find a negative influence of obesity in dexmedetomidine clearance when doses were adjusted to lean body weight. Liver blood flow showed a significant effect on dexmedetomidine clearance. NCT02557867. Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

Effects of magnesium supplements on blood pressure, endothelial function and metabolic parameters in healthy young men with a family history of metabolic syndrome.

PubMed

Cosaro, E; Bonafini, S; Montagnana, M; Danese, E; Trettene, M S; Minuz, P; Delva, P; Fava, C

2014-11-01

Magnesium plays an important role in the modulation of vascular tone and endothelial function and can regulate glucose and lipid metabolism. Patients with hypertension, metabolic syndrome (MetS) and diabetes mellitus (T2DM) have low body magnesium content; indeed, magnesium supplementation has been shown to have a positive effect on blood pressure (BP) and gluco-metabolic parameters. The aim of our study was to evaluate the effect of magnesium supplements on hemodynamic and metabolic parameters in healthy men with a positive family history of MetS or T2DM. In a randomized, double-blind, placebo-controlled 8-week crossover trial with a 4 week wash-out period, oral supplements of 8.1 mmol of magnesium-pidolate or placebo were administered twice a day to 14 healthy normomagnesemic participants, aged 23-33 years. The primary endpoint was office BP, measured with a semiautomatic oscillometric device. Secondary endpoints included characteristics of the MetS, namely endothelial function, arterial stiffness and inflammation. Plasma and urinary magnesium were measured in all participants while free intracellular magnesium was measured only in a subsample. There was no significant difference in either systolic and diastolic BP in participants post-magnesium supplementation and post-placebo treatment when compared to baseline BP measurements. Further, the metabolic, inflammatory and hemodynamic parameters did not vary significantly during the study. Our study showed no beneficial effect of magnesium supplements on BP, vascular function and glycolipid profile in young men with a family history of MetS/T2DM (trial registration at clinicaltrial.gov ID: NCT01181830; 12th of Aug 2010). Copyright © 2014 Elsevier B.V. All rights reserved.

Xylitol Affects the Intestinal Microbiota and Metabolism of Daidzein in Adult Male Mice

PubMed Central

Tamura, Motoi; Hoshi, Chigusa; Hori, Sachiko

2013-01-01

This study examined the effects of xylitol on mouse intestinal microbiota and urinary isoflavonoids. Xylitol is classified as a sugar alcohol and used as a food additive. The intestinal microbiota seems to play an important role in isoflavone metabolism. Xylitol feeding appears to affect the gut microbiota. We hypothesized that dietary xylitol changes intestinal microbiota and, therefore, the metabolism of isoflavonoids in mice. Male mice were randomly divided into two groups: those fed a 0.05% daidzein with 5% xylitol diet (XD group) and those fed a 0.05% daidzein-containing control diet (CD group) for 28 days. Plasma total cholesterol concentrations were significantly lower in the XD group than in the CD group (p < 0.05). Urinary amounts of equol were significantly higher in the XD group than in the CD group (p < 0.05). The fecal lipid contents (% dry weight) were significantly greater in the XD group than in the CD group (p < 0.01). The cecal microbiota differed between the two dietary groups. The occupation ratios of Bacteroides were significantly greater in the CD than in the XD group (p < 0.05). This study suggests that xylitol has the potential to affect the metabolism of daidzein by altering the metabolic activity of the intestinal microbiota and/or gut environment. Given that equol affects bone health, dietary xylitol plus isoflavonoids may exert a favorable effect on bone health. PMID:24336061

Efficacy comparison of Korean ginseng and American ginseng on body temperature and metabolic parameters.

PubMed

Park, Eun-Young; Kim, Mi-Hwi; Kim, Eung-Hwi; Lee, Eun-Kyu; Park, In-Sun; Yang, Duck-Choon; Jun, Hee-Sook

2014-01-01

Ginseng has beneficial effects in cancer, diabetes and aging. There are two main varieties of ginseng: Panax ginseng (Korean ginseng) and Panax quinquefolius (American ginseng). There are anecdotal reports that American ginseng helps reduce body temperature, whereas Korean ginseng improves blood circulation and increases body temperature; however, their respective effects on body temperature and metabolic parameters have not been studied. We investigated body temperature and metabolic parameters in mice using a metabolic cage. After administering ginseng extracts acutely (single dose of 1000 mg/kg) or chronically (200 mg/kg/day for four weeks), core body temperature, food intake, oxygen consumption and activity were measured, as well as serum levels of pyrogen-related factors and mRNA expression of metabolic genes. Acute treatment with American ginseng reduced body temperature compared with PBS-treated mice during the night; however, there was no significant effect of ginseng treatment on body temperature after four weeks of treatment. VO 2, VCO 2, food intake, activity and energy expenditure were unchanged after both acute and chronic ginseng treatment compared with PBS treatment. In acutely treated mice, serum thyroxin levels were reduced by red and American ginseng, and the serum prostaglandin E2 level was reduced by American ginseng. In chronically treated mice, red and white ginseng reduced thyroxin levels. We conclude that Korean ginseng does not stimulate metabolism in mice, whereas a high dose of American ginseng may reduce night-time body temperature and pyrogen-related factors.

Total solids content: a key parameter of metabolic pathways in dry anaerobic digestion

PubMed Central

2013-01-01

Background In solid-state anaerobic digestion (AD) bioprocesses, hydrolytic and acidogenic microbial metabolisms have not yet been clarified. Since these stages are particularly important for the establishment of the biological reaction, better knowledge could optimize the process performances by process parameters adjustment. Results This study demonstrated the effect of total solids (TS) content on microbial fermentation of wheat straw with six different TS contents ranging from wet to dry conditions (10 to 33% TS). Three groups of metabolic behaviors were distinguished based on wheat straw conversion rates with 2,200, 1,600, and 1,400 mmol.kgVS-1 of fermentative products under wet (10 and 14% TS), dry (19 to 28% TS), and highly dry (28 to 33% TS) conditions, respectively. Furthermore, both wet and dry fermentations showed acetic and butyric acid metabolisms, whereas a mainly butyric acid metabolism occurred in highly dry fermentation. Conclusion Substrate conversion was reduced with no changes of the metabolic pathways until a clear limit at 28% TS content, which corresponded to the threshold value of free water content of wheat straw. This study suggested that metabolic pathways present a limit of TS content for high-solid AD. PMID:24261971

Free triiodothyronine/free thyroxine ratio rather than thyrotropin is more associated with metabolic parameters in healthy euthyroid adult subjects.

PubMed

Park, So Young; Park, Se Eun; Jung, Sang Won; Jin, Hyun Seok; Park, Ie Byung; Ahn, Song Vogue; Lee, Sihoon

2017-07-01

The interrelation between TSH, thyroid hormones and metabolic parameters is complex and has not been confirmed. This study aimed to determine the association of TSH and thyroid hormones in euthyroid subjects and the relationship between thyroid function and metabolic risk factors. Furthermore, this study examined whether thyroid function has predictive power for metabolic syndrome. This is a cross-sectional study that included subjects in a medical health check-up programme at a single institution. The study included 132 346 participants (66 991 men and 65 355 women) aged over 18 years who had TSH, free T4 (FT4) and free T3 (FT3) levels within the institutional reference ranges. Thyrotropin, FT4, FT3 and metabolic parameters including height, weight, waist circumference, blood pressure, serum levels of total cholesterol, triglyceride, high-density lipoprotein cholesterol, insulin and glucose were measured. There was a positive association between FT3/FT4 ratio and TSH in both men and women after adjusting for age, body mass index, smoking status and menopausal status (in women). The FT3/FT4 ratio and TSH were positively associated with risk of metabolic syndrome parameters including insulin resistance. The FT3/FT4 ratio had a greater predictive power than TSH for metabolic syndrome in both men and women. Thyrotropin levels were positively associated with FT3/FT4 ratio within the euthyroid range. The higher FT3/FT4 ratio is associated with increased risk of metabolic syndrome parameters and insulin resistance. FT3/FT4 ratio has a better predictive power for metabolic syndrome than TSH. © 2017 John Wiley & Sons Ltd.

Short-term fructose ingestion affects the brain independently from establishment of metabolic syndrome.

PubMed

Jiménez-Maldonado, Alberto; Ying, Zhe; Byun, Hyae Ran; Gomez-Pinilla, Fernando

2018-01-01

Chronic fructose ingestion is linked to the global epidemic of metabolic syndrome (MetS), and poses a serious threat to brain function. We asked whether a short period (one week) of fructose ingestion potentially insufficient to establish peripheral metabolic disorder could impact brain function. We report that the fructose treatment had no effect on liver/body weight ratio, weight gain, glucose tolerance and insulin sensitivity, was sufficient to reduce several aspects of hippocampal plasticity. Fructose consumption reduced the levels of the neuronal nuclear protein NeuN, Myelin Basic Protein, and the axonal growth-associated protein 43, concomitant with a decline in hippocampal weight. A reduction in peroxisome proliferator-activated receptor gamma coactivator-1 alpha and Cytochrome c oxidase subunit II by fructose treatment is indicative of mitochondrial dysfunction. Furthermore, the GLUT5 fructose transporter was increased in the hippocampus after fructose ingestion suggesting that fructose may facilitate its own transport to brain. Fructose elevated levels of ketohexokinase in the liver but did not affect SIRT1 levels, suggesting that fructose is metabolized in the liver, without severely affecting liver function commensurable to an absence of metabolic syndrome condition. These results advocate that a short period of fructose can influence brain plasticity without a major peripheral metabolic dysfunction. Copyright © 2017 Elsevier B.V. All rights reserved.

Identifying tectonic parameters that affect tsunamigenesis

NASA Astrophysics Data System (ADS)

van Zelst, I.; Brizzi, S.; Heuret, A.; Funiciello, F.; van Dinther, Y.

2016-12-01

The role of tectonics in tsunami generation is at present poorly understood. However, the fact thatsome regions produce more tsunamis than others indicates that tectonics could influencetsunamigenesis. Here, we complement a global earthquake database that contains geometrical,mechanical, and seismicity parameters of subduction zones with tsunami data. We statisticallyanalyse the database to identify the tectonic parameters that affect tsunamigenesis. The Pearson'sproduct-moment correlation coefficients reveal high positive correlations of 0.65 between,amongst others, the maximum water height of tsunamis and the seismic coupling in a subductionzone. However, these correlations are mainly caused by outliers. The Spearman's rank correlationcoefficient results in statistically significant correlations of 0.60 between the number of tsunamisin a subduction zone and subduction velocity (positive correlation) and the sediment thickness atthe trench (negative correlation). Interestingly, there is a positive correlation between the latter andtsunami magnitude. These bivariate statistical methods are extended to a binary decision tree(BDT) and multivariate analysis. Using the BDT, the tectonic parameters that distinguish betweensubduction zones with tsunamigenic and non-tsunamigenic earthquakes are identified. To assessphysical causality of the tectonic parameters with regard to tsunamigenesis, we complement ouranalysis by a numerical study of the most promising parameters using a geodynamic seismic cyclemodel. We show that the inclusion of sediments on the subducting plate results in an increase insplay fault activity, which could lead to larger vertical seafloor displacements due to their steeperdips and hence a larger tsunamigenic potential. We also show that the splay fault is the preferredrupture path for a strongly velocity strengthening friction regime in the shallow part of thesubduction zone, which again increases the tsunamigenic potential.

Parameters of metabolic quantification in clinical practice. Is it now time to include them in reports?

PubMed

Mucientes, J; Calles, L; Rodríguez, B; Mitjavila, M

2018-01-18

Qualitative techniques have traditionally been the standard for the diagnostic assessment with 18 F-FDG PET studies. Since the introduction of the technique, quantitative parameters have been sought, more accurate and with better diagnostic precision, that may offer relevant information of the behavior, aggressiveness or prognosis of tumors. Nowadays, more and more studies with high quality evidence show the utility of other metabolic parameters different from the SUV maximum, which despite being widely used in clinical practice is controversial and many physicians still do not know its real meaning. The objective of this paper has been to review the key concepts of these metabolic parameters that could be relevant in normal practice in the future. It has been seen that there is more evidence in the complete evaluation of the metabolism of a lesion, through volumetric parameters that more adequately reflect the patient's tumor burden. Basically, these parameters calculate the volume of tumor that fulfills certain characteristics. A software available in the majority of the workstations has been used for this purpose and it has allowed to calculate these volumes using more or less complex criteria. The simplest threshold-based segmentation methods are available in most equipments, they are easy to calculate and they have been shown in many studies to have an important prognostic significance. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

Vascular affection in relation to oxidative DNA damage in metabolic syndrome.

PubMed

Abd El Aziz, Rokayaa; Fawzy, Mary Wadie; Khalil, Noha; Abdel Atty, Sahar; Sabra, Zainab

2018-02-01

Obesity has become an important issue affecting both males and females. Obesity is now regarded as an independent risk factor for atherosclerosis-related diseases. Metabolic syndrome is associated with increased risk for development of cardiovascular disease. Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine concentration has been used to express oxidation status. Twenty-seven obese patients with metabolic syndrome, 25 obese patients without metabolic syndrome and 31 healthy subjects were included in our study. They were subjected to full history and clinical examination; fasting blood sugar (FBS), 2 hour post prandial blood sugar (2HPP), lipid profile, urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine and carotid duplex, A/B index and tibial diameters were all assessed. There was a statistically significant difference ( p = 0.027) in diameter of the right anterior tibial artery among the studied groups, with decreased diameter of the right anterior tibial artery in obese patients with metabolic syndrome compared to those without metabolic syndrome; the ankle brachial index revealed a lower index in obese patients with metabolic syndrome compared to those without metabolic syndrome. There was a statistically insignificant difference ( p = 0.668) in the 8-oxodG in the studied groups. In obese patients with metabolic syndrome there was a positive correlation between 8-oxodG and total cholesterol and LDL. Urinary 8-oxodG is correlated to total cholesterol and LDL in obese patients with metabolic syndrome; signifying its role in the mechanism of dyslipidemia in those patients. Our study highlights the importance of anterior tibial artery diameter measurement and ankle brachial index as an early marker of atherosclerosis, and how it may be an earlier marker than carotid intima-media thickness.

Automated measurements of metabolic tumor volume and metabolic parameters in lung PET/CT imaging

NASA Astrophysics Data System (ADS)

Orologas, F.; Saitis, P.; Kallergi, M.

2017-11-01

Patients with lung tumors or inflammatory lung disease could greatly benefit in terms of treatment and follow-up by PET/CT quantitative imaging, namely measurements of metabolic tumor volume (MTV), standardized uptake values (SUVs) and total lesion glycolysis (TLG). The purpose of this study was the development of an unsupervised or partially supervised algorithm using standard image processing tools for measuring MTV, SUV, and TLG from lung PET/CT scans. Automated metabolic lesion volume and metabolic parameter measurements were achieved through a 5 step algorithm: (i) The segmentation of the lung areas on the CT slices, (ii) the registration of the CT segmented lung regions on the PET images to define the anatomical boundaries of the lungs on the functional data, (iii) the segmentation of the regions of interest (ROIs) on the PET images based on adaptive thresholding and clinical criteria, (iv) the estimation of the number of pixels and pixel intensities in the PET slices of the segmented ROIs, (v) the estimation of MTV, SUVs, and TLG from the previous step and DICOM header data. Whole body PET/CT scans of patients with sarcoidosis were used for training and testing the algorithm. Lung area segmentation on the CT slices was better achieved with semi-supervised techniques that reduced false positive detections significantly. Lung segmentation results agreed with the lung volumes published in the literature while the agreement between experts and algorithm in the segmentation of the lesions was around 88%. Segmentation results depended on the image resolution selected for processing. The clinical parameters, SUV (either mean or max or peak) and TLG estimated by the segmented ROIs and DICOM header data provided a way to correlate imaging data to clinical and demographic data. In conclusion, automated MTV, SUV, and TLG measurements offer powerful analysis tools in PET/CT imaging of the lungs. Custom-made algorithms are often a better approach than the manufacturer�

Factors affecting urethrocystographic parameters in urinary continent women.

PubMed

Yang, J M

1996-06-01

To evaluate the urethrocystographic changes in different conditions, 154 women were evaluated by using introital sonography. Patients were divided into three groups: group 1 (n = 103) normal, including 10 postmenopausal women; group 2 (n = 46) pregnant, including 16 women in the first trimester, 15 in the second trimester, and 15 in the third trimester; group 3 (n = 15) severe genitourinary prolapse. None of the 154 women had a history of urinary incontinence. The following parameters were measured at rest: urethral thickness, uretheral length, urethral inclination, and posterior urethrovesical angle. On maximum straining, urethral inclination, posterior urethrovesical angle, and rotational angle were measured. In general, age, parity, and menopause did not affect the urethrocystographic parameters in Group 1 patients. Postmenopausal women had a significant decrease in the urethral thickness compared with the premenopausal women (p = 0.026). Patients in Groups 2 and 3 had a significantly lower urethral position than those in group 1. However, hypermobility of the urethra was found only in Group 3. Different menstrual ages did not affect the urethral position but could affect the posterior urethrovesical angle at rest in the first trimester. Introital sonography, without the risk of radiation exposure, enables the observation of static and dynamic changes in the lower urinary tract, both repeatedly and reproducibly.

Physical activity and metabolic disease among people with affective disorders: Prevention, management and implementation.

PubMed

Vancampfort, Davy; Stubbs, Brendon

2017-12-15

One in ten and one in three of people with affective disorders experience diabetes and metabolic syndrome respectively. Physical activity (PA) and sedentary behaviour (SB) are key risk factors that can ameliorate the risk of metabolic disease among this population. However, PA is often seen as luxury and/or a secondary component within the management of people with affective disorders. The current article provides a non-systematic best-evidence synthesis of the available literature, detailing a number of suggestions for the implementation of PA into clinical practice. Whilst the evidence is unequivocal for the efficacy of PA to prevent and manage metabolic disease in the general population, it is in its infancy in this patient group. Nonetheless, action must be taken now to ensure that PA and reducing SB are given a priority to prevent and manage metabolic diseases and improve wider health outcomes. PA should be treated as a vital sign and all people with affective disorders asked about their activity levels and if appropriate advised to increase this. There is a need for investment in qualified exercise specialists in clinical practice such as physiotherapists to undertake and oversee PA in practice. Behavioural strategies such as the self-determined theory should be employed to encourage adherence. Funding is required to develop the evidence base and elucidate the optimal intervention characteristics. PA interventions should form an integral part of the multidisciplinary management of people with affective disorders and our article outlines the evidence and strategies to implement this in practice. Copyright © 2016 Elsevier B.V. All rights reserved.

Assessment of Chitosan-Affected Metabolic Response by Peroxisome Proliferator-Activated Receptor Bioluminescent Imaging-Guided Transcriptomic Analysis

PubMed Central

Kao, Chia-Hung; Hsiang, Chien-Yun; Ho, Tin-Yun

2012-01-01

Chitosan has been widely used in food industry as a weight-loss aid and a cholesterol-lowering agent. Previous studies have shown that chitosan affects metabolic responses and contributes to anti-diabetic, hypocholesteremic, and blood glucose-lowering effects; however, the in vivo targeting sites and mechanisms of chitosan remain to be clarified. In this study, we constructed transgenic mice, which carried the luciferase genes driven by peroxisome proliferator-activated receptor (PPAR), a key regulator of fatty acid and glucose metabolism. Bioluminescent imaging of PPAR transgenic mice was applied to report the organs that chitosan acted on, and gene expression profiles of chitosan-targeted organs were further analyzed to elucidate the mechanisms of chitosan. Bioluminescent imaging showed that constitutive PPAR activities were detected in brain and gastrointestinal tract. Administration of chitosan significantly activated the PPAR activities in brain and stomach. Microarray analysis of brain and stomach showed that several pathways involved in lipid and glucose metabolism were regulated by chitosan. Moreover, the expression levels of metabolism-associated genes like apolipoprotein B (apoB) and ghrelin genes were down-regulated by chitosan. In conclusion, these findings suggested the feasibility of PPAR bioluminescent imaging-guided transcriptomic analysis on the evaluation of chitosan-affected metabolic responses in vivo. Moreover, we newly identified that downregulated expression of apoB and ghrelin genes were novel mechanisms for chitosan-affected metabolic responses in vivo. PMID:22496881

The effect of abdominal obesity in patients with polycystic ovary syndrome on metabolic parameters.

PubMed

Franik, G; Bizoń, A; Włoch, S; Pluta, D; Blukacz, Ł; Milnerowicz, H; Madej, P

2017-11-01

Polycystic ovarian syndrome and obesity contribute to the metabolic complications for women of reproductive age. The aim of present study was to analyze the effect of abdominal obesity expressed using waist/hip ratio (WHR) in patients with polycystic ovary syndrome on metabolic parameters. The study included 659 women with PCOS with WHR <0.8 and ≥0.8 aged between 17 and 44 years. Patients were tested for follicular stimulating hormone, luteinizing hormone, 17-beta-estradiol, dehydroepiandrosterone sulfate, androstenedione, sex hormone binding globulin, and total lipid profile during the follicular phase (within 3 and 5 days of their menstrual cycle). Also, fasting glucose and insulin concentrations, and after, oral-glucose glucose administration, were determinate. De Ritis and Castelli index I and II were calculated. Women with WHR ≥0.8 had higher concentration of glucose and  insulin (both fasting and after 120 min of oral administration of 75 g glucose), as well as HOMA-IR value, than women with WHR value < 0.8. Also, abdominal obesity disorders hormonal parameters. Higher free androgen index and lower concentration of sex hormone binding globulin and dehydroepiandrosterone sulfate were found in female with WHR ≥ 0.8. Follicular stimulating hormone, luteinizing hormone, androstenedione, and 17-beta-estradiol, were on similar level in both groups. Elevation in triglycerides, total cholesterol, and low-density lipoprotein levels, as well as decrease in high density lipoprotein level in serum of women with WHR value ≥ 0.8, were found when compared to women with WHR < 0.8. A statistically significant correlation was found between WHR value and glucose, insulin, sex hormone binding globulin, free androgen index and lipid profile parameters. Abdominal obesity causes additional disorders in metabolic and hormonal parameters in PCOS women, which confirmed changes in analyzed parameters between PCOS women with WHR < 0.8 and WHR ≥ 0.8 and statistically

Multiscale structures of lipids in foods as parameters affecting fatty acid bioavailability and lipid metabolism.

PubMed

Michalski, M C; Genot, C; Gayet, C; Lopez, C; Fine, F; Joffre, F; Vendeuvre, J L; Bouvier, J; Chardigny, J M; Raynal-Ljutovac, K

2013-10-01

On a nutritional standpoint, lipids are now being studied beyond their energy content and fatty acid (FA) profiles. Dietary FA are building blocks of a huge diversity of more complex molecules such as triacylglycerols (TAG) and phospholipids (PL), themselves organised in supramolecular structures presenting different thermal behaviours. They are generally embedded in complex food matrixes. Recent reports have revealed that molecular and supramolecular structures of lipids and their liquid or solid state at the body temperature influence both the digestibility and metabolism of dietary FA. The aim of the present review is to highlight recent knowledge on the impact on FA digestion, absorption and metabolism of: (i) the intramolecular structure of TAG; (ii) the nature of the lipid molecules carrying FA; (iii) the supramolecular organization and physical state of lipids in native and formulated food products and (iv) the food matrix. Further work should be accomplished now to obtain a more reliable body of evidence and integrate these data in future dietary recommendations. Additionally, innovative lipid formulations in which the health beneficial effects of either native or recomposed structures of lipids will be taken into account can be foreseen. Copyright © 2013 Elsevier Ltd. All rights reserved.

Complete Proteomic-Based Enzyme Reaction and Inhibition Kinetics Reveal How Monolignol Biosynthetic Enzyme Families Affect Metabolic Flux and Lignin in Populus trichocarpa[W

PubMed Central

Wang, Jack P.; Naik, Punith P.; Chen, Hsi-Chuan; Shi, Rui; Lin, Chien-Yuan; Liu, Jie; Shuford, Christopher M.; Li, Quanzi; Sun, Ying-Hsuan; Tunlaya-Anukit, Sermsawat; Williams, Cranos M.; Muddiman, David C.; Ducoste, Joel J.; Sederoff, Ronald R.; Chiang, Vincent L.

2014-01-01

We established a predictive kinetic metabolic-flux model for the 21 enzymes and 24 metabolites of the monolignol biosynthetic pathway using Populus trichocarpa secondary differentiating xylem. To establish this model, a comprehensive study was performed to obtain the reaction and inhibition kinetic parameters of all 21 enzymes based on functional recombinant proteins. A total of 104 Michaelis-Menten kinetic parameters and 85 inhibition kinetic parameters were derived from these enzymes. Through mass spectrometry, we obtained the absolute quantities of all 21 pathway enzymes in the secondary differentiating xylem. This extensive experimental data set, generated from a single tissue specialized in wood formation, was used to construct the predictive kinetic metabolic-flux model to provide a comprehensive mathematical description of the monolignol biosynthetic pathway. The model was validated using experimental data from transgenic P. trichocarpa plants. The model predicts how pathway enzymes affect lignin content and composition, explains a long-standing paradox regarding the regulation of monolignol subunit ratios in lignin, and reveals novel mechanisms involved in the regulation of lignin biosynthesis. This model provides an explanation of the effects of genetic and transgenic perturbations of the monolignol biosynthetic pathway in flowering plants. PMID:24619611

Fermentation and Hydrogen Metabolism Affect Uranium Reduction by Clostridia

DOE PAGES

Gao, Weimin; Francis, Arokiasamy J.

2013-01-01

Previously, it has been shown that not only is uranium reduction under fermentation condition common among clostridia species, but also the strains differed in the extent of their capability and the pH of the culture significantly affected uranium(VI) reduction. In this study, using HPLC and GC techniques, metabolic properties of those clostridial strains active in uranium reduction under fermentation conditions have been characterized and their effects on capability variance of uranium reduction discussed. Then, the relationship between hydrogen metabolism and uranium reduction has been further explored and the important role played by hydrogenase in uranium(VI) and iron(III) reduction by clostridiamore » demonstrated. When hydrogen was provided as the headspace gas, uranium(VI) reduction occurred in the presence of whole cells of clostridia. This is in contrast to that of nitrogen as the headspace gas. Without clostridia cells, hydrogen alone could not result in uranium(VI) reduction. In alignment with this observation, it was also found that either copper(II) addition or iron depletion in the medium could compromise uranium reduction by clostridia. In the end, a comprehensive model was proposed to explain uranium reduction by clostridia and its relationship to the overall metabolism especially hydrogen (H 2 ) production.« less

The metabolic footprint of aging in mice.

PubMed

Houtkooper, Riekelt H; Argmann, Carmen; Houten, Sander M; Cantó, Carles; Jeninga, Ellen H; Andreux, Pénélope A; Thomas, Charles; Doenlen, Raphaël; Schoonjans, Kristina; Auwerx, Johan

2011-01-01

Aging is characterized by a general decline in cellular function, which ultimately will affect whole body homeostasis. Although DNA damage and oxidative stress all contribute to aging, metabolic dysfunction is a common hallmark of aging at least in invertebrates. Since a comprehensive overview of metabolic changes in otherwise healthy aging mammals is lacking, we here compared metabolic parameters of young and 2 year old mice. We systemically integrated in vivo phenotyping with gene expression, biochemical analysis, and metabolomics, thereby identifying a distinguishing metabolic footprint of aging. Among the affected pathways in both liver and muscle we found glucose and fatty acid metabolism, and redox homeostasis. These alterations translated in decreased long chain acylcarnitines and increased free fatty acid levels and a marked reduction in various amino acids in the plasma of aged mice. As such, these metabolites serve as biomarkers for aging and healthspan.

The metabolic footprint of aging in mice

PubMed Central

Houtkooper, Riekelt H.; Argmann, Carmen; Houten, Sander M.; Cantó, Carles; Jeninga, Ellen H.; Andreux, Pénélope A.; Thomas, Charles; Doenlen, Raphaël; Schoonjans, Kristina; Auwerx, Johan

2011-01-01

Aging is characterized by a general decline in cellular function, which ultimately will affect whole body homeostasis. Although DNA damage and oxidative stress all contribute to aging, metabolic dysfunction is a common hallmark of aging at least in invertebrates. Since a comprehensive overview of metabolic changes in otherwise healthy aging mammals is lacking, we here compared metabolic parameters of young and 2 year old mice. We systemically integrated in vivo phenotyping with gene expression, biochemical analysis, and metabolomics, thereby identifying a distinguishing metabolic footprint of aging. Among the affected pathways in both liver and muscle we found glucose and fatty acid metabolism, and redox homeostasis. These alterations translated in decreased long chain acylcarnitines and increased free fatty acid levels and a marked reduction in various amino acids in the plasma of aged mice. As such, these metabolites serve as biomarkers for aging and healthspan. PMID:22355651

Perceived stress correlates with visceral obesity and lipid parameters of the metabolic syndrome: A systematic review and meta-analysis.

PubMed

Tenk, Judit; Mátrai, Péter; Hegyi, Péter; Rostás, Ildikó; Garami, András; Szabó, Imre; Hartmann, Petra; Pétervári, Erika; Czopf, László; Hussain, Alizadeh; Simon, Mária; Szujó, Szabina; Balaskó, Márta

2018-05-12

Perceived stress has been proposed as a risk factor of metabolic syndrome. However, correlations between perceived stress and parameters of the metabolic syndrome have not been properly analyzed despite extensive research data on the topic. Our current meta-analysis aimed to examine the mutual association between perceived stress of patients and parameters of metabolic syndrome. This systematic review has been registered on the PROSPERO database (registration number CRD42017055293). Eligible studies divided participants based on their stress level or on the presence of metabolic syndrome. They reported at least one parameter of the metabolic syndrome or the stress level of the participants measured with some stress scale. Data from 17 articles met the eligibility criteria and were included. Random effects model with the DerSimonian and Laird weighting methods was applied. I-squared indicator and Q test were performed to assess heterogeneity. Although the majority of individual studies failed to demonstrate correlations between stress and their analyzed parameters of metabolic syndrome, our meta-analysis showed a significant association between stress and BMI [average effect size (ES) with 95% confidence interval (95%CI), ES = 0.65, 95%CI 0.16, 1.14), waist circumference (ES = 1.84 cm, 95%CI 0.79, 2.89) and serum triglyceride level (ES = 7.52 mg/dl, 95%CI 0.07, 14.96). Additional analysis confirmed effects of stress on serum HDL (ES = - 1.699 mg/dl, 95%CI -2.966, -0.432) and diastolic blood pressure (ES = 1.04 mmHg, 95%CI 0.18, 1.89). No correlations were found for fasting glucose or systolic blood pressure. No association between metabolic syndrome and stress level of patients was detected either. The potentially key role of visceral obesity in the association between perceived stress and dyslipidemia or diastolic blood pressure are discussed together with potential moderators (e.g. gender-differences, variations in stress assessment and

A review of the meteorological parameters which affect aerial application

NASA Technical Reports Server (NTRS)

Christensen, L. S.; Frost, W.

1979-01-01

The ambient wind field and temperature gradient were found to be the most important parameters. Investigation results indicated that the majority of meteorological parameters affecting dispersion were interdependent and the exact mechanism by which these factors influence the particle dispersion was largely unknown. The types and approximately ranges of instrumented capabilities for a systematic study of the significant meteorological parameters influencing aerial applications were defined. Current mathematical dispersion models were also briefly reviewed. Unfortunately, a rigorous dispersion model which could be applied to aerial application was not available.

Evaluation of an S-system root-finding method for estimating parameters in a metabolic reaction model.

PubMed

Iwata, Michio; Miyawaki-Kuwakado, Atsuko; Yoshida, Erika; Komori, Soichiro; Shiraishi, Fumihide

2018-02-02

In a mathematical model, estimation of parameters from time-series data of metabolic concentrations in cells is a challenging task. However, it seems that a promising approach for such estimation has not yet been established. Biochemical Systems Theory (BST) is a powerful methodology to construct a power-law type model for a given metabolic reaction system and to then characterize it efficiently. In this paper, we discuss the use of an S-system root-finding method (S-system method) to estimate parameters from time-series data of metabolite concentrations. We demonstrate that the S-system method is superior to the Newton-Raphson method in terms of the convergence region and iteration number. We also investigate the usefulness of a translocation technique and a complex-step differentiation method toward the practical application of the S-system method. The results indicate that the S-system method is useful to construct mathematical models for a variety of metabolic reaction networks. Copyright © 2018 Elsevier Inc. All rights reserved.

[Metabolic acidosis].

PubMed

Regolisti, Giuseppe; Fani, Filippo; Antoniotti, Riccardo; Castellano, Giuseppe; Cremaschi, Elena; Greco, Paolo; Parenti, Elisabetta; Morabito, Santo; Sabatino, Alice; Fiaccadori, Enrico

2016-01-01

Metabolic acidosis is frequently observed in clinical practice, especially among critically ill patients and/or in the course of renal failure. Complex mechanisms are involved, in most cases identifiable by medical history, pathophysiology-based diagnostic reasoning and measure of some key acid-base parameters that are easily available or calculable. On this basis the bedside differential diagnosis of metabolic acidosis should be started from the identification of the two main subtypes of metabolic acidosis: the high anion gap metabolic acidosis and the normal anion gap (or hyperchloremic) metabolic acidosis. Metabolic acidosis, especially in its acute forms with elevated anion gap such as is the case of lactic acidosis, diabetic and acute intoxications, may significantly affect metabolic body homeostasis and patients hemodynamic status, setting the stage for true medical emergencies. The therapeutic approach should be first aimed at early correction of concurrent clinical problems (e.g. fluids and hemodynamic optimization in case of shock, mechanical ventilation in case of concomitant respiratory failure, hemodialysis for acute intoxications etc.), in parallel to the formulation of a diagnosis. In case of severe acidosis, the administration of alkalizing agents should be carefully evaluated, taking into account the risk of side effects, as well as the potential need of renal replacement therapy.

The chitosan affects severely the carbon metabolism in mango (Mangifera indica L. cv. Palmer) fruit during storage.

PubMed

Cosme Silva, Gláucia Michelle; Silva, Willian Batista; Medeiros, David B; Salvador, Acácio Rodrigues; Cordeiro, Maria Helena Menezes; da Silva, Natália Martins; Santana, Diederson Bortolini; Mizobutsi, Gisele Polete

2017-12-15

Mango is a highly perishable fruit with a short post-harvest time due to the intense metabolic activity after harvesting. In attempt to evaluate the effects of chitosan in mango fruits, it was treated with 0%, 1%, 2% or 3% of chitosan solutions, placed into plastic trays, and stored at room temperature. Changes in physical and chemical parameters were evaluated. Chitosan delayed the climacteric peak, water loss and firmness. Further, few changes in soluble solid content, titratable acidity, pH of the pulp as well as in sugar content and decreased starch degradation were observed. Altogether, our results suggest chitosan edible coating effectively prolongs the quality attributes, affecting basic mitochondrial respiration and starch degradation rate. Copyright © 2017 Elsevier Ltd. All rights reserved.

Postoperative Changes in Metabolic Parameters of Patients with Surgically Controlled Acromegaly: Assessment of New Stringent Cure Criteria.

PubMed

Yonenaga, Masanori; Fujio, Shingo; Habu, Mika; Arimura, Hiroshi; Hiwatari, Takaaki; Tanaka, Shunichi; Kinoshita, Yasuyuki; Hosoyama, Hiroshi; Hirano, Hirofumi; Arita, Kazunori

2018-04-15

The criteria for surgical cure of acromegaly have become more stringent during the past decades and a change from Cortina to new consensus criteria has recently been proposed. However, the superiority of the new consensus over Cortina criteria with respect to postoperative metabolic parameters remains to be ascertained. We retrospectively assessed metabolic parameters, the body habitus, and other health-related parameters of 48 patients with surgically controlled acromegaly who met the Cortina criteria [normalized insulin-like growth factor-1 (IGF-1) level and nadir growth hormone (GH) level <1.0 ng/ml during postoperative oral glucose tolerance test]. The 48 patients were divided into two groups. Group A (n = 33) met the new consensus criteria (normalized IGF-1 and nadir GH level <0.4 ng/ml). Group B (n = 15) met Cortina criteria, but their nadir GH ranged from 0.4 to 1.0 ng/ml. In both groups, the level of triglyceride and homeostasis model assessment-insulin resistance (HOMA-IR) was significantly decreased 1 year after the operation (P < 0.05). High-density lipoprotein cholesterol showed a significant increase only in group B (P = 0.02). However, the two groups did not differ with respect to the postoperative improvement rate of these parameters and the other health-related parameters including body mass index, blood pressure, anterior pituitary function, and self-estimated quality of life scale. In conclusion, our findings show that with respect to changes in metabolic parameters and the body habitus assessed 1 year after surgery, the stricter consensus criteria seemed not to be superior to Cortina criteria.

Intensive lifestyle intervention improves cardiometabolic and exercise parameters in metabolically healthy obese and metabolically unhealthy obese individuals.

PubMed

Dalzill, Claudie; Nigam, Anil; Juneau, Martin; Guilbeault, Valérie; Latour, Elise; Mauriège, Pascale; Gayda, Mathieu

2014-04-01

The effects of an intensive lifestyle intervention including Mediterranean diet nutritional counselling and high-intensity interval training (HIIT) on body composition, cardiometabolic, and exercise parameters were studied in metabolically unhealthy obese (NMHO) and metabolically healthy but obese (MHO) subjects. Fifty-five MHO (51 ± 8 years; waist circumference, 109 ± 13 cm) and 79 NMHO subjects (54 ± 9 years; waist circumference, 112 ± 13 cm) participated in an intensive lifestyle modification program based on Mediterranean diet nutritional counselling and HIIT 2-3 times per week. Body composition, cardiometabolic, and exercise parameters were measured at baseline and after 9 months. Initially, MHO patients had a lower blood pressure (BP), fasting glycemia, triglycerides, and a higher high-density lipoprotein cholesterol and peak oxygen uptake (VO2 peak) (P < 0.05) vs NMHO patients. Body mass (P < 0.05), waist circumference (P < 0.0001), total and trunk fat mass (P < 0.001), systolic and diastolic BP (P < 0.001), fasting glucose (P < 0.0001), insulin sensitivity (P < 0.05), VO2 peak and muscle endurance (P < 0.0001) were similarly improved in both groups after the program. Prevalence of NMHO was reduced by 17.91% (P < 0.01) after the program. Similar improvements in body composition, BP, and exercise parameters were found for MHO and NMHO men and women (P < 0.05). In all patients, improvement of VO2 peak was negatively correlated with improvements in body composition, systolic blood pressure, and resting heart rate (HR) (R = -0.61 to -0.24; P < 0.05). A long-term intensive lifestyle program including Mediterranean diet nutritional counselling and HIIT is an appropriate intervention in MHO and NMHO subjects with similar potential clinical health benefits including an improved body composition, BP, fasting glycemia, insulin sensitivity, VO2 peak, and muscle endurance. Copyright © 2014 Canadian Cardiovascular Society. All rights reserved.

Factors affecting human heterocyclic amine intake and the metabolism of PhIP.

PubMed

Knize, Mark G; Kulp, Kristen S; Salmon, Cynthia P; Keating, Garrett A; Felton, James S

2002-09-30

We are working to understand possible human health effects from exposure to heterocyclic amines that are formed in meat during cooking. Laboratory-cooked beef, pork, and chicken are capable of producing tens of nanograms of MeIQx, IFP, and PhIP per gram of meat and smaller amounts of other heteroyclic amines. Well-done restaurant-cooked beef, pork, and chicken may contain PhIP and IFP at concentrations as high as tens of nanograms per gram and MeIQx at levels up to 3 ng/g. Although well-done chicken breast prepared in the laboratory may contain large amounts of PhIP, a survey of flame-grilled meat samples cooked in private homes showed PhIP levels in beef steak and chicken breast are not significantly different (P=0.36). The extremely high PhIP levels reported in some studies of grilled chicken are not seen in home-cooked samples.Many studies suggest individuals may have varying susceptibility to carcinogens and that diet may influence metabolism, thus affecting cancer susceptibility. To understand the human metabolism of PhIP, we examined urinary metabolites of PhIP in volunteers following a single well-done meat exposure. Using solid-phase extraction and LC/MS/MS, we quantified four major PhIP metabolites in human urine. In addition to investigating individual variation, we examined the interaction of PhIP with a potentially chemopreventive food. In a preliminary study of the effect of broccoli on PhIP metabolism, we fed chicken to six volunteers before and after eating steamed broccoli daily for 3 days. Preliminary results suggest that broccoli, which contains isothiocyanates shown to induce Phases I and II metabolism in vitro, may affect both the rate of metabolite excretion and the metabolic products of a dietary carcinogen. This newly developed methodology will allow us to assess prevention strategies that reduce the possible risks associated with PhIP exposure.

Vitamin A status affects obesity development and hepatic expression of key genes for fuel metabolism in Zucker fatty rats.

PubMed

Zhang, Yan; Li, Rui; Li, Yang; Chen, Wei; Zhao, Shi; Chen, Guoxun

2012-08-01

We hypothesized that vitamin A (VA) status may affect obesity development. Male Zucker lean (ZL) and fatty (ZF) rats after weaning were fed a synthetic VA deficient (VAD) or VA sufficient (VAS) diet for 8 weeks before their plasma parameters and hepatic genes' expression were analyzed. The body mass (BM) of ZL or ZF rats fed the VAD diet was lower than that of their corresponding controls fed the VAS diet at 5 or 2 weeks, respectively. The VAD ZL and ZF rats had less food intake than the VAS rats after 5 weeks. The VAD ZL and ZF rats had lower plasma glucose, triglyceride, insulin, and leptin levels, as well as lower liver glycogen content, net mass of epididymal fat, and liver/BM and epididymal fat/BM ratios (ZL only) than their respective VAS controls. VAD rats had lower hepatic Cyp26a1, Srebp-1c, Fas, Scd1, Me1, Gck, and Pklr (ZL and ZF); and higher Igfbp1 (ZL and ZF), Pck1(ZF only), and G6pc (ZF only) mRNA levels than their respective VAS controls. We conclude that ZL and ZF rats responded differently to dietary VA deficiency. VA status affected obesity development and altered the expression of hepatic genes for fuel metabolism in ZF rats. The mechanisms will help us to combat metabolic diseases.

Significant differences in parameters of glucose metabolism in children of hypertensive and normotensive parents.

PubMed

Gryko, Anna; Głowińska-Olszewska, Barbara; Płudowska, Katarzyna; Smithson, W Henry; Owłasiuk, Anna; Żelazowska-Rutkowska, Beata; Wojtkielewicz, Katarzyna; Milewski, Robert; Chlabicz, Sławomir

2017-01-01

In the recent years, alterations in the carbohydrate metabolism, including insulin resistance, are considered as risk factors in the development of hypertension and its complications in young age. Hypertension is associated with significant cardiovascular morbidity and mortality. The onset of pathology responsible for the development of hypertension, as well as levels of biomarkers specific for early stages of atherosclerosis are poorly understood. To compare a group of children whose parents have a history of hypertension (study group) with a group of children with normotensive parents (reference group), with consideration of typical risk factors for atherosclerosis, parameters of lipid and carbohydrate metabolism, anthropometric data and new biomarkers of early cardiovascular disease (hsCRP, adiponectin, sICAM-1). The study population consists of 84 children. Of these, 40 children (mean age 13.6±2.7 years) had a parental history of hypertension, and 44 aged 13.1±3.7 yrs were children of normotensive parents. Anthropometric measurements were taken, and measurements of blood pressure, lipid profile, glucose and insulin levels were carried out. The insulin resistance index (HOMA IR) was calculated. Levels of hsCRP, soluble cell adhesion molecules (sICAM) and adiponectin were measured. There were no statistically significant differences in anthropometric parameters (body mass, SDS BMI, skin folds) between groups. Values of systolic blood pressure were statistically significantly higher in the study group (Me 108 vs. 100 mmHg, p= 0.031), as were glycaemia (Me 80 vs. 67 mg/dl p<0.001) and insulinaemia levels (Me 8.89 vs. 5.34 µIU/ml, p=0.024). Higher, statistically significant values of HOMA IR were found in the study group (children of hypertensive parents) (Me 1.68 vs. 0.80 mmol/l × mU/l, p=0.007). Lower adiponectin levels (Me 13959.45 vs. 16822 ng/ml, p=0.020) were found in children with a family history of hypertension. No significant differences were found in

Perinatal Exposure to Perfluorooctane Sulfonate Affects Glucose Metabolism in Adult Offspring

PubMed Central

Wan, Hin T.; Zhao, Yin G.; Leung, Pik Y.; Wong, Chris K. C.

2014-01-01

Perfluoroalkyl acids (PFAAs) are globally present in the environment and are widely distributed in human populations and wildlife. The chemicals are ubiquitous in human body fluids and have a long serum elimination half-life. The notorious member of PFAAs, perfluorooctane sulfonate (PFOS) is prioritized as a global concerning chemical at the Stockholm Convention in 2009, due to its harmful effects in mammals and aquatic organisms. PFOS is known to affect lipid metabolism in adults and was found to be able to cross human placenta. However the effects of in utero exposure to the susceptibility of metabolic disorders in offspring have not yet been elucidated. In this study, pregnant CD-1 mice (F0) were fed with 0, 0.3 or 3 mg PFOS/kg body weight/day in corn oil by oral gavage daily throughout gestational and lactation periods. We investigated the immediate effects of perinatal exposure to PFOS on glucose metabolism in both maternal and offspring after weaning (PND 21). To determine if the perinatal exposure predisposes the risk for metabolic disorder to the offspring, weaned animals without further PFOS exposure, were fed with either standard or high-fat diet until PND 63. Fasting glucose and insulin levels were measured while HOMA-IR index and glucose AUCs were reported. Our data illustrated the first time the effects of the environmental equivalent dose of PFOS exposure on the disturbance of glucose metabolism in F1 pups and F1 adults at PND 21 and 63, respectively. Although the biological effects of PFOS on the elevated levels of fasting serum glucose and insulin levels were observed in both pups and adults of F1, the phenotypes of insulin resistance and glucose intolerance were only evident in the F1 adults. The effects were exacerbated under HFD, highlighting the synergistic action at postnatal growth on the development of metabolic disorders. PMID:24498028

Correlation of platelet to lymphocyte and neutrophil to lymphocyte ratio with hormonal and metabolic parameters in women with PCOS.

PubMed

Pergialiotis, Vasilios; Trakakis, Eftihios; Parthenis, Christos; Hatziagelaki, Erifili; Chrelias, Charalampos; Thomakos, Nikolaos; Papantoniou, Nikolaos

2018-04-25

Background The purpose of our study is to evaluate the association of platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) with hormonal and metabolic parameters in patients with polycystic ovarian syndrome (PCOS) in order to assess whether these ratios may become useful tools during the evaluation of the severity of low grade inflammation. Methods The present study is based in secondary outcomes from a prospectively collected patient database. A total of 266 women with PCOS participated in this study and blood a complete blood count examination (CBC) that was used for the calculation of PLR and NLR was available in 182 patients. Results Association statistics revealed that PLR had a significant correlation to 17-OH progesterone (r = -0.177, p = 0.024) and Matsuda index values (r = 0.234, p = 0.009), whereas NLR was correlated with follicle stimulating hormone (FSH) (r = -0.204, p = 0.007), free testosterone (r = 320, p < 0.001), Δ4-androstendione (r = 0.234, p = 0.003), sex hormone binding globulin (SHBG) (r = -0.350, p < 0.002) and high-density lipoprotein (HDL) (r = -0.171, p = 0.039). Conclusion According to the findings of our study, both PLR and NLR seem to be correlated with some hormonal and metabolic indices. This association is clearer in the case of NLR and serum androgens as it seems to be positively affected by their levels. PLR and NLR were not affected by the presence of obesity.

Black leaf streak disease affects starch metabolism in banana fruit.

PubMed

Saraiva, Lorenzo de Amorim; Castelan, Florence Polegato; Shitakubo, Renata; Hassimotto, Neuza Mariko Aymoto; Purgatto, Eduardo; Chillet, Marc; Cordenunsi, Beatriz Rosana

2013-06-12

Black leaf streak disease (BLSD), also known as black sigatoka, represents the main foliar disease in Brazilian banana plantations. In addition to photosynthetic leaf area losses and yield losses, this disease causes an alteration in the pre- and postharvest behavior of the fruit. The aim of this work was to investigate the starch metabolism of fruits during fruit ripening from plants infected with BLSD by evaluating carbohydrate content (i.e., starch, soluble sugars, oligosaccharides, amylose), phenolic compound content, phytohormones, enzymatic activities (i.e., starch phosphorylases, α- and β-amylase), and starch granules. The results indicated that the starch metabolism in banana fruit ripening is affected by BLSD infection. Fruit from infested plots contained unusual amounts of soluble sugars in the green stage and smaller starch granules and showed a different pattern of superficial degradation. Enzymatic activities linked to starch degradation were also altered by the disease. Moreover, the levels of indole-acetic acid and phenolic compounds indicated an advanced fruit physiological age for fruits from infested plots.

Mathematical modelling of metabolic pathways affected by an enzyme deficiency. Energy and redox metabolism of glucose-6-phosphate-dehydrogenase-deficient erythrocytes.

PubMed

Schuster, R; Jacobasch, G; Holzhütter, H G

1989-07-01

The effects of various forms of glucose-6-phosphate dehydrogenase deficiency on erythrocyte metabolism have been studied on the basis of a complex mathematical model which comprises the main pathways of this cell: glycolysis, pentose pathway, reactions of the glutathione and adenine nucleotide metabolism. The calculated flux rates through the oxidative pentose pathway with and without methylene blue are in good accord with experimental results. The degree of deficiency as predicted by the model on the basis of calculated upper oxidative load boundaries, as well as of maximal methylene blue stimulation, correlates with the individual clinical manifestation of the metabolic disease. Therefore, the model allows one to judge the degree of metabolic disorder in the presence of glucose-6-phosphate dehydrogenase enzymopathies if the kinetic properties of the defect enzyme are known. Experimentally accessible parameters for an assessment of the oxidative load capacity of cells in vivo are proposed. It is pointed out that the threshold of tolerance as to energetic load is drastically reduced in the case of severe glucose-6-phosphate dehydrogenase deficiency.

The Hsp72 response in peri-parturient dairy cows: relationships with metabolic and immunological parameters

PubMed Central

Catalani, Elisabetta; Amadori, Massimo; Vitali, Andrea; Bernabucci, Umberto; Nardone, Alessandro

2010-01-01

The study was aimed at assessing whether the peri-parturient period is associated with changes of intracellular and plasma inducible heat shock proteins (Hsp) 72 kDa molecular weight in dairy cows, and to establish possible relationships between Hsp72, metabolic, and immunological parameters subjected to changes around calving. The study was carried out on 35 healthy peri-parturient Holstein cows. Three, two, and one week before the expected calving, and 1, 2, 3, 4, and 5 weeks after calving, body conditions score (BCS) was measured and blood samples were collected to separate plasma and peripheral blood mononuclear cells (PBMC). Concentrations of Hsp72 in PBMC and plasma increased sharply after calving. In the post-calving period, BCS and plasma glucose declined, whereas plasma nonesterified fatty acids (NEFA) and tumor necrosis factor-alpha increased. The proliferative responses of PBMC to lipopolysaccharide (LPS) declined progressively after calving. The percentage of PBMC expressing CD14 receptors and Toll-like receptors (TLR)-4 increased and decreased in the early postpartum period, respectively. Correlation analysis revealed significant positive relationships between Hsp72 and NEFA, and between PBMC proliferation in response to LPS and the percentage of PBMC expressing TLR-4. Conversely, significant negative relationships were found between LPS-triggered proliferation of PBMC and both intracellular and plasma Hsp72. Literature data and changes of metabolic and immunological parameters reported herein authorize a few interpretative hypotheses and encourage further studies aimed at assessing possible cause and effect relationships between changes of PBMC and circulating Hsp72, metabolic, and immune parameters in dairy cows. PMID:20349286

Pilot study on the effects of a 2-week hiking vacation at moderate versus low altitude on plasma parameters of carbohydrate and lipid metabolism in patients with metabolic syndrome.

PubMed

Gutwenger, Ivana; Hofer, Georg; Gutwenger, Anna K; Sandri, Marco; Wiedermann, Christian J

2015-03-28

Hypoxic and hypobaric conditions may augment the beneficial influence of training on cardiovascular risk factors. This pilot study aimed to explore for effects of a two-week hiking vacation at moderate versus low altitude on adipokines and parameters of carbohydrate and lipid metabolism in patients with metabolic syndrome. Fourteen subjects (mean age: 55.8 years, range: 39 - 69) with metabolic syndrome participated in a 2-week structured training program (3 hours of guided daily hiking 4 times a week, training intensity at 55-65% of individual maximal heart rate; total training time, 24 hours). Participants were divided for residence and training into two groups, one at moderate altitude (1,900 m; n = 8), and the other at low altitude (300 m; n = 6). Anthropometric, cardiovascular and metabolic parameters were measured before and after the training period. In study participants, training overall reduced circulating levels of total cholesterol (p = 0.024), low-density lipoprotein cholesterol (p = 0.025) and adiponectin (p < 0.001). In the group training at moderate altitude (n = 8), lowering effects on circulating levels were significant not only for total cholesterol, low-density-lipoprotein cholesterol and adiponectin (all, p < 0.05) but also for triglycerides (p = 0.025) and leptin (p = 0.015), whereas in the low altitude group (n = 6), none of the lipid parameters was significantly changed (each p > 0.05). Hiking-induced relative changes of triglyceride levels were positively associated with reductions in leptin levels (p = 0.006). As compared to 300 m altitude, training at 1,900 m showed borderline significant differences in the pre-post mean reduction rates of triglyceride (p = 0.050) and leptin levels (p = 0.093). Preliminary data on patients with metabolic syndrome suggest that a 2-week hiking vacation at moderate altitude may be more beneficial for adipokines and parameters of lipid metabolism than training at low altitude. In order to draw firm conclusions

Stretching Your Energetic Budget: How Tendon Compliance Affects the Metabolic Cost of Running

PubMed Central

Uchida, Thomas K.; Hicks, Jennifer L.; Dembia, Christopher L.; Delp, Scott L.

2016-01-01

Muscles attach to bones via tendons that stretch and recoil, affecting muscle force generation and metabolic energy consumption. In this study, we investigated the effect of tendon compliance on the metabolic cost of running using a full-body musculoskeletal model with a detailed model of muscle energetics. We performed muscle-driven simulations of running at 2–5 m/s with tendon force–strain curves that produced between 1 and 10% strain when the muscles were developing maximum isometric force. We computed the average metabolic power consumed by each muscle when running at each speed and with each tendon compliance. Average whole-body metabolic power consumption increased as running speed increased, regardless of tendon compliance, and was lowest at each speed when tendon strain reached 2–3% as muscles were developing maximum isometric force. When running at 2 m/s, the soleus muscle consumed less metabolic power at high tendon compliance because the strain of the tendon allowed the muscle fibers to operate nearly isometrically during stance. In contrast, the medial and lateral gastrocnemii consumed less metabolic power at low tendon compliance because less compliant tendons allowed the muscle fibers to operate closer to their optimal lengths during stance. The software and simulations used in this study are freely available at simtk.org and enable examination of muscle energetics with unprecedented detail. PMID:26930416

Hallux valgus surgery affects kinematic parameters during gait

PubMed Central

Klugarova, J.; Janura, M.; Svoboda, Z.; Sos, Z.; Stergiou, N.; Klugar, M.

2017-01-01

Background The aim of our study was to compare spatiotemporal parameters and lower limb and pelvis kinematics during the walking in patients with hallux valgus before and after surgery and in relation to a control group. Methods Seventeen females with hallux valgus, who underwent first metatarsal osteotomy, constituted our experimental group. The control group consisted of thirteen females. Kinematic data during walking were obtained using the Vicon MX system. Findings Our results showed that hallux valgus before surgery affects spatiotemporal parameters and lower limb and pelvis kinematics during walking. Hallux valgus surgery further increased the differences that were present before surgery. Specifically after hallux valgus surgery, the walking speed decreased even more (p=0.09, η2= 0.19) while step time increased (p=0.002, η2=0.44) on both legs. The maximum ankle plantar flexion of the operated leg during toe off decreased to a greater extend (p=0.03, η2=0.26). The asymmetry in the hip and the pelvis movements in the frontal plane (present preoperatively) persisted after surgery. Interpretation Hallux valgus is not an isolated problem of the first ray, which could be just surgically addressed by correcting the foot’s alignment. It is a long-term progressive malfunction of the foot affecting the entire kinematic chain of the lower extremity. PMID:27792950

Effect of fed- versus fasted state resistance training during Ramadan on body composition and selected metabolic parameters in bodybuilders

PubMed Central

2013-01-01

Background Muslim bodybuilders often continue training during Ramadan. However, the effect of resistance training in a fasted versus a fed state during Ramadan on body composition and metabolic parameters in bodybuilders is not well known. The aim of this study was to evaluate the effects of resistance training in a fasted versus a fed state during Ramadan on body composition and metabolic parameters in bodybuilders. Methods Sixteen men were allocated to two groups: Eight practicing resistance training in the late afternoon in a fasted state (FAST), and eight training in the late evening in an acutely fed state (FED) during Ramadan. All visited the laboratory in the morning two days before the start of Ramadan (Bef-R) and on the 29th day of Ramadan (End-R) for anthropometric measurement, completion of a dietary questionnaire, and provision of fasting blood and urine samples. Results Body mass and body fat percentage remained unchanged in FAST and FED during the whole period of the investigation. Both FAST and FED experienced an increase in the following parameters from Bef-R to End-R: urine specific gravity (1%; p = 0.028, p = 0.004 respectively), serum concentrations of urea (4%, p = 0.006; 7%, p = 0.004 respectively), creatinine (5%, p = 0.015; 6%, p = 0.04 respectively), uric acid (17%; p < 0.001, p = 0.04 respectively), sodium (1%; p = 0.029, p = 0.019 respectively), chloride (2%; p = 0.039, p = 0.004 respectively), and high-density lipoprotein cholesterol (11%, p = 0.04; 10%, p = 0.04 respectively). Conclusion Hypertrophic training in a fasted or in a fed state during Ramadan does not affect body mass and body composition of bodybuilders. Additionally, Ramadan fasting induced changes in urinary and some biochemical parameters, but these changes were not different according to when the training occurred. PMID:23617897

Olanzapine and aripiprazole differentially affect glucose uptake and energy metabolism in human mononuclear blood cells.

PubMed

Stapel, Britta; Kotsiari, Alexandra; Scherr, Michaela; Hilfiker-Kleiner, Denise; Bleich, Stefan; Frieling, Helge; Kahl, Kai G

2017-05-01

The use of antipsychotics carries the risk of metabolic side effects, such as weight gain and new onset type-2 diabetes mellitus. The mechanisms of the observed metabolic alterations are not fully understood. We compared the effects of two atypical antipsychotics, one known to favor weight gain (olanzapine), the other not (aripiprazole), on glucose metabolism. Primary human peripheral blood mononuclear cells (PBMC) were isolated and stimulated with olanzapine or aripiprazole for 72 h. Cellular glucose uptake was analyzed in vitro by 18F-FDG uptake. Further measurements comprised mRNA expression of glucose transporter (GLUT) 1 and 3, GLUT1 protein expression, DNA methylation of GLUT1 promoter region, and proteins involved in downstream glucometabolic processes. We observed a 2-fold increase in glucose uptake after stimulation with aripiprazole. In contrast, olanzapine stimulation decreased glucose uptake by 40%, accompanied by downregulation of the cellular energy sensor AMP activated protein kinase (AMPK). GLUT1 protein expression increased, GLUT1 mRNA expression decreased, and GLUT1 promoter was hypermethylated with both antipsychotics. Pyruvat-dehydrogenase (PDH) complex activity decreased with olanzapine only. Our findings suggest that the atypical antipsychotics olanzapine and aripiprazole differentially affect energy metabolism in PBMC. The observed decrease in glucose uptake in olanzapine stimulated PBMC, accompanied by decreased PDH point to a worsening in cellular energy metabolism not compensated by AMKP upregulation. In contrast, aripiprazole stimulation lead to increased glucose uptake, while not affecting PDH complex expression. The observed differences may be involved in the different metabolic profiles observed in aripiprazole and olanzapine treated patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Low-dose aspartame consumption differentially affects gut microbiota-host metabolic interactions in the diet-induced obese rat.

PubMed

Palmnäs, Marie S A; Cowan, Theresa E; Bomhof, Marc R; Su, Juliet; Reimer, Raylene A; Vogel, Hans J; Hittel, Dustin S; Shearer, Jane

2014-01-01

Aspartame consumption is implicated in the development of obesity and metabolic disease despite the intention of limiting caloric intake. The mechanisms responsible for this association remain unclear, but may involve circulating metabolites and the gut microbiota. Aims were to examine the impact of chronic low-dose aspartame consumption on anthropometric, metabolic and microbial parameters in a diet-induced obese model. Male Sprague-Dawley rats were randomized into a standard chow diet (CH, 12% kcal fat) or high fat (HF, 60% kcal fat) and further into ad libitum water control (W) or low-dose aspartame (A, 5-7 mg/kg/d in drinking water) treatments for 8 week (n = 10-12 animals/treatment). Animals on aspartame consumed fewer calories, gained less weight and had a more favorable body composition when challenged with HF compared to animals consuming water. Despite this, aspartame elevated fasting glucose levels and an insulin tolerance test showed aspartame to impair insulin-stimulated glucose disposal in both CH and HF, independently of body composition. Fecal analysis of gut bacterial composition showed aspartame to increase total bacteria, the abundance of Enterobacteriaceae and Clostridium leptum. An interaction between HF and aspartame was also observed for Roseburia ssp wherein HF-A was higher than HF-W (P<0.05). Within HF, aspartame attenuated the typical HF-induced increase in the Firmicutes:Bacteroidetes ratio. Serum metabolomics analysis revealed aspartame to be rapidly metabolized and to be associated with elevations in the short chain fatty acid propionate, a bacterial end product and highly gluconeogenic substrate, potentially explaining its negative affects on insulin tolerance. How aspartame influences gut microbial composition and the implications of these changes on the development of metabolic disease require further investigation.

Low-Dose Aspartame Consumption Differentially Affects Gut Microbiota-Host Metabolic Interactions in the Diet-Induced Obese Rat

PubMed Central

Palmnäs, Marie S. A.; Cowan, Theresa E.; Bomhof, Marc R.; Su, Juliet; Reimer, Raylene A.; Vogel, Hans J.; Hittel, Dustin S.; Shearer, Jane

2014-01-01

Aspartame consumption is implicated in the development of obesity and metabolic disease despite the intention of limiting caloric intake. The mechanisms responsible for this association remain unclear, but may involve circulating metabolites and the gut microbiota. Aims were to examine the impact of chronic low-dose aspartame consumption on anthropometric, metabolic and microbial parameters in a diet-induced obese model. Male Sprague-Dawley rats were randomized into a standard chow diet (CH, 12% kcal fat) or high fat (HF, 60% kcal fat) and further into ad libitum water control (W) or low-dose aspartame (A, 5–7 mg/kg/d in drinking water) treatments for 8 week (n = 10–12 animals/treatment). Animals on aspartame consumed fewer calories, gained less weight and had a more favorable body composition when challenged with HF compared to animals consuming water. Despite this, aspartame elevated fasting glucose levels and an insulin tolerance test showed aspartame to impair insulin-stimulated glucose disposal in both CH and HF, independently of body composition. Fecal analysis of gut bacterial composition showed aspartame to increase total bacteria, the abundance of Enterobacteriaceae and Clostridium leptum. An interaction between HF and aspartame was also observed for Roseburia ssp wherein HF-A was higher than HF-W (P<0.05). Within HF, aspartame attenuated the typical HF-induced increase in the Firmicutes:Bacteroidetes ratio. Serum metabolomics analysis revealed aspartame to be rapidly metabolized and to be associated with elevations in the short chain fatty acid propionate, a bacterial end product and highly gluconeogenic substrate, potentially explaining its negative affects on insulin tolerance. How aspartame influences gut microbial composition and the implications of these changes on the development of metabolic disease require further investigation. PMID:25313461

The prevalence of abnormal metabolic parameters in obese and overweight children.

PubMed

Salvatore, Deborah; Satnick, Ava; Abell, Rebecca; Messina, Catherine R; Chawla, Anupama

2014-09-01

This retrospective study aimed to determine the prevalence of abnormal metabolic parameters in obese children and its correlation to the degree of obesity determined by body mass index (BMI). In total, 101 children seen at the Pediatric Gastroenterology Obesity Clinic at Stony Brook Children's University Hospital were enrolled in the study. The degree of obesity was characterized according to the following formula: (patient's BMI/BMI at 95th percentile) × 100%, with class I obesity >100%-120%, class II obesity >120%-140%, and class III obesity >140%. A set of metabolic parameters was evaluated in these patients. Frequency distributions of all study variables were examined using the χ(2) test of independence. Mean differences among the obesity classes and continuous measures were examined using 1-way analysis of variance. Within our study population, we found that 80% of our obese children had a low high-density lipoprotein (HDL) cholesterol level, 58% had elevated fasting insulin levels, and 32% had an elevated alanine aminotransferase (ALT) level. Class II obese children had a 2-fold higher ALT value when compared with class I children (P = .036). Fasting insulin, ALT, HDL cholesterol, and triglyceride levels trended with class of obesity. Obese children in classes II and III are at higher risk for developing abnormal laboratory values. We recommend obese children be further classified to reflect the severity of the obesity since this has predictive significance for comorbidities. Obesity classes I, II, and III could help serve as a screening tool to help communicate risk assessment. © 2013 American Society for Parenteral and Enteral Nutrition.

Trichoderma secondary metabolites that affect plant metabolism.

PubMed

Vinale, Francesco; Sivasithamparam, Krishnapillai; Ghisalberti, Emilio L; Ruocco, Michelina; Wood, Sheridan; Lorito, Matteo

2012-11-01

Recently, there have been many exciting new developments relating to the use of Trichoderma spp. as agents for biocontrol of pathogens and as plant growth promoters. Several mechanisms have been proposed to explain the positive effects of these microorganisms on the plant host. One factor that contributes to their beneficial biological activities is related to the wide variety of metabolites that they produce. These metabolites have been found not only to directly inhibit the growth and pathogenic activities of the parasites, but also to increase disease resistance by triggering the system of defence in the plant host. In addition, these metabolites are also capable of enhancing plant growth, which enables the plant to counteract the disease with compensatory vegetative growth by the augmented production of root and shoot systems. This review takes into account the Trichoderma secondary metabolites that affect plant metabolism and that may play an important role in the complex interactions of this biocontrol agent with the plant and pathogens.

Effects of dietary history on energy metabolism and physiological parameters in C57BL/6J mice.

PubMed

Hoevenaars, Femke P M; Keijer, Jaap; Swarts, Hans J; Snaas-Alders, Sophie; Bekkenkamp-Grovenstein, Melissa; van Schothorst, Evert M

2013-05-01

Understanding body weight regulation is essential to fight obesity. Mouse studies, using different types of diets, showed conflicting results in terms of body weight persistence after changing from an ad libitum high-fat diet to an ad libitum low-fat diet. In this study, we questioned specifically whether the energy content of the diet has a lasting effect on energy balance and body weight, using multiple switches and two purified diets with a different fat-to-sugar ratio, but otherwise identical ingredients. Young-adult obesity-prone male C57BL/6J mice were fed single or double switches of semi-purified diets with either 10 energy % (en%) fat (LF) or 40en% fat (HF), with starch replaced by fat, while protein content remained equal. After none, one or two dietary changes, energy metabolism was assessed at 5, 14 and 19 weeks. We observed no systematic continuous compensation in diet and energy intake when returning to LF after HF consumption. Body weight, white adipose tissue mass and histology, serum metabolic parameters, energy expenditure and substrate usage all significantly reflected the current diet intake, independent of dietary changes. This contrasts with studies that used diets with different ingredients and showed persistent effects of dietary history on body weight, suggesting diet-dependent metabolic set points. We conclude that body weight and metabolic parameters 'settle', based on current energetic input and output. This study also highlights the importance of considering the choice of diet in physiological and metabolic intervention studies.

Monoglyceride lipase deficiency affects hepatic cholesterol metabolism and lipid-dependent gut transit in ApoE-/- mice.

PubMed

Vujic, Nemanja; Korbelius, Melanie; Leopold, Christina; Duta-Mare, Madalina; Rainer, Silvia; Schlager, Stefanie; Goeritzer, Madeleine; Kolb, Dagmar; Eichmann, Thomas O; Diwoky, Clemens; Zimmer, Andreas; Zimmermann, Robert; Lass, Achim; Radovic, Branislav; Kratky, Dagmar

2017-05-16

Monoglyceride lipase (MGL) hydrolyzes monoglycerides (MGs) to glycerol and fatty acids. Among various MG species MGL also degrades 2-arachidonoylglycerol (2-AG), the most abundant endocannabinoid and potent activator of cannabinoid receptors (CBR) 1 and 2. MGL-knockout (-/-) mice exhibit pronounced 2-AG accumulation, but lack central cannabimimetic effects due to CB1R desensitization. We have previously shown that MGL affects plaque stability in apolipoprotein E (ApoE)-/- mice, an established animal model for dyslipidemia and atherosclerosis. In the current study, we investigated functional consequences of MGL deficiency on lipid and energy metabolism in ApoE/MGL double knockout (DKO) mice. MGL deficiency affected hepatic cholesterol metabolism by causing increased cholesterol elimination via the biliary pathway. Moreover, DKO mice exhibit lipid-triggered delay in gastric emptying without major effects on overall triglyceride and cholesterol absorption. The observed phenotype of DKO mice is likely not a consequence of potentiated CB1R signaling but rather dependent on the activation of alternative signaling pathways. We conclude that MGL deficiency causes complex metabolic changes including cholesterol metabolism and regulation of gut transit independent of the endocannabinoid system.

Extracellular Citrate Affects Critical Elements of Cancer Cell Metabolism and Supports Cancer Development In Vivo.

PubMed

Mycielska, Maria E; Dettmer, Katja; Rümmele, Petra; Schmidt, Katharina; Prehn, Cornelia; Milenkovic, Vladimir M; Jagla, Wolfgang; Madej, Gregor M; Lantow, Margareta; Schladt, Moritz; Cecil, Alexander; Koehl, Gudrun E; Eggenhofer, Elke; Wachsmuth, Christian J; Ganapathy, Vadivel; Schlitt, Hans J; Kunzelmann, Karl; Ziegler, Christine; Wetzel, Christian H; Gaumann, Andreas; Lang, Sven A; Adamski, Jerzy; Oefner, Peter J; Geissler, Edward K

2018-05-15

Glycolysis and fatty acid synthesis are highly active in cancer cells through cytosolic citrate metabolism, with intracellular citrate primarily derived from either glucose or glutamine via the tricarboxylic acid cycle. We show here that extracellular citrate is supplied to cancer cells through a plasma membrane-specific variant of the mitochondrial citrate transporter (pmCiC). Metabolomic analysis revealed that citrate uptake broadly affected cancer cell metabolism through citrate-dependent metabolic pathways. Treatment with gluconate specifically blocked pmCiC and decreased tumor growth in murine xenografts of human pancreatic cancer. This treatment altered metabolism within tumors, including fatty acid metabolism. High expression of pmCiC was associated with invasion and advanced tumor stage across many human cancers. These findings support the exploration of extracellular citrate transport as a novel potential target for cancer therapy. Significance: Uptake of extracellular citrate through pmCiC can be blocked with gluconate to reduce tumor growth and to alter metabolic characteristics of tumor tissue. Cancer Res; 78(10); 2513-23. ©2018 AACR . ©2018 American Association for Cancer Research.

Arterial function parameters in patients with metabolic syndrome and severe hypertriglyceridemia.

PubMed

Rinkūnienė, Egidija; Butkutė, Eglė; Puronaitė, Roma; Petrulionienė, Žaneta; Dženkevičiūtė, Vilma; Kasiulevičius, Vytautas; Laucevičius, Aleksandras

Hypertriglyceridemia (hTG) is 1 of the dyslipidemia manifestations in patients with metabolic syndrome (MetS). However, for several decades, the role of hTG in cardiovascular risk was not well established. The aim of this study was to assess the parameters of the vascular structure and function in patients with MetS and different degree of hTG. Patients (aged 40-65 years) with MetS were divided into 3 groups by triglyceride (TG) levels according to National Cholesterol Education Program Adult Treatment Panel III Guidelines: severe hTG (TG ≥ 500 mg/dL), moderate hTG (TG 200-499 mg/dL), and a control (TG < 150 mg/dL) groups. Noninvasive assessment of vascular parameters (aortic augmentation index adjusted for heart rate 75 bpm [AixHR75], pulse wave velocity [PWV], flow-mediated dilatation, and common carotid artery intima-media thickness (IMT)) were performed. Among the 1938 patients analyzed, 1041 had hTG. Moderate hTG was observed in 90.40% (n = 941), whereas severe TG was observed in 9.6% (n = 100) of patients. Overall TG concentration was 231.17 ± 184.23 mg/dL; in severe hTG group, TG concentration was 795.36 ± 368.45 mg/dL, in moderate hTG group 285.20 ± 70.86 mg/dL, and 112.48 ± 24.80 mg/dL in control group. AIxHR75 and IMT were the lowest in the severe hTG group (P < .001 for both). Mean arterial pressure, carotid-radial PWV (9.25 ± 1.13 vs 9.24 ± 1.28 vs 8.91 ± 1.28; P < .001) as well as carotid-femoral PWV (8.63 ± 1.65 vs 8.75 ± 1.58 vs 8.51 ± 1.6; P = .006) were the higher in hTG groups compared with control. There were no significant differences between groups in flow-mediated dilatation (3.39 ± 2.01 vs 3.26 ± 2.43 vs 3.45 ± 2.61, P = .283). Patients with MetS and severe hTG have lower IMT and AIxHR75 and higher PWV and mean arterial pressure. Many factors could affect arterial parameters, and more research are needed to investigate arterial parameters and hTG connection. Copyright © 2017

Relationships between lifestyle patterns and cardio-renal-metabolic parameters in patients with type 2 diabetes mellitus: A cross-sectional study.

PubMed

Ogihara, Takeshi; Mita, Tomoya; Osonoi, Yusuke; Osonoi, Takeshi; Saito, Miyoko; Tamasawa, Atsuko; Nakayama, Shiho; Someya, Yuki; Ishida, Hidenori; Gosho, Masahiko; Kanazawa, Akio; Watada, Hirotaka

2017-01-01

While individuals tend to show accumulation of certain lifestyle patterns, the effect of such patterns in real daily life on cardio-renal-metabolic parameters remains largely unknown. This study aimed to assess clustering of lifestyle patterns and investigate the relationships between such patterns and cardio-renal-metabolic parameters. The study participants were 726 Japanese type 2 diabetes mellitus (T2DM) outpatients free of history of cardiovascular diseases. The relationship between lifestyle patterns and cardio-renal-metabolic parameters was investigated by linear and logistic regression analyses. Factor analysis identified three lifestyle patterns. Subjects characterized by evening type, poor sleep quality and depressive status (type 1 pattern) had high levels of HbA1c, alanine aminotransferase and albuminuria. Subjects characterized by high consumption of food, alcohol and cigarettes (type 2 pattern) had high levels of γ-glutamyl transpeptidase, triglycerides, HDL-cholesterol, blood pressure, and brachial-ankle pulse wave velocity. Subjects characterized by high physical activity (type 3 pattern) had low uric acid and mild elevation of alanine aminotransferase and aspartate aminotransferase. In multivariate regression analysis adjusted by age, gender and BMI, type 1 pattern was associated with higher HbA1c levels, systolic BP and brachial-ankle pulse wave velocity. Type 2 pattern was associated with higher HDL-cholesterol levels, triglycerides, aspartate aminotransferase, ɤ- glutamyl transpeptidase levels, and diastolic BP. The study identified three lifestyle patterns that were associated with distinct cardio-metabolic-renal parameters in T2DM patients. UMIN000010932.

Tamoxifen affects glucose and lipid metabolism parameters, causes browning of subcutaneous adipose tissue and transient body composition changes in C57BL/6NTac mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hesselbarth, Nico; Pettinelli, Chiara; Gericke, Martin

Tamoxifen is a selective estrogen receptor (ER) modulator which is widely used to generate inducible conditional transgenic mouse models. Activation of ER signaling plays an important role in the regulation of adipose tissue (AT) metabolism. We therefore tested the hypothesis that tamoxifen administration causes changes in AT biology in vivo. 12 weeks old male C57BL/6NTac mice were treated with either tamoxifen (n = 18) or vehicle (n = 18) for 5 consecutive days. Tamoxifen treatment effects on body composition, energy homeostasis, parameters of AT biology, glucose and lipid metabolism were investigated up to an age of 18 weeks. We found that tamoxifen treatment causes: I)more » significantly increased HbA{sub 1c}, triglyceride and free fatty acid serum concentrations (p < 0.01), II) browning of subcutaneous AT and increased UCP-1 expression, III) increased AT proliferation marker Ki67 mRNA expression, IV) changes in adipocyte size distribution, and V) transient body composition changes. Tamoxifen may induce changes in body composition, whole body glucose and lipid metabolism and has significant effects on AT biology, which need to be considered when using Tamoxifen as a tool to induce conditional transgenic mouse models. Our data further suggest that tamoxifen-treated wildtype mice should be characterized in parallel to experimental transgenic models to control for tamoxifen administration effects. - Highlights: • Tamoxifen treatment causes significantly increased HbA{sub 1c}, triglyceride and free fatty acid serum concentrations. • Tamoxifen induces browning of subcutaneous AT and increased UCP-1 expression. • Tamoxifen changes adipocyte size distribution, and transient body composition.« less

Relation of periodontitis and metabolic syndrome with gestational glucose metabolism disorder.

PubMed

Bullon, Pedro; Jaramillo, Reyes; Santos-Garcia, Rocio; Rios-Santos, Vicente; Ramirez, Maria; Fernandez-Palacin, Ana; Fernandez-Riejos, Patricia

2014-02-01

Gestational diabetes mellitus (GDM) and metabolic syndrome have been related to periodontitis. This study's objective is to establish the relationship between them in pregnant women affected by gestational glucose metabolism disorder. In 188 pregnant women with positive O'Sullivan test (POT) results, an oral glucose tolerance test (OGTT) was performed to diagnose GDM. The mother's periodontal parameters, age, prepregnancy weight and height and body mass index (BMI), blood pressure, gestational age, and birth weight were recorded at 24 to 28 weeks of pregnancy, as well as levels of glucose, C-reactive protein, triglycerides, glycated hemoglobin (HbA1c), and total, low-density lipoprotein, high-density lipoprotein (HDL), and very-low-density lipoprotein (VLDL) cholesterol levels. Prepregnancy weight, prepregnancy BMI, systolic and diastolic blood pressure, VLDL cholesterol, and glucose parameters were higher in GDM compared with POT (P <0.05). VLDL cholesterol, triglycerides, and 2-hour OGTT were higher in patients with periodontitis than in patients without periodontitis (P <0.05). HbA1c, triglycerides, and 1- and 2-hour OGTT were positively related with probing depth and clinical attachment level; blood glucose was related only to bleeding on probing (P <0.05). HbA1c, basal OGTT, and 1- and 2-hour OGTT were positively related to prepregnancy BMI and blood pressure; HDL cholesterol was negatively related to prepregnancy BMI; C-reactive protein was positively related to prepregnancy BMI and diastolic blood pressure (P <0.05). These data support the relationships among periodontal disease and some biochemical parameters such as lipid and glucose data in pregnancy, and also among metabolic syndrome and biochemical parameters.

Metabolic parameters and cognitive function in a cohort of older diabetic patients.

PubMed

Herghelegiu, Anna Marie; Nacu, Raluca Mihaela; Prada, Gabriel Ioan

2016-12-01

Dementia is one of the most disabling conditions associated with old age. With increasing life expectancy, prevalence of both dementia and diabetes is rising. The complex pathological relationship between diabetes mellitus (DM) and dementia has been studied, but is not yet fully understood. The main objective of this study was to investigate the relationship between metabolic parameters and the cognitive function in older diabetics. A total number of 360 diabetic subjects, age 65 years and over, and 300 older people controls were included. Clinical and biological parameters, together with the cognitive function, were assessed every 6 months over a 18-month period, for each study participant. By employing a multivariate linear regression analysis, several significant relationships have been identified: between Clock Drawing Test (CDT) scores and HbA1c (R 2  = 0.68); between CDT scores (R 2  = 0.51) and overall MMSE scores (R 2  = 0.43) on one hand, and DM duration in years, on the other hand; also between CDT scores and BMI (R 2  = 0.59). There was no significant association between fasting serum glucose (FSG), total serum cholesterol, LDL cholesterol or triglycerides levels and cognitive function scores (p > 0.05). The close detailed monitoring of the cognitive function and a rigorous metabolic control are important, especially in the very early stages of DM. Addressing factors such as weight control in older diabetic patients could contribute to better cognitive outcomes.

Relationship of Eating Patterns and Metabolic Parameters, and Teneligliptin Treatment: Interim Results from Post-marketing Surveillance in Japanese Type 2 Diabetes Patients.

PubMed

Kadowaki, Takashi; Haneda, Masakazu; Ito, Hiroshi; Sasaki, Kazuyo; Hiraide, Sonoe; Matsukawa, Miyuki; Ueno, Makoto

2018-06-01

Healthy eating is a critical aspect of the prevention and management of type 2 diabetes (T2DM). Disrupted eating patterns can result in poor glucose control and increase the likelihood of diabetic complications. Teneligliptin inhibits dipeptidyl peptidase-4 activity for 24 h and suppresses postprandial hyperglycemia after all three daily meals. This interim analysis of data from the large-scale post-marketing surveillance of teneligliptin (RUBY) in Japan examined eating patterns and their relationship with metabolic parameters and diabetic complications. We also examined whether eating patterns affected safety and efficacy of teneligliptin. We analyzed baseline data from survey forms collected in RUBY between May 2013 and June 2017, including patient characteristics, metabolic parameters, and eating patterns (eating three meals per day or not; timing of evening meal) before teneligliptin treatment was initiated. Safety and efficacy of 12 months' teneligliptin (20-40 mg/day) treatment was assessed. Data from 10,532 patients were available for analysis. Most patients who did not eat three meals per day (n  =757) or who ate their evening meal after 10 PM (n  =206) were 64 years old or younger. At baseline, glycated hemoglobin (HbA1c), fasting blood glucose, triglycerides, total and low-density lipoprotein cholesterol, body mass index, alanine aminotransferase, and aspartate aminotransferase levels were higher in those patients who did not eat three meals per day (p < 0.05) or who ate their evening meal late (p < 0.05). Diabetic complications were more common in patients who did not eat three meals per day. Treatment with teneligliptin reduced HbA1c over 6 or 12 months across all eating patterns, with a low incidence of adverse drug reactions. Eating patterns may be associated with altered metabolic parameters and diabetic complications among Japanese patients with T2DM. Teneligliptin may be well tolerated and improve hyperglycemia in patients

Age and the metabolic syndrome affect salivary cortisol rhythm: data from a community sample.

PubMed

Ceccato, Filippo; Barbot, Mattia; Zilio, Marialuisa; Ferasin, Sergio; De Lazzari, Paola; Lizzul, Laura; Boscaro, Marco; Scaroni, Carla

2015-01-01

Measurement of cortisol levels in saliva is a marker of free hormone. How salivary cortisol rhythm is affected by age, gender, the metabolic syndrome and estrogen-progestin therapy was evaluated in a community sample of adults. One hundred twenty volunteers recruited from the Hospital staff and family members of the Endocrinology Unit were instructed to collect 7 salivary samples: the first on awakening (F(0)) and 6 more (F(1.5), F(5), F(6), F(10), F(11.5) and F(14)) over the next 14 hours. Each volunteer also underwent a complete physical evaluation and a comprehensive medical history was taken. Salivary cortisol was measured using a radioimmunometric assay. Daily cortisol secretion was evaluated computing the Area Under the Curve (AUC(F0)(→)(F14)); the F(14)/F(0) ratio was calculated as a marker of cortisol rhythm. Median F(14) levels were higher in the subjects in the third tertile of age than in those falling in the second or in the first age tertile (respectively, 2.09 vs 1.33 vs 1.25 ng/mL, p=0.023 and p=0.006), in the hypertensive volunteers (2.44 vs 1.44 ng/mL, p=0.030) and in those with the metabolic syndrome (2.95 vs 1.4 ng/mL, p=0.002), with an elevated median F(14)/F(0) ratio (0.48 vs 0.19, p=0.006). According to the Kruskal-Wallis analysis of variance, the most important factor affecting F(14) value was age (p=0.001). AUC(F0)(→)(F14) was not influenced by gender, age, metabolic syndrome or estrogen-progestin therapy. While it did not affect the daily cortisol rate, late-night salivary cortisol levels were found to be increased in the subjects in the higher age tertile and in those with the metabolic syndrome.

Effects of in Utero Exposure to Arsenic during the Second Half of Gestation on Reproductive End Points and Metabolic Parameters in Female CD-1 Mice

PubMed Central

Rodriguez, Karina F.; Ungewitter, Erica K.; Crespo-Mejias, Yasmin; Liu, Chang; Nicol, Barbara; Kissling, Grace E.; Yao, Humphrey Hung-Chang

2015-01-01

Background Mice exposed to high levels of arsenic in utero have increased susceptibility to tumors such as hepatic and pulmonary carcinomas when they reach adulthood. However, the effects of in utero arsenic exposure on general physiological functions such as reproduction and metabolism remain unclear. Objectives We evaluated the effects of in utero exposure to inorganic arsenic at the U.S. Environmental Protection Agency (EPA) drinking water standard (10 ppb) and at tumor-inducing levels (42.5 ppm) on reproductive end points and metabolic parameters when the exposed females reached adulthood. Methods Pregnant CD-1 mice were exposed to sodium arsenite [none (control), 10 ppb, or 42.5 ppm] in drinking water from gestational day 10 to birth, the window of organ formation. At birth, exposed offspring were fostered to unexposed dams. We examined reproductive end points (age at vaginal opening, reproductive hormone levels, estrous cyclicity, and fertility) and metabolic parameters (body weight changes, hormone levels, body fat content, and glucose tolerance) in the exposed females when they reached adulthood. Results Arsenic-exposed females (10 ppb and 42.5 ppm) exhibited early onset of vaginal opening. Fertility was not affected when females were exposed to the 10-ppb dose. However, the number of litters per female was decreased in females exposed to 42.5 ppm of arsenic in utero. In both 10-ppb and 42.5-ppm groups, arsenic-exposed females had significantly greater body weight gain, body fat content, and glucose intolerance. Conclusion Our findings revealed unexpected effects of in utero exposure to arsenic: exposure to both a human-relevant low dose and a tumor-inducing level led to early onset of vaginal opening and to obesity in female CD-1 mice. Citation Rodriguez KF, Ungewitter EK, Crespo-Mejias Y, Liu C, Nicol B, Kissling GE, Yao HH. 2016. Effects of in utero exposure to arsenic during the second half of gestation on reproductive end points and metabolic

Diet-induced alterations of host cholesterol metabolism are likely to affect the gut microbiota composition in hamsters.

PubMed

Martínez, Inés; Perdicaro, Diahann J; Brown, Andrew W; Hammons, Susan; Carden, Trevor J; Carr, Timothy P; Eskridge, Kent M; Walter, Jens

2013-01-01

The gastrointestinal microbiota affects the metabolism of the mammalian host and has consequences for health. However, the complexity of gut microbial communities and host metabolic pathways make functional connections difficult to unravel, especially in terms of causation. In this study, we have characterized the fecal microbiota of hamsters whose cholesterol metabolism was extensively modulated by the dietary addition of plant sterol esters (PSE). PSE intake induced dramatic shifts in the fecal microbiota, reducing several bacterial taxa within the families Coriobacteriaceae and Erysipelotrichaceae. The abundance of these taxa displayed remarkably high correlations with host cholesterol metabolites. Most importantly, the associations between several bacterial taxa with fecal and biliary cholesterol excretion showed an almost perfect fit to a sigmoidal nonlinear model of bacterial inhibition, suggesting that host cholesterol excretion can shape microbiota structure through the antibacterial action of cholesterol. In vitro experiments suggested a modest antibacterial effect of cholesterol, and especially of cholesteryl-linoleate, but not plant sterols when included in model bile micelles. The findings obtained in this study are relevant to our understanding of gut microbiota-host lipid metabolism interactions, as they provide the first evidence for a role of cholesterol excreted with the bile as a relevant host factor that modulates the gut microbiota. The findings further suggest that the connections between Coriobacteriaceae and Erysipelotrichaceae and host lipid metabolism, which have been observed in several studies, could be caused by a metabolic phenotype of the host (cholesterol excretion) affecting the gut microbiota.

The new total Western diet for rodents does not induce an overweight phenotype or alter parameters of metabolic syndrome in mice.

PubMed

Monsanto, Stephany P; Hintze, Korry J; Ward, Robert E; Larson, Deanna P; Lefevre, Michael; Benninghoff, Abby D

2016-09-01

In this study, we determined the impact of the total Western diet (TWD) for rodents and its macro- and micronutrient components on weight gain and biomarkers of metabolic function in mice compared to a 45% fat diet-induced obesity (DIO) diet and the standard AIN93G diet. We hypothesized that mice fed the TWD would have increased body fat with indicators of metabolic syndrome similar to mice consuming the DIO diet. As expected, DIO-fed mice acquired a metabolic syndrome phenotype typified by increased energy intake, increased body weight gain, increased fat mass, higher fasting glucose, impaired glucose tolerance, and higher plasma leptin relative to the AIN93G diet. Mice fed a macronutrient-modified (MM) diet (with standard vitamin and mineral composition) had a similar response, albeit to a lesser degree than mice fed the DIO diet. Mice fed a vitamin- and mineral-modified diet (with standard macronutrient composition) were not different from mice fed the AIN93G diet. Surprisingly, the TWD (with modified macronutrients, vitamins and minerals) did not significantly affect any of these parameters, despite the fact that the TWD macronutrient profile was identical to the MM diet. These data suggest that, in the context of the TWD, vitamin and mineral intakes in mice that reflect a Western dietary pattern inhibit the hyperphagia and resulting increased weight gain associated with the higher fat content of the TWD. In conclusion, these observations underscore the need to consider the influence of micronutrient intakes in pre-clinical models of obesity and metabolic syndrome. Copyright © 2016 Elsevier Inc. All rights reserved.

Relationships between lifestyle patterns and cardio-renal-metabolic parameters in patients with type 2 diabetes mellitus: A cross-sectional study

PubMed Central

Ogihara, Takeshi; Osonoi, Yusuke; Osonoi, Takeshi; Saito, Miyoko; Tamasawa, Atsuko; Nakayama, Shiho; Someya, Yuki; Ishida, Hidenori; Gosho, Masahiko; Kanazawa, Akio; Watada, Hirotaka

2017-01-01

Introduction While individuals tend to show accumulation of certain lifestyle patterns, the effect of such patterns in real daily life on cardio-renal—metabolic parameters remains largely unknown. This study aimed to assess clustering of lifestyle patterns and investigate the relationships between such patterns and cardio-renal-metabolic parameters. Participants and methods The study participants were 726 Japanese type 2 diabetes mellitus (T2DM) outpatients free of history of cardiovascular diseases. The relationship between lifestyle patterns and cardio-renal-metabolic parameters was investigated by linear and logistic regression analyses. Results Factor analysis identified three lifestyle patterns. Subjects characterized by evening type, poor sleep quality and depressive status (type 1 pattern) had high levels of HbA1c, alanine aminotransferase and albuminuria. Subjects characterized by high consumption of food, alcohol and cigarettes (type 2 pattern) had high levels of γ-glutamyl transpeptidase, triglycerides, HDL-cholesterol, blood pressure, and brachial-ankle pulse wave velocity. Subjects characterized by high physical activity (type 3 pattern) had low uric acid and mild elevation of alanine aminotransferase and aspartate aminotransferase. In multivariate regression analysis adjusted by age, gender and BMI, type 1 pattern was associated with higher HbA1c levels, systolic BP and brachial-ankle pulse wave velocity. Type 2 pattern was associated with higher HDL-cholesterol levels, triglycerides, aspartate aminotransferase, ɤ- glutamyl transpeptidase levels, and diastolic BP. Conclusions The study identified three lifestyle patterns that were associated with distinct cardio-metabolic-renal parameters in T2DM patients. Trial registration UMIN000010932 PMID:28273173

Monoglyceride lipase deficiency affects hepatic cholesterol metabolism and lipid-dependent gut transit in ApoE−/− mice

PubMed Central

Vujic, Nemanja; Korbelius, Melanie; Leopold, Christina; Duta-Mare, Madalina; Rainer, Silvia; Schlager, Stefanie; Goeritzer, Madeleine; Kolb, Dagmar; Eichmann, Thomas O.; Diwoky, Clemens; Zimmer, Andreas; Zimmermann, Robert; Lass, Achim; Radovic, Branislav; Kratky, Dagmar

2017-01-01

Monoglyceride lipase (MGL) hydrolyzes monoglycerides (MGs) to glycerol and fatty acids. Among various MG species MGL also degrades 2-arachidonoylglycerol (2-AG), the most abundant endocannabinoid and potent activator of cannabinoid receptors (CBR) 1 and 2. MGL-knockout (−/−) mice exhibit pronounced 2-AG accumulation, but lack central cannabimimetic effects due to CB1R desensitization. We have previously shown that MGL affects plaque stability in apolipoprotein E (ApoE)−/− mice, an established animal model for dyslipidemia and atherosclerosis. In the current study, we investigated functional consequences of MGL deficiency on lipid and energy metabolism in ApoE/MGL double knockout (DKO) mice. MGL deficiency affected hepatic cholesterol metabolism by causing increased cholesterol elimination via the biliary pathway. Moreover, DKO mice exhibit lipid-triggered delay in gastric emptying without major effects on overall triglyceride and cholesterol absorption. The observed phenotype of DKO mice is likely not a consequence of potentiated CB1R signaling but rather dependent on the activation of alternative signaling pathways. We conclude that MGL deficiency causes complex metabolic changes including cholesterol metabolism and regulation of gut transit independent of the endocannabinoid system. PMID:28380440

NOVEL POLYPHENOLS THAT INHIBIT COLON CANCER CELL GROWTH AFFECTING CANCER CELL METABOLISM.

PubMed

Gomez de Cedron, Marta; Vargas, Teodoro; Madrona, Andres; Jimenez, Aranza; Perez Perez, Maria Jesus; Quintela, Jose Carlos; Reglero, Guillermo; San-Felix, Ana Rosa; Ramirez de Molina, Ana

2018-06-05

New series of polyphenols with a hydrophilic galloyl based "head" and a hydrophobic N-acyl "tail", linked through a serinol moiety, have been synthesized and tested against colon cancer cell growth. Our structure activity relationship studies revealed that galloyl moieties are essential for growth inhibition. Moreover, the length of the N-acyl chain is crucial for the activity. Introduction of a (Z) double bond in the acyl chain increased the anti-cancer properties. Our findings demonstrate that 16, the most potent compound within this series, has inhibitory effects on colon cancer cell growth and metabolism (glycolysis and mitochondrial respiration) at the same time that activates AMPK and induces apoptotic cell death. Based on these results we propose that 16 might reprogram colon cancer cell metabolism through AMPK activation. This might lead to alterations on cancer cell bioenergy compromising cancer cell viability. Importantly, these anti-proliferative and pro-apoptotic effects are selective for cancer cells. Accordingly, these results indicate that 16, with an unsaturated C18 chain, might be a useful prototype for the development of novel colon cancer cell growth inhibitors affecting cell metabolism. The American Society for Pharmacology and Experimental Therapeutics.

Measures of GCM Performance as Functions of Model Parameters Affecting Clouds and Radiation

NASA Astrophysics Data System (ADS)

Jackson, C.; Mu, Q.; Sen, M.; Stoffa, P.

2002-05-01

This abstract is one of three related presentations at this meeting dealing with several issues surrounding optimal parameter and uncertainty estimation of model predictions of climate. Uncertainty in model predictions of climate depends in part on the uncertainty produced by model approximations or parameterizations of unresolved physics. Evaluating these uncertainties is computationally expensive because one needs to evaluate how arbitrary choices for any given combination of model parameters affects model performance. Because the computational effort grows exponentially with the number of parameters being investigated, it is important to choose parameters carefully. Evaluating whether a parameter is worth investigating depends on two considerations: 1) does reasonable choices of parameter values produce a large range in model response relative to observational uncertainty? and 2) does the model response depend non-linearly on various combinations of model parameters? We have decided to narrow our attention to selecting parameters that affect clouds and radiation, as it is likely that these parameters will dominate uncertainties in model predictions of future climate. We present preliminary results of ~20 to 30 AMIPII style climate model integrations using NCAR's CCM3.10 that show model performance as functions of individual parameters controlling 1) critical relative humidity for cloud formation (RHMIN), and 2) boundary layer critical Richardson number (RICR). We also explore various definitions of model performance that include some or all observational data sources (surface air temperature and pressure, meridional and zonal winds, clouds, long and short-wave cloud forcings, etc...) and evaluate in a few select cases whether the model's response depends non-linearly on the parameter values we have selected.

Effects of pistachio nuts on body composition, metabolic, inflammatory and oxidative stress parameters in Asian Indians with metabolic syndrome: a 24-wk, randomized control trial.

PubMed

Gulati, Seema; Misra, Anoop; Pandey, Ravindra Mohan; Bhatt, Surya Prakash; Saluja, Shelza

2014-02-01

The aim of this study was to evaluate the effects of pistachio nuts as an adjunct to diet and exercise on body composition, metabolic, inflammatory, and oxidative stress parameters in Asian Indians with metabolic syndrome. In this 24-wk randomized control trial, 60 individuals with the metabolic syndrome were randomized to either pistachio (intervention group) or control group (diet as per weight and physical activity profile, modulated according to dietary guidelines for Asian Indians) after 3 wk of a diet and exercise run in. In the first group, unsalted pistachios (20% energy) were given daily. A standard diet and exercise protocol was followed for both groups. Body weight, waist circumference (WC), magnetic resonance imaging estimation of intraabdominal adipose tissue and subcutaneous abdominal adipose tissue, fasting blood glucose (FBG), fasting serum insulin, glycosylated hemoglobin, lipid profile, high-sensitivity C-reactive protein (hs-CRP), adiponectin, free fatty acids (FFAs), tumor necrosis factor (TNF)-α, leptin, and thiobarbituric acid reactive substances (TBARS) were assessed before and after the intervention. Statistically significant improvement in mean values for various parameters in the intervention group compared with control group were as follows: WC (P < 0.02), FBG (P < 0.04), total cholesterol (P < 0.02), low-density lipoprotein cholesterol (P < 0.006), hs-CRP (P < 0.05), TNF-α (P < 0.03), FFAs (P < 0.001), TBARS (P < 0.01), and adiponectin levels (P < 0.001). A single food intervention with pistachios leads to beneficial effects on the cardiometabolic profile of Asian Indians with metabolic syndrome. Copyright © 2014 Elsevier Inc. All rights reserved.

Rewiring carbohydrate catabolism differentially affects survival of pancreatic cancer cell lines with diverse metabolic profiles

PubMed Central

Tataranni, Tiziana; Agriesti, Francesca; Ruggieri, Vitalba; Mazzoccoli, Carmela; Simeon, Vittorio; Laurenzana, Ilaria; Scrima, Rosella; Pazienza, Valerio; Capitanio, Nazzareno; Piccoli, Claudia

2017-01-01

An increasing body of evidence suggests that targeting cellular metabolism represents a promising effective approach to treat pancreatic cancer, overcome chemoresistance and ameliorate patient's prognosis and survival. In this study, following whole-genome expression analysis, we selected two pancreatic cancer cell lines, PANC-1 and BXPC-3, hallmarked by distinct metabolic profiles with specific concern to carbohydrate metabolism. Functional comparative analysis showed that BXPC-3 displayed a marked deficit of the mitochondrial respiratory and oxidative phosphorylation activity and a higher production of reactive oxygen species and a reduced NAD+/NADH ratio, indicating their bioenergetic reliance on glycolysis and a different redox homeostasis as compared to PANC-1. Both cell lines were challenged to rewire their metabolism by substituting glucose with galactose as carbon source, a condition inhibiting the glycolytic flux and fostering full oxidation of the sugar carbons. The obtained data strikingly show that the mitochondrial respiration-impaired-BXPC-3 cell line was unable to sustain the metabolic adaptation required by glucose deprivation/substitution, thereby resulting in a G2\\M cell cycle shift, unbalance of the redox homeostasis, apoptosis induction. Conversely, the mitochondrial respiration-competent-PANC-1 cell line did not show clear evidence of cell sufferance. Our findings provide a strong rationale to candidate metabolism as a promising target for cancer therapy. Defining the metabolic features at time of pancreatic cancer diagnosis and likely of other tumors, appears to be crucial to predict the responsiveness to therapeutic approaches or coadjuvant interventions affecting metabolism. PMID:28476035

Metabolic syndrome parameters in adolescents may be determinants for the future periodontal diseases.

PubMed

Lee, Kyeong-Soo; Lee, Sang Gyu; Kim, Eun-Kyong; Jin, Hye-Jung; Im, Sang-Uk; Lee, Hee-Kyung; Merchant, Anwar T; Song, Keun-Bae; Choi, Youn-Hee

2015-02-01

The prevalence of metabolic syndrome (MetS) increases even in adolescents. The evidence that MetS is associated with the periodontal diseases in adolescents has been understudied. Therefore, our aim was to assess the association between MetS parameters and gingivitis in adolescents. A total of 941 participants (590 boys, 351 girls), aged 12-18 years was selected from the Fourth Korea National Health and Nutrition Examination Survey, a cross-sectional and nationally representative survey, which had had information on waist circumference, blood pressure, serum triglyceride, high-density lipoprotein (HDL) cholesterol, and the fasting blood sugar and community periodontal Index (CPI). The number of positive parameters of MetS showed significant positive correlation with gingivitis; adjusted and crude ORs with one positive parameters of MetS were 1.92 (95% CI: 1.21-3.04) and 1.88(95% CI: 1.28-2.76), respectively. And adjusted OR with three or more positive parameters of MetS was 3.29 (95% CI: 1.24-8.71). Among five parameters of MetS, Low HDL-cholesterol showed significant association with gingivitis (crude OR 2.12, 95% CI 1.20-3.73; adjusted OR 1.96, 95% CI 1.24-3.12). Having more positive parameters of MetS and low HDL-cholesterol parameter had an independent relationship with the prevalence of gingivitis, which may be determinants for the future periodontal diseases even in adolescents. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Systematic Sensitivity Analysis of Metabolic Controllers During Reductions in Skeletal Muscle Blood Flow

NASA Technical Reports Server (NTRS)

Radhakrishnan, Krishnan; Cabrera, Marco

2000-01-01

An acute reduction in oxygen delivery to skeletal muscle is generally associated with profound derangements in substrate metabolism. Given the complexity of the human bioenergetic system and its components, it is difficult to quantify the interaction of cellular metabolic processes to maintain ATP homeostasis during stress (e.g., hypoxia, ischemia, and exercise). Of special interest is the determination of mechanisms relating tissue oxygenation to observed metabolic responses at the tissue, organ, and whole body levels and the quantification of how changes in oxygen availability affect the pathways of ATP synthesis and their regulation. In this study, we apply a previously developed mathematical model of human bioenergetics to study effects of ischemia during periods of increased ATP turnover (e.g., exercise). By using systematic sensitivity analysis the oxidative phosphorylation rate was found to be the most important rate parameter affecting lactate production during ischemia under resting conditions. Here we examine whether mild exercise under ischemic conditions alters the relative importance of pathways and parameters previously obtained.

Visual food cues decrease postprandial glucose concentrations in lean and obese men without affecting food intake and related endocrine parameters.

PubMed

Brede, Swantje; Sputh, Annika; Hartmann, Ann-Christin; Hallschmid, Manfred; Lehnert, Hendrik; Klement, Johanna

2017-10-01

The abundance of highly palatable food items in our environment represents a possible cause of overconsumption. Neuroimaging studies in humans have demonstrated that watching pictures of food increases activation in brain areas involved in homeostatic and hedonic food cue processing. Nevertheless, the impact of food cues on actual food intake and metabolic parameters has not been systematically investigated. We tested the hypothesis that watching high-calorie food cues increases food intake and modifies anticipatory blood parameters in lean and especially in obese men. In 20 normal-weight and 20 obese healthy fasted men, we assessed the effects of watching pictures of high-calorie food items versus neutral contents on food intake measured during a standardized test buffet and subsequent snacking as well as on glucose homeostasis and endocrine parameters. Compared to neutral pictures, viewing food pictures reduced postprandial blood glucose concentrations in lean (p = 0.016) and obese (p = 0.044) subjects, without any differences in insulin or C-peptide concentrations (all p > 0.4). Viewing food pictures did not affect total calorie intake during the buffet (all p > 0.5) and snack consumption (all p > 0.4). Concentrations of ghrelin, adrenocorticotropic hormone (ACTH), cortisol, and glucagon also remained unaffected (all p > 0.08). These data indicate that preprandial processing of food cues curbs postprandial blood glucose excursions, without immediately affecting eating behavior in normal-weight and obese men. Findings indicate that exposure to food cues does not acutely trigger calorie overconsumption but rather improves the glucoregulatory response to food intake. Copyright © 2017 Elsevier Ltd. All rights reserved.

Exercise training dose differentially alters muscle and heart capillary density and metabolic functions in an obese rat with metabolic syndrome.

PubMed

Machado, Marcus Vinicius; Vieira, Aline Bomfim; da Conceição, Fabiana Gomes; Nascimento, Alessandro Rodrigues; da Nóbrega, Antonio Claudio Lucas; Tibirica, Eduardo

2017-12-01

What is the central question of this study? Regular exercise is recommended as a non-pharmacological approach for the prevention and treatment of metabolic syndrome. However, the impact of different combinations of intensity, duration and frequency of exercise on metabolic syndrome and microvascular density has not been reported. What is the main finding and its importance? We provide evidence on the impact of aerobic exercise dose on metabolic and microvascular alterations in an experimental model of metabolic syndrome induced by high-fat diet. We found that the exercise frequency and duration were the main factors affecting anthropometric and metabolic parameters and microvascular density in the skeletal muscle. Exercise intensity was related only to microvascular density in the heart. We evaluated the effect of the frequency, duration and intensity of exercise training on metabolic parameters and structural capillary density in obese rats with metabolic syndrome. Wistar-Kyoto rats were fed either a standard commercial diet (CON) or a high-fat diet (HFD). Animals that received the HFD were randomly separated into either a sedentary (SED) group or eight different exercise groups that varied according to the frequency, duration and intensity of training. After 12 weeks of aerobic exercise training, the body composition, aerobic capacity, haemodynamic variables, metabolic parameters and capillary density in the heart and skeletal muscle were evaluated. All the exercise training groups showed reduced resting systolic blood pressure and heart rate and normalized fasting glucose. The minimal amount of exercise (90 min per week) produced little effect on metabolic syndrome parameters. A moderate amount of exercise (150 min per week) was required to reduce body weight and improve capillary density. However, only the high amount of exercise (300 min per week) significantly reduced the amount of body fat depots. The three-way ANOVA showed a main effect of exercise

Gold nanoparticles alter parameters of oxidative stress and energy metabolism in organs of adult rats.

PubMed

Ferreira, Gabriela Kozuchovski; Cardoso, Eria; Vuolo, Francieli Silva; Michels, Monique; Zanoni, Elton Torres; Carvalho-Silva, Milena; Gomes, Lara Mezari; Dal-Pizzol, Felipe; Rezin, Gislaine Tezza; Streck, Emilio L; Paula, Marcos Marques da Silva

2015-12-01

This study evaluated the parameters of oxidative stress and energy metabolism after the acute and long-term administration of gold nanoparticles (GNPs, 10 and 30 nm in diameter) in different organs of rats. Adult male Wistar rats received a single intraperitoneal injection or repeated injections (once daily for 28 days) of saline solution, GNPs-10 or GNPs-30. Twenty-four hours after the last administration, the animals were killed, and the liver, kidney, and heart were isolated for biochemical analysis. We demonstrated that acute administration of GNPs-30 increased the TBARS levels, and that GNPs-10 increased the carbonyl protein levels. The long-term administration of GNPs-10 increased the TBARS levels, and the carbonyl protein levels were increased by GNPs-30. Acute administration of GNPs-10 and GNPs-30 increased SOD activity. Long-term administration of GNPs-30 increased SOD activity. Acute administration of GNPs-10 decreased the activity of CAT, whereas long-term administration of GNP-10 and GNP-30 altered CAT activity randomly. Our results also demonstrated that acute GNPs-30 administration decreased energy metabolism, especially in the liver and heart. Long-term GNPs-10 administration increased energy metabolism in the liver and decreased energy metabolism in the kidney and heart, whereas long-term GNPs-30 administration increased energy metabolism in the heart. The results of our study are consistent with other studies conducted in our research group and reinforce the fact that GNPs can lead to oxidative damage, which is responsible for DNA damage and alterations in energy metabolism.

Changes in gut microbiota in rats fed a high fat diet correlate with obesity-associated metabolic parameters.

PubMed

Lecomte, Virginie; Kaakoush, Nadeem O; Maloney, Christopher A; Raipuria, Mukesh; Huinao, Karina D; Mitchell, Hazel M; Morris, Margaret J

2015-01-01

The gut microbiota is emerging as a new factor in the development of obesity. Many studies have described changes in microbiota composition in response to obesity and high fat diet (HFD) at the phylum level. In this study we used 16s RNA high throughput sequencing on faecal samples from rats chronically fed HFD or control chow (n = 10 per group, 16 weeks) to investigate changes in gut microbiota composition at the species level. 53.17% dissimilarity between groups was observed at the species level. Lactobacillus intestinalis dominated the microbiota in rats under the chow diet. However this species was considerably less abundant in rats fed HFD (P<0.0001), this being compensated by an increase in abundance of propionate/acetate producing species. To further understand the influence of these species on the development of the obese phenotype, we correlated their abundance with metabolic parameters associated with obesity. Of the taxa contributing the most to dissimilarity between groups, 10 presented significant correlations with at least one of the tested parameters, three of them correlated positively with all metabolic parameters: Phascolarctobacterium, Proteus mirabilis and Veillonellaceae, all propionate/acetate producers. Lactobacillus intestinalis was the only species whose abundance was negatively correlated with change in body weight and fat mass. This species decreased drastically in response to HFD, favouring propionate/acetate producing bacterial species whose abundance was strongly correlated with adiposity and deterioration of metabolic factors. Our observations suggest that these species may play a key role in the development of obesity in response to a HFD.

How does metabolism affect cell death in cancer?

PubMed

Villa, Elodie; Ricci, Jean-Ehrland

2016-07-01

In cancer research, identifying a specificity of tumor cells compared with 'normal' proliferating cells for targeted therapy is often considered the Holy Grail for researchers and clinicians. Although diverse in origin, most cancer cells share characteristics including the ability to escape cell death mechanisms and the utilization of different methods of energy production. In the current paradigm, aerobic glycolysis is considered the central metabolic characteristic of cancer cells (Warburg effect). However, recent data indicate that cancer cells also show significant changes in other metabolic pathways. Indeed, it was recently suggested that Kreb's cycle, pentose phosphate pathway intermediates, and essential and nonessential amino acids have key roles. Renewed interest in the fact that cancer cells have to reprogram their metabolism in order to proliferate or resist treatment must take into consideration the ability of tumor cells to adapt their metabolism to the local microenvironment (low oxygen, low nutrients). This variety of metabolic sources might be either a strength, resulting in infinite possibilities for adaptation and increased ability to resist chemotherapy-induced death, or a weakness that could be targeted to kill cancer cells. Here, we discuss recent insights showing how energetic metabolism may regulate cell death and how this might be relevant for cancer treatment. © 2015 FEBS.

Water deficit alters differentially metabolic pathways affecting important flavor and quality traits in grape berries of Cabernet Sauvignon and Chardonnay

PubMed Central

Deluc, Laurent G; Quilici, David R; Decendit, Alain; Grimplet, Jérôme; Wheatley, Matthew D; Schlauch, Karen A; Mérillon, Jean-Michel; Cushman, John C; Cramer, Grant R

2009-01-01

Background Water deficit has significant effects on grape berry composition resulting in improved wine quality by the enhancement of color, flavors, or aromas. While some pathways or enzymes affected by water deficit have been identified, little is known about the global effects of water deficit on grape berry metabolism. Results The effects of long-term, seasonal water deficit on berries of Cabernet Sauvignon, a red-wine grape, and Chardonnay, a white-wine grape were analyzed by integrated transcript and metabolite profiling. Over the course of berry development, the steady-state transcript abundance of approximately 6,000 Unigenes differed significantly between the cultivars and the irrigation treatments. Water deficit most affected the phenylpropanoid, ABA, isoprenoid, carotenoid, amino acid and fatty acid metabolic pathways. Targeted metabolites were profiled to confirm putative changes in specific metabolic pathways. Water deficit activated the expression of numerous transcripts associated with glutamate and proline biosynthesis and some committed steps of the phenylpropanoid pathway that increased anthocyanin concentrations in Cabernet Sauvignon. In Chardonnay, water deficit activated parts of the phenylpropanoid, energy, carotenoid and isoprenoid metabolic pathways that contribute to increased concentrations of antheraxanthin, flavonols and aroma volatiles. Water deficit affected the ABA metabolic pathway in both cultivars. Berry ABA concentrations were highly correlated with 9-cis-epoxycarotenoid dioxygenase (NCED1) transcript abundance, whereas the mRNA expression of other NCED genes and ABA catabolic and glycosylation processes were largely unaffected. Water deficit nearly doubled ABA concentrations within berries of Cabernet Sauvignon, whereas it decreased ABA in Chardonnay at véraison and shortly thereafter. Conclusion The metabolic responses of grapes to water deficit varied with the cultivar and fruit pigmentation. Chardonnay berries, which lack any

Metabolic and anthropometric parameters contribute to ART-mediated CD4+ T cell recovery in HIV-1-infected individuals: an observational study.

PubMed

Azzoni, Livio; Foulkes, Andrea S; Firnhaber, Cynthia; Yin, Xiangfan; Crowther, Nigel J; Glencross, Deborah; Lawrie, Denise; Stevens, Wendy; Papasavvas, Emmanouil; Sanne, Ian; Montaner, Luis J

2011-07-29

The degree of immune reconstitution achieved in response to suppressive ART is associated with baseline individual characteristics, such as pre-treatment CD4 count, levels of viral replication, cellular activation, choice of treatment regimen and gender. However, the combined effect of these variables on long-term CD4 recovery remains elusive, and no single variable predicts treatment response. We sought to determine if adiposity and molecules associated with lipid metabolism may affect the response to ART and the degree of subsequent immune reconstitution, and to assess their ability to predict CD4 recovery. We studied a cohort of 69 (48 females and 21 males) HIV-infected, treatment-naïve South African subjects initiating antiretroviral treatment (d4T, 3Tc and lopinavir/ritonavir). We collected information at baseline and six months after viral suppression, assessing anthropometric parameters, dual energy X-ray absorptiometry and magnetic resonance imaging scans, serum-based clinical laboratory tests and whole blood-based flow cytometry, and determined their role in predicting the increase in CD4 count in response to ART. We present evidence that baseline CD4+ T cell count, viral load, CD8+ T cell activation (CD95 expression) and metabolic and anthropometric parameters linked to adiposity (LDL/HDL cholesterol ratio and waist/hip ratio) significantly contribute to variability in the extent of CD4 reconstitution (ΔCD4) after six months of continuous ART. Our final model accounts for 44% of the variability in CD4+ T cell recovery in virally suppressed individuals, representing a workable predictive model of immune reconstitution.

Maternal Metabolic Health Parameters During Pregnancy in Relation to Early Childhood BMI Trajectories.

PubMed

Montazeri, Parisa; Vrijheid, Martine; Martinez, David; Basterrechea, Mikel; Fernandez-Somoano, Ana; Guxens, Monica; Iñiguez, Carmen; Lertxundi, Aitana; Murcia, Mario; Tardon, Adonina; Sunyer, Jordi; Valvi, Damaskini

2018-03-01

The objective of this study was to evaluate the associations between maternal metabolic parameters and early childhood BMI trajectories. Two thousand two hundred fifty-one children born in Spain between 2004 and 2008 were analyzed. Five BMI z score trajectories from birth to age 4 years were identified by using latent class growth analysis. Multinomial regression assessed the associations between maternal metabolic parameters and offspring's BMI trajectories. Children in the reference BMI trajectory had average size at birth followed by a slower BMI gain. Maternal prepregnancy obesity was associated with trajectories of accelerated BMI gain departing from either higher (relative risk ratio [RRR] = 1.77; 95% CI: 1.07-2.91) or lower size at birth (RRR = 1.91; 95% CI: 1.17-3.12). Gestational weight gain (GWG) above clinical guidelines was associated with a trajectory of higher birth size followed by accelerated BMI gain (RRR = 2.14; 95% CI: 1.53-2.97). Maternal serum triglycerides were negatively associated with BMI trajectories departing from lower birth sizes. Gestational diabetes, maternal serum cholesterol, and C-reactive protein were unrelated to children's BMI trajectories. Maternal prepregnancy obesity, GWG, and serum triglycerides are associated with longitudinal BMI trajectories in early childhood that may increase disease risk in later life. Health initiatives should promote healthy weight status before and during pregnancy to improve maternal and child health. © 2018 The Obesity Society.

How coffee affects metabolic syndrome and its components.

PubMed

Baspinar, B; Eskici, G; Ozcelik, A O

2017-06-21

Metabolic syndrome, with its increasing prevalence, is becoming a major public health problem throughout the world. Many risk factors including nutrition play a role in the emergence of metabolic syndrome. Of the most-consumed beverages in the world, coffee contains more than 1000 components such as caffeine, chlorogenic acid, diterpenes and trigonelline. It has been proven in many studies that coffee consumption has a positive effect on chronic diseases. In this review, starting from the beneficial effects of coffee on health, the relationship between coffee consumption and metabolic syndrome and its components has been investigated. There are few studies investigating the relationship between coffee and metabolic syndrome, and the existing ones put forward different findings. The factors leading to the differences are thought to stem from coffee variety, the physiological effects of coffee elements, and the nutritional ingredients (such as milk and sugar) added to coffee. It is reported that consumption of coffee in adults up to three cups a day reduces the risk of Type-2 diabetes and metabolic syndrome.

C282Y-HFE Gene Variant Affects Cholesterol Metabolism in Human Neuroblastoma Cells

PubMed Central

Ali-Rahmani, Fatima; Huang, Michael A.; Schengrund, C.-L.; Connor, James R.; Lee, Sang Y.

2014-01-01

Although disruptions in the maintenance of iron and cholesterol metabolism have been implicated in several cancers, the association between variants in the HFE gene that is associated with cellular iron uptake and cholesterol metabolism has not been studied. The C282Y-HFE variant is a risk factor for different cancers, is known to affect sphingolipid metabolism, and to result in increased cellular iron uptake. The effect of this variant on cholesterol metabolism and its possible relevance to cancer phenotype was investigated using wild type (WT) and C282Y-HFE transfected human neuroblastoma SH-SY5Y cells. Expression of C282Y-HFE in SH-SY5Y cells resulted in a significant increase in total cholesterol as well as increased transcription of a number of genes involved in its metabolism compared to cells expressing WT-HFE. The marked increase in expression of NPC1L1 relative to that of most other genes, was accompanied by a significant increase in expression of NPC1, a protein that functions in cholesterol uptake by cells. Because inhibitors of cholesterol metabolism have been proposed to be beneficial for treating certain cancers, their effect on the viability of C282Y-HFE neuroblastoma cells was ascertained. C282Y-HFE cells were significantly more sensitive than WT-HFE cells to U18666A, an inhibitor of desmosterol Δ24-reductase the enzyme catalyzing the last step in cholesterol biosynthesis. This was not seen for simvastatin, ezetimibe, or a sphingosine kinase inhibitor. These studies indicate that cancers presenting in carriers of the C282Y-HFE allele might be responsive to treatment designed to selectively reduce cholesterol content in their tumor cells. PMID:24533143

C282Y-HFE gene variant affects cholesterol metabolism in human neuroblastoma cells.

PubMed

Ali-Rahmani, Fatima; Huang, Michael A; Schengrund, C-L; Connor, James R; Lee, Sang Y

2014-01-01

Although disruptions in the maintenance of iron and cholesterol metabolism have been implicated in several cancers, the association between variants in the HFE gene that is associated with cellular iron uptake and cholesterol metabolism has not been studied. The C282Y-HFE variant is a risk factor for different cancers, is known to affect sphingolipid metabolism, and to result in increased cellular iron uptake. The effect of this variant on cholesterol metabolism and its possible relevance to cancer phenotype was investigated using wild type (WT) and C282Y-HFE transfected human neuroblastoma SH-SY5Y cells. Expression of C282Y-HFE in SH-SY5Y cells resulted in a significant increase in total cholesterol as well as increased transcription of a number of genes involved in its metabolism compared to cells expressing WT-HFE. The marked increase in expression of NPC1L1 relative to that of most other genes, was accompanied by a significant increase in expression of NPC1, a protein that functions in cholesterol uptake by cells. Because inhibitors of cholesterol metabolism have been proposed to be beneficial for treating certain cancers, their effect on the viability of C282Y-HFE neuroblastoma cells was ascertained. C282Y-HFE cells were significantly more sensitive than WT-HFE cells to U18666A, an inhibitor of desmosterol Δ24-reductase the enzyme catalyzing the last step in cholesterol biosynthesis. This was not seen for simvastatin, ezetimibe, or a sphingosine kinase inhibitor. These studies indicate that cancers presenting in carriers of the C282Y-HFE allele might be responsive to treatment designed to selectively reduce cholesterol content in their tumor cells.

High intake of orange juice and cola differently affects metabolic risk in healthy subjects.

PubMed

Büsing, Franziska; Hägele, Franziska A; Nas, Alessa; Döbert, Laura-Verena; Fricker, Alena; Dörner, Elisabeth; Podlesny, Daniel; Aschoff, Julian; Pöhnl, Tobias; Schweiggert, Ralf; Fricke, W Florian; Carle, Reinhold; Bosy-Westphal, Anja

2018-03-03

Higher consumption of sugar-containing beverages has been associated with an elevated risk of type 2 diabetes and gout. Whether this equally applies to cola with an unhealthy image and orange juice (OJ) having a healthy image remains unknown. In order to investigate whether OJ and cola differently affect metabolic risk 26 healthy adults (24.7 ± 3.2 y; BMI 23.2 ± 3.3 kg/m 2 ) participated in a 2 × 2-wk intervention and consumed either OJ or caffeine-free cola (20% Ereq as sugar from beverages) in-between 3 meals/d at ad libitum energy intake. Glycemic control, uric acid metabolism and gut microbiota were assessed as outcome parameters. Fecal microbiota, body weight, basal and OGTT-derived insulin sensitivity remained unchanged in both intervention periods. Levels of uric acid were normal at baseline and did not change with 2-wk cola consumption (-0.03 ± 0.67 mg/dL; p > 0.05), whereas they decreased with OJ intervention (-0.43 ± 0.56 mg/dL; p < 0.01) due to increased uric acid excretion (+130.2 ± 130.0 mg/d; p < 0.001). Compared to OJ, consumption of cola led to a higher daylong glycemia (ΔiAUC: 36.9 ± 83.2; p < 0.05), an increase in glucose variability (ΔMAGE-Index: 0.29 ± 0.44; p < 0.05), and a lower 24 h-insulin secretion (ΔC-peptide excretion: -31.76 ± 38.61 μg/d; p < 0.001), which may be explained by a decrease in serum potassium levels (-0.11 ± 0.24 mmol/L; p < 0.05). Despite its sugar content, regular consumption of large amounts of OJ do not increase the risk of gout but may even contribute to lower uric acid levels. The etiology of impaired insulin secretion with cola consumption needs to be further investigated. Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Preliminary validation of assays to measure parameters of calcium metabolism in captive Asian and African elephants in western Europe.

PubMed

van Sonsbeek, Gerda R; van der Kolk, Johannes H; van Leeuwen, Johannes P T M; Schaftenaar, Willem

2011-05-01

Hypocalcemia is a well known cause of dystocia in animals, including elephants in captivity. In order to study calcium metabolism in elephants, it is of utmost importance to use properly validated assays, as these might be prone to specific matrix effects in elephant blood. The aim of the current study was to conduct preliminary work for validation of various parameters involved in calcium metabolism in both blood and urine of captive elephants. Basal values of these parameters were compared between Asian elephants (Elephas maximus) and African elephants (Loxodonta africana). Preliminary testing of total calcium, inorganic phosphorus, and creatinine appeared valid for use in plasma and creatinine in urine in both species. Furthermore, measurements of bone alkaline phosphatase and N-terminal telopeptide of type I collagen appeared valid for use in Asian elephants. Mean heparinized plasma ionized calcium concentration and pH were not significantly affected by 3 cycles of freezing and thawing. Storage at 4 °C, room temperature, and 37 °C for 6, 12, and 24 hr did not alter the heparinized plasma ionized calcium concentration in Asian elephants. The following linear regression equation using pH (range: 6.858-7.887) and ionized calcium concentration in heparinized plasma was utilized: iCa(7.4) (mmol/l) = -2.1075 + 0.3130·pH(actual) + 0.8296·iCa(actual) (mmol/l). Mean basal values for pH and plasma in Asian elephant whole blood were 7.40 ± 0.048 and 7.49 ± 0.077, respectively. The urinary specific gravity and creatinine concentrations in both Asian and African elephants were significantly correlated and both were significantly lower in Asian elephants. © 2011 The Author(s)

Circulating insulin-like peptide 5 levels and its association with metabolic and hormonal parameters in women with polycystic ovary syndrome.

PubMed

Bicer, M; Alan, M; Alarslan, P; Guler, A; Kocabas, G U; Imamoglu, C; Aksit, M; Bozkaya, G; Isil, A M; Baloglu, A; Aslanipoiur, B; Calan, Mehmet

2018-06-28

Insulin-like peptide 5 (INSL5) is a gut peptide hormone that is a member of relaxin/insulin superfamily. Growing evidence implicates the crucial role of the peptide in some metabolisms including food intake, glucose homeostasis and reproductive system. Polycystic ovary syndrome (PCOS) is involved in both reproductive and metabolic issues. The aim of the study was determination of circulating levels of INSL5 alteration in women with PCOS and evaluation of the relationship between INSL5 and hormonal-metabolic parameters as well as carotid intima media thickness (cIMT). A total of 164 subjects were recruited in this cross-sectional study (82 women with PCOS and 82 age- and BMI-matched controls). Circulating INSL5 levels were assessed via ELISA method. High-resolution B-mode ultrasound was used to measure cIMT. The hormonal and metabolic parameters of the recruited subjects were determined. Circulating INSL5 levels were significantly elevated in women with PCOS compared to controls (27.63 ± 7.74 vs. 19.90 ± 5.85 ng/ml, P < 0.001). The mean values of INSL5 were significantly higher in overweight subjects compared to lean weight subjects in both groups. The women with PCOS having insulin resistance have increased INSL5 compared to those of PCOS subjects without insulin resistance. INSL5 is associated with insulin resistance, BMI, luteinizing hormone and free androgen index. Multivariate logistic regression analyses revealed that the odds ratio for having PCOS in the highest tertile of INSL5 was higher than in the lowest tertile. PCOS subjects exhibited an elevation in circulating INSL5 levels along with a link between INSL5 level induction and metabolic-hormonal parameters.

Genetic alterations affecting cholesterol metabolism and human fertility.

PubMed

DeAngelis, Anthony M; Roy-O'Reilly, Meaghan; Rodriguez, Annabelle

2014-11-01

Single nucleotide polymorphisms (SNPs) represent genetic variations among individuals in a population. In medicine, these small variations in the DNA sequence may significantly impact an individual's response to certain drugs or influence the risk of developing certain diseases. In the field of reproductive medicine, a significant amount of research has been devoted to identifying polymorphisms which may impact steroidogenesis and fertility. This review discusses current understanding of the effects of genetic variations in cholesterol metabolic pathways on human fertility that bridge novel linkages between cholesterol metabolism and reproductive health. For example, the role of the low-density lipoprotein receptor (LDLR) in cellular metabolism and human reproduction has been well studied, whereas there is now an emerging body of research on the role of the high-density lipoprotein (HDL) receptor scavenger receptor class B type I (SR-BI) in human lipid metabolism and female reproduction. Identifying and understanding how polymorphisms in the SCARB1 gene or other genes related to lipid metabolism impact human physiology is essential and will play a major role in the development of personalized medicine for improved diagnosis and treatment of infertility. © 2014 by the Society for the Study of Reproduction, Inc.

Systematic variation of prosthetic foot spring affects center-of-mass mechanics and metabolic cost during walking.

PubMed

Zelik, Karl E; Collins, Steven H; Adamczyk, Peter G; Segal, Ava D; Klute, Glenn K; Morgenroth, David C; Hahn, Michael E; Orendurff, Michael S; Czerniecki, Joseph M; Kuo, Arthur D

2011-08-01

Lower-limb amputees expend more energy to walk than non-amputees and have an elevated risk of secondary disabilities. Insufficient push-off by the prosthetic foot may be a contributing factor. We aimed to systematically study the effect of prosthetic foot mechanics on gait, to gain insight into fundamental prosthetic design principles. We varied a single parameter in isolation, the energy-storing spring in a prototype prosthetic foot, the controlled energy storage and return (CESR) foot, and observed the effect on gait. Subjects walked on the CESR foot with three different springs. We performed parallel studies on amputees and on non-amputees wearing prosthetic simulators. In both groups, spring characteristics similarly affected ankle and body center-of-mass (COM) mechanics and metabolic cost. Softer springs led to greater energy storage, energy return, and prosthetic limb COM push-off work. But metabolic energy expenditure was lowest with a spring of intermediate stiffness, suggesting biomechanical disadvantages to the softest spring despite its greater push-off. Disadvantages of the softest spring may include excessive heel displacements and COM collision losses. We also observed some differences in joint kinetics between amputees and non-amputees walking on the prototype foot. During prosthetic push-off, amputees exhibited reduced energy transfer from the prosthesis to the COM along with increased hip work, perhaps due to greater energy dissipation at the knee. Nevertheless, the results indicate that spring compliance can contribute to push-off, but with biomechanical trade-offs that limit the degree to which greater push-off might improve walking economy. © 2011 IEEE

Systematic variation of prosthetic foot spring affects center-of-mass mechanics and metabolic cost during walking

PubMed Central

Zelik, Karl E.; Collins, Steven H.; Adamczyk, Peter G.; Segal, Ava D.; Klute, Glenn K.; Morgenroth, David C.; Hahn, Michael E.; Orendurff, Michael S.; Czerniecki, Joseph M.; Kuo, Arthur D.

2014-01-01

Lower-limb amputees expend more energy to walk than non-amputees and have an elevated risk of secondary disabilities. Insufficient push-off by the prosthetic foot may be a contributing factor. We aimed to systematically study the effect of prosthetic foot mechanics on gait, to gain insight into fundamental prosthetic design principles. We varied a single parameter in isolation, the energy-storing spring in a prototype prosthetic foot, the Controlled Energy Storage and Return (CESR) foot, and observed the effect on gait. Subjects walked on the CESR foot with three different springs. We performed parallel studies on amputees and on non-amputees wearing prosthetic simulators. In both groups, spring characteristics similarly affected ankle and body center-of-mass (COM) mechanics and metabolic cost. Softer springs led to greater energy storage, energy return and prosthetic limb COM push-off work. But metabolic energy expenditure was lowest with a spring of intermediate stiffness, suggesting biomechanical disadvantages to the softest spring despite its greater push-off. Disadvantages of the softest spring may include excessive heel displacements and COM collision losses. We also observed some differences in joint kinetics between amputees and non-amputees walking on the prototype foot. During prosthetic push-off, amputees exhibited reduced energy transfer from the prosthesis to the COM along with increased hip work, perhaps due to greater energy dissipation at the knee. Nevertheless, the results indicate that spring compliance can contribute to push-off, but with biomechanical trade-offs that limit the degree to which greater push-off might improve walking economy. PMID:21708509

Dietary carbohydrate deprivation increases 24-hour nitrogen excretion without affecting postabsorptive hepatic or whole body protein metabolism in healthy men.

PubMed

Bisschop, P H; De Sain-Van Der Velden, M G M; Stellaard, F; Kuipers, F; Meijer, A J; Sauerwein, H P; Romijn, J A

2003-08-01

Because insulin is an important regulator of protein metabolism, we hypothesized that physiological modulation of insulin secretion, by means of extreme variations in dietary carbohydrate content, affects postabsorptive protein metabolism. Therefore, we studied the effects of three isocaloric diets with identical protein content and low-carbohydrate/high-fat (2% and 83% of total energy, respectively), intermediate-carbohydrate/intermediate-fat (44% and 41% of total energy, respectively), and high-carbohydrate/low-fat (85% and 0% of total energy, respectively) content in six healthy men. Whole body protein metabolism was assessed by 24-h urinary nitrogen excretion, postabsorptive leucine kinetics, and fibrinogen and albumin synthesis by infusion of [1-(13)C]leucine and [1-(13)C]valine. The low-carbohydrate/high-fat diet resulted in lower absorptive and postabsorptive plasma insulin concentrations, and higher rates of nitrogen excretion compared with the other two diets: 15.3 +/- 0.9 vs. 12.1 +/- 1.1 (P = 0.03) and 10.8 +/- 0.5 g/24 h (P = 0.005), respectively. Postabsorptive rates of appearance of leucine and of leucine oxidation were not different among the three diets. In addition, dietary carbohydrate content did not affect the synthesis rates of fibrinogen and albumin. In conclusion, eucaloric carbohydrate deprivation increases 24-h nitrogen loss but does not affect postabsorptive protein metabolism at the hepatic and whole body level. By deduction, dietary carbohydrate is required for an optimal regulation of absorptive, rather than postabsorptive, protein metabolism.

Relationships between certain metabolic diseases and selected serum biochemical parameters in seropositive dairy cows against Neospora caninum infection in different stages of lactation

PubMed

Alekish, Myassar O.; Talafha, Abdelsalam Q; Alshehabat, Musa A; Ismail, Zuhair A Bani

Neospora caninum is an important cause of abortion in dairy cattle. The general health of affected cows has not been investigated before. Therefore, the main objective of this study was to identify possible relationships between certain metabolic diseases and selected serum biochemical parameters in seropositive dairy cows against N. caninum antibodies in different stages of lactation. The study was carried out using 72 N. caninum seropositive cows and 61 seronegative dairy cows (control). Serum from all cows was tested to determine their N. caninum status (seropositive vs seronegative) using commercially available indirect enzyme-linked immunosorbent assay test kit (iELISA). In addition, serum biochemical parameters including beta-hydroxybutyrate (BHB), glucose, creatinine, blood urea nitrogen, total protein, albumin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH) and gamma-glutamyltranspeptidase (GGT) were determined using routine laboratory methods. The stage of lactation was obtained at the time of sampling from farm records. Student independent t-test showed that there was a significant difference in the serum concentrations of BHB, AST, ALT, and LDH between seropositive and seronegative cows. There was no significant association between seropositivity and the stage of lactation. However, multivariable logistic regression analysis showed that there was a strong association between seropositivity and BHB concentrations. Results of this study indicate a possible relationship between N. caninum seropositivity and certain metabolic diseases such as ketosis and fatty liver syndrome in dairy cows.

Plant species affect colonization patterns and metabolic activity of associated endophytes during phytoremediation of crude oil-contaminated soil.

PubMed

Fatima, K; Imran, A; Amin, I; Khan, Q M; Afzal, M

2016-04-01

Plants coupled with endophytic bacteria hold great potential for the remediation of polluted environment. The colonization patterns and activity of inoculated endophytes in rhizosphere and endosphere of host plant are among the primary factors that may influence the phytoremediation process. However, these colonization patterns and metabolic activity of the inoculated endophytes are in turn controlled by none other than the host plant itself. The present study aims to determine such an interaction specifically for plant-endophyte systems remediating crude oil-contaminated soil. A consortium (AP) of two oil-degrading endophytic bacteria (Acinetobacter sp. strain BRSI56 and Pseudomonas aeruginosa strain BRRI54) was inoculated to two grasses, Brachiaria mutica and Leptochloa fusca, vegetated in crude oil-contaminated soil. Colonization patterns and metabolic activity of the endophytes were monitored in the rhizosphere and endosphere of the plants. Bacterial augmentation enhanced plant growth and crude oil degradation. Maximum crude oil degradation (78%) was achieved with B. mutica plants inoculated with AP consortium. This degradation was significantly higher than those treatments, where plants and bacteria were used individually or L. fusca and endophytes were used in combination. Moreover, colonization and metabolic activity of the endophytes were higher in the rhizosphere and endosphere of B. mutica than L. fusca. The plant species affected not only colonization pattern and biofilm formation of the inoculated bacteria in the rhizosphere and endosphere of the host plant but also affected the expression of alkane hydroxylase gene, alkB. Hence, the investigation revealed that plant species can affect colonization patterns and metabolic activity of inoculated endophytic bacteria and ultimately the phytoremediation process.

Metabolic syndrome 2 years after laparoscopic gastric bypass.

PubMed

Guilbert, Lizbeth; Ortiz, Cristian J; Espinosa, Omar; Sepúlveda, Elisa M; Piña, Tatiana; Joo, Paul; Zerrweck, Carlos

2018-04-01

The latest diabetes consensus identified obesity as key component of the metabolic syndrome. The role of bariatric surgery over such syndrome has been less explored with a lack of long term studies, and especially among Mexicans. Retrospective study including patients with metabolic syndrome submitted to laparoscopic gastric bypass at a single institution with complete data after 24 months. The objective was to analyze the improvement of the syndrome and each component. Demographic, anthropometric, biochemical and clinical parameters were analyzed at 12 and 24 months. Secondarily weight loss and other parameters were also analyzed. Finally, an analysis of syndrome improvement related to weight loss was performed. Sixty-three patients were included. The 2 most common components associated with obesity were reduced HDL and raised glucose or Type 2 diabetes. There was a significant improvement of metabolic syndrome and its components, as well as for the rest of the analyzed data, from the first check point and throughout follow-up. Prevalence of such syndrome was 6.3% at 12 and 24 months. Hypertension and raised glucose or Type 2 diabetes were the components with the greatest and fastest improvement; HDL levels and obesity were the least improved. There was a direct relationship between percentage of excess weight loss or percentage of excess BMI loss, and syndrome's improvement. Patients with metabolic syndrome improved after gastric bypass, with results lasting after 2 years; other metabolic parameters important for cardiovascular risk were also positively affected. There was a relationship between the amount of weight loss and improvement of metabolic syndrome. Copyright © 2018 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Improvement of metabolic parameters in healthy older adult men following a fasting calorie restriction intervention.

PubMed

Teng, Nur Islami Mohd Fahmi; Shahar, Suzana; Rajab, Nor Fadilah; Manaf, Zahara Abdul; Johari, Mohamad Hanapi; Ngah, Wan Zurinah Wan

2013-12-01

Calorie restriction and intermittent fasting are two dietary interventions that can improve aging. Religious fasting also suggested having similar benefit; however, such studies are still scarce. Thus, this study aimed to determine the effect of fasting calorie restriction (FCR) on metabolic parameters and DNA damage among healthy older adult men. A randomized controlled study was done on men, aged 50-70 years in Klang Valley, Malaysia. Subjects were divided into two groups; FCR (reduction of 300-500 kcal/d combined with 2 days/week of Muslim Sunnah Fasting) and control. Assessment was ascertained at three time point; baseline, weeks 6 and 12. Blood samples were analyzed for lipid profile, DNA damage and malondialdehyde (MDA). The FCR group reduced their energy intake for approximately 18% upon completion of the study. A significant interaction effect was found in body weight, body mass index, fat percentage, fat mass, blood pressure, total cholesterol, low-density lipoprotein cholesterol and the ratio of total cholesterol/high-density lipoprotein cholesterol (p < 0.05). A significant improvement (p < 0.001) in total DNA rejoining cells and MDA (p < 0.05) was also observed in the FCR group. FCR improved metabolic parameters and DNA damage in healthy older adult men. Therefore, there is a need to further examine the mechanism of FCR.

Dietary folate and choline status differentially affect lipid metabolism and behavior-mediated neurotransmitters in young rats

USDA-ARS?s Scientific Manuscript database

The relationship between choline and folate metabolisms is an important issue due to the essential role of these nutrients in brain plasticity and cognitive functions. Present study was designed to investigate whether modification of the dietary folate-choline status in young rats would affect brain...

Effects of food texture change on metabolic parameters: short- and long-term feeding patterns and body weight.

PubMed

Labouré, H; Saux, S; Nicolaidis, S

2001-03-01

A complete diet was prepared with cooked pieces of meat, beans, cream starch, and water and presented to the rats in two different textures: a blended purée and a rough mixture that required a lot of chewing. We hypothesized that this texture modification might change both anticipatory reflexes and feeding behavior. Feeding rate, meal size, intermeal intervals, and their correlation were monitored in response to each texture. The long-term (6 wk) effect on body weight was assessed. Periprandial plasma glucose, insulin, glucagon, and lipid concentrations were assayed. Whole and background metabolism, respiratory quotient, and locomotion were measured using a computerized calorimeter of original design. In the short term, rats preferred the mixture. However, after 3 wk, they ingested more purée than mixture and gained more body weight per gram of food ingested as purée. Insulin response declined earlier with the mixture. During meals, glycerol and free fatty acid increased earlier with purée, whereas in the postprandial period, glycerol increased earlier with mixture. The metabolic rate, however, was not significantly affected. We concluded that texture, an everyday manipulation performed on food for human consumption, affects not only palatability of ingestants but also their metabolic management in the short and long term.

Effects of acupuncture on serum metabolic parameters in premenopausal obese women: study protocol for a randomized controlled trial.

PubMed

Kim, Koh-Woon; Yoo, Hye Hyun; Cho, Jae-Heung; Yang, Yo-Chan; Kim, Je-In; Kim, Song-Yi; Park, Ji-Yeun; Park, Hi-Joon; Song, Mi-Yeon

2015-08-04

Complex metabolic changes cause obesity, making weight loss difficult. For this reason, understanding metabolism is important, and considering the shortcomings of conventional treatment options for obesity, acupuncture is a possible option. However, evidence supporting its efficacy on metabolic parameters in obese patients is lacking. The aim of this study is to investigate the effects of acupuncture on serum metabolic parameters in premenopausal obese women. This ongoing study is a randomized, patient-assessor blind, two-arm parallel non-penetrating sham-controlled clinical trial. Eligible participants, premenopausal adult women (19 years of age or older) with a clinical diagnosis of obesity (body mass index of 25 kg/m(2) or more) blinded to the treatment received, will be randomly allocated blindly into the real acupuncture treatment group (manual acupuncture plus electroacupuncture, n = 60) or the sham acupuncture control group (sham acupuncture plus placebo acupuncture without electrical stimulation, n = 60) and receive treatment two times a week for a total of 12 sessions over 6 weeks. The primary outcome measure is the serum cholesterol and triglyceride (TG) levels at baseline and endpoint. The secondary outcomes are body weight, body fat mass, muscle mass, waist and hip circumference, other serum metabolic profiles, International Physical Activity Questionnaire (IPAQ), Social Readjustment Rating Scale (SRRS), Stress Response Inventory (SRI), Fatigue Severity Scale (FSS), the Korean version of the Beck Depression Inventory (BDI), and urine metabolites. Adverse events will be assessed at every visit. The results of this trial (which will be available in 2015) will provide important clinical evidence for the effect of acupuncture on serum metabolites and demonstrate how acupuncture can be helpful for the treatment of obesity. Trial registration registered via US National Institutes of Health Clinical Trials registry (ClinicalTrials.gov) on 11 November 2014

Resistin, visfatin, leptin and omentin are differently related to hormonal and metabolic parameters in growth hormone-deficient children.

PubMed

Ciresi, A; Pizzolanti, G; Leotta, M; Guarnotta, V; Teresi, G; Giordano, C

2016-09-01

The effect of growth hormone (GH) on adipose tissue and the role of adipokines in modulating metabolism are documented, but with discordant data. Our aim was to evaluate the impact of GH treatment on a series of selected adipokines known to have a metabolic role and poorly investigated in this setting. This is a prospective study. Thirty-one prepubertal children (25 M, 6 F; aged 8.5 ± 1.6 years) with isolated GH deficiency treated with GH for at least 12 months and 30 matched controls were evaluated. Auxological and metabolic parameters, insulin sensitivity indexes, leptin, soluble leptin receptor, adiponectin, visfatin, resistin, omentin, adipocyte fatty acid-binding protein and retinol-binding protein-4 were evaluated before and after 12 months of treatment. At baseline, no significant difference in metabolic parameters was found between GHD children and controls, except for higher LDL cholesterol (p = 0.004) in the first group. At multivariate analysis, LDL cholesterol was independently associated with resistin (B 0.531; p = 0.002), while IGF-I was the only variable independently associated with visfatin (B 0.688; p < 0.001). After 12 months, a significant increase in fasting insulin (p = 0.008), Homa-IR (p = 0.007) and visfatin (p < 0.001) was found, with a concomitant decrease in LDL cholesterol (p = 0.015), QUICKI (p = 0.001), ISI Matsuda (p = 0.006), leptin (p = 0.015) and omentin (p = 0.003)]. At multivariate analysis, BMI was the only variable independently associated with leptin (B 0.485; p = 0.040). GH treatment modifies adipokine secretion and the perturbation of some adipokine levels could contribute to the clinical and metabolic changes observed during the follow-up.

The glycaemic index values of foods containing fructose are affected by metabolic differences between subjects.

PubMed

Wolever, T M S; Jenkins, A L; Vuksan, V; Campbell, J

2009-09-01

Glycaemic responses are influenced by carbohydrate absorption rate, type of monosaccharide absorbed and the presence of fat; the effect of some of these factors may be modulated by metabolic differences between subjects. We hypothesized that glycaemic index (GI) values are affected by the metabolic differences between subjects for foods containing fructose or fat, but not for starchy foods. The GI values of white bread (WB), fruit leather (FL) and chocolate-chip cookies (CCC) (representing starch, fructose and fat, respectively) were determined in subjects (n=77) recruited to represent all 16 possible combinations of age (< or =40, >40 years), sex (male, female), ethnicity (Caucasian, non-Caucasian) and body mass index (BMI) (< or =25, >25 kg/m2) using glucose as the reference. At screening, fasting insulin, lipids, c-reactive protein (CRP), aspartate transaminase (AST) and waist circumference (WC) were measured. There were no significant main effects of age, sex, BMI or ethnicity on GI, but there were several food x subject-factor interactions. Different factors affected each food's area under the curve (AUC) and GI. The AUC after oral glucose was related to ethnicity, age and triglycerides (r 2=0.27); after WB to ethnicity, age, triglycerides, sex and CRP (r 2=0.43); after CCC to age and weight (r 2=0.18); and after FL to age and CRP (r 2=0.12). GI of WB was related to ethnicity (r 2=0.12) and of FL to AST, insulin and WC (r 2=0.23); but there were no significant correlations for CCC. The GI values of foods containing fructose might be influenced by metabolic differences between -subjects, whereas the GI of starchy foods might be affected by ethnicity. However, the proportion of variation explained by subject factors is small.

Metabolic and anthropometric parameters contribute to ART-mediated CD4+ T cell recovery in HIV-1-infected individuals: an observational study

PubMed Central

2011-01-01

Background The degree of immune reconstitution achieved in response to suppressive ART is associated with baseline individual characteristics, such as pre-treatment CD4 count, levels of viral replication, cellular activation, choice of treatment regimen and gender. However, the combined effect of these variables on long-term CD4 recovery remains elusive, and no single variable predicts treatment response. We sought to determine if adiposity and molecules associated with lipid metabolism may affect the response to ART and the degree of subsequent immune reconstitution, and to assess their ability to predict CD4 recovery. Methods We studied a cohort of 69 (48 females and 21 males) HIV-infected, treatment-naïve South African subjects initiating antiretroviral treatment (d4T, 3Tc and lopinavir/ritonavir). We collected information at baseline and six months after viral suppression, assessing anthropometric parameters, dual energy X-ray absorptiometry and magnetic resonance imaging scans, serum-based clinical laboratory tests and whole blood-based flow cytometry, and determined their role in predicting the increase in CD4 count in response to ART. Results We present evidence that baseline CD4+ T cell count, viral load, CD8+ T cell activation (CD95 expression) and metabolic and anthropometric parameters linked to adiposity (LDL/HDL cholesterol ratio and waist/hip ratio) significantly contribute to variability in the extent of CD4 reconstitution (ΔCD4) after six months of continuous ART. Conclusions Our final model accounts for 44% of the variability in CD4+ T cell recovery in virally suppressed individuals, representing a workable predictive model of immune reconstitution. PMID:21801351

Effect of Graft Weight to Recipient Body Weight Ratio on Hemodynamic and Metabolic Parameters in Pediatric Liver Transplant: A Retrospective Analysis.

PubMed

Ersoy, Zeynep; Kaplan, Serife; Ozdemirkan, Aycan; Torgay, Adnan; Arslan, Gulnaz; Pirat, Arash; Haberal, Mehmet

2017-02-01

To analyze how graft-weight-to-bodyweight ratio in pediatric liver transplant affects intraoperative and early postoperative hemodynamic and metabolic parameters. We reviewed data from 130 children who underwent liver transplant between 2005 and 2015. Recipients were divided into 2 groups: those with a graft weight to body weight ratio > 4% (large for size) and those with a ratio ≤ 4% (normal for size). Data included demographics, preoperative laboratory findings, intraoperative metabolic and hemodynamic parameters, and intensive care follow-up parameters. Patients in the large-graft-for-size group (>4%) received more colloid solution (57.7 ± 20.1 mL/kg vs 45.1 ± 21.9 mL/kg; P = .08) and higher doses of furosemide (0.7 ± 0.6 mg/kg vs 0.4 ± 0.7 mg/kg; P = .018). They had lower mean pH (7.1 ± 0.1 vs 7.2 ± 0.1; P = .004) and PO2 (115.4 ± 44.6 mm Hg vs 147.6 ± 49.3 mm Hg; P = .004) values, higher blood glucose values (352.8 ± 96.9 mg/dL vs 262.8 ± 88.2 mg/dL; P < .001), and lower mean body temperature (34.8 ± 0.7°C vs 35.2 ± 0.6°C; P = .016) during the neohepatic phase. They received more blood transfusions during both the anhepatic (30.3 ± 24.3 mL/kg vs 18.8 ± 21.8 mL/kg; P = .013) and neohepatic (17.7 ± 20.4 mL/kg vs 10.3 ± 15.5 mL/kg; P = .031) phases and more fresh frozen plasma (13.6 ± 17.6 mL/kg vs 6.2 ± 10.2 mL/kg; P = .012) during the neohepatic phase. They also were more likely to be hypotensive (P < .05) and to receive norepinephrine infusion more often (44% vs 22%; P < .05) intraoperatively. More patients in this group were mechanically ventilated in the intensive care unit (56% vs 31%; P = .035). There were no significant differences between the groups in postoperative acute renal dysfunction, graft rejection or loss, infections, length of intensive care stay, and mortality (P > .05). High graft weight-to-body-weight ratio is associated with adverse metabolic and hemodynamic changes during the intraoperative and early postoperative

The relationship between biventricular myocardial performance and metabolic parameters during incremental exercise and recovery in healthy adolescents

PubMed Central

Gowing, Lucy; Forsey, Jonathan; Ramanujam, Paramanantham; Miller, Felicity; Stuart, A Graham; Williams, Craig A.

2015-01-01

Background left ventricular (LV) and right ventricular (RV) myocardial reserve during exercise in adolescents has not been directly characterized. The aim of this study was to quantify myocardial performance response to exercise by using two-dimensional (2-D) speckle tracking echocardiography and describe the relationship between myocardial reserve, respiratory, and metabolic exercise parameters. A total of 23 healthy boys and girls (mean age 13.2 ± 2.7 yr; stature 159.1 ± 16.4 cm; body mass 49.5 ± 16.6 kg; BSA 1.47 ± 0.33 m2) completed an incremental cardiopulmonary exercise test (25 W·3 min increments) with simultaneous acquisition of 2-D transthoracic echocardiography at rest, each exercise stage up to 100 W, and in recovery at 2 min and 10 min. Two-dimensional LV (LV Sl) and RV (RV Sl) longitudinal strain and LV circumferential strain (LV Sc) were analyzed to define the relationship between myocardial performance reserve and metabolic exercise parameters. Participants achieved a peak oxygen uptake (V̇o2peak) of 40.6 ± 8.9 ml·kg−1·min−1 and a work rate of 154 ± 42 W. LV Sl and LV Sc and RV Sl increased significantly across work rates (P < 0.05). LV Sl during exercise was significantly correlated to resting strain, V̇o2peak, oxygen pulse, and work rate (0.530 ≤ r ≤ 0.784, P < 0.05). This study identifies a positive and moderate relationship between LV and RV myocardial performance and metabolic parameters during exercise by using a novel methodology. Relationships detected present novel data directly describing myocardial adaptation at different stages of exercise and recovery that in the future can help directly assess cardiac reserve in patients with cardiac pathology. PMID:26475589

Ibogaine affects brain energy metabolism.

PubMed

Paskulin, Roman; Jamnik, Polona; Zivin, Marko; Raspor, Peter; Strukelj, Borut

2006-12-15

Ibogaine is an indole alkaloid present in the root of the plant Tabernanthe iboga. It is known to attenuate abstinence syndrome in animal models of drug addiction. Since the anti-addiction effect lasts longer than the presence of ibogaine in the body, some profound metabolic changes are expected. The aim of this study was to investigate the effect of ibogaine on protein expression in rat brains. Rats were treated with ibogaine at 20 mg/kg body weight i.p. and subsequently examined at 24 and 72 h. Proteins were extracted from whole brain and separated by two-dimensional (2-D) electrophoresis. Individual proteins were identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). Enzymes of glycolysis and tricarboxylic acid (TCA) cycle namely glyceraldehyde-3-phosphate dehydrogenase, aldolase A, pyruvate kinase and malate dehydrogenase were induced. The results suggest that the remedial effect of ibogaine could be mediated by the change in energy availability. Since energy dissipating detoxification and reversion of tolerance to different drugs of abuse requires underlying functional and structural changes in the cell, higher metabolic turnover would be favourable. Understanding the pharmacodynamics of anti-addiction drugs highlights the subcellular aspects of addiction diseases, in addition to neurological and psychological perspectives.

Correlation of magnesium intake with metabolic parameters, depression and physical activity in elderly type 2 diabetes patients: a cross-sectional study

PubMed Central

2012-01-01

Background Type 2 diabetes mellitus is a major global public health problem in the worldwide and is increasing in aging populations. Magnesium intake may be one of the most important factors for diabetes prevention and management. Low magnesium intake may exacerbate metabolic abnormalities. In this study, the relationships of magnesium intake with metabolic parameters, depression and physical activity in elderly patients with type 2 diabetes were investigated. Methods This cross-sectional study involved 210 type 2 diabetes patients aged 65 years and above. Participants were interviewed to obtain information on lifestyle and 24-hour dietary recall. Assessment of depression was based on DSM-IV criteria. Clinical variables measured included anthropometric measurements, blood pressure, and biochemical determinations of blood and urine samples. Linear regression was applied to determine the relationships of magnesium intake with nutritional variables and metabolic parameters. Results Among all patients, 88.6% had magnesium intake which was less than the dietary reference intake, and 37.1% had hypomagnesaemia. Metabolic syndromes and depression were associated with lower magnesium intake (p < 0.05). A positive relationship was found between magnesium intake and HDL-cholesterol (p = 0.005). Magnesium intake was inversely correlated with triglyceride, waist circumference, body fat percent and body mass index (p < 0.005). After controlling confounding factor, HDL-cholesterol was significantly higher with increasing quartile of magnesium intake (p for trend = 0005). Waist circumference, body fat percentage, and body mass index were significantly lower with increase quartile of magnesium intake (p for trend < 0.001). The odds of depression, central obesity, high body fat percentage, and high body mass index were significantly lower with increasing quartile of magnesium intake (p for trend < 0.05). In addition, magnesium intake was related to high

WISP1 is a novel adipokine linked to metabolic parameters in gestational diabetes mellitus.

PubMed

Sahin Ersoy, Gulcin; Altun Ensari, Tugba; Subas, Seda; Giray, Burak; Simsek, Engin Ersin; Cevik, Ozge

2017-04-01

To investigate Wnt1-inducible signaling pathway protein-1 (WISP1) levels and their correlation with metabolic parameters in pregnant women with gestational diabetes mellitus (GDM) and non-GDM healthy pregnant women. In this prospective cross-sectional study, the study group was composed of 62 women with GDM and 73 healthy pregnant women matched for age, body mass index (BMI) and gestational age. Blood samples were collected at 25-29th gestational week. Serum WISP1, betatrophin, glucose, fasting insulin, glycosylated hemoglobin A1c, total cholesterol, triglyceride, high density lipoprotein cholesterol, low density lipoprotein cholesterol, C reactive protein, alanine aminotransferase and creatinine levels were measured. Homeostasis model assessment of insulin resistance (HOMA-IR) values was calculated. The level of significance was accepted as p < 0.05. Circulating WISP1 in the GDM group was significantly higher than the control group (p <0.001). Further, WISP1 was positively correlated with BMI, HOMA-IR values and fasting glucose, fasting insulin, triglyceride, betatrophin levels. BMI, HOMA-IR and betatrophin independently and positively predicted WISP1 levels. These results demonstrate a relationship between WISP1 and the metabolic parameters of GDM. And, WISP1 might be involved in the pathophysiology of GDM. As a part of this pathophysiological mechanism, the activation of WISP1 and betatrophin might take place through several ways; WISP1 and betatrophin might either use same signaling pathways and potentiate each other or they might also constitute the sequential steps of a common pathway.

Multi-scale modularity and motif distributional effect in metabolic networks.

PubMed

Gao, Shang; Chen, Alan; Rahmani, Ali; Zeng, Jia; Tan, Mehmet; Alhajj, Reda; Rokne, Jon; Demetrick, Douglas; Wei, Xiaohui

2016-01-01

Metabolism is a set of fundamental processes that play important roles in a plethora of biological and medical contexts. It is understood that the topological information of reconstructed metabolic networks, such as modular organization, has crucial implications on biological functions. Recent interpretations of modularity in network settings provide a view of multiple network partitions induced by different resolution parameters. Here we ask the question: How do multiple network partitions affect the organization of metabolic networks? Since network motifs are often interpreted as the super families of evolved units, we further investigate their impact under multiple network partitions and investigate how the distribution of network motifs influences the organization of metabolic networks. We studied Homo sapiens, Saccharomyces cerevisiae and Escherichia coli metabolic networks; we analyzed the relationship between different community structures and motif distribution patterns. Further, we quantified the degree to which motifs participate in the modular organization of metabolic networks.

The fungicide triadimefon affects beer flavor and composition by influencing Saccharomyces cerevisiae metabolism

NASA Astrophysics Data System (ADS)

Kong, Zhiqiang; Li, Minmin; An, Jingjing; Chen, Jieying; Bao, Yuming; Francis, Frédéric; Dai, Xiaofeng

2016-09-01

Despite the fact that beer is produced on a large scale, the effects of pesticide residues on beer have been rarely investigated. In this study, we used micro-brewing settings to determine the effect of triadimefon on the growth of Saccharomyces cerevisiae and beer flavor. The yeast growth in medium was significantly inhibited (45%) at concentrations higher than 5 mg L-1, reaching 80% and 100% inhibition at 10 mg L-1 and 50 mg L-1, respectively. There were significant differences in sensory quality between beer samples fermented with and without triadimefon based on data obtained with an electronic tongue and nose. Such an effect was most likely underlain by changes in yeast fermentation activity, including decreased utilization of maltotriose and most amino acids, reduced production of isobutyl and isoamyl alcohols, and increased ethyl acetate content in the fungicide treated samples. Furthermore, yeast metabolic profiling by phenotype microarray and UPLC/TOF-MS showed that triadimefon caused significant changes in the metabolism of glutathione, phenylalanine and sphingolipids, and in sterol biosynthesis. Thus, triadimefon negatively affects beer sensory qualities by influencing the metabolic activity of S. cerevisiae during fermentation, emphasizing the necessity of stricter control over fungicide residues in brewing by the food industry.

The fungicide triadimefon affects beer flavor and composition by influencing Saccharomyces cerevisiae metabolism

PubMed Central

Kong, Zhiqiang; Li, Minmin; An, Jingjing; Chen, Jieying; Bao, Yuming; Francis, Frédéric; Dai, Xiaofeng

2016-01-01

Despite the fact that beer is produced on a large scale, the effects of pesticide residues on beer have been rarely investigated. In this study, we used micro-brewing settings to determine the effect of triadimefon on the growth of Saccharomyces cerevisiae and beer flavor. The yeast growth in medium was significantly inhibited (45%) at concentrations higher than 5 mg L−1, reaching 80% and 100% inhibition at 10 mg L−1 and 50 mg L−1, respectively. There were significant differences in sensory quality between beer samples fermented with and without triadimefon based on data obtained with an electronic tongue and nose. Such an effect was most likely underlain by changes in yeast fermentation activity, including decreased utilization of maltotriose and most amino acids, reduced production of isobutyl and isoamyl alcohols, and increased ethyl acetate content in the fungicide treated samples. Furthermore, yeast metabolic profiling by phenotype microarray and UPLC/TOF-MS showed that triadimefon caused significant changes in the metabolism of glutathione, phenylalanine and sphingolipids, and in sterol biosynthesis. Thus, triadimefon negatively affects beer sensory qualities by influencing the metabolic activity of S. cerevisiae during fermentation, emphasizing the necessity of stricter control over fungicide residues in brewing by the food industry. PMID:27629523

Metabolic regulation of yeast

NASA Astrophysics Data System (ADS)

Fiechter, A.

1982-12-01

Metabolic regulation which is based on endogeneous and exogeneous process variables which may act constantly or time dependently on the living cell is discussed. The observed phenomena of the regulation are the result of physical, chemical, and biological parameters. These parameters are identified. Ethanol is accumulated as an intermediate product and the synthesis of biomass is reduced. This regulatory effect of glucose is used for the aerobic production of ethanol. Very high production rates are thereby obtained. Understanding of the regulation mechanism of the glucose effect has improved. In addition to catabolite repression, several other mechanisms of enzyme regulation have been described, that are mostly governed by exogeneous factors. Glucose also affects the control of respiration in a third class of yeasts which are unable to make use of ethanol as a substrate for growth. This is due to the lack of any anaplerotic activity. As a consequence, diauxic growth behavior is reduced to a one-stage growth with a drastically reduced cell yield. The pulse chemostat technique, a systematic approach for medium design is developed and medium supplements that are essential for metabolic control are identified.

Glial Cell Line-Derived Neurotrophic Factor (GDNF) serum level in women with schizophrenia and depression, correlation with clinical and metabolic parameters.

PubMed

Skibinska, Maria; Kapelski, Pawel; Pawlak, Joanna; Rajewska-Rager, Aleksandra; Dmitrzak-Weglarz, Monika; Szczepankiewicz, Aleksandra; Czerski, Piotr; Twarowska-Hauser, Joanna

2017-10-01

Neurotrophic factors have been implicated in neuropsychiatric disorders, including schizophrenia and depression. Glial Cell Line-Derived Neurotrophic Factor (GDNF) promotes development, differentiation, and protection of dopaminergic, serotonergic, GABAergic and noradrenergic neurons as well as glial cells in different brain regions. This study examined serum levels of GDNF in schizophrenia and depression and its correlation with metabolic parameters during 8 weeks of treatment. Serum GDNF level, fasting serum glucose and lipid profile were measured at baseline and week 8 in 133 women: 55 with schizophrenia, 30 with a first episode depression and 48 healthy controls. The severity of the symptoms was evaluated using Positive and Negative Syndrome Scale (PANSS), 17-item Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory (BDI). There was statistically significant higher GDNF level in schizophrenia at baseline when compared with week 8. Correlations of GDNF with PANSS in schizophrenia and cholesterol level in depression have also been detected. To our knowledge, this is the first study which correlates GDNF levels with metabolic parameters. Our results show no differences in GDNF serum level between schizophrenia, a first depressive episode, and healthy controls. GDNF serum level did not correlate with metabolic parameters except for total cholesterol in depression. Copyright © 2017 Elsevier B.V. All rights reserved.

A Quantitative Study of Oxygen as a Metabolic Regulator

NASA Technical Reports Server (NTRS)

Radhakrishnan, Krishnan; LaManna, Joseph C.; Cabera, Marco E.

2000-01-01

An acute reduction in oxygen delivery to a tissue is associated with metabolic changes aimed at maintaining ATP homeostasis. However, given the complexity of the human bio-energetic system, it is difficult to determine quantitatively how cellular metabolic processes interact to maintain ATP homeostasis during stress (e.g., hypoxia, ischemia, and exercise). In particular, we are interested in determining mechanisms relating cellular oxygen concentration to observed metabolic responses at the cellular, tissue, organ, and whole body levels and in quantifying how changes in tissue oxygen availability affect the pathways of ATP synthesis and the metabolites that control these pathways. In this study; we extend a previously developed mathematical model of human bioenergetics, to provide a physicochemical framework that permits quantitative understanding of oxygen as a metabolic regulator. Specifically, the enhancement - sensitivity analysis - permits studying the effects of variations in tissue oxygenation and parameters controlling cellular respiration on glycolysis, lactate production, and pyruvate oxidation. The analysis can distinguish between parameters that must be determined accurately and those that require less precision, based on their effects on model predictions. This capability may prove to be important in optimizing experimental design, thus reducing use of animals.

Effects of chronic stress and high-fat diet on metabolic and nutritional parameters in Wistar rats.

PubMed

Bruder-Nascimento, Thiago; Campos, Dijon Henrique Salomé; Alves, Carlos; Thomaz, Samuel; Cicogna, Antônio Carlos; Cordellini, Sandra

2013-11-01

The aim of this study was assess the role of chronic stress on the metabolic and nutritional profile of rats exposed to a high-fat diet. Thirty-day-old male Wistar rats (70-100 g) were distributed into four groups: normal-diet (NC), chronic stress (St), high-fat diet (HD), and chronic stress/high-fat diet (HD/St). Stress consisted at immobilization during 15 weeks, 5 times per week, 1h per day; and exposure to the high-fat diet lasted 15 weeks. Nutritional and metabolic parameters were assessed. The level of significance was 5%. The HD group had final body weight, total fat, as well as insulin and leptin increased, and they were insulin resistant. The St and HD/St had arterial hypertension and increased levels of corticosterone. Stress blocked the effects of the high-fat diet. Chronic stress prevented the appearance of obesity. Our results help to clarify the mechanisms involved in metabolic and nutritional dysfunction, and contribute to clinical cases linked to stress and high-fat diet.

Changes on metabolic parameters induced by acute cannabinoid administration (CBD, THC) in a rat experimental model of nutritional vitamin A deficiency.

PubMed

El Amrani, Loubna; Porres, Jesús M; Merzouki, Abderrahmane; Louktibi, Abdelaziz; Aranda, Pilar; López-Jurado, María; Urbano, Gloria

2013-01-01

Vitamin A deficiency can result from malnutrition, malabsorption of vitamin A, impaired vitamin metabolism associated with liver disease, or chronic debilitating diseases like HIV infection or cancer. Cannabis administration has been described as a palliative symptom management therapy in such pathological stages. Therefore, this research aimed to study the effects of acute administration of cannabidiol (CBD) or thetrahydrocannabinol (THC) on the levels of retinol in plasma and in the liver, and biochemical parameters related to lipid and glucose metabolism (cholesterolaemia, triglyceridemia and glycemia) in a rat experimental model of vitamin A deficiency. The experimental animal model of Vitamin A deficiency was developed during a 50-day experimental period in which rats consumed a vitamin A-free diet. Cannabidiol (10 mg/kg body weight) or thetrahydrocannabinol (5 mg/kg body weight) were administered intraperitoneally 2 hours prior to sacrifice of the animals. The nutritional deficiency caused a significant decrease in plasmatic and liver contents of retinol and biochemical parameters of glycemic, lipidic, and mineral metabolism. Acute intraperitoneal administration of Cannabidiol and thetrahydrocannabinol did not improve the indices of vitamin A status in either control or vitamin A-deficient rats. However, it had a significant effect on specific biochemical parameters such as glucose, triglycerides, and cholesterol. Under our experimental conditions, the reported effects of cannabinoid administration on certain signs of nutritional vitamin A deficiency appeared to be mediated through mechanisms other than changes in retinol metabolism or its mobilization after the acute administration of such compounds. Copyright © AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.

Parameters Affecting the Mechanical Properties of Fly Ash-Based Geopolymer Binders – Experimental Results

NASA Astrophysics Data System (ADS)

Lăzărescu, A.; Szilagyi, H.; Ioani, A.; Baeră, C.

2018-06-01

As the demand for concrete and the needs to satisfy development of infrastructure facilities increase, it is essential to find alternatives to create environment-friendly concrete. The particular procedure of alkaline activation of fly ash - in which ash resulting from a power plant is combined with a specific alkaline activator in order to create a solid material, then dried at a certain temperature - opened new opportunities for this new material to get attention worldwide. In order to obtain a material with similar properties of ordinary Portland cement concrete and to obtain desirable compressive strengths, the parameters that affect this type of binders should be fully understood. The aim of this paper is to study the main parameters affecting the mechanical strength of the fly ash-based geopolymer paste and their interactions. Parameters such as molarity of sodium hydroxide (from 8M to 12M) and alkaline activators ratio (from 0,5 to 2,5) were analysed to observe how they affect the mechanical properties of the geopolymer paste. Experimental results show that the compressive strength of the fly ash-based geopolymer paste produced using Romanian local raw materials increases with the increase of the concentration of sodium hydroxide and higher ratios of Na2SiO3/NaOH solution.

Iron deficiency affects nitrogen metabolism in cucumber (Cucumis sativus L.) plants

PubMed Central

2012-01-01

Background Nitrogen is a principal limiting nutrient in plant growth and development. Among factors that may limit NO3- assimilation, Fe potentially plays a crucial role being a metal cofactor of enzymes of the reductive assimilatory pathway. Very few information is available about the changes of nitrogen metabolism occurring under Fe deficiency in Strategy I plants. The aim of this work was to study how cucumber (Cucumis sativus L.) plants modify their nitrogen metabolism when grown under iron deficiency. Results The activity of enzymes involved in the reductive assimilation of nitrate and the reactions that produce the substrates for the ammonium assimilation both at root and at leaf levels in Fe-deficient cucumber plants were investigated. Under Fe deficiency, only nitrate reductase (EC 1.7.1.1) activity decreased both at the root and leaf level, whilst for glutamine synthetase (EC 6.3.1.2) and glutamate synthase (EC 1.4.1.14) an increase was found. Accordingly, the transcript analysis for these enzymes showed the same behaviour except for root nitrate reductase which increased. Furthermore, it was found that amino acid concentration greatly decreased in Fe-deficient roots, whilst it increased in the corresponding leaves. Moreover, amino acids increased in the xylem sap of Fe-deficient plants. Conclusions The data obtained in this work provided new insights on the responses of plants to Fe deficiency, suggesting that this nutritional disorder differentially affected N metabolism in root and in leaf. Indeed under Fe deficiency, roots respond more efficiently, sustaining the whole plant by furnishing metabolites (i.e. aa, organic acids) to the leaves. PMID:23057967

Hemodynamic and metabolic parameters during prolonged cardiac arrest and reperfusion by extracorporeal circulation.

PubMed

Mlček, M; Ošťádal, P; Bělohlávek, J; Havránek, Š; Hrachovina, M; Huptych, M; Hála, P; Hrachovina, V; Neužil, P; Kittnar, O

2012-01-01

Extracorporeal membranous oxygenation (ECMO) is increasingly used in the management of refractory cardiac arrest. Our aim was to investigate early effects of ECMO after prolonged cardiac arrest. In fully anesthetized swine (48 kg, N=18) ventricular fibrillation (VF) was induced and untreated period (20 min) of cardiac arrest commenced, followed by 60 min extracorporeal reperfusion (ECMO flow 100 ml/kg.min). Hemodynamics, arterial blood gasses, plasma potassium, tissue oximetry (StO(2)) and cardiac (EGM) and cerebral (BIS) electrophysiological parameters were continuously recorded and analyzed. Within 3 minutes of VF hemodynamic and oximetry parameters fall abruptly while metabolic parameters destabilize gradually over 20 minutes peaking at pH 7.04 ± 0.05, pCO(2) 89 ± 14 mmHg, K(+) 8.5 ± 1.6 mmol/l. During reperfusion most parameters restore rapidly: within 3-5 minutes mean arterial pressure reaches >40 mmHg, StO(2)>50 %, paO(2)>100 mmHg, pCO(2)<50 mmHg, K(+)<5 mmol/l. EGMs mean amplitude peaks at 4.5 ± 2.4 min. Cerebral activity (BIS>60) reappeared in 5 animals after 87 ± 21 min. In 12/18 animals return of spontaneous circulation was achieved. In conclusions, ECMO provides rapid restitution of internal milieu even after prolonged arrest. However, despite normalization of global parameters full recovery was not guaranteed since cardiac and cerebral electrical activities were sufficiently restored only in some animals. More sensitive and organ specific indicators need to be identified in order to estimate adequacy of cardiac support devices.

Road transport and diet affect metabolic response to exercise in horses.

PubMed

Connysson, M; Muhonen, S; Jansson, A

2017-11-01

This study investigated the effects of transport and diet on metabolic response during a subsequent race-like test in Standardbred horses in training fed a forage-only diet and a 50:50 forage:oats diet. Six trained and raced Standardbred trotter mares were used. Two diets, 1 forage-only diet (FONLY) and 1 diet with 50% of DM intake from forage and 50% from oats (FOATS), were fed for two 29-d periods in a crossover design. At Day 21, the horses were subjected to transport for 100 km before and after they performed an exercise test (transport test [TT]). At Day 26, the horses performed a control test (CT), in which they were kept in their stall before and after the exercise test. Blood samples were collected throughout the study, and heart rate and water intake were recorded. Heart rate and plasma cortisol, glucose, and NEFA concentrations were greater for the TT than for the CT ( = 0.008, = 0.020, = 0.010, and = 0.0002, respectively) but were not affected by diet. Plasma acetate concentration was lower during the TT than during the CT ( = 0.034) and greater for the FONLY than for the FOATS ( = 0.003). There were no overall effects of the TT compared with the CT on total plasma protein concentration (TPP), but TPP was lower with the FONLY than with the FOATS ( = 0.016). There was no overall effect of the TT compared with the CT on water intake, but water intake was greater with the FONLY than the FOATS ( = 0.011). There were no overall effects of transport or diet on BW, plasma lactate, or plasma urea concentration. It was concluded that both transport and diet affect metabolic response during exercise in horses. Aerobic energy supply was most likely elevated by transportation and by the FONLY. The FONLY also decreased exercise-induced effects on extracellular fluid regulation. These results highlight the importance of experimental design in nutrition studies. If the aim is to examine how a diet affects exercise response in competition horses, transport should

A Case Study Showing Parameters Affecting the Quality of Education: Faculty Perspective

ERIC Educational Resources Information Center

Kumari, Neeraj

2014-01-01

The study aims to examine the faculty members' perspective (age Wise, Gender Wise and Work Experience wise) of parameters affecting the quality of education in an affiliated Undergraduate Engineering Institution in Haryana. It is a descriptive type of research. The data has been collected with the help of 'Questionnaire Based Survey'. The sample…

Monitoring the efficacy and metabolism of phenylcarbamates in sugar beet and black nightshade by chlorophyll fluorescence parameters.

PubMed

Abbaspoor, Majid; Streibig, Jens C

2007-06-01

Desmedipham, phenmedipham and a 50% mixture of the two decreased the maximum quantum efficiency of photosystem II (F(v)/F(m)) and the relative changes at the J step (F(vj)) immediately after spraying in both sugar beet and black nightshade grown in the greenhouse. Sugar beet recovered more rapidly from phenmedipham and the mixture than from desmedipham. Desmedipham and the mixture irreversibly affected F(v)/F(m) and F(vj) in black nightshade at much lower doses than in sugar beet. Black nightshade recovered from phenmedipham injury at the highest dose in the first experiment (120 g AI ha(-1)) but not in the second experiment (500 g AI ha(-1)). The dry matter dose-response relationships and the energy pipeline presentation confirmed the same trend. There was a relatively good correlation between F(vj) taken 1 day after spraying and dry matter taken 2 or 3 weeks after spraying. The differential speed of herbicide metabolism between weed and crop plays an important role in herbicide selectivity and can be studied by using appropriate chlorophyll a fluorescence parameters. Copyright 2007 Society of Chemical Industry.

4 Things That Affect Your Metabolism

Cancer.gov

Metabolism is how your body uses food as energy and then burns that energy to keep your body going. Even if you did nothing all day, your body would still need to use energy just to stay alive—for things like breathing and keeping your heart beating.

Summary of typical parameters that affect sound transmission through general aviation aircraft structures

NASA Technical Reports Server (NTRS)

Grosveld, F.; Navaneethan, R.; Roskam, J.

1981-01-01

This paper presents results of a systematic experimental investigation of parameters which affect sound transmission through general aviation structures. Parameters studied include angle of sound incidence, panel curvature, panel stresses, and edge conditions for bare panels; pane thickness, spacing, inclination of window panes, and depressurization for dual pane windows; densities of hard foam and sound absorption materials, air gaps, and trim panel thickness for multilayered panels. Based on the study, some promising methods for reducing interior noise in general aviation airplanes are discussed.

A fungal transcription factor essential for starch degradation affects integration of carbon and nitrogen metabolism

DOE PAGES

Xiong, Yi; Wu, Vincent W.; Lubbe, Andrea; ...

2017-05-03

In Neurospora crassa, the transcription factor COL-26 functions as a regulator of glucose signaling and metabolism. Its loss leads to resistance to carbon catabolite repression. Here, we report that COL-26 is necessary for the expression of amylolytic genes in N. crassa and is required for the utilization of maltose and starch. Additionally, the Δcol-26 mutant shows growth defects on preferred carbon sources, such as glucose, an effect that was alleviated if glutamine replaced ammonium as the primary nitrogen source. This rescue did not occur when maltose was used as a sole carbon source. Transcriptome and metabolic analyses of the Δcol-26more » mutant relative to its wild type parental strain revealed that amino acid and nitrogen metabolism, the TCA cycle and GABA shunt were adversely affected. Phylogenetic analysis showed a single col-26 homolog in Sordariales, Ophilostomatales, and the Magnaporthales, but an expanded number of col-26 homologs in other filamentous fungal species. Deletion of the closest homolog of col-26 in Trichoderma reesei, bglR, resulted in a mutant with similar preferred carbon source growth deficiency, and which was alleviated if glutamine was the sole nitrogen source, suggesting conservation of COL-26 and BglR function. Our finding provides novel insight into the role of COL-26 for utilization of starch and in integrating carbon and nitrogen metabolism for balanced metabolic activities for optimal carbon and nitrogen distribution.« less

A fungal transcription factor essential for starch degradation affects integration of carbon and nitrogen metabolism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xiong, Yi; Wu, Vincent W.; Lubbe, Andrea

In Neurospora crassa, the transcription factor COL-26 functions as a regulator of glucose signaling and metabolism. Its loss leads to resistance to carbon catabolite repression. Here, we report that COL-26 is necessary for the expression of amylolytic genes in N. crassa and is required for the utilization of maltose and starch. Additionally, the Δcol-26 mutant shows growth defects on preferred carbon sources, such as glucose, an effect that was alleviated if glutamine replaced ammonium as the primary nitrogen source. This rescue did not occur when maltose was used as a sole carbon source. Transcriptome and metabolic analyses of the Δcol-26more » mutant relative to its wild type parental strain revealed that amino acid and nitrogen metabolism, the TCA cycle and GABA shunt were adversely affected. Phylogenetic analysis showed a single col-26 homolog in Sordariales, Ophilostomatales, and the Magnaporthales, but an expanded number of col-26 homologs in other filamentous fungal species. Deletion of the closest homolog of col-26 in Trichoderma reesei, bglR, resulted in a mutant with similar preferred carbon source growth deficiency, and which was alleviated if glutamine was the sole nitrogen source, suggesting conservation of COL-26 and BglR function. Our finding provides novel insight into the role of COL-26 for utilization of starch and in integrating carbon and nitrogen metabolism for balanced metabolic activities for optimal carbon and nitrogen distribution.« less

A fungal transcription factor essential for starch degradation affects integration of carbon and nitrogen metabolism

PubMed Central

Xiong, Yi; Qin, Lina; Kennedy, Megan; Bauer, Diane; Barry, Kerrie; Northen, Trent R.; Grigoriev, Igor V.

2017-01-01

In Neurospora crassa, the transcription factor COL-26 functions as a regulator of glucose signaling and metabolism. Its loss leads to resistance to carbon catabolite repression. Here, we report that COL-26 is necessary for the expression of amylolytic genes in N. crassa and is required for the utilization of maltose and starch. Additionally, the Δcol-26 mutant shows growth defects on preferred carbon sources, such as glucose, an effect that was alleviated if glutamine replaced ammonium as the primary nitrogen source. This rescue did not occur when maltose was used as a sole carbon source. Transcriptome and metabolic analyses of the Δcol-26 mutant relative to its wild type parental strain revealed that amino acid and nitrogen metabolism, the TCA cycle and GABA shunt were adversely affected. Phylogenetic analysis showed a single col-26 homolog in Sordariales, Ophilostomatales, and the Magnaporthales, but an expanded number of col-26 homologs in other filamentous fungal species. Deletion of the closest homolog of col-26 in Trichoderma reesei, bglR, resulted in a mutant with similar preferred carbon source growth deficiency, and which was alleviated if glutamine was the sole nitrogen source, suggesting conservation of COL-26 and BglR function. Our finding provides novel insight into the role of COL-26 for utilization of starch and in integrating carbon and nitrogen metabolism for balanced metabolic activities for optimal carbon and nitrogen distribution. PMID:28467421

[Effect of recombinant human growth hormone therapy on metabolic parameters in patients with craniopharyngioma].

PubMed

Mao, J F; Wang, X; Xiong, S Y; Zheng, J J; Yu, B Q; Nie, M; Wu, X Y; Qi, S T

2017-11-14

Objective: To investigate the effects of recombinant human growth hormone (rhGH) on metabolic parameters in patients with craniopharyngioma surgeries. Methods: Totallys 30 patients with craniopharyngioma were included in this retrospective study. They were divided into growth hormone (GH) group and control group according to whether they received rhGH therapy or not. The following parameters, including body mass index (BMI), weight, waist circumstance, transaminase, fasting blood glucose, lipid profile and high-sensitivity C-reactive protein (hsCRP) were compared after rhGH therapy for 4-6 months. Results: In GH group, patients were 18-46 (30.0±8.8) years old. The duration after craniopharyngioma surgery was (12.9±5.4) years. Before rhGH therapy, they had got sufficient thyroid and glucocorticoid hormone replacement. After rhGH therapy, the body weight decreased from (92.3±20.1) to (87.6 ±14.6) kg ( P =0.190), with a reduction of BMI from (30.1±5.9) to (28.2±3.7) kg/m(2) ( P =0.120). The waist circumference decreased from (104.4±9.4) cm to (98.8±10.6) cm ( P =0.002). Alanine aminotransferase (ALT) decreased from (52±34) to (28±19) U/L ( P =0.029), with a reduction of aspartate transaminase (AST) from (46±21) to (33±18) U/L ( P =0.035) and γ-glutamyl transpeptadase (GGT) from (59±42) to (29±15) U/L ( P =0.02). hsCRP decreased from (5.3±4.9) to (2.3±2.8) mg/L ( P =0.006) and triglyceride (TG) decreased from (1.8±0.7) to (1.5±0.6) mmol/L ( P =0.028). Fasting blood glucose, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and free fat acid (FFA) were not significantly changed(all P >0.05). In the control group, the above mentioned parameters did not changed significantly during 4-6 months of observational period(all P >0.05). Conclusion: rhGH therapy improves metabolic parameters in patients after craniopharyngioma surgery by decreasing body weight, waist circumstance and fat deposit in liver, as well as

Comparison between electronic cigarette refill liquid and nicotine on metabolic parameters in rats.

PubMed

El Golli, Narges; Dkhili, Houssem; Dallagi, Yosra; Rahali, Dalila; Lasram, Montassar; Bini-Dhouib, Ines; Lebret, Maryline; Rosa, Jean-Philippe; El Fazaa, Saloua; Allal-El Asmi, Monia

2016-02-01

Nicotine is known to promote body weight loss and to disturb glucose homeostasis and lipoprotein metabolism. Electronic cigarettes, as a substitute to nicotine, are becoming increasingly popular, although there is no evidence regarding their safety. Considering the dearth of information about e-cigarette toxicity, the present study was designed to compare nicotine alone to e-liquid with or without nicotine on metabolic parameters in Wistar rats. For this purpose, e-liquid with or without nicotine and nicotine alone (0.5mg/kg of body weight) were administered intra-peritoneally during 28 days. Our results show a significant decrease in food and energy intake after nicotine or e-liquid with nicotine exposure, when compared to control or e-liquid without nicotine. Analysis of lipid status identified a significant decrease in cholesterol and LDL levels in e-cigarette groups, suggesting an improvement in lipid profile. Interestingly, e-liquid without nicotine induced hyperglycemia which is negatively correlated to hepatic glycogen level, acting like nicotine alone. Furthermore, an increase in liver biomarkers was observed in all treated groups. qRT-PCR analysis showed GSK3β up-regulation in e-liquid with nicotine as well as, surprisingly, in e-liquid without nicotine exposure. In contrast, PEPCK genes were only up-regulated in e-liquid with nicotine. While some features observed in rats may not be observed in human smokers, most of our data are consistent with, e-liquid per se i.e. without nicotine, not being neutral from a metabolic stand point since disrupting glucose homeostasis in rats. Copyright © 2016 Elsevier Inc. All rights reserved.

Correlation of human papilloma virus status with quantitative perfusion/diffusion/metabolic imaging parameters in the oral cavity and oropharyngeal squamous cell carcinoma: comparison of primary tumour sites and metastatic lymph nodes.

PubMed

Han, M; Lee, S J; Lee, D; Kim, S Y; Choi, J W

2018-05-17

To investigate the differences in perfusion/diffusion/metabolic imaging parameters according to human papilloma virus (HPV) status in the oral cavity and oropharyngeal squamous cell carcinoma (OC-OPSCC), separately in primary tumour sites and metastatic lymph nodes. This retrospective study comprised 41 patients with primary OC-OPSCCs and 29 patients with metastatic lymph nodes. The perfusion/diffusion/metabolic imaging parameters were measured at the primary tumour and the largest ipsilateral metastatic lymph node. The quantitative parameters were compared between the HPV-positive and -negative groups. The HPV-positivity was 39% (16 patients) for the primary tumours and 51.7% (15 patients) for the metastatic lymph nodes. Patients with HPV-positive tumours had a lower T stage (p=0.034). The metastatic lymph nodes for the HPV-positive patients were bulkier (p=0.016) and more frequently had cystic morphology (p=0.005). The perfusion parameters were not different, regardless of HPV status. The diffusion parameter (ADC min , p=0.011) of the metastatic lymph nodes in the HPV-positive groups was lower and metabolic parameter (metabolic tumour volume p=0.035 and total lesion glycolysis p=0.037) were higher than those in HPV-negative groups. The diffusion and metabolic parameters of metastatic lymph nodes from OC-OPSCC were different according to HPV status. The perfusion parameters did not clearly represent HPV status. Copyright © 2018 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Resveratrol shows vasoprotective effect reducing oxidative stress without affecting metabolic disturbances in insulin-dependent diabetes of rabbits.

PubMed

Akar, Fatma; Pektas, M Bilgehan; Tufan, Can; Soylemez, Selen; Sepici, Aylin; Ulus, A Tulga; Gokalp, Burcu; Ozturk, Kamile; Surucu, H Selcuk

2011-04-01

Resveratrol has been shown to have vasoprotective effects by upregulating oxidative defense mechanisms in a variety of pathophysiological conditions. However, the effect of resveratrol on diabetic oxidative stress and vascular and metabolic abnormalities is not completely understood. Therefore, this study was designed to evaluate whether long-term resveratrol supplementation has a protective effect on vascular function and integrity in association with metabolic parameters and oxidative stress in insulin-dependent diabetes. Diabetes was induced in rabbits with alloxan and maintained for 8 weeks. We used a resveratrol dose of 5 mg/L (10 weeks, starting 14 days before alloxan injection) and 50 mg/L (8 or 10 weeks, starting concomitantly or 14 days before alloxan injection) in the drinking water of rabbits. Relaxation to acetylcholine was impaired (control 75.6 ± 3.59%, versus diabetic 42.23 ± 2.53%) and contractions to phenylephrine increased (control 136.89 ± 2.27%, versus diabetic 159.37 ± 6.27%) in aortas from diabetic animals. These changes were associated with increased basal or NAD(P)H-induced superoxide production, as well as lipid peroxide and superoxide dismutase (SOD) levels in the aortic samples. The maximal relaxation to acetylcholine improved by 75.74 ± 9.04% in diabetic rabbits treated with resveratrol. The increased contractions to phenylephrine were not restored to control values after resveratrol treatments, but sensitivity to the contractions tended to decrease. Resveratrol increased nitrite/nitrate levels and suppressed basal or NAD(P)H-induced superoxide production and lipid peroxide levels in the aortas. Importantly, resveratrol increased serum insulin levels without affecting blood glucose and the lipid profile in diabetic rabbits. Using electron microscopic examinations, resveratrol was found to markedly protect the endothelial integrity from diabetes. Overall, there was no noticeable difference between resveratrol

Cannibalism Affects Core Metabolic Processes in Helicoverpa armigera Larvae—A 2D NMR Metabolomics Study

PubMed Central

Vergara, Fredd; Shino, Amiu; Kikuchi, Jun

2016-01-01

Cannibalism is known in many insect species, yet its impact on insect metabolism has not been investigated in detail. This study assessed the effects of cannibalism on the metabolism of fourth-instar larvae of the non-predatory insect Helicoverpa armigera (Lepidotera: Noctuidea). Two groups of larvae were analyzed: one group fed with fourth-instar larvae of H. armigera (cannibal), the other group fed with an artificial plant diet. Water-soluble small organic compounds present in the larvae were analyzed using two-dimensional nuclear magnetic resonance (NMR) and principal component analysis (PCA). Cannibalism negatively affected larval growth. PCA of NMR spectra showed that the metabolic profiles of cannibal and herbivore larvae were statistically different with monomeric sugars, fatty acid- and amino acid-related metabolites as the most variable compounds. Quantitation of 1H-13C HSQC (Heteronuclear Single Quantum Coherence) signals revealed that the concentrations of glucose, glucono-1,5-lactone, glycerol phosphate, glutamine, glycine, leucine, isoleucine, lysine, ornithine, proline, threonine and valine were higher in the herbivore larvae. PMID:27598144

Cannibalism Affects Core Metabolic Processes in Helicoverpa armigera Larvae-A 2D NMR Metabolomics Study.

PubMed

Vergara, Fredd; Shino, Amiu; Kikuchi, Jun

2016-09-02

Cannibalism is known in many insect species, yet its impact on insect metabolism has not been investigated in detail. This study assessed the effects of cannibalism on the metabolism of fourth-instar larvae of the non-predatory insect Helicoverpa armigera (Lepidotera: Noctuidea). Two groups of larvae were analyzed: one group fed with fourth-instar larvae of H. armigera (cannibal), the other group fed with an artificial plant diet. Water-soluble small organic compounds present in the larvae were analyzed using two-dimensional nuclear magnetic resonance (NMR) and principal component analysis (PCA). Cannibalism negatively affected larval growth. PCA of NMR spectra showed that the metabolic profiles of cannibal and herbivore larvae were statistically different with monomeric sugars, fatty acid- and amino acid-related metabolites as the most variable compounds. Quantitation of ¹H-(13)C HSQC (Heteronuclear Single Quantum Coherence) signals revealed that the concentrations of glucose, glucono-1,5-lactone, glycerol phosphate, glutamine, glycine, leucine, isoleucine, lysine, ornithine, proline, threonine and valine were higher in the herbivore larvae.

Effects of Metformin on Endocrine and Metabolic Parameters in Patients with Polycystic Ovary Syndrome.

PubMed

Zahra, M; Shah, M; Ali, A; Rahim, R

2017-02-01

The present study was designed to evaluate the effects of metformin on metabolic and endocrine parameters in patients with polycystic ovary syndrome (PCOS). The study included 40 patients with PCOS. Patients were divided into 2 groups based on whether they will receive metformin (500 mg 3 times a day, n=20) or placebo (n=20) for 3 consecutive months. Serum concentrations of fasting blood glucose, insulin, HOMA-IR, INSL-3, visfatin, FSH, and LH were measured at baseline and after 3 months of therapy. The key endocrine and metabolic parameters significantly changed after metformin treatment. The systolic and diastolic blood pressures were significantly reduced in the metformin group after treatment compared to placebo (p<0.001). A significant reduction in the size of the right ovary was observed after metformin treatment (p=0.05), while no change was found in the size of left ovary (p>0.12). Moreover, a significant reduction was observed in the serum levels of FSH (p>0.01), LH (p>0.001), and visfatin (p>0.001) after metformin treatment. However, HOMA-IR (which is used to assess insulin resistance) failed to reach the statistical significance (p=0.20). We conclude that metformin treatment in females with PCOS showed significant improvement in systolic and diastolic blood pressures. In addition, an improvement in the hormonal profile in the form of reduction in LH, FSH, and visfatin levels was observed. Thus, therapeutic intervention with metformin could be of clinical importance in high-risk group of young females with PCOS. © Georg Thieme Verlag KG Stuttgart · New York.

Genetic Alterations Affecting Cholesterol Metabolism and Human Fertility1

PubMed Central

DeAngelis, Anthony M.; Roy-O'Reilly, Meaghan; Rodriguez, Annabelle

2014-01-01

ABSTRACT Single nucleotide polymorphisms (SNPs) represent genetic variations among individuals in a population. In medicine, these small variations in the DNA sequence may significantly impact an individual's response to certain drugs or influence the risk of developing certain diseases. In the field of reproductive medicine, a significant amount of research has been devoted to identifying polymorphisms which may impact steroidogenesis and fertility. This review discusses current understanding of the effects of genetic variations in cholesterol metabolic pathways on human fertility that bridge novel linkages between cholesterol metabolism and reproductive health. For example, the role of the low-density lipoprotein receptor (LDLR) in cellular metabolism and human reproduction has been well studied, whereas there is now an emerging body of research on the role of the high-density lipoprotein (HDL) receptor scavenger receptor class B type I (SR-BI) in human lipid metabolism and female reproduction. Identifying and understanding how polymorphisms in the SCARB1 gene or other genes related to lipid metabolism impact human physiology is essential and will play a major role in the development of personalized medicine for improved diagnosis and treatment of infertility. PMID:25122065

Comprehensive assessment of variables affecting metabolic control in patients with type 2 diabetes mellitus in Jordan.

PubMed

Qteishat, Rola Reyad; Ghananim, Abdel Rahman Al

2016-01-01

The aim of the study was to identify variables affecting metabolic control among diabetic patients treated at diabetes and endocrine clinic in Jordan. A total of 200 patients were studied by using a cross sectional study design. Data were collected from patients' medical records, glycemic control tests and prestructured questionnaires about variables that were potentially important based on previous researches and clinical judgment: Adherence evaluation, Patients' knowledge about drug therapy and non-pharmacological therapy, Anxiety and depression, Beliefs about diabetes treatment (benefits and barriers of treatment), Knowledge about treatment goals, Knowledge about diabetes, Self efficacy, and Social support. The mean (±SD) age was 53.5 (±10.38) years and mean HbA1c was 8.4 (±1.95). In the multivariate analysis, education level, and self efficacy found to have significantly independent association with metabolic control (P<0.03). Adequate knowledge and high self efficacy was significant in patients with good metabolic control. Emphasizing the importance of continuous educational programs and improving the self efficacy as well, could warrant achieving good metabolic control. Copyright © 2015 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Prosthetic model, but not stiffness or height, affects the metabolic cost of running for athletes with unilateral transtibial amputations.

PubMed

Beck, Owen N; Taboga, Paolo; Grabowski, Alena M

2017-07-01

Running-specific prostheses enable athletes with lower limb amputations to run by emulating the spring-like function of biological legs. Current prosthetic stiffness and height recommendations aim to mitigate kinematic asymmetries for athletes with unilateral transtibial amputations. However, it is unclear how different prosthetic configurations influence the biomechanics and metabolic cost of running. Consequently, we investigated how prosthetic model, stiffness, and height affect the biomechanics and metabolic cost of running. Ten athletes with unilateral transtibial amputations each performed 15 running trials at 2.5 or 3.0 m/s while we measured ground reaction forces and metabolic rates. Athletes ran using three different prosthetic models with five different stiffness category and height combinations per model. Use of an Ottobock 1E90 Sprinter prosthesis reduced metabolic cost by 4.3 and 3.4% compared with use of Freedom Innovations Catapult [fixed effect (β) = -0.177; P < 0.001] and Össur Flex-Run (β = -0.139; P = 0.002) prostheses, respectively. Neither prosthetic stiffness ( P ≥ 0.180) nor height ( P = 0.062) affected the metabolic cost of running. The metabolic cost of running was related to lower peak (β = 0.649; P = 0.001) and stance average (β = 0.772; P = 0.018) vertical ground reaction forces, prolonged ground contact times (β = -4.349; P = 0.012), and decreased leg stiffness (β = 0.071; P < 0.001) averaged from both legs. Metabolic cost was reduced with more symmetric peak vertical ground reaction forces (β = 0.007; P = 0.003) but was unrelated to stride kinematic symmetry ( P ≥ 0.636). Therefore, prosthetic recommendations based on symmetric stride kinematics do not necessarily minimize the metabolic cost of running. Instead, an optimal prosthetic model, which improves overall biomechanics, minimizes the metabolic cost of running for athletes with unilateral transtibial amputations. NEW & NOTEWORTHY The metabolic cost of running for

The impact of long-term growth hormone treatment on metabolic parameters in Japanese patients with short stature born small for gestational age.

PubMed

Kappelgaard, Anne-Marie; Kiyomi, Fumiaki; Horikawa, Reiko; Yokoya, Susumu; Tanaka, Toshiaki

2014-01-01

An examination of the effects of up to 260 weeks of growth hormone (GH) therapy on metabolic parameters in Japanese children born small for gestational age (SGA). Data were analysed from a 156-week extension of a 104-week multicentre, randomised, double-blind, parallel-group trial. Sixty-five children born SGA (age 3-<8 years) received 33 μg/kg/day (n = 31, 64.5% male) or 67 μg/kg/day (n = 34, 58.8% male) GH for 260 weeks. Changes in metabolic parameters - glucose, insulin, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol - were recorded. Alterations in weight, body mass index standard deviation score (BMI SDS) and vital signs were also evaluated. Over 260 weeks of GH treatment, a positive correlation between Δheight SDS and Δinsulin-like growth factor-I SDS was observed. Insulin and glucose levels were generally unaffected. Favourable changes in lipid profiles were recorded, which were maintained for the study duration. No adverse alterations in weight, BMI SDS or vital signs were noted. Long-term, continuous GH treatment in children born SGA appears to be efficacious, associated with potential benefits for several metabolic parameters and associated with no long-term safety concerns.

Parameter estimation in tree graph metabolic networks.

PubMed

Astola, Laura; Stigter, Hans; Gomez Roldan, Maria Victoria; van Eeuwijk, Fred; Hall, Robert D; Groenenboom, Marian; Molenaar, Jaap J

2016-01-01

We study the glycosylation processes that convert initially toxic substrates to nutritionally valuable metabolites in the flavonoid biosynthesis pathway of tomato (Solanum lycopersicum) seedlings. To estimate the reaction rates we use ordinary differential equations (ODEs) to model the enzyme kinetics. A popular choice is to use a system of linear ODEs with constant kinetic rates or to use Michaelis-Menten kinetics. In reality, the catalytic rates, which are affected among other factors by kinetic constants and enzyme concentrations, are changing in time and with the approaches just mentioned, this phenomenon cannot be described. Another problem is that, in general these kinetic coefficients are not always identifiable. A third problem is that, it is not precisely known which enzymes are catalyzing the observed glycosylation processes. With several hundred potential gene candidates, experimental validation using purified target proteins is expensive and time consuming. We aim at reducing this task via mathematical modeling to allow for the pre-selection of most potential gene candidates. In this article we discuss a fast and relatively simple approach to estimate time varying kinetic rates, with three favorable properties: firstly, it allows for identifiable estimation of time dependent parameters in networks with a tree-like structure. Secondly, it is relatively fast compared to usually applied methods that estimate the model derivatives together with the network parameters. Thirdly, by combining the metabolite concentration data with a corresponding microarray data, it can help in detecting the genes related to the enzymatic processes. By comparing the estimated time dynamics of the catalytic rates with time series gene expression data we may assess potential candidate genes behind enzymatic reactions. As an example, we show how to apply this method to select prominent glycosyltransferase genes in tomato seedlings.

Dietary electrolyte balance affects growth performance, amylase activity and metabolic response in the meagre (Argyrosomus regius).

PubMed

Magnoni, Leonardo J; Salas-Leiton, Emilio; Peixoto, Maria-João; Pereira, Luis; Silva-Brito, Francisca; Fontinha, Filipa; Gonçalves, José F M; Wilson, Jonathan M; Schrama, Johan W; Ozório, Rodrigo O A

2017-09-01

Dietary ion content is known to alter the acid-base balance in freshwater fish. The current study investigated the metabolic impact of acid-base disturbances produced by differences in dietary electrolyte balance (DEB) in the meagre (Argyrosomus regius), an euryhaline species. Changes in fish performance, gastric chyme characteristics, pH and ion concentrations in the bloodstream, digestive enzyme activities and metabolic rates were analyzed in meagre fed ad libitum two experimental diets (DEB 200 or DEB 700mEq/kg) differing in the Na 2 CO 3 content for 69days. Fish fed the DEB 200 diet had 60-66% better growth performance than the DEB 700 group. Meagre consuming the DEB 200 diet were 90-96% more efficient than fish fed the DEB 700 diet at allocating energy from feed into somatic growth. The pH values in blood were significantly lower in the DEB 700 group 2h after feeding when compared to DEB 200, indicating that acid-base balance in meagre was affected by electrolyte balance in diet. Osmolality, and Na + and K + concentrations in plasma did not vary with the dietary treatment. Gastric chyme in the DEB 700 group had higher pH values, dry matter, protein and energy contents, but lower lipid content than in the DEB 200 group. Twenty-four hours after feeding, amylase activity was higher in the gastrointestinal tract of DEB 700 group when compared to the DEB 200 group. DEB 700 group had lower routine metabolic (RMR) and standard metabolic (SMR) rates, indicating a decrease in maintenance energy expenditure 48h after feeding the alkaline diet. The current study demonstrates that feeding meagre with an alkaline diet not only causes acid-base imbalance, but also negatively affects digestion and possibly nutrient assimilation, resulting in decreased growth performance. Copyright © 2017 Elsevier Inc. All rights reserved.

Food odors trigger an endocrine response that affects food ingestion and metabolism.

PubMed

Lushchak, Oleh V; Carlsson, Mikael A; Nässel, Dick R

2015-08-01

Food odors stimulate appetite and innate food-seeking behavior in hungry animals. The smell of food also induces salivation and release of gastric acid and insulin. Conversely, sustained odor exposure may induce satiation. We demonstrate novel effects of food odors on food ingestion, metabolism and endocrine signaling in Drosophila melanogaster. Acute exposure to attractive vinegar odor triggers a rapid and transient increase in circulating glucose, and a rapid upregulation of genes encoding the glucagon-like hormone adipokinetic hormone (AKH), four insulin-like peptides (DILPs) and some target genes in peripheral tissues. Sustained exposure to food odors, however, decreases food intake. Hunger-induced strengthening of synaptic signaling from olfactory sensory neurons (OSNs) to brain neurons increases food-seeking behavior, and conversely fed flies display reduced food odor sensitivity and feeding. We show that increasing the strength of OSN signaling chronically by genetic manipulation of local peptide neuromodulation reduces feeding, elevates carbohydrates and diminishes lipids. Furthermore, constitutively strengthened odor sensitivity altered gene transcripts for AKH, DILPs and some of their targets. Thus, we show that food odor can induce a transient anticipatory endocrine response, and that boosted sensitivity to this odor affects food intake, as well as metabolism and hormonal signaling.

Effect of Slow Wave Sleep Disruption on Metabolic Parameters in Adolescents.

PubMed

Shaw, Natalie D; McHill, Andrew W; Schiavon, Michele; Kangarloo, Tairmae; Mankowski, Piotr W; Cobelli, Claudio; Klerman, Elizabeth B; Hall, Janet E

2016-08-01

Cross-sectional studies report a correlation between slow wave sleep (SWS) duration and insulin sensitivity (SI) in children and adults. Suppression of SWS causes insulin resistance in adults but effects in children are unknown. This study was designed to determine the effect of SWS fragmentation on SI in children. Fourteen pubertal children (11.3-14.1 y, body mass index 29(th) to 97(th) percentile) were randomized to sleep studies and mixed meal (MM) tolerance tests with and without SWS disruption. Beta-cell responsiveness (Φ) and SI were determined using oral minimal modeling. During the disruption night, auditory stimuli (68.1 ± 10.7/night; mean ± standard error) decreased SWS by 40.0 ± 8.0%. SWS fragmentation did not affect fasting glucose (non-disrupted 76.9 ± 2.3 versus disrupted 80.6 ± 2.1 mg/dL), insulin (9.2 ± 1.6 versus 10.4 ± 2.0 μIU/mL), or C-peptide (1.9 ± 0.2 versus 1.9 ± 0.1 ng/mL) levels and did not impair SI (12.9 ± 2.3 versus 10.1 ± 1.6 10(-4) dL/kg/min per μIU/mL) or Φ (73.4 ± 7.8 versus 74.4 ± 8.4 10(-9) min(-1)) to a MM challenge. Only the subjects in the most insulin-sensitive tertile demonstrated a consistent decrease in SI after SWS disruption. Pubertal children across a range of body mass indices may be resistant to the adverse metabolic effects of acute SWS disruption. Only those subjects with high SI (i.e., having the greatest "metabolic reserve") demonstrated a consistent decrease in SI. These results suggest that adolescents may have a unique ability to adapt to metabolic stressors, such as acute SWS disruption, to maintain euglycemia. Additional studies are necessary to confirm that this resiliency is maintained in settings of chronic SWS disruption. © 2016 Associated Professional Sleep Societies, LLC.

A review of dopamine agonist therapy in type 2 diabetes and effects on cardio-metabolic parameters.

PubMed

Lamos, E M; Levitt, D L; Munir, K M

2016-02-01

Dopamine action appears to play a role in changes that are seen in obesity, metabolic syndrome and type 2 diabetes mellitus. Bromocriptine-QR (Quick Release), a dopamine agonist, is approved for use in treatment of type 2 diabetes. It has demonstrated modest improvement in glycemic parameters, cholesterol and weight in certain cohorts. Limited data using cabergoline, a long-acting dopamine agonist, also demonstrate glycemic efficacy. Additionally, bromocriptine-QR appears to have a favorable cardiovascular risk reduction. The direct mechanism by which bromocriptine-QR, or central dopamine agonism, achieves modest glycemic control and favorable cardio-metabolic profile is unclear. This relationship appears to be more complex than the historical explanation of "resetting" the circadian clock and may further be elucidated using data in individuals with hyperprolactinemia and prolactinoma. Copyright © 2015 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

Does family history of metabolic syndrome affect the metabolic profile phenotype in young healthy individuals?

PubMed

Lipińska, Anna; Koczaj-Bremer, Magdalena; Jankowski, Krzysztof; Kaźmierczak, Agnieszka; Ciurzyński, Michał; Ou-Pokrzewińska, Aisha; Mikocka, Ewelina; Lewandowski, Zbigniew; Demkow, Urszula; Pruszczyk, Piotr

2014-01-01

Early identification of high-risk individuals is key for the prevention of cardiovascular disease (CVD). The aim of this study was to assess the potential impact of a family history of metabolic syndrome (fhMetS) on the risk of metabolic disorders (abnormal body mass, lipid profile, glucose metabolism, insulin resistance, and blood pressure) in healthy young individuals. We studied CVD risk factors in 90 healthy volunteers, aged 27-39 years; of these, 78 had fhMetS and 12 were without fhMetS (control group). Fasting serum lipids, glucose, and insulin levels were assayed, and anthropometric parameters and blood pressure using, an ambulatory blood pressure monitoring system, were measured. Nutritional and physical activity habits were assessed. Despite similar nutritional and physical activity habits, abnormal body mass was found in 53.2% of the fhMetS participants and 46.1% of the control participants (p = 0.54). The occurrence of obesity was 19.4% and 0%, respectively (p = 0.69). Compared to the control participants, fhMetS was associated with significantly higher total cholesterol (5.46 mmol/L vs. 4.69 mmol/L, p < 0.030), low-density lipoprotein cholesterol ( 3.28 mmol/L vs. 2.90 mmol/L, p < 0.032), and non-high-density lipoprotein cholesterol ( 3.74 mmol/L vs. 3.25 mmol/L, p < 0.016) levels, in addition to lower fasting glucose levels ( 4.51 mmol/L vs. 4.81 mmol/L, p < 0.042). A positive correlation between fasting glucose and insulin levels (r = 0.28; p < 0.015) was detected in the fhMetS participants. Higher mean daytime systolic blood pressure (121.5 mmHg vs. 113.3 mmHg, p < 0.035), mean daytime diastolic blood pressure ( 79.0 mmHg vs. 74.5 mmHg, p < 0.045), and mean nighttime diastolic blood pressure ( 64.0 mmHg vs. 59.5 mmHg, p < 0.019) were observed in the fhMetS group. More than 50% of the fhMetS participants had excess weight or a lipid disorder, which may indicate an increased risk of cardiovascular disease and the need for regular ambulatory

Characterization of the cytochrome P450 enzymes and enzyme kinetic parameters for metabolism of BVT.2938 using different in vitro systems.

PubMed

Baranczewski, Pawel; Edlund, Per Olof; Postlind, Hans

2006-03-18

An important step in the drug development process is identification of enzymes responsible for metabolism of drug candidates and determination of enzyme kinetic parameters. These data are used to increase understanding of the pharmacokinetics and possible metabolic-based drug interactions of drug candidates. The aim of the present study was to characterize the cytochrome P450 enzymes and enzyme kinetic parameters for metabolism of BVT.2938 [1-(3-{2-[(2-ethoxy-3-pyridinyl)oxy]ethoxy}-2-pyrazinyl)-2(R)-methylpiperazine], a potent and selective 5HT2c-receptor agonist. The enzyme kinetic parameters were determined for formation of three main metabolites of BVT.2938 using human liver microsomes and expressed cytochrome P450 (CYP) isoforms. The major metabolite was formed by hydroxylation of the pyridine ring (CL(int)=27 microl/mgmin), and was catalysed by both CYP2D6*1 and CYP1A1, with K(m) values corresponding to 1.4 and 2.7 microM, respectively. The results from enzyme kinetic studies were confirmed by incubation of BVT.2938 in the presence of the chemical inhibitor of CYP2D6*1, quinidine. Quinidine inhibited the formation of the major metabolite by approximately 90%. Additionally, studies with recombinant expressed CYP isoforms from rat indicated that formation of the major metabolite of BVT.2938 was catalysed by CYP2D2. This result was further confirmed by experiments with liver slices from different rat strains, where the formation of the metabolite correlated with phenotype of CYP2D2 isoform (Sprague-Dawley male, extensive; Dark Agouti male, intermediate; Dark Agouti female, poor metabolizer). The present study showed that the major metabolite of BVT.2938 is formed by hydroxylation of the pyridine ring and catalysed by CYP2D6*1. CYP1A1 is also involved in this reaction and its role in extra-hepatic metabolism of BVT.2938 might be significant.

Hyperthyroidism affects lipid metabolism in lactating and suckling rats.

PubMed

Varas, S M; Jahn, G A; Giménez, M S

2001-08-01

Two per thousand pregnant women have hyperthyroidism (HT), and although the symptoms are attenuated during pregnancy, they rebound after delivery, affecting infant development. To examine the effects of hyperthyroidism on lactation, we studied lipid metabolism in maternal mammary glands and livers of hyperthyroid rats and their pups. Thyroxine (10 microg/100 g body weight/d) or vehicle-treated rats were made pregnant 2 wk after commencement of treatment and sacrificed on days 7, 14, and 21 of lactation with the litters. Circulating triiodothyronine and tetraiodothyronine concentrations in the HT mothers were increased on all days. Hepatic esterified cholesterol (EC) and free cholesterol (FC) and triglyceride (TG) concentrations were diminished on days 14 and 21. Lipid synthesis, measured by incorporation of [3H]H2O into EC, FC, and TG, fatty acid synthase, and acetyl CoA carboxylase activities increased at day 14, while incorporation into FC and EC decreased at days 7 and 21, respectively. Mammary FC and TG concentrations were diminished at day 14; incorporation of [3H]H2O into TG decreased at days 7 and 21, and incorporation of [3H]H2O into FC increased at day 14. In the HT pups, growth rate was diminished, tetraiodothyronine concentration rose at days 7 and 14 of lactation, and triiodothyronine increased only at day 14. Liver TG concentrations increased at day 7 and fell at day 14, while FC increased at day 14 and only acetyl CoA carboxylase activity fell at day 14. Thus, hyperthyroidism changed maternal liver and mammary lipid metabolism, with decreased lipid concentration in spite of increased liver rate of synthesis and decreases in mammary synthesis. These changes, along with the mild hyperthyroidism of the litters, may have contributed to their reduced growth rate.

Age and natural metabolically-intensive behavior affect oxidative stress and antioxidant mechanisms.

PubMed

Williams, Jason B; Roberts, Stephen P; Elekonich, Michelle M

2008-06-01

Flying honey bees have among the highest mass-specific metabolic rates ever measured, suggesting that their flight muscles may experience high levels of oxidative stress during normal daily activities. We measured parameters of oxidative stress and antioxidant capacity in highly metabolic flight muscle and less active head tissue in cohorts of age-matched nurse bees, which rarely fly, and foragers, which fly several hours per a day. Naturally occurring foraging flight elicited an increase in flight muscle Hsp70 content in both young and old foragers; however catalase and total antioxidant capacity increased only in young flight muscle. Surprisingly, young nurse bees also showed a modest daily increase in Hsp70, catalase levels and antioxidant capacity, and these effects were likely due to collecting the young nurses soon after orientation flights. There were no differences in flight muscle carbonyl content over the course of daily activity and few differences in Hsp70, catalase, total antioxidant capacity and protein carbonyl levels in head tissue regardless of age or activity. In summary, honey bee flight likely produces high levels of reactive oxygen species in flight muscle that, when coupled with age-related decreases in antioxidant activity may be responsible for behavioral senescence and reduced longevity.

Factors affecting metabolic cost of transport during a multi-stage running race.

PubMed

Lazzer, Stefano; Taboga, Paolo; Salvadego, Desy; Rejc, Enrico; Simunic, Bostjan; Narici, Marco V; Buglione, Antonio; Giovanelli, Nicola; Antonutto, Guglielmo; Grassi, Bruno; Pisot, Rado; di Prampero, Pietro E

2014-03-01

The aim of this study was to investigate: (1) the role of , the fraction of (F) and the metabolic cost of transport (CoT) in determining performance during an ultra-endurance competition and (2) the effects of the race on several biomechanical and morphological parameters of the lower limbs that are likely to affect CoT. Eleven runners (aged 29-54 years) participated in an ultra-endurance competition consisting of three running stages of 25, 55 and 13 km on three consecutive days. Anthropometric characteristics, body composition, morphological properties of the gastrocnemius medialis, maximal explosive power of the lower limb and were determined before the competition. In addition, biomechanics of running and CoT were determined, before and immediately after each running stage. Performance was directly proportional to (r=0.77) and F (r=0.36), and inversely proportional to CoT (r=-0.30). Low CoT values were significantly related to high maximal power of the lower limbs (r=-0.74) and vertical stiffness (r=-0.65) and low footprint index (FPI, r=0.70), step frequency (r=0.62) and external work (r=0.60). About 50% of the increase in CoT during the stages of the competition was accounted for by changes in FPI, which represents a global evaluation of medio-lateral displacement of the foot during the whole stance phase, which in turn is associated with the myotendinous characteristics of the lower limb. Thus, lower CoT values were related to greater muscular power and lower FPI, suggesting that a better ankle stability is likely to achieve better performance in an ultra-endurance running competition.

Metabolomics and proteomics technologies to explore the herbal preparation affecting metabolic disorders using high resolution mass spectrometry.

PubMed

Zhang, Aihua; Zhou, Xiaohang; Zhao, Hongwei; Zou, Shiyu; Ma, Chung Wah; Liu, Qi; Sun, Hui; Liu, Liang; Wang, Xijun

2017-01-31

An integrative metabolomics and proteomics approach can provide novel insights in the understanding of biological systems. We have integrated proteome and metabolome data sets for a holistic view of the molecular mechanisms in disease. Using quantitative iTRAQ-LC-MS/MS proteomics coupled with UPLC-Q-TOF-HDMS based metabolomics, we determined the protein and metabolite expression changes in the kidney-yang deficiency syndrome (KYDS) rat model and further investigated the intervention effects of the Jinkui Shenqi Pill (JSP). The VIP-plot of the orthogonal PLS-DA (OPLS-DA) was used for discovering the potential biomarkers to clarify the therapeutic mechanisms of JSP in treating KYDS. The results showed that JSP can alleviate the kidney impairment induced by KYDS. Sixty potential biomarkers, including 5-l-glutamyl-taurine, phenylacetaldehyde, 4,6-dihydroxyquinoline, and xanthurenic acid etc., were definitely up- or down-regulated. The regulatory effect of JSP on the disturbed metabolic pathways was proved by the established metabonomic method. Using pathway analyses, we identified the disturbed metabolic pathways such as taurine and hypotaurine metabolism, pyrimidine metabolism, tyrosine metabolism, tryptophan metabolism, histidine metabolism, steroid hormone biosynthesis, etc. Furthermore, using iTRAQ-based quantitative proteomics analysis, seventeen differential proteins were identified and significantly altered by the JSP treatment. These proteins appear to be involved in Wnt, chemokine, PPAR, and MAPK signaling pathways, etc. Functional pathway analysis revealed that most of the proteins were found to play a key role in the regulation of metabolism pathways. Bioinformatics analysis with the IPA software found that these differentially-expressed moleculars had a strong correlation with the α-adrenergic signaling, FGF signaling, etc. Our data indicate that high-throughput metabolomics and proteomics can provide an insight on the herbal preparations affecting the

Central Metabolic Responses to Ozone and Herbivory Affect Photosynthesis and Stomatal Closure1[OPEN

PubMed Central

Khaling, Eliezer; Lassueur, Steve

2016-01-01

Plants have evolved adaptive mechanisms that allow them to tolerate a continuous range of abiotic and biotic stressors. Tropospheric ozone (O3), a global anthropogenic pollutant, directly affects living organisms and ecosystems, including plant-herbivore interactions. In this study, we investigate the stress responses of Brassica nigra (wild black mustard) exposed consecutively to O3 and the specialist herbivore Pieris brassicae. Transcriptomics and metabolomics data were evaluated using multivariate, correlation, and network analyses for the O3 and herbivory responses. O3 stress symptoms resembled those of senescence and phosphate starvation, while a sequential shift from O3 to herbivory induced characteristic plant defense responses, including a decrease in central metabolism, induction of the jasmonic acid/ethylene pathways, and emission of volatiles. Omics network and pathway analyses predicted a link between glycerol and central energy metabolism that influences the osmotic stress response and stomatal closure. Further physiological measurements confirmed that while O3 stress inhibited photosynthesis and carbon assimilation, sequential herbivory counteracted the initial responses induced by O3, resulting in a phenotype similar to that observed after herbivory alone. This study clarifies the consequences of multiple stress interactions on a plant metabolic system and also illustrates how omics data can be integrated to generate new hypotheses in ecology and plant physiology. PMID:27758847

In Ovo injection of betaine affects hepatic cholesterol metabolism through epigenetic gene regulation in newly hatched chicks.

PubMed

Hu, Yun; Sun, Qinwei; Li, Xiaoliang; Wang, Min; Cai, Demin; Li, Xi; Zhao, Ruqian

2015-01-01

Betaine is reported to regulate hepatic cholesterol metabolism in mammals. Chicken eggs contain considerable amount of betaine, yet it remains unknown whether and how betaine in the egg affects hepatic cholesterol metabolism in chicks. In this study, eggs were injected with betaine at 2.5 mg/egg and the hepatic cholesterol metabolism was investigated in newly hatched chicks. Betaine did not affect body weight or liver weight, but significantly increased the serum concentration (P < 0.05) and the hepatic content (P < 0.01) of cholesterol. Accordingly, the cholesterol biosynthetic enzyme HMGCR was up-regulated (P < 0.05 for both mRNA and protein), while CYP7A1 which converts cholesterol to bile acids was down-regulated (P < 0.05 for mRNA and P = 0.07 for protein). Moreover, hepatic protein content of the sterol-regulatory element binding protein 1 which regulates cholesterol and lipid biosynthesis, and the mRNA abundance of ATP binding cassette sub-family A member 1 (ABCA1) which mediates cholesterol counter transport were significantly (P < 0.05) increased in betaine-treated chicks. Meanwhile, hepatic protein contents of DNA methyltransferases 1 and adenosylhomocysteinase-like 1 were increased (P < 0.05), which was associated with global genomic DNA hypermethylation (P < 0.05) and diminished gene repression mark histone H3 lysine 27 trimethylation (P < 0.05). Furthermore, CpG methylation level on gene promoters was found to be increased (P < 0.05) for CYP7A1 yet decreased (P < 0.05) for ABCA1. These results indicate that in ovo betaine injection regulates hepatic cholesterol metabolism in chicks through epigenetic mechanisms including DNA and histone methylations.

In Ovo Injection of Betaine Affects Hepatic Cholesterol Metabolism through Epigenetic Gene Regulation in Newly Hatched Chicks

PubMed Central

Hu, Yun; Sun, Qinwei; Li, Xiaoliang; Wang, Min; Cai, Demin; Li, Xi; Zhao, Ruqian

2015-01-01

Betaine is reported to regulate hepatic cholesterol metabolism in mammals. Chicken eggs contain considerable amount of betaine, yet it remains unknown whether and how betaine in the egg affects hepatic cholesterol metabolism in chicks. In this study, eggs were injected with betaine at 2.5 mg/egg and the hepatic cholesterol metabolism was investigated in newly hatched chicks. Betaine did not affect body weight or liver weight, but significantly increased the serum concentration (P < 0.05) and the hepatic content (P < 0.01) of cholesterol. Accordingly, the cholesterol biosynthetic enzyme HMGCR was up-regulated (P < 0.05 for both mRNA and protein), while CYP7A1 which converts cholesterol to bile acids was down-regulated (P < 0.05 for mRNA and P = 0.07 for protein). Moreover, hepatic protein content of the sterol-regulatory element binding protein 1 which regulates cholesterol and lipid biosynthesis, and the mRNA abundance of ATP binding cassette sub-family A member 1 (ABCA1) which mediates cholesterol counter transport were significantly (P < 0.05) increased in betaine-treated chicks. Meanwhile, hepatic protein contents of DNA methyltransferases 1 and adenosylhomocysteinase-like 1 were increased (P < 0.05), which was associated with global genomic DNA hypermethylation (P < 0.05) and diminished gene repression mark histone H3 lysine 27 trimethylation (P < 0.05). Furthermore, CpG methylation level on gene promoters was found to be increased (P < 0.05) for CYP7A1 yet decreased (P < 0.05) for ABCA1. These results indicate that in ovo betaine injection regulates hepatic cholesterol metabolism in chicks through epigenetic mechanisms including DNA and histone methylations. PMID:25860502

Prognosis estimation under the light of metabolic tumor parameters on initial FDG-PET/CT in patients with primary extranodal lymphoma

PubMed Central

Okuyucu, Kursat; Ozaydın, Sukru; Alagoz, Engin; Ozgur, Gokhan; Oysul, Fahrettin Guven; Ozmen, Ozlem; Tuncel, Murat; Ozturk, Mustafa; Arslan, Nuri

2016-01-01

Abstract Background Non-Hodgkin’s lymphomas arising from the tissues other than primary lymphatic organs are named primary extranodal lymphoma. Most of the studies evaluated metabolic tumor parameters in different organs and histopathologic variants of this disease generally for treatment response. We aimed to evaluate the prognostic value of metabolic tumor parameters derived from initial FDG-PET/CT in patients with a medley of primary extranodal lymphoma in this study. Patients and methods There were 67 patients with primary extranodal lymphoma for whom FDG-PET/CT was requested for primary staging. Quantitative PET/CT parameters: maximum standardized uptake value (SUVmax), average standardized uptake value (SUVmean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were used to estimate disease-free survival and overall survival. Results SUVmean, MTV and TLG were found statistically significant after multivariate analysis. SUVmean remained significant after ROC curve analysis. Sensitivity and specificity were calculated as 88% and 64%, respectively, when the cut-off value of SUVmean was chosen as 5.15. After the investigation of primary presentation sites and histo-pathological variants according to recurrence, there is no difference amongst the variants. Primary site of extranodal lymphomas however, is statistically important (p = 0.014). Testis and central nervous system lymphomas have higher recurrence rate (62.5%, 73%, respectively). Conclusions High SUVmean, MTV and TLG values obtained from primary staging FDG-PET/CT are potential risk factors for both disease-free survival and overall survival in primary extranodal lymphoma. SUVmean is the most significant one amongst them for estimating recurrence/metastasis. PMID:27904443

Alteration of metabolomic markers of amino-acid metabolism in piglets with in-feed antibiotics.

PubMed

Mu, Chunlong; Yang, Yuxiang; Yu, Kaifan; Yu, Miao; Zhang, Chuanjian; Su, Yong; Zhu, Weiyun

2017-04-01

In-feed antibiotics have been used to promote growth in piglets, but its impact on metabolomics profiles associated with host metabolism is largely unknown. In this study, to test the hypothesis that antibiotic treatment may affect metabolite composition both in the gut and host biofluids, metabolomics profiles were analyzed in antibiotic-treated piglets. Piglets were fed a corn-soy basal diet with or without in-feed antibiotics from postnatal day 7 to day 42. The serum biochemical parameters, metabolomics profiles of the serum, urine, and jejunal digesta, and indicators of microbial metabolism (short-chain fatty acids and biogenic amines) were analyzed. Compared to the control group, antibiotics treatment did not have significant effects on serum biochemical parameters except that it increased (P < 0.05) the concentration of urea. Antibiotics treatment increased the relative concentrations of metabolites involved in amino-acid metabolism in the serum, while decreased the relative concentrations of most amino acids in the jejunal content. Antibiotics reduced urinary 2-ketoisocaproate and hippurate. Furthermore, antibiotics decreased (P < 0.05) the concentrations of propionate and butyrate in the feces. Antibiotics significantly affected the concentrations of biogenic amines, which are derived from microbial amino-acid metabolism. The three major amines, putrescine, cadaverine, and spermidine, were all increased (P < 0.05) in the large intestine of antibiotics-treated piglets. These results identified the phenomena that in-feed antibiotics may have significant impact on the metabolomic markers of amino-acid metabolism in piglets.

How does the host population's network structure affect the estimation accuracy of epidemic parameters?

NASA Astrophysics Data System (ADS)

Yashima, Kenta; Ito, Kana; Nakamura, Kazuyuki

2013-03-01

When an Infectious disease where to prevail throughout the population, epidemic parameters such as the basic reproduction ratio, initial point of infection etc. are estimated from the time series data of infected population. However, it is unclear how does the structure of host population affects this estimation accuracy. In other words, what kind of city is difficult to estimate its epidemic parameters? To answer this question, epidemic data are simulated by constructing a commuting network with different network structure and running the infection process over this network. From the given time series data for each network structure, we would like to analyzed estimation accuracy of epidemic parameters.

Metabolic health assessment of zoo elephants: Management factors predicting leptin levels and the glucose-to-insulin ratio and their associations with health parameters

PubMed Central

Brown, Janine L.

2017-01-01

Screening for metabolic-related health problems can enhance animal welfare, so the purpose of this study was to conduct the first metabolic health assessment of zoo elephants and use epidemiological methods to determine how factors in the captive environment were associated with metabolic hormone concentrations. In addition, we examined relationships between metabolic status and several fitness parameters: foot health, musculoskeletal health, reproductive cyclicity, and body condition. Two blood samples were collected 2 weeks apart from 87 Asian (Elephas maximus) and 105 African (Loxodonta africana) elephants managed by zoos accredited by the Association of Zoos and Aquariums for analysis of serum leptin, insulin, glucose and the glucose-to-insulin ratio (G:I). In females, mean (± SD) leptin concentrations and the G:I were lower (P<0.05) in Asian (3.93 ± 2.21 ng/ml and 110 ± 86 units) compared to African (4.37 ± 2.89 ng/ml and 208 ± 133 units) elephants, respectively. For males, mean leptin and the G:I were 4.99 ± 3.61 ng/ml and 253 ± 181 units for Asian, and 3.72 ± 2.00 ng/ml and 326 ± 231 units for African elephants, respectively, with no differences between species (P>0.05). As mean leptin concentration increased there was an increase in the odds of a female being non-cycling (P = 0.0083). The G:I was associated inversely with body condition (P = 0.0002); as the G:I increased there was a decreased risk of BCS = 4 or 5 as compared to the ideal, or BCS = 3. Neither leptin nor G:I were predictive of foot or musculoskeletal health scores. Factors related to walking and feeding practices were most influential in predicting metabolic status, whereas social and housing factors showed smaller, but significant effects. The metabolic health benefits of walking were detected if the time spent in staff-directed walking was 7 hours or more per week. The most protective feeding practices included implementing a random rather than predictable feeding schedule and

Metabolic health assessment of zoo elephants: Management factors predicting leptin levels and the glucose-to-insulin ratio and their associations with health parameters.

PubMed

Morfeld, Kari A; Brown, Janine L

2017-01-01

Screening for metabolic-related health problems can enhance animal welfare, so the purpose of this study was to conduct the first metabolic health assessment of zoo elephants and use epidemiological methods to determine how factors in the captive environment were associated with metabolic hormone concentrations. In addition, we examined relationships between metabolic status and several fitness parameters: foot health, musculoskeletal health, reproductive cyclicity, and body condition. Two blood samples were collected 2 weeks apart from 87 Asian (Elephas maximus) and 105 African (Loxodonta africana) elephants managed by zoos accredited by the Association of Zoos and Aquariums for analysis of serum leptin, insulin, glucose and the glucose-to-insulin ratio (G:I). In females, mean (± SD) leptin concentrations and the G:I were lower (P<0.05) in Asian (3.93 ± 2.21 ng/ml and 110 ± 86 units) compared to African (4.37 ± 2.89 ng/ml and 208 ± 133 units) elephants, respectively. For males, mean leptin and the G:I were 4.99 ± 3.61 ng/ml and 253 ± 181 units for Asian, and 3.72 ± 2.00 ng/ml and 326 ± 231 units for African elephants, respectively, with no differences between species (P>0.05). As mean leptin concentration increased there was an increase in the odds of a female being non-cycling (P = 0.0083). The G:I was associated inversely with body condition (P = 0.0002); as the G:I increased there was a decreased risk of BCS = 4 or 5 as compared to the ideal, or BCS = 3. Neither leptin nor G:I were predictive of foot or musculoskeletal health scores. Factors related to walking and feeding practices were most influential in predicting metabolic status, whereas social and housing factors showed smaller, but significant effects. The metabolic health benefits of walking were detected if the time spent in staff-directed walking was 7 hours or more per week. The most protective feeding practices included implementing a random rather than predictable feeding schedule and

Resistance Training Effects on Metabolic Function Among Youth: A Systematic Review.

PubMed

Bea, Jennifer W; Blew, Robert M; Howe, Carol; Hetherington-Rauth, Megan; Going, Scott B

2017-08-01

This systematic review evaluates the relationship between resistance training and metabolic function in youth. PubMed, Embase, Cochrane Library, Web of Science, CINAHL, and ClinicalTrials. gov were searched for articles that (1): studied children (2); included resistance training (3); were randomized interventions; and (4) reported markers of metabolic function. The selected studies were analyzed using the Cochrane Risk-of-Bias Tool. Thirteen articles met inclusion criteria. Mean age ranged from 12.2 to 16.9 years, but most were limited to high school (n = 11) and overweight/obese (n = 12). Sample sizes (n = 22-304), session duration (40-60min), and intervention length (8-52 wks) varied. Exercise frequency was typically 2-3 d/wk. Resistance training was metabolically beneficial compared with control or resistance plus aerobic training in 5 studies overall and 3 out of the 4 studies with the fewest threats to bias (p ≤ .05); each was accompanied by beneficial changes in body composition, but only one study adjusted for change in body composition. Limited evidence suggests that resistance training may positively affect metabolic parameters in youth. Well-controlled resistance training interventions of varying doses are needed to definitively determine whether resistance training can mitigate metabolic dysfunction in youth and whether training benefits on metabolic parameters are independent of body composition changes.

Metabolism, obesity and the metabolic syndrome.

PubMed

Persson, Pontus B; Bondke Persson, Anja

2018-05-13

The current obesity epidemic has not only spread from Western to developing economies, but is affecting ever younger individuals. While oftentimes blamed on a slow metabolism or a hereditary component, one might consider whether family recipes and dietary habits are hereditary to a much higher degree than slow metabolism or big bones could ever be. Education is critical, so how do we explain metabolism to a layman, e.g. a parent of an obese child? - Metabolism denotes all the processes, which turn nutrients from our food into energy. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

L-carnosine affects the growth of Saccharomyces cerevisiae in a metabolism-dependent manner.

PubMed

Cartwright, Stephanie P; Bill, Roslyn M; Hipkiss, Alan R

2012-01-01

The dipeptide L-carnosine (β-alanyl-L-histidine) has been described as enigmatic: it inhibits growth of cancer cells but delays senescence in cultured human fibroblasts and extends the lifespan of male fruit flies. In an attempt to understand these observations, the effects of L-carnosine on the model eukaryote, Saccharomyces cerevisiae, were examined on account of its unique metabolic properties; S. cerevisiae can respire aerobically, but like some tumor cells, it can also exhibit a metabolism in which aerobic respiration is down regulated. L-Carnosine exhibited both inhibitory and stimulatory effects on yeast cells, dependent upon the carbon source in the growth medium. When yeast cells were not reliant on oxidative phosphorylation for energy generation (e.g. when grown on a fermentable carbon source such as 2% glucose), 10-30 mM L-carnosine slowed growth rates in a dose-dependent manner and increased cell death by up to 17%. In contrast, in media containing a non-fermentable carbon source in which yeast are dependent on aerobic respiration (e.g. 2% glycerol), L-carnosine did not provoke cell death. This latter observation was confirmed in the respiratory yeast, Pichia pastoris. Moreover, when deletion strains in the yeast nutrient-sensing pathway were treated with L-carnosine, the cells showed resistance to its inhibitory effects. These findings suggest that L-carnosine affects cells in a metabolism-dependent manner and provide a rationale for its effects on different cell types.

Acute exposure to the biopesticide azadirachtin affects parameters in the gills of common carp (Cyprinus carpio).

PubMed

Murussi, Camila R; Costa, Maiara D; Leitemperger, Jossiele W; Flores-Lopes, Fábio; Menezes, Charlene C; Loebens, Luisa; de Avila, Luis Antonio; Rizzetti, Tiele M; Adaime, Martha B; Zanella, Renato; Loro, Vania L

2016-02-01

The biopesticide, azadirachtin (Aza) is less hazardous to the environment, but may cause several toxic effects in aquatic organisms. The Cyprinus carpio (n=12, for all concentrations) after 10days of acclimation under controlled conditions, were exposed at 20, 40, and 60μL/L of Aza during 96h. After this period, fish were anesthetized and euthanized then mucus layer and gills collected. In this study, the effects of exposure to different Aza concentrations were analysed through a set of biomarkers: Na(+)/K(+-)ATPase, lipid peroxidation (TBARS), protein carbonyl (PC), superoxide dismutase (SOD), glutathione-S-transferase (GST), catalase (CAT), glutathione peroxidase (GPx), non-protein thiols (NPSH), ascorbic acid (AsA) and histological parameters and, yet, protein and glucose concentration in the surface area of mucous layer. Na(+)K(+-)ATPase was inhibited at 40 and 60μL/L compared to control. TBARS decreased at 40μL/L compared to control. PC, SOD and GST increased at 60μL/L in comparison to control. CAT increased at 20 and 60μL/L, and GPx increased in all Aza concentrations compared to control. NPSH decreased and AsA increased in all concentrations in comparison to control. Histological analyses demonstrated an increase in the intensity of the damage with increasing Aza concentration. Alterations in histological examination were elevation and hypertrophy of the epithelial cells of the secondary filament, hypertrophy and hyperplasia of the mucous and chlorate cells and lamellar aneurism. Glucose and protein concentrations in mucus layer increased at 60μL/L compared to control. In general, we suggest that 60μL/L Aza concentration affected several parameters causing disruptions carp metabolism. Copyright © 2015 Elsevier Inc. All rights reserved.

Deletion of Adseverin in Osteoclasts Affects Cell Structure But Not Bone Metabolism.

PubMed

Cao, Yixuan; Wang, Yongqiang; Sprangers, Sara; Picavet, Daisy I; Glogauer, Michael; McCulloch, Christopher A; Everts, Vincent

2017-08-01

Adseverin is an actin-severing/capping protein that may contribute to osteoclast differentiation in vitro but its role in bone remodeling of healthy animals is not defined. We analyzed bone and osteoclast structure in adseverin conditional null mice at alveolar and long bone sites. In wild-type and adseverin null mice, as measured by dual-energy X-ray absorptiometry, there were no differences of bone mineral content or bone mineral density, indicating no change of bone metabolism. In tibiae, TRAcP + osteoclasts were formed in comparable numbers in adseverin null and wild-type mice. Ultrastructural analysis showed normal and similar abundance of ruffled borders, sealing zones, and mitochondria, and with no difference of osteoclast nuclear numbers. In contrast, analyses of long bone showed that in the absence of adseverin osteoclasts were smaller (120 ± 13 vs. 274 ± 19 µm 2 ; p < 0.05), as were nuclear size and the surface area of cytoplasm. The nuclei of adseverin null osteoclasts exhibited more heterochromatin (31 ± 3%) than wild-type cells (8 ± 1%), suggesting that adseverin affects cell differentiation. The data indicate that in healthy, developing tissues, adseverin contributes to the regulation of osteoclast structure but not to bone metabolism in vivo.

A real-time measurement system for parameters of live biology metabolism process with fiber optics

NASA Astrophysics Data System (ADS)

Tao, Wei; Zhao, Hui; Liu, Zemin; Cheng, Jinke; Cai, Rong

2010-08-01

Energy metabolism is one of the basic life activities of cellular in which lactate, O2 and CO2 will be released into the extracellular environment. By monitoring the quantity of these parameters, the mitochondrial performance will be got. A continuous measurement system for the concentration of O2, CO2 and PH value is introduced in this paper. The system is made up of several small-sized fiber optics biosensors corresponding to the container. The setup of the system and the principle of measurement of several parameters are explained. The setup of the fiber PH sensor based on principle of light absorption is also introduced in detail and some experimental results are given. From the results we can see that the system can measure the PH value precisely suitable for cell cultivation. The linear and repeatable accuracies are 3.6% and 6.7% respectively, which can fulfill the measurement task.

Low-Dose of Bergamot-Derived Polyphenolic Fraction (BPF) Did Not Improve Metabolic Parameters in Second Generation Antipsychotics-Treated Patients: Results from a 60-days Open-Label Study.

PubMed

Bruno, Antonio; Pandolfo, Gianluca; Crucitti, Manuela; Cacciola, Massimo; Santoro, Vincenza; Spina, Edoardo; Zoccali, Rocco A; Muscatello, Maria R A

2017-01-01

Objectives: The nutraceutical approach to the management of metabolic syndrome (MetS) might be a promising strategy in the prevention of cardio-metabolic risk. Low-dose bergamot-derived polyphenolic fraction (BPF) has been proven effective in patients with MetS, as demonstrated by a concomitant improvement in lipemic and glycemic profiles. The present study was aimed to further explore, in a sample of subjects receiving second generation antipsychotics (SGAs), the effects on body weight and metabolic parameters of a low dose of BPF (500 mg/day) administered for 60 days. Methods: Twenty-eight outpatients treated with SGAs assumed BPF at single daily dose of 500 mg/day for 60 days. Body weight, BMI, fasting levels of glucose, total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol and triglycerides were determined; moreover, Brief Psychiatric Rating Scale (BPRS) was administered. Results: Low-dose BPF administration did not change clinical and metabolic parameters, as well as clinical symptoms in the study sample. At the end of the trial, among completers ( n = 24) only nine patients (37.5%) reached an LDL reduction >0 but <50%. Conclusions: Our results demonstrate that patients treated with SGAs may need higher BPF doses for obtaining the positive effects on body weight and metabolic parameters previously found in the general population at lower doses.

Low-Dose of Bergamot-Derived Polyphenolic Fraction (BPF) Did Not Improve Metabolic Parameters in Second Generation Antipsychotics-Treated Patients: Results from a 60-days Open-Label Study

PubMed Central

Bruno, Antonio; Pandolfo, Gianluca; Crucitti, Manuela; Cacciola, Massimo; Santoro, Vincenza; Spina, Edoardo; Zoccali, Rocco A.; Muscatello, Maria R. A.

2017-01-01

Objectives: The nutraceutical approach to the management of metabolic syndrome (MetS) might be a promising strategy in the prevention of cardio-metabolic risk. Low-dose bergamot-derived polyphenolic fraction (BPF) has been proven effective in patients with MetS, as demonstrated by a concomitant improvement in lipemic and glycemic profiles. The present study was aimed to further explore, in a sample of subjects receiving second generation antipsychotics (SGAs), the effects on body weight and metabolic parameters of a low dose of BPF (500 mg/day) administered for 60 days. Methods: Twenty-eight outpatients treated with SGAs assumed BPF at single daily dose of 500 mg/day for 60 days. Body weight, BMI, fasting levels of glucose, total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol and triglycerides were determined; moreover, Brief Psychiatric Rating Scale (BPRS) was administered. Results: Low-dose BPF administration did not change clinical and metabolic parameters, as well as clinical symptoms in the study sample. At the end of the trial, among completers (n = 24) only nine patients (37.5%) reached an LDL reduction >0 but <50%. Conclusions: Our results demonstrate that patients treated with SGAs may need higher BPF doses for obtaining the positive effects on body weight and metabolic parameters previously found in the general population at lower doses. PMID:28443024

Metabolic regulation and maximal reaction optimization in the central metabolism of a yeast cell

NASA Astrophysics Data System (ADS)

Kasbawati, Gunawan, A. Y.; Hertadi, R.; Sidarto, K. A.

2015-03-01

Regulation of fluxes in a metabolic system aims to enhance the production rates of biotechnologically important compounds. Regulation is held via modification the cellular activities of a metabolic system. In this study, we present a metabolic analysis of ethanol fermentation process of a yeast cell in terms of continuous culture scheme. The metabolic regulation is based on the kinetic formulation in combination with metabolic control analysis to indicate the key enzymes which can be modified to enhance ethanol production. The model is used to calculate the intracellular fluxes in the central metabolism of the yeast cell. Optimal control is then applied to the kinetic model to find the optimal regulation for the fermentation system. The sensitivity results show that there are external and internal control parameters which are adjusted in enhancing ethanol production. As an external control parameter, glucose supply should be chosen in appropriate way such that the optimal ethanol production can be achieved. For the internal control parameter, we find three enzymes as regulation targets namely acetaldehyde dehydrogenase, pyruvate decarboxylase, and alcohol dehydrogenase which reside in the acetaldehyde branch. Among the three enzymes, however, only acetaldehyde dehydrogenase has a significant effect to obtain optimal ethanol production efficiently.

Changes in bone mineral metabolism parameters, including FGF23, after discontinuing cinacalcet at kidney transplantation.

PubMed

Barros, Xoana; Fuster, David; Paschoalin, Raphael; Oppenheimer, Federico; Rubello, Domenico; Perlaza, Pilar; Pons, Francesca; Torregrosa, Jose V

2015-05-01

Little is known about the effects of the administration of cinacalcet in dialytic patients who are scheduled for kidney transplantation, and in particular about the changes in FGF23 and other mineral metabolism parameters after surgery compared with recipients not on cinacalcet at kidney transplantation. We performed a prospective observational cohort study with recruitment of consecutive kidney transplant recipients at our institution. Patients were classified according to whether they were under treatment with cinacalcet before transplantation. Bone mineral metabolism parameters, including C-terminal FGF23, were measured at baseline, on day 15, and at 1, 3, and 6 months after transplantation. In previously cinacalcet-treated patients, cinacalcet therapy was discontinued on the day of surgery and was not restarted after transplantation. A total of 48 kidney transplant recipients, 20 on cinacalcet at surgery and 28 cinacalcet non-treated patients, completed the follow-up. Serum phosphate declined significantly in the first 15 days after transplantation with no differences between the two groups, whereas cinacalcet-treated patients showed higher FGF23 levels, although not significant. After transplantation, PTH and serum calcium were significantly higher in cinacalcet-treated patients. We conclude that patients receiving cinacalcet on dialysis presented similar serum phosphate levels but higher PTH and serum calcium levels during the initial six months after kidney transplantation than cinacalcet non-treated patients. The group previously treated with cinacalcet before transplantation showed higher FGF23 levels without significant differences, so further studies should investigate its relevance in the management of these patients.

Altered erythropoiesis and iron metabolism in carriers of thalassemia

PubMed Central

Guimarães, Jacqueline S.; Cominal, Juçara G.; Silva-Pinto, Ana Cristina; Olbina, Gordana; Ginzburg, Yelena Z.; Nandi, Vijay; Westerman, Mark; Rivella, Stefano; de Souza, Ana Maria

2014-01-01

The thalassemia syndromes (α- and β-thalassemia) are the most common and frequent disorders associated with ineffective erythropoiesis. Imbalance of α- or β-globin chain production results in impaired red blood cell synthesis, anemia and more erythroid progenitors in the blood stream. While patients affected by these disorders show definitive altered parameters related to erythropoiesis, the relationship between the degree of anemia, altered erythropoiesis and dysfunctional iron metabolism have not been investigated in both α-thalassemia carriers (ATC) and β-thalassemia carriers (BTC). Here we demonstrate that ATC have a significantly reduced hepcidin and increased soluble transferrin receptor levels but relatively normal hematological findings. In contrast, BTC have several hematological parameters significantly different from controls, including increased soluble transferrin receptor and erythropoietin levels. These changings in both groups suggest an altered balance between erythropoiesis and iron metabolism. The index sTfR/log ferrin and (hepcidin/ferritin)/sTfR are respectively increased and reduced relative to controls, proportional to the severity of each thalassemia group. In conclusion, we showed in this study, for the first time in the literature, that thalassemia carriers have altered iron metabolism and erythropoiesis. PMID:25307880

Multiple dietary supplements do not affect metabolic and cardiovascular health

PubMed Central

Holloszy, John O.; Fontana, Luigi

2014-01-01

Dietary supplements are widely used for health purposes. However, little is known about the metabolic and cardiovascular effects of combinations of popular over-the-counter supplements, each of which has been shown to have anti-oxidant, anti-inflammatory and pro-longevity properties in cell culture or animal studies. This study was a 6-month randomized, single-blind controlled trial, in which 56 non-obese (BMI 21.0-29.9 kg/m2) men and women, aged 38 to 55 yr, were assigned to a dietary supplement (SUP) group or control (CON) group, with a 6-month follow-up. The SUP group took 10 dietary supplements each day (100 mg of resveratrol, a complex of 800 mg each of green, black, and white tea extract, 250 mg of pomegranate extract, 650 mg of quercetin, 500 mg of acetyl-l-carnitine, 600 mg of lipoic acid, 900 mg of curcumin, 1 g of sesamin, 1.7 g of cinnamon bark extract, and 1.0 g fish oil). Both the SUP and CON groups took a daily multivitamin/mineral supplement. The main outcome measures were arterial stiffness, endothelial function, biomarkers of inflammation and oxidative stress, and cardiometabolic risk factors. Twenty-four weeks of daily supplementation with 10 dietary supplements did not affect arterial stiffness or endothelial function in nonobese individuals. These compounds also did not alter body fat measured by DEXA, blood pressure, plasma lipids, glucose, insulin, IGF-1, and markers of inflammation and oxidative stress. In summary, supplementation with a combination of popular dietary supplements has no cardiovascular or metabolic effects in non-obese relatively healthy individuals. PMID:24659610

Resistin, an adipokine, may affect the improvement of insulin sensitivity in the metabolic syndrome patient treated with metformin.

PubMed

Yuan, Hong; Weng, Chunyan; Yang, Youbo; Huang, Lihua; Xing, Xiaowei

2013-12-01

The metabolic syndrome (MS) is a cluster of metabolic disorders arising from insulin resistance, characterized by the presence of central obesity, impaired fasting glucose level, dyslipidemia and hypertension. As the first-line medication, metformin is commonly used for MS to reduce insulin resistance. Comparing with rosiglitazone, metformin does not increase cardiovascular mortality risk in patients with MS. However, metformin is not good enough in improving insulin sensitivity. Its molecular mechanism is still not clear. Recent studies have demonstrated that resistin, an adipokine, could induce IR by both AMPK-dependent and AMPK-independent pathways. Though there were conflicting findings of resistin in metabolic syndrome or type 2 diabetes mellitus in different studies, resistin was significant decreased in the rosiglitazone treated patients than in the metformin-treated patients in most of studies. Here, we hypothesized that resistin, an adipokine, may affect the improvement of insulin sensitivity in the metabolic syndrome patient treated with metformin. This hypothesis could explain why rosiglitazone is superior to metformin in enhancement of insulin sensitivity. Copyright © 2013. Published by Elsevier Ltd.

Identifying critical road geometry parameters affecting crash rate and crash type.

PubMed

Othman, Sarbaz; Thomson, Robert; Lannér, Gunnar

2009-10-01

The objective of this traffic safety investigation was to find critical road parameters affecting crash rate (CR). The study was based on crash and road maintenance data from Western Sweden. More than 3000 crashes, reported from 2000 to 2005 on median-separated roads, were collected and combined with road geometric and surface data. The statistical analysis showed variations in CR when road elements changed confirming that road characteristics affect CR. The findings indicated that large radii right-turn curves were more dangerous than left curves, in particular, during lane changing manoeuvres. However sharper curves are more dangerous in both left and right curves. Moreover, motorway carriageways with no or limited shoulders have the highest CR when compared to other carriageway widths, while one lane carriageway sections on 2+1 roads were the safest. Road surface results showed that both wheel rut depth and road roughness have negative impacts on traffic safety.

In vitro fertilization affects growth and glucose metabolism in a sex-specific manner in an outbred mouse model.

PubMed

Donjacour, Annemarie; Liu, Xiaowei; Lin, Wingka; Simbulan, Rhodel; Rinaudo, Paolo F

2014-04-01

The preimplantation period is a time of reprogramming that may be vulnerable to disruption. This question has wide clinical relevance since the number of children conceived by in vitro fertilization (IVF) is rising. To examine this question, outbred mice (CF1 × B6D2F1) conceived by IVF and cultured using Whitten medium and 20% O2 (IVFWM group, less optimal) or K simplex optimized medium with amino acids and 5% O2 (IVFKAA group, more optimal and similar to conditions used in human IVF) were studied postnatally. We found that flushed blastocysts transferred to recipient mice provided the best control group (FB group), as this accounted for the effects of superovulation, embryo transfer, and litter size. We observed that many physiological parameters were normal. Reassuringly, IVFKAA offspring did not differ significantly from FB offspring. However, male IVFWM mice (but not females) were larger during the first 19 wk of life and exhibited glucose intolerance. Male IVFWM mice also showed enlarged left heart despite normal blood pressure. Expression of candidate imprinted genes (H19, Igf2, and Slc38a4) in multiple adult tissues did not show differences among the groups; only Slc38a4 was down-regulated following IVF (in both culture conditions) in female adipose tissue. These studies demonstrate that adult metabolism is affected by the type of conditions encountered during the preimplantation stage. Further, the postnatal growth trajectory and glucose homeostasis following ex vivo manipulation may be sexual dimorphic. Future work on the long-term effects of IVF offspring should focus on glucose metabolism and the cardiovascular system.

Early changes in parameters of bone and mineral metabolism during therapy for hyper- and hypothyroidism.

PubMed

Sabuncu, T; Aksoy, N; Arikan, E; Ugur, B; Tasan, E; Hatemi, H

2001-01-01

The effects of thyroid hormones on various organs and metabolic systems have been the focus of intensive research. In this study we investigated the mechanisms of the changes in some parameters of bone and mineral metabolism before and during treatment of hyper- and hypothyroidism. Our study groups were as follows; 1) Untreated hyperthyroid patients (n= 38), 2) Hyperthyroid patients treated for three months (n=21), 3) Untreated hypothyroid patients (n=27), 4) Hypothyroid patients treated for three months (n= 20), and 5) Euthyroid control subjects (age, weight, sex and menopausal status matched) (n = 47). As expected, the mean serum calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), and urinary Ca/creatinine and deoxypyridinoline (D-Pyr)/creatinine levels were higher in group-1 than in the control group. Serum PTH level was lower in group-1 than in group-5. However, after treatment for three months (group-2) we found that the serum and urinary levels of these parameters (except ALP) were not different than in the control group. Group-3 and group-4 did not show any differences in these parameters compared with group-5. Covariance analysis showed that urinary D-Pyr excretion had a positive, independent relationship to the serum free T3 level and age (P < 0.001 and P = 0.02, respectively). These results suggest that both bone formation and resorption markers increase in hyperthyroid patients, and with the treatment, particularly, in the period of first three months the bone resorption markers decrease rapidly. If the treatment is maintained the decrease slows, becoming more gradual. However, bone formation markers like ALP remain high in hyperthyroid patients during the treatment. In the light of this data, it is possible to conclude that osteoblastic activity lasts longer in hyperthyroidism. On the other hand, we demonstrated that these bone formation and resorption markers do not seem to be different in hypothyroid patients, even during the treatment, compared

Metabolic intervention to affect myocardial recovery following ischemia.

PubMed Central

Pasque, M K; Wechsler, A S

1984-01-01

Myocardial recovery during reperfusion following ischemia is critical to patient survival in a broad spectrum of clinical settings. Myocardial functional recovery following ischemia correlates well with recovery of myocardial adenosine triphosphate (ATP). Adenosine triphosphate recovery is uniformly incomplete during reperfusion following moderate ischemic injury and is therefore subject to manipulation by metabolic intervention. By definition ATP recovery is limited either by (1) energy availability and application in the phosphorylation of adenosine monophosphate (AMP) to ATP or (2) availability of AMP for this conversion. Experimental data suggest that substrate energy and the mechanisms required for its application in the creation of high energy phosphate bonds (AMP conversion to ATP) are more than adequate during reperfusion following moderate ischemic injury. Adenosine monophosphate availability, however, is inadequate following ischemia due to loss of diffusable adenine nucleotide purine metabolites. These purine precursors are necessary to fuel adenine nucleotide salvage pathways. Metabolic interventions that enhance AMP recovery rather than those that improve substrate energy availability during reperfusion are therefore recommended. The mechanisms of various metabolic interventions are discussed in this framework along with the rationale for or against their clinical application. PMID:6428332

[Association of cognitive impairments with carbohydrate and lipid metabolic parameters in type 2 diabetes mellitus patients undergoing coronary bypass surgery].

PubMed

Trubnikova, О А; Mamontova, A S; Tarasova, I V; Maleva, O V; Kuzmina, A A; Barbarash, O L

2015-01-01

AIM. To comparatively analyze neuropsychological parameters in patients with coronary artery disease (CAD) depending on the presence of type 2 diabetes mellitus (DM) and to evaluate their relationship to carbohydrate and lipid metabolic parameters. Fifty-two male patients with type 2 DM (mean age 58.0 ± 5.7 years) and 46 male patients without this condition (mean age 57.1 ± 6.2 years) were examined. Besides standard clinical examination, neurophysiological testing and determinations of glycated hemoglobin (HbA(1c),) and insulin concentrations, QUICKI index, and blood lipid profile were made. The patients with DM differed from those without DM in the lower speeds of sensorimotor reactions during neurodynamic testing and in worse attention values. In the patients with type 2 DM, the worse neuropsychological status was associated with the higher plasma concentrations of glucose, insulin, HbA(1c), total cholesterol, low-density lipoproteins, and triglycerides and with the lower levels of high-density lipoproteins. These relationships were not observed in the patients without DM. The patients with CAD concurrent with DM had a worse neurophysiological status than those without DM. Only the DM group demonstrated a relationship between cognitive impairments and carbohydrate metabolic markers. Carbohydrate and lipid metabolic disturbances may be assumed to make a negative contribution to the development of cognitive impairments in patients with CAD concurrent with type 2 DM.

High-fat diet reprograms the epigenome of rat spermatozoa and transgenerationally affects metabolism of the offspring

PubMed Central

de Castro Barbosa, Thais; Ingerslev, Lars R.; Alm, Petter S.; Versteyhe, Soetkin; Massart, Julie; Rasmussen, Morten; Donkin, Ida; Sjögren, Rasmus; Mudry, Jonathan M.; Vetterli, Laurène; Gupta, Shashank; Krook, Anna; Zierath, Juleen R.; Barrès, Romain

2015-01-01

Objectives Chronic and high consumption of fat constitutes an environmental stress that leads to metabolic diseases. We hypothesized that high-fat diet (HFD) transgenerationally remodels the epigenome of spermatozoa and metabolism of the offspring. Methods F0-male rats fed either HFD or chow diet for 12 weeks were mated with chow-fed dams to generate F1 and F2 offspring. Motile spermatozoa were isolated from F0 and F1 breeders to determine DNA methylation and small non-coding RNA (sncRNA) expression pattern by deep sequencing. Results Newborn offspring of HFD-fed fathers had reduced body weight and pancreatic beta-cell mass. Adult female, but not male, offspring of HFD-fed fathers were glucose intolerant and resistant to HFD-induced weight gain. This phenotype was perpetuated in the F2 progeny, indicating transgenerational epigenetic inheritance. The epigenome of spermatozoa from HFD-fed F0 and their F1 male offspring showed common DNA methylation and small non-coding RNA expression signatures. Altered expression of sperm miRNA let-7c was passed down to metabolic tissues of the offspring, inducing a transcriptomic shift of the let-7c predicted targets. Conclusion Our results provide insight into mechanisms by which HFD transgenerationally reprograms the epigenome of sperm cells, thereby affecting metabolic tissues of offspring throughout two generations. PMID:26977389

Factors affecting the sensitivity and specificity of the Heidelberg Retina Tomograph parameters to glaucomatous progression in disc photographs.

PubMed

Saarela, Ville; Falck, Aura; Airaksinen, P Juhani; Tuulonen, Anja

2012-03-01

To evaluate the factors affecting the sensitivity and specificity of the stereometric optic nerve head (ONH) parameters of the Heidelberg Retina Tomograph (HRT) to glaucomatous progression in stereoscopic ONH photographs. The factors affecting the sensitivity and specificity of the vertical cup : disc ratio, the cup : disc area ratio, the cup volume, the rim area and a linear discriminant function to progression were analysed. These parameters were the best indicators of progression in a retrospective study of 476 eyes. The reference standard for progression was the masked evaluation of stereoscopic ONH photographs. The factors having the most significant effect on the sensitivity and specificity of the stereometric ONH parameters were the reference height difference and the mean topography standard deviation (TSD), indicating image quality. Also, the change in the TSD and age showed consistent, but variably significant, influence on all parameters tested. The sensitivity and specificity improved when there was little change in the reference height, the image quality was good and stable, and the patients were younger. The sensitivity and specificity of the vertical cup : disc ratio was improved by a large disc area and high baseline cup : disc area ratio. The rim area showed a better sensitivity and specificity for progression with a small disc area and low baseline cup : disc area ratio. The factors affecting the sensitivity and specificity of the stereometric ONH parameters to glaucomatous progression in disc photographs are essentially the same as those affecting the measurement variability of the HRT. © 2010 The Authors. Acta Ophthalmologica © 2010 Acta Ophthalmologica Scandinavica Foundation.

Obesity, but not metabolic syndrome, negatively affects outcome in bipolar disorder.

PubMed

McElroy, S L; Kemp, D E; Friedman, E S; Reilly-Harrington, N A; Sylvia, L G; Calabrese, J R; Rabideau, D J; Ketter, T A; Thase, M E; Singh, V; Tohen, M; Bowden, C L; Bernstein, E E; Brody, B D; Deckersbach, T; Kocsis, J H; Kinrys, G; Bobo, W V; Kamali, M; McInnis, M G; Leon, A C; Faraone, S; Nierenberg, A A; Shelton, R C

2015-06-26

Examine the effects of obesity and metabolic syndrome on outcome in bipolar disorder. The Comparative Effectiveness of a Second Generation Antipsychotic Mood Stabilizer and a Classic Mood Stabilizer for Bipolar Disorder (Bipolar CHOICE) study randomized 482 participants with bipolar disorder in a 6-month trial comparing lithium- and quetiapine-based treatment. Baseline variables were compared between groups with and without obesity, with and without abdominal obesity, and with and without metabolic syndrome respectively. The effects of baseline obesity, abdominal obesity, and metabolic syndrome on outcomes were examined using mixed effects linear regression models. At baseline, 44.4% of participants had obesity, 48.0% had abdominal obesity, and 27.3% had metabolic syndrome; neither obesity, nor abdominal obesity, nor metabolic syndrome were associated with increased global severity, mood symptoms, or suicidality, or with poorer functioning or life satisfaction. Treatment groups did not differ on prevalence of obesity, abdominal obesity, or metabolic syndrome. By contrast, among the entire cohort, obesity was associated with less global improvement and less improvement in total mood and depressive symptoms, suicidality, functioning, and life satisfaction after 6 months of treatment. Abdominal obesity was associated with similar findings. Metabolic syndrome had no effect on outcome. Obesity and abdominal obesity, but not metabolic syndrome, were associated with less improvement after 6 months of lithium- or quetiapine-based treatment. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Respiratory and metabolic acidosis differentially affect the respiratory neuronal network in the ventral medulla of neonatal rats.

PubMed

Okada, Yasumasa; Masumiya, Haruko; Tamura, Yoshiyasu; Oku, Yoshitaka

2007-11-01

Two respiratory-related areas, the para-facial respiratory group/retrotrapezoid nucleus (pFRG/RTN) and the pre-Bötzinger complex/ventral respiratory group (preBötC/VRG), are thought to play key roles in respiratory rhythm. Because respiratory output patterns in response to respiratory and metabolic acidosis differ, we hypothesized that the responses of the medullary respiratory neuronal network to respiratory and metabolic acidosis are different. To test these hypotheses, we analysed respiratory-related activity in the pFRG/RTN and preBötC/VRG of the neonatal rat brainstem-spinal cord in vitro by optical imaging using a voltage-sensitive dye, and compared the effects of respiratory and metabolic acidosis on these two populations. We found that the spatiotemporal responses of respiratory-related regional activities to respiratory and metabolic acidosis are fundamentally different, although both acidosis similarly augmented respiratory output by increasing respiratory frequency. PreBötC/VRG activity, which is mainly inspiratory, was augmented by respiratory acidosis. Respiratory-modulated pixels increased in the preBötC/VRG area in response to respiratory acidosis. Metabolic acidosis shifted the respiratory phase in the pFRG/RTN; the pre-inspiratory dominant pattern shifted to inspiratory dominant. The responses of the pFRG/RTN activity to respiratory and metabolic acidosis are complex, and involve either augmentation or reduction in the size of respiratory-related areas. Furthermore, the activation pattern in the pFRG/RTN switched bi-directionally between pre-inspiratory/inspiratory and post-inspiratory. Electrophysiological study supported the results of our optical imaging study. We conclude that respiratory and metabolic acidosis differentially affect activities of the pFRG/RTN and preBötC/VRG, inducing switching and shifts of the respiratory phase. We suggest that they differently influence the coupling states between the pFRG/RTN and preBötC/VRG.

Identifying Critical Road Geometry Parameters Affecting Crash Rate and Crash Type

PubMed Central

Othman, Sarbaz; Thomson, Robert; Lannér, Gunnar

2009-01-01

The objective of this traffic safety investigation was to find critical road parameters affecting crash rate (CR). The study was based on crash and road maintenance data from Western Sweden. More than 3000 crashes, reported from 2000 to 2005 on median-separated roads, were collected and combined with road geometric and surface data. The statistical analysis showed variations in CR when road elements changed confirming that road characteristics affect CR. The findings indicated that large radii right-turn curves were more dangerous than left curves, in particular, during lane changing manoeuvres. However sharper curves are more dangerous in both left and right curves. Moreover, motorway carriageways with no or limited shoulders have the highest CR when compared to other carriageway widths, while one lane carriageway sections on 2+1 roads were the safest. Road surface results showed that both wheel rut depth and road roughness have negative impacts on traffic safety. PMID:20184841

Effects of cytochalasin B, colchicine and vincristine on the metabolism of isolated fat-cells

PubMed Central

Loten, Ernest G.; Jeanrenaud, Bernard

1974-01-01

1. Colchicine and vincristine only slightly inhibit the metabolism of glucose to CO2 and lipids by isolated fat-cells. 2. Prolonged incubation with these agents causes no further inhibition. 3. Cytochalasin B, however, inhibits glucose metabolism to both CO2 and lipids in fat-cells. 4. However, at a concentration that causes a strong inhibition of glucose metabolism cytochalasin B is without effect on the metabolism of pyruvate, lactate or arginine to these end products. The uptake of labelled α-aminoisobutyrate is likewise not modified. Similarly it does not affect release of glycerol or free fatty acid, or the actions of adrenaline, insulin or caffeine on these parameters. At 10μg/ml it slightly lowers ATP concentrations, an effect that does not occur at 2μg/ml. 5. The transport of fructose into adipocytes by a specific fructose-transport system is also not affected by the agent, but the uptake of 2-deoxyglucose is strongly inhibited. It is concluded that cytochalasin B may specifically inhibit the glucose-transport system of isolated fat-cells. 6. Cytochalasin A has a much weaker action than cytochalasin B on glucose metabolism. PMID:4455189

Atmospheric oxygen level affects growth trajectory, cardiopulmonary allometry and metabolic rate in the American alligator (Alligator mississippiensis)

PubMed Central

Owerkowicz, Tomasz; Elsey, Ruth M.; Hicks, James W.

2009-01-01

Summary Recent palaeoatmospheric models suggest large-scale fluctuations in ambient oxygen level over the past 550 million years. To better understand how global hypoxia and hyperoxia might have affected the growth and physiology of contemporary vertebrates, we incubated eggs and raised hatchlings of the American alligator. Crocodilians are one of few vertebrate taxa that survived these global changes with distinctly conservative morphology. We maintained animals at 30°C under chronic hypoxia (12% O2), normoxia (21% O2) or hyperoxia (30% O2). At hatching, hypoxic animals were significantly smaller than their normoxic and hyperoxic siblings. Over the course of 3 months, post-hatching growth was fastest under hyperoxia and slowest under hypoxia. Hypoxia, but not hyperoxia, caused distinct scaling of major visceral organs–reduction of liver mass, enlargement of the heart and accelerated growth of lungs. When absorptive and post-absorptive metabolic rates were measured in juvenile alligators, the increase in oxygen consumption rate due to digestion/absorption of food was greatest in hyperoxic alligators and smallest in hypoxic ones. Hyperoxic alligators exhibited the lowest breathing rate and highest oxygen consumption per breath. We suggest that, despite compensatory cardiopulmonary remodelling, growth of hypoxic alligators is constrained by low atmospheric oxygen supply, which may limit their food utilisation capacity. Conversely, the combination of elevated metabolism and low cost of breathing in hyperoxic alligators allows for a greater proportion of metabolised energy to be available for growth. This suggests that growth and metabolic patterns of extinct vertebrates would have been significantly affected by changes in the atmospheric oxygen level. PMID:19376944

Impaired copper and iron metabolism in blood cells and muscles of patients affected by copper deficiency myeloneuropathy.

PubMed

Spinazzi, Marco; Sghirlanzoni, Angelo; Salviati, Leonardo; Angelini, Corrado

2014-12-01

Severe copper deficiency leads in humans to a treatable multisystem disease characterized by anaemia and degeneration of spinal cord and nerves, but its mechanisms have not been investigated. We tested whether copper deficit leads to alterations in fundamental copper-dependent proteins and in iron metabolism in blood and muscles of patients affected by copper deficiency myeloneuropathy, and if these metabolic abnormalities are associated with compensatory mechanisms for copper maintenance. We evaluated the expression of critical copper enzymes, of iron-related proteins, and copper chaperones and transporters in blood and muscles from five copper-deficient patients presenting with subacute sensory ataxia, muscle paralysis, liver steatosis and variable anaemia. Severe copper deficiency was caused by chronic zinc intoxication in all of the patients, with an additional history of gastrectomy in two cases. The antioxidant enzyme SOD1 and subunit 2 of cytochrome c oxidase were significantly decreased in blood cells and in muscles of copper-deficient patients compared with controls. In muscle, the iron storage protein ferritin was dramatically reduced despite normal serum ferritin, and the expression of the haem-proteins cytochrome c and myoglobin was impaired. Muscle expression of the copper transporter CTR1 and of the copper chaperone CCS, was strikingly increased, while antioxidant protein 1 was diminished. copper-dependent enzymes with critical functions in antioxidant defences, in mitochondrial energy production, and in iron metabolism are affected in blood and muscles of patients with profound copper deficiency leading to myeloneuropathy. Homeostatic mechanisms are strongly activated to increase intracellular copper retention. © 2013 British Neuropathological Society.

Network reconstruction of platelet metabolism identifies metabolic signature for aspirin resistance

NASA Astrophysics Data System (ADS)

Thomas, Alex; Rahmanian, Sorena; Bordbar, Aarash; Palsson, Bernhard Ø.; Jamshidi, Neema

2014-01-01

Recently there has not been a systematic, objective assessment of the metabolic capabilities of the human platelet. A manually curated, functionally tested, and validated biochemical reaction network of platelet metabolism, iAT-PLT-636, was reconstructed using 33 proteomic datasets and 354 literature references. The network contains enzymes mapping to 403 diseases and 231 FDA approved drugs, alluding to an expansive scope of biochemical transformations that may affect or be affected by disease processes in multiple organ systems. The effect of aspirin (ASA) resistance on platelet metabolism was evaluated using constraint-based modeling, which revealed a redirection of glycolytic, fatty acid, and nucleotide metabolism reaction fluxes in order to accommodate eicosanoid synthesis and reactive oxygen species stress. These results were confirmed with independent proteomic data. The construction and availability of iAT-PLT-636 should stimulate further data-driven, systems analysis of platelet metabolism towards the understanding of pathophysiological conditions including, but not strictly limited to, coagulopathies.

Personality and performance are affected by age and early life parameters in a small primate.

PubMed

Zablocki-Thomas, Pauline B; Herrel, Anthony; Hardy, Isabelle; Rabardel, Lucile; Perret, Martine; Aujard, Fabienne; Pouydebat, Emmanuelle

2018-05-01

A whole suite of parameters is likely to influence the behavior and performance of individuals as adults, including correlations between phenotypic traits or an individual's developmental context. Here, we ask the question whether behavior and physical performance traits are correlated and how early life parameters such as birth weight, litter size, and growth can influence these traits as measured during adulthood. We studied 486 captive gray mouse lemurs ( Microcebus murinus ) and measured two behavioral traits and two performance traits potentially involved in two functions: exploration behavior with pull strength and agitation score with bite force. We checked for the existence of behavioral consistency in behaviors and explored correlations between behavior, performance, morphology. We analyzed the effect of birth weight, growth, and litter size, while controlling for age, sex, and body weight. Behavior and performance were not correlated with one another, but were both influenced by age. Growth rate had a positive effect on adult morphology, and birth weight significantly affected emergence latency and bite force. Grip strength was not directly affected by early life traits, but bite performance and exploration behavior were impacted by birth weight. This study shows how early life parameters impact personality and performance.

Pseudotachometer for mobile metabolic analyzer

NASA Technical Reports Server (NTRS)

Currie, J. R.

1974-01-01

Metabolic analyzer determines a patient's walking or ambulation speed and simultaneously measures his metabolic parameters. Analyzer is designed to move at some preselected human ambulation speed. During test, patient is connected to system and follows analyzer closely while his metabolic data is being monitored.

Anaesthesia and changes in parameters that reflect glucose metabolism in pigs - a pilot study.

PubMed

Manell, Elin; Jensen-Waern, Marianne; Hedenqvist, Patricia

2017-10-01

Pigs are commonly used in diabetes research due to their many physiological similarities to humans. They are especially useful in imaging procedures because of their large size. However, to achieve imaging procedures the pig must lie completely still, and thus needs to be anaesthetized. Most anaesthetic drugs used in laboratory animals affect carbohydrate metabolism by the inhibition of insulin release. The aim of this pilot study was primarily to develop an anaesthetic protocol for pigs that did not have an effect on blood glucose levels throughout the 3 h of anaesthesia; and secondly, to evaluate the most promising protocol in combination with an oral glucose tolerance test (OGTT). Two anaesthetic protocols were used in four growing pigs. Intravenous propofol infusion caused hyperglycaemia in three out of four pigs within 5-10 min after induction and was therefore excluded. Intravenous infusion with tiletamine, zolazepam and butorphanol (TZB) for 3 h did not affect blood glucose levels. The pigs underwent OGTT twice, once without anaesthesia and once with TZB induction after glucose intake. Anaesthesia during OGTT resulted in a lower area under the curve (AUC) of glucose ( P < 0.05), higher AUC of glucagon ( P < 0.05) and an insulin response less than 10% of that during OGTT without anaesthesia. In conclusion, long-term infusion anaesthesia with TZB does not affect glucose homeostasis in pigs. However, the protocol is not effective when combined with OGTT, as glucose, insulin and glucagon levels are affected.

A Quantitative Study of Oxygen as a Metabolic Regulator

NASA Technical Reports Server (NTRS)

Radhakrishnan, Krishnan; LaManna, Joseph C.; Cabrera, Marco E.

1999-01-01

An acute reduction in oxygen (O2) delivery to a tissue is generally associated with a decrease in phosphocreatine, increases in ADP, NADH/NAD, and inorganic phosphate, increased rates of glycolysis and lactate production, and reduced rates of pyruvate and fatty acid oxidation. However, given the complexity of the human bioenergetic system and its components, it is difficult to determine quantitatively how cellular metabolic processes interact to maintain ATP homeostasis during stress (e.g., hypoxia, ischemia, and exercise). Of special interest is the determination of mechanisms relating tissue oxygenation to observed metabolic responses at the tissue, organ, and whole body levels and the quantification of how changes in tissue O2 availability affect the pathways of ATP synthesis and the metabolites that control these pathways. In this study, we extend a previously developed mathematical model of human bioenergetics to provide a physicochemical framework that permits quantitative understanding of O2 as a metabolic regulator. Specifically, the enhancement permits studying the effects of variations in tissue oxygenation and in parameters controlling the rate of cellular respiration on glycolysis, lactate production, and pyruvate oxidation. The whole body is described as a bioenergetic system consisting of metabolically distinct tissue/organ subsystems that exchange materials with the blood. In order to study the dynamic response of each subsystem to stimuli, we solve the ordinary differential equations describing the temporal evolution of metabolite levels, given the initial concentrations. The solver used in the present study is the packaged code LSODE, as implemented in the NASA Lewis kinetics and sensitivity analysis code, LSENS. A major advantage of LSENS is the efficient procedures supporting systematic sensitivity analysis, which provides the basic methods for studying parameter sensitivities (i.e., changes in model behavior due to parameter variation

β-adrenergic receptor inhibition affects cerebral glucose metabolism, motor performance, and inflammatory response after traumatic brain injury.

PubMed

Ley, Eric J; Clond, Morgan A; Bukur, Marko; Park, Ryan; Chervonski, Michael; Dagliyan, Grant; Margulies, Dan R; Lyden, Patrick D; Conti, Peter S; Salim, Ali

2012-07-01

The purpose of this study was to evaluate how β-adrenergic receptor inhibition after traumatic brain injury (TBI) alters changes in early cerebral glucose metabolism and motor performance, as well as cerebral cytokine and heat shock protein (HSP) expression. Mouse cerebral glucose metabolism was measured by microPET fluorodeoxyglucose uptake and converted into standardized uptake values (SUV). Four groups of C57/Bl6 mice (wild type [WT]) were initially evaluated: sham or TBI, followed by tail vein injection of either saline or a nonselective β-adrenergic receptor inhibitor (propranolol, 4 mg/kg). Then motor performance, cerebral cytokine, and HSP70 expression were studied at 12 hours and 24 hours after sham injury or TBI in WT mice treated with saline or propranolol and in β1-adrenergic/β2-adrenergic receptor knockout (BARKO) mice treated with saline. Cerebral glucose metabolism was significantly reduced after TBI (mean SUV TBI, 1.63 vs. sham 1.97, p < 0.01) and propranolol attenuated this reduction (mean SUV propranolol, 1.89 vs. saline 1.63, p < 0.01). Both propranolol and BARKO reduced motor deficits at 24 hours after injury, but only BARKO had an effect at 12 hours after injury. TBI WT mice treated with saline performed worse than propranolol mice at 24 hours after injury on rotarod (23 vs. 44 seconds, p < 0.01) and rearing (130 vs. 338 events, p = 0.01) results. At 24 hours after injury, sham BARKO and TBI BARKO mice were similar on rotarod (21 vs. 19 seconds, p = 0.53), ambulatory testing (2,891 vs. 2,274 events, p = 0.14), and rearing (129 vs. 64 events, p = 0.09) results. Interleukin 1β expression was affected by BARKO and propranolol after TBI; attenuation of interleukin 6 and increased HSP70 expression were noted only with BARKO. β-adrenergic receptor inhibition affects cerebral glucose metabolism, motor performance, as well as cerebral cytokine and HSP expression after TBI.

The effects of diet, sulfonylurea, and Repaglinide therapy on clinical and metabolic parameters in type 2 diabetic patients during Ramadan.

PubMed

Sari, Ramazan; Balci, Mustafa Kemal; Akbas, Sadika Halide; Avci, Berkant

2004-05-01

Diabetes and its treatment can cause problems for the Muslim population. The aim of this study was to evaluate the effect of different therapy models on clinical and metabolic status in type 2 diabetic patients during Ramadan. Fifty-two type 2 diabetic patients were included to this study. Twelve of patients were on diabetic diet only before and during Ramadan (Group 1). Forty of patients had had sulfonylurea (Glimepiride 23 patients, gliclazide 17 patients) before Ramadan. Thirteen of these patients were on a single dose sulfonylurea (Glimepiride 8 patients, gliclazide 5 patients) (Group 2) and 27 were on Repaglinide 2 x 2 mg (Group 3) during Ramadan. Beta-hydroxybutyric acid, glucose, fructosamine, HbA1c, lipid levels and body weight were measured before and after Ramadan. Body weight, fasting plasma glucose, fructosamine, HbA1c, total cholesterol were not changed in groups during the study. Triglyceride level decreased after Ramadan in groups 2 (p = 0.002) and 3 (p = 0.024). HDL-cholesterol level increased in group 3 (p = 0.022). Fasting capillary beta-hydroxybutyric acid level increased in group 1 (p = 0.034) and didn't change in groups 2 and 3 during the Ramadan. Only one hypoglycemic event occurred at day 6 of Ramadan in patients in group 2 (the patient was on 3 mg glimepiride). Our results conclude that Ramadan fasting affects metabolic parameters in type 2 diabetes and hypoglycemia should be kept in mind especially in patients using sulfonylurea treatment. Ramadan fasting is not advised for type 2 diabetics while taking medical therapy. If the patient wants Ramadan fasting, these patients using Repaglinide can reduce the frequency of hypoglycemia.

Effects of hiking at moderate and low altitude on cardiovascular parameters in male patients with metabolic syndrome: Austrian Moderate Altitude Study.

PubMed

Neumayr, Günther; Fries, Dietmar; Mittermayer, Markus; Humpeler, Egon; Klingler, Anton; Schobersberger, Wolfgang; Spiesberger, Reinhard; Pokan, Rochus; Schmid, Peter; Berent, Robert

2014-09-01

Physical activity is a cornerstone in therapy for patients with metabolic syndrome. Walking and hiking in a mountain scenery represents an ideal approach to make them move. The Austrian Moderate Altitude Study (AMAS) 2000 main study is a randomized controlled trial to investigate the cardiovascular effects of hiking at moderate altitude on patients with metabolic syndrome compared with a control group at low altitude, to assess a potential altitude-specific effect. Seventy-one male patients with metabolic syndrome were randomly assigned to a moderate altitude group (at 1700 m), with 36 participants, or to a low altitude group (at 200 m), with 35 participants. The 3-week vacation program included 12 hiking tours (4 per week, average duration 2.5 hours, intensity 55% to 65% of heart rate maximum). Physical parameters, performance capacity, 24-hour blood pressure, and heart rate profiles were obtained before, during, and after the stay. In both groups, we found a significant mean weight loss of -3.13 kg; changes in performance capacity were minor. Systolic, diastolic, and mean arterial pressures and circadian heart rate profiles were significantly reduced in both groups, with no differences between them. Consequently, the pressure-rate product was reduced as well. All study participants tolerated the vacation well without any adverse events. A 3-week hiking vacation at moderate or low altitude is safe for patients with metabolic syndrome and provides several improvements in their cardiovascular parameters. The cardiovascular benefits achieved are more likely to be the result of regular physical activity than the altitude-specific effect of a mountain environment. Copyright © 2014 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

Association of adiponectin/leptin ratio with carbohydrate and lipid metabolism parameters in HIV-infected patients during antiretroviral therapy.

PubMed

Tiliscan, Catalin; Arama, Victoria; Mihailescu, Raluca; Munteanu, Daniela; Iacob, Diana Gabriela; Popescu, Cristina; Catana, Remulus; Negru, Anca; Lobodan, Alina; Arama, Stefan Sorin

2018-02-16

Adiponectin and leptin are adipose tissue hormones that regulate important lipid and glucose metabolic pathways. Our objective was to evaluate the interplay of these hormones described by the adiponectin/leptin ratio (ALR) in correlation to lipid and carbohydrate metabolism parameters in nondiabetic HIV-infected patients during antiretroviral therapy (ART). We enrolled consecutive nondiabetic patients with confirmed HIV infection, undergoing stable ART regimens for at least six months. Blood samples were collected and tested for immunological and virological parameters, adiponectin and leptin, fasting insulin, fasting plasma glucose, fasting triglycerides, total cholesterol, LDL cholesterol, and HDL cholesterol. ALR was computed for each patient. Resistance to insulin was assessed by calculating the Quantitative Insulin Sensitivity Check Index (QUICKI). We enrolled 87 HIV-infected persons, with a mean age of 31.7 years (range: 18-65), including 47 men (mean age = 32.8 years) and 40 women (mean age = 30.5 years). The median value of ALR was 6.8 (interquartile range - IQR = 17.1). In male patients, ALR was inversely associated with the serum level of triglycerides (R = 0.285, p = 0.05), total cholesterol (R = 0.326, p = 0.02), and LDL cholesterol (R = 0.298, p = 0.04). Also for the male cohort, an increase in ALR seemed to improve insulin sensitivity (R = 0.323, p = 0.02) and serum HDL cholesterol (R = 0.597, p = 0.01). None of these correlations were observed in HIV-infected women. Adiponectin and leptin seem to play important but different gender-specific roles in the pathogenesis of lipid and glucose metabolism of HIV-infected patients undergoing antiretroviral therapy. ALR, adiponectin/leptin ratio; BMI, body mass index; LDL, low-density lipoprotein; HDL, high-density lipoprotein; QUICKI, Quantitative Insulin Sensitivity Check Index.

MAPK14/p38α-dependent modulation of glucose metabolism affects ROS levels and autophagy during starvation.

PubMed

Desideri, Enrico; Vegliante, Rolando; Cardaci, Simone; Nepravishta, Ridvan; Paci, Maurizio; Ciriolo, Maria Rosa

2014-09-01

Increased glycolytic flux is a common feature of many cancer cells, which have adapted their metabolism to maximize glucose incorporation and catabolism to generate ATP and substrates for biosynthetic reactions. Indeed, glycolysis allows a rapid production of ATP and provides metabolic intermediates required for cancer cells growth. Moreover, it makes cancer cells less sensitive to fluctuations of oxygen tension, a condition usually occurring in a newly established tumor environment. Here, we provide evidence for a dual role of MAPK14 in driving a rearrangement of glucose metabolism that contributes to limiting reactive oxygen species (ROS) production and autophagy activation in condition of nutrient deprivation. We demonstrate that MAPK14 is phosphoactivated during nutrient deprivation and affects glucose metabolism at 2 different levels: on the one hand, it increases SLC2A3 mRNA and protein levels, resulting in a higher incorporation of glucose within the cell. This event involves the MAPK14-mediated enhancement of HIF1A protein stability. On the other hand, MAPK14 mediates a metabolic shift from glycolysis to the pentose phosphate pathway (PPP) through the modulation of PFKFB3 (6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase 3) degradation by the proteasome. This event requires the presence of 2 distinct degradation sequences, KEN box and DSG motif Ser273, which are recognized by 2 different E3 ligase complexes. The mutation of either motif increases PFKFB3 resistance to starvation-induced degradation. The MAPK14-driven metabolic reprogramming sustains the production of NADPH, an important cofactor for many reduction reactions and for the maintenance of the proper intracellular redox environment, resulting in reduced levels of ROS. The final effect is a reduced activation of autophagy and an increased resistance to nutrient deprivation.

Working parameters affecting earth-air heat exchanger (EAHE) system performance for passive cooling: A review

NASA Astrophysics Data System (ADS)

Darius, D.; Misaran, M. S.; Rahman, Md. M.; Ismail, M. A.; Amaludin, A.

2017-07-01

The study on the effect of the working parameters such as pipe material, pipe length, pipe diameter, depth of burial of the pipe, air flow rate and different types of soils on the thermal performance of earth-air heat exchanger (EAHE) systems is very crucial to ensure that thermal comfort can be achieved. In the past decade, researchers have performed studies to develop numerical models for analysis of EAHE systems. Until recently, two-dimensional models replaced the numerical models in the 1990s and in recent times, more advanced analysis using three-dimensional models, specifically the Computational Fluid Dynamics (CFD) simulation in the analysis of EAHE system. This paper reviews previous models used to analyse the EAHE system and working parameters that affects the earth-air heat exchanger (EAHE) thermal performance as of February 2017. Recent findings on the parameters affecting EAHE performance are also presented and discussed. As a conclusion, with the advent of CFD methods, investigational work have geared up to modelling and simulation work as it saves time and cost. Comprehension of the EAHE working parameters and its effect on system performance is largely established. However, the study on type of soil and its characteristics on the performance of EAHEs systems are surprisingly barren. Therefore, future studies should focus on the effect of soil characteristics such as moisture content, density of soil, and type of soil on the thermal performance of EAHEs system.

Acidosis, but Not Alkalosis, Affects Anaerobic Metabolism and Performance in a 4-km Time Trial.

PubMed

Correia-Oliveira, Carlos Rafaell; Lopes-Silva, João Paulo; Bertuzzi, Romulo; McConell, Glenn K; Bishop, David John; Lima-Silva, Adriano Eduardo; Kiss, Maria Augusta Peduti Dal'molin

2017-09-01

This study aimed to determine the effect of preexercise metabolic acidosis and alkalosis on power output (PO) and aerobic and anaerobic energy expenditure during a 4-km cycling time trial (TT). Eleven recreationally trained cyclists (V˙O2peak 54.1 ± 9.3 mL·kg·min) performed a 4-km TT 100 min after ingesting in a double-blind matter 0.15 g·kg of body mass of ammonium chloride (NH4Cl, acidosis), 0.3 g·kg of sodium bicarbonate (NaHCO3, alkalosis), or 0.15 g·kg of CaCO3 (placebo). A preliminary study (n = 7) was conducted to establish the optimal doses to promote the desirable preexercise blood pH alterations without gastrointestinal distress. Data for PO, aerobic and anaerobic energy expenditure, and blood and respiratory parameters were averaged for each 1 km and compared between conditions using two-way repeated-measures ANOVA (condition and distance factors). Gastrointestinal discomfort was analyzed qualitatively. Compared with placebo (pH 7.37 ± 0.02, [HCO3]: 27.5 ± 2.6 mmol·L), the NaHCO3 ingestion resulted in a preexercise blood alkalosis (pH +0.06 ± 0.04, [HCO3]: +4.4 ± 2.0 mmol·L, P < 0.05), whereas NH4Cl resulted in a blood acidosis (pH -0.05 ± 0.03, [HCO3]: -4.8 ± 2.1 mmol·L, P < 0.05). Anaerobic energy expenditure rate and PO were reduced throughout the trial in NH4Cl compared with placebo and NaHCO3, resulting in a lower total anaerobic work and impaired performance (P < 0.05). Plasma lactate, V˙CO2, and end-tidal CO2 partial pressure were lower and the V˙E/V˙CO2 higher throughout the trial in NH4Cl compared with placebo and NaHCO3 (P < 0.05). There was no difference between NaHCO3 and placebo for any of these variables (P > 0.05). Minimal gastrointestinal distress was noted in all conditions. Preexercise acidosis, but not alkalosis, affects anaerobic metabolism and PO during a 4-km cycling TT.

Different metabolic responses induced by long-term interdisciplinary therapy in obese adolescents related to ACE I/D polymorphism

PubMed Central

Almeida, Sandro S; Corgosinho, Flavia C; Amorim, Carlos EN; Gregnani, Marcos F; Campos, Raquel MS; Masquio, Deborah CL; Sanches, Priscila L; Ganen, Aline P; Pesquero, João B; Dâmaso, Ana R; Mello, Marco T; Tufik, Sergio; Araújo, Ronaldo C

2017-01-01

Introduction: The main purpose of the present study was to investigate whether I/D polymorphism of the ACE gene might affect metabolic changes related to the metabolic syndrome through a long-term interdisciplinary therapy in obese adolescents. Methods: In total, 125 obese adolescents who entered the interdisciplinary obesity programme were assigned to the following two subgroups: metabolic syndrome or non-metabolic syndrome. They were evaluated at baseline and after 1 year. Genomic DNA was extracted from circulating leukocytes. Results: Subjects with the II genotype in the non-metabolic syndrome group were only to increase their fat-free mass after therapy. Regarding lipid profile, subjects with ID and DD genotypes from both groups reduced their low-density lipoprotein cholesterol levels significantly. The metabolic parameters from the ID and DD genotypes of the non-metabolic syndrome group showed a significantly improved insulin response. Conclusion: In the present study, we showed that the ACE polymorphism was able to influence the fat-free mass in the I-carry allele in the non-metabolic syndrome group positively. In addition, the I-carry allele was able to improve the insulin resistance of the metabolic syndrome group significantly. These results suggest that the ACE I/D genotypes can influence, in different ways, the specific parameters of metabolism among obese adolescents submitted for long-term interdisciplinary therapy. PMID:28504003

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

PubMed

Basu, Arpita; Sanchez, Karah; Leyva, Misti J; Wu, Mingyuan; Betts, Nancy M; Aston, Christopher E; Lyons, Timothy J

2010-02-01

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. Randomized, controlled prospective trial. General Clinical Research Center (GCRC) at University of Oklahoma Health Sciences Center (OUHSC). Thirty-five subjects with obesity and metabolic syndrome were recruited in age- and gender-matched trios and were randomly assigned to the control (4 cups water/d), green tea (4 cups/d), or green tea extract (2 capsules and 4 cups water/d) group for 8 weeks. The tea and extract groups had similar dosing of epiogallocatechin-3-gallate (EGCG), the active compound in green tea. Anthropometrics, blood pressure, fasting glucose and lipids, nuclear magnetic resonance (NMR)-based lipid particle size, safety parameters, biomarkers of oxidative stress (oxidized low-density lipoprotein [LDL], myeloperoxidase [MPO], malondialdehyde and hydroxynonenals [MDA and HNE]), and free catechins were analyzed at screen and at 4 and 8 weeks of the study. Pairwise comparisons showed green tea beverage and green tea extracts caused a significant decrease in body weight and body mass index (BMI) versus controls at 8 weeks (-2.5 +/- 0.7 kg, p < 0.01, and -1.9 +/- 0.6, p < 0.05, respectively). Green tea beverage showed a decreasing trend in LDL-cholesterol and LDL/high-density lipoprotein (HDL) versus controls (p < 0.1). Green tea beverage also significantly decreased MDA and HNE (-0.39 +/- 0.06 microM, p < 0.0001) versus controls. Plasma free catechins were detectable in both beverage and extract groups versus controls at screen and at 8 weeks, indicating compliance and bioavailability of green tea catechins. Green tea beverage consumption (4 cups/d) or extract supplementation (2 capsules/d) for 8 weeks significantly decreased body weight and BMI. Green tea beverage further lowered lipid peroxidation versus age- and

Role of androgen excess on metabolic aberrations and cardiovascular risk in women with polycystic ovary syndrome.

PubMed

Christakou, Charikleia D; Diamanti-Kandarakis, Evanthia

2008-11-01

Polycystic ovary syndrome (PCOS) is associated with a clustering of metabolic and cardiovascular risk factors. Insulin resistance is implicated as the major player in the metabolic abnormalities and contributes to the increased cardiovascular risk associated with the syndrome. However, androgen excess appears to participate as an independent parameter, which further aggravates the cardiovascular and metabolic aberrations in affected women with PCOS. The resultant impact of hyperandrogenemia possibly acquires clinical significance for women's health in the context of PCOS, particularly since recent data support an increased incidence of coronary artery disease and of cardiovascular events directly related to androgen levels in women with the syndrome.

An Investigation of TIG welding parameters on microhardness and microstructure of heat affected zone of HSLA steel

NASA Astrophysics Data System (ADS)

Musa, M. H. A.; Maleque, M. A.; Ali, M. Y.

2018-01-01

Nowadays a wide variety of metal joining methods are used in fabrication industries. In this study, the effect of various welding parameters of the TIG welding process on microhardness, depth, and microstructure of the heat-affected zone (HAZ) of L450 HSLA steel and optimizing these process parameters following Taguchi experimental design was investigated. The microhardness tended to increase significantly with the increase of welding speed from 1.0 to 2.5 mm/s whereas the width of HAZ decreased. The current and arc voltage was found to be less significant in relative comparison. Microstructures of the welded samples were also studied to analyze the changes in the microstructure of the material in terms of ferrite, pearlite, bainite, and martensite formations. Welding speed was found to be the most significant factors leading to changes in microhardness and metallurgical properties. The increase of welding heat input caused an increase in width (depth) of HAZ and the growth of prior austenite grains and then enlarged the grain size of coarse grain heat affected zone (CGHAZ). However, the amount of martensite in the HAZ decreased accompanied by an opposite change of paint. It was observed that the hardness properties and the microstructural feature of HAZ area was strongly affected by the welding parameters.

4D dose simulation in volumetric arc therapy: Accuracy and affecting parameters

PubMed Central

Werner, René

2017-01-01

Radiotherapy of lung and liver lesions has changed from normofractioned 3D-CRT to stereotactic treatment in a single or few fractions, often employing volumetric arc therapy (VMAT)-based techniques. Potential unintended interference of respiratory target motion and dynamically changing beam parameters during VMAT dose delivery motivates establishing 4D quality assurance (4D QA) procedures to assess appropriateness of generated VMAT treatment plans when taking into account patient-specific motion characteristics. Current approaches are motion phantom-based 4D QA and image-based 4D VMAT dose simulation. Whereas phantom-based 4D QA is usually restricted to a small number of measurements, the computational approaches allow simulating many motion scenarios. However, 4D VMAT dose simulation depends on various input parameters, influencing estimated doses along with mitigating simulation reliability. Thus, aiming at routine use of simulation-based 4D VMAT QA, the impact of such parameters as well as the overall accuracy of the 4D VMAT dose simulation has to be studied in detail–which is the topic of the present work. In detail, we introduce the principles of 4D VMAT dose simulation, identify influencing parameters and assess their impact on 4D dose simulation accuracy by comparison of simulated motion-affected dose distributions to corresponding dosimetric motion phantom measurements. Exploiting an ITV-based treatment planning approach, VMAT treatment plans were generated for a motion phantom and different motion scenarios (sinusoidal motion of different period/direction; regular/irregular motion). 4D VMAT dose simulation results and dose measurements were compared by local 3% / 3 mm γ-evaluation, with the measured dose distributions serving as ground truth. Overall γ-passing rates of simulations and dynamic measurements ranged from 97% to 100% (mean across all motion scenarios: 98% ± 1%); corresponding values for comparison of different day repeat measurements were

4D dose simulation in volumetric arc therapy: Accuracy and affecting parameters.

PubMed

Sothmann, Thilo; Gauer, Tobias; Werner, René

2017-01-01

Radiotherapy of lung and liver lesions has changed from normofractioned 3D-CRT to stereotactic treatment in a single or few fractions, often employing volumetric arc therapy (VMAT)-based techniques. Potential unintended interference of respiratory target motion and dynamically changing beam parameters during VMAT dose delivery motivates establishing 4D quality assurance (4D QA) procedures to assess appropriateness of generated VMAT treatment plans when taking into account patient-specific motion characteristics. Current approaches are motion phantom-based 4D QA and image-based 4D VMAT dose simulation. Whereas phantom-based 4D QA is usually restricted to a small number of measurements, the computational approaches allow simulating many motion scenarios. However, 4D VMAT dose simulation depends on various input parameters, influencing estimated doses along with mitigating simulation reliability. Thus, aiming at routine use of simulation-based 4D VMAT QA, the impact of such parameters as well as the overall accuracy of the 4D VMAT dose simulation has to be studied in detail-which is the topic of the present work. In detail, we introduce the principles of 4D VMAT dose simulation, identify influencing parameters and assess their impact on 4D dose simulation accuracy by comparison of simulated motion-affected dose distributions to corresponding dosimetric motion phantom measurements. Exploiting an ITV-based treatment planning approach, VMAT treatment plans were generated for a motion phantom and different motion scenarios (sinusoidal motion of different period/direction; regular/irregular motion). 4D VMAT dose simulation results and dose measurements were compared by local 3% / 3 mm γ-evaluation, with the measured dose distributions serving as ground truth. Overall γ-passing rates of simulations and dynamic measurements ranged from 97% to 100% (mean across all motion scenarios: 98% ± 1%); corresponding values for comparison of different day repeat measurements were

The degree of cycle irregularity correlates with the grade of endocrine and metabolic disorders in PCOS patients.

PubMed

Strowitzki, Thomas; Capp, Edison; von Eye Corleta, Helena

2010-04-01

PCOS (polycystic ovarian syndrome) is a clinically heterogeneous endocrine disorder which affects up to 4-10% of women of reproductive age. A standardized definition is still difficult because of a huge variety of different phenotypes. The aim of this study was to evaluate possible correlations between the degree of cycle irregularity and the grade of endocrine and metabolic abnormalities. A cross-sectional study was carried out. Hyperandrogenic and/or hirsute women with regular menstrual cycles and polycystic ovaries on ultrasound (PCOS eumenorr, n=45), PCOS patients with oligomenorrhea (PCOS oligo, n=42) and PCOS patients with amenorrhea (PCOS amenorr, n=31) were recruited from the Department of Gynecological Endocrinology and Reproductive Medicine of the Women's University Hospital Heidelberg (Heidelberg, Germany). Normocyclic patients demonstrated significantly better metabolic parameters (BMI, fasting insulin, HOMA-IR) than patients with oligo/amenorrhea. Hormonal parameters (LH, FSH, FAI and testosterone) were significantly different between patients with different menstrual patterns and patients with regular cycles. Determining the degree of cycle irregularity as a simple clinical parameter might be a valuable instrument to estimate the degree of metabolic and endocrine disorders. Emphasis should be given to those parameters as a first step to characterize PCOS patients with a risk of endocrine and metabolic disorders leading to consequent detailed examination. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Breathing metabolic simulator

NASA Technical Reports Server (NTRS)

Bartlett, R. G.; Hendricks, C. M.; Morison, W. B.

1972-01-01

The development of a breathing metabolic simulator (BMS) is reported. This BMS simulates all of the breathing and metabolic parameters required for complete evaluation and test of life support and resuscitation equipment. It is also useful for calibrating and validating mechanical and gaseous pulmonary function test procedures. Breathing rate, breathing depth, breath velocity contour, oxygen uptake, and carbon dioxide release are all variable over wide ranges simulating conditions from sleep to hard work with respiratory exchange ratios covering the range from hypoventilation. In addition, all of these parameters are remotely controllable to facilitate use of the device in hostile or remote environments. The exhaled breath is also maintained at body temperature and a high humidity. The simulation is accurate to the extent of having a variable functional residual capacity independent of other parameters.

Metabolic syndrome and atypical antipsychotics: Possibility of prediction and control.

PubMed

Franch Pato, Clara M; Molina Rodríguez, Vicente; Franch Valverde, Juan I

Schizophrenia and other psychotic disorders are associated with high morbidity and mortality, due to inherent health factors, genetic factors, and factors related to psychopharmacological treatment. Antipsychotics, like other drugs, have side-effects that can substantially affect the physical health of patients, with substantive differences in the side-effect profile and in the patients in which these side-effects occur. To understand and identify these risk groups could help to prevent the occurrence of the undesired effects. A prospective study, with 24 months follow-up, was conducted in order to analyse the physical health of severe mental patients under maintenance treatment with atypical antipsychotics, as well as to determine any predictive parameters at anthropometric and/or analytical level for good/bad outcome of metabolic syndrome in these patients. There were no significant changes in the physical and biochemical parameters individually analysed throughout the different visits. The baseline abdominal circumference (lambda Wilks P=.013) and baseline HDL-cholesterol levels (lambda Wilks P=.000) were the parameters that seem to be more relevant above the rest of the metabolic syndrome constituents diagnosis criteria as predictors in the long-term. In the search for predictive factors of metabolic syndrome, HDL-cholesterol and abdominal circumference at the time of inclusion were selected, as such that the worst the baseline results were, the higher probability of long-term improvement. Copyright © 2016 SEP y SEPB. Publicado por Elsevier España, S.L.U. All rights reserved.

[Effects of dietary habits modifications on selected metabolic parameters during weight loss in obese persons].

PubMed

Ostrowska, Lucyna; Stefańska, Ewa; Jastrzebska, Marta; Adamska, Edyta; Wujek, Anita; Waszczeniuk, Magdalena

2012-01-01

Obesity is a serious social problem, one of the most important health issues of the modern world, especially in industrialized countries. Due to the prevalence obesity is a social disease, chronic and also a risk factor for many diseases such as hypertension, type 2 diabetes mellitus, coronary heart disease, gall stones or cancers. The aim of the study was to examine and evaluation whether the systematic one-year modifications of dietary habits affect the changes in body weight and some metabolic parameters in obese patients. 30 women and 30 men who declared intentions to decrease body weight were examined. The mean age of women was 48 +/- 12.5 years (range 31-72 years), men 51 +/- 13.2 years (range 23-70 years). The questionnaire survey concerning the subject matter was designed in the Department of Dietetics and Clinical Nutrition, Medical University of Bialystok. At the initial and final visit the frequency of some products consumption were assessed and concentrations of some biochemical parameters in the peripheral blood were measured. Women after one-year dietotherapy significantly reduced the incidence of eating: pasta, fruit and vegetable juices, potatoes, ripening cheese, sugar, meat, bacon and lard, butter and cream, and increased incidence of eating dark bread, groats, rice, vegetables and fruit, cottage cheese, fish and vegetable oils. Men significantly reduced the incidence of eating: pasta, potatoes, ripening cheese, sweet beverages, bacon and lard, margarine, and increased the incidence of eating dark bread, groats, rice, vegetables, cottage cheese and fish. After one year the average body weight decrease was 2.8 +/- 7.1 kg in women and 1.4 +/- 3.2 kg in men. The average reduction in waist circumference was 3.6 +/- 6.5 cm in women and 3.6 +/- 4,8 cm in men. HDL cholesterol levels increased significantly in women and not significantly in men. LDL cholesterol and triglyceride levels decreased significantly in both groups. In women systolic blood

Dynamic Modelling under Uncertainty: The Case of Trypanosoma brucei Energy Metabolism

PubMed Central

Achcar, Fiona; Kerkhoven, Eduard J.; Bakker, Barbara M.; Barrett, Michael P.; Breitling, Rainer

2012-01-01

Kinetic models of metabolism require detailed knowledge of kinetic parameters. However, due to measurement errors or lack of data this knowledge is often uncertain. The model of glycolysis in the parasitic protozoan Trypanosoma brucei is a particularly well analysed example of a quantitative metabolic model, but so far it has been studied with a fixed set of parameters only. Here we evaluate the effect of parameter uncertainty. In order to define probability distributions for each parameter, information about the experimental sources and confidence intervals for all parameters were collected. We created a wiki-based website dedicated to the detailed documentation of this information: the SilicoTryp wiki (http://silicotryp.ibls.gla.ac.uk/wiki/Glycolysis). Using information collected in the wiki, we then assigned probability distributions to all parameters of the model. This allowed us to sample sets of alternative models, accurately representing our degree of uncertainty. Some properties of the model, such as the repartition of the glycolytic flux between the glycerol and pyruvate producing branches, are robust to these uncertainties. However, our analysis also allowed us to identify fragilities of the model leading to the accumulation of 3-phosphoglycerate and/or pyruvate. The analysis of the control coefficients revealed the importance of taking into account the uncertainties about the parameters, as the ranking of the reactions can be greatly affected. This work will now form the basis for a comprehensive Bayesian analysis and extension of the model considering alternative topologies. PMID:22379410

Arachidonic Acid and Eicosapentaenoic Acid Metabolism in Juvenile Atlantic Salmon as Affected by Water Temperature.

PubMed

Norambuena, Fernando; Morais, Sofia; Emery, James A; Turchini, Giovanni M

2015-01-01

Salmons raised in aquaculture farms around the world are increasingly subjected to sub-optimal environmental conditions, such as high water temperatures during summer seasons. Aerobic scope increases and lipid metabolism changes are known plasticity responses of fish for a better acclimation to high water temperature. The present study aimed at investigating the effect of high water temperature on the regulation of fatty acid metabolism in juvenile Atlantic salmon fed different dietary ARA/EPA ratios (arachidonic acid, 20:4n-6/ eicosapentaenoic acid, 20:5n-3), with particular focus on apparent in vivo enzyme activities and gene expression of lipid metabolism pathways. Three experimental diets were formulated to be identical, except for the ratio EPA/ARA, and fed to triplicate groups of Atlantic salmon (Salmo salar) kept either at 10°C or 20°C. Results showed that fatty acid metabolic utilisation, and likely also their dietary requirements for optimal performance, can be affected by changes in their relative levels and by environmental temperature in Atlantic salmon. Thus, the increase in temperature, independently from dietary treatment, had a significant effect on the β-oxidation of a fatty acid including EPA, as observed by the apparent in vivo enzyme activity and mRNA expression of pparα -transcription factor in lipid metabolism, including β-oxidation genes- and cpt1 -key enzyme responsible for the movement of LC-PUFA from the cytosol into the mitochondria for β-oxidation-, were both increased at the higher water temperature. An interesting interaction was observed in the transcription and in vivo enzyme activity of Δ5fad-time-limiting enzyme in the biosynthesis pathway of EPA and ARA. Such, at lower temperature, the highest mRNA expression and enzyme activity was recorded in fish with limited supply of dietary EPA, whereas at higher temperature these were recorded in fish with limited ARA supply. In consideration that fish at higher water temperature

Genetic parameters of product quality and hepatic metabolism in fattened mule ducks.

PubMed

Marie-Etancelin, C; Basso, B; Davail, S; Gontier, K; Fernandez, X; Vitezica, Z G; Bastianelli, D; Baéza, E; Bernadet, M-D; Guy, G; Brun, J-M; Legarra, A

2011-03-01

Genetic parameters of traits related to hepatic lipid metabolism, carcass composition, and product quality of overfed mule ducks were estimated on both parental lines of this hybrid: the common duck line for the maternal side and the Muscovy line for the paternal side. The originality of the statistical model was to include simultaneously the additive genetic effect of the common ducks and that of the Muscovy ducks, revealing a greater genetic determinism in common than in Muscovy. Plasma metabolic indicators (glucose, triglyceride, and cholesterol contents) were heritable, in particular at the end of the overfeeding period, and heritabilities increased with the overfeeding stage. Carcass composition traits were highly heritable in the common line, with values ranging from 0.15 for liver weight, 0.21 for carcass weight, and 0.25 for abdominal fat weight to 0.32 for breast muscle weight. Heritabilities of technological outputs were greater for the fatty liver (0.19 and 0.08, respectively, on common and Muscovy sides for liver melting rate) than for the pectoralis major muscle (between 0.02 and 0.05 on both parental sides for cooking losses). Fortunately, the processing industry is mainly facing problems in liver quality, such as too high of a melting rate, than in meat quality. The meat quality appraisal criteria (such as texture and cooking losses), usually dependent on pH and the rate of decline of pH, were also very lowly heritable. This study demonstrated that genetic determinism of meat quality and ability of overfeeding is not similar in the common population and in the Muscovy population; traits related to fattening, muscle development, and BW have heritability values from 2 to 4 times greater on the common line than on the Muscovy line, which is relevant for considering different selection strategies.

The effect of a combination therapy with myo-inositol and a combined oral contraceptive pill versus a combined oral contraceptive pill alone on metabolic, endocrine, and clinical parameters in polycystic ovary syndrome.

PubMed

Minozzi, Massimo; Costantino, Demetrio; Guaraldi, Claudia; Unfer, Vittorio

2011-11-01

Compare the effects of a combined contraceptive pill (OCP) in combination with myo-inositol (MI) on endocrine, metabolic, and clinical parameters in patients with polycystic ovary syndrome (PCOS). One hundred fifty-five patients with PCOS were enrolled in this prospective, open-label clinical study. Patients were assigned to receive oral treatment with OCP alone (estradiol (EE) 30 μg/gestodene 75 μg) or in combination with myo-inositol 4 g/die, for 12 months. OCP plus MI therapy resulted in a higher reduction of FG score compared with OCP alone therapy. The combined therapy (OCP plus MI) significantly decreased hyperinsulinaemia, by positively affecting the fasting insulin and glucose levels and homeostasis model assessment-insulin resistance parameters, while no significant changes were observed in the OCP group. Androgens serum levels decreased in both groups, but significantly more in the combined therapy group. The lipid profile was improved in the combined therapy group, by reducing low-density lipoprotein cholesterol levels and enhancing high-density lipoprotein cholesterol levels. Our data show that a combination of combined contraceptive pill and MI may be more effective in controlling endocrine, metabolic, and clinical profile in patients with PCOS than OCP alone, and may reduce insulin levels and insulin resistance. Hence, combined treatment may become a more effective long-term therapeutic choice for controlling PCOS symptoms.

Metabolism of plasma cholesterol and lipoprotein parameters are related to a higher degree of insulin sensitivity in high HDL-C healthy normal weight subjects.

PubMed

Leança, Camila C; Nunes, Valéria S; Panzoldo, Natália B; Zago, Vanessa S; Parra, Eliane S; Cazita, Patrícia M; Jauhiainen, Matti; Passarelli, Marisa; Nakandakare, Edna R; de Faria, Eliana C; Quintão, Eder C R

2013-11-22

We have searched if plasma high density lipoprotein-cholesterol (HDL-C) concentration interferes simultaneously with whole-body cholesterol metabolism and insulin sensitivity in normal weight healthy adult subjects. We have measured the activities of several plasma components that are critically influenced by insulin and that control lipoprotein metabolism in subjects with low and high HDL-C concentrations. These parameters included cholesteryl ester transfer protein (CETP), phospholipid transfer protein (PLTP), lecithin cholesterol acyl transferase (LCAT), post-heparin lipoprotein lipase (LPL), hepatic lipase (HL), pre-beta-₁HDL, and plasma sterol markers of cholesterol synthesis and intestinal absorption. In the high-HDL-C group, we found lower plasma concentrations of triglycerides, alanine aminotransferase, insulin, HOMA-IR index, activities of LCAT and HL compared with the low HDL-C group; additionally, we found higher activity of LPL and pre-beta-₁HDL concentration in the high-HDL-C group. There were no differences in the plasma CETP and PLTP activities. These findings indicate that in healthy hyperalphalipoproteinemia subjects, several parameters that control the metabolism of plasma cholesterol and lipoproteins are related to a higher degree of insulin sensitivity.

68Ga-PSMA-11 PET/CT-derived metabolic parameters for determination of whole-body tumor burden and treatment response in prostate cancer.

PubMed

Schmidkonz, Christian; Cordes, Michael; Schmidt, Daniela; Bäuerle, Tobias; Goetz, Theresa Ida; Beck, Michael; Prante, Olaf; Cavallaro, Alexander; Uder, Michael; Wullich, Bernd; Goebell, Peter; Kuwert, Torsten; Ritt, Philipp

2018-05-03

We aimed at evaluating the role of 68 Ga-PSMA-11 PET/CT-derived metabolic parameters for assessment of whole-body tumor burden and its capability to determine therapeutic response in patients with prostate cancer. A total of 142 patients with biochemical recurrence of prostate cancer underwent PET/CT with [ 68 Ga]Ga-PSMA-HBED-CC ( 68 Ga-PSMA-11). Quantitative assessment of all 641 68 Ga-PSMA-11-positive lesions in the field of view was performed to calculate PSMA-derived parameters, including whole-body PSMA tumor volume (PSMA-TV) and whole-body total lesion PSMA (TL-PSMA), as well as the established SUVmax and SUVmean values. All PET-derived parameters were tested for correlation with serum PSA levels and for association with Gleason scores. In 23 patients who underwent 68 Ga-PSMA-11 PET/CT before and after therapy with either external beam radiation, androgen deprivation, or docetaxel chemotherapy, SUVmax and TL-PSMA were compared to radiographic response assessment of CT images based on RECIST 1.1 criteria and to biochemical response determined by changes of serum PSA levels. PSMA-TV and TL-PSMA demonstrated a significant correlation with serum PSA levels (P < 0.0001) and TL-PSMA was significantly different for different Gleason scores. The agreement rate between TL-PSMA derived from PET and biochemical response was 87% (95% confidence interval, 0.66-0.97; Cohen's κ = 0.78; P < 0.01) and, thus, higher than for SUVmax, which was 74% (95% CI, 0.52-0.90; κ = 0.55; P < 0.01). Furthermore, agreement with PSA was higher for TL-PSMA and SUVmax than for CT-based response evaluation. Discordant findings between PET and CT were most likely due to limitations of CT and RECIST in rating small lymph nodes as metastases, as well as bone involvement, which was sometimes not detectable in CT. 68 Ga-PSMA-11 PET/CT-derived metabolic tumor parameters showed promising results for evaluation of treatment response. Especially, TL-PSMA demonstrated higher agreement

Effects of salicylic acid-induced wine rich in anthocyanins on metabolic parameters and adipose insulin signaling in high-fructose fed rats.

PubMed

Rodriguez Lanzi, Cecilia; de Rosas, Inés; Perdicaro, Diahann J; Ponce, María Teresa; Martinez, Liliana; Miatello, Roberto M; Cavagnaro, Bruno; Vazquez Prieto, Marcela A

2016-12-01

We evaluated the effects of Syrah red wine treated with salicylic acid (RW SA) and its control red wine (RW) on metabolic parameters, systolic blood pressure and adipose tissue insulin signaling in high-fructose (F) fed rats. Grape treated with SA increased the anthocyanin (ANTs) levels in RW. F induced increased systolic blood pressure, dislipidemia and insulin resistance (HOMA:IR). F rats treated with RW significantly prevented these alterations while RW SA partially attenuated triglycerides levels and HOMA:IR without modifications in HDL cholesterol levels. F impaired the adipose tissue response to insulin. Supplementation with RW and RW SA partially attenuated these alterations. Rats supplemented with RW SA had lesser beneficial effects on metabolic alterations than control RW, while both RW and RW SA attenuated altered adipose response to insulin. More studies are necessary to deeply evaluate the effect on SA-induced RW rich in ANTs levels on metabolic alterations associated to MetS.

Metabolic depression during warm torpor in the Golden spiny mouse (Acomys russatus) does not affect mitochondrial respiration and hydrogen peroxide release.

PubMed

Grimpo, Kirsten; Kutschke, Maria; Kastl, Anja; Meyer, Carola W; Heldmaier, Gerhard; Exner, Cornelia; Jastroch, Martin

2014-01-01

Small mammals actively decrease metabolism during daily torpor and hibernation to save energy. Recently, depression of mitochondrial substrate oxidation in isolated liver mitochondria was observed and associated to hypothermic/hypometabolic states in Djungarian hamsters, mice and hibernators. We aimed to clarify whether hypothermia or hypometabolism causes mitochondrial depression during torpor by studying the Golden spiny mouse (Acomys russatus), a desert rodent which performs daily torpor at high ambient temperatures of 32°C. Notably, metabolic rate but not body temperature is significantly decreased under these conditions. In isolated liver, heart, skeletal muscle or kidney mitochondria we found no depression of respiration. Moderate cold exposure lowered torpor body temperature but had minor effects on minimal metabolic rate in torpor. Neither decreased body temperature nor metabolic rate impacted mitochondrial respiration. Measurements of mitochondrial proton leak kinetics and determination of P/O ratio revealed no differences in mitochondrial efficiency. Hydrogen peroxide release from mitochondria was not affected. We conclude that interspecies differences of mitochondrial depression during torpor do not support a general relationship between mitochondrial respiration, body temperature and metabolic rate. In Golden spiny mice, reduction of metabolic rate at mild temperatures is not triggered by depression of substrate oxidation as found in liver mitochondria from other cold-exposed rodents. © 2013.

Structural kinetic modeling of metabolic networks.

PubMed

Steuer, Ralf; Gross, Thilo; Selbig, Joachim; Blasius, Bernd

2006-08-08

To develop and investigate detailed mathematical models of metabolic processes is one of the primary challenges in systems biology. However, despite considerable advance in the topological analysis of metabolic networks, kinetic modeling is still often severely hampered by inadequate knowledge of the enzyme-kinetic rate laws and their associated parameter values. Here we propose a method that aims to give a quantitative account of the dynamical capabilities of a metabolic system, without requiring any explicit information about the functional form of the rate equations. Our approach is based on constructing a local linear model at each point in parameter space, such that each element of the model is either directly experimentally accessible or amenable to a straightforward biochemical interpretation. This ensemble of local linear models, encompassing all possible explicit kinetic models, then allows for a statistical exploration of the comprehensive parameter space. The method is exemplified on two paradigmatic metabolic systems: the glycolytic pathway of yeast and a realistic-scale representation of the photosynthetic Calvin cycle.

Genetic variants of the folate metabolic system and mild hyperhomocysteinemia may affect ADHD associated behavioral problems.

PubMed

Saha, Tanusree; Chatterjee, Mahasweta; Verma, Deepak; Ray, Anirban; Sinha, Swagata; Rajamma, Usha; Mukhopadhyay, Kanchan

2018-06-08

An etiologically complex disorder, Attention Deficit Hyperactivity Disorder (ADHD), is often associated with various levels of cognitive deficit. Folate/vitamin B 9 is crucial for numerous biochemical pathways including neural stem cell proliferation and differentiation, regulation of gene expression, neurotransmitter synthesis, myelin synthesis and repair, etc. and a scarcity has often been linked to cognitive deficit. Our pilot study in the field revealed significant association of few genetic variants with ADHD. Mild hyperhomocysteinemia and vitamin B 12 deficiency was also noticed in the probands. In the present study additional genetic variants, folate and vitamin B 6 , which may affect folate-homocysteine metabolic pathway, were investigated in 866 individuals including nuclear families with ADHD probands (N=221) and ethnically matched controls (N=286) to find out whether ADHD associated traits are affected by these factors. Population based analysis revealed significant over representation of MTRR rs1801394 "G" allele and "GG" genotype in all as well as male probands. Stratified analysis showed significantly higher frequency of RFC1 rs1051266 and BHMT rs3733890 "AG" genotypes in full term and prematurely delivered ADHD probands respectively. Probands with rs1801394 "GG" genotype and BHMT rs3733890 "G" allele showed association with hyperhomocysteinemia. MTHFR rs1801131, MTR rs1805087 and BHMT rs3733890 also showed association with ADHD index. While rs1051266, rs1801131, and rs1805087 showed association with behavioral problems, rs3733890 was associated with ODD score. Conduct problem exhibited association with RFC1 rs1051266, MTHFR rs1801133 and MTRR rs1801394. Gene-gene interaction analysis revealed positive synergistic interactions between rs1051266, rs1801131 and rs1801394 in the probands as compared to the controls. It can be inferred from the data obtained that folate system genetic variants and mild hyperhomocysteimenia may affect ADHD associated

Altered sterol metabolism in budding yeast affects mitochondrial iron-sulfur (Fe-S) cluster synthesis.

PubMed

Ward, Diane M; Chen, Opal S; Li, Liangtao; Kaplan, Jerry; Bhuiyan, Shah Alam; Natarajan, Selvamuthu K; Bard, Martin; Cox, James E

2018-05-17

Ergosterol synthesis is essential for cellular growth and viability of the budding yeast Saccharomyces cerevisiae, and intracellular sterol distribution and homeostasis are therefore highly regulated in this species. Erg25 is an iron-containing C4-methyl sterol oxidase that contributes to the conversion of 4,4-dimethylzymosterol to zymosterol, a precursor of ergosterol. The ERG29 gene encodes an endoplasmic reticulum (ER)-associated protein, and here we identified a role for Erg29 in the methyl sterol oxidase step of ergosterol synthesis. ERG29 deletion resulted in lethality in respiring cells, but respiration-incompetent (Rho- or Rho0) cells survived, suggesting that Erg29 loss leads to accumulation of oxidized sterol metabolites that affect cell viability. Down-regulation of ERG29 expression in Δerg29 cells indeed led to accumulation of methyl sterol metabolites, resulting in increased mitochondrial oxidants and a decreased ability of mitochondria to synthesize iron-sulfur (Fe-S) clusters due to reduced levels of Yfh1, the mammalian frataxin homolog, which is involved in mitochondrial Fe metabolism. Using a high-copy genomic library, we identified suppressor genes that permitted growth of Δerg29 cells on respiratory substrates, and these included genes encoding the mitochondrial proteins Yfh1, Mmt1, Mmt2, and Pet20, which reversed all phenotypes associated with loss of ERG29. Of note, loss of Erg25 also resulted in accumulation of methyl sterol metabolites and also increased mitochondrial oxidants and degradation of Yfh1. We propose that accumulation of toxic intermediates of the methyl sterol oxidase reaction increase mitochondrial oxidants, which affect Yfh1 protein stability. These results indicate an interaction between sterols generated by ER proteins and mitochondrial iron metabolism. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

Long-term high-intensity interval training associated with lifestyle modifications improves QT dispersion parameters in metabolic syndrome patients.

PubMed

Drigny, J; Gremeaux, V; Guiraud, T; Gayda, M; Juneau, M; Nigam, A

2013-07-01

QT dispersion (QTd) is a marker of myocardial electrical instability, and is increased in metabolic syndrome (MetS). Moderate intensity continuous exercise (MICE) training was shown to improve QTd in MetS patients. To describe long-term effects of MICE and high-intensity interval exercise training (HIIT) on QTd parameters in MetS. Sixty-five MetS patients (53 ± 9 years) were assigned to either a MICE (60% of peak power output [PPO]), or a HIIT program (alternating phases of 15-30 s at 80% of PPO interspersed by passive recovery phases of equal duration), twice weekly during 9 months. Ventricular repolarization indices (QT dispersion=QTd, standard deviation of QT = sdQT, relative dispersion of QT = rdQT, QT corrected dispersion = QTcd), metabolic, anthropometric and exercise parameters were measured before and after the intervention. No adverse events were noted during exercise. QTd decreased significantly in both groups (51 vs 56 ms in MICE, P < 0.05; 34 vs 38 ms in HIIT, P < 0.05). Changes in QTd were correlated with changes in maximal heart rate (r = -0.69, P < 0.0001) and in heart rate recovery (r = -0.49, P < 0.01) in the HIIT group only. When compared to MICE, HIIT training induced a greater decrease in weight, BMI and waist circumference. Exercise capacity significantly improved by 0.82 and 1.25 METs in MICE and HIIT groups respectively (P < 0.0001). Lipid parameters also improved to the same degree in both groups. In MetS, long-term HIIT and MICE training led to comparable effects on ventricular repolarization indices, and HIIT might be associated with greater improvements in certain cardiometabolic risk factors. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Metabolic parameters and blood leukocyte profiles in cows from herds with high or low mastitis incidence.

PubMed

Holtenius, K; Persson Waller, K; Essén-Gustavsson, B; Holtenius, P; Hallén Sandgren, C

2004-07-01

The objective of this study was to determine whether there were differences in metabolic parameters and blood leukocyte profiles between cows in herds with high or low yearly mastitis incidence. In this study, 271 cows from 20 high yielding dairy herds were examined. According to the selection criteria, all herds had low somatic cell counts. Ten of the selected herds represented low mastitis treatment incidence (LMI) and ten herds had high mastitis treatment incidence (HMI). The farms were visited once and blood samples were taken from each cow that was in the interval from three weeks before to 15 weeks after parturition. The eosinophil count was significantly lower among cows from the HMI herds in the period from four weeks to 15 weeks after parturition. The plasma concentrations of beta-hydroxybutyrate, glucose, insulin and urea did not differ between groups, but the concentration of nonesterified fatty acids was significantly higher among HMI cows during the period three weeks after parturition. The concentration of the amino acid tryptophan in plasma was significantly lower among the HMI cows prior to parturition. Glutamine was significantly lower in cows from HMI herds during the first three weeks after parturition. Arginine was consistently lower in HMI cows, although the decrease was only significant during the period from four to fifteen weeks after parturition. The results suggest that there were differences in the metabolism and immune status between herds with high or low yearly mastitis treatment incidence indicating an increased metabolic stress in HMI cows.

How Glucosinolates Affect Generalist Lepidopteran Larvae: Growth, Development and Glucosinolate Metabolism

PubMed Central

Jeschke, Verena; Kearney, Emily E.; Schramm, Katharina; Kunert, Grit; Shekhov, Anton; Gershenzon, Jonathan; Vassão, Daniel G.

2017-01-01

Multiple lepidopteran larvae feed successfully on plants containing glucosinolates despite the diverse array of toxic and deterrent breakdown products, such as isothiocyanates (ITCs), formed upon plant damage. While much is known about how specialist lepidopterans metabolize and tolerate glucosinolates, there is little information about the metabolic fate of these plant defense compounds in specialized herbivores. Employing 13C- and 14C-labeled 4-methylsulfinylbutyl glucosinolate (glucoraphanin), we identified and quantified the major detoxification products of glucosinolates and ITCs in selected specialized and generalist larvae. While specialists prevented glucosinolate hydrolysis or diverted hydrolysis to form nitriles, hydrolysis in generalists proceeded to toxic ITCs, of which a portion were conjugated to glutathione. However, a large amount of ITCs remained unmodified, which may have led to the observed negative effects on growth and development. The performance of two generalist-feeding caterpillars, Spodoptera littoralis (African cotton leafworm) and Mamestra brassicae (cabbage moth) on Arabidopsis thaliana Col-0 and various glucosinolate-deficient mutants was investigated from hatching until pupation. We found that glucosinolates negatively affected larval growth and development, but not survival, with aliphatic glucosinolates having stronger effects than indolic glucosinolates, and the combination of the two glucosinolate types being even more detrimental to growth and development. Curiously, last instar larvae grew better on wild type than on non-glucosinolate-containing plant lines, but this could not be attributed to a change in detoxification rate or feeding behavior. Glucosinolates thus appear to be effective defenses against generalist lepidopteran herbivores at least during most stages of larval development. Nevertheless, the reversal of negative effects in the oldest instar is intriguing, and further investigation of this phenomenon may shed light

Effects of drinking water monochloramine on lipid and thyroid metabolism in healthy men.

PubMed Central

Wones, R G; Deck, C C; Stadler, B; Roark, S; Hogg, E; Frohman, L A

1993-01-01

The purpose of this study was to determine whether a 4-week consumption of 1.5L per day of drinking water containing monochloramine at a concentration of 2 ppm (ppm = mg/L) or 15 ppm under controlled conditions would alter parameters of lipid or thyroid metabolism in healthy men. Forty-eight men completed an 8-week protocol during which diet (600 mg cholesterol per day, 40% calories as fat) and other factors known to affect lipid metabolism were controlled. During the first 4 weeks of the protocol, all subjects consumed distilled water. During the second 4 weeks, one-third of the subjects were assigned randomly to drink 1.5 L per day of water containing 2 ppm of monochloramine, to drink 1.5 L per day of water containing 15 ppm monochloramine, or to continue drinking distilled water. Four blood samples were collected from each subject at the end of each 4-week study period. Subjects drinking monochloramine at a concentration of 2 ppm showed no significant changes in total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, apolipoproteins A1, A2, or B when compared to the distilled water group. Parameters of thyroid function also were unchanged by exposure to monochloramine at this concentration. However, subjects drinking monochloramine at a concentration of 15 ppm experienced an increase in the level of apolipoprotein B. Other parameters of lipid and thyroid metabolism did not change. We conclude that consumption of drinking water containing 2 ppm of monochloramine does not alter parameters of lipid and thyroid metabolism in healthy men. Consumption of water containing 15 ppm monochloramine may be associated with increased levels of plasma apolipoprotein B. PMID:8319653

Natural toxins that affect plant amino acid metabolism

USDA-ARS?s Scientific Manuscript database

A diverse range of natural compounds interfere with the synthesis and other aspects of amino acid metabolism. Some are amino acid analogues, but most are not. This review covers a number of specific natural phytotoxic compounds by molecular target site. Inhibition of glutamine synthetase is of part...

An empirical model for parameters affecting energy consumption in boron removal from boron-containing wastewaters by electrocoagulation.

PubMed

Yilmaz, A Erdem; Boncukcuoğlu, Recep; Kocakerim, M Muhtar

2007-06-01

In this study, it was investigated parameters affecting energy consumption in boron removal from boron containing wastewaters prepared synthetically, via electrocoagulation method. The solution pH, initial boron concentration, dose of supporting electrolyte, current density and temperature of solution were selected as experimental parameters affecting energy consumption. The obtained experimental results showed that boron removal efficiency reached up to 99% under optimum conditions, in which solution pH was 8.0, current density 6.0 mA/cm(2), initial boron concentration 100mg/L and solution temperature 293 K. The current density was an important parameter affecting energy consumption too. High current density applied to electrocoagulation cell increased energy consumption. Increasing solution temperature caused to decrease energy consumption that high temperature decreased potential applied under constant current density. That increasing initial boron concentration and dose of supporting electrolyte caused to increase specific conductivity of solution decreased energy consumption. As a result, it was seen that energy consumption for boron removal via electrocoagulation method could be minimized at optimum conditions. An empirical model was predicted by statistically. Experimentally obtained values were fitted with values predicted from empirical model being as following; [formula in text]. Unfortunately, the conditions obtained for optimum boron removal were not the conditions obtained for minimum energy consumption. It was determined that support electrolyte must be used for increase boron removal and decrease electrical energy consumption.

The correlations of glycated hemoglobin and carbohydrate metabolism parameters with heart rate variability in apparently healthy sedentary young male subjects

PubMed Central

Cherkas, Andriy; Abrahamovych, Orest; Golota, Sergii; Nersesyan, Armen; Pichler, Christoph; Serhiyenko, Victoria; Knasmüller, Siegfried; Zarkovic, Neven; Eckl, Peter

2015-01-01

Introduction Sedentary lifestyle is a major risk factor for diabetes, cardiovascular and many other age-related diseases. Heart rate variability (HRV) reflects the function of regulatory systems of internal organs and may sensitively indicate early metabolic disturbances. We hypothesize that quantitative and qualitative changes of HRV in young subjects may reflect early metabolic derangements responsible for further development of clinically significant disease. Aim The aim of our study was to determine whether the parameters of carbohydrate metabolism (fasting blood glucose, HBA1c and surrogate insulin sensitivity/resistance indices) correlate with anthropometric data and HRV. Methods The study group consisted of 30 healthy sedentary male subjects aged 20–40, nonsmokers, mainly office and research employees, medical staff and students. Athletes, actively training more than one hour per week, severely obese and men of physical work were excluded from the study. HRV parameters were derived from short term ECG records (five minutes intervals) in supine position and during orthostatic test. Anthropometric data included height, weight, body mass index (BMI), age and body composition (estimation by bioelectric impedance method). The fasting blood glucose, insulin and C-peptide, homeostatic model assessment (HOMA-IR) index and glycated hemoglobin (HbA1c) were evaluated. Linear correlation coefficient (r) was calculated using Statistica 10.0 software. Results and discussion HOMA-IR index correlated positively with body weight, visceral fat and BMI (p=0.047, 0.027 and 0.017 respectively). In supine position pNN50 positively correlated with glucose/insulin ratio (p=0.011) and heart rate with HOMA-IR (p=0.006). In orthostatic test negative correlations of HBA1c with standard deviation, total and low frequency power were determined (p=0.034, 0.400 and 0.403 respectively), which indicates a gradual worsening of functional capacity of cardiovascular system with low

Modeling of mouse eye and errors in ocular parameters affecting refractive state

NASA Astrophysics Data System (ADS)

Bawa, Gurinder

Rodents eye are particularly used to study refractive error state of an eye and development of refractive eye. Genetic organization of rodents is similar to that of humans, which makes them interesting candidates to be researched upon. From rodents family mice models are encouraged over rats because of availability of genetically engineered models. Despite of extensive work that has been performed on mice and rat models, still no one is able to quantify an optical model, due to variability in the reported ocular parameters. In this Dissertation, we have extracted ocular parameters and generated schematics of eye from the raw data from School of Medicine, Detroit. In order to see how the rays would travel through an eye and the defects associated with an eye; ray tracing has been performed using ocular parameters. Finally we have systematically evaluated the contribution of various ocular parameters, such as radii of curvature of ocular surfaces, thicknesses of ocular components, and refractive indices of ocular refractive media, using variational analysis and a computational model of the rodent eye. Variational analysis revealed that variation in all the ocular parameters does affect the refractive status of the eye, but depending upon the magnitude of the impact those parameters are listed as critical or non critical. Variation in the depth of the vitreous chamber, thickness of the lens, radius of the anterior surface of the cornea, radius of the anterior surface of the lens, as well as refractive indices for the lens and vitreous, appears to have the largest impact on the refractive error and thus are categorized as critical ocular parameters. The radii of the posterior surfaces of the cornea and lens have much smaller contributions to the refractive state, while the radii of the anterior and posterior surfaces of the retina have no effect on the refractive error. These data provide the framework for further refinement of the optical models of the rat and mouse

Nectar resource limitation affects butterfly flight performance and metabolism differently in intensive and extensive agricultural landscapes.

PubMed

Lebeau, Julie; Wesselingh, Renate A; Van Dyck, Hans

2016-05-11

Flight is an essential biological ability of many insects, but is energetically costly. Environments under rapid human-induced change are characterized by habitat fragmentation and may impose constraints on the energy income budget of organisms. This may, in turn, affect locomotor performance and willingness to fly. We tested flight performance and metabolic rates in meadow brown butterflies (Maniola jurtina) of two contrasted agricultural landscapes: intensively managed, nectar-poor (IL) versus extensively managed, nectar-rich landscapes (EL). Young female adults were submitted to four nectar treatments (i.e. nectar quality and quantity) in outdoor flight cages. IL individuals had better flight capacities in a flight mill and had lower resting metabolic rates (RMR) than EL individuals, except under the severest treatment. Under this treatment, RMR increased in IL individuals, but decreased in EL individuals; flight performance was maintained by IL individuals, but dropped by a factor 2.5 in EL individuals. IL individuals had more canalized (i.e. less plastic) responses relative to the nectar treatments than EL individuals. Our results show significant intraspecific variation in the locomotor and metabolic response of a butterfly to different energy income regimes relative to the landscape of origin. Ecophysiological studies help to improve our mechanistic understanding of the eco-evolutionary impact of anthropogenic environments on rare and widespread species. © 2016 The Author(s).

DEPTOR in POMC neurons affects liver metabolism but is dispensable for the regulation of energy balance.

PubMed

Caron, Alexandre; Labbé, Sébastien M; Mouchiroud, Mathilde; Huard, Renaud; Lanfray, Damien; Richard, Denis; Laplante, Mathieu

2016-06-01

We have recently demonstrated that specific overexpression of DEP-domain containing mTOR-interacting protein (DEPTOR) in the mediobasal hypothalamus (MBH) protects mice against high-fat diet-induced obesity, revealing DEPTOR as a significant contributor to energy balance regulation. On the basis of evidence that DEPTOR is expressed in the proopiomelanocortin (POMC) neurons of the MBH, the present study aimed to investigate whether these neurons mediate the metabolic effects of DEPTOR. Here, we report that specific DEPTOR overexpression in POMC neurons does not recapitulate any of the phenotypes observed when the protein was overexpressed in the MBH. Unlike the previous model, mice overexpressing DEPTOR only in POMC neurons 1) did not show differences in feeding behavior, 2) did not exhibit changes in locomotion activity and oxygen consumption, 3) did not show an improvement in systemic glucose metabolism, and 4) were not resistant to high-fat diet-induced obesity. These results support the idea that other neuronal populations are responsible for these phenotypes. Nonetheless, we observed a mild elevation in fasting blood glucose, insulin resistance, and alterations in liver glucose and lipid homeostasis in mice overexpressing DEPTOR in POMC neurons. Taken together, these results show that DEPTOR overexpression in POMC neurons does not affect energy balance regulation but could modulate metabolism through a brain-liver connection. Copyright © 2016 the American Physiological Society.

Nectar resource limitation affects butterfly flight performance and metabolism differently in intensive and extensive agricultural landscapes

PubMed Central

Lebeau, Julie; Wesselingh, Renate A.; Van Dyck, Hans

2016-01-01

Flight is an essential biological ability of many insects, but is energetically costly. Environments under rapid human-induced change are characterized by habitat fragmentation and may impose constraints on the energy income budget of organisms. This may, in turn, affect locomotor performance and willingness to fly. We tested flight performance and metabolic rates in meadow brown butterflies (Maniola jurtina) of two contrasted agricultural landscapes: intensively managed, nectar-poor (IL) versus extensively managed, nectar-rich landscapes (EL). Young female adults were submitted to four nectar treatments (i.e. nectar quality and quantity) in outdoor flight cages. IL individuals had better flight capacities in a flight mill and had lower resting metabolic rates (RMR) than EL individuals, except under the severest treatment. Under this treatment, RMR increased in IL individuals, but decreased in EL individuals; flight performance was maintained by IL individuals, but dropped by a factor 2.5 in EL individuals. IL individuals had more canalized (i.e. less plastic) responses relative to the nectar treatments than EL individuals. Our results show significant intraspecific variation in the locomotor and metabolic response of a butterfly to different energy income regimes relative to the landscape of origin. Ecophysiological studies help to improve our mechanistic understanding of the eco-evolutionary impact of anthropogenic environments on rare and widespread species. PMID:27147100

Sex-dependent effects of developmental exposure to bisphenol A and ethinyl estradiol on metabolic parameters and voluntary physical activity

PubMed Central

Johnson, S. A.; Painter, M. S.; Javurek, A. B.; Ellersieck, M. R.; Wiedmeyer, C. E.; Thyfault, J. P.; Rosenfeld, C. S.

2016-01-01

Endocrine disrupting chemicals (EDC) have received considerable attention as potential obesogens. Past studies examining obesogenic potential of one widespread EDC, bisphenol A (BPA), have generally focused on metabolic and adipose tissue effects. However, physical inactivity has been proposed to be a leading cause of obesity. A paucity of studies has considered whether EDC, including BPA, affects this behavior. To test whether early exposure to BPA and ethinyl estradiol (EE, estrogen present in birth control pills) results in metabolic and such behavioral disruptions, California mice developmentally exposed to BPA and EE were tested as adults for energy expenditure (indirect calorimetry), body composition (echoMRI) and physical activity (measured by beam breaks and voluntary wheel running). Serum glucose and metabolic hormones were measured. No differences in body weight or food consumption were detected. BPA-exposed females exhibited greater variation in weight than females in control and EE groups. During the dark and light cycles, BPA females exhibited a higher average respiratory quotient than control females, indicative of metabolizing carbohydrates rather than fats. Various assessments of voluntary physical activity in the home cage confirmed that during the dark cycle, BPA and EE-exposed females were significantly less active in this setting than control females. Similar effects were not observed in BPA or EE-exposed males. No significant differences were detected in serum glucose, insulin, adiponectin and leptin concentrations. Results suggest that females developmentally exposed to BPA exhibit decreased motivation to engage in voluntary physical activity and altered metabolism of carbohydrates v. fats, which could have important health implications. PMID:26378919

High-fat diet effects on metabolic responses to chronic stress.

PubMed

Nemati, Marzieh; Zardooz, Homeira; Rostamkhani, Fatemeh; Abadi, Alireza; Foroughi, Forough

2017-07-01

High-fat diets and chronic stress are prevalent risk factors for various chronic diseases in modern societies. This study investigated the effect of high-fat diet on glucose-related metabolic responses to chronic foot-shock stress. Male rats were divided into high-fat diet (containing 54.21% saturated and 44.89% unsaturated fatty acids) and normal diet groups and then into stress and non-stress subgroups. The diets were applied for 5 weeks, and stress was induced during the last week of the diet course. Plasma levels of metabolic parameters, HOMA-IR index, intra-abdominal fat weight, and islets' insulin secretion were assessed. High-fat diet increased abdominal fat weight and plasma leptin, and insulin levels in response to stress without affecting HOMA-IR index and islets' insulin secretion. High proportion of unsaturated fat may not lead to deleterious metabolic responses; however combined with chronic stress has a synergistic and adverse effect on visceral adiposity and results in elevated plasma leptin.

Effects of controlled discontinuation of long-term used antipsychotics on weight and metabolic parameters in individuals with intellectual disability.

PubMed

de Kuijper, Gerda; Mulder, Hans; Evenhuis, Heleen; Visser, Frank; Hoekstra, Pieter J

2013-08-01

Antipsychotics are frequently prescribed agents in individuals with intellectual disability, often for behavioral symptoms. Efficacy of antipsychotics for this is ambiguous, so discontinuation should be considered. Weight gain and metabolic dysregulation are well-known adverse effects of antipsychotics which increase the risk of the metabolic syndrome. We performed a discontinuation study in 99 adults with intellectual disability, living in residential facilities who used antipsychotics for behavioral symptoms for more than 1 year. The aim of the present study was to investigate the effects of discontinuation of long-term used antipsychotics on weight, body mass index (BMI), and parameters of the metabolic syndrome and to investigate the influence of genetic polymorphisms and medication factors on these outcomes. Discontinuation of antipsychotics led to a mean decrease of 4 cm waist circumference, of 3.5 kg weight, 1.4 kg/m2 BMI, and 7.1 mm Hg systolic blood pressure. In those participants who had not completely discontinued use of antipsychotics we found a decrease in weight and BMI and an increase in fasting glucose. The presence of the C-allele of serotonin 5-hydroxytryptamine receptor polymorphism rs141334 was associated with higher waist circumference and higher plasma levels of triglycerides and lower levels of high-density lipoprotein. Achievement of complete discontinuation predicted a larger decrease in waist circumference and BMI. In conclusion, results of the study show the beneficial effects of discontinuation of long-term used antipsychotics on metabolic outcomes.

Vitamin D Improves Selected Metabolic Parameters but Not Neuropsychological or Quality of Life Indices in OSA: A Pilot Study

PubMed Central

Kerley, Conor P.; Hutchinson, Katrina; Bramham, Jessica; McGowan, Aisling; Faul, John; Cormican, Liam

2017-01-01

Study Objectives: Our group and others have reported a high rate of vitamin D deficiency in obstructive sleep apnea (OSA), where vitamin D levels (25(OH) D) correlate negatively with OSA severity and some of its associated metabolic alterations. Data regarding vitamin D supplementation in OSA are lacking. We wanted to evaluate the effect of vitamin D3 supplementation on OSA symptoms and metabolic parameters. Methods: We conducted a pilot, double-blind, randomized, placebo-controlled trial of daily supplementation with 4,000 IU vitamin D3 (D3) or placebo (PL). We studied 19 Caucasian adults (14 male, mean age 55 y, mean body mass index [BMI] 30.4 kg/m2) with OSA. Fifteen patients were stable on continuous positive airways pressure (CPAP) therapy, whereas four were CPAP naïve. Assessments were completed at baseline and after 15 weeks of supplementation. Outcomes included sleepiness (Epworth Sleepiness Scale), quality of life (Sleep Apnea Quality of Life Inventory), fatigue (fatigue severity scale) and neuropsychological function (trail making test and Connor's Continuous Performance Test II). In addition, we assessed biochemical indices of vitamin D status (25(OH)D, calcium), inflammation (high sensitivity C-reactive protein, and lipoprotein-associated phospholipase A2), lipids (total cholesterol [low-density and high-density lipoprotein]) and glycemic indices (fasting glucose, oral glucose tolerance test). Results: There was no change in BMI, medication, or CPAP usage. Although there was no change in neuropsychological or quality of life indices, we observed a significant increase in 25(OH)D (p = 0.00001) and significant decreases in both low-density lipoprotein (p = 0.04) and lipoprotein-associated phospholipase A2 (p = 0.037) as well as trends toward decreased fasting glucose (p = 0.09) and increased high-density lipoprotein (p = 0.07) in the D3 group compared to PL. Conclusions: Vitamin D3 supplementation increased vitamin D levels and decreased metabolic

Apple Peel Supplemented Diet Reduces Parameters of Metabolic Syndrome and Atherogenic Progression in ApoE-/- Mice.

PubMed

Gonzalez, Jaime; Donoso, Wendy; Sandoval, Nathalie; Reyes, María; Gonzalez, Priscila; Gajardo, Monica; Morales, Erik; Neira, Amalia; Razmilic, Iván; Yuri, José A; Moore-Carrasco, Rodrigo

2015-01-01

Cardiovascular Diseases (CVD) represent about 30% of all causes of death worldwide. The development of CVD is related in many cases with the previous existence of metabolic syndrome (MS). It is known that apple consumption has a cardiovascular protecting effect, containing phenolic compounds with antioxidant effect, which are concentrated in the fruit peel. The objective of this study was to test the effect of apple peel consumption in a murine model of MS and apoE-/- mice. Apple supplemented diets reduced the biochemical parameters (glycaemia, total cholesterol, HDL-cholesterol, LDL-cholesterol, ureic nitrogen, triglycerides, insulin, and asymmetric dimethylarginine (ADMA)) of MS model in CF1 mice significantly. The model apoE-/- mouse was used to evaluate the capacity of the apple peel to revert the progression of the atherogenesis. FD with HAP reverts cholesterol significantly and slows down the progression of the plate diminishing the cholesterol accumulation area. With these results, it can be concluded that the consumption of apple peel reduces several MS parameters and the atherogenic progression in mice.

Substituting whole grains for refined grains in a 6-week randomized trial favorably affects energy balance parameters in healthy men and post-menopausal women

USDA-ARS?s Scientific Manuscript database

Background: The effect of whole grains on the regulation of energy balance remains controversial. Objective: To determine the effects of substituting whole grains for refined grains, independent of body weight change, on energy metabolism parameters and glycemic control. Design: A randomized, con...

Arachidonic Acid and Eicosapentaenoic Acid Metabolism in Juvenile Atlantic Salmon as Affected by Water Temperature

PubMed Central

Norambuena, Fernando; Morais, Sofia; Emery, James A.; Turchini, Giovanni M.

2015-01-01

Salmons raised in aquaculture farms around the world are increasingly subjected to sub-optimal environmental conditions, such as high water temperatures during summer seasons. Aerobic scope increases and lipid metabolism changes are known plasticity responses of fish for a better acclimation to high water temperature. The present study aimed at investigating the effect of high water temperature on the regulation of fatty acid metabolism in juvenile Atlantic salmon fed different dietary ARA/EPA ratios (arachidonic acid, 20:4n-6/ eicosapentaenoic acid, 20:5n-3), with particular focus on apparent in vivo enzyme activities and gene expression of lipid metabolism pathways. Three experimental diets were formulated to be identical, except for the ratio EPA/ARA, and fed to triplicate groups of Atlantic salmon (Salmo salar) kept either at 10°C or 20°C. Results showed that fatty acid metabolic utilisation, and likely also their dietary requirements for optimal performance, can be affected by changes in their relative levels and by environmental temperature in Atlantic salmon. Thus, the increase in temperature, independently from dietary treatment, had a significant effect on the β-oxidation of a fatty acid including EPA, as observed by the apparent in vivo enzyme activity and mRNA expression of pparα -transcription factor in lipid metabolism, including β-oxidation genes- and cpt1 -key enzyme responsible for the movement of LC-PUFA from the cytosol into the mitochondria for β-oxidation-, were both increased at the higher water temperature. An interesting interaction was observed in the transcription and in vivo enzyme activity of Δ5fad–time-limiting enzyme in the biosynthesis pathway of EPA and ARA. Such, at lower temperature, the highest mRNA expression and enzyme activity was recorded in fish with limited supply of dietary EPA, whereas at higher temperature these were recorded in fish with limited ARA supply. In consideration that fish at higher water temperature

Increasing Phosphatidylinositol (4,5)-Bisphosphate Biosynthesis Affects Basal Signaling and Chloroplast Metabolism in Arabidopsis thaliana

PubMed Central

Im, Yang Ju; Smith, Caroline M.; Phillippy, Brian Q.; Strand, Deserah; Kramer, David M.; Grunden, Amy M.; Boss, Wendy F.

2014-01-01

One challenge in studying the second messenger inositol(1,4,5)-trisphosphate (InsP3) is that it is present in very low amounts and increases only transiently in response to stimuli. To identify events downstream of InsP3, we generated transgenic plants constitutively expressing the high specific activity, human phosphatidylinositol 4-phosphate 5-kinase Iα (HsPIPKIα). PIP5K is the enzyme that synthesizes phosphatidylinositol (4,5)-bisphosphate (PtdIns(4,5)P2); this reaction is flux limiting in InsP3 biosynthesis in plants. Plasma membranes from transgenic Arabidopsis expressing HsPIPKIα had 2–3 fold higher PIP5K specific activity, and basal InsP3 levels in seedlings and leaves were >2-fold higher than wild type. Although there was no significant difference in photosynthetic electron transport, HsPIPKIα plants had significantly higher starch (2–4 fold) and 20% higher anthocyanin compared to controls. Starch content was higher both during the day and at the end of dark period. In addition, transcripts of genes involved in starch metabolism such as SEX1 (glucan water dikinase) and SEX4 (phosphoglucan phosphatase), DBE (debranching enzyme), MEX1 (maltose transporter), APL3 (ADP-glucose pyrophosphorylase) and glucose-6-phosphate transporter (Glc6PT) were up-regulated in the HsPIPKIα plants. Our results reveal that increasing the phosphoinositide (PI) pathway affects chloroplast carbon metabolism and suggest that InsP3 is one component of an inter-organelle signaling network regulating chloroplast metabolism. PMID:27135490

Machine Learning Methods for Analysis of Metabolic Data and Metabolic Pathway Modeling

PubMed Central

Cuperlovic-Culf, Miroslava

2018-01-01

Machine learning uses experimental data to optimize clustering or classification of samples or features, or to develop, augment or verify models that can be used to predict behavior or properties of systems. It is expected that machine learning will help provide actionable knowledge from a variety of big data including metabolomics data, as well as results of metabolism models. A variety of machine learning methods has been applied in bioinformatics and metabolism analyses including self-organizing maps, support vector machines, the kernel machine, Bayesian networks or fuzzy logic. To a lesser extent, machine learning has also been utilized to take advantage of the increasing availability of genomics and metabolomics data for the optimization of metabolic network models and their analysis. In this context, machine learning has aided the development of metabolic networks, the calculation of parameters for stoichiometric and kinetic models, as well as the analysis of major features in the model for the optimal application of bioreactors. Examples of this very interesting, albeit highly complex, application of machine learning for metabolism modeling will be the primary focus of this review presenting several different types of applications for model optimization, parameter determination or system analysis using models, as well as the utilization of several different types of machine learning technologies. PMID:29324649

Machine Learning Methods for Analysis of Metabolic Data and Metabolic Pathway Modeling.

PubMed

Cuperlovic-Culf, Miroslava

2018-01-11

Machine learning uses experimental data to optimize clustering or classification of samples or features, or to develop, augment or verify models that can be used to predict behavior or properties of systems. It is expected that machine learning will help provide actionable knowledge from a variety of big data including metabolomics data, as well as results of metabolism models. A variety of machine learning methods has been applied in bioinformatics and metabolism analyses including self-organizing maps, support vector machines, the kernel machine, Bayesian networks or fuzzy logic. To a lesser extent, machine learning has also been utilized to take advantage of the increasing availability of genomics and metabolomics data for the optimization of metabolic network models and their analysis. In this context, machine learning has aided the development of metabolic networks, the calculation of parameters for stoichiometric and kinetic models, as well as the analysis of major features in the model for the optimal application of bioreactors. Examples of this very interesting, albeit highly complex, application of machine learning for metabolism modeling will be the primary focus of this review presenting several different types of applications for model optimization, parameter determination or system analysis using models, as well as the utilization of several different types of machine learning technologies.

Selection of meteorological parameters affecting rainfall estimation using neuro-fuzzy computing methodology

NASA Astrophysics Data System (ADS)

Hashim, Roslan; Roy, Chandrabhushan; Motamedi, Shervin; Shamshirband, Shahaboddin; Petković, Dalibor; Gocic, Milan; Lee, Siew Cheng

2016-05-01

Rainfall is a complex atmospheric process that varies over time and space. Researchers have used various empirical and numerical methods to enhance estimation of rainfall intensity. We developed a novel prediction model in this study, with the emphasis on accuracy to identify the most significant meteorological parameters having effect on rainfall. For this, we used five input parameters: wet day frequency (dwet), vapor pressure (e̅a), and maximum and minimum air temperatures (Tmax and Tmin) as well as cloud cover (cc). The data were obtained from the Indian Meteorological Department for the Patna city, Bihar, India. Further, a type of soft-computing method, known as the adaptive-neuro-fuzzy inference system (ANFIS), was applied to the available data. In this respect, the observation data from 1901 to 2000 were employed for testing, validating, and estimating monthly rainfall via the simulated model. In addition, the ANFIS process for variable selection was implemented to detect the predominant variables affecting the rainfall prediction. Finally, the performance of the model was compared to other soft-computing approaches, including the artificial neural network (ANN), support vector machine (SVM), extreme learning machine (ELM), and genetic programming (GP). The results revealed that ANN, ELM, ANFIS, SVM, and GP had R2 of 0.9531, 0.9572, 0.9764, 0.9525, and 0.9526, respectively. Therefore, we conclude that the ANFIS is the best method among all to predict monthly rainfall. Moreover, dwet was found to be the most influential parameter for rainfall prediction, and the best predictor of accuracy. This study also identified sets of two and three meteorological parameters that show the best predictions.

Analysis of stationary and dynamic factors affecting highway accident occurrence: A dynamic correlated grouped random parameters binary logit approach.

PubMed

Fountas, Grigorios; Sarwar, Md Tawfiq; Anastasopoulos, Panagiotis Ch; Blatt, Alan; Majka, Kevin

2018-04-01

Traditional accident analysis typically explores non-time-varying (stationary) factors that affect accident occurrence on roadway segments. However, the impact of time-varying (dynamic) factors is not thoroughly investigated. This paper seeks to simultaneously identify pre-crash stationary and dynamic factors of accident occurrence, while accounting for unobserved heterogeneity. Using highly disaggregate information for the potential dynamic factors, and aggregate data for the traditional stationary elements, a dynamic binary random parameters (mixed) logit framework is employed. With this approach, the dynamic nature of weather-related, and driving- and pavement-condition information is jointly investigated with traditional roadway geometric and traffic characteristics. To additionally account for the combined effect of the dynamic and stationary factors on the accident occurrence, the developed random parameters logit framework allows for possible correlations among the random parameters. The analysis is based on crash and non-crash observations between 2011 and 2013, drawn from urban and rural highway segments in the state of Washington. The findings show that the proposed methodological framework can account for both stationary and dynamic factors affecting accident occurrence probabilities, for panel effects, for unobserved heterogeneity through the use of random parameters, and for possible correlation among the latter. The comparative evaluation among the correlated grouped random parameters, the uncorrelated random parameters logit models, and their fixed parameters logit counterpart, demonstrate the potential of the random parameters modeling, in general, and the benefits of the correlated grouped random parameters approach, specifically, in terms of statistical fit and explanatory power. Published by Elsevier Ltd.

Maternal metabolism affects endometrial expression of oxidative stress and FOXL2 genes in cattle

PubMed Central

Forde, Niamh; Poirée, Mélanie; Healey, Gareth D.; Giraud-Delville, Corinne; Reinaud, Pierrette; Eozenou, Caroline; Vitorino Carvalho, Anaïs; Galio, Laurent; Raliou, Mariam; Oudin, Jean-François; Richard, Christophe; Sheldon, I. Martin; Charpigny, Gilles; Lonergan, Pat; Sandra, Olivier

2017-01-01

Intensive selection for milk production has led to reduced reproductive efficiency in high-producing dairy cattle. The impact of intensive milk production on oocyte quality as well as early embryo development has been established but few analyses have addressed this question at the initiation of implantation, a critical milestone ensuring a successful pregnancy and normal post-natal development. Our study aimed to determine if contrasted maternal metabolism affects the previously described sensory properties of the endometrium to the conceptus in cattle. Following embryo transfer at Day 7 post-oestrus, endometrial caruncular (CAR) and intercaruncular (ICAR) areas were collected at Day 19 from primiparous postpartum Holstein-Friesian cows that were dried-off immediately after parturition (i.e., never milked; DRY) or milked twice daily (LACT). Gene quantification indicated no significant impact of lactation on endometrial expression of transcripts previously reported as conceptus-regulated (PLET1, PTGS2, SOCS6) and interferon-tau stimulated (RSAD2, SOCS1, SOCS3, STAT1) factors or known as female hormone-regulated genes (FOXL2, SCARA5, PTGS2). Compared with LACT cows, DRY cows exhibited mRNA levels with increased expression for FOXL2 transcription factor and decreased expression for oxidative stress-related genes (CAT, SOD1, SOD2). In vivo and in vitro experiments highlighted that neither interferon-tau nor FOXL2 were involved in transcriptional regulation of CAT, SOD1 and SOD2. In addition, our data showed that variations in maternal metabolism had a higher impact on gene expression in ICAR areas. Collectively, our findings prompt the need to fully understand the extent to which modifications in endometrial physiology drive the trajectory of conceptus development from implantation onwards when maternal metabolism is altered. PMID:29281695

Maternal metabolism affects endometrial expression of oxidative stress and FOXL2 genes in cattle.

PubMed

Lesage-Padilla, Audrey; Forde, Niamh; Poirée, Mélanie; Healey, Gareth D; Giraud-Delville, Corinne; Reinaud, Pierrette; Eozenou, Caroline; Vitorino Carvalho, Anaïs; Galio, Laurent; Raliou, Mariam; Oudin, Jean-François; Richard, Christophe; Sheldon, I Martin; Charpigny, Gilles; Lonergan, Pat; Sandra, Olivier

2017-01-01

Intensive selection for milk production has led to reduced reproductive efficiency in high-producing dairy cattle. The impact of intensive milk production on oocyte quality as well as early embryo development has been established but few analyses have addressed this question at the initiation of implantation, a critical milestone ensuring a successful pregnancy and normal post-natal development. Our study aimed to determine if contrasted maternal metabolism affects the previously described sensory properties of the endometrium to the conceptus in cattle. Following embryo transfer at Day 7 post-oestrus, endometrial caruncular (CAR) and intercaruncular (ICAR) areas were collected at Day 19 from primiparous postpartum Holstein-Friesian cows that were dried-off immediately after parturition (i.e., never milked; DRY) or milked twice daily (LACT). Gene quantification indicated no significant impact of lactation on endometrial expression of transcripts previously reported as conceptus-regulated (PLET1, PTGS2, SOCS6) and interferon-tau stimulated (RSAD2, SOCS1, SOCS3, STAT1) factors or known as female hormone-regulated genes (FOXL2, SCARA5, PTGS2). Compared with LACT cows, DRY cows exhibited mRNA levels with increased expression for FOXL2 transcription factor and decreased expression for oxidative stress-related genes (CAT, SOD1, SOD2). In vivo and in vitro experiments highlighted that neither interferon-tau nor FOXL2 were involved in transcriptional regulation of CAT, SOD1 and SOD2. In addition, our data showed that variations in maternal metabolism had a higher impact on gene expression in ICAR areas. Collectively, our findings prompt the need to fully understand the extent to which modifications in endometrial physiology drive the trajectory of conceptus development from implantation onwards when maternal metabolism is altered.

Affective state influences perception by affecting decision parameters underlying bias and sensitivity.

PubMed

Lynn, Spencer K; Zhang, Xuan; Barrett, Lisa Feldman

2012-08-01

Studies of the effect of affect on perception often show consistent directional effects of a person's affective state on perception. Unpleasant emotions have been associated with a "locally focused" style of stimulus evaluation, and positive emotions with a "globally focused" style. Typically, however, studies of affect and perception have not been conducted under the conditions of perceptual uncertainty and behavioral risk inherent to perceptual judgments outside the laboratory. We investigated the influence of perceivers' experienced affect (valence and arousal) on the utility of social threat perception by combining signal detection theory and behavioral economics. We compared 3 perceptual decision environments that systematically differed with respect to factors that underlie uncertainty and risk: the base rate of threat, the costs of incorrect identification threat, and the perceptual similarity of threats and nonthreats. We found that no single affective state yielded the best performance on the threat perception task across the 3 environments. Unpleasant valence promoted calibration of response bias to base rate and costs, high arousal promoted calibration of perceptual sensitivity to perceptual similarity, and low arousal was associated with an optimal adjustment of bias to sensitivity. However, the strength of these associations was conditional upon the difficulty of attaining optimal bias and high sensitivity, such that the effect of the perceiver's affective state on perception differed with the cause and/or level of uncertainty and risk.

Salmonella Typhimurium metabolism affects virulence in the host - A mini-review.

PubMed

Herrero-Fresno, Ana; Olsen, John Elmerdhahl

2018-05-01

Salmonella enterica remains an important food borne pathogen in all regions of the world with S. Typhimurium as one of the most frequent serovars causing food borne disease. Since the majority of human cases are caused by food of animal origin, there has been a high interest in understanding how S. Typhimurium interacts with the animal host, mostly focusing on factors that allow it to breach host barriers and to manipulate host cells to the benefit of itself. Up to recently, such studies have ignored the metabolic factors that allow the bacteria to multiply in the host, but this is changing rapidly, and we are now beginning to understand that virulence and metabolism in the host are closely linked. The current review highlights which metabolic factors that are essential for Salmonella Typhimurium growth in the intestine, in cultured epithelial and macrophage-like cell lines, at systemic sites during invasive salmonellosis, and during long term asymptomatic colonization of the host. It also points to the limitations in our current knowledge, most notably that most studies have been carried out with few well-characterized laboratory strains, that we do not know how much the in vivo metabolism differs between serotypes, and that most results are based on challenges in the mouse model of infection. It will be very important to realize whether the current understanding of Salmonella metabolism in the host is true for all serotypes and all possible hosts. Copyright © 2017 Elsevier Ltd. All rights reserved.

Opportunities for genetic improvement of metabolic diseases

USDA-ARS?s Scientific Manuscript database

Metabolic disorders are disturbances to one or more of the metabolic processes in dairy cattle. Dysfunction of any of these processes is associated with the manifestation of metabolic diseases or disorders. In this review, data recording, incidences, genetic parameters, predictors and status of gene...

Deanol affects choline metabolism in peripheral tissues of mice.

PubMed

Haubrich, D R; Gerber, N H; Pflueger, A B

1981-08-01

Administration of 2-dimethylaminoethanol (deanol) to mice induced an increase in both the concentration and the rate of turnover of free choline in blood. Treatment with deanol also caused an increase in the concentration of choline in kidneys, and markedly inhibited the rates of oxidation and phosphorylation of intravenously administered [3H-methyl]choline. In the liver, deanol inhibited the rate of phosphorylation of [3H-methyl]choline, but did not inhibit its rate of oxidation or cause an increase in the level of free choline. These findings suggest that deanol increases the choline concentration in blood by inhibition of its metabolism in tissues. Deanol may ultimately produce its central cholinergic effects by inhibition of choline metabolism in peripheral tissues, causing free choline choline to accumulate in blood, enter the brain, and stimulate cholinergic receptors.

Affective State Influences Perception by Affecting Decision Parameters Underlying Bias and Sensitivity

PubMed Central

Lynn, Spencer K.; Zhang, Xuan; Barrett, Lisa Feldman

2012-01-01

Studies of the effect of affect on perception often show consistent directional effects of a person’s affective state on perception. Unpleasant emotions have been associated with a “locally focused” style of stimulus evaluation, and positive emotions with a “globally focused” style. Typically, however, studies of affect and perception have not been conducted under the conditions of perceptual uncertainty and behavioral risk inherent to perceptual judgments outside the laboratory. We investigated the influence of perceivers’ experience affect (valence and arousal) on the utility of social threat perception by combining signal detection theory and behavioral economics. We created three perceptual decision environments that systematically differed with respect to factors that underlie uncertainty and risk: the base rate of threat, the costs of incorrect identification threat, and the perceptual similarity of threats and non-threats. We found that no single affective state yielded the best performance on the threat perception task across the three environments. Unpleasant valence promoted calibration of response bias to base rate and costs, high arousal promoted calibration of perceptual sensitivity to perceptual similarity, and low arousal was associated with an optimal adjustment of bias to sensitivity. However, the strength of these associations was conditional upon the difficulty of attaining optimal bias and high sensitivity, such that the effect of the perceiver’s affective state on perception differed with the cause and/or level of uncertainty and risk. PMID:22251054

Multi-Criteria Optimization of Regulation in Metabolic Networks

PubMed Central

Higuera, Clara; Villaverde, Alejandro F.; Banga, Julio R.; Ross, John; Morán, Federico

2012-01-01

Determining the regulation of metabolic networks at genome scale is a hard task. It has been hypothesized that biochemical pathways and metabolic networks might have undergone an evolutionary process of optimization with respect to several criteria over time. In this contribution, a multi-criteria approach has been used to optimize parameters for the allosteric regulation of enzymes in a model of a metabolic substrate-cycle. This has been carried out by calculating the Pareto set of optimal solutions according to two objectives: the proper direction of flux in a metabolic cycle and the energetic cost of applying the set of parameters. Different Pareto fronts have been calculated for eight different “environments” (specific time courses of end product concentrations). For each resulting front the so-called knee point is identified, which can be considered a preferred trade-off solution. Interestingly, the optimal control parameters corresponding to each of these points also lead to optimal behaviour in all the other environments. By calculating the average of the different parameter sets for the knee solutions more frequently found, a final and optimal consensus set of parameters can be obtained, which is an indication on the existence of a universal regulation mechanism for this system.The implications from such a universal regulatory switch are discussed in the framework of large metabolic networks. PMID:22848435

Gut microbiota and metabolic syndrome.

PubMed

Festi, Davide; Schiumerini, Ramona; Eusebi, Leonardo Henry; Marasco, Giovanni; Taddia, Martina; Colecchia, Antonio

2014-11-21

Gut microbiota exerts a significant role in the pathogenesis of the metabolic syndrome, as confirmed by studies conducted both on humans and animal models. Gut microbial composition and functions are strongly influenced by diet. This complex intestinal "superorganism" seems to affect host metabolic balance modulating energy absorption, gut motility, appetite, glucose and lipid metabolism, as well as hepatic fatty storage. An impairment of the fine balance between gut microbes and host's immune system could culminate in the intestinal translocation of bacterial fragments and the development of "metabolic endotoxemia", leading to systemic inflammation and insulin resistance. Diet induced weight-loss and bariatric surgery promote significant changes of gut microbial composition, that seem to affect the success, or the inefficacy, of treatment strategies. Manipulation of gut microbiota through the administration of prebiotics or probiotics could reduce intestinal low grade inflammation and improve gut barrier integrity, thus, ameliorating metabolic balance and promoting weight loss. However, further evidence is needed to better understand their clinical impact and therapeutic use.

Constraint based modeling of metabolism allows finding metabolic cancer hallmarks and identifying personalized therapeutic windows.

PubMed

Bordel, Sergio

2018-04-13

In order to choose optimal personalized anticancer treatments, transcriptomic data should be analyzed within the frame of biological networks. The best known human biological network (in terms of the interactions between its different components) is metabolism. Cancer cells have been known to have specific metabolic features for a long time and currently there is a growing interest in characterizing new cancer specific metabolic hallmarks. In this article it is presented a method to find personalized therapeutic windows using RNA-seq data and Genome Scale Metabolic Models. This method is implemented in the python library, pyTARG. Our predictions showed that the most anticancer selective (affecting 27 out of 34 considered cancer cell lines and only 1 out of 6 healthy mesenchymal stem cell lines) single metabolic reactions are those involved in cholesterol biosynthesis. Excluding cholesterol biosynthesis, all the considered cell lines can be selectively affected by targeting different combinations (from 1 to 5 reactions) of only 18 metabolic reactions, which suggests that a small subset of drugs or siRNAs combined in patient specific manners could be at the core of metabolism based personalized treatments.

Identifying the myogenic and metabolic components of cerebral autoregulation.

PubMed

Payne, S J

2018-05-14

Cerebral autoregulation is the term used to describe a number of mechanisms that act together to maintain a near constant cerebral blood flow in response to changes in arterial blood pressure. These mechanisms are complex and known to be affected in a range of cerebrovascular diseases. However, it can be difficult to assign an alteration in cerebral autoregulation to one of the underlying physiological mechanisms without the use of a complex mathematical model. In this paper, we thus set out a new approach that enables these mechanisms to be related to the autoregulation behaviour and hence inferred from experimental measurements. We show that the arteriolar response is a function of just three parameters, which we term the elastic, the myogenic and the metabolic sensitivity coefficients, and that the full vascular response is dependent upon only seven parameters. The ratio of the strengths of the myogenic and the metabolic responses is found to be in the range 2.5 to 5 over a wide range of pressure, indicating that the balance between the two appears to lie within this range. We validate the model with existing experimental data both at the level of an individual vessel and across the whole vasculature, and show that the results are consistent with findings from the literature. We then conduct a sensitivity analysis of the model to demonstrate which parameters are most important in determining the strength of static autoregulation, showing that autoregulation strength is predominantly set by the arteriolar sensitivity coefficients. This new approach could be used in future studies to help to interpret the components of the autoregulation response and how they are affected under different conditions, providing a greater insight into the fundamental processes that govern autoregulation. Copyright © 2018. Published by Elsevier Ltd.

Triglyceride level affecting shared susceptibility genes in metabolic syndrome and coronary artery disease.

PubMed

Kisfali, P; Polgár, N; Sáfrány, E; Sümegi, K; Melegh, B I; Bene, J; Wéber, A; Hetyésy, K; Melegh, B

2010-01-01

Metabolic syndrome is characterized primarily by abdominal obesity, high triglyceride- and low HDL cholesterol levels, elevated blood pressure, and increased fasting glucose levels, which are often associated with coronary heart diseases. Several factors, such as physical inactivity, age, and several endocrine and genetic factors can increase the risk of the development of the disease. Gathered evidence shows, that metabolic syndrome is not only a risk factor for cardiovascular disease, but often both of them have the same shared susceptibility genes, as several genetic variants have shown a predisposition to both diseases. Due to the spread of robust genome wide association studies, the number of candidate genes in metabolic syndrome and coronary heart disease susceptibility increases very rapidly. From the growing spectrum of the genes influencing lipid metabolism (like the LPL; PPARA; APOE; APOAI/CIII/AIV genecluster and APOAS5), the current review focuses on shared susceptibility variants involved in triglyceride metabolism and consequently the effects on the circulating triglyceride levels. As the elevated levels of triglycerides can be associated with disease phenotypes, some of these SNPs can have susceptibility features in both metabolic syndrome and in coronary heart disease, thereby some of them can even represent a kind of susceptibility link between metabolic syndrome and coronary artery disease.

Dietary cranberry, blueberry, and black raspberry affects the development of dyslipidemia and insulin insensitivity associated with metabolic syndrome in high fructose fed rats

USDA-ARS?s Scientific Manuscript database

Effects of feeding cranberry, blueberry, and black raspberry powder on selected parameters of metabolic syndrome were investigated in 40 growing male Sprague Dawley rats. Animals were divided into five dietary treatments of 1) control AIN93G diet, 2) high fructose (65% by weight, HF) diet, and 3-5) ...

Endocrine and metabolic changes in transition dairy cows are affected by prepartum infusions of a serotonin precursor.

PubMed

Hernández-Castellano, Lorenzo E; Hernandez, Laura L; Sauerwein, Helga; Bruckmaier, Rupert M

2017-06-01

Serotonin (5-HT) has been shown to be involved in calcium homeostasis, modulating calcium concentration in blood. In addition, 5-HT participates in a variety of metabolic pathways, mainly through the modulation of glucose and lipid metabolism. The hypothesis of the present study was that the prepartum administration of 5-hydroxy-l-tryptophan (5-HTP), a 5-HT precursor, would affect endocrine systems related to calcium homeostasis, and interact with other endocrine and metabolic pathways during the transition period. In this study, 20 Holstein dairy cows were randomly assigned to 2 experimental groups. Both groups received a daily i.v. infusion of 1 L of either 0.9% NaCl (control group; n = 10) or 0.9% NaCl containing 1 mg of 5-HTP/kg of BW (5-HTP group, n = 10). Infusions started d 10 before estimated parturition date and ended the day of parturition, resulting in a minimum of 4 d of infusion (8.4 ± 0.7 d of infusion). Until parturition, blood samples were collected before the daily infusions, and postpartum daily until d 7, and on d 30. Plasma concentrations of parathyroid hormone (PTH) were transiently increased at parturition and on d 1 in control cows. In the 5-HTP group PTH remained unchanged. The concentration of pyridinoline (PYD), an established marker for calcium release from the bone to the bloodstream, increased on d 1 postpartum only in the 5-HTP group. In control cows, PYD concentrations did not change on d 1 postpartum. Melatonin concentrations were slightly but significantly increased in the 5-HTP group compared with the control group. Insulin concentrations decreased in both groups postpartum. Before parturition, leptin concentrations decreased in both groups and remained at this level until d 30 postpartum. Plasma IgG concentrations decreased in both groups on d -1 postpartum. Haptoglobin increased in both groups on d -1 and remained at this level until d 7 postpartum. No differences between groups were observed for insulin, glucagon, IgG, leptin

Comparison of parameters affecting GNP-loaded choroidal melanoma dosimetry; Monte Carlo study

NASA Astrophysics Data System (ADS)

Sharabiani, Marjan; Asadi, Somayeh; Barghi, Amir Rahnamai; Vaezzadeh, Mehdi

2018-04-01

The current study reports the results of tumor dosimetry in the presence of gold nanoparticles (GNPs) with different sizes and concentrations. Due to limited number of works carried out on the brachytherapy of choroidal melanoma in combination with GNPs, this study was performed to determine the optimum size and concentration for GNPs which contributes the highest dose deposition in tumor region, using two phantom test cases namely water phantom and a full Monte Carlo model of human eye. Both water and human eye phantoms were simulated with MCNP5 code. Tumor dosimetry was performed for a typical point photon source with an energy of 0.38 MeV as a high energy source and 103Pd brachytherapy source with an average energy of 0.021 MeV as a low energy source in water phantom and eye phantom respectively. Such a dosimetry was done for different sizes and concentrations of GNPs. For all of the diameters, increase in concentration of GNPs resulted in an increase in dose deposited in the region of interest. In a certain concentration, GNPs with larger diameters contributed more dose to the tumor region, which was more pronounced using eye phantom. 100 nm was reported as the optimum size in order to achieve the highest energy deposition within the target. This work investigated the optimum parameters affecting macroscopic dose enhancement in GNP-aided brachytherapy of choroidal melanoma. The current work also had implications on using low energy photon sources in the presence of GNPs to acquire the highest dose enhancement. This study is conducted through four different sizes and concentrations of GNPs. Considering the sensitivity of human eye tissue, in order to report the precise optimum parameters affecting radiosensitivity, a comprehensive study on a wide range of sizes and concentrations are required.

Polymorphism of the beta3-adrenergic receptor gene affects basal metabolic rate in obese Finns.

PubMed

Sipiläinen, R; Uusitupa, M; Heikkinen, S; Rissanen, A; Laakso, M

1997-01-01

Low basal metabolic rate (BMR) is a risk factor for weight gain and obesity. The polymorphism at codon 64 of the beta3-adrenergic receptor gene has been suggested to be associated with BMR. We investigated the frequency of the Trp64Arg of the beta3-adrenergic receptor gene and the effects of this polymorphism on BMR in obese Finns. Altogether, 170 obese subjects (29 men, 141 women, BMI 34.7 +/- 3.8 kg/m2, mean +/- SD) participated in the study. The frequency of the Trp64Arg polymorphism was 19%. None of the obese subjects were homozygous for the Arg-encoding allele. The frequency of the Trp64Arg polymorphism in obese Finns did not differ from nonobese and normoglycemic control subjects. BMR adjusted for lean body mass and age was lower in subjects with the Trp64Arg polymorphism (n = 20) than in normal homozygotes Trp64Trp (n = 99) (1,569 +/- 73 vs. 1,635 +/- 142 kcal/day, P = 0.004). For the female group (n = 98), the respective values were 1,501 +/- 66 kcal/day vs. 1,568 +/- 127 kcal/day (P = 0.004). There were no significant differences in weight, BMI, waist-to-hip ratio, lean body mass, percentage of fat, and respiratory quotient between the groups with or without the Trp64Arg polymorphism. Neither serum glucose nor insulin levels differed between the two groups. We conclude that the Trp64Arg polymorphism of the beta3-adrenergic receptor gene affects basal metabolic rate in obese Finns but does not have significant effect on glucose metabolism.

[Comparison of HbA1c, fructosamine and the main metabolic parameters in a non-insulin-dependent diabetic population].

PubMed

Magnati, G; Arsenio, L; Baroni, M C; Bodria, P; Bossi, S; Delsignore, R; Ippolito, L; Mineo, F; Strata, A

1990-01-01

Our objective was the checking of clinical data obtainable from the assay of some parameters in NID diabetic individuals. To this end, we studied 133 patients--57 males and 76 females, average age 74.36 +/- 1.01 years, 72.6% of which were above 65 years of age. The control population was subdivided as follows: 50 subjects, 26 F and 24 M; average age 71.25 +/- 1.32 years, with normal glucidic tolerance as assessed by OGTT. Current glycemia, average glycemia, fructosamine, glycosylated hemoglobin, triglycerides, LDL-cholesterol and apolipoprotein B were obviously much higher than normal in the individuals admitted to the study. A statistically significant correlation was found between average glycemia, glycosylated hemoglobin, LDL-cholesterol and blood triglycerides (p less than 0.05). No correlation was found between current glycemia, fructosamine and glycosylated hemoglobin. Similarly, serum fructosamine was unrelated to the parameters studied. In our study, fructosamine, glycosylated hemoglobin and current glycemia offered unrelatable data. Hence, in our opinion it is necessary to assay these three parameters contemporaneously for a reliable assessment of metabolic compensation.

Foliar nitrogen metabolism of adult Douglas-fir trees is affected by soil water availability and varies little among provenances.

PubMed

Du, Baoguo; Kreuzwieser, Jürgen; Dannenmann, Michael; Junker, Laura Verena; Kleiber, Anita; Hess, Moritz; Jansen, Kirstin; Eiblmeier, Monika; Gessler, Arthur; Kohnle, Ulrich; Ensminger, Ingo; Rennenberg, Heinz; Wildhagen, Henning

2018-01-01

The coniferous forest tree Douglas-fir (Pseudotsuga menziesii) is native to the pacific North America, and is increasingly planted in temperate regions worldwide. Nitrogen (N) metabolism is of great importance for growth, resistance and resilience of trees. In the present study, foliar N metabolism of adult trees of three coastal and one interior provenance of Douglas-fir grown at two common gardens in southwestern Germany (Wiesloch, W; Schluchsee, S) were characterized in two subsequent years. Both the native North American habitats of the seed sources and the common garden sites in Germany differ in climate conditions. Total and mineral soil N as well as soil water content were higher in S compared to W. We hypothesized that i) provenances differ constitutively in N pool sizes and composition, ii) N pools are affected by environmental conditions, and iii) that effects of environmental factors on N pools differ among interior and coastal provenances. Soil water content strongly affected the concentrations of total N, soluble protein, total amino acids (TAA), arginine and glutamate. Foliar concentrations of total N, soluble protein, structural N and TAA of trees grown at W were much higher than in trees at S. Provenance effects were small but significant for total N and soluble protein content (interior provenance showed lowest concentrations), as well as arginine, asparagine and glutamate. Our data suggest that needle N status of adult Douglas-fir is independent from soil N availability and that low soil water availability induces a re-allocation of N from structural N to metabolic N pools. Small provenance effects on N pools suggest that local adaptation of Douglas-fir is not dominated by N conditions at the native habitats.

Anthropometry in cardio-metabolic risk assessment.

PubMed

Mišigoj-Duraković, Marjeta; Sorić, Maroje; Duraković, Zijad

2014-03-01

High prevalence of obesity, as a major public health problem, is connected with chronic cardiovascular and metabolic diseases. That is why some simple anthropometric parameters were developed to estimate overweight and obesity, and in the primary screening of risk groups. In this field, body mass index (BMI) is the most frequent parameter, both in epidemiological research and in everyday practice. It is a part of the algorithm used in the early detection of overweight and obese persons. However, BMI does not provide any data on body composition. This is why it is particularly insufficient in estimating body mass in physically active persons and in athletes who are often overweight, with a higher proportion of lean body mass but without any excess fat, as well as in those with normal weight but lower than normal lean body mass and/ or gentle skeleton. Over the last few decades, attention has been especially directed to different body fat distribution in relation to chronic cardio-vascular and metabolic diseases. Waist circumference (WC) is the best anthropometric predictor of cardiovascular risk. It is considered an indirect parameter of visceral fat. WC and waist-to-hip ratio are good parameters showing body fat distribution and cardio-metabolic risk. Waist-to-height ratio is suggested by some authors to be an even better parameter of cardio-vascular risk and metabolic syndrome. Hypertriglyceridemia combined with increased WC is considered a marker of atherogenic metabolic risk. The paper also deals with procedures of body composition analysis. Anthropometric assessment of body composition analysis belongs to a group of simple and inexpensive procedures. Development of generalised equations for body density prediction introduced anthropometric methods in the analysis of body composition in everyday practice.

Students' Perspective (Age Wise, Gender Wise and Year Wise) of Parameters Affecting the Undergraduate Engineering Education

ERIC Educational Resources Information Center

Kumari, Neeraj

2014-01-01

The objective of the study is to examine the students' perspective (age wise, gender wise and year wise) of parameters affecting the undergraduate engineering education system present in a private technical institution in NCR [National Capital Region], Haryana. It is a descriptive type of research in nature. The data has been collected with the…

Activity affects intraspecific body-size scaling of metabolic rate in ectothermic animals.

PubMed

Glazier, Douglas Stewart

2009-10-01

Metabolic rate is commonly thought to scale with body mass (M) to the 3/4 power. However, the metabolic scaling exponent (b) may vary with activity state, as has been shown chiefly for interspecific relationships. Here I use a meta-analysis of literature data to test whether b changes with activity level within species of ectothermic animals. Data for 19 species show that b is usually higher during active exercise (mean +/- 95% confidence limits = 0.918 +/- 0.038) than during rest (0.768 +/- 0.069). This significant upward shift in b to near 1 is consistent with the metabolic level boundaries hypothesis, which predicts that maximal metabolic rate during exercise should be chiefly influenced by volume-related muscular power production (scaling as M (1)). This dependence of b on activity level does not appear to be a simple temperature effect because body temperature in ectotherms changes very little during exercise.

Dietary starch types affect liver nutrient metabolism of finishing pigs.

PubMed

Xie, Chen; Li, Yanjiao; Li, Jiaolong; Zhang, Lin; Zhou, Guanghong; Gao, Feng

2017-09-01

This study aimed to evaluate the effect of different starch types on liver nutrient metabolism of finishing pigs. In all ninety barrows were randomly allocated to three diets with five replicates of six pigs, containing purified waxy maize starch (WMS), non-waxy maize starch (NMS) and pea starch (PS) (the amylose to amylopectin ratios were 0·07, 0·19 and 0·28, respectively). After 28 d of treatments, two per pen (close to the average body weight of the pen) were weighed individually, slaughtered and liver samples were collected. Compared with the WMS diet, the PS diet decreased the activities of glycogen phosphorylase, phosphoenolpyruvate carboxykinase and the expression of phosphoenolpyruvate carboxykinase 1 in liver (P0·05). Compared with the WMS diet, the PS diet reduced the expressions of glutamate dehydrogenase and carbamoyl phosphate synthetase 1 in liver (P<0·05). PS diet decreased the expression of the insulin receptor, and increased the expressions of mammalian target of rapamycin complex 1 and ribosomal protein S6 kinase β-1 in liver compared with the WMS diet (P<0·05). These findings indicated that the diet with higher amylose content could down-regulate gluconeogenesis, and cause less fat deposition and more protein deposition by affecting the insulin/PI3K/protein kinase B signalling pathway in liver of finishing pigs.

Effect on oxidative stress, hepatic chemical metabolizing parameters, and genotoxic damage of mad honey intake in rats.

PubMed

Eraslan, G; Kanbur, M; Karabacak, M; Arslan, K; Siliğ, Y; Soyer Sarica, Z; Tekeli, M Y; Taş, A

2017-01-01

A total of 66 male Wistar rats were used and six groups (control: 10 animals and experimental: 12 animals) were formed. While a separate control group was established for each study period, mad honey application to the animals in the experimental group was carried out with a single dose (12.5 g kg -1 body weight (b.w.); acute stage), at a dose of 7.5 g kg -1 b.w. for 21 days (subacute stage), and at a dose of 5 g kg -1 b.w. for 60 days (chronic stage). Tissue and blood oxidative stress markers (malondialdehyde (MDA), nitric oxide (NO), 4-hydroxynonenal (HNE), superoxide dismutase, catalase, glutathione (GSH) peroxidase, and glucose-6-phosphate dehydrogenase), hepatic chemical metabolizing parameters in the liver (cytochrome P450 2E1, nicotinamide adenine dinucleotide (NADH)-cytochrome b5 reductase, nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome c reductase (CYTC), GSH S-transferase (GST), and GSH), and micronucleus and comet test in some samples were examined. Findings from the study showed that single and repeated doses given over the period increased MDA, NO, and HNE levels while decreasing/increasing tissue and blood antioxidant enzyme activities. From hepatic chemical metabolizing parameters, GST activity increased in the subacute and chronic stages and CYTC activity increased in the acute period, whereas GSH level decreased in the subacute stage. Changes in tail and head intensities were found in most of the comet results. Mad honey caused oxidative stresses for each exposure period and made some significant changes on the comet test in certain periods for some samples obtained. In other words, according to the available research results obtained, careless consumption of mad honey for different medical purposes is not appropriate.

Apple Peel Supplemented Diet Reduces Parameters of Metabolic Syndrome and Atherogenic Progression in ApoE−/− Mice

PubMed Central

Gonzalez, Jaime; Donoso, Wendy; Sandoval, Nathalie; Reyes, María; Gonzalez, Priscila; Gajardo, Monica; Morales, Erik; Neira, Amalia; Razmilic, Iván; Yuri, José A.

2015-01-01

Cardiovascular Diseases (CVD) represent about 30% of all causes of death worldwide. The development of CVD is related in many cases with the previous existence of metabolic syndrome (MS). It is known that apple consumption has a cardiovascular protecting effect, containing phenolic compounds with antioxidant effect, which are concentrated in the fruit peel. The objective of this study was to test the effect of apple peel consumption in a murine model of MS and apoE−/− mice. Apple supplemented diets reduced the biochemical parameters (glycaemia, total cholesterol, HDL-cholesterol, LDL-cholesterol, ureic nitrogen, triglycerides, insulin, and asymmetric dimethylarginine (ADMA)) of MS model in CF1 mice significantly. The model apoE−/− mouse was used to evaluate the capacity of the apple peel to revert the progression of the atherogenesis. FD with HAP reverts cholesterol significantly and slows down the progression of the plate diminishing the cholesterol accumulation area. With these results, it can be concluded that the consumption of apple peel reduces several MS parameters and the atherogenic progression in mice. PMID:26075004

Comparison between repaglinide and glimepiride in patients with type 2 diabetes mellitus: a one-year, randomized, double-blind assessment of metabolic parameters and cardiovascular risk factors.

PubMed

Derosa, Giuseppe; Mugellini, Amedeo; Ciccarelli, Leonardina; Crescenzi, Giuseppe; Fogari, Roberto

2003-02-01

Repaglinide and glimepiride are relatively new oral hypoglycemic agents. Few data are available concerning their effects on metabolic parameters other than measures of glycemic control. In addition to assessing the effects of repaglinide and glimepiride on glycemic control in patients with type 2 diabetes mellitus, this study also examined the effects of these agents on 3 metabolic parameters known to be cardiovascular risk factors--lipoprotein(a) (Lp[a]), plasminogen activator inhibitor-1 (PAI-1), and homocysteine (Hcy). This randomized, placebo-controlled, double-blind trial was conducted at a single center in Italy. Eligible patients were nonsmokers; had no hypertension or coronary heart disease; were taking no hypolipidemic drugs, diuretics, beta-blockers, or thyroxin; and had normal renal function. After an initial 4-week placebo washout period, patients were randomized to receive repaglinide 1 mg/d or glimepiride 1 mg/d. The dose of study drug was optimized over an 8-week titration period, which was followed by a 12-month treatment period. Measures of glycemic control (glycated hemoglobin [HbA1c], fasting plasma glucose [FPG], postprandial plasma glucose [PPG], fasting plasma insulin [FPI], postprandial plasma insulin [PPI]) and the other metabolic parameters of interest were assessed after 6 and 12 months of treatment. One hundred twenty-four patients (63 women, 61 men) completed the study, 62 in each treatment group. There were no significant differences in demographic characteristics between groups. After 6 and 12 months of treatment, FPG levels and HbA1c values were significantly reduced from baseline in both groups (6 months, P < 0.05; 12 months, P < 0.01). After 6 months, PPG levels were significantly decreased only in the repaglinide group (P < 0.05 vs baseline); at 12 months, however, PPG levels were significantly reduced from baseline in both groups (P < 0.01 repaglinide, P < 0.05 glimepiride). No significant changes from baseline in FPI or PPI

Starch Granule Re-Structuring by Starch Branching Enzyme and Glucan Water Dikinase Modulation Affects Caryopsis Physiology and Metabolism

PubMed Central

Shaik, Shahnoor S.; Obata, Toshihiro; Hebelstrup, Kim H.; Schwahn, Kevin; Fernie, Alisdair R.; Mateiu, Ramona V.; Blennow, Andreas

2016-01-01

Starch is of fundamental importance for plant development and reproduction and its optimized molecular assembly is potentially necessary for correct starch metabolism. Re-structuring of starch granules in-planta can therefore potentially affect plant metabolism. Modulation of granule micro-structure was achieved by decreasing starch branching and increasing starch-bound phosphate content in the barley caryopsis starch by RNAi suppression of all three Starch Branching Enzyme (SBE) isoforms or overexpression of potato Glucan Water Dikinase (GWD). The resulting lines displayed Amylose-Only (AO) and Hyper-Phosphorylated (HP) starch chemotypes, respectively. We studied the influence of these alterations on primary metabolism, grain composition, starch structural features and starch granule morphology over caryopsis development at 10, 20 and 30 days after pollination (DAP) and at grain maturity. While HP showed relatively little effect, AO showed significant reduction in starch accumulation with re-direction to protein and β-glucan (BG) accumulation. Metabolite profiling indicated significantly higher sugar accumulation in AO, with re-partitioning of carbon to accumulate amino acids, and interestingly it also had high levels of some important stress-related metabolites and potentially protective metabolites, possibly to elude deleterious effects. Investigations on starch molecular structure revealed significant increase in starch phosphate and amylose content in HP and AO respectively with obvious differences in starch granule morphology at maturity. The results demonstrate that decreasing the storage starch branching resulted in metabolic adjustments and re-directions, tuning to evade deleterious effects on caryopsis physiology and plant performance while only little effect was evident by increasing starch-bound phosphate as a result of overexpressing GWD. PMID:26891365

Atrogin-1 affects muscle protein synthesis and degradation when energy metabolism is impaired by the antidiabetes drug berberine.

PubMed

Wang, Huiling; Liu, Dajun; Cao, Peirang; Lecker, Stewart; Hu, Zhaoyong

2010-08-01

Defects in insulin/IGF-1 signaling stimulate muscle protein loss by suppressing protein synthesis and increasing protein degradation. Since an herbal compound, berberine, lowers blood levels of glucose and lipids, we proposed that it would improve insulin/IGF-1 signaling, blocking muscle protein losses. We evaluated whether berberine ameliorates muscle atrophy in db/db mice, a model of type 2 diabetes, by measuring protein synthesis and degradation in muscles of normal and db/db mice treated with or without berberine. We also examined mechanisms for berberine-induced changes in muscle protein metabolism. Berberine administration decreased protein synthesis and increased degradation in muscles of normal and db/db mice. The protein catabolic mechanism depended on berberine-stimulated expression of the E3 ubiquitin ligase, atrogin-1. Atrogin-1 not only increased proteolysis but also reduced protein synthesis by mechanisms that were independent of decreased phosphorylation of Akt or forkhead transcription factors. Impaired protein synthesis was dependent on a reduction in eIF3-f, an essential regulator of protein synthesis. Berberine impaired energy metabolism, activating AMP-activated protein kinase and providing an alternative mechanism for the stimulation of atrogin-1 expression. When we increased mitochondrial biogenesis by expressing peroxisome proliferator-activated receptor gamma coactivator-1alpha, berberine-induced changes in muscle protein metabolism were prevented. Berberine impairs muscle metabolism by two novel mechanisms. It impairs mitochonidrial function stimulating the expression of atrogin-1 without affecting phosphorylation of forkhead transcription factors. The increase in atrogin-1 not only stimulated protein degradation but also suppressed protein synthesis, causing muscle atrophy.

Acclimation temperature affects the metabolic response of amphibian skeletal muscle to insulin.

PubMed

Petersen, Ann M; Gleeson, Todd T

2011-09-01

Frog skeletal muscle mainly utilizes the substrates glucose and lactate for energy metabolism. The goal of this study was to determine the effect of insulin on the uptake and metabolic fate of lactate and glucose at rest in skeletal muscle of the American bullfrog, Lithobates catesbeiana, under varying temperature regimens. We hypothesize that lactate and glucose metabolic pathways will respond differently to the presence of insulin in cold versus warm acclimated frog tissues, suggesting an interaction between temperature and metabolism under varying environmental conditions. We employed radiolabeled tracer techniques to measure in vitro uptake, oxidation, and incorporation of glucose and lactate into glycogen by isolated muscles from bullfrogs acclimated to 5 °C (cold) or 25 °C (warm). Isolated bundles from Sartorius muscles were incubated at 5 °C, 15 °C, or 25 °C, and in the presence and absence of 0.05 IU/mL bovine insulin. Insulin treatment in the warm acclimated and incubated frogs resulted in an increase in glucose incorporation into glycogen, and an increase in intracellular [glucose] of 0.5 μmol/g (P<0.05). Under the same conditions lactate incorporation into glycogen was reduced (P<0.05) in insulin-treated muscle. When compared to the warm treatment group, cold acclimation and incubation resulted in increased rates of glucose oxidation and glycogen synthesis, and a reduction in free intracellular glucose levels (P<0.05). When muscles from either acclimation group were incubated at an intermediate temperature of 15 °C, insulin's effect on substrate metabolism was attenuated or even reversed. Therefore, a significant interaction between insulin and acclimation condition in controlling skeletal muscle metabolism appears to exist. Our findings further suggest that one of insulin's actions in frog muscle is to increase glucose incorporation into glycogen, and to reduce reliance on lactate as the primary metabolic fuel. Copyright © 2011 Elsevier Inc. All

Gestational Heat Stress Alters Postnatal Offspring Body Composition Indices and Metabolic Parameters in Pigs

PubMed Central

Boddicker, Rebecca L.; Seibert, Jacob T.; Johnson, Jay S.; Pearce, Sarah C.; Selsby, Joshua T.; Gabler, Nicholas K.; Lucy, Matthew C.; Safranski, Timothy J.; Rhoads, Robert P.; Baumgard, Lance H.; Ross, Jason W.

2014-01-01

The study objectives were to test the hypothesis that heat stress (HS) during gestational development alters postnatal growth, body composition, and biological response to HS conditions in pigs. To investigate this, 14 first parity crossbred gilts were exposed to one of four environmental treatments (TNTN, TNHS, HSTN, or HSHS) during gestation. TNTN and HSHS dams were exposed to thermal neutral (TN, cyclical 18–22°C) or HS conditions (cyclical 28–34°C) during the entire gestation, respectively. Dams assigned to HSTN and TNHS treatments were heat-stressed for the first or second half of gestation, respectively. Postnatal offspring were exposed to one of two thermal environments for an acute (24 h) or chronic (five weeks) duration in either constant TN (21°C) or HS (35°C) environment. Exposure to chronic HS during their growth phase resulted in decreased longissimus dorsi cross-sectional area (LDA) in offspring from HSHS and HSTN treated dams whereas LDA was larger in offspring from dams in TNTN and TNHS conditions. Irrespective of HS during prepubertal postnatal growth, pigs from dams that experienced HS during the first half of gestation (HSHS and HSTN) had increased (13.9%) subcutaneous fat thickness compared to pigs from dams exposed to TN conditions during the first half of gestation. This metabolic repartitioning towards increased fat deposition in pigs from dams heat-stressed during the first half of gestation was accompanied by elevated blood insulin concentrations (33%; P = 0.01). Together, these results demonstrate HS during the first half of gestation altered metabolic and body composition parameters during future development and in biological responses to a subsequent HS challenge. PMID:25383953

Effects of canrenone in patients with metabolic syndrome.

PubMed

Derosa, Giuseppe; Bonaventura, Aldo; Bianchi, Lucio; Romano, Davide; D'Angelo, Angela; Fogari, Elena; Maffioli, Pamela

2013-11-01

Metabolic syndrome is becoming a common disease due to a rise in obesity rates among adults. The aim was to evaluate the effects of canrenone compared to placebo on metabolic and inflammatory parameters in patients affected by metabolic syndrome. A total of 145 patients were treated with placebo or canrenone, 50 mg/day, for 3 months and then 50 mg b.i.d. till the end of the study. Blood pressure, body weight, body mass index, fasting plasma glucose (FPG), fasting plasma insulin, HOMA-IR, lipid profile, plasma aldosterone, brain natriuretic peptide, high-sensitivity C-reactive protein (Hs-CRP), tumor necrosis factor-α (TNF-α) and M value were evaluated. A decrease of blood pressure was observed in canrenone group compared to baseline; moreover, systolic blood pressure value recorded after 6 months of canrenone therapy was lower than the one recorded with placebo. Canrenone gave a significant decrease of FPI and HOMA index, and an increase of M value both compared to baseline and to placebo. Canrenone also decreased triglycerides and FPG was not observed with placebo. Canrenone also decreased plasma aldosterone, Hs-CRP and TNF-α compared to baseline and to placebo. Canrenone seems to be effective in reducing some factors involved in metabolic syndrome and in improving insulin-resistance and the inflammatory state observed in these patients.

Measuring Rates of Herbicide Metabolism in Dicot Weeds with an Excised Leaf Assay.

PubMed

Ma, Rong; Skelton, Joshua J; Riechers, Dean E

2015-09-07

In order to isolate and accurately determine rates of herbicide metabolism in an obligate-outcrossing dicot weed, waterhemp (Amaranthus tuberculatus), we developed an excised leaf assay combined with a vegetative cloning strategy to normalize herbicide uptake and remove translocation as contributing factors in herbicide-resistant (R) and -sensitive (S) waterhemp populations. Biokinetic analyses of organic pesticides in plants typically include the determination of uptake, translocation (delivery to the target site), metabolic fate, and interactions with the target site. Herbicide metabolism is an important parameter to measure in herbicide-resistant weeds and herbicide-tolerant crops, and is typically accomplished with whole-plant tests using radiolabeled herbicides. However, one difficulty with interpreting biokinetic parameters derived from whole-plant methods is that translocation is often affected by rates of herbicide metabolism, since polar metabolites are usually not mobile within the plant following herbicide detoxification reactions. Advantages of the protocol described in this manuscript include reproducible, accurate, and rapid determination of herbicide degradation rates in R and S populations, a substantial decrease in the amount of radiolabeled herbicide consumed, a large reduction in radiolabeled plant materials requiring further handling and disposal, and the ability to perform radiolabeled herbicide experiments in the lab or growth chamber instead of a greenhouse. As herbicide resistance continues to develop and spread in dicot weed populations worldwide, the excised leaf assay method developed and described herein will provide an invaluable technique for investigating non-target site-based resistance due to enhanced rates of herbicide metabolism and detoxification.

Measuring Rates of Herbicide Metabolism in Dicot Weeds with an Excised Leaf Assay

PubMed Central

Ma, Rong; Skelton, Joshua J.; Riechers, Dean E.

2015-01-01

In order to isolate and accurately determine rates of herbicide metabolism in an obligate-outcrossing dicot weed, waterhemp (Amaranthus tuberculatus), we developed an excised leaf assay combined with a vegetative cloning strategy to normalize herbicide uptake and remove translocation as contributing factors in herbicide-resistant (R) and –sensitive (S) waterhemp populations. Biokinetic analyses of organic pesticides in plants typically include the determination of uptake, translocation (delivery to the target site), metabolic fate, and interactions with the target site. Herbicide metabolism is an important parameter to measure in herbicide-resistant weeds and herbicide-tolerant crops, and is typically accomplished with whole-plant tests using radiolabeled herbicides. However, one difficulty with interpreting biokinetic parameters derived from whole-plant methods is that translocation is often affected by rates of herbicide metabolism, since polar metabolites are usually not mobile within the plant following herbicide detoxification reactions. Advantages of the protocol described in this manuscript include reproducible, accurate, and rapid determination of herbicide degradation rates in R and S populations, a substantial decrease in the amount of radiolabeled herbicide consumed, a large reduction in radiolabeled plant materials requiring further handling and disposal, and the ability to perform radiolabeled herbicide experiments in the lab or growth chamber instead of a greenhouse. As herbicide resistance continues to develop and spread in dicot weed populations worldwide, the excised leaf assay method developed and described herein will provide an invaluable technique for investigating non-target site-based resistance due to enhanced rates of herbicide metabolism and detoxification. PMID:26383604

Gut microbiota and metabolic syndrome

PubMed Central

Festi, Davide; Schiumerini, Ramona; Eusebi, Leonardo Henry; Marasco, Giovanni; Taddia, Martina; Colecchia, Antonio

2014-01-01

Gut microbiota exerts a significant role in the pathogenesis of the metabolic syndrome, as confirmed by studies conducted both on humans and animal models. Gut microbial composition and functions are strongly influenced by diet. This complex intestinal “superorganism” seems to affect host metabolic balance modulating energy absorption, gut motility, appetite, glucose and lipid metabolism, as well as hepatic fatty storage. An impairment of the fine balance between gut microbes and host’s immune system could culminate in the intestinal translocation of bacterial fragments and the development of “metabolic endotoxemia”, leading to systemic inflammation and insulin resistance. Diet induced weight-loss and bariatric surgery promote significant changes of gut microbial composition, that seem to affect the success, or the inefficacy, of treatment strategies. Manipulation of gut microbiota through the administration of prebiotics or probiotics could reduce intestinal low grade inflammation and improve gut barrier integrity, thus, ameliorating metabolic balance and promoting weight loss. However, further evidence is needed to better understand their clinical impact and therapeutic use. PMID:25473159

The early effects of stavudine compared with tenofovir on adipocyte gene expression, mitochondrial DNA copy number and metabolic parameters in South African HIV-infected patients: a randomized trial.

PubMed

Menezes, C N; Duarte, R; Dickens, C; Dix-Peek, T; Van Amsterdam, D; John, M-A; Ive, P; Maskew, M; Macphail, P; Fox, M P; Raal, F; Sanne, I; Crowther, N J

2013-04-01

Stavudine is being phased out because of its mitochondrial toxicity and tenofovir (TDF) is recommended as part of first-line highly active antiretroviral therapy (HAART) in South Africa. A prospective, open-label, randomized controlled trial comparing standard- and low-dose stavudine with TDF was performed to assess early differences in adipocyte mtDNA copy number, gene expression and metabolic parameters in Black South African HIV-infected patients. Sixty patients were randomized 1:1:1 to either standard-dose (30-40 mg) or low-dose (20-30 mg) stavudine or TDF (300 mg) each combined with lamivudine and efavirenz. Subcutaneous fat biopsies were obtained at weeks 0 and 4. Adipocyte mtDNA copies/cell and gene expression were measured using quantitative polymerase chain reaction (qPCR). Markers of inflammation and lipid and glucose metabolism were also assessed. A 29% and 32% decrease in the mean mtDNA copies/cell was noted in the standard-dose (P < 0.05) and low-dose stavudine (P < 0.005) arms, respectively, when compared with TDF at 4 weeks. Nuclear respiratory factor-1 (NRF1) and mitochondrial cytochrome B (MTCYB) gene expression levels were affected by stavudine, with a significantly (P < 0.05) greater fall in expression observed with the standard, but not the low dose compared with TDF. No significant differences were observed in markers of inflammation and lipid and glucose metabolism. These results demonstrate early mitochondrial depletion among Black South African patients receiving low and standard doses of stavudine, with preservation of gene expression levels, except for NRF1 and MTCYB, when compared with patients on TDF. © 2012 British HIV Association.

Temporal Expression-based Analysis of Metabolism

PubMed Central

Segrè, Daniel

2012-01-01

Metabolic flux is frequently rerouted through cellular metabolism in response to dynamic changes in the intra- and extra-cellular environment. Capturing the mechanisms underlying these metabolic transitions in quantitative and predictive models is a prominent challenge in systems biology. Progress in this regard has been made by integrating high-throughput gene expression data into genome-scale stoichiometric models of metabolism. Here, we extend previous approaches to perform a Temporal Expression-based Analysis of Metabolism (TEAM). We apply TEAM to understanding the complex metabolic dynamics of the respiratorily versatile bacterium Shewanella oneidensis grown under aerobic, lactate-limited conditions. TEAM predicts temporal metabolic flux distributions using time-series gene expression data. Increased predictive power is achieved by supplementing these data with a large reference compendium of gene expression, which allows us to take into account the unique character of the distribution of expression of each individual gene. We further propose a straightforward method for studying the sensitivity of TEAM to changes in its fundamental free threshold parameter θ, and reveal that discrete zones of distinct metabolic behavior arise as this parameter is changed. By comparing the qualitative characteristics of these zones to additional experimental data, we are able to constrain the range of θ to a small, well-defined interval. In parallel, the sensitivity analysis reveals the inherently difficult nature of dynamic metabolic flux modeling: small errors early in the simulation propagate to relatively large changes later in the simulation. We expect that handling such “history-dependent” sensitivities will be a major challenge in the future development of dynamic metabolic-modeling techniques. PMID:23209390

Metabolic dysregulation in first-episode schizophrenia patients with respect to genetic variation in one-carbon metabolism.

PubMed

Misiak, Błażej; Łaczmański, Łukasz; Słoka, Natalia Kinga; Szmida, Elżbieta; Piotrowski, Patryk; Loska, Olga; Ślęzak, Ryszard; Kiejna, Andrzej; Frydecka, Dorota

2016-04-30

The aim of this study was to investigate the prevalence of metabolic disturbances in patients with first-episode schizophrenia (FES) and test the hypothesis that genetic variation in one-carbon metabolism may account for metabolic dysregulation in early psychosis. We measured fasting glucose, lipid profile parameters, homocysteine, folate and vitamin B12 in 135 patients with FES and 146 healthy controls (HCs). Polymorphisms in the following genes were determined: MTHFR (C677T and A1298C), MTHFD1 (G1958A), MTRR (A66G) and BHMT (G742A). Serum levels of folate and high-density lipoproteins (HDL) were significantly lower in patients with FES compared to HCs. In turn, serum levels of homocysteine and triglycerides were significantly higher in patients with FES than in HCs. Prevalence of hyperhomocysteinemia, low folate and HDL levels together with dyslipidemia was significantly higher in patients with FES compared to HCs. Higher homocysteine levels, lower vitamin B12 levels and the presence of metabolic syndrome were associated with higher severity of negative symptoms. None of studied polymorphisms was associated with schizophrenia risk. Several associations between studied polymorphisms and cardio-metabolic parameters were found. None of them remained significant after Bonferroni correction. Our results indicate that metabolic dysregulation in patients with FES is not associated with genetic variation in one-carbon metabolism. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Clinical, Hormonal, and Metabolic Parameters in Women with Subclinical Hypothyroidism and Polycystic Ovary Syndrome: A Cross-Sectional Study.

PubMed

Bedaiwy, Mohamed A; Abdel-Rahman, Mohamed Y; Tan, Justin; AbdelHafez, Faten F; Abdelkareem, Amr O; Henry, Drisana; Lisonkova, Sarka; Hurd, William W; Liu, James H

2018-05-01

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in reproductive age women, yet its clinical presentation shares similarities with several other endocrine disorders such as thyroid disease. Hence, the objective of this study was to further evaluate this association by investigating the clinical, hormonal, and metabolic parameters between subclinical hypothyroidism (SCH) and PCOS. This is a cross-sectional study conducted in a tertiary care clinic at Cleveland, Ohio, USA. A total of 137 women diagnosed with PCOS by Rotterdam criteria were examined. SCH was defined as thyroid-stimulating hormone >2.5 mIU/L in the absence of symptoms of overt hypothyroidism. The mean age, body mass index (BMI), fasting plasma glucose (FPG), glucose tolerance test, hemoglobin A1c, fasting insulin, a 2 hours insulin level after 75 g glucose load, cholesterol, LDL, HDL, and homeostatic model assessment (HOMA) were compared between women with and without SCH. Logistic regression was used to adjust for age and BMI. Among 137 women with PCOS, 21.9% had SCH. Comparison groups were similar in both age and BMI and there was no difference in the mean values of all endocrine and metabolic parameters tested. However, abnormal FPG levels (OR 3.01; CI: 1.12-8.07. p = 0.03) and abnormal HOMA (OR 3.7; CI: 1.14-12.00. p = 0.03) were more likely in women who had SCH than in women without SCH independent of age and BMI. Women with PCOS and SCH are more likely to have impaired FPG values and impaired insulin sensitivity even after adjusting for age and BMI. Hence, close monitoring of PCOS patients for SCH may be beneficial.

Effects of acute blood pressure elevation on biochemical-metabolic parameters in individuals with hypertensive crisis.

PubMed

Andrade, Days Oliveira; Santos, Sara Patrícia O; Pinhel, Marcela Augusta S; Valente, Flávia Mariana; Giannini, Marcela Cavichiolo; Gregório, Michele Lima; De Godoy, Moacir Fernandes; Souza, Dorotéia Rossi S; Vilela-Martin, José Fernando

2017-01-01

Hypertensive crisis is a common clinical situation that presents a high rate of morbidity and mortality and it is characterized by symptomatic rise of blood pressure (BP), systolic (SBP) ≥ 180 mmHg and/or diastolic (DBP) ≥ 120 mmHg. It is classified as emergency (HE) or hypertensive urgency (HU). There is no description of laboratory findings in patients who present acute BP elevation. Thus, this study had the objective to assess the biochemical-metabolic parameters of patients with HC. We studied 74 normotensive individuals (NT), 74 controlled hypertensive patients (ContrHT), 50 subjects with HU, and 78 with HE for evaluating biochemical-metabolic parameters. HE occurs in older individuals and more frequently in those with known hypertension. More patients with HE had dyslipidemia than those with HU (58% vs. 38%). The diastolic BP and heart rate were higher in the HE group (120 mmHg and 87 bpm) compared to ContrHT (71 mmHg and 71 bpm; p < 0.0001) and NT groups (75 mmHg and 68 bpm; p < 0.0001). Glycemia was higher in HE vs. NT and ContrHT (p < 0.05). HDL cholesterol was lower in HE than NT (p = 0.0088). Potassium was lower in HE vs. NT, ContrHT and HU groups (p < 0.05). Creatinine was higher in the HC group vs. NT and ContrHT (p < 0.05). The GFR was significantly lower in HE group vs. HU, ContrHT and NT (p < 0.001). In conclusion, individuals with HC show biochemical alterations when compared to ContrHT and NT. Acute BP elevations are associated with hyperglycemia, dyslipidemia, and higher potassium and creatinine levels and lower renal function. Abbreviations BMI = body mass index BP = blood pressure CH = hypertensive crisis ContrHT = controlled hypertensive DBP = diastolic blood pressure GFR = glomerular filtration rate HbA1c = glycated hemoglobin HDLc = high-density lipoprotein cholesterol HE = hypertensive emergency HPLC = high-performance liquid chromatography HR = heart rate HU = hypertensive urgency JNC 7 = VII Joint National Committee on the Detection

Do diabetes and obesity affect the metabolic response to exercise?

PubMed

Plomgaard, Peter; Weigert, Cora

2017-07-01

Exercise is recommended as therapeutic intervention for people at risk to develop type 2 diabetes to prevent or treat the disease. Recent studies on the influence of obesity and type 2 diabetes on the outcome of exercise programs are discussed. Poor glycemic control before an intervention can be a risk factor of reduced therapeutic benefit from exercise. But the acute metabolic response to exercise and the transcriptional profile of the working muscle is similar in healthy controls and type 2 diabetic patients, including but not limited to intact activation of skeletal muscle AMP-activated kinase signaling, glucose uptake and expression of peroxisome proliferator-activated receptor gamma coactivator 1α. The increase in plasma acylcarnitines during exercise is not influenced by type 2 diabetes or obesity. The hepatic response to exercise is dependent on the glucagon/insulin ratio and the exercise-induced increase in hepatokines such as fibroblast growth factor 21 and follistatin is impaired in type 2 diabetes and obesity, but consequences for the benefit from exercise are unknown yet. Severe metabolic dysregulation can reduce the benefit from exercise, but the intact response of key metabolic regulators in exercising skeletal muscle of diabetic patients demonstrates the effectiveness of exercise programs to treat the disease.

Skeletal muscle expression of p43, a truncated thyroid hormone receptor α, affects lipid composition and metabolism.

PubMed

Casas, François; Fouret, Gilles; Lecomte, Jérome; Cortade, Fabienne; Pessemesse, Laurence; Blanchet, Emilie; Wrutniak-Cabello, Chantal; Coudray, Charles; Feillet-Coudray, Christine

2018-02-01

Thyroid hormone is a major regulator of metabolism and mitochondrial function. Thyroid hormone also affects reactions in almost all pathways of lipids metabolism and as such is considered as the main hormonal regulator of lipid biogenesis. The aim of this study was to explore the possible involvement of p43, a 43 Kda truncated form of the nuclear thyroid hormone receptor TRα1 which stimulates mitochondrial activity. Therefore, using mouse models overexpressing p43 in skeletal muscle (p43-Tg) or lacking p43 (p43-/-), we have investigated the lipid composition in quadriceps muscle and in mitochondria. Here, we reported in the quadriceps muscle of p43-/- mice, a fall in triglycerides, an inhibition of monounsaturated fatty acids (MUFA) synthesis, an increase in elongase index and an decrease in desaturase index. However, in mitochondria from p43-/- mice, fatty acid profile was barely modified. In the quadriceps muscle of p43-Tg mice, MUFA content was decreased whereas the unsaturation index was increased. In addition, in quadriceps mitochondria of p43-Tg mice, we found an increase of linoleic acid level and unsaturation index. Last, we showed that cardiolipin content, a key phospholipid for mitochondrial function, remained unchanged both in quadriceps muscle and in its mitochondria whatever the mice genotype. In conclusion, this study shows that muscle lipid content and fatty acid profile are strongly affected in skeletal muscle by p43 levels. We also demonstrate that regulation of cardiolipin biosynthesis by the thyroid hormone does not imply p43.

Nature's inordinate fondness for metabolic enzymes: why metabolic enzyme loci are so frequently targets of selection.

PubMed

Marden, James H

2013-12-01

Metabolic enzyme loci were some of the first genes accessible for molecular evolution and ecology research. New technologies now make the whole genome, transcriptome or proteome readily accessible, allowing unbiased scans for loci exhibiting significant differences in allele frequency or expression level and associated with phenotypes and/or responses to natural selection. With surprising frequency and in many cases in proportions greater than chance relative to other genes, glycolysis and TCA cycle enzyme loci appear among the genes with significant associations in these studies. Hence, there is an ongoing need to understand the basis for fitness effects of metabolic enzyme polymorphisms. Allele-specific effects on the binding affinity and catalytic rate of individual enzymes are well known, but often of uncertain significance because metabolic control theory and in vivo studies indicate that many individual metabolic enzymes do not affect pathway flux rate. I review research, so far little used in evolutionary biology, showing that metabolic enzyme substrates affect signalling pathways that regulate cell and organismal biology, and that these enzymes have moonlighting functions. To date there is little knowledge of how alleles in natural populations affect these phenotypes. I discuss an example in which alleles of a TCA enzyme locus associate with differences in a signalling pathway and development, organismal performance, and ecological dynamics. Ultimately, understanding how metabolic enzyme polymorphisms map to phenotypes and fitness remains a compelling and ongoing need for gaining robust knowledge of ecological and evolutionary processes. © 2013 John Wiley & Sons Ltd.

Foliar nitrogen metabolism of adult Douglas-fir trees is affected by soil water availability and varies little among provenances

PubMed Central

Du, Baoguo; Kreuzwieser, Jürgen; Dannenmann, Michael; Junker, Laura Verena; Kleiber, Anita; Hess, Moritz; Jansen, Kirstin; Eiblmeier, Monika; Gessler, Arthur; Kohnle, Ulrich; Ensminger, Ingo; Rennenberg, Heinz

2018-01-01

The coniferous forest tree Douglas-fir (Pseudotsuga menziesii) is native to the pacific North America, and is increasingly planted in temperate regions worldwide. Nitrogen (N) metabolism is of great importance for growth, resistance and resilience of trees. In the present study, foliar N metabolism of adult trees of three coastal and one interior provenance of Douglas-fir grown at two common gardens in southwestern Germany (Wiesloch, W; Schluchsee, S) were characterized in two subsequent years. Both the native North American habitats of the seed sources and the common garden sites in Germany differ in climate conditions. Total and mineral soil N as well as soil water content were higher in S compared to W. We hypothesized that i) provenances differ constitutively in N pool sizes and composition, ii) N pools are affected by environmental conditions, and iii) that effects of environmental factors on N pools differ among interior and coastal provenances. Soil water content strongly affected the concentrations of total N, soluble protein, total amino acids (TAA), arginine and glutamate. Foliar concentrations of total N, soluble protein, structural N and TAA of trees grown at W were much higher than in trees at S. Provenance effects were small but significant for total N and soluble protein content (interior provenance showed lowest concentrations), as well as arginine, asparagine and glutamate. Our data suggest that needle N status of adult Douglas-fir is independent from soil N availability and that low soil water availability induces a re-allocation of N from structural N to metabolic N pools. Small provenance effects on N pools suggest that local adaptation of Douglas-fir is not dominated by N conditions at the native habitats. PMID:29566035

[Carbon source metabolic diversity of soil microbial community under different climate types in the area affected by Wenchuan earthquake].

PubMed

Zhang, Guang-Shuai; Lin, Yong-Ming; Ma, Rui-Feng; Deng, Hao-Jun; Du, Kun; Wu, Cheng-Zhen; Hong, Wei

2015-02-01

The MS8.0 Wenchuan earthquake in 2008 led to huge damage to land covers in northwest Sichuan, one of the critical fragile eco-regions in China which can be divided into Semi-arid dry hot climate zone (SDHC) and Subtropical humid monsoon climate zone (SHMC). Using the method of Bilog-ECO-microplate technique, this paper aimed to determine the functional diversity of soil microbial community in the earthquake-affected areas which can be divided into undamaged area (U), recover area (R) and damaged area without recovery (D) under different climate types, in order to provide scientific basis for ecological recovery. The results indicated that the average-well-color-development (AWCD) in undamaged area and recovery area showed SDHC > SHMC, which was contrary to the AWCD in the damaged area without recovery. The AWCD of damaged area without recovery was the lowest in both climate zones. The number of carbon source utilization types of soil microbial in SHMC zone was significantly higher than that in SDHC zone. The carbon source utilization types in both climate zones presented a trend of recover area > undamaged area > damaged area without recovery. The carbon source metabolic diversity characteristic of soil microbial community was significantly different in different climate zones. The diversity index and evenness index both showed a ranking of undamaged area > recover area > damaged area without recovery. In addition, the recovery area had the highest richness index. The soil microbial carbon sources metabolism characteristic was affected by soil nutrient, aboveground vegetation biomass and vegetation coverage to some extent. In conclusion, earthquake and its secondary disasters influenced the carbon source metabolic diversity characteristic of soil microbial community mainly through the change of aboveground vegetation and soil environmental factors.

Advanced Oxidation Processes: Process Mechanisms, Affecting Parameters and Landfill Leachate Treatment.

PubMed

Su-Huan, Kow; Fahmi, Muhammad Ridwan; Abidin, Che Zulzikrami Azner; Soon-An, Ong

2016-11-01

  Advanced oxidation processes (AOPs) are of special interest in treating landfill leachate as they are the most promising procedures to degrade recalcitrant compounds and improve the biodegradability of wastewater. This paper aims to refresh the information base of AOPs and to discover the research gaps of AOPs in landfill leachate treatment. A brief overview of mechanisms involving in AOPs including ozone-based AOPs, hydrogen peroxide-based AOPs and persulfate-based AOPs are presented, and the parameters affecting AOPs are elaborated. Particularly, the advancement of AOPs in landfill leachate treatment is compared and discussed. Landfill leachate characterization prior to method selection and method optimization prior to treatment are necessary, as the performance and practicability of AOPs are influenced by leachate matrixes and treatment cost. More studies concerning the scavenging effects of leachate matrixes towards AOPs, as well as the persulfate-based AOPs in landfill leachate treatment, are necessary in the future.

Stabilometric parameters are affected by anthropometry and foot placement.

PubMed

Chiari, Lorenzo; Rocchi, Laura; Cappello, Angelo

2002-01-01

To recognize and quantify the influence of biomechanical factors, namely anthropometry and foot placement, on the more common measures of stabilometric performance, including new-generation stochastic parameters. Fifty normal-bodied young adults were selected in order to cover a sufficiently wide range of anthropometric properties. They were allowed to choose their preferred side-by-side foot position and their quiet stance was recorded with eyes open and closed by a force platform. biomechanical factors are known to influence postural stability but their impact on stabilometric parameters has not been extensively explored yet. Principal component analysis was used for feature selection among several biomechanical factors. A collection of 55 stabilometric parameters from the literature was estimated from the center-of-pressure time series. Linear relations between stabilometric parameters and selected biomechanical factors were investigated by robust regression techniques. The feature selection process returned height, weight, maximum foot width, base-of-support area, and foot opening angle as the relevant biomechanical variables. Only eleven out of the 55 stabilometric parameters were completely immune from a linear dependence on these variables. The remaining parameters showed a moderate to high dependence that was strengthened upon eye closure. For these parameters, a normalization procedure was proposed, to remove what can well be considered, in clinical investigations, a spurious source of between-subject variability. Care should be taken when quantifying postural sway through stabilometric parameters. It is suggested as a good practice to include some anthropometric measurements in the experimental protocol, and to standardize or trace foot position. Although the role of anthropometry and foot placement has been investigated in specific studies, there are no studies in the literature that systematically explore the relationship between such BF and

Evaluation of the parameters affecting bone temperature during drilling using a three-dimensional dynamic elastoplastic finite element model.

PubMed

Chen, Yung-Chuan; Tu, Yuan-Kun; Zhuang, Jun-Yan; Tsai, Yi-Jung; Yen, Cheng-Yo; Hsiao, Chih-Kun

2017-11-01

A three-dimensional dynamic elastoplastic finite element model was constructed and experimentally validated and was used to investigate the parameters which influence bone temperature during drilling, including the drill speed, feeding force, drill bit diameter, and bone density. Results showed the proposed three-dimensional dynamic elastoplastic finite element model can effectively simulate the temperature elevation during bone drilling. The bone temperature rise decreased with an increase in feeding force and drill speed, however, increased with the diameter of drill bit or bone density. The temperature distribution is significantly affected by the drilling duration; a lower drilling speed reduced the exposure duration, decreases the region of the thermally affected zone. The constructed model could be applied for analyzing the influence parameters during bone drilling to reduce the risk of thermal necrosis. It may provide important information for the design of drill bits and surgical drilling powers.

High infestation levels of Schizotetranychus oryzae severely affects rice metabolism.

PubMed

Blasi, Édina A R; Buffon, Giseli; Rativa, Angie G S; Lopes, Mara C B; Berger, Markus; Santi, Lucélia; Lavallée-Adam, Mathieu; Yates, John R; Schwambach, Joséli; Beys-da-Silva, Walter O; Sperotto, Raul A

2017-12-01

High levels of Schizotetranychus oryzae phytophagous mite infestation on rice leaves can severely affect productivity. Physiological characterization showed that S. oryzae promotes a decrease in chlorophyll concentration and the establishment of a senescence process in rice leaves. Late-infested leaves also present high levels of superoxide radical and hydrogen peroxide accumulation, along with high levels of membrane integrity loss, which is indicative of cell death. To better understand the rice molecular responses to high levels of mite infestation, we employed the Multidimensional Protein Identification Technology (MudPIT) approach to identify differentially expressed proteins. We identified 83 and 88 proteins uniquely present in control and late-infested leaves, respectively, along with 11 and one proteins more abundant in control and late-infested leaves, respectively. S. oryzae infestation induces a decreased abundance of proteins related to translation, protease inhibition, and photosynthesis. On the other hand, infestation caused increased abundance of proteins involved in protein modification and degradation. Our results also suggest that S. oryzae infestation interferes with intracellular transport, DNA structure maintenance, and amino acid and lipid metabolism in rice leaves. Proteomic data were positively correlated with enzymatic assays and RT-qPCR analysis. Our findings describe the protein expression patterns of late-infested rice leaves and suggest several targets which could be tested in future biotechnological approaches aiming to avoid the population increase of phytophagous mite in rice plants. Copyright © 2017 Elsevier GmbH. All rights reserved.

Does Cigarette Smoking Affect Seminal Fluid Parameters? A Comparative Study

PubMed Central

Meri, Zakarya Bani; Irshid, Ibrahim Bani; Migdadi, Mohammad; Irshid, Ayat Bani; Mhanna, Somia A.

2013-01-01

Objective To study the effect of cigarette smoking on seminal fluid parameters, namely; volume, sperm concentration, and motility, as well as morphology, leukocyte infiltration, among males complaining of infertility. Methods Between August 2010 and July 2011, seminal fluid analysis was done for 1438 males who are partners of couples who visited the infertility clinic at Prince Rashid Ben Al Hassan Hospital (PRH) for infertility. The men who fit the inclusion criteria (n=960) were classified into two groups: group a (non-smokers; n=564) and group B (smokers; n=396), which represents 41.25% of the study group. Seminal fluid was collected using masturbation after 3-5 days of abstinence then analyzed for volume, sperm count, sperm concentration, motility and morphology. In order to analyze whether the number of cigarettes smoked per day has an effect on the spermatogram; the smoking men were divided into two subgroups: the heavy smokers (n=266) and non-heavy smokers (n=130). Results A total of 960 adult males were enrolled. Their age ranged between 21 and 76 years, 564 were non-smokers with mean age of 36. 45±6.27 (Mean±SD). Three-hundred-and-ninety-six were smokers with a mean age of 34.35±4.25 (Mean±SD). There was a significant effect of smoking on the motility of sperms and the ratios of abnormality (p<0.005). Concentration appeared not to be affected by smoking. Furthermore, the group of heavy smokers were found to have lower sperm concentrations and a higher percentage of abnormal sperms compared to the non-heavy smokers. Conclusion Cigarette smoking has a deleterious effect on some of the seminal fluid parameters (motility, morphology and leukocyte count) which in turn may result in male subfertility. PMID:23386938

Maternal cardiac metabolism in pregnancy

PubMed Central

Liu, Laura X.; Arany, Zolt

2014-01-01

Pregnancy causes dramatic physiological changes in the expectant mother. The placenta, mostly foetal in origin, invades maternal uterine tissue early in pregnancy and unleashes a barrage of hormones and other factors. This foetal ‘invasion’ profoundly reprogrammes maternal physiology, affecting nearly every organ, including the heart and its metabolism. We briefly review here maternal systemic metabolic changes during pregnancy and cardiac metabolism in general. We then discuss changes in cardiac haemodynamic during pregnancy and review what is known about maternal cardiac metabolism during pregnancy. Lastly, we discuss cardiac diseases during pregnancy, including peripartum cardiomyopathy, and the potential contribution of aberrant cardiac metabolism to disease aetiology. PMID:24448314

Changes in whole-body metabolic parameters associated with radiation

NASA Astrophysics Data System (ADS)

Ahlers, I.

1994-10-01

Continuous irradiation of experimental animals is an appropriate model for the research in space radiobiology. The onset and recovery of radiation injury can be estimated on the basis of the concentration/content of glycogen in liver, the phospholipid content in thymus and other radiosensitive organs and the triacylglycerol concentration in bone marrow. Further, the picture of the metabolism in irradiated organism may be completed by the analysis of serum glucocorticoid and thyroid hormone levels.

Heat and Moisture Transport and Storage Parameters of Bricks Affected by the Environment

NASA Astrophysics Data System (ADS)

Kočí, Václav; Čáchová, Monika; Koňáková, Dana; Vejmelková, Eva; Jerman, Miloš; Keppert, Martin; Maděra, Jiří; Černý, Robert

2018-05-01

The effect of external environment on heat and moisture transport and storage properties of the traditional fired clay brick, sand-lime brick and highly perforated ceramic block commonly used in the Czech Republic and on their hygrothermal performance in building envelopes is analyzed by a combination of experimental and computational techniques. The experimental measurements of thermal, hygric and basic physical parameters are carried out in the reference state and after a 3-year exposure of the bricks to real climatic conditions of the city of Prague. The obtained results showed that after 3 years of weathering the porosity of the analyzed bricks increased up to five percentage points which led to an increase in liquid and gaseous moisture transport parameters and a decrease in thermal conductivity. Computational modeling of hygrothermal performance of building envelopes made of the studied bricks was done using both reference and weather-affected data. The simulated results indicated an improvement in the annual energy balances and a decrease in the time-of-wetness functions as a result of the use of data obtained after the 3-year exposure to the environment. The effects of weathering on both heat and moisture transport and storage parameters of the analyzed bricks and on their hygrothermal performance were found significant despite the occurrence of warm winters in the time period of 2012-2015 when the brick specimens were exposed to the environment.

Associations of dietary intake and metabolic syndrome risk parameters in Vietnamese female marriage immigrants in South Korea: The KoGES follow-up study

PubMed Central

Yang, Hyesu; Kim, Hyesook; Kim, Ji-Myung; Chung, Hye Won

2016-01-01

BACKGROUND/OBJECTIVES This study was conducted to compare the overall changes in dietary intake and metabolic syndrome risk parameters in Vietnamese marriage-based female immigrants over time. SUBJECTS/METHODS The subjects of this study were 581 Vietnamese marriage-based female immigrants, who were recruited from local clinical centers in Korea. Baseline data were collected from 2006-2011 and the follow-up data were collected from 2012-2014. Dietary food intake was assessed by a 1-day 24-hour recall method. RESULTS Compared to the baseline, the mean body weight, body mass index, waist circumference, high density lipoprotein (HDL)-cholesterol, systolic blood pressure and diastolic blood pressure increased while the fasting blood sugar, triglycerides and low density lipoprotein-cholesterol decreased at follow-up. The total consumption of foods such as vegetables/fruits/seaweeds/mushrooms, oil and fat, and eggs decreased during the follow-up period, whereas the consumption of sugars, beverages and meats increased. Partial correlation between the rate of change [(Follow-up - Baseline) / Baseline × 100] in metabolic syndrome risk parameters and food intake after controlling for confounding factors showed that the waist circumference was positively correlated with either the total plant food intake (r = 0.1042, P = 0.0129) or the total food intake (r = 0.0880, P = 0.0359). The plasma levels of total cholesterol (r = -0.1918, P = 0.0289) and HDL-cholesterol (r = -0.1424, P = 0.0007) were negatively correlated with the percentage of total intake from plant food, and HDL-cholesterol levels were positively correlated with the intake of total animal food (r = 0.0980, P = 0.0217). The serum C-reactive protein levels were positively correlated with the total intake of animal food (r = 0.2374, P < 0.0001) or the percentage of total intake from animal food (r = 0.1346, P = 0.0016). CONCLUSIONS These results suggest that the change rate of dietary intake such as total plant food

Paternal epigenetic programming: evolving metabolic disease risk.

PubMed

Hur, Suzy S J; Cropley, Jennifer E; Suter, Catherine M

2017-04-01

Parental health or exposures can affect the lifetime health outcomes of offspring, independently of inherited genotypes. Such 'epigenetic' effects occur over a broad range of environmental stressors, including defects in parental metabolism. Although maternal metabolic effects are well documented, it has only recently been established that that there is also an independent paternal contribution to long-term metabolic health. Both paternal undernutrition and overnutrition can induce metabolic phenotypes in immediate offspring, and in some cases, the induced phenotype can affect multiple generations, implying inheritance of an acquired trait. The male lineage transmission of metabolic disease risk in these cases implicates a heritable factor carried by sperm. Sperm-based transmission provides a tractable system to interrogate heritable epigenetic factors influencing metabolism, and as detailed here, animal models of paternal programming have already provided some significant insights. Here, we review the evidence for paternal programming of metabolism in humans and animal models, and the available evidence on potential underlying mechanisms. Programming by paternal metabolism can be observed in multiple species across animal phyla, suggesting that this phenomenon may have a unique evolutionary significance. © 2017 Society for Endocrinology.

Dynamic modeling of lactic acid fermentation metabolism with Lactococcus lactis.

PubMed

Oh, Euhlim; Lu, Mingshou; Park, Changhun; Park, Changhun; Oh, Han Bin; Lee, Sang Yup; Lee, Jinwon

2011-02-01

A dynamic model of lactic acid fermentation using Lactococcus lactis was constructed, and a metabolic flux analysis (MFA) and metabolic control analysis (MCA) were performed to reveal an intensive metabolic understanding of lactic acid bacteria (LAB). The parameter estimation was conducted with COPASI software to construct a more accurate metabolic model. The experimental data used in the parameter estimation were obtained from an LC-MS/ MS analysis and time-course simulation study. The MFA results were a reasonable explanation of the experimental data. Through the parameter estimation, the metabolic system of lactic acid bacteria can be thoroughly understood through comparisons with the original parameters. The coefficients derived from the MCA indicated that the reaction rate of L-lactate dehydrogenase was activated by fructose 1,6-bisphosphate and pyruvate, and pyruvate appeared to be a stronger activator of L-lactate dehydrogenase than fructose 1,6-bisphosphate. Additionally, pyruvate acted as an inhibitor to pyruvate kinase and the phosphotransferase system. Glucose 6-phosphate and phosphoenolpyruvate showed activation effects on pyruvate kinase. Hexose transporter was the strongest effector on the flux through L-lactate dehydrogenase. The concentration control coefficient (CCC) showed similar results to the flux control coefficient (FCC).

Monte-Carlo Modeling of the Central Carbon Metabolism of Lactococcus lactis: Insights into Metabolic Regulation

PubMed Central

Murabito, Ettore; Verma, Malkhey; Bekker, Martijn; Bellomo, Domenico; Westerhoff, Hans V.; Teusink, Bas; Steuer, Ralf

2014-01-01

Metabolic pathways are complex dynamic systems whose response to perturbations and environmental challenges are governed by multiple interdependencies between enzyme properties, reactions rates, and substrate levels. Understanding the dynamics arising from such a network can be greatly enhanced by the construction of a computational model that embodies the properties of the respective system. Such models aim to incorporate mechanistic details of cellular interactions to mimic the temporal behavior of the biochemical reaction system and usually require substantial knowledge of kinetic parameters to allow meaningful conclusions. Several approaches have been suggested to overcome the severe data requirements of kinetic modeling, including the use of approximative kinetics and Monte-Carlo sampling of reaction parameters. In this work, we employ a probabilistic approach to study the response of a complex metabolic system, the central metabolism of the lactic acid bacterium Lactococcus lactis, subject to perturbations and brief periods of starvation. Supplementing existing methodologies, we show that it is possible to acquire a detailed understanding of the control properties of a corresponding metabolic pathway model that is directly based on experimental observations. In particular, we delineate the role of enzymatic regulation to maintain metabolic stability and metabolic recovery after periods of starvation. It is shown that the feedforward activation of the pyruvate kinase by fructose-1,6-bisphosphate qualitatively alters the bifurcation structure of the corresponding pathway model, indicating a crucial role of enzymatic regulation to prevent metabolic collapse for low external concentrations of glucose. We argue that similar probabilistic methodologies will help our understanding of dynamic properties of small-, medium- and large-scale metabolic networks models. PMID:25268481

Effect of several environmental parameters on carbon metabolism in histosols.

PubMed

Tate, R L

1980-12-01

High specific activity(14)C-labeled glucose, succinate, acetate, salicylate, and amino acids were used to examine carbon metabolism by the microbial community of Pahokee muck (aLithic medisaprist), a drained, cultivated soil of the Florida Everglades. Variations in carbon oxidation were observed from the end of the wet season through the dry season in a fallow (bare) field. Evolution of(14)CO2 varied with the substrate added and time. Calculation of(14)CO2 evolution for each substrate as a proportion of total respiration of the microbial community which was measured by succinate oxidation (relative oxidation) allowed for determination of the proportion of metabolic activity contributed by the oxidation of each carbon source. Except for the May sample when an approximate 30% decline in relative salicylate oxidation activity was observed, the proportion of total catabolic activity contributed by salicylate oxidation and acetate degradation was constant with time. Relative oxidation of glucose and amino acids ranged from 0.12 to 0.52 and 0.10 to 0.23, respectively. At two times during the dry season, the effect of depth of soil and crop on the carbon oxidation was examined. Relative acetate and amino acid oxidation were constant with depth whereas statistically significant variation was observed in glucose and salicylate oxidation. Generally, with the latter substrates, the activity declined with increased soil depth. Greatest effect of crop on these metabolic activities was noted with oxidation of salicylate in soils from a St. Augustinegrass [Stenatophrum secundatum (Walt.) Kuntz] pasture. In these soils, oxidation of salicylate was nearly double that of the fallow field or of soil planted with sugarcane (Saccharum sp.).

A coupled metabolic-hydraulic model and calibration scheme for estimating of whole-river metabolism during dynamic flow conditions

USGS Publications Warehouse

Payn, Robert A.; Hall, Robert O Jr.; Kennedy, Theodore A.; Poole, Geoff C; Marshall, Lucy A.

2017-01-01

Conventional methods for estimating whole-stream metabolic rates from measured dissolved oxygen dynamics do not account for the variation in solute transport times created by dynamic flow conditions. Changes in flow at hourly time scales are common downstream of hydroelectric dams (i.e. hydropeaking), and hydrologic limitations of conventional metabolic models have resulted in a poor understanding of the controls on biological production in these highly managed river ecosystems. To overcome these limitations, we coupled a two-station metabolic model of dissolved oxygen dynamics with a hydrologic river routing model. We designed calibration and parameter estimation tools to infer values for hydrologic and metabolic parameters based on time series of water quality data, achieving the ultimate goal of estimating whole-river gross primary production and ecosystem respiration during dynamic flow conditions. Our case study data for model design and calibration were collected in the tailwater of Glen Canyon Dam (Arizona, USA), a large hydropower facility where the mean discharge was 325 m3 s 1 and the average daily coefficient of variation of flow was 0.17 (i.e. the hydropeaking index averaged from 2006 to 2016). We demonstrate the coupled model’s conceptual consistency with conventional models during steady flow conditions, and illustrate the potential bias in metabolism estimates with conventional models during unsteady flow conditions. This effort contributes an approach to solute transport modeling and parameter estimation that allows study of whole-ecosystem metabolic regimes across a more diverse range of hydrologic conditions commonly encountered in streams and rivers.

Assessing the effect of selection with deltamethrin on biological parameters and detoxifying enzymes in Aedes aegypti (L.).

PubMed

Alvarez-Gonzalez, Leslie C; Briceño, Arelis; Ponce-Garcia, Gustavo; Villanueva-Segura, O Karina; Davila-Barboza, Jesus A; Lopez-Monroy, Beatriz; Gutierrez-Rodriguez, Selene M; Contreras-Perera, Yamili; Rodriguez-Sanchez, Iram P; Flores, Adriana E

2017-11-01

Resistance to insecticides through one or several mechanisms has a cost for an insect in various parameters of its biological cycle. The present study evaluated the effect of deltamethrin on detoxifying enzymes and biological parameters in a population of Aedes aegypti selected for 15 generations. The enzyme activities of alpha- and beta-esterases, mixed-function oxidases and glutathione-S-transferases were determined during selection, along with biological parameters. Overexpression of mixed-function oxidases as a mechanism of metabolic resistance to deltamethrin was found. There were decreases in percentages of eggs hatching, pupation and age-specific survival and in total survival at the end of the selection (F 16 ). Although age-specific fecundity was not affected by selection with deltamethrin, total fertility, together with lower survival, significantly affected gross reproduction rate, gradually decreasing due to deltamethrin selection. Similarly, net reproductive rate and intrinsic growth rate were affected by selection. Alterations in life parameters could be due to the accumulation of noxious effects or deleterious genes related to detoxifying enzymes, specifically those coding for mixed-function oxidases, along with the presence of recessive alleles of the V1016I and F1534C mutations, associating deltamethrin resistance with fitness cost in Ae. aegypti. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Relation of Biochemical Parameters with Flow-mediated Dilatation in Patients with Metabolic Syndrome

PubMed Central

Sipahioglu, Nurver Turfaner; Ilerigelen, Barıs; Gungor, Zeynep B.; Ayaz, Gulsel; Ekmekci, Hakan; Gurel, Cigdem Bayram; Can, Gunay; Sonmez, Huseyin; Ulutin, Turgut; Sipahioglu, Fikret

2017-01-01

Background: Metabolic syndrome (MetS) is one of the high cardiovascular (CV) situations. Endothelial dysfunction, which is a common finding in patients with MetS, is related with increased CV risk. In patients with MetS, the effect of the major CV risk factors, not included in the MetS definition, on endothelial dysfunction is not well known. The aim of this study was to determine the effect of major CV risk factors such as gender, smoking, family history, and biochemical parameters on endothelial dysfunction in patients with MetS. Methods: The study was performed between December 2010 and August 2014. A total of 55 patients (15 females and 40 males) with MetS and 81 healthy controls (37 females and 44 males) with a body mass index <25 kg/m2 were enrolled in the study. Endothelial dysfunction was measured by flow-mediated dilatation (FMD), oxidative stress parameters; high-sensitivity C-reactive protein (hs-CRP), oxidized low-density lipoprotein (ox-LDL), endothelial nitric oxide synthase (e-NOS), nitric oxide, and cell adhesion markers; von Willebrand factor, and e-selectin. Platelet aggregation (endothelial adenosine diphosphate), total platelet count, and mean platelet volume were additionally analyzed and demographic parameters were explored. Student's t-test, Mann-Whitney U-test, and Chi-square test were used to analyze the results. Results: The fasting blood glucose (z = 3.52, P = 0.001), hs-CRP (z = 3.23, P = 0.004), ox-LDL (z = 2.62, P = 0.013), and e-NOS (z = 2.22, P = 0.026) levels and cardiac risk score (z = 5.23, P < 0.001) were significantly higher in patients with MetS compared with the control group. Smoking was correlated with decreased FMD (χ2 = 9.26, P = 0.002) in MetS patients but not in the control group. Conclusions: Increased ox-LDL, hs-CRP, and e-NOS are likely to be a result of oxidative stress, a condition in which an imbalance occurs between the production and inactivation of reactive nitrogen and oxygen species. In addition, in patients

Plasma metabolic profiling of dairy cows affected with clinical ketosis using LC/MS technology.

PubMed

Li, Y; Xu, C; Xia, C; Zhang, Hy; Sun, Lw; Gao, Y

2014-01-01

Ketosis in dairy cattle is an important metabolic disorder. Currently, the plasma metabolic profile of ketosis as determined using liquid chromatography-mass spectrometry (LC/MS) has not been reported. To investigate plasma metabolic profiles from cows with clinical ketosis in comparison to control cows. Twenty Holstein dairy cows were divided into two groups based on clinical signs and plasma β-hydroxybutyric acid and glucose concentrations 7-21 days postpartum: clinical ketosis and control cows. Plasma metabolic profiles were analyzed using LC/MS. Data were processed using principal component analysis and orthogonal partial least-squares discriminant analysis. Compared to control cows, the levels of valine, glycine, glycocholic, tetradecenoic acid, and palmitoleic acid increased significantly in clinical ketosis. On the other hand, the levels of arginine, aminobutyric acid, leucine/isoleucine, tryptophan, creatinine, lysine, norcotinine, and undecanoic acid decreased markedly. Our results showed that the metabolic changes in cows with clinical ketosis involve complex metabolic networks and signal transduction. These results are important for future studies elucidating the pathogenesis, diagnosis, and prevention of clinical ketosis in dairy cows.

Seagrass Parameter Affect the Fish Assemblages in Karimunjawa Archipelago

NASA Astrophysics Data System (ADS)

Sri Susilo, Endang; Nugroho Sugianto, Denny; Munasik; Nirwani; Adhi Suryono, Chrisna

2018-02-01

Seagrass beds promote high species diversity, abundance and biomass, and become important habitats for some economically important fishes. Plants of seagrasses result in structurally highly complex habitats and offering feeding grounds, shelter from predation as well as nursery areas for diverse fish assemblages. However, research on fish communities in Southeast Asian seagrass bed is rarely conducted. In the present study fish assemblages in seagrass beds with different parameters (cover, diversity and similarity indices, domination) was investigated in the Karimunjawa Islands, Indonesia. The purpose of this study were to assess whether fish assemblages differ concerning on the abundance and the species number. This study was conducted on the seagrass bed on Karimunjawa Islands in Java Sea, particularly in the water of Menjangan Besar and Menjangan Kecil Island. Line-quadrant transect was used to assess seagrass data, while the occurrence and individual number of fish harboured in the selected seagrass bed was counted by using underwater visual census in the stationary point count transects. Seagrass cover in Menjangan Kecil Island (41%) with various canopy included both upper and lower canopy was considerable higher than those in Menjangan Besar Island (5%). Fish diversity, species composition and abundance are considerably different between the two study sites. This study revealed that seagrass density or cover and canopy structure affected the fish abundance and species number harboured.

Metabolic regulation of inflammation.

PubMed

Gaber, Timo; Strehl, Cindy; Buttgereit, Frank

2017-05-01

Immune cells constantly patrol the body via the bloodstream and migrate into multiple tissues where they face variable and sometimes demanding environmental conditions. Nutrient and oxygen availability can vary during homeostasis, and especially during the course of an immune response, creating a demand for immune cells that are highly metabolically dynamic. As an evolutionary response, immune cells have developed different metabolic programmes to supply them with cellular energy and biomolecules, enabling them to cope with changing and challenging metabolic conditions. In the past 5 years, it has become clear that cellular metabolism affects immune cell function and differentiation, and that disease-specific metabolic configurations might provide an explanation for the dysfunctional immune responses seen in rheumatic diseases. This Review outlines the metabolic challenges faced by immune cells in states of homeostasis and inflammation, as well as the variety of metabolic configurations utilized by immune cells during differentiation and activation. Changes in cellular metabolism that contribute towards the dysfunctional immune responses seen in rheumatic diseases are also briefly discussed.

Testicular Metabolic Reprogramming in Neonatal Streptozotocin-Induced Type 2 Diabetic Rats Impairs Glycolytic Flux and Promotes Glycogen Synthesis

PubMed Central

Rato, L.; Alves, M. G.; Dias, T. R.; Cavaco, J. E.; Oliveira, Pedro F.

2015-01-01

Defects in testicular metabolism are directly implicated with male infertility, but most of the mechanisms associated with type 2 diabetes- (T2DM) induced male infertility remain unknown. We aimed to evaluate the effects of T2DM on testicular glucose metabolism by using a neonatal-streptozotocin- (n-STZ) T2DM animal model. Plasma and testicular hormonal levels were evaluated using specific kits. mRNA and protein expression levels were assessed by real-time PCR and Western Blot, respectively. Testicular metabolic profile was assessed by 1H-NMR spectroscopy. T2DM rats showed increased glycemic levels, impaired glucose tolerance and hyperinsulinemia. Both testicular and serum testosterone levels were decreased, whereas those of 17β-estradiol were not altered. Testicular glycolytic flux was not favored in testicles of T2DM rats, since, despite the increased expression of both glucose transporters 1 and 3 and the enzyme phosphofructokinase 1, lactate dehydrogenase activity was severely decreased contributing to lower testicular lactate content. However, T2DM enhanced testicular glycogen accumulation, by modulating the availability of the precursors for its synthesis. T2DM also affected the reproductive sperm parameters. Taken together these results indicate that T2DM is able to reprogram testicular metabolism by enhancing alternative metabolic pathways, particularly glycogen synthesis, and such alterations are associated with impaired sperm parameters. PMID:26064993

Testicular Metabolic Reprogramming in Neonatal Streptozotocin-Induced Type 2 Diabetic Rats Impairs Glycolytic Flux and Promotes Glycogen Synthesis.

PubMed

Rato, L; Alves, M G; Dias, T R; Cavaco, J E; Oliveira, Pedro F

2015-01-01

Defects in testicular metabolism are directly implicated with male infertility, but most of the mechanisms associated with type 2 diabetes- (T2DM) induced male infertility remain unknown. We aimed to evaluate the effects of T2DM on testicular glucose metabolism by using a neonatal-streptozotocin- (n-STZ) T2DM animal model. Plasma and testicular hormonal levels were evaluated using specific kits. mRNA and protein expression levels were assessed by real-time PCR and Western Blot, respectively. Testicular metabolic profile was assessed by (1)H-NMR spectroscopy. T2DM rats showed increased glycemic levels, impaired glucose tolerance and hyperinsulinemia. Both testicular and serum testosterone levels were decreased, whereas those of 17β-estradiol were not altered. Testicular glycolytic flux was not favored in testicles of T2DM rats, since, despite the increased expression of both glucose transporters 1 and 3 and the enzyme phosphofructokinase 1, lactate dehydrogenase activity was severely decreased contributing to lower testicular lactate content. However, T2DM enhanced testicular glycogen accumulation, by modulating the availability of the precursors for its synthesis. T2DM also affected the reproductive sperm parameters. Taken together these results indicate that T2DM is able to reprogram testicular metabolism by enhancing alternative metabolic pathways, particularly glycogen synthesis, and such alterations are associated with impaired sperm parameters.

Isocaloric fructose restriction and metabolic improvement in children with obesity and metabolic syndrome.

PubMed

Lustig, Robert H; Mulligan, Kathleen; Noworolski, Susan M; Tai, Viva W; Wen, Michael J; Erkin-Cakmak, Ayca; Gugliucci, Alejandro; Schwarz, Jean-Marc

2016-02-01

Dietary fructose is implicated in metabolic syndrome, but intervention studies are confounded by positive caloric balance, changes in adiposity, or artifactually high amounts. This study determined whether isocaloric substitution of starch for sugar would improve metabolic parameters in Latino (n = 27) and African-American (n = 16) children with obesity and metabolic syndrome. Participants consumed a diet for 9 days to deliver comparable percentages of protein, fat, and carbohydrate as their self-reported diet; however, dietary sugar was reduced from 28% to 10% and substituted with starch. Participants recorded daily weights, with calories adjusted for weight maintenance. Participants underwent dual-energy X-ray absorptiometry and oral glucose tolerance testing on Days 0 and 10. Biochemical analyses were controlled for weight change by repeated measures ANCOVA. Reductions in diastolic blood pressure (-5 mmHg; P = 0.002), lactate (-0.3 mmol/L; P < 0.001), triglyceride, and LDL-cholesterol (-46% and -0.3 mmol/L; P < 0.001) were noted. Glucose tolerance and hyperinsulinemia improved (P < 0.001). Weight reduced by 0.9 ± 0.2 kg (P < 0.001) and fat-free mass by 0.6 kg (P = 0.04). Post hoc sensitivity analysis demonstrates that results in the subcohort that did not lose weight (n = 10) were directionally consistent. Isocaloric fructose restriction improved surrogate metabolic parameters in children with obesity and metabolic syndrome irrespective of weight change. © 2015 The Obesity Society.

TNFα Altered Inflammatory Responses, Impaired Health and Productivity, but Did Not Affect Glucose or Lipid Metabolism in Early-Lactation Dairy Cows

PubMed Central

Mamedova, Laman K.; Sordillo, Lorraine M.; Bradford, Barry J.

2013-01-01

Inflammation may be a major contributing factor to peripartum metabolic disorders in dairy cattle. We tested whether administering an inflammatory cytokine, recombinant bovine tumor necrosis factor-α (rbTNFα), affects milk production, metabolism, and health during this period. Thirty-three Holstein cows (9 primiparous and 24 multiparous) were randomly assigned to 1 of 3 treatments at parturition. Treatments were 0 (Control), 1.5, or 3.0 µg/kg body weight rbTNFα, which were administered once daily by subcutaneous injection for the first 7 days of lactation. Statistical contrasts were used to evaluate the treatment and dose effects of rbTNFα administration. Plasma TNFα concentrations at 16 h post-administration tended to be increased (P<0.10) by rbTNFα administration, but no dose effect (P>0.10) was detected; rbTNFα treatments increased (P<0.01) concentrations of plasma haptoglobin. Most plasma eicosanoids were not affected (P>0.10) by rbTNFα administration, but 6 out of 16 measured eicosanoids changed (P<0.05) over the first week of lactation, reflecting elevated inflammatory mediators in the days immediately following parturition. Dry matter and water intake, milk yield, and milk fat and protein yields were all decreased (P<0.05) by rbTNFα treatments by 15 to 18%. Concentrations of plasma glucose, insulin, β-hydroxybutyrate, non-esterified fatty acids, triglyceride, 3-methylhistidine, and liver triglyceride were unaffected (P>0.10) by rbTNFα treatment. Glucose turnover rate was unaffected (P = 0.18) by rbTNFα administration. The higher dose of rbTNFα tended to increase the risk of cows developing one or more health disorders (P = 0.08). Taken together, these results indicate that administration of rbTNFα daily for the first 7 days of lactation altered inflammatory responses, impaired milk production and health, but did not significantly affect liver triglyceride accumulation or nutrient metabolism in dairy cows. PMID:24260367

Parameter Balancing in Kinetic Models of Cell Metabolism†

PubMed Central

2010-01-01

Kinetic modeling of metabolic pathways has become a major field of systems biology. It combines structural information about metabolic pathways with quantitative enzymatic rate laws. Some of the kinetic constants needed for a model could be collected from ever-growing literature and public web resources, but they are often incomplete, incompatible, or simply not available. We address this lack of information by parameter balancing, a method to complete given sets of kinetic constants. Based on Bayesian parameter estimation, it exploits the thermodynamic dependencies among different biochemical quantities to guess realistic model parameters from available kinetic data. Our algorithm accounts for varying measurement conditions in the input data (pH value and temperature). It can process kinetic constants and state-dependent quantities such as metabolite concentrations or chemical potentials, and uses prior distributions and data augmentation to keep the estimated quantities within plausible ranges. An online service and free software for parameter balancing with models provided in SBML format (Systems Biology Markup Language) is accessible at www.semanticsbml.org. We demonstrate its practical use with a small model of the phosphofructokinase reaction and discuss its possible applications and limitations. In the future, parameter balancing could become an important routine step in the kinetic modeling of large metabolic networks. PMID:21038890

Which parameters affect long-term mortality in older adults: is comprehensive geriatric assessment a predictor of mortality?

PubMed

Kara, Ozgur; Canbaz, Busra; Kizilarslanoglu, Muhammet Cemal; Arik, Gunes; Sumer, Fatih; Aycicek, Gozde Sengul; Varan, Hacer Dogan; Kilic, Mustafa Kemal; Dogru, Rana Tuna; Cınar, Esat; Kuyumcu, Mehmet Emin; Yesil, Yusuf; Ulger, Zekeriya; Yavuz, Burcu Balam; Halil, Meltem; Cankurtaran, Mustafa

2017-06-01

Determining predictors of mortality among older adults might help identify high-risk patients and enable timely intervention. The aim of the study was to identify which variables predict geriatric outpatient mortality, using routine geriatric assessment tools. We analyzed the data of 1141 patients who were admitted to the geriatric medicine outpatient clinic between 2001 and 2004. Comprehensive geriatric assessment was performed by an interdisciplinary geriatric team. Mortality rate was determined in 2015. The parameters predicting survival were examined. Median age of the patients (415 male, 726 female) was 71.7 years (53-95 years). Mean survival time was 12.2 years (95 % CI; 12-12.4 years). In multivariate analysis, age (OR: 1.16, 95 % CI: 1.09-1.23, p < 0.001), smoking (OR: 2.51, 95 % CI: 1.18-5.35, p = 0.017) and metabolic syndrome (OR: 2.20, 95 % CI: 1.05-4.64, p = 0.038) were found to be independent risk factors for mortality. MNA-SF scores (OR: 0.84, 95 % CI: 0.71-1.00, p = 0.050) and free T3 levels (OR: 0.70, 95 % CI: 0.49-1.00, p = 0.052) had borderline significance. The present study showed that the risk conferred by metabolic syndrome is beyond its individual components. Our findings confirm previous studies on the prognostic role of nutritional status, as reflected by MNA-SF. Serum fT3, a simple laboratory test, may also be used in geriatric outpatient clinics to identify individuals at risk. The results of the study demonstrated the need for addressing modifiable risk factors such as smoking, metabolic syndrome, and undernutrition in older adults.

Metabolic phenotyping and systems biology approaches to understanding metabolic syndrome and fatty liver disease.

PubMed

Dumas, Marc-Emmanuel; Kinross, James; Nicholson, Jeremy K

2014-01-01

Metabolic syndrome, a cluster of risk factors for type 2 diabetes mellitus and cardiovascular disease, is becoming an increasing global health concern. Insulin resistance is often associated with metabolic syndrome and also typical hepatic manifestations such as nonalcoholic fatty liver disease. Profiling of metabolic products (metabolic phenotyping or metabotyping) has provided new insights into metabolic syndrome and nonalcoholic fatty liver disease. Data from nuclear magnetic resonance spectroscopy and mass spectrometry combined with statistical modeling and top-down systems biology have allowed us to analyze and interpret metabolic signatures in terms of metabolic pathways and protein interaction networks and to identify the genomic and metagenomic determinants of metabolism. For example, metabolic phenotyping has shown that relationships between host cells and the microbiome affect development of the metabolic syndrome and fatty liver disease. We review recent developments in metabolic phenotyping and systems biology technologies and how these methodologies have provided insights into the mechanisms of metabolic syndrome and nonalcoholic fatty liver disease. We discuss emerging areas of research in this field and outline our vision for how metabolic phenotyping could be used to study metabolic syndrome and fatty liver disease. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Effects of two calculolytic diets on parameters of feline mineral metabolism.

PubMed

Pineda, C; Aguilera-Tejero, E; Raya, A I; Montes de Oca, A; Rodriguez, M; Lopez, I

2015-08-01

To evaluate the influence of two feline calculolytic diets on selected parameters of mineral metabolism. Two dry commercial diets designed for struvite urolith dissolution were evaluated in 14 cats. The study was designed as a two-sequence, four-period crossover protocol with a baseline period, two 60-day "run-in" periods in which calculolytic diets (Diet 1 and Diet 2) were fed and one 30-day "wash-out" period. Data are expressed as median (range). Feeding the calculolytic diets for two months did not alter plasma concentrations of calcium, phosphorus, magnesium and parathyroid hormone. A significant (P < 0.05 in each case) decline in calcitriol was observed after administering both diets from 236.4 (122.4-429.6) to 170.4 (108.0-394.3) pmol/L (Diet 1) and from 278.4 (153.6-492.0) to 177.1 (87.6-392.4) pmol/L (Diet 2). Cats fed Diet 1 showed a significant increase in urine calcium concentration (from 0.3 (0.2-0.5) to 0.4 (0.3-0.7) mmol/L). Magnesium concentration in urine was significantly increased with both diets, from 1.4 (0.1-1.7) to 1.5 (1.3-2.4) mmol/L (Diet 1) and from 1.1 (0.4-1.9) to 2.0 (0.1-3.1) mmol/L (Diet 2). Both diets resulted in an increased urinary concentration of magnesium, through different mechanisms: urine acidification (Diet 1) and increased sodium load (Diet 2). © 2015 British Small Animal Veterinary Association.

The Association between Breakfast Skipping and Body Weight, Nutrient Intake, and Metabolic Measures among Participants with Metabolic Syndrome

PubMed Central

Zhang, Lijuan; Cordeiro, Lorraine S.; Liu, Jinghua; Ma, Yunsheng

2017-01-01

The effect of skipping breakfast on health, especially in adults, remains a controversial topic. A secondary data analysis was conducted to examine associations between breakfast eating patterns and weight loss, nutrient intake, and metabolic parameters among participants with metabolic syndrome (MetS) (n = 240). Three randomly selected 24-h dietary recalls were collected from each participant at baseline and at the one-year visit. Skipped breakfast was seen in 32.9% at baseline and in 17.4% at the one-year visit, respectively. At baseline, after adjustment for demographics and physical activity, participants who ate breakfast had a higher thiamin, niacin, and folate intake than did breakfast skippers (p < 0.05); other selected parameters including body weight, dietary quality scores, nutrient intake, and metabolic parameters showed no significant differences between the two groups (p ≥ 0.05). From baseline to one year, after adjustment for covariates, mean fat intake increased by 2.7% (95% confidence intervals (CI): −1.0, 6.5%) of total energy in breakfast skippers in comparison to the 1.2% decrease observed in breakfast eaters (95% CI: −3.4, 1.1%) (p = 0.02). Mean changes in other selected parameters showed no significant differences between breakfast skippers and eaters (p > 0.05). This study did not support the hypothesis that skipping breakfast has impact on body weight, nutrient intakes, and selected metabolic measures in participants with MetS. PMID:28420112

Cellular metabolism in colorectal carcinogenesis: Influence of lifestyle, gut microbiome and metabolic pathways.

PubMed

Hagland, Hanne R; Søreide, Kjetil

2015-01-28

The interconnectivity between diet, gut microbiota and cell molecular responses is well known; however, only recently has technology allowed the identification of strains of microorganisms harbored in the gastrointestinal tract that may increase susceptibility to cancer. The colonic environment appears to play a role in the development of colon cancer, which is influenced by the human metabolic lifestyle and changes in the gut microbiome. Studying metabolic changes at the cellular level in cancer be useful for developing novel improved preventative measures, such as screening through metabolic breath-tests or treatment options that directly affect the metabolic pathways responsible for the carcinogenicity. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Inflammatory-metabolic parameters in obese and nonobese normoandrogenemic polycystic ovary syndrome during metformin and oral contraceptive treatment.

PubMed

Kilic, Sevtap; Yilmaz, Nafiye; Zulfikaroglu, Ebru; Erdogan, Gokcen; Aydin, Murat; Batioglu, Sertac

2011-09-01

Our aim was to evaluate the optimal treatment strategy addressing cardiovascular risk in obese and nonobese patients with polycystic ovary syndrome (PCOS). We planned a prospectıve randomized clinical study. Normoandrogenemic and oligoamenorrheic women with PCOS and impaired glucose tolerance (n = 96) were enrolled in the study. Six months of treatment with metformin HCL or oral contraceptive pills (OCPs) were given to the patients. Group 1 were obese and receiving metformin. Group 2 were obese and receiving OCPs. Group 3 were nonobese and receiving metformin, and Group 4 were nonobese receiving OCPs. ADMA, homocysteine, high sensitive C-reactive protein (hs-CRP) and homeostasis model assessment estimate of insulin resistance (HOMA-IR) were investigated. ADMA, homocysteine, hs-CRP and HOMA-IR were similar in obese and nonobese groups before the treatment. After 6 months of treatment, a significant decrease was observed in ADMA, homocysteine and HOMA-IR levels in Groups 1 and 3. An increase in ADMA and hs-CRP levels was observed in Groups 2 and 4. In this study, metformin treatment leads to improvement in hormonal and metabolic parameters and decreases ADMA and homocysteine levels possibly independent of BMI. However, the use of oral contraceptives in obese and nonobese patients with PCOS with impaired glucose tolerance increases ADMA and hs-CRP levels and creates an increase in the metabolic risk.

Topiramate in schizophrenia: a review of effects on psychopathology and metabolic parameters.

PubMed

Hahn, Margaret K; Cohn, Tony; Teo, Celine; Remington, Gary

2013-01-01

Less than half of patients with schizophrenia obtain full response to antipsychotic drugs and, while clozapine represents the treatment of choice for refractory psychosis, a significant number of individuals remain only partially responsive. Despite a need for augmentation in this subpopulation, to date clear choices have not been forthcoming. Because clozapine, along with the majority of second-generation agents (SGAs), are linked to metabolic disturbances, augmentation strategies that do not further exacerbate these side effects are needed. Topiramate, unlike other anticonvulsants used for augmentation purposes, has been associated with weight loss. This article reviews the safety and efficacy of topiramate in treatment-refractory schizophrenia, including effects on metabolic disturbances, which burden this population. While current evidence specifically examining improvements in psychopathology demonstrates small to moderate benefits with topiramate augmentation, a growing body of evidence suggests that topiramate may have beneficial effects on antipsychotic-induced weight gain. We conclude that topiramate's metabolic profile, taken together with a current lack of evidence supporting a particular augmentation strategy, argues for further well-controlled studies examining its potential as an augmentation strategy in schizophrenia.

Metabolic markers in sports medicine.

PubMed

Banfi, Giuseppe; Colombini, Alessandra; Lombardi, Giovanni; Lubkowska, Anna

2012-01-01

Physical exercise induces adaptations in metabolism considered beneficial for health. Athletic performance is linked to adaptations, training, and correct nutrition in individuals with genetic traits that can facilitate such adaptations. Intense and continuous exercise, training, and competitions, however, can induce changes in the serum concentrations of numerous laboratory parameters. When these modifications, especially elevated laboratory levels, result outside the reference range, further examinations are ordered or participation in training and competition is discontinued or sports practice loses its appeal. In order to correctly interpret commonly used laboratory data, laboratory professionals and sport physicians need to know the behavior of laboratory parameters during and after practice and competition. We reviewed the literature on liver, kidney, muscle, heart, energy, and bone parameters in athletes with a view to increase the knowledge about clinical chemistry applied to sport and to stimulate studies in this field. In liver metabolism, the interpretation of serum aminotransferases concentration in athletes should consider the release of aspartate aminotransferase (AST) from muscle and of alanine aminotransferase (ALT) mainly from the liver, when bilirubin can be elevated because of continuous hemolysis, which is typical of exercise. Muscle metabolism parameters such as creatine kinase (CK) are typically increased after exercise. This parameter can be used to interpret the physiological release of CK from muscle, its altered release due to rhabdomyolysis, or incomplete recovery due to overreaching or trauma. Cardiac markers are released during exercise, and especially endurance training. Increases in these markers should not simply be interpreted as a signal of cardiac damage or wall stress but rather as a sign of regulation of myocardial adaptation. Renal function can be followed in athletes by measuring serum creatinine concentration, but it should

Intra-Seasonal Flexibility in Avian Metabolic Performance Highlights the Uncoupling of Basal Metabolic Rate and Thermogenic Capacity

PubMed Central

Petit, Magali; Lewden, Agnès; Vézina, François

2013-01-01

Stochastic winter weather events are predicted to increase in occurrence and amplitude at northern latitudes and organisms are expected to cope through phenotypic flexibility. Small avian species wintering in these environments show acclimatization where basal metabolic rate (BMR) and maximal thermogenic capacity (MSUM) are typically elevated. However, little is known on intra-seasonal variation in metabolic performance and on how population trends truly reflect individual flexibility. Here we report intra-seasonal variation in metabolic parameters measured at the population and individual levels in black-capped chickadees ( Poecile atricapillus ). Results confirmed that population patterns indeed reflect flexibility at the individual level. They showed the expected increase in BMR (6%) and MSUM (34%) in winter relative to summer but also, and most importantly, that these parameters changed differently through time. BMR began its seasonal increase in November, while MSUM had already achieved more than 20% of its inter-seasonal increase by October, and declined to its starting level by March, while MSUM remained high. Although both parameters co-vary on a yearly scale, this mismatch in the timing of variation in winter BMR and MSUM likely reflects different constraints acting on different physiological components and therefore suggests a lack of functional link between these parameters. PMID:23840843

Linking neuronal brain activity to the glucose metabolism.

PubMed

Göbel, Britta; Oltmanns, Kerstin M; Chung, Matthias

2013-08-29

Energy homeostasis ensures the functionality of the entire organism. The human brain as a missing link in the global regulation of the complex whole body energy metabolism is subject to recent investigation. The goal of this study is to gain insight into the influence of neuronal brain activity on cerebral and peripheral energy metabolism. In particular, the tight link between brain energy supply and metabolic responses of the organism is of interest. We aim to identifying regulatory elements of the human brain in the whole body energy homeostasis. First, we introduce a general mathematical model describing the human whole body energy metabolism. It takes into account the two central roles of the brain in terms of energy metabolism. The brain is considered as energy consumer as well as regulatory instance. Secondly, we validate our mathematical model by experimental data. Cerebral high-energy phosphate content and peripheral glucose metabolism are measured in healthy men upon neuronal activation induced by transcranial direct current stimulation versus sham stimulation. By parameter estimation we identify model parameters that provide insight into underlying neurophysiological processes. Identified parameters reveal effects of neuronal activity on regulatory mechanisms of systemic glucose metabolism. Our examinations support the view that the brain increases its glucose supply upon neuronal activation. The results indicate that the brain supplies itself with energy according to its needs, and preeminence of cerebral energy supply is reflected. This mechanism ensures balanced cerebral energy homeostasis. The hypothesis of the central role of the brain in whole body energy homeostasis as active controller is supported.

Linking neuronal brain activity to the glucose metabolism

PubMed Central

2013-01-01

Background Energy homeostasis ensures the functionality of the entire organism. The human brain as a missing link in the global regulation of the complex whole body energy metabolism is subject to recent investigation. The goal of this study is to gain insight into the influence of neuronal brain activity on cerebral and peripheral energy metabolism. In particular, the tight link between brain energy supply and metabolic responses of the organism is of interest. We aim to identifying regulatory elements of the human brain in the whole body energy homeostasis. Methods First, we introduce a general mathematical model describing the human whole body energy metabolism. It takes into account the two central roles of the brain in terms of energy metabolism. The brain is considered as energy consumer as well as regulatory instance. Secondly, we validate our mathematical model by experimental data. Cerebral high-energy phosphate content and peripheral glucose metabolism are measured in healthy men upon neuronal activation induced by transcranial direct current stimulation versus sham stimulation. By parameter estimation we identify model parameters that provide insight into underlying neurophysiological processes. Identified parameters reveal effects of neuronal activity on regulatory mechanisms of systemic glucose metabolism. Results Our examinations support the view that the brain increases its glucose supply upon neuronal activation. The results indicate that the brain supplies itself with energy according to its needs, and preeminence of cerebral energy supply is reflected. This mechanism ensures balanced cerebral energy homeostasis. Conclusions The hypothesis of the central role of the brain in whole body energy homeostasis as active controller is supported. PMID:23988084

Dim Light at Night Disrupts Molecular Circadian Rhythms and Affects Metabolism

PubMed Central

Fonken, Laura K.; Aubrecht, Taryn G.; Meléndez-Fernández, O. Hecmarie; Weil, Zachary M.; Nelson, Randy J.

2014-01-01

With the exception of high latitudes, life has evolved under bright days and dark nights. Most organisms have developed endogenously driven circadian rhythms which are synchronized to this daily light/dark cycle. In recent years, humans have shifted away from the naturally occurring solar light cycle in favor of artificial and sometimes irregular light schedules produced by electrical lighting. Exposure to unnatural light cycles is increasingly associated with obesity and metabolic syndrome; however the means by which environmental lighting alters metabolism are poorly understood. Thus, we exposed mice to nighttime light and investigated changes in the circadian system and body weight. Here we report that exposure to ecologically relevant levels of dim (5 lux) light at night attenuate core circadian clock rhythms in the SCN at both the gene and protein level. Moreover, circadian clock rhythms were perturbed in the liver by nighttime light exposure. Changes in the circadian clock were associated with temporal alterations in feeding behavior and increased weight gain. These results are significant because they provide mechanistic evidence for how mild changes in environmental lighting can alter circadian and metabolic function. PMID:23929553

Why does offspring size affect performance? Integrating metabolic scaling with life-history theory

PubMed Central

Pettersen, Amanda K.; White, Craig R.; Marshall, Dustin J.

2015-01-01

Within species, larger offspring typically outperform smaller offspring. While the relationship between offspring size and performance is ubiquitous, the cause of this relationship remains elusive. By linking metabolic and life-history theory, we provide a general explanation for why larger offspring perform better than smaller offspring. Using high-throughput respirometry arrays, we link metabolic rate to offspring size in two species of marine bryozoan. We found that metabolism scales allometrically with offspring size in both species: while larger offspring use absolutely more energy than smaller offspring, larger offspring use proportionally less of their maternally derived energy throughout the dependent, non-feeding phase. The increased metabolic efficiency of larger offspring while dependent on maternal investment may explain offspring size effects—larger offspring reach nutritional independence (feed for themselves) with a higher proportion of energy relative to structure than smaller offspring. These findings offer a potentially universal explanation for why larger offspring tend to perform better than smaller offspring but studies on other taxa are needed. PMID:26559952

Refrigeration and cryopreservation of platelets differentially affect platelet metabolism and function: a comparison with conventional platelet storage conditions.

PubMed

Johnson, Lacey; Tan, Shereen; Wood, Ben; Davis, April; Marks, Denese C

2016-07-01

Alternatives to room temperature storage of platelets (PLTs) may be beneficial to extend the limited shelf life and support transfusion logistics in rural and military areas. The aim of this study was to assess the morphologic, metabolic, and functional aspects of PLTs stored at room temperature or in refrigerated conditions or cryopreserved. A three-arm pool-and-split study was carried out using buffy coat-derived PLTs stored in 30% plasma/70% SSP+. The three matched treatment arms were room temperature stored (20-24°C), cold-stored (2-6°C), and cryopreserved (-80°C with dimethyl sulfoxide). Liquid-stored PLTs were tested over a 21-day period, while cryopreserved PLTs were examined immediately after thawing and after 6 and 24 hours of storage at room temperature. Cold-stored and cryopreserved PLTs underwent a significant shape change, although the cryopreserved PLTs appeared to recover from this during subsequent storage. Glycolytic metabolism was reduced in cold-stored PLTs, but accelerated in cryopreserved PLTs, while oxidative phosphorylation was negatively affected by both storage conditions. PLT aggregation was potentiated by cold storage and diminished by cryopreservation in comparison to room temperature-stored PLTs. Cold storage and cryopreservation resulted in faster clot formation (R-time; thromboelastography), which was associated with an increase in microparticles. Cold storage and cryopreservation of PLTs led to morphologic and metabolic changes. However, storage under these conditions appears to maintain or even enhance certain aspects of in vitro PLT function. © 2016 AABB.

A new parametric method to smooth time-series data of metabolites in metabolic networks.

PubMed

Miyawaki, Atsuko; Sriyudthsak, Kansuporn; Hirai, Masami Yokota; Shiraishi, Fumihide

2016-12-01

Mathematical modeling of large-scale metabolic networks usually requires smoothing of metabolite time-series data to account for measurement or biological errors. Accordingly, the accuracy of smoothing curves strongly affects the subsequent estimation of model parameters. Here, an efficient parametric method is proposed for smoothing metabolite time-series data, and its performance is evaluated. To simplify parameter estimation, the method uses S-system-type equations with simple power law-type efflux terms. Iterative calculation using this method was found to readily converge, because parameters are estimated stepwise. Importantly, smoothing curves are determined so that metabolite concentrations satisfy mass balances. Furthermore, the slopes of smoothing curves are useful in estimating parameters, because they are probably close to their true behaviors regardless of errors that may be present in the actual data. Finally, calculations for each differential equation were found to converge in much less than one second if initial parameters are set at appropriate (guessed) values. Copyright © 2016 Elsevier Inc. All rights reserved.

Cerebral oxygen metabolism in neonatal hypoxic ischemic encephalopathy during and after therapeutic hypothermia

PubMed Central

Dehaes, Mathieu; Aggarwal, Alpna; Lin, Pei-Yi; Rosa Fortuno, C; Fenoglio, Angela; Roche-Labarbe, Nadège; Soul, Janet S; Franceschini, Maria Angela; Grant, P Ellen

2014-01-01

Pathophysiologic mechanisms involved in neonatal hypoxic ischemic encephalopathy (HIE) are associated with complex changes of blood flow and metabolism. Therapeutic hypothermia (TH) is effective in reducing the extent of brain injury, but it remains uncertain how TH affects cerebral blood flow (CBF) and metabolism. Ten neonates undergoing TH for HIE and seventeen healthy controls were recruited from the NICU and the well baby nursery, respectively. A combination of frequency domain near infrared spectroscopy (FDNIRS) and diffuse correlation spectroscopy (DCS) systems was used to non-invasively measure cerebral hemodynamic and metabolic variables at the bedside. Results showed that cerebral oxygen metabolism (CMRO2i) and CBF indices (CBFi) in neonates with HIE during TH were significantly lower than post-TH and age-matched control values. Also, cerebral blood volume (CBV) and hemoglobin oxygen saturation (SO2) were significantly higher in neonates with HIE during TH compared with age-matched control neonates. Post-TH CBV was significantly decreased compared with values during TH whereas SO2 remained unchanged after the therapy. Thus, FDNIRS–DCS can provide information complimentary to SO2 and can assess individual cerebral metabolic responses to TH. Combined FDNIRS–DCS parameters improve the understanding of the underlying physiology and have the potential to serve as bedside biomarkers of treatment response and optimization. PMID:24064492

FT3/FT4 ratio predicts non-alcoholic fatty liver disease independent of metabolic parameters in patients with euthyroidism and hypothyroidism

PubMed Central

Gökmen, Fatma Yahyaoğlu; Ahbab, Süleyman; Ataoğlu, Hayriye Esra; Türker, Betül Çavuşoğlu; Çetin, Faik; Türker, Fatih; Mamaç, Rabia Yahyaoğlu; Yenigün, Mustafa

2016-01-01

OBJECTIVE: This study was performed to evaluate the effects of metabolic parameters and thyroid dysfunction on the development of non-alcoholic fatty liver disease (NAFLD). METHODS: The current study evaluated a total of 115 patients, 75 female and 40 male. Physical examination and anthropometric measurements were applied to all participants. Hypothyroidism was considered at a thyroid stimulating hormone level ≥ 4.1 mIU/L. Patients with euthyroidism and patients with hypothyroidism were compared. Abdominal ultrasonography was used to diagnose non-alcoholic fatty liver disease. The participants were further compared with regard to the presence of non-alcoholic fatty liver disease. Logistic regression modeling was performed to identify the relationship between non-alcoholic fatty liver disease and independent variables, such as metabolic parameters and insulin resistance. RESULTS: Non-alcoholic fatty liver disease was identified in 69 patients. The mean waist circumference, body mass index, fasting plasma insulin, HOMA-IR (p<0.001) and FT3/FT4 ratio (p=0.01) values were significantly higher in the patients with NAFLD compared to those without it. Multivariate regression analysis revealed that FT3/FT4 ratio, waist circumference and insulin resistance were independent risk factors for non-alcoholic fatty liver disease. CONCLUSION: Insulin resistance, enlarged waist circumference, elevated body mass index, higher FT3/FT4 ratio and hypertriglyceridemia are independent risk factors for NADLF, whereas hypothyroidism is not directly related to the condition. PMID:27166773

Lactobacillus fermentum CRL1446 Ameliorates Oxidative and Metabolic Parameters by Increasing Intestinal Feruloyl Esterase Activity and Modulating Microbiota in Caloric-Restricted Mice

PubMed Central

Russo, Matias; Fabersani, Emanuel; Abeijón-Mukdsi, María C.; Ross, Romina; Fontana, Cecilia; Benítez-Páez, Alfonso; Gauffin-Cano, Paola; Medina, Roxana B.

2016-01-01

The purpose of this study was to determine whether the administration of the feruloyl esterase (FE)-producing strain Lactobacillus fermentum CRL1446 enhances metabolic and oxidative parameters in caloric-restricted (CR) mice. Balb/c male mice were divided into ad libitum fed Group (ALF Group), CR diet Group (CR Group) and CR diet plus L. fermentum Group (CR-Lf Group). CR diet was administered during 45 days and CRL1446 strain was given in the dose of 108 cells/mL/day/mouse. FE activity was determined in intestinal mucosa and content at Day 1, 20 and 45. Triglyceride, total cholesterol, glucose, thiobarbituric acid reactive substances (TBARS) levels and glutathione reductase activity were determined in plasma. Gut microbiota was evaluated by high-throughput sequencing of 16S rRNA gene amplicons. At Day 45, total intestinal FE activity in CR-Lf Group was higher (p = 0.020) than in CR and ALF groups and an improvement in both metabolic (reductions in triglyceride (p = 0.0025), total cholesterol (p = 0.005) and glucose (p < 0.0001) levels) and oxidative (decrease of TBARS levels and increase of plasmatic glutathione reductase activity (p = 0.006)) parameters was observed, compared to ALF Group. CR diet increased abundance of Bacteroidetes and CRL1446 administration increased abundance of Bifidobacterium and Lactobacillus genus. L. fermentun CRL1446 exerted a bifidogenic effect under CR conditions. PMID:27399766

Lactobacillus fermentum CRL1446 Ameliorates Oxidative and Metabolic Parameters by Increasing Intestinal Feruloyl Esterase Activity and Modulating Microbiota in Caloric-Restricted Mice.

PubMed

Russo, Matias; Fabersani, Emanuel; Abeijón-Mukdsi, María C; Ross, Romina; Fontana, Cecilia; Benítez-Páez, Alfonso; Gauffin-Cano, Paola; Medina, Roxana B

2016-07-07

The purpose of this study was to determine whether the administration of the feruloyl esterase (FE)-producing strain Lactobacillus fermentum CRL1446 enhances metabolic and oxidative parameters in caloric-restricted (CR) mice. Balb/c male mice were divided into ad libitum fed Group (ALF Group), CR diet Group (CR Group) and CR diet plus L. fermentum Group (CR-Lf Group). CR diet was administered during 45 days and CRL1446 strain was given in the dose of 10⁸ cells/mL/day/mouse. FE activity was determined in intestinal mucosa and content at Day 1, 20 and 45. Triglyceride, total cholesterol, glucose, thiobarbituric acid reactive substances (TBARS) levels and glutathione reductase activity were determined in plasma. Gut microbiota was evaluated by high-throughput sequencing of 16S rRNA gene amplicons. At Day 45, total intestinal FE activity in CR-Lf Group was higher (p = 0.020) than in CR and ALF groups and an improvement in both metabolic (reductions in triglyceride (p = 0.0025), total cholesterol (p = 0.005) and glucose (p < 0.0001) levels) and oxidative (decrease of TBARS levels and increase of plasmatic glutathione reductase activity (p = 0.006)) parameters was observed, compared to ALF Group. CR diet increased abundance of Bacteroidetes and CRL1446 administration increased abundance of Bifidobacterium and Lactobacillus genus. L. fermentun CRL1446 exerted a bifidogenic effect under CR conditions.

Parameters for calcium metabolism in women with polycystic ovary syndrome who undergo clomiphene citrate stimulation: a prospective cohort study.

PubMed

Ott, J; Wattar, L; Kurz, C; Seemann, R; Huber, J C; Mayerhofer, K; Vytiska-Binstorfer, E

2012-05-01

To evaluate whether parameters for calcium metabolism were associated with characteristics of polycystic ovary syndrome (PCOS). A prospective cohort study. Ninety-one anovulatory, infertile women with PCOS patients underwent clomiphene citrate (CC) stimulation. Main outcome measures were parathyroid hormone (PTH); 25-hydroxyvitamin D3 (25OHD3); serum levels of calcium, phosphorus, magnesium, albumin, and total protein; the serum calcium-phosphorus product; LH; FSH; sexual hormone binding globulin; testosterone; and androstenedione. PTH correlated inversely with serum calcium (r=-0.235; P=0.004) and 25OHD3 (r=-0.664; P<0.001), whereas positive correlations were found between PTH and body mass index (BMI; r=0.270; P=0.010) and between PTH and testosterone (r=0.347; P=0.001). After stimulation with 50 mg CC, 57.1% (52/91) developed a follicle, whereas 26.4% (24/91) became pregnant. In a multivariate model to predict both follicle development and pregnancy, BMI and 25OHD3 deficiency were significant predictive parameters. 25OHD3 deficiency was an independent predictive parameter of CC stimulation outcome, in terms of follicle development and pregnancy. Our results suggest a substantial role of vitamin D in PCOS and infertility treatment in these patients.

Nutritional Status Differentially Alters Cytochrome P450 3A4 (CYP3A4) and Uridine 5'-Diphospho-Glucuronosyltransferase (UGT) Mediated Drug Metabolism: Effect of Short-Term Fasting and High Fat Diet on Midazolam Metabolism.

PubMed

Lammers, Laureen A; Achterbergh, Roos; Romijn, Johannes A; Mathôt, Ron A A

2018-06-06

Previous studies have shown that nutritional status can alter drug metabolism which may result in treatment failure or untoward side effects. This study assesses the effect of two nutritional conditions, short-term fasting, and a short-term high fat diet (HFD) on cytochrome P450 3A4 (CYP3A4) and uridine 5'-diphospho-glucuronosyltransferase (UGT) mediated drug metabolism by studying the pharmacokinetics of midazolam and its main metabolites. In a randomized-controlled cross-over trial, nine healthy subjects received a single intravenous administration of 0.015 mg/kg midazolam after: (1) an overnight fast (control); (2) 36 h of fasting; and (3) an overnight fast after 3 days of a HFD consisting of 500 ml of cream supplemented to their regular diet. Pharmacokinetic parameters were analyzed simultaneously using non-linear mixed-effects modeling. Short-term fasting increased CYP3A4-mediated midazolam clearance by 12% (p < 0.01) and decreased UGT-mediated metabolism apparent 1-OH-midazolam clearance by 13% (p < 0.01) by decreasing the ratio of clearance and the fraction metabolite formed (ΔCL 1-OH-MDZ /f 1-OH-MDZ ). Furthermore, short-term fasting decreased apparent clearance of 1-OH-midazolam-O-glucuronide (CL 1-OH-MDZ-glucuronide /(f 1-OH-MDZ-glucuronide  × f 1-OH-MDZ )) by 20% (p < 0.01). The HFD did not affect systemic clearance of midazolam or metabolites. Short-term fasting differentially alters midazolam metabolism by increasing CYP3A4-mediated metabolism but by decreasing UGT-mediated metabolism. In contrast, a short-term HFD did not affect systemic clearance of midazolam.

Aldolase B-Mediated Fructose Metabolism Drives Metabolic Reprogramming of Colon Cancer Liver Metastasis.

PubMed

Bu, Pengcheng; Chen, Kai-Yuan; Xiang, Kun; Johnson, Christelle; Crown, Scott B; Rakhilin, Nikolai; Ai, Yiwei; Wang, Lihua; Xi, Rui; Astapova, Inna; Han, Yan; Li, Jiahe; Barth, Bradley B; Lu, Min; Gao, Ziyang; Mines, Robert; Zhang, Liwen; Herman, Mark; Hsu, David; Zhang, Guo-Fang; Shen, Xiling

2018-06-05

Cancer metastasis accounts for the majority of cancer-related deaths and remains a clinical challenge. Metastatic cancer cells generally resemble cells of the primary cancer, but they may be influenced by the milieu of the organs they colonize. Here, we show that colorectal cancer cells undergo metabolic reprogramming after they metastasize and colonize the liver, a key metabolic organ. In particular, via GATA6, metastatic cells in the liver upregulate the enzyme aldolase B (ALDOB), which enhances fructose metabolism and provides fuel for major pathways of central carbon metabolism during tumor cell proliferation. Targeting ALDOB or reducing dietary fructose significantly reduces liver metastatic growth but has little effect on the primary tumor. Our findings suggest that metastatic cells can take advantage of reprogrammed metabolism in their new microenvironment, especially in a metabolically active organ such as the liver. Manipulation of involved pathways may affect the course of metastatic growth. Copyright © 2018 Elsevier Inc. All rights reserved.

Nonfunctioning adrenal incidentaloma affecting central blood pressure and arterial stiffness parameters.

PubMed

Akkan, Tolga; Altay, Mustafa; Ünsal, Yasemin; Dağdeviren, Murat; Beyan, Esin

2017-12-01

Recently, cardiovascular risk is thought to be increased in patients with nonfunctioning adrenal incidentaloma (NFAI). There are no sufficient studies in the literature to evaluate this situation in NFAI patients without cardiovascular risk. The objective of this study is to compare peripheral and central blood pressure and arterial stiffness between patients with NFAI and healthy volunteers (of a similar age, gender and body mass index as the NFAI group) who have no traditional cardiovascular risk factors and autonomous cortisol secretion, with pulse wave analysis (PWA). In this cross-sectional study, we evaluated 35 NFAI patients who have no traditional cardiovascular risk factors and 35 healthy volunteers. PWA was performed in the participants of similar gender, age and body mass index, with a Mobil-O-Graph PWA/ABPM (I.E.M. GmBH, Stolberg, Germany) device. Radiological and biochemical data were obtained retrospectively in the NFAI group. In our study, systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), central SBP, central DBP, peripheral vascular resistance, augmentation pressure (AP), heart rate-corrected augmentation index (Aix@75) and pulse wave velocity (PWV) values were significantly higher in the NFAI group compared to the control group. In addition, peripheral and central blood pressure and arterial stiffness parameters were correlated with age and duration of NFAI diagnosis of more than 1 year. NFAIs are known as cardiometabolically innocent, but in our study, both peripheral and central blood pressure values and arterial stiffness parameters were negatively affected in patients diagnosed with NFAI who have no traditional cardiovascular risk factors. These patients are at risk of cardiovascular diseases.

Association of pharmacokinetic and metabolic parameters derived using simultaneous PET/MRI: Initial findings and impact on response evaluation in breast cancer.

PubMed

Jena, Amarnath; Taneja, Sangeeta; Singh, Aru; Negi, Pradeep; Mehta, Shashi Bhushan; Ahuja, Aashim; Singhal, Manish; Sarin, Ramesh

2017-07-01

To study relationships among pharmacokinetic and 18 F-fluorodeoxyglucose ( 18 F-FDG) PET parameters obtained through simultaneous PET/MRI in breast cancer patients and evaluate their combined potential for response evaluation. The study included 41 breast cancer patients for correlation study and 9 patients (pre and post therapy) for response evaluation. All patients underwent simultaneous PET/MRI with dedicated breast imaging. Pharmacokinetic parameters and PET parameters for tumor were derived using an in- house developed and vendor provided softwares respectively. Relationships between SUV and pharmacokinetic parameters and clinical as well as histopathologic parameters were evaluated using Spearman correlation analysis. Response to chemotherapy was derived as percentage reduction in size and in parameters post therapy. Significant correlations were observed between SUVmean, max, peak, TLG with K trans (ρ=0.446, 0.417, 0.491, 0.430; p≤0.01); with Kep(ρ=0.303, ρ=0.315, ρ=0.319; p≤0.05); and with iAUC(ρ=0.401, ρ=0.410, ρ=0.379; p≤0.05, p≤0.01). The ratio of ve/iAUC showed significant negative correlation to SUVmean, max, peak and TLG (ρ=0.420, 0.446, 0.443, 0.426; p≤0.01). Ability of SUV as well as pharmacokinetic parameters to predict response to therapy matched the RECIST criteria in 9 out of 11 lesions in 9 patients. Maximum post therapy quantitative reduction was observed in SUVpeak, TLG and K trans . Simultaneous PET/MRI enables illustration of close interactions between glucose metabolism and pharmacokinetic parameters in breast cancer patients and potential of their simultaneity in response assessment to therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Gut Microbiota and Metabolic Disorders

PubMed Central

Hur, Kyu Yeon

2015-01-01

Gut microbiota plays critical physiological roles in the energy extraction and in the control of local or systemic immunity. Gut microbiota and its disturbance also appear to be involved in the pathogenesis of diverse diseases including metabolic disorders, gastrointestinal diseases, cancer, etc. In the metabolic point of view, gut microbiota can modulate lipid accumulation, lipopolysaccharide content and the production of short-chain fatty acids that affect food intake, inflammatory tone, or insulin signaling. Several strategies have been developed to change gut microbiota such as prebiotics, probiotics, certain antidiabetic drugs or fecal microbiota transplantation, which have diverse effects on body metabolism and on the development of metabolic disorders. PMID:26124989

Psychosocial factors and metabolic parameters: is there any association in elderly people? The Massa Lombarda Project

PubMed Central

Bove, Marilisa; Carnevali, Lucio; Cicero, Arrigo FG; Grandi, Elisa; Gaddoni, Morena; Noera, Giorgio; Gaddi, Antonio V

2010-01-01

Objective Several Studies claim that psychophysical stress and depression contribute significantly to cardiovascular disease (CVD) development. The aim of our research is to discover and analyse a possible relationship between two psychosocial disorders (Depression and Perceived Mental Stress) and traditional cardiovascular risk markers. Methods We selected 106 subjects (M:58, F:48), mean age 79,5 ± 3,8 years old, from The Massa Lombarda Project, an epidemiological study including 7000 north Italian adult subjects. We carried out anamnesis, clinical and blood tests. Then we administered the Perceived Stress Questionnaire (PSQ range-score 0-1) and the Self Rating Depression Scale (SRDS range score 50-70 Z), as validated instruments for depression and stress evaluation, which focus on the individual's subjective perception and emotional response. Statistical descriptive and inferential analysis of data collected were performed. Results The Multiple linear regression analysis showed a negative correlation between PSQ Index score and Uric Acid, LDL-C, BMI, Systolic and Diastolic Blood Pressure values, a positive and statistically significant correlation between PSQ Index score and Triglycerides(P<0.05). We found an inverse relationship between Zung SRDS score and LDL-C, Uric Acid, Glucose, Waist Circumference values, this correlation was significant only for Uric Acid (P<0.01); besides a positive and significant correlation between Zung SRDS and Triglycerides (P<0.05) was observed. Conclusion We suppose that psycho-emotional stress and depression disorder, often diagnosed in elderly people, may influence different metabolic parameters (triglycerides, Uric Acid, BMI) that are involved in the complex process of Metabolic Syndrome. PMID:20635238

Altered drug metabolism during pregnancy: Hormonal regulation of drug-metabolizing enzymes

PubMed Central

Jeong, Hyunyoung

2013-01-01

Importance of the field Medication use during pregnancy is prevalent, but pharmacokinetic information of most drugs used during pregnancy is lacking in spite of known effects of pregnancy on drug disposition. Accurate pharmacokinetic information is essential for optimal drug therapy in mother and fetus. Thus, understanding how pregnancy influences drug disposition is important for better prediction of pharmacokinetic changes of drugs in pregnant women. Areas covered in this review Pregnancy is known to affect hepatic drug metabolism, but the underlying mechanisms remain unknown. Physiological changes accompanying pregnancy are likely responsible for the reported alteration in drug metabolism during pregnancy. These include elevated concentrations of various hormones such as estrogen, progesterone, placental growth hormones and prolactin. This review covers how these hormones influence expression of drug-metabolizing enzymes, thus potentially responsible for altered drug metabolism during pregnancy. What the reader will gain The reader will gain a greater understanding of the altered drug metabolism in pregnant women and the regulatory effects of pregnancy hormones on expression of drug-metabolizing enzymes. Take home message In-depth studies in hormonal regulatory mechanisms as well as confirmatory studies in pregnant women are warranted for systematic understanding and prediction of the changes in hepatic drug metabolism during pregnancy. PMID:20367533

Graded Maximal Exercise Testing to Assess Mouse Cardio-Metabolic Phenotypes

PubMed Central

Petrosino, Jennifer M.; Heiss, Valerie J.; Maurya, Santosh K.; Kalyanasundaram, Anuradha; Periasamy, Muthu; LaFountain, Richard A.; Wilson, Jacob M.; Simonetti, Orlando P.; Ziouzenkova, Ouliana

2016-01-01

Functional assessments of cardiovascular fitness (CVF) are needed to establish animal models of dysfunction, test the effects of novel therapeutics, and establish the cardio-metabolic phenotype of mice. In humans, the graded maximal exercise test (GXT) is a standardized diagnostic for assessing CVF and mortality risk. These tests, which consist of concurrent staged increases in running speed and inclination, provide diagnostic cardio-metabolic parameters, such as, VO2max, anaerobic threshold, and metabolic crossover. Unlike the human-GXT, published mouse treadmill tests have set, not staged, increases in inclination as speed progress until exhaustion (PXT). Additionally, they often lack multiple cardio-metabolic parameters. Here, we developed a mouse-GXT with the intent of improving mouse-exercise testing sensitivity and developing translatable parameters to assess CVF in healthy and dysfunctional mice. The mouse-GXT, like the human-GXT, incorporated staged increases in inclination, speed, and intensity; and, was designed by considering imitations of the PXT and differences between human and mouse physiology. The mouse-GXT and PXTs were both tested in healthy mice (C57BL/6J, FVBN/J) to determine their ability to identify cardio-metabolic parameters (anaerobic threshold, VO2max, metabolic crossover) observed in human-GXTs. Next, theses assays were tested on established diet-induced (obese-C57BL/6J) and genetic (cardiac isoform Casq2-/-) models of cardiovascular dysfunction. Results showed that both tests reported VO2max and provided reproducible data about performance. Only the mouse-GXT reproducibly identified anaerobic threshold, metabolic crossover, and detected impaired CVF in dysfunctional models. Our findings demonstrated that the mouse-GXT is a sensitive, non-invasive, and cost-effective method for assessing CVF in mice. This new test can be used as a functional assessment to determine the cardio-metabolic phenotype of various animal models or the effects of

Graded Maximal Exercise Testing to Assess Mouse Cardio-Metabolic Phenotypes.

PubMed

Petrosino, Jennifer M; Heiss, Valerie J; Maurya, Santosh K; Kalyanasundaram, Anuradha; Periasamy, Muthu; LaFountain, Richard A; Wilson, Jacob M; Simonetti, Orlando P; Ziouzenkova, Ouliana

2016-01-01

Functional assessments of cardiovascular fitness (CVF) are needed to establish animal models of dysfunction, test the effects of novel therapeutics, and establish the cardio-metabolic phenotype of mice. In humans, the graded maximal exercise test (GXT) is a standardized diagnostic for assessing CVF and mortality risk. These tests, which consist of concurrent staged increases in running speed and inclination, provide diagnostic cardio-metabolic parameters, such as, VO2max, anaerobic threshold, and metabolic crossover. Unlike the human-GXT, published mouse treadmill tests have set, not staged, increases in inclination as speed progress until exhaustion (PXT). Additionally, they often lack multiple cardio-metabolic parameters. Here, we developed a mouse-GXT with the intent of improving mouse-exercise testing sensitivity and developing translatable parameters to assess CVF in healthy and dysfunctional mice. The mouse-GXT, like the human-GXT, incorporated staged increases in inclination, speed, and intensity; and, was designed by considering imitations of the PXT and differences between human and mouse physiology. The mouse-GXT and PXTs were both tested in healthy mice (C57BL/6J, FVBN/J) to determine their ability to identify cardio-metabolic parameters (anaerobic threshold, VO2max, metabolic crossover) observed in human-GXTs. Next, theses assays were tested on established diet-induced (obese-C57BL/6J) and genetic (cardiac isoform Casq2-/-) models of cardiovascular dysfunction. Results showed that both tests reported VO2max and provided reproducible data about performance. Only the mouse-GXT reproducibly identified anaerobic threshold, metabolic crossover, and detected impaired CVF in dysfunctional models. Our findings demonstrated that the mouse-GXT is a sensitive, non-invasive, and cost-effective method for assessing CVF in mice. This new test can be used as a functional assessment to determine the cardio-metabolic phenotype of various animal models or the effects of

Influence of a 10-Day Mimic of Our Ancient Lifestyle on Anthropometrics and Parameters of Metabolism and Inflammation: The "Study of Origin".

PubMed

Pruimboom, Leo; Ruiz-Núñez, Begoña; Raison, Charles L; Muskiet, Frits A J

2016-01-01

Chronic low-grade inflammation and insulin resistance are intimately related entities that are common to most, if not all, chronic diseases of affluence. We hypothesized that a short-term intervention based on "ancient stress factors" may improve anthropometrics and clinical chemical indices. We executed a pilot study of whether a 10-day mimic of a hunter-gatherer lifestyle favorably affects anthropometrics and clinical chemical indices. Fifty-five apparently healthy subjects, in 5 groups, engaged in a 10-day trip through the Pyrenees. They walked 14 km/day on average, carrying an 8-kilo backpack. Raw food was provided and self-prepared and water was obtained from waterholes. They slept outside in sleeping bags and were exposed to temperatures ranging from 12 to 42°C. Anthropometric data and fasting blood samples were collected at baseline and the study end. We found important significant changes in most outcomes favoring better metabolic functioning and improved anthropometrics. Coping with "ancient mild stress factors," including physical exercise, thirst, hunger, and climate, may influence immune status and improve anthropometrics and metabolic indices in healthy subjects and possibly patients suffering from metabolic and immunological disorders.

β-Catenin Knockdown Affects Mitochondrial Biogenesis and Lipid Metabolism in Breast Cancer Cells.

PubMed

Vergara, Daniele; Stanca, Eleonora; Guerra, Flora; Priore, Paola; Gaballo, Antonio; Franck, Julien; Simeone, Pasquale; Trerotola, Marco; De Domenico, Stefania; Fournier, Isabelle; Bucci, Cecilia; Salzet, Michel; Giudetti, Anna M; Maffia, Michele

2017-01-01

β-catenin plays an important role as regulatory hub in several cellular processes including cell adhesion, metabolism, and epithelial mesenchymal transition. This is mainly achieved by its dual role as structural component of cadherin-based adherens junctions, and as a key nuclear effector of the Wnt pathway. For this dual role, different classes of proteins are differentially regulated via β-catenin dependent mechanisms. Here, we applied a liquid chromatography-mass spectrometry (LC-MS/MS) approach to identify proteins modulated after β-catenin knockdown in the breast cancer cell line MCF-7. We used a label free analysis to compare trypsin-digested proteins from CTR (shCTR) and β-catenin knockout cells (shβcat). This led to the identification of 98 differentially expressed proteins, 53 of them were up-regulated and 45 down-regulated. Loss of β-catenin induced morphological changes and a significant modulation of the expression levels of proteins associated with primary metabolic processes. In detail, proteins involved in carbohydrate metabolism and tricarboxylic acid cycle were found to be down-regulated, whereas proteins associated to lipid metabolism were found up-regulated in shβcat compared to shCTR. A loss of mitochondrial mass and membrane potential was also assessed by fluorescent probes in shβcat cells with respect to the controls. These data are consistent with the reduced expression of transcriptional factors regulating mitochondrial biogenesis detected in shβcat cells. β-catenin driven metabolic reprogramming resulted also in a significant modulation of lipogenic enzyme expression and activity. Compared to controls, β-catenin knockout cells showed increased incorporation of [1- 14 C]acetate and decreased utilization of [U- 14 C]glucose for fatty acid synthesis. Our data highlight a role of β-catenin in the regulation of metabolism and energy homeostasis in breast cancer cells.

Altered drug metabolism during pregnancy: hormonal regulation of drug-metabolizing enzymes.

PubMed

Jeong, Hyunyoung

2010-06-01

Medication use during pregnancy is prevalent, but pharmacokinetic information of most drugs used during pregnancy is lacking in spite of known effects of pregnancy on drug disposition. Accurate pharmacokinetic information is essential for optimal drug therapy in mother and fetus. Thus, understanding how pregnancy influences drug disposition is important for better prediction of pharmacokinetic changes of drugs in pregnant women. Pregnancy is known to affect hepatic drug metabolism, but the underlying mechanisms remain unknown. Physiological changes accompanying pregnancy are probably responsible for the reported alteration in drug metabolism during pregnancy. These include elevated concentrations of various hormones such as estrogen, progesterone, placental growth hormones and prolactin. This review covers how these hormones influence expression of drug-metabolizing enzymes (DMEs), thus potentially responsible for altered drug metabolism during pregnancy. The reader will gain a greater understanding of the altered drug metabolism in pregnant women and the regulatory effects of pregnancy hormones on expression of DMEs. In-depth studies in hormonal regulatory mechanisms as well as confirmatory studies in pregnant women are warranted for systematic understanding and prediction of the changes in hepatic drug metabolism during pregnancy.

The Effects of Physiological and Environmental Factors on Hepatic Perfusion and First-Pass Metabolism.

NASA Astrophysics Data System (ADS)

Modi, Marlene Woodruff

The interaction of three important parameters; hepatic blood flow (Q_{rm H} ), plasma protein binding (f), and hepatic intrinsic clearance (CL_{rm int}) determines the disposition of agents undergoing extensive first-pass metabolism. This collection of studies focuses on the interaction of these parameters in man and the rat in the presence and absence of a given physiological and environmental perturbation. Potential mechanisms implicated in the "Food Effect" phenomenon whereby concomitant food intake increases the bioavailability a basic lipophilic drug are examined. These investigations provide insight as to the physiological response of the liver in the face of nutritional, pharmacological and physiological perturbations. The measurement of hepatic blood flow is a necessary endeavor before and understanding of the hepatic circulation or hepatic clearance concepts can be realized. Preliminary studies were performed to improve our understanding of the factors affecting the interpretation of hepatic blood flow estimates. It has been postulated that this food effect is caused at least in part by a transient increase in Q _{rm H} with its associated decrease in hepatic first-pass metabolism. Posture was manipulated in such a manner as to simulate the hepatic blood flow pattern observed in postprandial subjects. Although transient changes in Q_{rm H } comparable in magnitude and duration to those encountered after food consumption were observed, the AUC _{rm oral} for propanolol was not affected. It is important to assess the free concentration being presented to the organ which is highly extracting the drug. Single macronutrient feedings of glucose and vitamin-free casein to male Sprague-Dawley rats did not produce significant changes in the serum protein binding of a model basic lipophilic drug (quinidine) in systemic or hepatic blood. It has been postulated that food intake may have a greater influence on the bioavailability of metoprolol (a high clearance drug

Experimental study on effect of hydroalcoholic extract of Emblica officinalis fruits on glucose homeostasis and metabolic parameters

PubMed Central

Patel, Snehal S.; Goyal, Ramesh K.; Shah, Rajendra S.; Tirgar, Pravin R.; Jadav, Pinakin D.

2013-01-01

Polyphenols from natural source are potential therapeutics that act alone or supplement anti-diabetic drugs in the prevention and treatment of diabetes. The present investigation was undertaken to study the effect of hydroalcoholic extract (HE) of fruits of Emblica officinalis on type 1 diabetic rats. Diabetes was induced by streptozotocin (STZ) (45 mg/kg i.v.). HE (100 mg/kg, p.o.) was administered for 4 weeks and at the end of treatment, blood samples were collected and analyzed for various biochemical parameters. STZ produced a diabetic state exhibiting all the cardinal symptoms such as loss of body weight, polydipsia, polyuria, glucosuria, polyphagia, hypoinsulinemia, and hyperglycemia associated with hypercholesterolemia and hypertriglyceridemia. Treatment with HE prevented cardinal symptoms and caused significant decrease in fasting serum glucose, AUCglucose, cholesterol, triglyceride, low-density lipoprotein (LDL) and very LDL in diabetic rats. However, insulin, AUCinsulin, and serum high-density lipoprotein level were not significantly altered by treatment. Treatment also reduced lipid peroxidation and increased anti-oxidant parameters in the liver homogenates of diabetic rats. Polyphenol enriched fraction of HE significantly improved disarranged carbohydrate and lipid metabolism of chemically induced diabetes in rats. The mechanism of its anti-diabetic activity appears to be either improvement in peripheral glucose utilization, increased insulin sensitivity, or anti-oxidant property. PMID:24696584

Maternal Nutrition during Pregnancy Affects Testicular and Bone Development, Glucose Metabolism and Response to Overnutrition in Weaned Horses Up to Two Years

PubMed Central

Mendoza, Luis; Peugnet, Pauline; Dubois, Cédric; Dahirel, Michèle; Lejeune, Jean-Philippe; Caudron, Isabelle; Guenon, Isabelle; Camous, Sylvaine; Tarrade, Anne; Wimel, Laurence; Serteyn, Didier; Bouraima-Lelong, Hélène; Chavatte-Palmer, Pascale

2017-01-01

Introduction Pregnant mares and post-weaning foals are often fed concentrates rich in soluble carbohydrates, together with forage. Recent studies suggest that the use of concentrates is linked to alterations of metabolism and the development of osteochondrosis in foals. The aim of this study was to determine if broodmare diet during gestation affects metabolism, osteoarticular status and growth of yearlings overfed from 20 to 24 months of age and/or sexual maturity in prepubertal colts. Material and methods Twenty-four saddlebred mares were fed forage only (n = 12, group F) or cracked barley and forage (n = 12, group B) from mid-gestation until foaling. Colts were gelded at 12 months of age. Between 20 and 24 months of age, all yearlings were overfed (+140% of requirements) using an automatic concentrate feeder. Offspring were monitored for growth between 6 and 24 months of age, glucose homeostasis was evaluated via modified frequently sampled intra veinous glucose tolerance test (FSIGT) at 19 and 24 months of age and osteoarticular status was investigated using radiographic examinations at 24 months of age. The structure and function of testicles from prepubertal colts were analyzed using stereology and RT-qPCR. Results Post-weaning weight growth was not different between groups. Testicular maturation was delayed in F colts compared to B colts at 12 months of age. From 19 months of age, the cannon bone was wider in B vs F yearlings. F yearlings were more insulin resistant at 19 months compared to B yearlings but B yearlings were affected more severely by overnutrition with reduced insulin sensitivity. The osteoarticular status at 24 months of age was not different between groups. Conclusion In conclusion, nutritional management of the pregnant broodmare and the growing foal may affect sexual maturity of colts and the metabolism of foals until 24 months of age. These effects may be deleterious for reproductive and sportive performances in older horses. PMID

Do perfluoroalkyl substances affect metabolic function and plasma lipids?--Analysis of the 2007-2009, Canadian Health Measures Survey (CHMS) Cycle 1.

PubMed

Fisher, Mandy; Arbuckle, Tye E; Wade, Mike; Haines, Douglas A

2013-02-01

Perfluorinated compounds (PFCs) are man-made chemicals that are heat stable, non-flammable and able to repel both water and oils. Biomonitoring research shows global distribution in human, animal and aquatic environments of these chemicals. PFCs have been shown to activate the peroxisome proliferator-activated receptors which play a large role in metabolism and the regulation of energy homeostasis. Previous epidemiological research has also suggested a potential role of PFCs on lipid and glucose metabolism. The objectives of this study were to examine the association between the levels of perfluorinated compounds perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), and perfluorohexane sulfonate (PFHxS) in plasma and metabolic function and plasma lipid levels. Using cross-sectional data from the Canadian Health Measures Survey (Cycle 1 2007-2009) we examined the association in adults between plasma levels of PFOA, PFOS and PFHxS (n=2700) on cholesterol outcomes, metabolic syndrome and glucose homeostasis using multivariate linear and logistic regression models. We found some evidence of a significant association between perfluoroalkyl substances, notably PFHxS, with total cholesterol (TC), low-density lipoprotein cholesterol (LDL), total cholesterol/high density lipoprotein cholesterol ratio (TC/HDL) and non-HDL cholesterol as well as an elevated odds of high cholesterol. We found some associations with PFOA and PFOS in our unweighted models but these results did not remain significant after weighting for sampling strategy. We found no association with metabolic syndrome, or glucose homeostasis parameters. This study showed lower levels of PFOA and PFOS and slightly higher levels of PFHxS than other published population studies. Our results did not give significant evidence to support the association with cholesterol outcomes with PFOS and PFOA. However, we did observe several significant associations with the PFHxS and cholesterol outcomes (LDL, TC, NON

Cardiac Metabolism in Heart Failure - Implications beyond ATP production

PubMed Central

Doenst, Torsten; Nguyen, T. Dung; Abel, E. Dale

2013-01-01

The heart has a high rate of ATP production and turnover which is required to maintain its continuous mechanical work. Perturbations in ATP generating processes may therefore affect contractile function directly. Characterizing cardiac metabolism in heart failure revealed several metabolic alterations termed metabolic remodeling, ranging from changes in substrate utilization to mitochondrial dysfunction, ultimately resulting in ATP deficiency and impaired contractility. However, ATP depletion is not the only relevant consequence of metabolic remodeling during heart failure. By providing cellular building blocks and signaling molecules, metabolic pathways control essential processes such as cell growth and regeneration. Thus, alterations in cardiac metabolism may also affect the progression to heart failure by mechanisms beyond ATP supply. Our aim is therefore to highlight that metabolic remodeling in heart failure not only results in impaired cardiac energetics, but also induces other processes implicated in the development of heart failure such as structural remodeling and oxidative stress. Accordingly, modulating cardiac metabolism in heart failure may have significant therapeutic relevance that goes beyond the energetic aspect. PMID:23989714

Stocking density affects the growth performance and metabolism of Amur sturgeon by regulating expression of genes in the GH/IGF axis

NASA Astrophysics Data System (ADS)

Ren, Yuanyuan; Wen, Haishen; Li, Yun; Li, Jifang

2017-07-01

The effects of stocking density on the growth and metabolism of Amur sturgeon were assessed. Amur sturgeon were grown for 70 days at three different stocking densities (low stocking density, LSD: 5.5 kg/m3; medium stocking density, MSD: 8.0 kg/m3; and high stocking density, HSD: 11.0 kg/m3), and the biometric index, muscle composition, and serum biochemical parameters were evaluated. In addition, pituitary, liver, and muscle samples were collected for gene cloning and expression analyses. After 70 days of growth, the fish maintained at HSD had significantly lower final body weight and specific growth rate, and a higher feed conversion ratio than those of the fish in the MSD and LSD groups. The HSD group had the lowest lipid and protein concentrations in serum and muscle. The serum cortisol concentration increased significantly in the HSD group, indicating that the stress-response system was activated in these fish. There was no change in the concentration of serum insulin-like growth factor 2 (IGF-2), while the concentrations of serum growth hormone (GH) and insulin-like growth factor 1 (IGF-1) decreased in the HSD group. The full-length cDNAs of GH and IGF-2 genes (995-bp and 1 207-bp long, respectively), were cloned and analyzed. In the HSD group, the expressions of GH in the pituitary and growth hormone receptor (GHR) and IGF-1 in the liver were down-regulated at the end of the 70-day experiment. In the HSD group, the transcript level of IGF-2 significantly decreased in the liver, but did not change in muscle. Overall, our results indicated that a HSD negatively affects the growth performance and leads to changes in lipid and protein metabolism in Amur sturgeon. The down-regulated expression of genes related to the GH/IGF axis may be responsible for the poor growth performance of Amur sturgeon under crowding stress.

Bioenergetic properties of human sarcoma cells help define sensitivity to metabolic inhibitors

PubMed Central

Issaq, Sameer H; Teicher, Beverly A; Monks, Anne

2014-01-01

Sarcomas represent a diverse group of malignancies with distinct molecular and pathological features. A better understanding of the alterations associated with specific sarcoma subtypes is critically important to improve sarcoma treatment. Renewed interest in the metabolic properties of cancer cells has led to an exploration of targeting metabolic dependencies as a therapeutic strategy. In this study, we have characterized key bioenergetic properties of human sarcoma cells in order to identify metabolic vulnerabilities between sarcoma subtypes. We have also investigated the effects of compounds that inhibit glycolysis or mitochondrial respiration, either alone or in combination, and examined relationships between bioenergetic parameters and sensitivity to metabolic inhibitors. Using 2-deoxy-D-glucose (2-DG), a competitive inhibitor of glycolysis, oligomycin, an inhibitor of mitochondrial ATP synthase, and metformin, a widely used anti-diabetes drug and inhibitor of complex I of the mitochondrial respiratory chain, we evaluated the effects of metabolic inhibition on sarcoma cell growth and bioenergetic function. Inhibition of glycolysis by 2-DG effectively reduced the viability of alveolar rhabdomyosarcoma cells vs. embryonal rhabdomyosarcoma, osteosarcoma, and normal cells. Interestingly, inhibitors of mitochondrial respiration did not significantly affect viability, but were able to increase sensitivity of sarcomas to inhibition of glycolysis. Additionally, inhibition of glycolysis significantly reduced intracellular ATP levels, and sensitivity to 2-DG-induced growth inhibition was related to respiratory rates and glycolytic dependency. Our findings demonstrate novel relationships between sarcoma bioenergetics and sensitivity to metabolic inhibitors, and suggest that inhibition of metabolic pathways in sarcomas should be further investigated as a potential therapeutic strategy. PMID:24553119

Glycogen metabolism in brain and neurons - astrocytes metabolic cooperation can be altered by pre- and neonatal lead (Pb) exposure.

PubMed

Baranowska-Bosiacka, Irena; Falkowska, Anna; Gutowska, Izabela; Gąssowska, Magdalena; Kolasa-Wołosiuk, Agnieszka; Tarnowski, Maciej; Chibowska, Karina; Goschorska, Marta; Lubkowska, Anna; Chlubek, Dariusz

2017-09-01

Lead (Pb) is an environmental neurotoxin which particularly affects the developing brain but the molecular mechanism of its neurotoxicity still needs clarification. The aim of this paper was to examine whether pre- and neonatal exposure to Pb (concentration of Pb in rat offspring blood below the "threshold level") may affect the brain's energy metabolism in neurons and astrocytes via the amount of available glycogen. We investigated the glycogen concentration in the brain, as well as the expression of the key enzymes involved in glycogen metabolism in brain: glycogen synthase 1 (Gys1), glycogen phosphorylase (PYGM, an isoform active in astrocytes; and PYGB, an isoform active in neurons) and phosphorylase kinase β (PHKB). Moreover, the expression of connexin 43 (Cx43) was evaluated to analyze whether Pb poisoning during the early phase of life may affect the neuron-astrocytes' metabolic cooperation. This work shows for the first time that exposure to Pb in early life can impair brain energy metabolism by reducing the amount of glycogen and decreasing the rate of its metabolism. This reduction in brain glycogen level was accompanied by a decrease in Gys1 expression. We noted a reduction in the immunoreactivity and the gene expression of both PYGB and PYGM isoform, as well as an increase in the expression of PHKB in Pb-treated rats. Moreover, exposure to Pb induced decrease in connexin 43 immunoexpression in all the brain structures analyzed, both in astrocytes as well as in neurons. Our data suggests that exposure to Pb in the pre- and neonatal periods results in a decrease in the level of brain glycogen and a reduction in the rate of its metabolism, thereby reducing glucose availability, which as a further consequence may lead to the impairment of brain energy metabolism and the metabolic cooperation between neurons and astrocytes. Copyright © 2017 Elsevier B.V. All rights reserved.

Determinants of physical health parameters in individuals with intellectual disability who use long-term antipsychotics.

PubMed

de Kuijper, Gerda; Mulder, Hans; Evenhuis, Heleen; Scholte, Frans; Visser, Frank; Hoekstra, Pieter J

2013-09-01

Individuals with intellectual disability frequently use antipsychotics for many years. This may have detrimental health effects, including neurological symptoms and metabolic and hormonal dysregulation, the latter possibly affecting bone metabolism. There is large variability in the degree in which antipsychotic agents lead to these health problems. In the current study we investigated potential determinants of physical symptoms and biological parameters known to be associated with use of antipsychotics in a convenience sample of 99 individuals with intellectual disability who had used antipsychotics for more than one year for behavioural symptoms. We focused on extrapyramidal symptoms; on overweight and presence of components of the metabolic syndrome; and on elevated plasma prolactin and bone turnover parameters. As predictor variables, we used patient (sex, age, genetic polymorphisms, and severity of intellectual disability) and medication use (type and dosage) characteristics. We found extrapyramidal symptoms to be present in 53%, overweight or obesity in 46%, and the metabolic syndrome in 11% of participants. Hyperprolactineaemia and one or more elevated bone turnover markers were present in 17% and 25%, respectively. Higher age and more severe intellectual disability were associated with dyskinesia and a higher dosage of the antipsychotic drug was associated with parkinsonism. Less severe intellectual disability was related to higher Body Mass Index. Use of atypical antipsychotics was associated with higher diastolic blood pressure and elevated fasting glucose. Clinicians who prescribe antipsychotics in individuals with intellectual disability should carefully balance the potential benefits of prolonged treatment against the risk of health hazards associated with the use of antipsychotics. Copyright © 2013 Elsevier Ltd. All rights reserved.

Taxonomy of rare genetic metabolic bone disorders.

PubMed

Masi, L; Agnusdei, D; Bilezikian, J; Chappard, D; Chapurlat, R; Cianferotti, L; Devolgelaer, J-P; El Maghraoui, A; Ferrari, S; Javaid, M K; Kaufman, J-M; Liberman, U A; Lyritis, G; Miller, P; Napoli, N; Roldan, E; Papapoulos, S; Watts, N B; Brandi, M L

2015-10-01

This article reports a taxonomic classification of rare skeletal diseases based on metabolic phenotypes. It was prepared by The Skeletal Rare Diseases Working Group of the International Osteoporosis Foundation (IOF) and includes 116 OMIM phenotypes with 86 affected genes. Rare skeletal metabolic diseases comprise a group of diseases commonly associated with severe clinical consequences. In recent years, the description of the clinical phenotypes and radiographic features of several genetic bone disorders was paralleled by the discovery of key molecular pathways involved in the regulation of bone and mineral metabolism. Including this information in the description and classification of rare skeletal diseases may improve the recognition and management of affected patients. IOF recognized this need and formed a Skeletal Rare Diseases Working Group (SRD-WG) of basic and clinical scientists who developed a taxonomy of rare skeletal diseases based on their metabolic pathogenesis. This taxonomy of rare genetic metabolic bone disorders (RGMBDs) comprises 116 OMIM phenotypes, with 86 affected genes related to bone and mineral homeostasis. The diseases were divided into four major groups, namely, disorders due to altered osteoclast, osteoblast, or osteocyte activity; disorders due to altered bone matrix proteins; disorders due to altered bone microenvironmental regulators; and disorders due to deranged calciotropic hormonal activity. This article provides the first comprehensive taxonomy of rare metabolic skeletal diseases based on deranged metabolic activity. This classification will help in the development of common and shared diagnostic and therapeutic pathways for these patients and also in the creation of international registries of rare skeletal diseases, the first step for the development of genetic tests based on next generation sequencing and for performing large intervention trials to assess efficacy of orphan drugs.

[Metabolic and hemodynamic effects of the growth hormone system - insulin-like growth factor].

PubMed

Manhylova, T A; Gafarova, N H

2015-01-01

Significant congenital deficiency of growth factor (GF) results in pituitary nanism (dwarfism) and its substantial excess is accompanied by the development of gigantism or acromegaly. Its impact on the growth of the whole body or its individual parts is impossible without affecting metabolic processes and hemodynamic parameters. A number of investigations have proven that GF has a direct lipolytic effect: adequate replacement therapy for pituitary nanism gives rise to a reduction in fat depots. Since the concentration of GF is lower in obesity, Whether it may be used to treat this abnormality is considered.

Mild Cognitive Dysfunction Does Not Affect Diabetes Mellitus Control in Minority Elderly Adults

PubMed Central

Palta, Priya; Golden, Sherita H.; Teresi, Jeanne; Palmas, Walter; Weinstock, Ruth S.; Shea, Steven; Manly, Jennifer J.; Luchsinger, Jose A.

2015-01-01

OBJECTIVES To determine whether older adults with type 2 diabetes mellitus and cognitive dysfunction have poorer metabolic control of glycosylated hemoglobin, systolic blood pressure, and low-density lipoprotein cholesterol than those without cognitive dysfunction. DESIGN Prospective cohort study. SETTING A minority cohort in New York City previously recruited for a trial of telemedicine. PARTICIPANTS Persons aged 73.0 ± 3.0 (N = 613; 69.5% female; 82.5% Hispanic, 15.5% non-Hispanic black). MEASUREMENTS Participants were classified with executive or memory dysfunction based on standardized score cutoffs (<16th percentile) for the Color Trails Test and Selective Reminding Test. Linear mixed models were used to compare repeated measures of the metabolic measures and evaluate the rates of change in individuals with and without dysfunction. RESULTS Of the 613 participants, 331 (54%) had executive dysfunction, 202 (33%) had memory dysfunction, and 96 (16%) had both. Over a median of 2 years, participants with executive or memory dysfunction did not exhibit significantly poorer metabolic control than those without executive function or memory type cognitive dysfunction. CONCLUSION Cognitive dysfunction in the mild range did not seem to affect diabetes mellitus control parameters in this multiethnic cohort of older adults with diabetes mellitus, although it cannot be excluded that cognitive impairment was overcome through assistance from formal or informal caregivers. It is possible that more-severe cognitive dysfunction could affect control. PMID:25439094

Role of hormones in cartilage and joint metabolism: understanding an unhealthy metabolic phenotype in osteoarthritis.

PubMed

Bay-Jensen, Anne C; Slagboom, Eline; Chen-An, Pingping; Alexandersen, Peter; Qvist, Per; Christiansen, Claus; Meulenbelt, Ingrid; Karsdal, Morten A

2013-05-01

Joint health is affected by local and systemic hormones. It is well accepted that systemic factors regulate the metabolism of joint tissues, and that substantial cross-talk between tissues actively contributes to homeostasis. In the current review, we try to define a subtype of osteoarthritis (OA), metabolic OA, which is dependent on an unhealthy phenotype. Peer-reviewed research articles and reviews were reviewed and summarized. Only literature readily available online, either by download or by purchase order, was included. OA is the most common joint disease and is more common in women after menopause. OA is a disease that affects the whole joint, including cartilage, subchondral bone, synovium, tendons, and muscles. The clinical endpoints of OA are pain and joint space narrowing, which is characterized by cartilage erosion and subchondral sclerosis, suggesting that cartilage is a central tissue of joint health. Thus, the joint, more specifically the cartilage, may be considered a target of endocrine function in addition to the well-described traditional risk factors of disease initiation and progression such as long-term loading of the joint due to obesity. Metabolic syndrome affects a range of tissues and may in part be molecularly described as a dysregulation of cytokines, adipokines, and hormones (e.g., estrogen and thyroid hormone). Consequently, metabolic imbalance may both directly and indirectly influence joint health and cartilage turnover, altering the progression of diseases such as OA. There is substantial evidence for a connection between metabolic health and development of OA. We propose that more focus be directed to understanding this connection to improve the management of menopausal health and associated comorbidities.

Effect of oral cinnamon intervention on metabolic profile and body composition of Asian Indians with metabolic syndrome: a randomized double -blind control trial.

PubMed

Gupta Jain, Sonal; Puri, Seema; Misra, Anoop; Gulati, Seema; Mani, Kalaivani

2017-06-12

Nutritional modulation remains central to the management of metabolic syndrome. Intervention with cinnamon in individuals with metabolic syndrome remains sparsely researched. We investigated the effect of oral cinnamon consumption on body composition and metabolic parameters of Asian Indians with metabolic syndrome. In this 16-week double blind randomized control trial, 116 individuals with metabolic syndrome were randomized to two dietary intervention groups, cinnamon [6 capsules (3 g) daily] or wheat flour [6 capsules (2.5 g) daily]. Body composition, blood pressure and metabolic parameters were assessed. Significantly greater decrease [difference between means, (95% CI)] in fasting blood glucose (mmol/L) [0.3 (0.2, 0.5) p = 0.001], glycosylated haemoglobin (mmol/mol) [2.6 (0.4, 4.9) p = 0.023], waist circumference (cm) [4.8 (1.9, 7.7) p = 0.002] and body mass index (kg/m2 ) [1.3 (0.9, 1.5) p = 0.001] was observed in the cinnamon group compared to placebo group. Other parameters which showed significantly greater improvement were: waist-hip ratio, blood pressure, serum total cholesterol, low-density lipoprotein cholesterol, serum triglycerides, and high-density lipoprotein cholesterol. Prevalence of defined metabolic syndrome was significantly reduced in the intervention group (34.5%) vs. the placebo group (5.2%). A single supplement intervention with 3 g cinnamon for 16 weeks resulted in significant improvements in all components of metabolic syndrome in a sample of Asian Indians in north India. The clinical trial was retrospectively registered (after the recruitment of the participants) in ClinicalTrial.gov under the identification number: NCT02455778 on 25th May 2015.

Ontogenetic scaling of metabolism, growth, and assimilation: testing metabolic scaling theory with Manduca sexta larvae.

PubMed

Sears, Katie E; Kerkhoff, Andrew J; Messerman, Arianne; Itagaki, Haruhiko

2012-01-01

Metabolism, growth, and the assimilation of energy and materials are essential processes that are intricately related and depend heavily on animal size. However, models that relate the ontogenetic scaling of energy assimilation and metabolism to growth rely on assumptions that have yet to be rigorously tested. Based on detailed daily measurements of metabolism, growth, and assimilation in tobacco hornworms, Manduca sexta, we provide a first experimental test of the core assumptions of a metabolic scaling model of ontogenetic growth. Metabolic scaling parameters changed over development, in violation of the model assumptions. At the same time, the scaling of growth rate matches that of metabolic rate, with similar scaling exponents both across and within developmental instars. Rates of assimilation were much higher than expected during the first two instars and did not match the patterns of scaling of growth and metabolism, which suggests high costs of biosynthesis early in development. The rapid increase in size and discrete instars observed in larval insect development provide an ideal system for understanding how patterns of growth and metabolism emerge from fundamental cellular processes and the exchange of materials and energy between an organism and its environment.

718F-FDG PET/CT metabolic tumor parameters and radiomics features in aggressive non-Hodgkin's lymphoma as predictors of treatment outcome and survival.

PubMed

Parvez, Aatif; Tau, Noam; Hussey, Douglas; Maganti, Manjula; Metser, Ur

2018-05-12

To determine whether metabolic tumor parameters and radiomic features extracted from 18 F-FDG PET/CT (PET) can predict response to therapy and outcome in patients with aggressive B-cell lymphoma. This institutional ethics board-approved retrospective study included 82 patients undergoing PET for aggressive B-cell lymphoma staging. Whole-body metabolic tumor volume (MTV) using various thresholds and tumor radiomic features were assessed on representative tumor sites. The extracted features were correlated with treatment response, disease-free survival (DFS) and overall survival (OS). At the end of therapy, 66 patients (80.5%) had shown complete response to therapy. The parameters correlating with response to therapy were bulky disease > 6 cm at baseline (p = 0.026), absence of a residual mass > 1.5 cm at the end of therapy CT (p = 0.028) and whole-body MTV with best performance using an SUV threshold of 3 and 6 (p = 0.015 and 0.009, respectively). None of the tumor texture features were predictive of first-line therapy response, while a few of them including GLNU correlated with disease-free survival (p = 0.013) and kurtosis correlated with overall survival (p = 0.035). Whole-body MTV correlates with response to therapy in patient with aggressive B-cell lymphoma. Tumor texture features could not predict therapy response, although several features correlated with the presence of a residual mass at the end of therapy CT and others correlated with disease-free and overall survival. These parameters should be prospectively validated in a larger cohort to confirm clinical prognostication.

Theobromine does not affect postprandial lipid metabolism and duodenal gene expression, but has unfavorable effects on postprandial glucose and insulin responses in humans.

PubMed

Smolders, Lotte; Mensink, Ronald P; Boekschoten, Mark V; de Ridder, Rogier J J; Plat, Jogchum

2018-04-01

Chocolate consumption is associated with a decreased risk for CVD. Theobromine, a compound in cocoa, may explain these effects as it favorably affected fasting serum lipids. However, long-term effects of theobromine on postprandial metabolism as well as underlying mechanisms have never been studied. The objective was to evaluate the effects of 4-week theobromine consumption (500 mg/day) on fasting and postprandial lipid, lipoprotein and glucose metabolism, and duodenal gene expression. In a randomized, double-blind crossover study, 44 healthy men and women, with low baseline HDL-C concentrations consumed 500 mg theobromine or placebo daily. After 4-weeks, fasting blood was sampled and subjects participated in a 4-h postprandial test. Blood was sampled frequently for analysis of lipid and glucose metabolism. In a subgroup of 10 men, 5 h after meal consumption duodenal biopsies were taken for microarray analysis. 4-weeks theobromine consumption lowered fasting LDL-C (-0.21 mmol/L; P = 0.006), and apoB100 (-0.04 g/L; P = 0.022), tended to increase HDL-C (0.03 mmol/L; P = 0.088) and increased hsCRP (1.2 mg/L; P = 0.017) concentrations. Fasting apoA-I, TAG, FFA, glucose and insulin concentrations were unchanged. In the postprandial phase, theobromine consumption increased glucose (P = 0.026), insulin (P = 0.011) and FFA (P = 0.003) concentrations, while lipids and (apo)lipoproteins were unchanged. In duodenal biopsies, microarray analysis showed no consistent changes in expression of genes, pathways or gene sets related to lipid, cholesterol or glucose metabolism. It is not likely that the potential beneficial effects of cocoa on CVD can be ascribed to theobromine. Although theobromine lowers serum LDL-C concentrations, it did not change fasting HDL-C, apoA-I, or postprandial lipid concentrations and duodenal gene expression, and unfavorably affected postprandial glucose and insulin responses. This trial was registered on clinicaltrials.gov under

Restoration of type 1 iodothyronine deiodinase expression in renal cancer cells downregulates oncoproteins and affects key metabolic pathways as well as anti-oxidative system.

PubMed

Popławski, Piotr; Wiśniewski, Jacek R; Rijntjes, Eddy; Richards, Keith; Rybicka, Beata; Köhrle, Josef; Piekiełko-Witkowska, Agnieszka

2017-01-01

Type 1 iodothyronine deiodinase (DIO1) contributes to deiodination of 3,5,3',5'-tetraiodo-L-thyronine (thyroxine, T4) yielding of 3,5,3'-triiodothyronine (T3), a powerful regulator of cell differentiation, proliferation, and metabolism. Our previous work showed that loss of DIO1 enhances proliferation and migration of renal cancer cells. However, the global effects of DIO1 expression in various tissues affected by cancer remain unknown. Here, the effects of stable DIO1 re-expression were analyzed on the proteome of renal cancer cells, followed by quantitative real-time PCR validation in two renal cancer-derived cell lines. DIO1-induced changes in intracellular concentrations of thyroid hormones were quantified by L-MS/MS and correlations between expression of DIO1 and potential target genes were determined in tissue samples from renal cancer patients. Stable re-expression of DIO1, resulted in 26 downregulated proteins while 59 proteins were overexpressed in renal cancer cells. The 'downregulated' group consisted mainly of oncoproteins (e.g. STAT3, ANPEP, TGFBI, TGM2) that promote proliferation, migration and invasion. Furthermore, DIO1 re-expression enhanced concentrations of two subunits of thyroid hormone transporter (SLC7A5, SLC3A2), enzymes of key pathways of cellular energy metabolism (e.g. TKT, NAMPT, IDH2), sex steroid metabolism and anti-oxidative response (AKR1C2, AKR1B10). DIO1 expression resulted in elevated intracellular concentration of T4. Expression of DIO1-affected genes strongly correlated with DIO1 transcript levels in tissue samples from renal cancer patients as well as with their poor survival. This first study addressing effects of deiodinase re-expression on proteome of cancer cells demonstrates that induced DIO1 re-expression in renal cancer robustly downregulates oncoproteins, affects key metabolic pathways, and triggers proteins involved in anti-oxidative protection. This data supports the notion that suppressed DIO1 expression and changes

Restoration of type 1 iodothyronine deiodinase expression in renal cancer cells downregulates oncoproteins and affects key metabolic pathways as well as anti-oxidative system

PubMed Central

Rijntjes, Eddy; Richards, Keith; Rybicka, Beata; Köhrle, Josef

2017-01-01

Type 1 iodothyronine deiodinase (DIO1) contributes to deiodination of 3,5,3’,5’-tetraiodo-L-thyronine (thyroxine, T4) yielding of 3,5,3’-triiodothyronine (T3), a powerful regulator of cell differentiation, proliferation, and metabolism. Our previous work showed that loss of DIO1 enhances proliferation and migration of renal cancer cells. However, the global effects of DIO1 expression in various tissues affected by cancer remain unknown. Here, the effects of stable DIO1 re-expression were analyzed on the proteome of renal cancer cells, followed by quantitative real-time PCR validation in two renal cancer-derived cell lines. DIO1-induced changes in intracellular concentrations of thyroid hormones were quantified by L-MS/MS and correlations between expression of DIO1 and potential target genes were determined in tissue samples from renal cancer patients. Stable re-expression of DIO1, resulted in 26 downregulated proteins while 59 proteins were overexpressed in renal cancer cells. The ‘downregulated’ group consisted mainly of oncoproteins (e.g. STAT3, ANPEP, TGFBI, TGM2) that promote proliferation, migration and invasion. Furthermore, DIO1 re-expression enhanced concentrations of two subunits of thyroid hormone transporter (SLC7A5, SLC3A2), enzymes of key pathways of cellular energy metabolism (e.g. TKT, NAMPT, IDH2), sex steroid metabolism and anti-oxidative response (AKR1C2, AKR1B10). DIO1 expression resulted in elevated intracellular concentration of T4. Expression of DIO1-affected genes strongly correlated with DIO1 transcript levels in tissue samples from renal cancer patients as well as with their poor survival. This first study addressing effects of deiodinase re-expression on proteome of cancer cells demonstrates that induced DIO1 re-expression in renal cancer robustly downregulates oncoproteins, affects key metabolic pathways, and triggers proteins involved in anti-oxidative protection. This data supports the notion that suppressed DIO1 expression

Roostocks/Scion/Nitrogen Interactions Affect Secondary Metabolism in the Grape Berry

PubMed Central

Habran, Aude; Commisso, Mauro; Helwi, Pierre; Hilbert, Ghislaine; Negri, Stefano; Ollat, Nathalie; Gomès, Eric; van Leeuwen, Cornelis; Guzzo, Flavia; Delrot, Serge

2016-01-01

The present work investigates the interactions between soil content, rootstock, and scion by focusing on the effects of roostocks and nitrogen supply on grape berry content. Scions of Cabernet Sauvignon (CS) and Pinot Noir (PN) varieties were grafted either on Riparia Gloire de Montpellier (RGM) or 110 Richter (110R) rootstock. The 4 rooststock/scion combinations were fertilized with 3 different levels of nitrogen after fruit set. Both in 2013 and 2014, N supply increased N uptake by the plants, and N content both in vegetative and reproductory organs. Rootstock, variety and year affected berry weight at harvest, while nitrogen did not affect significantly this parameter. Grafting on RGM consistently increased berry weight compared to 110R. PN consistently produced bigger berries than CS. CS berries were heavier in 2014 than in 2013, but the year effect was less marked for PN berries. The berries were collected between veraison and maturity, separated in skin and pulp, and their content was analyzed by conventional analytical procedures and untargeted metabolomics. For anthocyanins, the relative quantitation was fairly comparable with both LC-MS determination and HPLC-DAD, which is a fully quantitative technique. The data show complex responses of the metabolite content (sugars, organic acids, amino acids, anthocyanins, flavonols, flavan-3-ols/procyanidins, stilbenes, hydroxycinnamic, and hydroxybenzoic acids) that depend on the rootstock, the scion, the vintage, the nitrogen level, the berry compartment. This opens a wide range of possibilities to adjust the content of these compounds through the choice of the roostock, variety and nitrogen fertilization. PMID:27555847

Roostocks/Scion/Nitrogen Interactions Affect Secondary Metabolism in the Grape Berry.

PubMed

Habran, Aude; Commisso, Mauro; Helwi, Pierre; Hilbert, Ghislaine; Negri, Stefano; Ollat, Nathalie; Gomès, Eric; van Leeuwen, Cornelis; Guzzo, Flavia; Delrot, Serge

2016-01-01

The present work investigates the interactions between soil content, rootstock, and scion by focusing on the effects of roostocks and nitrogen supply on grape berry content. Scions of Cabernet Sauvignon (CS) and Pinot Noir (PN) varieties were grafted either on Riparia Gloire de Montpellier (RGM) or 110 Richter (110R) rootstock. The 4 rooststock/scion combinations were fertilized with 3 different levels of nitrogen after fruit set. Both in 2013 and 2014, N supply increased N uptake by the plants, and N content both in vegetative and reproductory organs. Rootstock, variety and year affected berry weight at harvest, while nitrogen did not affect significantly this parameter. Grafting on RGM consistently increased berry weight compared to 110R. PN consistently produced bigger berries than CS. CS berries were heavier in 2014 than in 2013, but the year effect was less marked for PN berries. The berries were collected between veraison and maturity, separated in skin and pulp, and their content was analyzed by conventional analytical procedures and untargeted metabolomics. For anthocyanins, the relative quantitation was fairly comparable with both LC-MS determination and HPLC-DAD, which is a fully quantitative technique. The data show complex responses of the metabolite content (sugars, organic acids, amino acids, anthocyanins, flavonols, flavan-3-ols/procyanidins, stilbenes, hydroxycinnamic, and hydroxybenzoic acids) that depend on the rootstock, the scion, the vintage, the nitrogen level, the berry compartment. This opens a wide range of possibilities to adjust the content of these compounds through the choice of the roostock, variety and nitrogen fertilization.

Improvement of anthropometric and metabolic parameters, and quality of life following treatment with dual-release hydrocortisone in patients with Addison's disease.

PubMed

Giordano, Roberta; Guaraldi, Federica; Marinazzo, Elisa; Fumarola, Federica; Rampino, Alessia; Berardelli, Rita; Karamouzis, Ioannis; Lucchiari, Manuela; Manetta, Tilde; Mengozzi, Giulio; Arvat, Emanuela; Ghigo, Ezio

2016-02-01

In patients with Addison's disease (AD), a dual-release preparation of hydrocortisone (Plenadren, PLEN) has been demonstrated to maintain cortisol levels in a more physiological range than conventional glucocorticoid therapy, and to exert positive effects. This study aimed to assess variations of anthropometric, metabolic, and hormonal parameters in patients with AD after switching from conventional hydrocortisone (HC) treatment to PLEN. In nineteen AD patients (15 F and 4 M, age 27-65 years) treated with HC 20 mg/day thrice daily, body weight, BMI, waist circumference, fasting glucose, HbA1c, serum lipids, plasma renin activity, electrolytes, and blood pressure were evaluated at baseline, and 1, 3, 6, and 12 months after switching from HC to PLEN. At baseline, and after 1 and 12 months of PLEN, blood ACTH and cortisol (at 0800 h at fasting, and 30, 60, 90, 120, and 240 min after drug ingestion), and health-related quality of life (HRQoL), using 30-AddiQoL questionnaire, were evaluated. During PLEN, waist and serum lipid progressively decreased. After 12 months of PLEN, a significant difference was observed in waist circumference (P = 0.007), HbA1c (P = 0.002), total and LDL-cholesterol levels (P < 0.05). ACTH levels at 240 min and the area under the curve (AUC) were lower (P < 0.05) during PLEN than HC, while cortisol peaks and AUC were similar. 30-AddiQoL total score also improved (P = 0.04) during PLEN. In AD patients, PLEN reduces central adiposity, and improves glucose and metabolism parameters and HRQoL.

Unique effects on hepatic function, lipid metabolism, bone and growth endocrine parameters of estetrol in combined oral contraceptives

PubMed Central

Mawet, Marie; Maillard, Catherine; Klipping, Christine; Zimmerman, Yvette; Foidart, Jean-Michel; Coelingh Bennink, Herjan J.T.

2015-01-01

Abstract Objectives Estetrol (E4) is a natural estrogen produced by the human fetal liver. In combination with drospirenone (DRSP) or levonorgestrel (LNG), E4 blocks ovulation and has less effect on haemostatic biomarkers in comparison with ethinylestradiol (EE) combined with DRSP. This study evaluates the impact of several doses of E4/DRSP and E4/LNG on safety parameters such as liver function, lipid metabolism, bone markers and growth endocrine parameters. Methods This was a dose-finding, single-centre, controlled study performed in healthy women aged 18 to 35 years with a documented pretreatment ovulatory cycle. Participants received 5 mg or 10 mg E4/3 mg DRSP; 5 mg, 10 mg or 20 mg E4/150 μg LNG; or 20 μg EE/3 mg DRSP as a comparator for three consecutive cycles in a 24/4-day regimen. Changes from baseline to end of treatment in liver parameters, lipid metabolism, bone markers and growth endocrinology were evaluated. Results A total of 109 women were included in the study. Carrier proteins were minimally affected in the E4/DRSP and E4/LNG groups, in comparison with the EE/DRSP group, where a significant increase in sex hormone-binding globulin was observed. Similarly, minor effects on lipoproteins were observed in the E4 groups, and the effects on triglycerides elicited by the E4 groups were significantly lower than those in the EE/DRSP group. No imbalances in bone markers were observed in any groups. No alterations in insulin-like growth factor were observed in the E4 groups. Conclusions E4-containing combinations have a limited effect on liver function, lipid metabolism, and bone and growth endocrine parameters. Chinese Abstract 摘要 目的 雌四醇（E4）是来源于人胎儿肝脏的天然雌激素。雌四醇与屈螺酮（DRSP)或左炔诺孕酮(LNG)配伍的复方口服避孕药制剂，能够抑制排卵，同时相较于炔雌醇(EE)与屈螺酮配伍制剂，它对凝血功能的各�

Bone mineral metabolism parameters and urinary albumin excretion in a representative US population sample.

PubMed

Ellam, Timothy; Fotheringham, James; Wilkie, Martin E; Francis, Sheila E; Chico, Timothy J A

2014-01-01

Even within accepted normal ranges, higher serum phosphorus, dietary phosphorus density, parathyroid hormone (PTH) and alkaline phosphatase (ALP) are independent predictors of cardiovascular mortality. Lower serum 25-hydroxy vitamin D (25(OH)D) also predicts adverse cardiovascular outcomes. We hypothesized that vascular dysfunction accompanying subtle disturbances of these bone metabolism parameters would result in associations with increased low grade albuminuria. We examined participants in the National Health and Nutrition Examination Surveys 1999-2010 (N = 19,383) with estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m² and without severe albuminuria (urine albumin:creatinine ratio (ACR) <300 mg/g). Albuminuria was quantified as ACR and fractional albumin excretion (FE(alb)). Increasing quintiles of dietary phosphorus density, serum phosphorus and ALP were not associated with higher ACR or FE(alb). The lowest versus highest quintile of 25(OH)D was associated with greater albuminuria, but not after adjustment for other covariates including cardiovascular risk factors. An association between the highest versus lowest quintile of bone-specific ALP and greater ACR persisted after covariate adjustment, but was not accompanied by an independent association with FE(alb). Increasing quintiles of PTH demonstrated associations with both higher ACR and FE(alb) that were not abolished by adjusting for covariates including age, gender, race, body mass index, diabetes, blood pressure, history of cardiovascular disease, smoking, eGFR, 25(OH)D, season of measurement, lipids, hemoglobin and C-reactive protein. Adjusted increases in ACR and FE(alb) associated with the highest versus lowest quintile of PTH were 19% (95% confidence interval 7-28% p<0.001) and 17% (8-31% p = 0.001) respectively. In this population, of the bone mineral parameters associated with cardiovascular outcomes, only PTH is independently associated with ACR and FE(alb).

Effect of long-distance transportation on serum metabolic profiles of steer calves.

PubMed

Takemoto, Satoshi; Tomonaga, Shozo; Funaba, Masayuki; Matsui, Tohru

2017-12-01

Long-distance transportation is sometimes inevitable in the beef industry because of the geographic separation of major breeding and fattening areas. Long-distance transportation negatively impacts production and health of cattle, which may, at least partly, result from the disturbance of metabolism during and after transportation. However, alteration of metabolism remains elusive in transported cattle. We investigated the effects of transportation on the metabolomic profiles of Holstein steer calves. Non-targeted analysis of serum concentrations of low molecular weight metabolites was performed by gas chromatography mass spectrometry. Transportation affected 38 metabolites in the serum. A pathway analysis suggested that 26, 10, and 10 pathways were affected immediately after transportation, and 3 and 7 days after transportation, respectively. Some pathways were disturbed only immediately after transportation, likely because of feed and water withdrawal during transit. Nicotinate and nicotinamide metabolism, and citric acid cycle were affected for 3 days after transportation, whereas propionate metabolism, phenylalanine and tyrosine metabolism were affected throughout the experiment. Four pathways were not affected immediately after transportation, but were altered thereafter. These results suggested that many metabolic pathways had marked perturbations during transportation. Metabolites such as citric acid, propionate, tyrosine and niacin can be candidate supplements for mitigating transportation-induced adverse effects. © 2017 Japanese Society of Animal Science.

The Parameters Affecting the Success of Irrigation and Debridement with Component Retention in the Treatment of Acutely Infected Total Knee Arthroplasty

PubMed Central

Kim, Jae Gyoon; Bae, Ji Hoon; Lee, Seung Yup; Cho, Won Tae

2015-01-01

Background The aims of our study were to evaluate the success rate of irrigation and debridement with component retention (IDCR) for acutely infected total knee arthroplasty (TKA) (< 4 weeks of symptom duration) and to analyze the factors affecting prognosis of IDCR. Methods We retrospectively reviewed 28 knees treated by IDCR for acutely infected TKA from 2003 to 2012. We evaluated the success rate of IDCR. All variables were compared between the success and failure groups. Multivariable logistic regression analysis was also used to examine the relative contribution of these parameters to the success of IDCR. Results Seventeen knees (60.7%) were successfully treated. Between the success and failure groups, there were significant differences in the time from primary TKA to IDCR (p = 0.021), the preoperative erythrocyte sedimentation rate (ESR; p = 0.021), microorganism (p = 0.006), and polyethylene liner exchange (p = 0.017). Multivariable logistic regression analysis of parameters affecting the success of IDCR demonstrated that preoperative ESR (odds ratio [OR], 1.02; p = 0.041), microorganism (OR, 12.4; p = 0.006), and polyethylene liner exchange (OR, 0.07; p = 0.021) were significant parameters. Conclusions The results show that 60.7% of the cases were successfully treated by IDCR for acutely infected TKA. The preoperative ESR, microorganism, and polyethylene liner exchange were factors that affected the success of IDCR in acutely infected TKA. PMID:25729521

The Effect of Vegan Protein-Based Diets on Metabolic Parameters, Expressions of Adiponectin and Its Receptors in Wistar Rats

PubMed Central

Chen, Jie-Hua; Song, Jia; Chen, Yan; Ding, Qiang; Peng, Anfang; Mao, Limei

2016-01-01

Vegan protein-based diet has attracted increasing interest in the prevention of metabolic syndrome (MetS). Meanwhile, adiponectin has become a highly potential molecular target in the prevention of MetS. Our study will identify a potential vegan protein diet for the prevention of MetS using rat models. Thirty-six Wistar rats were randomly assigned into three groups and given diets containing one of the following proteins for 12 weeks: casein (CAS, control diet), soy protein (SOY), and gluten-soy mixed protein (GSM). Changes in metabolic parameters as well as the expressions of adiponectin and its receptors were identified. Compared to CAS diet, both SOY and GSM diets led to decreases in blood total cholesterol and triglycerides, but only GSM diet led to an increase in HDL-cholesterol; no marked difference was observed in blood glucose in all three groups; HOMA-IR was found lower only in SOY group. Among groups, the order of serum adiponectin level was found as GSM > SOY > CAS. Similar order pattern was also observed in expression of adiponectin in adipose tissue and AdipoR1 mRNA in skeletal muscle. Our results suggested for the first time that, besides SOY diet, GSM diet could also be a possible substitute of animal protein to prevent MetS. PMID:27763537

Effect of pre-slaughter shackling and wing flapping on plasma parameters, postmortem metabolism, AMPK, and meat quality of broilers.

PubMed

Huang, J C; Yang, J; Huang, M; Zhu, Z S; Sun, X B; Zhang, B H; Xu, X L; Meng, W G; Chen, K J; Xu, B C

2018-05-01

The objective of this study was to determine the effects of shackling and wing flapping on stress, postmortem metabolism, AMP-activated protein kinase (AMPK), and quality of broiler pectoralis major. Before slaughter, a total of 80 Arbor Acres broilers was randomly categorized into 2 replicate pens (40 broilers per pen) and each pen randomly divided into 2 groups (shackling, T; control, C). Corticosterone, creatine kinase, and lactate dehydrogenase were determined on blood plasma parameters. Pectoralis major were removed after evisceration and used for determination of energy metabolism, meat quality, and AMPK phosphorylation. In this study, shackling and wing flapping increased (P < 0.05) plasma corticosterone level, creatine kinase activity, and lactate dehydrogenase activity. Shackling and wing flapping increased (P < 0.05) AMPKα(Thr172) and acetyl-CoA carboxylase (ACC) phosphorylation, followed by rapid glycolysis and accumulation of lactic acid, and leading to a fast pH decline in the initial postmortem meat. Shackling and wing flapping have an adverse effect on final meat quality, which increased (P < 0.05) muscle lightness, drip loss, and cooking loss. The results indicate that antemortem shackling and wing flapping increased stress and AMPKα(Thr172) phosphorylation, which may accelerate glycolysis and lead to a low water-holding capacity of broiler meat.

The Effect of Vegan Protein-Based Diets on Metabolic Parameters, Expressions of Adiponectin and Its Receptors in Wistar Rats.

PubMed

Chen, Jie-Hua; Song, Jia; Chen, Yan; Ding, Qiang; Peng, Anfang; Mao, Limei

2016-10-18

Vegan protein-based diet has attracted increasing interest in the prevention of metabolic syndrome (MetS). Meanwhile, adiponectin has become a highly potential molecular target in the prevention of MetS. Our study will identify a potential vegan protein diet for the prevention of MetS using rat models. Thirty-six Wistar rats were randomly assigned into three groups and given diets containing one of the following proteins for 12 weeks: casein (CAS, control diet), soy protein (SOY), and gluten-soy mixed protein (GSM). Changes in metabolic parameters as well as the expressions of adiponectin and its receptors were identified. Compared to CAS diet, both SOY and GSM diets led to decreases in blood total cholesterol and triglycerides, but only GSM diet led to an increase in HDL-cholesterol; no marked difference was observed in blood glucose in all three groups; HOMA-IR was found lower only in SOY group. Among groups, the order of serum adiponectin level was found as GSM > SOY > CAS. Similar order pattern was also observed in expression of adiponectin in adipose tissue and AdipoR1 mRNA in skeletal muscle. Our results suggested for the first time that, besides SOY diet, GSM diet could also be a possible substitute of animal protein to prevent MetS.

Changes in Intestinal Microbiota Affect Metabolism of Ginsenoside Re.

PubMed

Zhang, Lei; Li, Fei; Qin, Wang-Jun; Fu, Chao; Zhang, Xiang-Lin

2018-05-10

Ginsenoside Re, an active ingredient in Panax ginseng, is widely used as a therapeutic and nutriment. Intestinal microbiota plays crucial roles in modulating the pharmacokinetics and pharmacological actions of ginsenoside Re. The aim of this study was to explore the relationship between bacterial community variety and the metabolic profiles of ginsenoside Re. We developed two models with intestinal dysbacteriosis: a pseudo-germ-free model induced by a non-absorbable antimicrobial mixture (ATM), and Qi-deficiency model established via over-fatigue and acute cold stress (OACS). First, the bacterial community structures in control, ATM, and OACS rats were compared via 16S rRNA amplicon sequencing. Then, gut microbial metabolism of ginsenoside Re was assessed qualitatively and quantitatively in the three groups by UPLC-Q-TOF/MS and HPLC-TQ-MS, respectively. Ten metabolites of ginsenoside Re were detected and tentatively identified, three of which were novel. Moreover, due to significant differences in bacterial communities, deglycosylated products, as the main metabolites of ginsenoside Re, were produced at lower levels in ATM and OACS models. Importantly, the levels of these deglycosylated metabolites correlated with alterations in Prevotella, Lactobacillus, and Bacteroides populations, as well as glycosidase activities. Collectively, biotransformation of ginsenoside Re is potentially influenced by regulating the composition of intestinal microbiota and glycosidase activities. This article is protected by copyright. All rights reserved.

Glycogen metabolism in the glucose-sensing and supply-driven β-cell.

PubMed

Andersson, Lotta E; Nicholas, Lisa M; Filipsson, Karin; Sun, Jiangming; Medina, Anya; Al-Majdoub, Mahmoud; Fex, Malin; Mulder, Hindrik; Spégel, Peter

2016-12-01

Glycogen metabolism in β-cells may affect downstream metabolic pathways controlling insulin release. We examined glycogen metabolism in human islets and in the rodent-derived INS-1 832/13 β-cells and found them to express the same isoforms of key enzymes required for glycogen metabolism. Our findings indicate that glycogenesis is insulin-independent but influenced by extracellular glucose concentrations. Levels of glycogen synthase decrease with increasing glucose concentrations, paralleling accumulation of glycogen. We did not find cAMP-elicited glycogenolysis and insulin secretion to be causally related. In conclusion, our results reveal regulated glycogen metabolism in human islets and insulin-secreting cells. Whether glycogen metabolism affects insulin secretion under physiological conditions remains to be determined. © 2016 Federation of European Biochemical Societies.

Anthropometric parameters and their associations with cardio-metabolic risk in Chinese working population.

PubMed

Ouyang, Xiaojun; Lou, Qinlin; Gu, Liubao; Ko, Gary T; Mo, Yongzhen; Wu, Haidi; Bian, Rongwen

2015-01-01

There remains controversy regarding which of the anthropometric indicators best defines obesity. In this study, we compared the efficacy of using body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) in the diagnosis of obesity and assessed their associations with diabetes, hypertension, and dyslipidemia in an urban working population in China. Anthropometric measurements, blood pressure, plasma lipids, fasting and 2-hour plasma glucose (PG) levels by a 75 gram oral glucose tolerance test (OGTT) were obtained from 2603 working Chinese who had no history of cardiovascular diseases or diabetes. Cardio-metabolic risk factors including high blood pressure, dyslipidemia, and glucose intolerance were evaluated. The diagnoses of overweight and obesity were based on the WHO definitions with BMI for general obesity and WC and WHR for central obesity. Based on BMI, WC and WHR, there were 31.3%, 16.6%, 35.2% of the studied subjects, respectively, being overweight and 2.0%, 5.6%, 9.2% being obese. Among women but not men, more overweight and obese subjects were diagnosed using WHR and WC. The number of cardio-metabolic risks was higher by WC criterion than BMI and WHR in the whole group (p <0.05) and female subjects (p <0.01). Comparing the three anthropometric indexes predicting hypertension, hyperglycemia, dyslipidemia and multiple cardio-metabolic risks, for women, it was WC having the largest areas under ROC curves (0.759, 0.746, 0.701 and 0.773 respectively); while in men, it was WC for hypertension, WHR for hyperglycemia, BMI for dyslipidemia and WC for multiple cardio-metabolic risks (areas under ROC curves were 0.658, 0.686, 0.618 and 0.695 respectively). Among Chinese working population, the need of lower cutoff values to define overweight and obesity were observed. Central obesity indicator (WC) is the preferred measure to predict the presence of cardio-metabolic risk in Chinese female subjects.

One-Carbon Metabolism in Prostate Cancer: The Role of Androgen Signaling

PubMed Central

Corbin, Joshua M.; Ruiz-Echevarría, Maria J.

2016-01-01

Cancer cell metabolism differs significantly from the metabolism of non-transformed cells. This altered metabolic reprogramming mediates changes in the uptake and use of nutrients that permit high rates of proliferation, growth, and survival. The androgen receptor (AR) plays an essential role in the establishment and progression of prostate cancer (PCa), and in the metabolic adaptation that takes place during this progression. In its role as a transcription factor, the AR directly affects the expression of several effectors and regulators of essential catabolic and biosynthetic pathways. Indirectly, as a modulator of the one-carbon metabolism, the AR can affect epigenetic processes, DNA metabolism, and redox balance, all of which are important factors in tumorigenesis. In this review, we focus on the role of AR-signaling on one-carbon metabolism in tumorigenesis. Clinical implications of one-carbon metabolism and AR-targeted therapies for PCa are discussed in this context. PMID:27472325

Prenatal dietary load of Maillard reaction products combined with postnatal Coca-Cola drinking affects metabolic status of female Wistar rats

PubMed Central

Gurecká, Radana; Koborová, Ivana; Janšáková, Katarína; Tábi, Tamás; Szökő, Éva; Somoza, Veronika; Šebeková, Katarína; Celec, Peter

2015-01-01

Aim To assess the impact of prenatal exposure to Maillard reaction products (MRPs) -rich diet and postnatal Coca-Cola consumption on metabolic status of female rats. Diet rich in MRPs and consumption of saccharose/fructose sweetened soft drinks is presumed to impose increased risk of development of cardiometabolic afflictions, such as obesity or insulin resistance. Methods At the first day of pregnancy, 9 female Wistar rats were randomized into two groups, pair-fed either with standard rat chow (MRP-) or MRPs-rich diet (MRP+). Offspring from each group of mothers was divided into two groups and given either water (Cola-) or Coca-Cola (Cola+) for drinking ad libitum for 18 days. Oral glucose tolerance test was performed, and circulating markers of inflammation, oxidative stress, glucose and lipid metabolism were assessed. Results MRP+ groups had higher weight gain, significantly so in the MRP+/Cola- vs MRP-/Cola-. Both prenatal and postnatal intervention increased carboxymethyllysine levels and semicarbazide-sensitive amine oxidase activity, both significantly higher in MRP+/Cola + than in MRP-/Cola-. Total antioxidant capacity was lower in MRP+ groups, with significant decrease in MRP+/Cola + vs MRP-/Cola+. Rats drinking Coca-Cola had higher insulin, homeostatic model assessment of insulin resistance, heart rate, advanced oxidation of protein products, triacylglycerols, and oxidative stress markers measured as thiobarbituric acid reactive substances compared to rats drinking water, with no visible effect of MRPs-rich diet. Conclusion Metabolic status of rats was affected both by prenatal and postnatal dietary intervention. Our results suggest that combined effect of prenatal MRPs load and postnatal Coca-Cola drinking may play a role in development of metabolic disorders in later life. PMID:25891868

Prenatal dietary load of Maillard reaction products combined with postnatal Coca-Cola drinking affects metabolic status of female Wistar rats.

PubMed

Gurecká, Radana; Koborová, Ivana; Janšáková, Katarína; Tábi, Tamás; Szökő, Éva; Somoza, Veronika; Šebeková, Katarína; Celec, Peter

2015-04-01

To assess the impact of prenatal exposure to Maillard reaction products (MRPs) -rich diet and postnatal Coca-Cola consumption on metabolic status of female rats. Diet rich in MRPs and consumption of saccharose/fructose sweetened soft drinks is presumed to impose increased risk of development of cardiometabolic afflictions, such as obesity or insulin resistance. At the first day of pregnancy, 9 female Wistar rats were randomized into two groups, pair-fed either with standard rat chow (MRP-) or MRPs-rich diet (MRP+). Offspring from each group of mothers was divided into two groups and given either water (Cola-) or Coca-Cola (Cola+) for drinking ad libitum for 18 days. Oral glucose tolerance test was performed, and circulating markers of inflammation, oxidative stress, glucose and lipid metabolism were assessed. MRP+ groups had higher weight gain, significantly so in the MRP+/Cola- vs MRP-/Cola-. Both prenatal and postnatal intervention increased carboxymethyllysine levels and semicarbazide-sensitive amine oxidase activity, both significantly higher in MRP+/Cola + than in MRP-/Cola-. Total antioxidant capacity was lower in MRP+ groups, with significant decrease in MRP+/Cola + vs MRP-/Cola+. Rats drinking Coca-Cola had higher insulin, homeostatic model assessment of insulin resistance, heart rate, advanced oxidation of protein products, triacylglycerols, and oxidative stress markers measured as thiobarbituric acid reactive substances compared to rats drinking water, with no visible effect of MRPs-rich diet. Metabolic status of rats was affected both by prenatal and postnatal dietary intervention. Our results suggest that combined effect of prenatal MRPs load and postnatal Coca-Cola drinking may play a role in development of metabolic disorders in later life.

Impact of Time-Restricted Feeding and Dawn-to-Sunset Fasting on Circadian Rhythm, Obesity, Metabolic Syndrome, and Nonalcoholic Fatty Liver Disease

PubMed Central

Gagan, Sood K.

2017-01-01

Obesity now affects millions of people and places them at risk of developing metabolic syndrome, nonalcoholic fatty liver disease (NAFLD), and even hepatocellular carcinoma. This rapidly emerging epidemic has led to a search for cost-effective methods to prevent the metabolic syndrome and NAFLD as well as the progression of NAFLD to cirrhosis and hepatocellular carcinoma. In murine models, time-restricted feeding resets the hepatic circadian clock and enhances transcription of key metabolic regulators of glucose and lipid homeostasis. Studies of the effect of dawn-to-sunset Ramadan fasting, which is akin to time-restricted feeding model, have also identified significant improvement in body mass index, serum lipid profiles, and oxidative stress parameters. Based on the findings of studies conducted on human subjects, dawn-to-sunset fasting has the potential to be a cost-effective intervention for obesity, metabolic syndrome, and NAFLD. PMID:29348746

Influence of a 10-Day Mimic of Our Ancient Lifestyle on Anthropometrics and Parameters of Metabolism and Inflammation: The “Study of Origin”

PubMed Central

Ruiz-Núñez, Begoña; Raison, Charles L.; Muskiet, Frits A. J.

2016-01-01

Chronic low-grade inflammation and insulin resistance are intimately related entities that are common to most, if not all, chronic diseases of affluence. We hypothesized that a short-term intervention based on “ancient stress factors” may improve anthropometrics and clinical chemical indices. We executed a pilot study of whether a 10-day mimic of a hunter-gatherer lifestyle favorably affects anthropometrics and clinical chemical indices. Fifty-five apparently healthy subjects, in 5 groups, engaged in a 10-day trip through the Pyrenees. They walked 14 km/day on average, carrying an 8-kilo backpack. Raw food was provided and self-prepared and water was obtained from waterholes. They slept outside in sleeping bags and were exposed to temperatures ranging from 12 to 42°C. Anthropometric data and fasting blood samples were collected at baseline and the study end. We found important significant changes in most outcomes favoring better metabolic functioning and improved anthropometrics. Coping with “ancient mild stress factors,” including physical exercise, thirst, hunger, and climate, may influence immune status and improve anthropometrics and metabolic indices in healthy subjects and possibly patients suffering from metabolic and immunological disorders. PMID:27366752

Evaluation of ovarian function and metabolic factors in women affected by polycystic ovary syndrome after treatment with D-Chiro-Inositol.

PubMed

Laganà, Antonio Simone; Barbaro, Luisa; Pizzo, Alfonsa

2015-05-01

To evaluate the effects of D-Chiro-Inositol in women affected by polycystic ovary syndrome (PCOS). We enrolled 48 patients, with homogeneous bio-physical characteristics, affected by PCOS and menstrual irregularities. These patients underwent treatment with 1 gr of D-Chiro-Inositol/die plus 400 mcg of Folic Acid/die orally for 6 months. We analyzed pre-treatment and post-treatment BMI, Systolic and Diastolic blood pressure, Ferriman-Gallwey score, Cremoncini score, serum LH, LH/FSH ratio, total and free testosterone, DHEA-S, Δ-4-androstenedione, SHBG, prolactin, glucose/IRI ratio, HOMA index, and resumption of regular menstrual cycles. We evidenced a statistically significant reduction of systolic blood pressure, Ferriman-Gallwey score, LH, LH/FSH ratio, total Testosterone, free Testosterone, ∆-4-Androstenedione, Prolactin, and HOMA Index; in the same patients, we noticed a statistically significant increase of SHBG and Glycemia/IRI ratio. Moreover, we observed statistically significant (62.5%; p < 0.05) post-treatment menstrual cycle regularization. D-Chiro-Inositol is effective in improving ovarian function and metabolism of patients affected by PCOS.

Optimization of brain metabolism using metabolic-targeted therapeutic hypothermia can reduce mortality from traumatic brain injury.

PubMed

Feng, Jin-Zhou; Wang, Wen-Yuan; Zeng, Jun; Zhou, Zhi-Yuan; Peng, Jin; Yang, Hao; Deng, Peng-Chi; Li, Shi-Jun; Lu, Charles D; Jiang, Hua

2017-08-01

Therapeutic hypothermia is widely used to treat traumatic brain injuries (TBIs). However, determining the best hypothermia therapy strategy remains a challenge. We hypothesized that reducing the metabolic rate, rather than reaching a fixed body temperature, would be an appropriate target because optimizing metabolic conditions especially the brain metabolic environment may enhance neurologic protection. A pilot single-blind randomized controlled trial was designed to test this hypothesis, and a nested metabolomics study was conducted to explore the mechanics thereof. Severe TBI patients (Glasgow Coma Scale score, 3-8) were randomly divided into the metabolic-targeted hypothermia treatment (MTHT) group, 50% to 60% rest metabolic ratio as the hypothermia therapy target, and the body temperature-targeted hypothermia treatment (BTHT) control group, hypothermia therapy target of 32°C to 35°C body temperature. Brain and circulatory metabolic pool blood samples were collected at baseline and on days 1, 3, and 7 during the hypothermia treatment, which were selected randomly from a subgroup of MTHT and BTHT groups. The primary outcome was mortality. Using H nuclear magnetic resonance technology, we tracked and located the disturbances of metabolic networks. Eighty-eight severe TBI patients were recruited and analyzed from December 2013 to December 2014, 44 each were assigned in the MTHT and BTHT groups (median age, 42 years; 69.32% men; mean Glasgow Coma Scale score, 6.17 ± 1.02). The mortality was significantly lower in the MTHT than the BTHT group (15.91% vs. 34.09%; p = 0.049). From these, eight cases of MTHT and six cases from BTHT group were enrolled for metabolomics analysis, which showed a significant difference between the brain and circulatory metabolic patterns in MTHT group on day 7 based on the model parameters and scores plots. Finally, metabolites representing potential neuroprotective monitoring parameters for hypothermia treatment were identified through

Effects of polymorphism rs3123554 in the cannabinoid receptor gene type 2 (CB2R) on metabolic and adiposity parameters after weight loss with two hypocaloric diets.

PubMed

de Luis, D A; Mulero, I; Primo, D; Izaola, O; Aller, R

2018-05-01

The role of CB2R gene variants on weight loss after a dietary intervention remained unclear. Our aim was to analyze the effects of rs3123554 of CB2R receptor gene on metabolic and adiposity parameters after two different hypocaloric diets in obese subjects. A Caucasian population of 280 obese patients was enrolled. Patients were randomly allocated during 3 months to one of two diets (Diet I - moderate in carbohydrate. Vs Diet II - normal in carbohydrate). In both genotype groups (GG vs GA + AA), body weight, body mass index (BMI), fat mass, waist circumference and systolic blood pressure decreased after diet I and II. The decrease of these parameters was higher in non A allele carriers than A allele carriers. Pre- and post-dietary intervention, body weight, BMI, fat mass and waist circumference were higher in A allele carriers than non A allele carriers. In non A allele carriers, the decrease of glucose, insulin, HOMA-IR and Interleukin-6 levels was higher than A allele carriers after both diets. Carriers of the minor allele of rs3123554 variant of CB2R gene loose less body weight during two different hypocaloric diets. The improvement of metabolic parameters was better in no A allele carriers than A allele carriers. Copyright © 2018 Elsevier B.V. All rights reserved.

Metabolic Diseases of Muscle

MedlinePlus

... diets. Your MDA clinic director can help you design a specific plan suited for your metabolic disorder ... respira- tory or speech therapy consultations • annual flu shots • support groups for those affected, spouses, parents or ...

L-Arginine Affects Aerobic Capacity and Muscle Metabolism in MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-Like Episodes) Syndrome

PubMed Central

Rodan, Lance H.; Wells, Greg D.; Banks, Laura; Thompson, Sara; Schneiderman, Jane E.; Tein, Ingrid

2015-01-01

Objective To study the effects of L-arginine (L-Arg) on total body aerobic capacity and muscle metabolism as assessed by 31Phosphorus Magnetic Resonance Spectroscopy (31P-MRS) in patients with MELAS (Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like episodes) syndrome. Methods We performed a case control study in 3 MELAS siblings (m.3243A>G tRNAleu(UUR) in MTTL1 gene) with different % blood mutant mtDNA to evaluate total body maximal aerobic capacity (VO2peak) using graded cycle ergometry and muscle metabolism using 31P-MRS. We then ran a clinical trial pilot study in MELAS sibs to assess response of these parameters to single dose and a 6-week steady-state trial of oral L-Arginine. Results At baseline (no L-Arg), MELAS had lower serum Arg (p = 0.001). On 31P-MRS muscle at rest, MELAS subjects had increased phosphocreatine (PCr) (p = 0.05), decreased ATP (p = 0.018), and decreased intracellular Mg2+ (p = 0.0002) when compared to matched controls. With L-arginine therapy, the following trends were noted in MELAS siblings on cycle ergometry: (1) increase in mean % maximum work at anaerobic threshold (AT) (2) increase in % maximum heart rate at AT (3) small increase in VO2peak. On 31P-MRS the following mean trends were noted: (1) A blunted decrease in pH after exercise (less acidosis) (2) increase in Pi/PCr ratio (ADP) suggesting increased work capacity (3) a faster half time of PCr recovery (marker of mitochondrial activity) following 5 minutes of moderate intensity exercise (4) increase in torque. Significance These results suggest an improvement in aerobic capacity and muscle metabolism in MELAS subjects in response to supplementation with L-Arg. Intramyocellular hypomagnesemia is a novel finding that warrants further study. Classification of Evidence Class III evidence that L-arginine improves aerobic capacity and muscle metabolism in MELAS subjects. Trial Registration ClinicalTrials.gov NCT01603446. PMID:25993630

L-Arginine Affects Aerobic Capacity and Muscle Metabolism in MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-Like Episodes) Syndrome.

PubMed

Rodan, Lance H; Wells, Greg D; Banks, Laura; Thompson, Sara; Schneiderman, Jane E; Tein, Ingrid

2015-01-01

To study the effects of L-arginine (L-Arg) on total body aerobic capacity and muscle metabolism as assessed by (31)Phosphorus Magnetic Resonance Spectroscopy ((31)P-MRS) in patients with MELAS (Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like episodes) syndrome. We performed a case control study in 3 MELAS siblings (m.3243A>G tRNA(leu(UUR)) in MTTL1 gene) with different % blood mutant mtDNA to evaluate total body maximal aerobic capacity (VO(2peak)) using graded cycle ergometry and muscle metabolism using 31P-MRS. We then ran a clinical trial pilot study in MELAS sibs to assess response of these parameters to single dose and a 6-week steady-state trial of oral L-Arginine. At baseline (no L-Arg), MELAS had lower serum Arg (p = 0.001). On 3(1)P-MRS muscle at rest, MELAS subjects had increased phosphocreatine (PCr) (p = 0.05), decreased ATP (p = 0.018), and decreased intracellular Mg(2+) (p = 0.0002) when compared to matched controls. With L-arginine therapy, the following trends were noted in MELAS siblings on cycle ergometry: (1) increase in mean % maximum work at anaerobic threshold (AT) (2) increase in % maximum heart rate at AT (3) small increase in VO(2peak). On (31)P-MRS the following mean trends were noted: (1) A blunted decrease in pH after exercise (less acidosis) (2) increase in Pi/PCr ratio (ADP) suggesting increased work capacity (3) a faster half time of PCr recovery (marker of mitochondrial activity) following 5 minutes of moderate intensity exercise (4) increase in torque. These results suggest an improvement in aerobic capacity and muscle metabolism in MELAS subjects in response to supplementation with L-Arg. Intramyocellular hypomagnesemia is a novel finding that warrants further study. Class III evidence that L-arginine improves aerobic capacity and muscle metabolism in MELAS subjects. ClinicalTrials.gov NCT01603446.

Metabolic Syndrome and Breast Cancer Risk.

PubMed

Wani, Burhan; Aziz, Shiekh Aejaz; Ganaie, Mohammad Ashraf; Mir, Mohammad Hussain

2017-01-01

The study was meant to estimate the prevalence of metabolic syndrome in patients with breast cancer and to establish its role as an independent risk factor on occurrence of breast cancer. Fifty women aged between 40 and 80 years with breast cancer and fifty controls of similar age were assessed for metabolic syndrome prevalence and breast cancer risk factors, including age at menarche, reproductive status, live births, breastfeeding, and family history of breast cancer, age at diagnosis of breast cancer, body mass index, and metabolic syndrome parameters. Metabolic syndrome prevalence was found in 40.0% of breast cancer patients, and 18.0% of those in control group ( P = 0.02). An independent and positive association was seen between metabolic syndrome and breast cancer risk (odds ratio = 3.037; 95% confidence interval 1.214-7.597). Metabolic syndrome is more prevalent in breast cancer patients and is an independent risk factor for breast cancer.

[Metabolic disorders as paraneoplastic syndromes].

PubMed

Krug, S; Michl, P

2018-02-01

Paraneoplastic syndromes are characterized by the tumor-induced release of peptide hormones and/or the initiation of immune phenomena, which elicit clinical changes and alterations in laboratory parameters independent of the tumor size and spread. In addition to neurological, endocrinal and rheumatological phenotypes, metabolic alterations play a special role in the clinical routine as they commonly present with acute symptoms in an emergency situation and necessitate immediate diagnosis and prompt initiation of treatment. Metabolic alterations within the framework of malignant diseases should be treated in a multidisciplinary team and it is often necessary to perform monitoring and treatment in an intensive care unit. This article focuses on the diagnostic and therapeutic options for metabolic disorders due to paraneoplastic syndromes, such as hypercalcemia, hypocalcemia, hyperglycemia, hypoglycemia and a special variant of tumor-induced metabolic disorders due to tumor lysis syndrome.

Vegetarian diets and gut microbiota: important shifts in markers of metabolism and cardiovascular disease.

PubMed

do Rosario, Vinicius A; Fernandes, Ricardo; Trindade, Erasmo B S de M

2016-07-01

Vegetarian diets have been associated with a lower incidence of several chronic diseases. The benefits of plant-based diets are related mainly to the improvement of metabolic parameters that can indicate risk for such diseases. Some metabolic factors, such as oxidative balance, lipid profile, and glucose homeostasis, can be improved directly by diet, but paradoxically, some characteristics of vegetarian diets may promote a negative scenario that increases the risk of certain chronic diseases. Additionally, many benefits of a vegetarian diet are mediated by the gut microbiota, members of which not only have taxonomic and functional differences but also produce diverse, specific metabolites that vary according to whether the host consumes an omnivorous or a vegetarian diet. This review examines the modulation of human metabolism and gut microbiota by vegetarian and omnivorous dietary patterns and explores how this modulation may affect the risk of cardiovascular disease. © The Author(s) 2016. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Endocrinological, metabolic and clinical features of treatment with oral contraceptive formulation containing ethinylestradiol plus chlormadinone acetate in nonobese women with polycystic ovary syndrome.

PubMed

Uras, Roberto; Orrù, Marisa; Pani, Fabiana; Marotto, Maria Francesca; Pilloni, Monica; Guerriero, Stefano; Etzi, Rossella; Zedda, Pierina; Sorge, Roberto; Lello, Stefano; Melis, Gian Benedetto; Paoletti, Anna Maria

2010-08-01

Chlormadinone acetate (CMA) is a progestin compound similar to progesterone, with antiandrogenic properties. In healthy eumenorrheic women, it was demonstrated that the monophasic estroprogestin formulation containing CMA (2 mg) plus ethinyl estradiol (EE) (30 mcg) (EE30+CMA) is efficacious both in reducing hyperandrogenic symptoms, fat mass and in improving lipoprotein panel, without changes in insulin-glucose metabolism. These metabolic properties are important for women affected by polycystic ovary syndrome (PCOS) in whom there is a predisposition to insulin resistance. We studied whether in young nonobese women with PCOS (15 subjects, EE30+CMA-PCOS group) a six-cycle treatment with EE30+CMA can reduce androgen levels, androgen bioavailability and the score of hirsutism and acne, and modify glucose-insulin metabolism evaluated by the oral glucose tolerance test and the body composition evaluated by bio-impedenziometry. These parameters were evaluated before (first visit) and during the sixth cycle of EE30+CMA (second visit). All the results were compared with those of a matched-age-group of nonobese PCOS women (15 subjects, no OC-PCOS group) evaluated before (first visit) and after six menstrual cycles in which they did not use any drug or oral contraceptive (second visit). In the EE30+CMA-PCOS group women, androgen levels and bioavailability, hirsutism and acne score were significantly lower at the second than at the first visit, whereas they did not change in no OC-PCOS group. At the second visit, in both groups, glucose-insulin metabolism and body composition parameters were not affected. A six-cycle treatment with EE30+CMA is efficacious in nonobese PCOS women to improve hyperandrogenic symptoms, without negative interferences both on body composition and on insulin-glucose metabolism. Copyright 2010 Elsevier Inc. All rights reserved.

Transcriptional and metabolic effects of glucose on Streptococcus pneumoniae sugar metabolism

PubMed Central

Paixão, Laura; Caldas, José; Kloosterman, Tomas G.; Kuipers, Oscar P.; Vinga, Susana; Neves, Ana R.

2015-01-01

Streptococcus pneumoniae is a strictly fermentative human pathogen that relies on carbohydrate metabolism to generate energy for growth. The nasopharynx colonized by the bacterium is poor in free sugars, but mucosa lining glycans can provide a source of sugar. In blood and inflamed tissues glucose is the prevailing sugar. As a result during progression from colonization to disease S. pneumoniae has to cope with a pronounced shift in carbohydrate nature and availability. Thus, we set out to assess the pneumococcal response to sugars found in glycans and the influence of glucose (Glc) on this response at the transcriptional, physiological, and metabolic levels. Galactose (Gal), N-acetylglucosamine (GlcNAc), and mannose (Man) affected the expression of 8 to 14% of the genes covering cellular functions including central carbon metabolism and virulence. The pattern of end-products as monitored by in vivo 13C-NMR is in good agreement with the fermentation profiles during growth, while the pools of phosphorylated metabolites are consistent with the type of fermentation observed (homolactic vs. mixed) and regulation at the metabolic level. Furthermore, the accumulation of α-Gal6P and Man6P indicate metabolic bottlenecks in the metabolism of Gal and Man, respectively. Glc added to cells actively metabolizing other sugar(s) was readily consumed and elicited a metabolic shift toward a homolactic profile. The transcriptional response to Glc was large (over 5% of the genome). In central carbon metabolism (most represented category), Glc exerted mostly negative regulation. The smallest response to Glc was observed on a sugar mix, suggesting that exposure to varied sugars improves the fitness of S. pneumoniae. The expression of virulence factors was negatively controlled by Glc in a sugar-dependent manner. Overall, our results shed new light on the link between carbohydrate metabolism, adaptation to host niches and virulence. PMID:26500614

Transcriptional and metabolic effects of glucose on Streptococcus pneumoniae sugar metabolism.

PubMed

Paixão, Laura; Caldas, José; Kloosterman, Tomas G; Kuipers, Oscar P; Vinga, Susana; Neves, Ana R

2015-01-01

Streptococcus pneumoniae is a strictly fermentative human pathogen that relies on carbohydrate metabolism to generate energy for growth. The nasopharynx colonized by the bacterium is poor in free sugars, but mucosa lining glycans can provide a source of sugar. In blood and inflamed tissues glucose is the prevailing sugar. As a result during progression from colonization to disease S. pneumoniae has to cope with a pronounced shift in carbohydrate nature and availability. Thus, we set out to assess the pneumococcal response to sugars found in glycans and the influence of glucose (Glc) on this response at the transcriptional, physiological, and metabolic levels. Galactose (Gal), N-acetylglucosamine (GlcNAc), and mannose (Man) affected the expression of 8 to 14% of the genes covering cellular functions including central carbon metabolism and virulence. The pattern of end-products as monitored by in vivo (13)C-NMR is in good agreement with the fermentation profiles during growth, while the pools of phosphorylated metabolites are consistent with the type of fermentation observed (homolactic vs. mixed) and regulation at the metabolic level. Furthermore, the accumulation of α-Gal6P and Man6P indicate metabolic bottlenecks in the metabolism of Gal and Man, respectively. Glc added to cells actively metabolizing other sugar(s) was readily consumed and elicited a metabolic shift toward a homolactic profile. The transcriptional response to Glc was large (over 5% of the genome). In central carbon metabolism (most represented category), Glc exerted mostly negative regulation. The smallest response to Glc was observed on a sugar mix, suggesting that exposure to varied sugars improves the fitness of S. pneumoniae. The expression of virulence factors was negatively controlled by Glc in a sugar-dependent manner. Overall, our results shed new light on the link between carbohydrate metabolism, adaptation to host niches and virulence.

Metabolic control of redox and redox control of metabolism in plants.

PubMed

Geigenberger, Peter; Fernie, Alisdair R

2014-09-20

Reduction-oxidation (Redox) status operates as a major integrator of subcellular and extracellular metabolism and is simultaneously itself regulated by metabolic processes. Redox status not only dominates cellular metabolism due to the prominence of NAD(H) and NADP(H) couples in myriad metabolic reactions but also acts as an effective signal that informs the cell of the prevailing environmental conditions. After relay of this information, the cell is able to appropriately respond via a range of mechanisms, including directly affecting cellular functioning and reprogramming nuclear gene expression. The facile accession of Arabidopsis knockout mutants alongside the adoption of broad-scale post-genomic approaches, which are able to provide transcriptomic-, proteomic-, and metabolomic-level information alongside traditional biochemical and emerging cell biological techniques, has dramatically advanced our understanding of redox status control. This review summarizes redox status control of metabolism and the metabolic control of redox status at both cellular and subcellular levels. It is becoming apparent that plastid, mitochondria, and peroxisome functions influence a wide range of processes outside of the organelles themselves. While knowledge of the network of metabolic pathways and their intraorganellar redox status regulation has increased in the last years, little is known about the interorganellar redox signals coordinating these networks. A current challenge is, therefore, synthesizing our knowledge and planning experiments that tackle redox status regulation at both inter- and intracellular levels. Emerging tools are enabling ever-increasing spatiotemporal resolution of metabolism and imaging of redox status components. Broader application of these tools will likely greatly enhance our understanding of the interplay of redox status and metabolism as well as elucidating and characterizing signaling features thereof. We propose that such information will enable

Enantiomeric metabolic interactions and stereoselective human methadone metabolism.

PubMed

Totah, Rheem A; Allen, Kyle E; Sheffels, Pamela; Whittington, Dale; Kharasch, Evan D

2007-04-01

Methadone is administered as a racemate, although opioid activity resides in the R-enantiomer. Methadone disposition is stereoselective, with considerable unexplained variability in clearance and plasma R/S ratios. N-Demethylation of methadone in vitro is predominantly mediated by cytochrome P450 CYP3A4 and CYP2B6 and somewhat by CYP2C19. This investigation evaluated stereoselectivity, models, and kinetic parameters for methadone N-demethylation by recombinant CYP2B6, CYP3A4, and CYP2C19, and the potential for interactions between enantiomers during racemate metabolism. CYP2B6 metabolism was stereoselective. CYP2C19 was less active, and stereoselectivity was opposite that for CYP2B6. CYP3A4 was not stereoselective. With all three isoforms, enantiomer N-dealkylation rates in the racemate were lower than those of (R)-(6-dimethyamino-4,4-diphenyl-heptan-3-one) hydrochloride (R-methadone) or (S)-(6-dimethyamino-4,4-diphenyl-heptan-3-one) hydrochloride (S-methadone) alone, suggesting an enantiomeric interaction and mutual metabolic inhibition. For CYP2B6, the interaction between enantiomers was stereoselective, with S-methadone as a more potent inhibitor of R-methadone N-demethylation than R-of S-methadone. In contrast, enantiomer interactions were not stereoselective with CYP2C19 or CYP3A4. For all three cytochromes P450, methadone N-demethylation was best described by two-site enzyme models with competitive inhibition. There were minor model differences between cytochromes P450 to account for stereoselectivity of metabolism and enantiomeric interactions. Changes in plasma R/S methadone ratios observed after rifampin or troleandomycin pretreatment in humans in vivo were successfully predicted by CYP2B6- but not CYP3A4-catalyzed methadone N-demethylation. CYP2B6 is a predominant catalyst of stereoselective methadone metabolism in vitro. In vivo, CYP2B6 may be a major determinant of methadone metabolism and disposition, and CYP2B6 activity and stereoselective metabolic