Combined treatment with melatonin and insulin improves glycemic control, white adipose tissue metabolism and reproductive axis of diabetic male rats.

Science.gov (United States)

Oliveira, Ariclecio Cunha de; Andreotti, Sandra; Sertie, Rogério António Laurato; Campana, Amanda Baron; de Proença, André Ricardo Gomes; Vasconcelos, Renata Prado; Oliveira, Keciany Alves de; Coelho-de-Souza, Andrelina Noronha; Donato-Junior, José; Lima, Fábio Bessa

2018-04-15

Melatonin treatment has been reported to be capable of ameliorating metabolic diabetes-related abnormalities but also to cause hypogonadism in rats. We investigated whether the combined treatment with melatonin and insulin can improve insulin resistance and other metabolic disorders in rats with streptozotocin-induced diabetes during neonatal period and the repercussion of this treatment on the hypothalamic-pituitary-gonadal axis. At the fourth week of age, diabetic animals started an 8-wk treatment with only melatonin (0.2 mg/kg body weight) added to drinking water at night or associated with insulin (NHP, 1.5 U/100 g/day) or only insulin. Animals were then euthanized, and the subcutaneous (SC), epididymal (EP), and retroperitoneal (RP) fat pads were excised, weighed and processed for adipocyte isolation for morphometric analysis as well as for measuring glucose uptake, oxidation, and incorporation of glucose into lipids. Hypothalamus was collected for gene expression and blood samples were collected for biochemical assays. The treatment with melatonin plus insulin (MI) was capable of maintaining glycemic control. In epididymal (EP) and subcutaneous (SC) adipocytes, the melatonin plus insulin (MI) treatment group recovered the insulin responsiveness. In the hypothalamus, melatonin treatment alone promoted a significant reduction in kisspeptin-1, neurokinin B and androgen receptor mRNA levels, in relation to control group. Combined treatment with melatonin and insulin promoted a better glycemic control, improving insulin sensitivity in white adipose tissue (WAT). Indeed, melatonin treatment reduced hypothalamic genes related to reproductive function. Copyright © 2017. Published by Elsevier Inc.

Bilateral Diabetic Papillopathy and Metabolic Control

DEFF Research Database (Denmark)

Ostri, Christoffer; Lund-Andersen, Henrik; Sander, Birgit

2010-01-01

OBJECTIVE: The pathogenesis of diabetic papillopathy largely is unknown, but case reports suggest that it may follow rapidly improved metabolic control. The present study was designed to investigate this hypothesis. DESIGN: Retrospective case-control study. PARTICIPANTS: Two thousand sixty......-six patients with type 1 diabetes. METHODS: Review of clinical, photographic, and clinical chemistry records from a large diabetology and ophthalmology unit between 2001 and 2008. MAIN OUTCOME MEASURES: Simultaneous, bilateral diabetic papillopathy. RESULTS: The mean follow-up was 4.9 years. During 10 020...... patient-years of observation, bilateral diabetic papillopathy developed in 5 patients. During the year preceding this incident, all 5 patients had experienced a decrease in glycosylated hemoglobin A(1c) (HbA(1C)) at a maximum rate of -2.5 (mean) percentage points per quarter year, which was significantly...

Blueberries improve endothelial function, but not blood pressure, in adults with metabolic syndrome: a randomized, double-blind, placebo-controlled clinical trial.

Science.gov (United States)

Stull, April J; Cash, Katherine C; Champagne, Catherine M; Gupta, Alok K; Boston, Raymond; Beyl, Robbie A; Johnson, William D; Cefalu, William T

2015-05-27

Blueberry consumption has been shown to have various health benefits in humans. However, little is known about the effect of blueberry consumption on blood pressure, endothelial function and insulin sensitivity in humans. The present study investigated the role of blueberry consumption on modifying blood pressure in subjects with metabolic syndrome. In addition, endothelial function and insulin sensitivity (secondary measurements) were also assessed. A double-blind and placebo-controlled study was conducted in 44 adults (blueberry, n = 23; and placebo, n = 21). They were randomized to receive a blueberry or placebo smoothie twice daily for six weeks. Twenty-four-hour ambulatory blood pressure, endothelial function and insulin sensitivity were assessed pre- and post-intervention. The blood pressure and insulin sensitivity did not differ between the blueberry and placebo groups. However, the mean change in resting endothelial function, expressed as reactive hyperemia index (RHI), was improved significantly more in the group consuming the blueberries versus the placebo group (p = 0.024). Even after adjusting for confounding factors, i.e., the percent body fat and gender, the blueberry group still had a greater improvement in endothelial function when compared to their counterpart (RHI; 0.32 ± 0.13 versus -0.33 ± 0.14; p = 0.0023). In conclusion, daily dietary consumption of blueberries did not improve blood pressure, but improved (i.e., increased) endothelial function over six weeks in subjects with metabolic syndrome.

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

Directory of Open Access Journals (Sweden)

Milene L. Brownlow

2017-05-01

Full Text Available 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

Body weight regulation and obesity: dietary strategies to improve the metabolic profile.

Science.gov (United States)

Munsters, M J M; Saris, W H M

2014-01-01

This review discusses dietary strategies that may improve the metabolic profile and body weight regulation in obesity. Recent evidence demonstrated that long-term health effects seem to be more beneficial for low-glycemic index (GI) diets compared to high-protein diets. Still, these results need to be confirmed by other prospective cohort studies and long-term clinical trials, and the discrepancy between these study designs needs to be explored in more detail. Furthermore, the current literature is mixed with regard to the efficacy of increased meal frequency (or snacking) regimens in causing metabolic alterations, particularly in relation to body weight control. In conclusion, a growing body of evidence suggests that dietary strategies with the aim to reduce postprandial insulin response and increase fat oxidation, and that tend to restore metabolic flexibility, have a place in the prevention and treatment of obesity and associated metabolic disorders.

Engineering of metabolic control

Science.gov (United States)

Liao, James C.

2004-03-16

The invention features a method of producing heterologous molecules in cells under the regulatory control of a metabolite and metabolic flux. The method can enhance the synthesis of heterologous polypeptides and metabolites.

Canagliflozin improves risk factors of metabolic syndrome in patients with type 2 diabetes mellitus and metabolic syndrome

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Davies MJ

2017-01-01

Full Text Available Michael J Davies,1 Katherine W Merton,1 Ujjwala Vijapurkar,2 Dainius A Balis,2 Mehul Desai2 1Janssen Scientific Affairs, LLC, Titusville, NJ, USA; 2Janssen Research & Development, LLC, Raritan, NJ, USA Objective: Metabolic syndrome refers to a collection of risk factors associated with the development of cardiovascular disease and type 2 diabetes mellitus (T2DM. Canagliflozin, a sodium glucose co-transporter 2 inhibitor, improves glycemic control and reduces body weight and blood pressure (BP in a broad range of patients with T2DM. This post hoc analysis assessed the effects of canagliflozin on the components of metabolic syndrome in patients with T2DM and metabolic syndrome.Methods: This analysis was based on data from 2 head-to-head studies of canagliflozin in patients with T2DM on background metformin versus glimepiride (study 1 and background metformin plus sulfonylurea versus sitagliptin 100 mg (study 2. Changes from baseline in glycemic efficacy, anthropometric measures, BP, and lipids were evaluated with canagliflozin versus glimepiride and sitagliptin at week 52 in patients who met ≥2 of the criteria for metabolic syndrome (in addition to T2DM: triglycerides ≥1.7 mmol/L; high-density lipoprotein cholesterol (HDL-C <1.0 mmol/L (men or <1.3 mmol/L (women; waist circumference ≥102 cm (non-Asian men, ≥88 cm (non-Asian women, >90 cm (Asian men, or >80 cm (Asian women; diagnosis of hypertension or meeting BP-related criteria (systolic BP ≥130 mmHg or diastolic BP ≥85 mmHg. Safety was assessed based on adverse event reports.Results: In study 1, canagliflozin 100 and 300 mg provided similar and greater HbA1c reductions versus glimepiride, respectively. In study 2, canagliflozin 300 mg provided greater HbA1c lowering versus sitagliptin 100 mg. Canagliflozin also reduced fasting plasma glucose, body weight, body mass index, waist circumference, BP, and triglycerides, and increased HDL-C and low-density lipoprotein cholesterol versus

Sense of coherence, self-esteem, and health locus of control in subjects with type 1 diabetes mellitus with/without satisfactory metabolic control.

Science.gov (United States)

Nuccitelli, C; Valentini, A; Caletti, M T; Caselli, C; Mazzella, N; Forlani, G; Marchesini, G

2018-03-01

Despite intensive training, a few individuals with Type 1 diabetes mellitus (T1DM) fail to reach the desired metabolic targets. To evaluate the association between disease-related emotional and cognitive aspects and metabolic control in subjects with T1DM. Health locus of control (HLOC), sense of coherence (SOC), and self-esteem were assessed in T1DM subjects using validated questionnaires. Sixty-seven consecutive subjects who did not attain the desired HbA1c target (mean HbA1c, 8.3% [67 mmol/mol]) were compared with 30 cases in satisfactory metabolic control (HbA1c levels satisfactory metabolic control tend to rely on significant others, trusting in the physicians' skills or on the efficiency of the health-care system. Strategies aimed at increasing self-efficacy and SOC, based on personal ability, are eagerly awaited to help patients improve diabetes care.

Phloretin Prevents High-Fat Diet-Induced Obesity and Improves Metabolic Homeostasis.

Science.gov (United States)

Alsanea, Sary; Gao, Mingming; Liu, Dexi

2017-05-01

Reactive oxygen species generated as a by-product in metabolism play a central role in the development of obesity and obesity-related metabolic complications. The objective of the current study is to explore the possibility to block obesity and improve metabolic homeostasis via phloretin, a natural antioxidant product from apple tree leaves and Manchurian apricot. Both preventive and therapeutic activities of phloretin were assessed using a high-fat diet-induced obesity mouse model. Phloretin was injected intraperitoneally twice weekly into regular and obese mice fed a high-fat diet. The effects of phloretin treatment on body weight and composition, fat content in the liver, glucose and lipid metabolism, and insulin resistance were monitored and compared to the control animals. Phloretin treatment significantly blocks high-fat diet-induced weight gain but did not induce weight loss in obese animals. Phloretin improved glucose homeostasis and insulin sensitivity and alleviated hepatic lipid accumulation. RT-PCR analysis showed that phloretin treatment suppresses expression of macrophage markers (F4/80 and Cd68) and pro-inflammatory genes (Mcp-1 and Ccr2) and enhances adiponectin gene expression in white adipose tissue. In addition, phloretin treatment elevated the expression of fatty acid oxidation genes such as carnitine palmitoyltransferase 1a and 1b (Cpt1a and Cpt1b) and reduced expression of monocyte chemoattractant protein-1 (Mcp-1), de novo lipogenesis transcriptional factor peroxisome proliferator-activated receptor-γ 2 (Pparγ2), and its target monoacylglycerol O-acyltransferase (Mgat-1) genes. These results provide direct evidence to support a possible use of phloretin for mitigation of obesity and maintenance of metabolic homeostasis.

Effect of strict metabolic control on regulation of subcutaneous blood flow in insulin-dependent diabetic patients

DEFF Research Database (Denmark)

Kastrup, J; Mathiesen, E R; Saurbrey, Nina

1987-01-01

washout technique. Mean arterial blood pressure was reduced by a maximum of 23 mmHg by elevating the limb above heart level and elevated to a maximum of 65 mmHg by head-up tilt; in the latter position venous pressure was kept constantly low by activation of the leg muscle vein pump (heel raising......The effect of 10 weeks of improved metabolic control on the impaired autoregulation of the subcutaneous blood flow was studied at the level of the lateral malleolus in eight long-term insulin-dependent diabetic patients with clinical microangiopathy. Blood flow was measured by the local 133-Xenon......). Improved metabolic control was achieved using either continuous subcutaneous insulin infusion or multiple insulin injections. The blood glucose concentration declined from (median) 12.7 to 6.8 mmol/l and the HbA1C level from 10.1 to 7.5% during strict metabolic control (p less than 0.01 and p less than 0...

Metabolic and cardiovascular improvements after biliopancreatic diversion in a severely obese patient

Directory of Open Access Journals (Sweden)

Lescelleur Odette

2004-04-01

Full Text Available Abstract Background Severe obesity is associated with important morbidity and increased mortality. The successes of lifestyle modifications and drug therapy have been partial and mostly unsustained in reducing obesity and its comorbidities. Bariatric surgery, particularly biliopancreatic diversion with duodenal switch reduces efficiently excess body weight and improves metabolic and cardiovascular functions. Case presentation A 56-year-old man with severe clinical obesity underwent a biliopancreatic diversion with a duodenal switch after unsuccessful treatment with weight loss pharmacotherapy. He had diabetes, hypertension and sleep apnea syndrome and was on three medications for hypertension and two hypoglycemic agents in addition to > 200 insulin units daily. Eleven months after the surgery, he had lost 40% of his body weight. The lipid profile showed great improvement and the hypertension and diabetes were more easily controlled with no more insulin needed. The pseudonormalized pattern of left ventricular diastolic function improved and ventricular walls showed decreased thickness. Conclusion Biliopancreatic diversion may bring metabolic and cardiovascular benefits in severely obese patients from a cardiovascular perspective.

Oxygen uptake rate (OUR) control strategy for improving avermectin B

African Journals Online (AJOL)

Glucose metabolism plays a crucial role in the process of avermectin B1a biosynthesis. Controlling glucose feeding based on oxygen uptake rate (OUR) was established to improve the efficiency of avermectin B1a production. The result showed that avermectin B1a production was greatly enhanced by OUR control strategy.

Lansoprazole Is Associated with Worsening Asthma Control in Children with the CYP2C19 Poor Metabolizer Phenotype.

Science.gov (United States)

Lang, Jason E; Holbrook, Janet T; Mougey, Edward B; Wei, Christine Y; Wise, Robert A; Teague, W Gerald; Lima, John J

2015-06-01

Gastric acid blockade in children with asymptomatic acid reflux has not improved asthma control in published studies. There is substantial population variability regarding metabolism of and response to proton pump inhibitors based on metabolizer phenotype. How metabolizer phenotype affects asthma responses to acid blockage is not known. To determine how metabolizer phenotype based on genetic analysis of CYP2C19 affects asthma control among children treated with a proton pump inhibitor. Asthma control as measured by the Asthma Control Questionnaire (ACQ) and other questionnaires from a 6-month clinical trial of lansoprazole in children with asthma was analyzed for associations with surrogates of lansoprazole exposure (based on treatment assignment and metabolizer phenotype). Groups included placebo-treated children; lansoprazole-treated extensive metabolizers (EMs); and lansoprazole-treated poor metabolizers (PMs). Metabolizer phenotypes were based on CYP2C19 haplotypes. Carriers of the CYP2C19*2, *3, *8, *9, or *10 allele were PMs; carriers of two wild-type alleles were extensive metabolizers (EMs). Asthma control through most of the treatment period was unaffected by lansoprazole exposure or metabolizer phenotype. At 6 months, PMs displayed significantly worsened asthma control compared with EMs (+0.16 vs. -0.13; P = 0.02) and placebo-treated children (+0.16 vs. -0.23; P lansoprazole-treated PMs. Children with the PM phenotype developed worse asthma control after 6 months of lansoprazole treatment for poorly controlled asthma. Increased exposure to proton pump inhibitor may worsen asthma control by altering responses to respiratory infections. Clinical trial registered with www.clinicaltrials.gov (NCT00604851).

[Improving industrial microbial stress resistance by metabolic engineering: a review].

Science.gov (United States)

Fu, Ruiyan; Li, Yin

2010-09-01

Metabolic engineering is a technologic platform for industrial strain improvement and aims not only at modifying microbial metabolic fluxes, but also improving the physiological performance of industrial microbes. Microbes will meet multiple stresses in industrial processes. Consequently, elicited gene responses might result in a decrease in overall cell fitness and the efficiency of biotransformation. Thus, it is crucial to develop robust and productive microbial strains that can be integrated into industrial-scale bioprocesses. In this review, we focus on the progress of these novel methods and strategies for engineering stress-tolerance phenotypes referring to rational metabolic engineering and inverse metabolic engineering in recent years. In addition, we also address problems existing in this area and future research needs of microbial physiological functionality engineering.

Low-Volume High-Intensity Interval Training in a Gym Setting Improves Cardio-Metabolic and Psychological Health

OpenAIRE

Shepherd, Sam O.; Wilson, Oliver J.; Taylor, Alexandra S.; Thøgersen-Ntoumani, Cecilie; Adlan, Ahmed M.; Wagenmakers, Anton J. M.; Shaw, Christopher S.

2015-01-01

Background\\ud Within a controlled laboratory environment, high-intensity interval training (HIT) elicits similar cardiovascular and metabolic benefits as traditional moderate-intensity continuous training (MICT). It is currently unclear how HIT can be applied effectively in a real-world environment.\\ud Purpose\\ud To investigate the hypothesis that 10 weeks of HIT, performed in an instructor-led, group-based gym setting, elicits improvements in aerobic capacity (VO2max), cardio-metabolic risk ...

Inhibition of Endothelial p53 Improves Metabolic Abnormalities Related to Dietary Obesity

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Masataka Yokoyama

2014-06-01

Full Text Available Accumulating evidence has suggested a role for p53 activation in various age-associated conditions. Here, we identified a crucial role of endothelial p53 activation in the regulation of glucose homeostasis. Endothelial expression of p53 was markedly upregulated when mice were fed a high-calorie diet. Disruption of endothelial p53 activation improved dietary inactivation of endothelial nitric oxide synthase that upregulated the expression of peroxisome proliferator-activated receptor-γ coactivator-1α in skeletal muscle, thereby increasing mitochondrial biogenesis and oxygen consumption. Mice with endothelial cell-specific p53 deficiency fed a high-calorie diet showed improvement of insulin sensitivity and less fat accumulation, compared with control littermates. Conversely, upregulation of endothelial p53 caused metabolic abnormalities. These results indicate that inhibition of endothelial p53 could be a novel therapeutic target to block the vicious cycle of cardiovascular and metabolic abnormalities associated with obesity.

Oral insulin improves metabolic parameters in high fat diet fed rats

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LEANDRO C. LIPINSKI

2017-08-01

Full Text Available ABSTRACT Introduction/Aim: The gut has shown to have a pivotal role on the pathophysiology of metabolic disease. Food stimulation of distal intestinal segments promotes enterohormones secretion influencing insulin metabolism. In diabetic rats, oral insulin has potential to change intestinal epithelium behavior. This macromolecule promotes positive effects on laboratorial metabolic parameters and decreases diabetic intestinal hypertrophy. This study aims to test if oral insulin can influence metabolic parameters and intestinal weight in obese non-diabetic rats. Methods: Twelve weeks old Wistar rats were divided in 3 groups: control (CTRL standard chow group; high fat diet low carbohydrates group (HFD and HFD plus daily oral 20U insulin gavage (HFD+INS. Weight and food consumption were weekly obtained. After eight weeks, fasting blood samples were collected for laboratorial analysis. After euthanasia gut samples were isolated. Results: Rat oral insulin treatment decreased body weight gain (p<0,001, fasting glucose and triglycerides serum levels (p<0,05 an increased intestinal weight of distal ileum (P<0,05. Animal submitted to high fat diet presented higher levels of HOMA-IR although significant difference to CT was not achieved. HOMA-beta were significantly higher (p<0.05 in HFD+INS. Visceral fat was 10% lower in HFD+INS but the difference was not significant. Conclusions: In non-diabetic obese rats, oral insulin improves metabolic malfunction associated to rescue of beta-cell activity.

Thermodynamics of the control of metabolism

NARCIS (Netherlands)

Westerhoff, H. V.; Plomp, P. J.; Groen, A. K.; Wanders, R. J.

1987-01-01

A theory is presented, describing the control analysis of metabolic systems in terms of Gibbs free energies, extending earlier work of Kacser and Burns (25), and Heinrich and Rapoport (29). It is shown that relationships exist between flux control coefficients (the degree to which enzymes control

Evaluation of empowerment model on indicators of metabolic control in patients with type 2 diabetes, a randomized clinical trial study.

Science.gov (United States)

Ebrahimi, Hossein; Sadeghi, Mahdi; Amanpour, Farzaneh; Vahedi, Hamid

2016-04-01

Diabetes education is a major subject in achieving optimal glycemic control. Effective empowerment approach can be beneficial for improving patients' health. The aim of this study was to evaluate the effect of empowerment model on indicators of metabolic control in patients with type 2 diabetes. a randomized controlled trial of 103 patients with type 2 diabetes were randomly assigned to either the intervention (empowerment approach training) or the control group (conventional training) 2014. Empowerment approach training were performed for the experimental group for eight weeks. Data collection tool included demographic information form and indicators of metabolic control checklist. Analysis was performed by one-way analysis of variance, chi-square test, paired t-test, independent t-test and multiple linear regression. Before the intervention, two groups were homogeneous in terms of demographic variables, glycosylated hemoglobin (HbA1C), and other indicators of metabolic control. After the intervention, average HbA1C and other metabolic indicators except for LDL showed significant differences in the experimental group compared to the control group. study results indicated the positive effects of applying the empowerment model on the metabolic control indicators. Therefore, applying this model is recommended to nurses and the relevant authorities in order to improve clinical outcomes in diabetic patients. Copyright © 2015 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

Metabolic effects of resistance or high-intensity interval training among glycemic control-nonresponsive children with insulin resistance.

Science.gov (United States)

Álvarez, C; Ramírez-Campillo, R; Ramírez-Vélez, R; Martínez, C; Castro-Sepúlveda, M; Alonso-Martínez, A; Izquierdo, M

2018-01-01

Little evidence exists on which variables of body composition or muscular strength mediates more glucose control improvements taking into account inter-individual metabolic variability to different modes of exercise training. We examined 'mediators' to the effects of 6-weeks of resistance training (RT) or high-intensity interval training (HIT) on glucose control parameters in physically inactive schoolchildren with insulin resistance (IR). Second, we also determined both training-induce changes and the prevalence of responders (R) and non-responders (NR) to decrease the IR level. Fifty-six physically inactive children diagnosed with IR followed a RT or supervised HIT program for 6 weeks. Participants were classified based on ΔHOMA-IR into glycemic control R (decrease in homeostasis model assessment-IR (HOMA-IR) training-induced changes to glucose control parameters; and third the report of R and NR to improve body composition, cardiovascular, metabolic and performance variables. Mediation analysis revealed that improvements (decreases) in abdominal fat by the waist circumference can explain more the effects (decreases) of HOMA-IR in physically inactive schoolchildren under RT or HIT regimes. The same analysis showed that increased one-maximum repetition leg-extension was correlated with the change in HOMA-IR (β=-0.058; P=0.049). Furthermore, a change in the waist circumference fully mediated the dose-response relationship between changes in the leg-extension strength and HOMA-IR (β'=-0.004; P=0.178). RT or HIT were associated with significant improvements in body composition, muscular strength, blood pressure and cardiometabolic parameters irrespective of improvement in glycemic control response. Both glucose control RT-R and HIT-R (respectively), had significant improvements in mean HOMA-IR, mean muscular strength leg-extension and mean measures of adiposity. The improvements in the lower body strength and the decreases in waist circumference can explain more

Vitamin C improves basal metabolic rate and lipid profile in alloxan ...

Indian Academy of Sciences (India)

MADU

3.1 Effect of vitamin C administration on basal metabolic rate. The basal metabolic rate values in diabetic rats and control are presented in figure 1. The basal metabolic rate (BMR) in diabetic rats was 1.19 ± 0.15 ml/h/g, while the BMR in control rats was 0.76 ± 0.89 ml/h/g. The BMR value in diabetic rats treated with vitamin ...

Slave nodes and the controllability of metabolic networks

International Nuclear Information System (INIS)

Kim, Dong-Hee; Motter, Adilson E

2009-01-01

Recent work on synthetic rescues has shown that the targeted deletion of specific metabolic genes can often be used to rescue otherwise non-viable mutants. This raises a fundamental biophysical question: to what extent can the whole-cell behavior of a large metabolic network be controlled by constraining the flux of one or more reactions in the network? This touches upon the issue of the number of degrees of freedom contained by one such network. Using the metabolic network of Escherichia coli as a model system, here we address this question theoretically by exploring not only reaction deletions, but also a continuum of all possible reaction expression levels. We show that the behavior of the metabolic network can be largely manipulated by the pinned expression of a single reaction. In particular, a relevant fraction of the metabolic reactions exhibits canalizing interactions, in that the specification of one reaction flux determines cellular growth as well as the fluxes of most other reactions in optimal steady states. The activity of individual reactions can thus be used as surrogates to monitor and possibly control cellular growth and other whole-cell behaviors. In addition to its implications for the study of control processes, our methodology provides a new approach to study how the integrated dynamics of the entire metabolic network emerges from the coordinated behavior of its component parts.

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

Science.gov (United States)

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 (Pknowledge 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.

TORCing up metabolic control in the brain.

Science.gov (United States)

Hietakangas, Ville; Cohen, Stephen M

2008-05-01

Transducer of regulated CREB activity 2 (TORC2) is a coactivator of CREB and an important regulator of energy balance in mammals through control of gluconeogenesis in the liver. In this issue of Cell Metabolism, Wang and coworkers (2008) report an intriguing role for Drosophila TORC in the neuronal regulation of metabolism.

A combination of physical activity and computerized brain training improves verbal memory and increases cerebral glucose metabolism in the elderly.

Science.gov (United States)

Shah, T; Verdile, G; Sohrabi, H; Campbell, A; Putland, E; Cheetham, C; Dhaliwal, S; Weinborn, M; Maruff, P; Darby, D; Martins, R N

2014-12-02

Physical exercise interventions and cognitive training programs have individually been reported to improve cognition in the healthy elderly population; however, the clinical significance of using a combined approach is currently lacking. This study evaluated whether physical activity (PA), computerized cognitive training and/or a combination of both could improve cognition. In this nonrandomized study, 224 healthy community-dwelling older adults (60-85 years) were assigned to 16 weeks home-based PA (n=64), computerized cognitive stimulation (n=62), a combination of both (combined, n=51) or a control group (n=47). Cognition was assessed using the Rey Auditory Verbal Learning Test, Controlled Oral Word Association Test and the CogState computerized battery at baseline, 8 and 16 weeks post intervention. Physical fitness assessments were performed at all time points. A subset (total n=45) of participants underwent [(18)F] fluorodeoxyglucose positron emission tomography scans at 16 weeks (post-intervention). One hundred and ninety-one participants completed the study and the data of 172 participants were included in the final analysis. Compared with the control group, the combined group showed improved verbal episodic memory and significantly higher brain glucose metabolism in the left sensorimotor cortex after controlling for age, sex, premorbid IQ, apolipoprotein E (APOE) status and history of head injury. The higher cerebral glucose metabolism in this brain region was positively associated with improved verbal memory seen in the combined group only. Our study provides evidence that a specific combination of physical and mental exercises for 16 weeks can improve cognition and increase cerebral glucose metabolism in cognitively intact healthy older adults.

Metabolic control of female puberty: potential therapeutic targets.

Science.gov (United States)

Castellano, Juan M; Tena-Sempere, Manuel

2016-10-01

The onset of puberty in females is highly sensitive to the nutritional status and the amount of energy reserves of the organism. This metabolic information is sensed and transmitted to hypothalamic GnRH neurons, considered to be ultimately responsible for triggering puberty through the coordinated action of different peripheral hormones, central neurotransmitters, and molecular mediators. This article will review and discuss (i) the relevant actions of the adipose hormone leptin, as a stimulatory/permissive signal, and the gut hormone ghrelin, as an inhibitory factor, in the metabolic control of female puberty; (ii) the crucial role of the hypothalamic kisspeptin neurons, recently emerged as essential gatekeepers of puberty, in transmitting this metabolic information to GnRH neurons; and (iii) the potential involvement of key cellular energy sensors, such as mTOR, as molecular mediators in this setting. The thorough characterization of the physiological roles of the above elements in the metabolic control of female puberty, along with the discovery of novel factors, pathways, and mechanisms involved, will promote our understanding of the complex networks connecting metabolism and puberty and, ultimately, will aid in the design of target-specific treatments for female pubertal disorders linked to conditions of metabolic stress.

Role of metabolic control on diabetic nephropathy

Directory of Open Access Journals (Sweden)

Macedo Célia Sperandéo

2002-01-01

Full Text Available OBJECTIVE: The aim of this investigation was studying the influence of glucose metabolic control on diabetic nephropathy. The authors observed the effect of acarbose, insulin, and both drugs on the metabolic control and development of mesangial enlargement of kidney glomeruli in alloxan-diabetic rats. METHODS: Five groups of Wistar rats were used: normal rats (N, non-treated alloxan-diabetic rats (D, alloxan-diabetic rats treated with acarbose (AD, alloxan-diabetic rats treated with insulin (ID, and alloxan-diabetic rats treated with insulin plus acarbose (IAD. The following parameters were evaluated: body weight; water and food intake; diuresis; blood and urine glucose levels; and the kidney lesions: mesangial enlargement and tubule cell vacuolization. Renal lesions were analysed using a semi-quantitative score 1, 3, 6, 9, and 12 months after diabetes induction. RESULTS: Diabetic rats showed a marked increase of glycemia, urinary glucose levels, diuresis, water and food intake, and weight loss, while the treated diabetic rats showed significant decreased levels of these parameters. The most satisfactory metabolic control was that of diabetic rats treated with acarbose + insulin. There was a significant mesangial enlargement in diabetic rats compared to normal rats from the third up to the 12th month after diabetes induction, with a significant difference between the animals treated with acarbose + insulin and non-treated diabetic rats. A difference between the animals treated with acarbose or insulin alone and non-treated diabetics rats was not seen. CONCLUSIONS: The authors discuss the results stressing the role of diabetic metabolic control in the prevention of diabetic nephropathy.

[DiabeTIC website: a pilot study of satisfaction and impact on metabolic control].

Science.gov (United States)

Carral San Laureano, Florentino; Ayala Ortega, María del Carmen; Jiménez Millán, Ana Isabel; Piñero Zaldivar, Antonia; García Calzado, Concepción; Prieto Ferrón, Matilde; Silva Rodríguez, Juan José

2013-10-01

To evaluate satisfaction and short-term impact on metabolic control of diabetes monitoring through the DiabeTIC website. A prospective, uncontrolled intervention study was conducted in 32 patients aged 29.7±9.7 years (65% female) incorporated to the telemedicine platform DiabeTIC between March and September 2012. All patients completed a satisfaction questionnaire in the first month, and impact on metabolic control was evaluated at three and six months. In the satisfaction survey conducted in the first month of follow-up, the following mean scores (0-10) were obtained: overall impression with the platform: 8.6±1.8; ease of use: 8.1±1.5; intuitive navigation: 6.7±3.0; value of measurements: 9.1±1.1; importance of the platform in diabetes management: 9.5±0.9; sense of security: 9.5±0.8; value of the library: 9.4±1.1; value of messages: 9.1±1.4, and recommendation to use the platform: 9.4±0.9. Glycosilated hemoglobin concentrations significantly improved at six months as compared to study start (7.0±0.8 versus 8.1±1.9; p=0.007). Nine patients were discharged from DiabeTIC before completing six months of follow-up. Patients with diabetes monitored through the DiabeTIC website report a high degree of satisfaction, showing improved metabolic control at short-term follow-up. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

Effect of oral cinnamon intervention on metabolic profile and body composition of Asian Indians with metabolic syndrome: a randomized double -blind control trial.

Science.gov (United States)

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.

Invited review: Opportunities for genetic improvement of metabolic diseases.

Science.gov (United States)

Pryce, J E; Parker Gaddis, K L; Koeck, A; Bastin, C; Abdelsayed, M; Gengler, N; Miglior, F; Heringstad, B; Egger-Danner, C; Stock, K F; Bradley, A J; Cole, J B

2016-09-01

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 genetic evaluations were examined for (1) ketosis, (2) displaced abomasum, (3) milk fever, and (4) tetany, as these are the most prevalent metabolic diseases where published genetic parameters are available. The reported incidences of clinical cases of metabolic disorders are generally low (less than 10% of cows are recorded as having a metabolic disease per herd per year or parity/lactation). Heritability estimates are also low and are typically less than 5%. Genetic correlations between metabolic traits are mainly positive, indicating that selection to improve one of these diseases is likely to have a positive effect on the others. Furthermore, there may also be opportunities to select for general disease resistance in terms of metabolic stability. Although there is inconsistency in published genetic correlation estimates between milk yield and metabolic traits, selection for milk yield may be expected to lead to a deterioration in metabolic disorders. Under-recording and difficulty in diagnosing subclinical cases are among the reasons why interest is growing in using easily measurable predictors of metabolic diseases, either recorded on-farm by using sensors and milk tests or off-farm using data collected from routine milk recording. Some countries have already initiated genetic evaluations of metabolic disease traits and currently most of these use clinical observations of disease. However, there are opportunities to use clinical diseases in addition to predictor traits and genomic information to strengthen genetic evaluations for metabolic health in the future. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Controlling cell-free metabolism through physiochemical perturbations.

Science.gov (United States)

Karim, Ashty S; Heggestad, Jacob T; Crowe, Samantha A; Jewett, Michael C

2018-01-01

Building biosynthetic pathways and engineering metabolic reactions in cells can be time-consuming due to complexities in cellular metabolism. These complexities often convolute the combinatorial testing of biosynthetic pathway designs needed to define an optimal biosynthetic system. To simplify the optimization of biosynthetic systems, we recently reported a new cell-free framework for pathway construction and testing. In this framework, multiple crude-cell extracts are selectively enriched with individual pathway enzymes, which are then mixed to construct full biosynthetic pathways on the time scale of a day. This rapid approach to building pathways aids in the study of metabolic pathway performance by providing a unique freedom of design to modify and control biological systems for both fundamental and applied biotechnology. The goal of this work was to demonstrate the ability to probe biosynthetic pathway performance in our cell-free framework by perturbing physiochemical conditions, using n-butanol synthesis as a model. We carried out three unique case studies. First, we demonstrated the power of our cell-free approach to maximize biosynthesis yields by mapping physiochemical landscapes using a robotic liquid-handler. This allowed us to determine that NAD and CoA are the most important factors that govern cell-free n-butanol metabolism. Second, we compared metabolic profile differences between two different approaches for building pathways from enriched lysates, heterologous expression and cell-free protein synthesis. We discover that phosphate from PEP utilization, along with other physiochemical reagents, during cell-free protein synthesis-coupled, crude-lysate metabolic system operation inhibits optimal cell-free n-butanol metabolism. Third, we show that non-phosphorylated secondary energy substrates can be used to fuel cell-free protein synthesis and n-butanol biosynthesis. Taken together, our work highlights the ease of using cell-free systems to explore

Angiotensin-converting enzyme inhibition improves cardiac fatty acid metabolism in patients with congestive heart failure.

Science.gov (United States)

Yamauchi, S; Takeishi, Y; Minamihaba, O; Arimoto, T; Hirono, O; Takahashi, H; Miyamoto, T; Nitobe, J; Nozaki, N; Tachibana, H; Watanabe, T; Fukui, A; Kubota, I

2003-08-01

This study aimed to examine whether angiotensin-converting enzyme (ACE) inhibition improved cardiac fatty acid metabolism in patients with congestive heart failure (CHF). Myocardial 123I-beta-methyl-iodophenylpentadecanoic acid (123I-BMIPP) imaging was performed in 25 patients with CHF and in 10 control subjects. Myocardial 123I-BMIPP images were obtained 30 min and 4 h after tracer injection. The heart-to-mediastinum (H/M) ratio of 123I-BMIPP uptake and the washout rate of 123I-BMIPP from the myocardium were calculated. Patients were given enalapril for 6 months, and 123I-BMIPP imaging was repeated. H/M ratios on early and delayed images were lower in CHF patients than in normal controls (Pacid metabolism by ACE inhibition may represent a new mechanism for the beneficial effect of this therapy in heart failure.

alpha-Ketoglutarate application in hemodialysis patients improves amino acid metabolism.

Science.gov (United States)

Riedel, E; Nündel, M; Hampl, H

1996-01-01

In hemodialysis patients, free amino acids and alpha-ketoacids in plasma were determined by fluorescence HPLC to assess the effect of alpha-ketoglutarate administration in combination with the phosphate binder calcium carbonate on the amino acid metabolism. During 1 year of therapy in parallel to inorganic phosphate, urea in plasma decreased significantly, histidine, arginine and proline as well as branched chain alpha-ketoacids, in particular alpha-ketoisocaproate, a regulator of protein metabolism, increased. Thus, administration of alpha-ketoglutarate with calcium carbonate effectively improves amino acid metabolism in hemodialysis patients as it decreases hyperphosphatemia.

Sleep and metabolic control: waking to a problem?

Science.gov (United States)

Trenell, Michael I; Marshall, Nathaniel S; Rogers, Naomi L

2007-01-01

1. The aim of the present review is to outline: (i) the association between sleep and metabolism; (ii) how sleep duration influences the development of disease; and (iii) how sex differences, ageing and obesity may potentially influence the relationship between sleep, metabolic control and subsequent disease. 2. Sleep is associated with a number of endocrine changes, including a change in insulin action in healthy young individuals. Sleep duration shows a prospective U-shaped relationship with all-cause mortality, cardiovascular disease and Type 2 diabetes. 3. Chronic sleep restriction is becoming more common. Experimental sleep restriction impedes daytime glucose control and increases appetite. 4. The sex hormones oestrogen and testosterone influence sleep duration and quality and may account for sex differences in the prevalence of sleep-related disorders. 5. Ageing is associated with a decreased sleep duration, decreased muscle mass and impaired insulin action. 6. Obesity impairs insulin action and is associated with the incidence and severity of obstructive sleep apnoea. 7. Sleep plays an integral role in metabolic control. Consequently, insufficient sleep may represent a modifiable risk factor for the development of Type 2 diabetes. The challenge ahead is to identify how sex differences, ageing and obesity could potentially influence the relationship between sleep and metabolism.

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.

Science.gov (United States)

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 pistachios leads to beneficial effects on the cardiometabolic profile of Asian Indians with metabolic syndrome. Copyright © 2014 Elsevier Inc. All rights reserved.

Eating patterns in adolescents with type 1 diabetes: Associations with metabolic control, insulin omission, and eating disorder pathology.

Science.gov (United States)

Wisting, Line; Reas, Deborah Lynn; Bang, Lasse; Skrivarhaug, Torild; Dahl-Jørgensen, Knut; Rø, Øyvind

2017-07-01

The purpose of this study was to investigate eating patterns among male and female adolescents with type 1 diabetes (T1D), and the associations with age, zBMI, eating disorder (ED) pathology, intentional insulin omission, and metabolic control. The sample consisted of 104 adolescents (58.6% females) with child-onset T1D, mean age of 15.7 years (SD 1.8) and mean zBMI of 0.4 (SD 0.8). The Child Eating Disorder Examination (ChEDE) assessed meal/snack frequency and ED pathology. T1D clinical data was obtained from the Norwegian Childhood Diabetes Registry. A significantly lower proportion of females than males (73.8% vs 97.7%) consumed breakfast on a daily basis. Approximately 50% of both genders ate lunch and 90% ate dinner daily. Among females, skipping breakfast was significantly associated with higher global ED psychopathology, shape concerns, self-induced vomiting, binge eating, insulin omission due to shape/weight concerns, and poorer metabolic control. Less frequent lunch consumption was significantly associated with poorer metabolic control. Skipping dinner was significantly associated with older age, higher dietary restraint, eating concerns, self-induced vomiting, and insulin omission. Among males, less frequent consumption of lunch and evening snacks was associated with attitudinal features of ED, including shape/weight concerns and dietary restraint. Among adolescents with T1D, irregular or infrequent meal consumption appears to signal potential ED pathology, as well as being associated with poorer metabolic control. These findings suggest the importance of routinely assessing eating patterns in adolescents with T1D to improve detection of ED pathology and to facilitate improved metabolic control and the associated risk of somatic complications. Copyright © 2017 Elsevier Ltd. All rights reserved.

Targeting Adipose Tissue Lipid Metabolism to Improve Glucose Metabolism in Cardiometabolic Disease

Directory of Open Access Journals (Sweden)

Johan W.E. Jocken

2014-10-01

Full Text Available With Type 2 diabetes mellitus and cardiovascular disease prevalence on the rise, there is a growing need for improved strategies to prevent or treat obesity and insulin resistance, both of which are major risk factors for these chronic diseases. Impairments in adipose tissue lipid metabolism seem to play a critical role in these disorders. In the classical picture of intracellular lipid breakdown, cytosolic lipolysis was proposed as the sole mechanism for triacylglycerol hydrolysis in adipocytes. Recent evidence suggests involvement of several hormones, membrane receptors, and intracellular signalling cascades, which has added complexity to the regulation of cytosolic lipolysis. Interestingly, a specific form of autophagy, called lipophagy, has been implicated as alternative lipolytic pathway. Defective regulation of cytosolic lipolysis and lipophagy might have substantial effects on lipid metabolism, thereby contributing to adipose tissue dysfunction, insulin resistance, and related cardiometabolic (cMet diseases. This review will discuss recent advances in our understanding of classical lipolysis and lipophagy in adipocyte lipid metabolism under normal and pathological conditions. Furthermore, the question of whether modulation of adipocyte lipolysis and lipophagy might be a potential therapeutic target to combat cMet disorders will be addressed.

Effects of testosterone treatment on glucose metabolism and symptoms in men with type 2 diabetes and the metabolic syndrome: a systematic review and meta-analysis of randomized controlled clinical trials.

Science.gov (United States)

Grossmann, Mathis; Hoermann, Rudolf; Wittert, Gary; Yeap, Bu B

2015-09-01

The effects of testosterone treatment on glucose metabolism and other outcomes in men with type 2 diabetes (T2D) and/or the metabolic syndrome are controversial. To perform a systematic review and meta-analysis of placebo-controlled double-blind randomized controlled clinical trials (RCT) of testosterone treatment in men with T2D and/or the metabolic syndrome. A systematic search of RCTs was conducted using Medline, Embase and the Cochrane Register of controlled trials from inception to July 2014 followed by a manual review of the literature. Eligible studies were published placebo-controlled double-blind RCTs published in English. Two reviewers independently selected studies, determined study quality and extracted outcome and descriptive data. Of the 112 identified studies, seven RCTs including 833 men were eligible for the meta-analysis. In studies using a simple linear equation to calculate the homeostatic model assessment of insulin resistance (HOMA1), testosterone treatment modestly improved insulin resistance, compared to placebo, pooled mean difference (MD) -1·58 [-2·25, -0·91], P treatment effect was nonsignificant for RCTs using a more stringent computer-based equation (HOMA2), MD -0·19 [-0·86, 0·49], P = 0·58). Testosterone treatment did not improve glycaemic (HbA1c) control, MD -0·15 [-0·39, 0·10], P = 0·25, or constitutional symptoms, Aging Male Symptom score, MD -2·49 [-5·81, 0·83], P = 0·14). This meta-analysis does not support the routine use of testosterone treatment in men with T2D and/or the metabolic syndrome without classical hypogonadism. Additional studies are needed to determine whether hormonal interventions are warranted in selected men with T2D and/or the metabolic syndrome. © 2014 John Wiley & Sons Ltd.

A Controlled Trial of CPAP Therapy on Metabolic Control in Individuals with Impaired Glucose Tolerance and Sleep Apnea

Science.gov (United States)

Weinstock, Tanya G.; Wang, Xuelei; Rueschman, Michael; Ismail-Beigi, Faramarz; Aylor, Joan; Babineau, Denise C.; Mehra, Reena; Redline, Susan

2012-01-01

Study Objectives: To address whether treatment of sleep apnea improves glucose tolerance. Design: Randomized, double-blind crossover study. Setting: Sleep clinic referrals. Patients: 50 subjects with moderate to severe sleep apnea (AHI > 15) and impaired glucose tolerance. Interventions: Subjects were randomized to 8 weeks of CPAP or sham CPAP, followed by the alternate therapy after a one-month washout. After each treatment, subjects underwent 2-hour OGTT, polysomnography, actigraphy, and measurements of indices of glucose control. Measurements and Results: The primary outcome was normalization of the mean 2-h OGTT; a secondary outcome was improvement in the Insulin Sensitivity Index (ISI (0,120). Subjects were 42% men, mean age of 54 (10), BMI of 39 (8), and AHI of 44 (27). Baseline fasting glucose was 104 (12), and mean 2-h OGTT was 110 (57) mg/dL. Seven subjects normalized their mean 2-h OGTT after CPAP but not after sham CPAP, while 5 subjects normalized after sham CPAP but not after CPAP. Overall, there was no improvement in ISI (0,120) between CPAP and sham CPAP (3.6%; 95% CI: [-2.2%, 9.7%]; P = 0.22). However, in those subjects with baseline AHI ≥ 30 (n = 25), there was a 13.3% (95% CI: [5.2%, 22.1%]; P CPAP compared to sham CPAP. Conclusions: This study did not show that IGT normalizes after CPAP in subjects with moderate sleep apnea and obesity. However, insulin sensitivity improved in those with AHI ≥ 30, suggesting beneficial metabolic effects of CPAP in severe sleep apnea. Clinical Trials Information: ClinicalTrials.gov Identifier: NCT01385995. Citation: Weinstock TG; Wang X; Rueschman M; Ismail-Beigi F; Aylor J; Babineau DC; Mehra R; Redline S. A controlled trial of CPAP therapy on metabolic control in individuals with impaired glucose tolerance and sleep apnea. SLEEP 2012;35(5):617-625. PMID:22547887

Exercise, Obesity and CNS Control of Metabolic Homeostasis: A Review

Science.gov (United States)

Smith, John K.

2018-01-01

This review details the manner in which the central nervous system regulates metabolic homeostasis in normal weight and obese rodents and humans. It includes a review of the homeostatic contributions of neurons located in the hypothalamus, the midbrain and limbic structures, the pons and the medullary area postrema, nucleus tractus solitarius, and vagus nucleus, and details how these brain regions respond to circulating levels of orexigenic hormones, such as ghrelin, and anorexigenic hormones, such as glucagon-like peptide 1 and leptin. It provides an insight as to how high intensity exercise may improve homeostatic control in overweight and obese subjects. Finally, it provides suggestions as to how further progress can be made in controlling the current pandemic of obesity and diabetes.

NRG1-Fc improves metabolic health via dual hepatic and central action.

Science.gov (United States)

Zhang, Peng; Kuang, Henry; He, Yanlin; Idiga, Sharon O; Li, Siming; Chen, Zhimin; Yang, Zhao; Cai, Xing; Zhang, Kezhong; Potthoff, Matthew J; Xu, Yong; Lin, Jiandie D

2018-03-08

Neuregulins (NRGs) are emerging as an important family of signaling ligands that regulate glucose and lipid homeostasis. NRG1 lowers blood glucose levels in obese mice, whereas the brown fat-enriched secreted factor NRG4 protects mice from high-fat diet-induced insulin resistance and hepatic steatosis. However, the therapeutic potential of NRGs remains elusive, given the poor plasma half-life of the native ligands. Here, we engineered a fusion protein using human NRG1 and the Fc domain of human IgG1 (NRG1-Fc) that exhibited extended half-life in circulation and improved potency in receptor signaling. We evaluated its efficacy in improving metabolic parameters and dissected the mechanisms of action. NRG1-Fc treatment triggered potent AKT activation in the liver, lowered blood glucose, improved insulin sensitivity, and suppressed food intake in obese mice. NRG1-Fc acted as a potent secretagogue for the metabolic hormone FGF21; however, the latter was largely dispensable for its metabolic effects. NRG1-Fc directly targeted the hypothalamic POMC neurons to promote membrane depolarization and increase firing rate. Together, NRG1-Fc exhibits improved pharmacokinetic properties and exerts metabolic benefits through dual inhibition of hepatic gluconeogenesis and caloric intake.

Improved cerebral energetics and ketone body metabolism in db/db mice

DEFF Research Database (Denmark)

Andersen, Jens V; Christensen, Sofie K; Nissen, Jakob D

2017-01-01

It is becoming evident that type 2 diabetes mellitus is affecting brain energy metabolism. The importance of alternative substrates for the brain in type 2 diabetes mellitus is poorly understood. The aim of this study was to investigate whether ketone bodies are relevant candidates to compensate...... metabolism in type 2 diabetes mellitus. The increased hippocampal ketone body utilization and improved mitochondrial function in db/db mice, may act as adaptive mechanisms in order to maintain cerebral energetics during hampered glucose metabolism....

Comparing metabolic control and complications in type 2 diabetes in two Pacific Islands at baseline and following diabetes care intervention

Directory of Open Access Journals (Sweden)

Si Thu Win Tin

2016-06-01

Conclusions: This study indicates improved metabolic control but little change in diabetes complications 15 months after intervention. Efforts to improve and evaluate the ongoing quality and accessibility of diabetes care in Pacific Island settings need to be further strengthened.

Dynamic optimal metabolic control theory: a cybernetic approach for modelling of the central nitrogen metabolism of S. cerevisiae

NARCIS (Netherlands)

Riel, van N.A.W.; Giuseppin, M.L.F.; Verrips, C.T.

2000-01-01

The theory of dynamic optimal metabolic control (DOMC), as developed by Giuseppin and Van Riel (Metab. Eng., 2000), is applied to model the central nitrogen metabolism (CNM) in Saccharomyces cerevisiae. The CNM represents a typical system encountered in advanced metabolic engineering. The CNM is the

Low-Volume High-Intensity Interval Training in a Gym Setting Improves Cardio-Metabolic and Psychological Health.

Directory of Open Access Journals (Sweden)

Sam O Shepherd

Full Text Available Within a controlled laboratory environment, high-intensity interval training (HIT elicits similar cardiovascular and metabolic benefits as traditional moderate-intensity continuous training (MICT. It is currently unclear how HIT can be applied effectively in a real-world environment.To investigate the hypothesis that 10 weeks of HIT, performed in an instructor-led, group-based gym setting, elicits improvements in aerobic capacity (VO2max, cardio-metabolic risk and psychological health which are comparable to MICT.Ninety physically inactive volunteers (42±11 y, 27.7±4.8 kg.m-2 were randomly assigned to HIT or MICT group exercise classes. HIT consisted of repeated sprints (15-60 seconds, >90% HRmax interspersed with periods of recovery cycling (≤25 min.session-1, 3 sessions.week-1. MICT participants performed continuous cycling (~70% HRmax, 30-45 min.session-1, 5 sessions.week-1. VO2max, markers of cardio-metabolic risk, and psychological health were assessed pre and post-intervention.Mean weekly training time was 55±10 (HIT and 128±44 min (MICT (p<0.05, with greater adherence to HIT (83±14% vs. 61±15% prescribed sessions attended, respectively; p<0.05. HIT improved VO2max, insulin sensitivity, reduced abdominal fat mass, and induced favourable changes in blood lipids (p<0.05. HIT also induced beneficial effects on health perceptions, positive and negative affect, and subjective vitality (p<0.05. No difference between HIT and MICT was seen for any of these variables.HIT performed in a real-world gym setting improves cardio-metabolic risk factors and psychological health in physically inactive adults. With a reduced time commitment and greater adherence than MICT, HIT offers a viable and effective exercise strategy to target the growing incidence of metabolic disease and psychological ill-being associated with physical inactivity.

Low-Volume High-Intensity Interval Training in a Gym Setting Improves Cardio-Metabolic and Psychological Health.

Science.gov (United States)

Shepherd, Sam O; Wilson, Oliver J; Taylor, Alexandra S; Thøgersen-Ntoumani, Cecilie; Adlan, Ahmed M; Wagenmakers, Anton J M; Shaw, Christopher S

2015-01-01

Within a controlled laboratory environment, high-intensity interval training (HIT) elicits similar cardiovascular and metabolic benefits as traditional moderate-intensity continuous training (MICT). It is currently unclear how HIT can be applied effectively in a real-world environment. To investigate the hypothesis that 10 weeks of HIT, performed in an instructor-led, group-based gym setting, elicits improvements in aerobic capacity (VO2max), cardio-metabolic risk and psychological health which are comparable to MICT. Ninety physically inactive volunteers (42±11 y, 27.7±4.8 kg.m-2) were randomly assigned to HIT or MICT group exercise classes. HIT consisted of repeated sprints (15-60 seconds, >90% HRmax) interspersed with periods of recovery cycling (≤25 min.session-1, 3 sessions.week-1). MICT participants performed continuous cycling (~70% HRmax, 30-45 min.session-1, 5 sessions.week-1). VO2max, markers of cardio-metabolic risk, and psychological health were assessed pre and post-intervention. Mean weekly training time was 55±10 (HIT) and 128±44 min (MICT) (pHIT (83±14% vs. 61±15% prescribed sessions attended, respectively; pHIT improved VO2max, insulin sensitivity, reduced abdominal fat mass, and induced favourable changes in blood lipids (pHIT also induced beneficial effects on health perceptions, positive and negative affect, and subjective vitality (pHIT and MICT was seen for any of these variables. HIT performed in a real-world gym setting improves cardio-metabolic risk factors and psychological health in physically inactive adults. With a reduced time commitment and greater adherence than MICT, HIT offers a viable and effective exercise strategy to target the growing incidence of metabolic disease and psychological ill-being associated with physical inactivity.

Unique attributes of cyanobacterial metabolism revealed by improved genome-scale metabolic modeling and essential gene analysis

Science.gov (United States)

Broddrick, Jared T.; Rubin, Benjamin E.; Welkie, David G.; Du, Niu; Mih, Nathan; Diamond, Spencer; Lee, Jenny J.; Golden, Susan S.; Palsson, Bernhard O.

2016-01-01

The model cyanobacterium, Synechococcus elongatus PCC 7942, is a genetically tractable obligate phototroph that is being developed for the bioproduction of high-value chemicals. Genome-scale models (GEMs) have been successfully used to assess and engineer cellular metabolism; however, GEMs of phototrophic metabolism have been limited by the lack of experimental datasets for model validation and the challenges of incorporating photon uptake. Here, we develop a GEM of metabolism in S. elongatus using random barcode transposon site sequencing (RB-TnSeq) essential gene and physiological data specific to photoautotrophic metabolism. The model explicitly describes photon absorption and accounts for shading, resulting in the characteristic linear growth curve of photoautotrophs. GEM predictions of gene essentiality were compared with data obtained from recent dense-transposon mutagenesis experiments. This dataset allowed major improvements to the accuracy of the model. Furthermore, discrepancies between GEM predictions and the in vivo dataset revealed biological characteristics, such as the importance of a truncated, linear TCA pathway, low flux toward amino acid synthesis from photorespiration, and knowledge gaps within nucleotide metabolism. Coupling of strong experimental support and photoautotrophic modeling methods thus resulted in a highly accurate model of S. elongatus metabolism that highlights previously unknown areas of S. elongatus biology. PMID:27911809

Effects of lifestyle intervention using patient-centered cognitive behavioral therapy among patients with cardio-metabolic syndrome: a randomized, controlled trial.

Science.gov (United States)

Zhang, Ying; Mei, Songli; Yang, Rui; Chen, Ling; Gao, Hang; Li, Li

2016-11-18

Cardio-metabolic syndrome (CMS) is a highly prevalent condition. There is an urgent need to identify effective and integrated multi-disciplinary approaches that can reduce risk factors for CMS. Sixty-two patients with a history of CMS were randomized 1:1 into two groups: a standard information -only group (control), or a self-regulated lifestyle waist circumference (patient-centered cognitive behavioral therapy) intervention group. A pretest and posttest, controlled, experimental design was used. Outcomes were measured at the baseline (week 0) and at the end of intervention (week 12). Comparisons were drawn between groups and over time. The mean (standard deviation) age of the subjects was 48.6 (5.8) years ranging from 32 to 63, and 56.9% of the participants were female. Both groups showed no significant differences in Demographic variables and the metabolic syndrome indicators at baseline. While the control group only showed modest improvement after 12 weeks, compared to baseline, the intervention group demonstrated significant improvement from baseline. This study controlled for patients' demographics and baseline characteristics when assessing the effects of intervention. After adjusting for age, education and baseline level, the experimental group and the control group were statistically significant different in the following post-treatment outcomes: WC (F = 35.96, P cognitive behavioral therapy can improve the physical and mental health conditions among individuals reporting a history of cardio-metabolic syndrome, and possibly provided preliminary benefits for the treatment of CMS. Chinese Clinical Trial Register #, ChiCTR15006148 .

Geniposide regulates glucose-stimulated insulin secretion possibly through controlling glucose metabolism in INS-1 cells.

Directory of Open Access Journals (Sweden)

Jianhui Liu

Full Text Available Glucose-stimulated insulin secretion (GSIS is essential to the control of metabolic fuel homeostasis. The impairment of GSIS is a key element of β-cell failure and one of causes of type 2 diabetes mellitus (T2DM. Although the KATP channel-dependent mechanism of GSIS has been broadly accepted for several decades, it does not fully describe the effects of glucose on insulin secretion. Emerging evidence has suggested that other mechanisms are involved. The present study demonstrated that geniposide enhanced GSIS in response to the stimulation of low or moderately high concentrations of glucose, and promoted glucose uptake and intracellular ATP levels in INS-1 cells. However, in the presence of a high concentration of glucose, geniposide exerted a contrary role on both GSIS and glucose uptake and metabolism. Furthermore, geniposide improved the impairment of GSIS in INS-1 cells challenged with a high concentration of glucose. Further experiments showed that geniposide modulated pyruvate carboxylase expression and the production of intermediates of glucose metabolism. The data collectively suggest that geniposide has potential to prevent or improve the impairment of insulin secretion in β-cells challenged with high concentrations of glucose, likely through pyruvate carboxylase mediated glucose metabolism in β-cells.

Improving metabolic monitoring in patients maintained on antipsychotics in Penang, Malaysia.

Science.gov (United States)

Hor, Esther Sl; Subramaniam, Sivasangari; Koay, Jun Min; Bharathy, Arokiamary; Vasudevan, Umadevi; Panickulam, Joseph J; Ng, InnTiong; Arif, Nor Hayati; Russell, Vincent

2016-02-01

To evaluate the monitoring of metabolic parameters among outpatients maintained on antipsychotic medications in a general hospital setting in Malaysia and to assess the impact of a local monitoring protocol. By performing a baseline audit of files from a random sample of 300 patients prescribed antipsychotic medications for at least 1 year; we determined the frequency of metabolic monitoring. The findings informed the design of a new local protocol, on which clinical staff was briefed. We re-evaluated metabolic monitoring immediately after implementation, in a small sample of new referrals and current patients. We explored staff perceptions of the initiative with a follow-up focus group, 6 months post-implementation. The baseline audit revealed a sub-optimal frequency of metabolic parameter recording. Re-audit, following implementation of the new protocol, revealed improved monitoring but persisting deficits. Dialogue with the clinical staff led to further protocol modification, clearer definition of staff roles and use of a standard recording template. Focus group findings revealed positive perceptions of the initiative, but persisting implementation barriers, including cultural issues surrounding waist circumference measurement. Responding to challenges in achieving improved routine metabolic monitoring of patients maintained on antipsychotics required on-going dialogue with the clinical staff, in order to address both service pressures and cultural concerns. © The Royal Australian and New Zealand College of Psychiatrists 2015.

Metabolic and improved organ scan studies. III. 13N-ammonia metabolic studies in hepatic encephalopathy

International Nuclear Information System (INIS)

Anon.

1976-01-01

Results are reported from an investigation into the nature of hepatic encephalopathy, through study of the uptake and metabolism of 13 N-labeled ammonia by the brain in relation to liver function, in order to develop improved methods for the management of patients with this condition

Eicosapentaenoic acid improves glycemic control in elderly bedridden patients with type 2 diabetes.

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Ogawa, Susumu; Abe, Takaaki; Nako, Kazuhiro; Okamura, Masashi; Senda, Miho; Sakamoto, Takuya; Ito, Sadayoshi

2013-01-01

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are ω3-polyunsaturated fatty acids mainly contained in the blue-backed fish oil, and are effective in decreasing the lipids disorder and the cardiovascular incidence among diabetic patients. Moreover, it has been suggested that EPA and DHA may improve the insulin resistance and glucose metabolism. However, the clinical effects of EPA and DHA on glucose metabolism remain unclear. We aimed to clarify the effects of EPA/DHA treatment on glycemic control in type 2 diabetes mellitus. This study was a multicenter prospective randomized controlled trial involving 30 elderly type 2 diabetic patients on a liquid diet. Their exercises were almost zero and the content of their meals was strictly managed and understood well. Therefore, the difference by the individual's life was a minimum. The subjects were divided into two groups: those receiving EPA/DHA-rich liquid diet [EPA/DHA (+)] or liquid diet lacking EPA/DHA [EPA/DHA (-)]. Changes in factors related to glucose and lipid metabolism were assessed after the three-month study. Serum concentrations of EPA rose in EPA/DHA (+), although the levels of DHA and fasting C-peptide remained unchanged in EPA/DHA (+). In addition, there was a significant decline in the fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), fasting remnant-like particles and apolipoprotein (apo) B in EPA/DHA (+), compared with the values in EPA/DHA (-). EPA/DHA-rich diet might improve glucose metabolism in elderly type 2 diabetic patients on a liquid diet. This phenomenon may be due to the improved insulin resistance mediated by the rise in serum EPA concentrations.

Treatment with soy isoflavones during early adulthood improves metabolism in early postnatally overfed rats.

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Silva, Pamelli; Ribeiro, Tatiane Aparecida; Tófolo, Laize Peron; Prates, Kelly Valério; Francisco, Flávio Andrade; Silveira, Sandra da Silva; Malta, Ananda; Lopes, Denise Alves; Miranda, Rosiane Aparecida; Palma-Rigo, Kesia; Torrezan, Rosana; Mathias, Paulo Cezar de Freitas

2018-01-01

The incidences of obesity and related diseases have reached epidemic proportions, and new therapeutic approaches are needed. Soy isoflavones have been identified as an important dietary factor for preventing and treating metabolic dysfunction. This study examined the effects of high doses of isoflavone on glucose and fat metabolism in a model of programmed obesity and evaluated its effects on the autonomic nervous system. Litters of Wistar rats were standardized at nine pups per dam in normal litters (NL) or reduced to three pups per dam at the third day of life (P3) in small litters (SL) to induce postnatal overfeeding. Gavage with a soy bean isoflavone mixture (1 g/day) diluted in water was started at P60 and continued for 30 days. The control animals received vehicle gavage. At P90, biometric and metabolic parameters as well as direct autonomic nerve activity were measured. Increases in glycaemia and insulinaemia observed in SL rats were reduced by isoflavone treatment, which also caused lower glucose-induced insulin secretion by pancreatic islets. Sympathetic activity in the major splanchnic nerve was increased, while vagus nerve activity was reduced by isoflavone treatment. The dyslipidaemia induced by overfeeding in SL rats was restored by isoflavone treatment. The present study shows that treatment with isoflavone reduces adiposity and improves glucose and lipid metabolism. Collectively, these effects may depend on autonomic changes.

Metabolic Control and Illness Perceptions in Adolescents with Type 1 Diabetes

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Line Wisting

2016-01-01

Full Text Available Background. Disturbed eating behavior and psychosocial variables have been found to influence metabolic control, but little is known about how these variables interact or how they influence metabolic control, separately and combined. Objective. To explore associations between metabolic control (measured by HbA1c and eating disorder psychopathology, coping strategies, illness perceptions, and insulin beliefs in adolescents with type 1 diabetes. Methods. A total of 105 patients (41.9% males with type 1 diabetes (12–20 years were interviewed with the Child Eating Disorder Examination. In addition, self-report psychosocial questionnaires were completed. Clinical data, including HbA1c, was obtained from the Norwegian Childhood Diabetes Registry. Results. Significant gender differences were demonstrated. Among females, HbA1c correlated significantly with eating restriction (.29, p < .05, the illness perception dimensions consequences, personal control, coherence, and concern (ranging from .33 to .48, and the coping strategy ventilating negative feelings (−.26, p < .05. Illness perception personal control contributed significantly to HbA1c in a regression model, explaining 23% of the variance among females (β .48, p < .001. None of the variables were significantly associated with HbA1c among males. Conclusions. Illness perceptions appear to be important contributors to metabolic control in females, but not males, with type 1 diabetes.

Periodontal treatment to improve glycaemic control in diabetic patients: study protocol of the randomized, controlled DIAPERIO trial.

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Vergnes, Jean-Noel; Arrivé, Elise; Gourdy, Pierre; Hanaire, Hélène; Rigalleau, Vincent; Gin, Henri; Sédarat, Cyril; Dorignac, Georges; Bou, Christophe; Sixou, Michel; Nabet, Cathy

2009-08-02

Periodontitis is a common, chronic inflammatory disease caused by gram-negative bacteria leading to destruction of tissues supporting the teeth. Epidemiological studies have consistently shown increased frequency, extent and severity of periodontitis among diabetic adults. More recently, some controlled clinical trials have also suggested that periodontal treatment could improve glycaemic control in diabetic patients. However current evidence does not provide sufficient information on which to confidently base any clinical recommendations. The main objective of this clinical trial is to assess whether periodontal treatment could lead to a decrease in glycated haemoglobin levels in metabolically unbalanced diabetic patients suffering from chronic periodontitis. The DIAPERIO trial is an open-label, 13-week follow-up, randomized, controlled trial. The total target sample size is planned at 150 participants, with a balanced (1:1) treatment allocation (immediate treatment vs delayed treatment). Periodontal treatment will include full mouth non-surgical scaling and root planing, systemic antibiotherapy, local antiseptics (chlorhexidine 0.12%) and oral health instructions. The primary outcome will be the difference in change of HbA1c between the two groups after the 13-weeks' follow-up. Secondary outcomes will be the difference in change of fructosamine levels and quality of life between the two groups. The DIAPERIO trial will provide insight into the question of whether periodontal treatment could lead to an improvement in glycaemic control in metabolically unbalanced diabetic patients suffering from periodontitis. The results of this trial will help to provide evidence-based recommendations for clinicians and a draft framework for designing national health policies. Current Controlled Trials ISRCTN15334496.

Roles for Orexin/Hypocretin in the Control of Energy Balance and Metabolism.

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Goforth, Paulette B; Myers, Martin G

The neuropeptide hypocretin is also commonly referred to as orexin, since its orexigenic action was recognized early. Orexin/hypocretin (OX) neurons project widely throughout the brain and the physiologic and behavioral functions of OX are much more complex than initially conceived based upon the stimulation of feeding. OX most notably controls functions relevant to attention, alertness, and motivation. OX also plays multiple crucial roles in the control of food intake, metabolism, and overall energy balance in mammals. OX signaling not only promotes food-seeking behavior upon short-term fasting to increase food intake and defend body weight, but, conversely, OX signaling also supports energy expenditure to protect against obesity. Furthermore, OX modulates the autonomic nervous system to control glucose metabolism, including during the response to hypoglycemia. Consistently, a variety of nutritional cues (including the hormones leptin and ghrelin) and metabolites (e.g., glucose, amino acids) control OX neurons. In this chapter, we review the control of OX neurons by nutritional/metabolic cues, along with our current understanding of the mechanisms by which OX and OX neurons contribute to the control of energy balance and metabolism.

Heart over mind: metabolic control of white adipose tissue and liver.

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Nakamura, Michinari; Sadoshima, Junichi

2014-12-01

Increasing evidence suggests that the heart controls the metabolism of peripheral organs. Olson and colleagues previously demonstrated that miR‐208a controls systemic energy homeostasis through the regulation of MED13 in cardiomyocytes (Grueter et al, 2012). In their follow‐up study in this issue of EMBO Molecular Medicine, white adipose tissue (WAT) and liver are identified as the physiological targets of cardiac MED13 signaling, most likely through cardiac‐derived circulating factors, which boost energy consumption by upregulating metabolic gene expression and increasing mitochondrial numbers (Baskin et al, 2014). In turn, increased energy expenditure in WAT and the liver confers leanness. These findings strengthen the evidence of metabolic crosstalk between the heart and peripheral tissues through cardiokines and also set the stage for the development of novel treatments for metabolic syndrome.

The Effects of Mindfulness-Based Interventions on Diabetes-Related Distress, Quality of Life, and Metabolic Control Among Persons with Diabetes: A Meta-Analytic Review.

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Bogusch, Leah M; O'Brien, William H

2018-04-04

Mindfulness-based interventions (MBIs) have improved psychological outcomes for multiple chronic health conditions, including diabetes. A meta-analytic review of the literature was conducted on all located studies (n = 14) investigating MBIs that targeted diabetes-related distress (DRD) and diabetes-related outcomes among people with Type 1 and Type 2 diabetes. PsychInfo, PubMed, Medline, and Web of Science were searched for MBIs that were designed to improve DRD and other secondary outcomes, including quality of life and measures of metabolic control. A meta-analysis of these outcomes uncovered small-to-moderate effect sizes for intervention studies measuring pretreatment to posttreatment changes in DRD and metabolic control among treatment group participants. However, the pretreatment to follow-up comparisons for DRD and metabolic control were small and unreliable. For control groups, all pre-treatment to post-treatment and pre-treatment to follow-up comparisons were unreliable for all outcomes. A moderate effect size for treatment-control comparisons was found for intervention studies measuring quality of life outcomes at posttreatment, but not at follow-up comparisons. All other effect sizes for treatment-control comparisons were unreliable. Limitations and implications for MBIs among individuals with diabetes are discussed.

Significance of family and peer support for metabolic control of type 1 diabetes in adolescents

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Đurović Dušanka

2009-01-01

Full Text Available The aim of the paper was to explore the significance of family and peer support for metabolic control of Type 1 diabetes in adolescents. Metabolic control refers to maintenance of acceptable blood glucose level thus diminishing risk for chronic complications. It involves regular insulin shots, measuring blood glucose and keeping diary, as the daily based self-control. Regular visits to endocrinologist and screening for chronic complications are compulsory. The sample comprised 79 adolescents age 10-17 years with diagnose of Type 1 diabetes and properly treated at the institute. The sample was divided in two groups - with good (N=40 and poor (N=39 metabolic control. A criterium for good metabolic control was glycosilated hemoglobin less than 7,6%. Social support was measured by Social Support Scale consisting of two parts - the first for estimation of registered family support (based upon modified Perceived Social Support Family Scale and the second for estimation of registered friends' support (modified Perceived Social Support Friend Scale. Adolescents with good metabolic control referred statistically more significant social support in the family, unlike the group with poor metabolic control. Considering peer social support, there was no statistically significant difference. Positive family history for diabetes also appeared to be directly linked to good metabolic control.

Metabolic control of puberty: roles of leptin and kisspeptins.

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Sanchez-Garrido, Miguel A; Tena-Sempere, Manuel

2013-07-01

This article is part of a Special Issue "Puberty and Adolescence". Reproduction is an energy-demanding function. Accordingly, puberty is metabolically gated, as a means to prevent fertility in conditions of energy insufficiency. In addition, obesity has been shown to impact the timing of puberty and may be among the causes for the earlier trends of pubertal age reported in various countries. The metabolic control of puberty in such a spectrum of situations, ranging from energy deficit to extreme overweight, is the result of the concerted action of different peripheral hormones and central transmitters that sense the metabolic state of the organism and transmit this information to the various elements of the reproductive axis, mainly the GnRH neurons. Among the peripheral signals involved, the adipose hormone, leptin, is known to play an essential role in the regulation of puberty, especially in females. Yet, although it is clear that the effects of leptin on puberty onset are predominantly permissive and mainly conducted at central (hypothalamic) levels, the primary sites and mechanisms of action of leptin within the reproductive brain remain unsolved. In this context, neurons expressing kisspeptins, the products of the Kiss1 gene that have emerged recently as essential upstream regulators of GnRH neurons, operate as key sensors of the metabolic state and funnel of the reproductive effects of leptin. Yet, much debate has arisen recently on whether the putative actions of leptin on the Kiss1 system are actually indirect and/or may primarily target Kiss1-independent pathways, such as those originating from the ventral premmamilary nucleus. Moreover, evidence has been presented for extra-hypothalamic or peripheral actions of leptin, including direct gonadal effects, which may contribute to the metabolic control of reproduction in extreme body weight conditions. In this work, we will critically review the experimental evidence supporting a role of leptin, kisspeptin

Effects of rosiglitazone on metabolic parameters and large artery sclerosis in nondiabetic patients with metabolic sydrome

International Nuclear Information System (INIS)

Shen Zhenhai; Lu Yun; Feng Yinbo; Jin Xian

2010-01-01

Objective: To observe the effects of rosiglitazone on metabolic parameters, carotid intimamedia thickness (IMT), brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI) in nondiabetic patients with metabolic syndrome. Methods: Seventy-nine nondiabetic patients with metabolic syndrome were randomly divided into treatment group (n = 41) and control group (n = 38). The patients in treatment group were treated with rosiglitazone on the basis of life-style intervention, those in control group were treated with life-style intervention for 9 months. All patients were followed up every 3 months. Body mass index (BMI) ,waist circumference(WC), systolic blood pressure (SBP), diastolic blood pressure(DBP), fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), highdendity lipoprotein (HDL-C), Low-density lipoprotein (LDL), high sensitivity C-reactive protein (hsCRP), HbA 1 C, fasting insulin (FIns), HOMA-IR, IMT, baPWV and ABI were measured in both groups before treatment and at the 6th, 9th month after treatment. Results: (1) After treatment with rosiglitazone for 6 months, FPG, TG, HDL-C, hsC RP, HbA 1 C, Fins and HOMA-IR in treatment group were improved (P 1 C, Fins and HOMA-IR got further improvement at the 9th month after treatment (P 1 C, Fins and HOMA-IR were changed significantly in treatment group compared to those in control group (P 1 C and HOMA-IR was independently related to the improvement of ABI by multivarient analysis. Conclusion: In nondiabetic patients with metabolic syndrome, rosiglitazone can significantly improve insulin resistance, correct metabolic disorders, has anti-inflammatory effect and retard atherosclerosis at some extent. (authors)

Transcriptional switches in the control of macronutrient metabolism.

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Wise, Alan

2008-06-01

This review shows how some transcription factors respond to alterations in macronutrients. Carbohydrates induce enzymes for their metabolism and fatty acid synthesis. Fatty acids reduce carbohydrate processing, induce enzymes for their metabolism, and increase both gluconeogenesis and storage of fat. Fat stores help control carbohydrate uptake by other cells. The following main transcription factors are discussed: carbohydrate response element-binding protein; sterol regulatory element-binding protein-1c, cyclic AMP response element-binding protein, peroxisome proliferator-activated receptor-alpha, and peroxisome proliferator-activated receptor-gamma.

[Metabolic parameters in patients with steatosis non alcoholic liver and controlled diabetes type 2 versus uncontrolled diabetes type 2].

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Miranda Manrique, Gonzalo

2016-01-01

Non-alcoholic fatty liver (NASH) is widely distributed around the world and is more common in subjects with dyslipidemia, metabolic syndrome obese and DM2 (34-74%). However, the prevalence of cirrhosis by NASH in general population is unknown which is still subject of research. To determine if there are significant differences between metabolic parameters of non-alcoholic fatty liver in controlled versus uncontrolled diabetes type 2 of recent diagnosis. retrospective case-control study, performed in the Hospital Guillermo Almenara Irigoyen, Lima, Peru from November 2014 to February 2015.This study included 231 patients: 147 patients (NASH with DM2 of recent diagnosis and poor control) and 84 patients (NASH with DM2 ofrecent diagnosis and adequate control). Levene test for evaluating homogeneity of variances intra groups and parametric test for independent samples. After applying Levene test of homogeneity and student test, significant metabolic parameters were the triglycerides, HbA1C level, metformin dose and gender. It is important in diabetic patients to diagnose NASH early for a tighter control, not only of glucose but other metabolic parameters mainly triglycerides which strongly supports existing concept of "multiple hits" which considers NASH affects glucose homeostasis, and it could be the starting point of new research to improve interventions for decreasing progression from to cirrhosis in diabetic patients and also to delay progression of diabetes mellitus in patients with non alcoholic steatohepatitis.

Engineering Mycorrhizal Symbioses to Alter Plant Metabolism and Improve Crop Health

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Katherine E. French

2017-07-01

Full Text Available Creating sustainable bioeconomies for the 21st century relies on optimizing the use of biological resources to improve agricultural productivity and create new products. Arbuscular mycorrhizae (phylum Glomeromycota form symbiotic relationships with over 80% of vascular plants. In return for carbon, these fungi improve plant health and tolerance to environmental stress. This symbiosis is over 400 million years old and there are currently over 200 known arbuscular mycorrhizae, with dozens of new species described annually. Metagenomic sequencing of native soil communities, from species-rich meadows to mangroves, suggests biologically diverse habitats support a variety of mycorrhizal species with potential agricultural, medical, and biotechnological applications. This review looks at the effect of mycorrhizae on plant metabolism and how we can harness this symbiosis to improve crop health. I will first describe the mechanisms that underlie this symbiosis and what physiological, metabolic, and environmental factors trigger these plant-fungal relationships. These include mycorrhizal manipulation of host genetic expression, host mitochondrial and plastid proliferation, and increased production of terpenoids and jasmonic acid by the host plant. I will then discuss the effects of mycorrhizae on plant root and foliar secondary metabolism. I subsequently outline how mycorrhizae induce three key benefits in crops: defense against pathogen and herbivore attack, drought resistance, and heavy metal tolerance. I conclude with an overview of current efforts to harness mycorrhizal diversity to improve crop health through customized inoculum. I argue future research should embrace synthetic biology to create mycorrhizal chasses with improved symbiotic abilities and potentially novel functions to improve plant health. As the effects of climate change and anthropogenic disturbance increase, the global diversity of arbuscular mycorrhizal fungi should be monitored

Metabolomics reveals that vine tea (Ampelopsis grossedentata prevents high-fat-diet-induced metabolism disorder by improving glucose homeostasis in rats.

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Wenting Wan

Full Text Available Vine tea (VT, derived from Ampelopsis grossedentata (Hand.-Mazz. W.T. Wang, is an alternative tea that has been consumed widely in south China for hundreds of years. It has been shown that drinking VT on a daily basis improves hyperlipidemia and hyperglycemia. However, little is known about the preventive functions of VT for metabolic dysregulation and the potential pathological mechanisms involved. This paper elucidates the preventive effects of VT on the dysregulation of lipid and glucose metabolism using rats maintained on a high-fat-diet (HFD in an attempt to explain the potential mechanisms involved.Sprague Dawley (SD rats were divided into five groups: a group given normal rat chow and water (control group; a group given an HFD and water (HFD group; a group given an HFD and Pioglitazone (PIO group, 5 mg /kg; and groups given an HFD and one of two doses of VT: 500 mg/L or 2000 mg/L. After 8 weeks, changes in food intake, tea consumption, body weight, serum and hepatic biochemical parameters were determined. Moreover, liver samples were isolated for pathology histology and liquid chromatography-mass spectrometry (LC-MS-based metabolomic research.VT reduced the serum levels of glucose and total cholesterol, decreased glucose area under the curve in the insulin tolerance test and visibly impaired hepatic lipid accumulation. Metabolomics showed that VT treatment modulated the contents of metabolic intermediates linked to glucose metabolism (including gluconeogenesis and glycolysis, the TCA cycle, purine metabolism and amino acid metabolism.The current results demonstrate that VT may prevent metabolic impairments induced by the consumption of an HFD. These effects may be caused by improved energy-related metabolism (including gluconeogenesis, glycolysis and TCA cycle, purine metabolism and amino acid metabolism, and reduced lipid levels in the HFD-fed rats.

Modified metabolic syndrome and second cancers in women: A case control study.

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Ortiz-Mendoza, Carlos-Manuel; Pérez-Chávez, Ernesto; Fuente-Vera, Tania-Angélica De-la

2016-01-01

According to some studies, the metabolic syndrome causes diverse primary cancers; however, there is no evidence about metabolic syndrome impact on second cancers development in women. To find out the implication of the modified metabolic syndrome in women with second cancers. This was a case-control study, at a general hospital in Mexico City, in women with second cancers (cases) and age-matched women with only one neoplasm (controls). The analysis comprised: Tumor (s), anthropometric features, and body mass index (BMI); moreover, presence of diabetes mellitus, hypertension, and fasting serum levels of total cholesterol, triglycerides and glucose. The sample was of nine cases and 27 controls. In cases, the metabolic syndrome (diabetes mellitus or glucose > 99 mg/dL + hypertension or blood pressure ≥ 135/85 mm Hg + triglycerides > 149 mg/dL or BMI ≥ 30 kg/m 2 ) was more frequent (odds ratio 20.8, 95% confidence interval: 1.9-227.1). Our results suggest that in women, the modified metabolic syndrome may be a risk factor for second cancers.

Modified metabolic syndrome and second cancers in women: A case control study

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Carlos-Manuel Ortiz-Mendoza

2016-01-01

Full Text Available Background: According to some studies, the metabolic syndrome causes diverse primary cancers; however, there is no evidence about metabolic syndrome impact on second cancers development in women. Aim: To find out the implication of the modified metabolic syndrome in women with second cancers. Materials and Methods: This was a case-control study, at a general hospital in Mexico City, in women with second cancers (cases and age-matched women with only one neoplasm (controls. The analysis comprised: Tumor (s, anthropometric features, and body mass index (BMI; moreover, presence of diabetes mellitus, hypertension, and fasting serum levels of total cholesterol, triglycerides and glucose. Results: The sample was of nine cases and 27 controls. In cases, the metabolic syndrome (diabetes mellitus or glucose > 99 mg/dL + hypertension or blood pressure ≥ 135/85 mm Hg + triglycerides > 149 mg/dL or BMI ≥ 30 kg/m 2 was more frequent (odds ratio 20.8, 95% confidence interval: 1.9-227.1. Conclusion: Our results suggest that in women, the modified metabolic syndrome may be a risk factor for second cancers.

Sense and nonsense in metabolic control of reproduction.

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Schneider, Jill E; Klingerman, Candice M; Abdulhay, Amir

2012-01-01

An exciting synergistic interaction occurs among researchers working at the interface of reproductive biology and energy homeostasis. Reproductive biologists benefit from the theories, experimental designs, and methodologies used by experts on energy homeostasis while they bring context and meaning to the study of energy homeostasis. There is a growing recognition that identification of candidate genes for obesity is little more than meaningless reductionism unless those genes and their expression are placed in a developmental, environmental, and evolutionary context. Reproductive biology provides this context because metabolic energy is the most important factor that controls reproductive success and gonadal hormones affect energy intake, storage, and expenditure. Reproductive hormone secretion changes during development, and reproductive success is key to evolutionary adaptation, the process that most likely molded the mechanisms that control energy balance. It is likely that by viewing energy intake, storage, and expenditure in the context of reproductive success, we will gain insight into human obesity, eating disorders, diabetes, and other pathologies related to fuel homeostasis. This review emphasizes the metabolic hypothesis: a sensory system monitors the availability of oxidizable metabolic fuels and orchestrates behavioral motivation to optimize reproductive success in environments where energy availability fluctuates or is unpredictable.

The impact of electronic education on metabolic control indicators in patients with diabetes who need insulin: a randomised clinical control trial.

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Moattari, Marzieh; Hashemi, Maryam; Dabbaghmanesh, Mohammad H

2013-01-01

To determine the impact of electronic education on metabolic control indicators in patients with diabetes who were insulin dependent. Education can play an important role in controlling diabetes. Electronic (web-based, telehealth) education may be an efficient way to improve the patients' ability to control this disease. Randomised clinical control study. The participants in this clinical study were 48 insulin-dependent patients referred to diabetes centres in Shiraz, Iran. Serum concentrations of haemoglobin A(1C) , fasting blood sugar, triglycerides and high-density and low-density lipoprotein cholesterol were measured. Then the participants were divided randomly into control and experimental groups (n = 24). Participants in the experimental group received a specially designed electronic education programme for twelve weeks. The main components of the programme were a consultation service, quick answers to patients' questions, contact with the healthcare team and educational materials. At the end of the intervention period, all serum values were measured again in both groups. The data were compared using spss v 13·5 software. Serum concentrations of haemoglobin A(1C) (p education programme was useful in lowering two metabolic indicators of diabetes. Electronic education can be associated with increased health and patient satisfaction, and can eliminate the need to train personnel. © 2012 Blackwell Publishing Ltd.

Metabolic gene polymorphism frequencies in control populations

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Garte, Seymour; Gaspari, Laura; Alexandrie, Anna-Karin

2001-01-01

Using the International Project on Genetic Susceptibility to Environmental Carcinogens (GSEC) database containing information on over 15,000 control (noncancer) subjects, the allele and genotype frequencies for many of the more commonly studied metabolic genes (CYP1A1, CYP2E1, CYP2D6, GSTM1, GSTT1...

Improved evidence-based genome-scale metabolic models for maize leaf, embryo, and endosperm

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Seaver, Samuel M. D.; Bradbury, Louis M. T.; Frelin, Océane; Zarecki, Raphy; Ruppin, Eytan; Hanson, Andrew D.; Henry, Christopher S.

2015-03-10

There is a growing demand for genome-scale metabolic reconstructions for plants, fueled by the need to understand the metabolic basis of crop yield and by progress in genome and transcriptome sequencing. Methods are also required to enable the interpretation of plant transcriptome data to study how cellular metabolic activity varies under different growth conditions or even within different organs, tissues, and developmental stages. Such methods depend extensively on the accuracy with which genes have been mapped to the biochemical reactions in the plant metabolic pathways. Errors in these mappings lead to metabolic reconstructions with an inflated number of reactions and possible generation of unreliable metabolic phenotype predictions. Here we introduce a new evidence-based genome-scale metabolic reconstruction of maize, with significant improvements in the quality of the gene-reaction associations included within our model. We also present a new approach for applying our model to predict active metabolic genes based on transcriptome data. This method includes a minimal set of reactions associated with low expression genes to enable activity of a maximum number of reactions associated with high expression genes. We apply this method to construct an organ-specific model for the maize leaf, and tissue specific models for maize embryo and endosperm cells. We validate our models using fluxomics data for the endosperm and embryo, demonstrating an improved capacity of our models to fit the available fluxomics data. All models are publicly available via the DOE Systems Biology Knowledgebase and PlantSEED, and our new method is generally applicable for analysis transcript profiles from any plant, paving the way for further in silico studies with a wide variety of plant genomes.

Will acarbose improve the metabolic abnormalities of insulin-resistant type 2 diabetes mellitus?

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Scott, R; Lintott, C J; Zimmet, P; Campbell, L; Bowen, K; Welborn, T

1999-03-01

Individuals with type 2 diabetes mellitus (n = 105; age 36-71 years) on diet therapy alone, and with quite good glycaemic control (mean HbA1c approximately 7.0%) were randomized to receive acarbose (100 mg three times daily) or placebo for 16 weeks, and changes in clinical and metabolic parameters indicative of Syndrome X were monitored. Fasting levels of glucose, glycosylated haemoglobin (HbA1c), true insulin, proinsulin, fibrinogen and lipids were measured four times weekly, and glucose, insulin, proinsulin and triglyceride responses to a standardized 1.6 MJ breakfast were determined at 0, 1 and 2 h post meal. Analysis was on an intention-to-treat basis. Fasting levels of glucose (P fasting glucose and triglyceride levels, lowers HbA1c and limits the glycaemic and insulin response to food in individuals with type 2 diabetes mellitus with Syndrome X. Pharmacological agents that improve the metabolic environment and reduce insulin resistance have the potential to limit the progression of atherogenesis associated with type 2 diabetes mellitus.

Glucagon-Like Peptide 1 Recruits Muscle Microvasculature and Improves Insulin’s Metabolic Action in the Presence of Insulin Resistance

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Chai, Weidong; Zhang, Xingxing; Barrett, Eugene J.

2014-01-01

Glucagon-like peptide 1 (GLP-1) acutely recruits muscle microvasculature, increases muscle delivery of insulin, and enhances muscle use of glucose, independent of its effect on insulin secretion. To examine whether GLP-1 modulates muscle microvascular and metabolic insulin responses in the setting of insulin resistance, we assessed muscle microvascular blood volume (MBV), flow velocity, and blood flow in control insulin-sensitive rats and rats made insulin-resistant acutely (systemic lipid infusion) or chronically (high-fat diet [HFD]) before and after a euglycemic-hyperinsulinemic clamp (3 mU/kg/min) with or without superimposed systemic GLP-1 infusion. Insulin significantly recruited muscle microvasculature and addition of GLP-1 further expanded muscle MBV and increased insulin-mediated glucose disposal. GLP-1 infusion potently recruited muscle microvasculature in the presence of either acute or chronic insulin resistance by increasing muscle MBV. This was associated with an increased muscle delivery of insulin and muscle interstitial oxygen saturation. Muscle insulin sensitivity was completely restored in the presence of systemic lipid infusion and significantly improved in rats fed an HFD. We conclude that GLP-1 infusion potently expands muscle microvascular surface area and improves insulin’s metabolic action in the insulin-resistant states. This may contribute to improved glycemic control seen in diabetic patients receiving incretin-based therapy. PMID:24658303

Resveratrol Is Not as Effective as Physical Exercise for Improving Reproductive and Metabolic Functions in Rats with Dihydrotestosterone-Induced Polycystic Ovary Syndrome

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Anna Benrick

2013-01-01

Full Text Available Polycystic ovary syndrome (PCOS is a reproductive and metabolic disorder associated with obesity and insulin resistance that often precedes the development of type-2 diabetes. Rats continuously exposed to dihydrotestosterone from prepuberty display typical reproductive and metabolic PCOS characteristics including anovulation, polycystic ovaries, insulin resistance, and obesity. Our aim was to investigate if resveratrol improves reproductive and metabolic functions in PCOS rats. The effect was compared to exercise. Control and PCOS rats were treated with vehicle or resveratrol (400 mg · kg−1 · day−1 for 5-6 weeks. Another group of PCOS rats received vehicle treatment and exercised for 5-6 weeks. Insulin sensitivity was determined by euglycemic-hyperinsulinemic clamp. The glucose infusion rate was lower in the PCOS-vehicle group compared to control-vehicle rats (P<0.05. Exercise increased insulin sensitivity compared with PCOS-vehicle rats (P<0.05, but resveratrol did not. Resveratrol treatment and exercise resulted in smaller adipocytes, upregulated estrogen-related receptor α gene expression in subcutaneous fat, and improved estrus cyclicity in the previously acyclic PCOS rats. Although resveratrol had positive effects on adiposity and cyclicity in a similar manner to exercise, resveratrol does not seem to be a good candidate for treating insulin resistance associated with PCOS because no improvement in insulin sensitivity was observed in PCOS rats on normal chow.

Relationship between patients' perception of the importance of diabetes and metabolic control and pursuing chronic complications of disease

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Mohammad Ebrahim Khamseh

2011-04-01

Full Text Available Introduction: Type II diabetes is a metabolic disorder. Environmental factors and patient awareness have major roles on chronic complications. The purpose of this study was to determine the association of patients' perception of t the importance of diabetes and metabolic- control and pursuing of chronic complications. Material and Methods: 194 patients with diabetes enrolled from diabetes clinic of Institute Endocrinology & Metabolism in a cross-sectional study, from February to March 2010. Data were collected using a questionnaire to assess the personal demographics, individual approach in pursuit of complications, and glycemic control, as well as patient perception and attitude toward the importance of disease process and follow-up. Level of perceptions was determined as well, moderate and weak. Results: Out of 194 patients, 77(39.7% were male and 117(60.3% female. Mean age was 52.18±10.17years. 69.2% did not know what the glycosylated hemoglobin was. In 71.4%, willing to participate in decisions making on medical treatment was good and they knew that with initiation of insulin therapy, they would have better metabolic control. 68.9% of patients had regular follow-up for eye complications, and 51% for cardiac complications. Follow-up for diabetic foot complication was poor. Patients with good perception had regular follow-up regarding cardiac, eye and renal complications. Conclusion: These results indicate that better perception of diabetic patients might improve their compliance for regular follow- up regarding the pursuit of chronic complications, especially cardiac, eye and renal problems. Although, the metabolic- control of patients had not the association with patient perception about the importance of diabetes

Improved Triacylglycerol Production in Acinetobacter baylyi ADP1 by Metabolic Engineering

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Karp Matti

2011-05-01

Full Text Available Abstract Background Triacylglycerols are used in various purposes including food applications, cosmetics, oleochemicals and biofuels. Currently the main sources for triacylglycerol are vegetable oils, and microbial triacylglycerol has been suggested as an alternative for these. Due to the low production rates and yields of microbial processes, the role of metabolic engineering has become more significant. As a robust model organism for genetic and metabolic studies, and for the natural capability to produce triacylglycerol, Acinetobacter baylyi ADP1 serves as an excellent organism for modelling the effects of metabolic engineering for energy molecule biosynthesis. Results Beneficial gene deletions regarding triacylglycerol production were screened by computational means exploiting the metabolic model of ADP1. Four deletions, acr1, poxB, dgkA, and a triacylglycerol lipase were chosen to be studied experimentally both separately and concurrently by constructing a knock-out strain (MT with three of the deletions. Improvements in triacylglycerol production were observed: the strain MT produced 5.6 fold more triacylglycerol (mg/g cell dry weight compared to the wild type strain, and the proportion of triacylglycerol in total lipids was increased by 8-fold. Conclusions In silico predictions of beneficial gene deletions were verified experimentally. The chosen single and multiple gene deletions affected beneficially the natural triacylglycerol metabolism of A. baylyi ADP1. This study demonstrates the importance of single gene deletions in triacylglycerol metabolism, and proposes Acinetobacter sp. ADP1 as a model system for bioenergetic studies regarding metabolic engineering.

Detection of driver metabolites in the human liver metabolic network using structural controllability analysis

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2014-01-01

Background Abnormal states in human liver metabolism are major causes of human liver diseases ranging from hepatitis to hepatic tumor. The accumulation in relevant data makes it feasible to derive a large-scale human liver metabolic network (HLMN) and to discover important biological principles or drug-targets based on network analysis. Some studies have shown that interesting biological phenomenon and drug-targets could be discovered by applying structural controllability analysis (which is a newly prevailed concept in networks) to biological networks. The exploration on the connections between structural controllability theory and the HLMN could be used to uncover valuable information on the human liver metabolism from a fresh perspective. Results We applied structural controllability analysis to the HLMN and detected driver metabolites. The driver metabolites tend to have strong ability to influence the states of other metabolites and weak susceptibility to be influenced by the states of others. In addition, the metabolites were classified into three classes: critical, high-frequency and low-frequency driver metabolites. Among the identified 36 critical driver metabolites, 27 metabolites were found to be essential; the high-frequency driver metabolites tend to participate in different metabolic pathways, which are important in regulating the whole metabolic systems. Moreover, we explored some other possible connections between the structural controllability theory and the HLMN, and find that transport reactions and the environment play important roles in the human liver metabolism. Conclusion There are interesting connections between the structural controllability theory and the human liver metabolism: driver metabolites have essential biological functions; the crucial role of extracellular metabolites and transport reactions in controlling the HLMN highlights the importance of the environment in the health of human liver metabolism. PMID:24885538

Mitofusin 2 as a driver that controls energy metabolism and insulin signaling.

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Zorzano, Antonio; Hernández-Alvarez, María Isabel; Sebastián, David; Muñoz, Juan Pablo

2015-04-20

Mitochondrial dynamics is a complex process that impacts on mitochondrial biology. Recent evidence indicates that proteins participating in mitochondrial dynamics have additional cellular roles. Mitofusin 2 (Mfn2) is a potent modulator of mitochondrial metabolism with an impact on energy metabolism in muscle, liver, and hypothalamic neurons. In addition, Mfn2 is subjected to tight regulation. Hence, factors such as proinflammatory cytokines, lipid availability, or glucocorticoids block its expression, whereas exercise and increased energy expenditure promote its upregulation. Importantly, Mfn2 controls cell metabolism and insulin signaling by limiting reactive oxygen species production and by modulation of endoplasmic reticulum stress. In this connection, it is critical to understand precisely the molecular mechanisms involved in the global actions of Mfn2. Future directions should concentrate into the analysis of those mechanisms, and to fully demonstrate that Mfn2 represents a cellular hub that senses the metabolic and hormonal milieu and drives the control of metabolic homeostasis.

LA sprouts randomized controlled nutrition and gardening program reduces obesity and metabolic risk in Latino youth.

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Gatto, Nicole M; Martinez, Lauren C; Spruijt-Metz, Donna; Davis, Jaimie N

2015-06-01

To assess the effects of a 12-week gardening, nutrition, and cooking intervention ("LA Sprouts") on dietary intake, obesity parameters, and metabolic disease risk among low-income, primarily Hispanic/Latino youth in Los Angeles. The randomized controlled trial involved four elementary schools [two schools randomized to intervention (172 third-through fifth-grade students); two schools randomized to control (147 third-through fifth-grade students)]. Classes were taught in 90-minute sessions once a week to each grade level for 12 weeks. Data collected at pre- and postintervention included dietary intake via food frequency questionnaire (FFQ), anthropometric measures [BMI, waist circumference (WC)], body fat, and fasting blood samples. LA Sprouts participants had significantly greater reductions in BMI z-scores (0.1-vs. 0.04-point decrease, respectively; P = 0.01) and WC (-1.2 cm vs. no change; P < 0.001). Fewer LA Sprouts participants had the metabolic syndrome (MetSyn) after the intervention than before, while the number of controls with MetSyn increased. LA Sprouts participants had improvements in dietary fiber intake (+3.5% vs. -15.5%; P = 0.04) and less decreases in vegetable intake (-3.6% vs. -26.4%; P = 0.04). Change in fruit intake before and after the intervention did not significantly differ between LA Sprouts and control subjects. LA Sprouts was effective in reducing obesity and metabolic risk. © 2015 The Obesity Society.

Intraoperative bowel irrigation improves anastomotic collagen metabolism in the left-sided colonic obstruction but not covering colostomy.

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Duraker, N; Bender, O; Memişoğlu, K; Yalçiner, A

1998-01-01

This study investigated the effects of intraoperative colonic irrigation and proximal diverting end colostomy after segmental bowel resection in experimental left-colonic obstruction on anastomotic healing. Simple obstruction of descending colon was performed in male Sprague-Dawley rats. After 24 h we performed segmental colonic resection and anastomosis in the control group (n = 15); resection, anastomosis, and covering colostomy in the colostomy group (n = 14); resection and anastomosis after antegrade colonic lavage through cecum by using isotonic saline solution in the irrigation group (n = 13). In rats that were killed 7 days later anastomotic dehiscence and bursting pressure and tissue hydroxyproline concentration at the anastomosis were measured. No significant differences were observed between groups in terms of anastomotic dehiscence, bursting site, or pressure. The hydroxyproline concentration was significantly higher in the irrigation group than the control group (P = 0.025) and the colostomy group (P = 0.029), but no difference was noted between the control group and the colostomy group. These findings suggest that intraoperative antegrade colonic irrigation in the acute left-sided colonic obstruction positively affects collagen metabolism at the anastomotic site; if the anastomosis is performed without bowel cleansing, covering colostomy does not improve collagen metabolism.

Metabolic Surgery

DEFF Research Database (Denmark)

Pareek, Manan; Schauer, Philip R; Kaplan, Lee M

2018-01-01

The alarming rise in the worldwide prevalence of obesity is paralleled by an increasing burden of type 2 diabetes mellitus. Metabolic surgery is the most effective means of obtaining substantial and durable weight loss in individuals with obesity. Randomized trials have recently shown...... the superiority of surgery over medical treatment alone in achieving improved glycemic control, as well as a reduction in cardiovascular risk factors. The mechanisms seem to extend beyond the magnitude of weight loss alone and include improvements in incretin profiles, insulin secretion, and insulin sensitivity....... Moreover, observational data suggest that the reduction in cardiovascular risk factors translates to better patient outcomes. This review describes commonly used metabolic surgical procedures and their current indications and summarizes the evidence related to weight loss and glycemic outcomes. It further...

Alcohol decreases baseline brain glucose metabolism more in heavy drinkers than controls but has no effect on stimulation-induced metabolic increases

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Volkow, Nora D.; Fowler, Joanna S.; Wang, Gene-Jack; Kojori, Eshan Shokri; Benveniste, Helene; Tomasi, Dardo

2015-01-01

During alcohol intoxication the human brain increases metabolism of acetate and decreases metabolism of glucose as energy substrate. Here we hypothesized that chronic heavy drinking facilitates this energy substrate shift both for baseline and stimulation conditions. To test this hypothesis we compared the effects of alcohol intoxication (0.75g/kg alcohol versus placebo) on brain glucose metabolism during video-stimulation (VS) versus when given with no-stimulation (NS), in 25 heavy drinkers (HD) and 23 healthy controls each of whom underwent four PET- 18 FDG scans. We showed that resting whole-brain glucose metabolism (placebo-NS) was lower in HD than controls (13%, p=0.04); that alcohol (compared to placebo) decreased metabolism more in HD (20±13%) than controls (9±11%, p=0.005) and in proportion to daily alcohol consumption (r=0.36, p=0.01) but found that alcohol did not reduce the metabolic increases in visual cortex from VS in either group. Instead, VS reduced alcohol-induced decreases in whole-brain glucose metabolism (10±12%) compared to NS in both groups (15±13%, p=0.04), consistent with stimulation-related glucose metabolism enhancement. These findings corroborate our hypothesis that heavy alcohol consumption facilitates use of alternative energy substrates (i.e. acetate) for resting activity during intoxication, which might persist through early sobriety, but indicate that glucose is still favored as energy substrate during brain stimulation. Our findings are consistent with reduced reliance on glucose as the main energy substrate for resting brain metabolism during intoxication (presumably shifting to acetate or other ketones) and a priming of this shift in heavy drinkers, which might make them vulnerable to energy deficits during withdrawal

Alcohol decreases baseline brain glucose metabolism more in heavy drinkers than controls but has no effect on stimulation-induced metabolic increases.

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Volkow, Nora D; Wang, Gene-Jack; Shokri Kojori, Ehsan; Fowler, Joanna S; Benveniste, Helene; Tomasi, Dardo

2015-02-18

During alcohol intoxication, the human brain increases metabolism of acetate and decreases metabolism of glucose as energy substrate. Here we hypothesized that chronic heavy drinking facilitates this energy substrate shift both for baseline and stimulation conditions. To test this hypothesis, we compared the effects of alcohol intoxication (0.75 g/kg alcohol vs placebo) on brain glucose metabolism during video stimulation (VS) versus when given with no stimulation (NS), in 25 heavy drinkers (HDs) and 23 healthy controls, each of whom underwent four PET-(18)FDG scans. We showed that resting whole-brain glucose metabolism (placebo-NS) was lower in HD than controls (13%, p = 0.04); that alcohol (compared with placebo) decreased metabolism more in HD (20 ± 13%) than controls (9 ± 11%, p = 0.005) and in proportion to daily alcohol consumption (r = 0.36, p = 0.01) but found that alcohol did not reduce the metabolic increases in visual cortex from VS in either group. Instead, VS reduced alcohol-induced decreases in whole-brain glucose metabolism (10 ± 12%) compared with NS in both groups (15 ± 13%, p = 0.04), consistent with stimulation-related glucose metabolism enhancement. These findings corroborate our hypothesis that heavy alcohol consumption facilitates use of alternative energy substrates (i.e., acetate) for resting activity during intoxication, which might persist through early sobriety, but indicate that glucose is still favored as energy substrate during brain stimulation. Our findings are consistent with reduced reliance on glucose as the main energy substrate for resting brain metabolism during intoxication (presumably shifting to acetate or other ketones) and a priming of this shift in HDs, which might make them vulnerable to energy deficits during withdrawal. Copyright © 2015 the authors 0270-6474/15/353248-08$15.00/0.

Chronic Caloric Restriction and Exercise Improve Metabolic Conditions of Dietary-Induced Obese Mice in Autophagy Correlated Manner without Involving AMPK

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Mingxia Cui

2013-01-01

Full Text Available Aim. To investigate the role of AMPK activation and autophagy in mediating the beneficial effects of exercise and caloric restriction in obesity. Methods. Dietary-induced obesity mice were made and divided into 5 groups; one additional group of normal mice serves as control. Mice in each group received different combinations of interventions including low fat diet, caloric restriction, and exercise. Then their metabolic conditions were assessed by measuring serum glucose and insulin, serum lipids, and liver function. AMPK phosphorylation and autophagy activity were detected by western blotting. Results. Obese mice models were successfully induced by high fat diet. Caloric restriction consistently improved the metabolic conditions of the obese mice, and the effects are more prominent than the mice that received only exercise. Also, caloric restriction, exercise, and low fat diet showed a synergistic effect in the improvement of metabolic conditions. Western blotting results showed that this improvement was not related with the activation of AMPK in liver, skeletal muscle, or heart but correlates well with the autophagy activity. Conclusion. Caloric restriction has more prominent beneficial effects than exercise in dietary-induced obese mice. These effects are correlated with the autophagy activity and may be independent of AMPK activation.

Supplementation with apple enriched with L-arginine may improve metabolic control and survival rate in alloxan-induced diabetic rats.

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Escudero, Andrea; Petzold, Guillermo; Moreno, Jorge; Gonzalez, Marcelo; Junod, Julio; Aguayo, Claudio; Acurio, Jesenia; Escudero, Carlos

2013-01-01

Supplementation with L-arginine or fresh food with high content of this amino acid is associated with favorable effects in the metabolic control of diabetes. We aimed to determine whether supplementation with apples enriched with L-arginine offer additional benefits compared to L-arginine by itself in a preclinical study of diabetes. This study combines food-engineer technologies with in vivo and in vitro analysis. In vitro experiments show that cells derived from non-diabetic animals and exposed to high glucose (25 mM, 12 H) and cells isolated from alloxan-induced diabetic animals exhibited a reduction (∼50%) in the L-arginine uptake. This effect was reverted by L-arginine pretreatment (12 H) in both the normal and diabetes-derived cells. In preclinical studies, normoglycemic (n = 25) and diabetic groups (n = 50) were divided into subgroups that received either L-arginine (375 mg/kg per 10 days) or apple enriched with L-arginine or vehicle (control). In a preliminary analysis, supplementation with L-arginine by itself (50%) or apple enriched with L-arginine (100%) improve survival rate in the diabetic group compared to control (0%) at the end of the follow up (17 days). This phenomenon was associated with a partial but sustained high plasma level of L-arginine, as well as plasma concentration of nitrites and insulin in the L-arginine or apple + L-arginine groups after supplementation. Apple + L-arginine supplementation in diabetic animals induced the highest and longest effects in the level of these three markers among the studied groups. Therefore, apple enriched by L-arginine offers more benefits than L-arginine by itself in this preclinical study. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.

Metabolic control analysis of xylose catabolism in Aspergillus

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Prathumpai, W.; Gabelgaard, J.B.; Wanchanthuek, P.; Vondervoort, van de P.J.I.; Groot, de M.J.L.; McIntyre, M.; Nielsen, J.

2003-01-01

A kinetic model for xylose catabolism in Aspergillus is proposed. From a thermodynamic analysis it was found that the intermediate xylitol will accumulate during xylose catabolism. Use of the kinetic model allowed metabolic control analysis (MCA) of the xylose catabolic pathway to be carried out,

What Is the Best Blood Sampling Time for Metabolic Control of Phenylalanine and Tyrosine Concentrations in Tyrosinemia Type 1 Patients?

NARCIS (Netherlands)

van Dam, Esther; Daly, Anne; Venema-Liefaard, Gineke; van Rijn, Margreet; Derks, Terry G J; McKiernan, Patrick J; Heiner-Fokkema, Rebecca; MacDonald, Anita; van Spronsen, Francjan J

2017-01-01

BACKGROUND: Treatment of hereditary tyrosinemia type 1 with nitisinone and phenylalanine and tyrosine restricted diet has largely improved outcome, but the best blood sampling time for assessment of metabolic control is not known. AIM: To study diurnal and day-to-day variation of phenylalanine and

Polyphenols and IUGR pregnancies: Maternal hydroxytyrosol supplementation improves prenatal and early-postnatal growth and metabolism of the offspring.

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Marta Vazquez-Gomez

Full Text Available Hydroxytyrosol is a polyphenol with antioxidant, metabolism-regulatory, anti-inflammatory and immuno-modulatory properties. The present study aimed to determine whether supplementing the maternal diet with hydroxytyrosol during pregnancy can improve pre- and early post-natal developmental patterns and metabolic traits of the offspring. Experiment was performed in Iberian sows fed a restricted diet in order to increase the risk of IUGR. Ten sows were treated daily with 1.5 mg of hydroxytyrosol per kg of feed between Day 35 of pregnancy (30% of total gestational period until delivery whilst 10 animals were left untreated as controls. Number and weight of offspring were assessed at birth, on post-natal Day 15 and at weaning (25 days-old. At weaning, body composition and plasma indexes of glucose and lipids were measured. Treatment with hydroxytyrosol was associated with higher mean birth weight, lower incidence of piglets with low birth weight. Afterwards, during the lactation period, piglets in the treated group showed a higher body-weight than control piglets; such effects were even stronger in the most prolific litters. These results suggest that maternal supplementation with hydroxytyrosol may improve pre- and early post-natal development of offspring in pregnancies at risk of IUGR.

Altitude training improves glycemic control.

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Chen, Shu-Man; Lin, Hsueh-Yi; Kuo, Chia-Hua

2013-08-31

Under altitude hypoxia condition, energy reliance on anaerobic glycolysis increases to compensate the shortfall caused by reduced fatty acid oxidation. Short-term moderate altitude exposure plus endurance physical activity has been found to improve glucose tolerance (not fasting glucose) in humans, which is associated with the improvement in the whole-body insulin sensitivity. However, most of people cannot accommodate high altitude exposure above 4500 M due to acute mountain sickness and insulin resistance. There is a wide variation among individuals in response to the altitude challenge. In particular, the improvement in glucose tolerance and insulin sensitivity by prolonged altitude hiking activity was not apparent in those individuals with low baseline dehydroepiandrosterone sulfate (DHEA-S) concentration. In rats, exercise training recovery under prolonged hypoxia exposure (14-15% oxygen, 8 h per day for 6 weeks) can also improve insulin sensitivity, secondary to an effective suppression of adiposity. After prolonged hypoxia training, obese abnormality in upregulated baseline levels of AMP-activated protein kinase (AMPK) and AS160 phosphorylation in skeletal muscle can be reversed. In humans, moderate hypoxia increases postprandial blood distribution towards skeletal muscle during a training recovery. This physiological response plays a role in the redistribution of fuel storage among important energy storage sites and may explain its potent effect on the favorable change in body composition. Altitude training can exert strong impact on our metabolic system, and has the potential to be designed as a non-pharmacological or recreational intervention regimen for correcting metabolic syndromes.

Carbohydrate restriction improves the features of Metabolic Syndrome. Metabolic Syndrome may be defined by the response to carbohydrate restriction.

Science.gov (United States)

Volek, Jeff S; Feinman, Richard D

2005-11-16

surprising but has not been explicitly stated before. The known effects of CHO-induced hypertriglyceridemia, the HDL-lowering effect of low fat, high CHO interventions and the obvious improvement in glucose and insulin from CHO restriction should have made this evident. In addition, recent studies suggest that a subset of MetS, the ratio of TAG/HDL, is a good marker for insulin resistance and risk of CVD, and this indicator is reliably reduced by CHO restriction and exacerbated by high CHO intake. Inability to make this connection in the past has probably been due to the fact that individual responses have been studied in isolation as well as to the emphasis of traditional therapeutic approaches on low fat rather than low CHO. We emphasize that MetS is not a disease but a collection of markers. Individual physicians must decide whether high LDL, or other risk factors are more important than the features of MetS in any individual case but if MetS is to be considered it should be recognized that reducing CHO will bring improvement. Response of symptoms to CHO restriction might thus provide a new experimental criterion for MetS in the face of on-going controversy about a useful definition. As a guide to future research, the idea that control of insulin metabolism by CHO intake is, to a first approximation, the underlying mechanism in MetS is a testable hypothesis.

Carbohydrate restriction improves the features of Metabolic Syndrome. Metabolic Syndrome may be defined by the response to carbohydrate restriction

Directory of Open Access Journals (Sweden)

Feinman Richard D

2005-11-01

conclusion is probably not surprising but has not been explicitly stated before. The known effects of CHO-induced hypertriglyceridemia, the HDL-lowering effect of low fat, high CHO interventions and the obvious improvement in glucose and insulin from CHO restriction should have made this evident. In addition, recent studies suggest that a subset of MetS, the ratio of TAG/HDL, is a good marker for insulin resistance and risk of CVD, and this indicator is reliably reduced by CHO restriction and exacerbated by high CHO intake. Inability to make this connection in the past has probably been due to the fact that individual responses have been studied in isolation as well as to the emphasis of traditional therapeutic approaches on low fat rather than low CHO. We emphasize that MetS is not a disease but a collection of markers. Individual physicians must decide whether high LDL, or other risk factors are more important than the features of MetS in any individual case but if MetS is to be considered it should be recognized that reducing CHO will bring improvement. Response of symptoms to CHO restriction might thus provide a new experimental criterion for MetS in the face of on-going controversy about a useful definition. As a guide to future research, the idea that control of insulin metabolism by CHO intake is, to a first approximation, the underlying mechanism in MetS is a testable hypothesis.

Glucose administration after traumatic brain injury improves cerebral metabolism and reduces secondary neuronal injury.

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Moro, Nobuhiro; Ghavim, Sima; Harris, Neil G; Hovda, David A; Sutton, Richard L

2013-10-16

Clinical studies have indicated an association between acute hyperglycemia and poor outcomes in patients with traumatic brain injury (TBI), although optimal blood glucose levels needed to maximize outcomes for these patients' remain under investigation. Previous results from experimental animal models suggest that post-TBI hyperglycemia may be harmful, neutral, or beneficial. The current studies determined the effects of single or multiple episodes of acute hyperglycemia on cerebral glucose metabolism and neuronal injury in a rodent model of unilateral controlled cortical impact (CCI) injury. In Experiment 1, a single episode of hyperglycemia (50% glucose at 2 g/kg, i.p.) initiated immediately after CCI was found to significantly attenuate a TBI-induced depression of glucose metabolism in cerebral cortex (4 of 6 regions) and subcortical regions (2 of 7) as well as to significantly reduce the number of dead/dying neurons in cortex and hippocampus at 24 h post-CCI. Experiment 2 examined effects of more prolonged and intermittent hyperglycemia induced by glucose administrations (2 g/kg, i.p.) at 0, 1, 3 and 6h post-CCI. The latter study also found significantly improved cerebral metabolism (in 3 of 6 cortical and 3 of 7 subcortical regions) and significant neuroprotection in cortex and hippocampus 1 day after CCI and glucose administration. These results indicate that acute episodes of post-TBI hyperglycemia can be beneficial and are consistent with other recent studies showing benefits of providing exogenous energy substrates during periods of increased cerebral metabolic demand. © 2013 Elsevier B.V. All rights reserved.

Simvastatin-induced cardiac autonomic control improvement in fructose-fed female rats

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Renata Juliana da Silva

2011-01-01

Full Text Available OBJECTIVE: Because autonomic dysfunction has been found to lead to cardiometabolic disorders and because studies have reported that simvastatin treatment has neuroprotective effects, the objective of the present study was to investigate the effects of simvastatin treatment on cardiovascular and autonomic changes in fructose-fed female rats. METHODS: Female Wistar rats were divided into three groups: controls (n=8, fructose (n=8, and fructose+ simvastatin (n=8. Fructose overload was induced by supplementing the drinking water with fructose (100 mg/L, 18 wks. Simvastatin treatment (5 mg/kg/day for 2 wks was performed by gavage. The arterial pressure was recorded using a data acquisition system. Autonomic control was evaluated by pharmacological blockade. RESULTS: Fructose overload induced an increase in the fasting blood glucose and triglyceride levels and insulin resistance. The constant rate of glucose disappearance during the insulin intolerance test was reduced in the fructose group (3.4+ 0.32%/min relative to that in the control group (4.4+ 0.29%/min. Fructose+simvastatin rats exhibited increased insulin sensitivity (5.4+0.66%/min. The fructose and fructose+simvastatin groups demonstrated an increase in the mean arterial pressure compared with controls rats (fructose: 124+2 mmHg and fructose+simvastatin: 126 + 3 mmHg vs. controls: 112 + 2 mmHg. The sympathetic effect was enhanced in the fructose group (73 + 7 bpm compared with that in the control (48 + 7 bpm and fructose+simvastatin groups (31+8 bpm. The vagal effect was increased in fructose+simvastatin animals (84 + 7 bpm compared with that in control (49 + 9 bpm and fructose animals (46+5 bpm. CONCLUSION: Simvastatin treatment improved insulin sensitivity and cardiac autonomic control in an experimental model of metabolic syndrome in female rats. These effects were independent of the improvements in the classical plasma lipid profile and of reductions in arterial pressure. These results

Metabolic Adaptation to Muscle Ischemia

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Cabrera, Marco E.; Coon, Jennifer E.; Kalhan, Satish C.; Radhakrishnan, Krishnan; Saidel, Gerald M.; Stanley, William C.

2000-01-01

Although all tissues in the body can adapt to varying physiological/pathological conditions, muscle is the most adaptable. To understand the significance of cellular events and their role in controlling metabolic adaptations in complex physiological systems, it is necessary to link cellular and system levels by means of mechanistic computational models. The main objective of this work is to improve understanding of the regulation of energy metabolism during skeletal/cardiac muscle ischemia by combining in vivo experiments and quantitative models of metabolism. Our main focus is to investigate factors affecting lactate metabolism (e.g., NADH/NAD) and the inter-regulation between carbohydrate and fatty acid metabolism during a reduction in regional blood flow. A mechanistic mathematical model of energy metabolism has been developed to link cellular metabolic processes and their control mechanisms to tissue (skeletal muscle) and organ (heart) physiological responses. We applied this model to simulate the relationship between tissue oxygenation, redox state, and lactate metabolism in skeletal muscle. The model was validated using human data from published occlusion studies. Currently, we are investigating the difference in the responses to sudden vs. gradual onset ischemia in swine by combining in vivo experimental studies with computational models of myocardial energy metabolism during normal and ischemic conditions.

Integration of Environmental and Developmental (or Metabolic) Control of Seed Mass by Sugar and Ethylene Metabolisms in Arabidopsis.

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Meng, Lai-Sheng; Xu, Meng-Ke; Wan, Wen; Wang, Jing-Yi

2018-04-04

In higher plants, seed mass is an important to evolutionary fitness. In this context, seedling establishment positively correlates with seed mass under conditions of environmental stress. Thus, seed mass constitutes an important agricultural trait. Here, we show loss-of-function of YODA (YDA), a MAPKK Kinase, and decreased seed mass, which leads to susceptibility to drought. Furthermore, we demonstrate that yda disrupts sugar metabolisms but not the gaseous plant hormone, ethylene. Our data suggest that the transcription factor EIN3 (ETHYLENE-INSENSITIVE3), integral to both sugar and ethylene metabolisms, physically interacts with YDA. Further, ein3-1 mutants exhibited increased seed mass. Genetic analysis indicated that YDA and EIN3 were integral to a sugar-mediated metabolism cascade which regulates seed mass by maternally controlling embryo size. It is well established that ethylene metabolism leads to the suppression of drought tolerance by the EIN3 mediated inhibition of CBF1, a transcription factor required for the expression genes of abiotic stress. Our findings help guide the synthesis of a model predicting how sugar/ethylene metabolisms and environmental stress are integrated at EIN3 to control both the establishment of drought tolerance and the production of seed mass. Collectively, these insights into the molecular mechanism underpinning the regulation of plant seed size may aid prospective breeding or design strategies to increase crop yield.

Hematopoietic stem cell fate through metabolic control.

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Ito, Kyoko; Ito, Keisuke

2018-05-25

Hematopoietic stem cells (HSCs) maintain a quiescent state in the bone marrow to preserve their self-renewal capacity, but also undergo cell divisions as required. Organelles such as the mitochondria sustain cumulative damage during these cell divisions, and this damage may eventually compromise the cells' self-renewal capacity. HSC divisions result in either self-renewal or differentiation, with the balance between the two directly impacting hematopoietic homeostasis; but the heterogeneity of available HSC-enriched fractions, together with the technical challenges of observing HSC behavior, has long hindered the analysis of individual HSCs, and prevented the elucidation of this process. However, recent advances in genetic models, metabolomics analyses and single-cell approaches have revealed the contributions made to HSC self-renewal by metabolic cues, mitochondrial biogenesis, and autophagy/mitophagy, which have highlighted mitochondrial quality as a key control factor in the equilibrium of HSCs. A deeper understanding of precisely how specific modes of metabolism control HSC fate at the single cell level is therefore not only of great biological interest, but will have clear clinical implications for the development of therapies for hematological disease. Copyright © 2018. Published by Elsevier Inc.

Association between metabolic control and oral health in adolescents with type 1 diabetes mellitus.

Science.gov (United States)

Saes Busato, Ivana Maria; Bittencourt, Mônica Sommer; Machado, Maria Angela Naval; Grégio, Ana Maria Trindade; Azevedo-Alanis, Luciana Reis

2010-03-01

The aim of this study was to evaluate the association between metabolic control and oral health of adolescents with type 1 diabetes mellitus (DM1). A case-control epidemiologic study was performed on adolescents allocated between 2 groups: DM1 group composed of 51 with DM1, and control group composed of 51 without diabetes. In the DM1 group, metabolic control data were observed (glycosylated hemoglobin (GHb) and capillary glucose), whereby GHb 8.0% poor metabolic control (DM1-B). Oral mucosal abnormalites, Community Periodontal Index (CPI), and decayed, missing, and filled (DMF) index were documented. Salivary flow was evaluated by means of stimulated saliva collection (SSFR). Glycosylated hemoglobin values of 8.0% (DM1-B) in 34 (76%) of the subjects. The average DMF indexes were 1.5 (control) and 3.3 (DM1-group) (P < or = .05). The average CPIs were 0.2 (control), 1.4 (DM1-A), and 2.0 (DM1-B) (P < or = .05). Average SSFRs were 0.997 (DM1-A), 0.903 (DM1-B), and 1.224 (control) mL/min. Oral health of adolescents with DM1 was impaired regardless of metabolic control. Copyright 2010 Mosby, Inc. All rights reserved.

Hypothalamic control of energy metabolism via the autonomic nervous system

NARCIS (Netherlands)

Kalsbeek, A.; Bruinstroop, E.; Yi, C. X.; Klieverik, L. P.; La Fleur, S. E.; Fliers, E.

2010-01-01

The hypothalamic control of hepatic glucose production is an evident aspect of energy homeostasis. In addition to the control of glucose metabolism by the circadian timing system, the hypothalamus also serves as a key relay center for (humoral) feedback information from the periphery, with the

[Metabolic control in children and adolescents with type 1 diabetes].

Science.gov (United States)

Díaz-Cárdenas, Claudia; Wong, Carolina; Vargas Catalán, Nelson A

2016-01-01

Type 1 diabetes mellitus (T1D) is an important disease in children and adolescent being a major risk factor for early morbidity and mortality. To know the degree of metabolic control and prevalence of cardiovascular risk factors in T1D patients. Retrospective study including patients under 19 years of age with T1D controlled at a Chilean hospital in 2011. 94 patients were evaluated (average age at diagnosis: 7.3 years; current age: 11,9 years; evolution time: 4.5 years). Seventy-nine percent (79.8%) of patients presented glycated hemoglobin (HbA1c) over the recommended level with an average of 8.9%. The group between 13 and 19 years of age exhibited the worst metabolic control (86% with HbA1c abnormal levels). Overweight or obesity occurred in 26.6% of patients, 20.3% had LDL >100mg/dl and 4.2% had hypertension. Only about twenty percent of patients had adequate metabolic control as measured by HbA1c, although cardiovascular risk profile was acceptable. Therapeutic and educational efforts must be reinforced mainly in adolescents, emphasizing the importance of adequate nutritional management as a primary method to treat this entity. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

A dual control mechanism synchronizes riboflavin and sulphur metabolism in Bacillus subtilis

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Pedrolli, Danielle Biscaro; Kühm, Christian; Sévin, Daniel C.; Vockenhuber, Michael P.; Sauer, Uwe; Suess, Beatrix; Mack, Matthias

2015-01-01

Flavin mononucleotide (FMN) riboswitches are genetic elements, which in many bacteria control genes responsible for biosynthesis and/or transport of riboflavin (rib genes). Cytoplasmic riboflavin is rapidly and almost completely converted to FMN by flavokinases. When cytoplasmic levels of FMN are sufficient (“high levels”), FMN binding to FMN riboswitches leads to a reduction of rib gene expression. We report here that the protein RibR counteracts the FMN-induced “turn-off” activities of both FMN riboswitches in Bacillus subtilis, allowing rib gene expression even in the presence of high levels of FMN. The reason for this secondary metabolic control by RibR is to couple sulfur metabolism with riboflavin metabolism. PMID:26494285

Computational methods in metabolic engineering for strain design.

Science.gov (United States)

Long, Matthew R; Ong, Wai Kit; Reed, Jennifer L

2015-08-01

Metabolic engineering uses genetic approaches to control microbial metabolism to produce desired compounds. Computational tools can identify new biological routes to chemicals and the changes needed in host metabolism to improve chemical production. Recent computational efforts have focused on exploring what compounds can be made biologically using native, heterologous, and/or enzymes with broad specificity. Additionally, computational methods have been developed to suggest different types of genetic modifications (e.g. gene deletion/addition or up/down regulation), as well as suggest strategies meeting different criteria (e.g. high yield, high productivity, or substrate co-utilization). Strategies to improve the runtime performances have also been developed, which allow for more complex metabolic engineering strategies to be identified. Future incorporation of kinetic considerations will further improve strain design algorithms. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mitochondrial quality control pathways as determinants of metabolic health

NARCIS (Netherlands)

Held, Ntsiki M.; Houtkooper, Riekelt H.

2015-01-01

Mitochondrial function is key for maintaining cellular health, while mitochondrial failure is associated with various pathologies, including inherited metabolic disorders and age-related diseases. In order to maintain mitochondrial quality, several pathways of mitochondrial quality control have

Metabolic Control and Academic Achievement over Time among Adolescents with Type 1 Diabetes

Science.gov (United States)

Winnick, Joel B.; Berg, Cynthia A.; Wiebe, Deborah J.; Schaefer, Barbara A.; Lei, Pui-Wa; Butner, Jonathan E.

2017-01-01

The relation between metabolic control (HbA1c) and achievement (grade point average [GPA]) was examined over a period of 2.5 years (every 6 months) employing a dynamical systems approach that allowed for the examination of whether HbA1c was associated with change in subsequent GPA and vice versa. Metabolic control tends to deteriorate (i.e., with…

Liraglutide Improves Hypertension and Metabolic Perturbation in a Rat Model of Polycystic Ovarian Syndrome

Science.gov (United States)

Hoang, Vanessa; Bi, Jiangjiang; Mohankumar, Sheba M.; Vyas, Arpita K.

2015-01-01

Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder in women of reproductive age, with a prevalence of 5–8%. Type 2 diabetes and cardiovascular disease (CVD) are its long-term complications. Targeted therapies addressing both these complications together are lacking. Glucagon like peptide-1 (GLP-1) agonists that are used to treat type 2 diabetes mellitus have beneficial effects on the cardiovascular system. Hence we hypothesized that a GLP-1 agonist would improve both cardiovascular and metabolic outcomes in PCOS. To test this hypothesis, we used an established rat model of PCOS. Prepubertal female Sprague Dawley rats were sham-implanted or implanted s.c. with dihydrotestosterone (DHT) pellets (90 day release; 83μg/day). At 12 wks of age, sham implanted rats received saline injections and the DHT treated animals were administered either saline or liraglutide (0.2mg/kg s.c twice daily) for 4 weeks. Subgroups of rats were implanted with telemeters between 12-13 weeks of age to monitor blood pressure. DHT implanted rats had irregular estrus cycles and were significantly heavier than the control females at 12 weeks (mean± SEM 251.9±3.4 vs 216.8±3.4 respectively; pDHT treated rats significantly decreased body weight (mean± SEM 294.75 ±3.2 in DHT+ saline vs 276.25±2.7 in DHT+ liraglutide group respectively; pDHT implanted rats significantly improved glucose excursion during oral glucose tolerance test (area under the curve: DHT+ saline 28674±310 vs 24990± 420 in DHT +liraglutide p DHT rats were hypertensive and liraglutide treatment significantly improved mean arterial pressure. These results suggest that GLP-1 treatment could improve DHT–induced metabolic and blood pressure deficits associated with PCOS. PMID:26010091

LA Sprouts Randomized Controlled Nutrition, Cooking and Gardening Program Reduces Obesity and Metabolic Risk in Latino Youth

Science.gov (United States)

Gatto, Nicole M.; Martinez, Lauren C.; Spruijt-Metz, Donna; Davis, Jaimie N.

2015-01-01

Objective To assess the effects of a 12-week gardening, nutrition, and cooking intervention (“LA Sprouts”) on dietary intake, obesity parameters and metabolic disease risk among low-income, primarily Hispanic/Latino youth in Los Angeles. Methods Randomized control trial involving four elementary schools [2 schools randomized to intervention (172, 3rd–5th grade students); 2 schools randomized to control (147, 3rd–5th grade students)]. Classes were taught in 90-minute sessions once a week to each grade level for 12 weeks. Data collected at pre- and post-intervention included dietary intake via food frequency questionnaire (FFQ), anthropometric measures [BMI, waist circumference (WC)], body fat, and fasting blood samples. Results LA Sprouts participants had significantly greater reductions in BMI z-scores (0.1 versus 0.04 point decrease, respectively; p=0.01) and WC (−1.2 cm vs. no change; p<0.001). Fewer LA Sprouts participants had the metabolic syndrome (MetSyn) after the intervention than before, while the number of controls with MetSyn increased. LA Sprouts participants had improvements in dietary fiber intake (+3.5% vs. −15.5%; p=0.04) and less decreases in vegetable intake (−3.6% vs. −26.4%; p=0.04). Change in fruit intake before and after the intervention did not significantly differ between LAS and control subjects. Conclusions LA Sprouts was effective in reducing obesity and metabolic risk. PMID:25960146

Impact of Vitamin D Replacement on Markers of Glucose Metabolism and Cardio-Metabolic Risk in Women with Former Gestational Diabetes--A Double-Blind, Randomized Controlled Trial.

Directory of Open Access Journals (Sweden)

Toh Peng Yeow

Full Text Available Gestational Diabetes Mellitus (GDM and vitamin D deficiency are related to insulin resistance and impaired beta cell function, with heightened risk for future development of diabetes. We evaluated the impact of vitamin D supplementation on markers of glucose metabolism and cardio metabolic risk in Asian women with former GDM and hypovitaminosis D. In this double blind, randomized controlled trial, 26 participants were randomized to receive either daily 4000 IU vitamin D3 or placebo capsules. 75 g Oral Glucose Tolerance Test (OGTT and biochemistry profiles were performed at baseline and 6 month visits. Mathematical models, using serial glucose, insulin and C peptide measurements from OGTT, were employed to calculate insulin sensitivity and beta cell function. Thirty three (76% women with former GDM screened had vitamin D level of <50 nmol/L at baseline. Supplementation, when compared with placebo, resulted in increased vitamin D level (+51.1 nmol/L vs 0.2 nmol/L, p<0.001 and increased fasting insulin (+20% vs 18%, p = 0.034. The vitamin D group also demonstrated a 30% improvement in disposition index and an absolute 0.2% (2 mmol/mol reduction in HbA1c. There was no clear change in insulin sensitivity or markers of cardio metabolic risk. This study highlighted high prevalence of vitamin D deficiency among Asian women with former GDM. Six months supplementation with 4000 IU of vitamin D3 safely restored the vitamin D level, improved basal pancreatic beta-cell function and ameliorated the metabolic state. There was no effect on markers of cardio metabolic risk. Further mechanistic studies exploring the role of vitamin D supplementation on glucose homeostasis among different ethnicities may be needed to better inform future recommendations for these women with former GDM at high risk of both hypovitaminosis D and future diabetes.

Larval starvation improves metabolic response to adult starvation in honey bees (Apis mellifera L.).

Science.gov (United States)

Wang, Ying; Campbell, Jacob B; Kaftanoglu, Osman; Page, Robert E; Amdam, Gro V; Harrison, Jon F

2016-04-01

Environmental changes during development have long-term effects on adult phenotypes in diverse organisms. Some of the effects play important roles in helping organisms adapt to different environments, such as insect polymorphism. Others, especially those resulting from an adverse developmental environment, have a negative effect on adult health and fitness. However, recent studies have shown that those phenotypes influenced by early environmental adversity have adaptive value under certain (anticipatory) conditions that are similar to the developmental environment, though evidence is mostly from morphological and behavioral observations and it is still rare at physiological and molecular levels. In the companion study, we applied a short-term starvation treatment to fifth instar honey bee larvae and measured changes in adult morphology, starvation resistance, hormonal and metabolic physiology and gene expression. Our results suggest that honey bees can adaptively respond to the predicted nutritional stress. In the present study, we further hypothesized that developmental starvation specifically improves the metabolic response of adult bees to starvation instead of globally affecting metabolism under well-fed conditions. Here, we produced adult honey bees that had experienced a short-term larval starvation, then we starved them for 12 h and monitored metabolic rate, blood sugar concentrations and metabolic reserves. We found that the bees that experienced larval starvation were able to shift to other fuels faster and better maintain stable blood sugar levels during starvation. However, developmental nutritional stress did not change metabolic rates or blood sugar levels in adult bees under normal conditions. Overall, our study provides further evidence that early larval starvation specifically improves the metabolic responses to adult starvation in honey bees. © 2016. Published by The Company of Biologists Ltd.

Chronic leucine supplementation improves glycemic control in etiologically distinct mouse models of obesity and diabetes mellitus

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Hou Jue

2010-07-01

Full Text Available Abstract Background Leucine may function as a signaling molecule to regulate metabolism. We have previously shown that dietary leucine supplementation significantly improves glucose and energy metabolism in diet-induced obese mice, suggesting that leucine supplementation could potentially be a useful adjuvant therapy for obesity and type 2 diabetes. Since the underlying cause for obesity and type 2 diabetes is multifold, we further investigated metabolic effects of leucine supplementation in obese/diabetes mouse models with different etiologies, and explored the underlying molecular mechanisms. Methods Leucine supplementation was carried out in NONcNZO10/LtJ (RCS10 - a polygenic model predisposed to beta cell failure and type 2 diabetes, and in B6.Cg-Ay/J (Ay - a monogenic model for impaired central melanocortin receptor signaling, obesity, and severe insulin resistance. Mice in the treatment group received the drinking water containing 1.5% leucine for up to 8 months; control mice received the tap water. Body weight, body composition, blood HbA1c levels, and plasma glucose and insulin levels were monitored throughout and/or at the end of the study period. Indirect calorimetry, skeletal muscle gene expression, and adipose tissue inflammation were also assessed in Ay mice. Results Leucine supplementation significantly reduced HbA1c levels throughout the study period in both RCS10 and Ay mice. However, the treatment had no long term effect on body weight or adiposity. The improvement in glycemic control was associated with an increased insulin response to food challenge in RCS10 mice and decreased plasma insulin levels in Ay mice. In leucine-treated Ay mice, energy expenditure was increased by ~10% (p y mice whereas the expression levels of MCP-1 and TNF-alpha and macrophage infiltration in adipose tissue were significantly reduced. Conclusions Chronic leucine supplementation significantly improves glycemic control in multiple mouse models of

Microbiological changes after periodontal therapy in diabetic patients with inadequate metabolic control

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Carina Maciel Silva-Boghossian

2014-05-01

Full Text Available The present study investigated the effect of non-surgical periodontal treatment (SRP on the composition of the subgingival microbiota of chronic periodontitis (CP in individuals with type 2 diabetes (DM2 with inadequate metabolic control and in systemically healthy (SH individuals. Forty individuals (20 DM2 and 20 SH with CP underwent full-mouth periodontal examination. Subgingival plaque was sampled from 4 deep sites of each individual and tested for mean prevalence and counts of 45 bacterial taxa by the checkerboard method. Clinical and microbiological assessments were performed before and 3 months after SRP. At baseline, those in the DM2 group presented a significantly higher percentage of sites with visible plaque and bleeding on probing compared with those in the SH group (p < 0.01. Those in the DM2 group presented significantly higher levels of C. rectus and P. gingivalis, and lower prevalence of P. micra and S. anginosus, compared with those in the SH group (p ≤ 0.001. At the 3-month visit, both groups showed a significant improvement in all clinical parameters (p < 0.01. Those in the DM2 group showed significantly higher prevalence and/or levels of A. gerencseriae, A. naeslundii I, A. oris, A. odontolyticus, C. sputigena, F. periodonticum, and G. morbillorum compared with those in the SH group (p ≤ 0.001. However, those in the DM2 group showed a significant reduction in the levels of P. intermedia, P. gingivalis, T. forsythia, and T. denticola (p ≤ 0.001 over time. Those in the SRP group showed improved periodontal status and reduced levels of putative periodontal pathogens at 3 months’ evaluation compared with those in the DM2 group with inadequate metabolic control.

Self-Efficacy, Self-Care, and Metabolic Control in Persons with Type 2, Diet and Exercised Controlled Diabetes

National Research Council Canada - National Science Library

Randall, Lisa

1998-01-01

... (Diabetes control and Complications Trial, 1993). Nurses' understanding of diabetes management coupled with a holistic view of person makes them the optimal professionals to facilitate patient movement toward tight metabolic control...

Metabolic sensing neurons and the control of energy homeostasis.

Science.gov (United States)

Levin, Barry E

2006-11-30

The brain and periphery carry on a constant conversation; the periphery informs the brain about its metabolic needs and the brain provides for these needs through its control of somatomotor, autonomic and neurohumoral pathways involved in energy intake, expenditure and storage. Metabolic sensing neurons are the integrators of a variety of metabolic, humoral and neural inputs from the periphery. Such neurons, originally called "glucosensing", also respond to fatty acids, hormones and metabolites from the periphery. They are integrated within neural pathways involved in the regulation of energy homeostasis. Unlike most neurons, they utilize glucose and other metabolites as signaling molecules to regulate their membrane potential and firing rate. For glucosensing neurons, glucokinase acts as the rate-limiting step in glucosensing while the pathways that mediate responses to metabolites like lactate, ketone bodies and fatty acids are less well characterized. Many metabolic sensing neurons also respond to insulin and leptin and other peripheral hormones and receive neural inputs from peripheral organs. Each set of afferent signals arrives with different temporal profiles and by different routes and these inputs are summated at the level of the membrane potential to produce a given neural firing pattern. In some obese individuals, the relative sensitivity of metabolic sensing neurons to various peripheral inputs is genetically reduced. This may provide one mechanism underlying their propensity to become obese when exposed to diets high in fat and caloric density. Thus, metabolic sensing neurons may provide a potential therapeutic target for the treatment of obesity.

NAMPT and NAMPT-controlled NAD Metabolism in Vascular Repair.

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Wang, Pei; Li, Wen-Lin; Liu, Jian-Min; Miao, Chao-Yu

2016-06-01

Vascular repair plays important roles in postischemic remodeling and rehabilitation in cardiovascular and cerebrovascular disease, such as stroke and myocardial infarction. Nicotinamide adenine dinucleotide (NAD), a well-known coenzyme involved in electron transport chain for generation of adenosine triphosphate, has emerged as an important controller regulating various biological signaling pathways. Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme for NAD biosynthesis in mammals. NAMPT may also act in a nonenzymatic manner, presumably mediated by unknown receptor(s). Rapidly accumulating data in the past decade show that NAMPT and NAMPT-controlled NAD metabolism regulate fundamental biological functions in endothelial cells, vascular smooth muscle cells, and endothelial progenitor cells. The NAD-consuming proteins, including sirtuins, poly-ADP-ribose polymerases (PARPs), and CD38, may contribute to the regulatory effects of NAMPT-NAD axis in these cells and vascular repair. This review discusses the current data regarding NAMPT and NAMPT-controlled NAD metabolism in vascular repair and the clinical potential translational application of NAMPT-related products in treatment of cardiovascular and cerebrovascular disease.

Neuroendocrine control by kisspeptins: role in metabolic regulation of fertility.

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Navarro, Victor M; Tena-Sempere, Manuel

2011-09-13

The neurohormonal control of reproduction involves a hierarchical network of central and peripheral signals in the hypothalamic-pituitary-gonadal (HPG) axis. Development and function of this neuroendocrine system is the result of a lifelong delicate balance between endogenous regulators and environmental cues, including nutritional and metabolic factors. Kisspeptins are the peptide products of KISS1, which operate via the G-protein-coupled receptor GPR54 (also known as Kiss1R). These peptides have emerged as essential upstream regulators of neurons secreting gonadotropin-releasing hormone (GnRH), the major hypothalamic node for the stimulatory control of the HPG axis. They are potent elicitors of gonadotropin secretion in various species and physiological settings. Moreover, Kiss1 neurons in the hypothalamus participate in crucial features of reproductive maturation and function, such as brain-level sex differentiation, puberty onset and the neuroendocrine regulation of gonadotropin secretion and ovulation. Cotransmitters of Kiss1 neurons, such as neurokinin B, with roles in controlling the HPG axis have been identified by genetic, neuroanatomical and physiological studies. In addition, a putative role has been proposed for Kiss1 neurons in transmitting metabolic information to GnRH neurons, although the precise mechanisms are as yet unclear. In this Review, we present the major reproductive features of kisspeptins, especially their interplay with neurokinin B and potential roles in the metabolic control of puberty and fertility, and suggest new avenues for research.

Role of Autophagy in the Control of Body Metabolism

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Wenying Quan

2013-03-01

Full Text Available Autophagy plays a crucial role in the maintenance of cellular nutrient balance and the function of organelles such as mitochondria or the endoplasmic reticulum, which are important in intracellular metabolism, insulin release, and insulin sensitivity. In the insulin-producing pancreatic β-cells, autophagy is important in the maintenance of β-cell mass, structure, and function. Mice with deficiencies in β-cell-specific autophagy show reduced β-cell mass and defects in insulin secretion that lead to hypoinsulinemia and hyperglycemia but not diabetes. However, these mice developed diabetes when bred with ob/ob mice, suggesting that autophagy-deficient β-cells have defects in dealing with the increased metabolic stress imposed by obesity. These results also imply that autophagy deficiency in β-cells could be a factor in the progression from obesity to diabetes. Another important function of autophagy is in hypothalamic neurons for the central control of energy expenditure, appetite, and body weight. In addition, mice with autophagy deficiencies in the target tissues of insulin have yielded diverse phenotypes. Taken together, these results suggest that autophagy is important in the control of whole body energy and nutrient homeostasis, and its dysregulation could play a role in the development of metabolic disorders and diabetes.

Pilates training improves 5-km run performance by changing metabolic cost and muscle activity in trained runners

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Finatto, Paula; Silva, Edson Soares Da; Okamura, Alexandre B.; Almada, Bruna P.; Oliveira, Henrique B.

2018-01-01

Purpose Strength training improves distance running economy and performance. This finding is based predominantly on maximal and explosive strength programmes applied to locomotor muscles, particularly on the lower limbs. It is not certain whether a minimization of metabolic cost (Cmet) and an improvement in running performance is feasible with strength training of the postural and trunk muscles. Methods Using kinematic, neuromuscular and metabolic measurements of running at two different speeds before and after a 12-week Pilates training programme, we tested the hypothesis that core training might improve the running Cmet and performance of trained runners. Thirty-two individuals were randomly assigned to the control group (CG, n = 16) or the Pilates group (PG, n = 16). Results Confirming our hypothesis, a significant improvement (p<0.05) was observed for running performance in the PG (pre: 25.65±0.4 min; post: 23.23±0.4 min) compared to the CG (pre: 25.33±0.58 min; post: 24.61±0.52 min). Similarly, the PG (4.33±0.07 J.kg-1.m-1) had better responses than the CG (4.71±0.11 J.kg-1.m-1) during post-training for Cmet. These findings were accompanied by decreased electromyographic activity of the postural muscles at submaximal running intensities in the PG. Conclusions Overall, these results provide a rationale for selecting strength training strategies that target adaptations on specific postural and locomotor muscles for trained distance runners. PMID:29561907

Pilates training improves 5-km run performance by changing metabolic cost and muscle activity in trained runners.

Directory of Open Access Journals (Sweden)

Paula Finatto

Full Text Available Strength training improves distance running economy and performance. This finding is based predominantly on maximal and explosive strength programmes applied to locomotor muscles, particularly on the lower limbs. It is not certain whether a minimization of metabolic cost (Cmet and an improvement in running performance is feasible with strength training of the postural and trunk muscles.Using kinematic, neuromuscular and metabolic measurements of running at two different speeds before and after a 12-week Pilates training programme, we tested the hypothesis that core training might improve the running Cmet and performance of trained runners. Thirty-two individuals were randomly assigned to the control group (CG, n = 16 or the Pilates group (PG, n = 16.Confirming our hypothesis, a significant improvement (p<0.05 was observed for running performance in the PG (pre: 25.65±0.4 min; post: 23.23±0.4 min compared to the CG (pre: 25.33±0.58 min; post: 24.61±0.52 min. Similarly, the PG (4.33±0.07 J.kg-1.m-1 had better responses than the CG (4.71±0.11 J.kg-1.m-1 during post-training for Cmet. These findings were accompanied by decreased electromyographic activity of the postural muscles at submaximal running intensities in the PG.Overall, these results provide a rationale for selecting strength training strategies that target adaptations on specific postural and locomotor muscles for trained distance runners.

Iron metabolism in critically ill patients developing anemia of inflammation: a case control study.

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Boshuizen, Margit; Binnekade, Jan M; Nota, Benjamin; van de Groep, Kirsten; Cremer, Olaf L; Tuinman, Pieter R; Horn, Janneke; Schultz, Marcus J; van Bruggen, Robin; Juffermans, Nicole P

2018-05-02

Anemia occurring as a result of inflammatory processes (anemia of inflammation, AI) has a high prevalence in critically ill patients. Knowledge on changes in iron metabolism during the course of AI is limited, hampering the development of strategies to counteract AI. This case control study aimed to investigate iron metabolism during the development of AI in critically ill patients. Iron metabolism in 30 patients who developed AI during ICU stay was compared with 30 septic patients with a high Hb and 30 non-septic patients with a high Hb. Patients were matched on age and sex. Longitudinally collected plasma samples were analyzed for levels of parameters of iron metabolism. A linear mixed model was used to assess the predictive values of the parameters. In patients with AI, levels of iron, transferrin and transferrin saturation showed an early decrease compared to controls with a high Hb, already prior to the development of anemia. Ferritin, hepcidin and IL-6 levels were increased in AI compared to controls. During AI development, erythroferrone decreased. Differences in iron metabolism between groups were not influenced by APACHE IV score. The results show that in critically ill patients with AI, iron metabolism is already altered prior to the development of anemia. Levels of iron regulators in AI differ from septic controls with a high Hb, irrespective of disease severity. AI is characterized by high levels of hepcidin, ferritin and IL-6 and low levels of iron, transferrin and erythroferrone.

Synergizing metabolic flux analysis and nucleotide sugar metabolism to understand the control of glycosylation of recombinant protein in CHO cells

LENUS (Irish Health Repository)

Burleigh, Susan C

2011-10-18

Abstract Background The glycosylation of recombinant proteins can be altered by a range of parameters including cellular metabolism, metabolic flux and the efficiency of the glycosylation process. We present an experimental set-up that allows determination of these key processes associated with the control of N-linked glycosylation of recombinant proteins. Results Chinese hamster ovary cells (CHO) were cultivated in shake flasks at 0 mM glutamine and displayed a reduced growth rate, glucose metabolism and a slower decrease in pH, when compared to other glutamine-supplemented cultures. The N-linked glycosylation of recombinant human chorionic gonadotrophin (HCG) was also altered under these conditions; the sialylation, fucosylation and antennarity decreased, while the proportion of neutral structures increased. A continuous culture set-up was subsequently used to understand the control of HCG glycosylation in the presence of varied glutamine concentrations; when glycolytic flux was reduced in the absence of glutamine, the glycosylation changes that were observed in shake flask culture were similarly detected. The intracellular content of UDP-GlcNAc was also reduced, which correlated with a decrease in sialylation and antennarity of the N-linked glycans attached to HCG. Conclusions The use of metabolic flux analysis illustrated a case of steady state multiplicity, where use of the same operating conditions at each steady state resulted in altered flux through glycolysis and the TCA cycle. This study clearly demonstrated that the control of glycoprotein microheterogeneity may be examined by use of a continuous culture system, metabolic flux analysis and assay of intracellular nucleotides. This system advances our knowledge of the relationship between metabolic flux and the glycosylation of biotherapeutics in CHO cells and will be of benefit to the bioprocessing industry.

Effect of metabolic control on parathyroid hormone secretion in diabetic patients

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Paula F.J.A.

2001-01-01

Full Text Available The metabolic derangement caused by diabetes mellitus may potentially affect bone mineral metabolism. In the present study we evaluated the effect of diabetes metabolic control on parathyroid hormone (PTH secretion during stimulation with EDTA infusion. The study was conducted on 24 individuals, 8 of them normal subjects (group N: glycated hemoglobin - HbA1C = 4.2 ± 0.2%; range = 3.5-5.0%, 8 patients with good and regular metabolic control (group G-R: HbA1C = 7.3 ± 0.4%; range = 6.0-8.5%, and 8 patients with poor metabolic control (group P: HbA1C = 12.5 ± 1.0%; range: 10.0-18.8%. Blood samples were collected at 10-min intervals throughout the study (a basal period of 30 min and a 2-h period of EDTA infusion, 30 mg/kg body weight and used for the determination of ionized calcium, magnesium, glucose and intact PTH. Basal ionized calcium levels were slightly lower in group P (1.19 ± 0.01 mmol/l than in group N (1.21 ± 0.01 mmol/l and group G-R (1.22 ± 0.01 mmol/l. After EDTA infusion, the three groups presented a significant fall in calcium, but with no significant difference among them at any time. Basal magnesium levels and levels determined during EDTA infusion were significantly lower (P<0.01 in group P than in group N. The induction of hypocalcemia caused an elevation in PTH which was similar in groups N and G-R but significantly higher than in group P throughout the infusion period (+110 min, N = 11.9 ± 2.1 vs G-R = 13.7 ± 1.6 vs P = 7.5 ± 0.7 pmol/l; P<0.05 for P vs N and G-R. The present results show that PTH secretion is impaired in patients with poorly controlled diabetes.

Lycium barbarum Reduces Abdominal Fat and Improves Lipid Profile and Antioxidant Status in Patients with Metabolic Syndrome.

Science.gov (United States)

de Souza Zanchet, Mayara Zagonel; Nardi, Geisson Marcos; de Oliveira Souza Bratti, Letícia; Filippin-Monteiro, Fabíola Branco; Locatelli, Claudriana

2017-01-01

Natural antioxidants present in fruits have attracted considerable interest due to their presumed safety and potential nutritional value. Even though antioxidant activities of many fruits have been reported, the effects of phytochemicals of goji berry (GB) in patients with metabolic syndrome have not been investigated. In this study, we examined anthropometric and biochemical parameters in patients with metabolic syndrome after the consumption of GB. The patients were divided into two groups, control (C) and supplemented (S), and followed up for 45 days. Participants were individually instructed to carry out a healthy diet, but additionally, an inclusion of 14 g of the natural form of goji berry in the diet during 45 days for the S group was proposed. After 45 days of study, a significant reduction in transaminases as well as an improvement in lipid profile in the S group was observed. Likewise, a significant reduction in the waist circumference of the S group was observed when compared with that of the C group, and increased glutathione and catalase levels associated with a reduction of lipid peroxidation. These results suggest that this is an effective dietary supplement for the prevention of cardiovascular diseases in individuals with metabolic syndrome.

Impact of changes in metabolic control on progression to photocoagulation for clinically significant macular oedema:a 20 year study of type 1 diabetes

DEFF Research Database (Denmark)

Sander, B.; Larsen, M.; Andersen, Elisabeth Wreford

2013-01-01

Aims/hypothesis Although increasing hyperglycaemia, arterial hypertension and longer duration of diabetes raise the risk of progression of diabetic retinopathy, short-term benefits in terms of improved metabolic control and lowered blood pressure have not been demonstrated. We therefore examined ...

Metabolic network model guided engineering ethylmalonyl-CoA pathway to improve ascomycin production in Streptomyces hygroscopicus var. ascomyceticus.

Science.gov (United States)

Wang, Junhua; Wang, Cheng; Song, Kejing; Wen, Jianping

2017-10-03

Ascomycin is a 23-membered polyketide macrolide with high immunosuppressant and antifungal activity. As the lower production in bio-fermentation, global metabolic analysis is required to further explore its biosynthetic network and determine the key limiting steps for rationally engineering. To achieve this goal, an engineering approach guided by a metabolic network model was implemented to better understand ascomycin biosynthesis and improve its production. The metabolic conservation of Streptomyces species was first investigated by comparing the metabolic enzymes of Streptomyces coelicolor A3(2) with those of 31 Streptomyces strains, the results showed that more than 72% of the examined proteins had high sequence similarity with counterparts in every surveyed strain. And it was found that metabolic reactions are more highly conserved than the enzymes themselves because of its lower diversity of metabolic functions than that of genes. The main source of the observed metabolic differences was from the diversity of secondary metabolism. According to the high conservation of primary metabolic reactions in Streptomyces species, the metabolic network model of Streptomyces hygroscopicus var. ascomyceticus was constructed based on the latest reported metabolic model of S. coelicolor A3(2) and validated experimentally. By coupling with flux balance analysis and using minimization of metabolic adjustment algorithm, potential targets for ascomycin overproduction were predicted. Since several of the preferred targets were highly associated with ethylmalonyl-CoA biosynthesis, two target genes hcd (encoding 3-hydroxybutyryl-CoA dehydrogenase) and ccr (encoding crotonyl-CoA carboxylase/reductase) were selected for overexpression in S. hygroscopicus var. ascomyceticus FS35. Both the mutants HA-Hcd and HA-Ccr showed higher ascomycin titer, which was consistent with the model predictions. Furthermore, the combined effects of the two genes were evaluated and the strain HA

A combined continuous and interval aerobic training improves metabolic syndrome risk factors in men

Directory of Open Access Journals (Sweden)

Sari-Sarraf V

2015-05-01

Full Text Available Vahid Sari-Sarraf,1 Akbar Aliasgarzadeh,2 Mohammad-Mahdi Naderali,3 Hamid Esmaeili,1 Ebrahim K Naderali4 1Department of Exercise Physiology, Faculty of Physical Education and Sport Sciences, University of Tabriz, 2Bone Research Centre, Endocrine Unit, Department of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran; 3The School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, 4Faculty of Science, Liverpool Hope University, Liverpool, UK Abstract: Individuals with metabolic syndrome have significantly higher risk of cardiovascular disease and type 2 diabetes leading to premature death mortality. Metabolic syndrome has a complex etiology; thus, it may require a combined and multi-targeted aerobic exercise regimen to improve risk factors associated with it. Therefore, the aim of this study was to evaluate the effect of combined continuous and interval aerobic training on patients with metabolic syndrome. Thirty adult male with metabolic syndrome (54±8 years were randomly divided into two groups: test training group (TTG; n=15 and control group (CG; n=15. Subjects in TTG performed combined continuous and interval aerobic training using a motorized treadmill three times per week for 16 weeks. Subjects in CG were advised to continue with their normal activities of life. Twenty-two men completed the study (eleven men in each group. At the end of the study, in TTG, there were significant (for all, P<0.05 reductions in total body weight (-3.2%, waist circumference (-3.43 cm, blood pressure (up to -12.7 mmHg, and plasma insulin, glucose, and triacylglyceride levels. Moreover, there were significant (for all, P<0.05 increases VO2max (-15.3% and isometric strength of thigh muscle (28.1% and high-density lipoprotein in TTG. None of the above indices were changed in CG at the end of 16-week study period. Our study suggests that adoption of a 16-week combined continuous and interval aerobic training regimen in men

Valsartan improves adipose tissue function in humans with impaired glucose metabolism: a randomized placebo-controlled double-blind trial.

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Gijs H Goossens

Full Text Available BACKGROUND: Blockade of the renin-angiotensin system (RAS reduces the incidence of type 2 diabetes mellitus. In rodents, it has been demonstrated that RAS blockade improved adipose tissue (AT function and glucose homeostasis. However, the effects of long-term RAS blockade on AT function have not been investigated in humans. Therefore, we examined whether 26-wks treatment with the angiotensin II type 1 receptor blocker valsartan affects AT function in humans with impaired glucose metabolism (IGM. METHODOLOGY/PRINCIPAL FINDINGS: We performed a randomized, double-blind, placebo-controlled parallel-group study, in which 38 subjects with IGM were treated with valsartan (VAL, 320 mg/d or placebo (PLB for 26 weeks. Before and after treatment, an abdominal subcutaneous AT biopsy was collected for measurement of adipocyte size and AT gene/protein expression of angiogenesis/capillarization, adipogenesis, lipolytic and inflammatory cell markers. Furthermore, we evaluated fasting and postprandial AT blood flow (ATBF ((133Xe wash-out, systemic inflammation and insulin sensitivity (hyperinsulinemic-euglycemic clamp. VAL treatment markedly reduced adipocyte size (P<0.001, with a shift toward a higher proportion of small adipocytes. In addition, fasting (P = 0.043 and postprandial ATBF (P = 0.049 were increased, whereas gene expression of angiogenesis/capillarization, adipogenesis and macrophage infiltration markers in AT was significantly decreased after VAL compared with PLB treatment. Interestingly, the change in adipocyte size was associated with alterations in insulin sensitivity and reduced AT gene expression of macrophage infiltration markers. VAL did not alter plasma monocyte-chemoattractant protein (MCP-1, TNF-α, adiponectin and leptin concentrations. CONCLUSIONS/SIGNIFICANCE: 26-wks VAL treatment markedly reduced abdominal subcutaneous adipocyte size and AT macrophage infiltration markers, and increased ATBF in IGM subjects. The VAL

Synthesis and formulation studies of griseofulvin analogues with improved solubility and metabolic stability

DEFF Research Database (Denmark)

Petersen, Asger Bjørn; Andersen, Nikolaj Sten; Konotop, Gleb

2017-01-01

Griseofulvin (1) is an important antifungal agent that has recently received attention due to its antiproliferative activity in mammalian cancer cells. Comprehensive SAR studies have led to the identification of 2'-benzyloxy griseofulvin 2, a more potent analogue with low micromolar anticancer...... potency in vitro. Analogue 2 was also shown to retard tumor growth through inhibition of centrosomal clustering in murine xenograft models of colon cancer and multiple myeloma. However, similar to griseofulvin, compound 2 exhibited poor metabolic stability and aqueous solubility. In order to improve...... studies. The 2'-benzylamine analogue 10 proved to be the most promising compound with low μM in vitro anticancer potency, a 200-fold increase in PBS solubility over compound 2, and with improved metabolic stability. Furthermore, this analogue proved compatible with formulations suitable for both oral...

A legume-based hypocaloric diet reduces proinflammatory status and improves metabolic features in overweight/obese subjects.

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Hermsdorff, Helen Hermana M; Zulet, M Ángeles; Abete, Itziar; Martínez, J Alfredo

2011-02-01

The nutritional composition of the dietary intake could produce specific effects on metabolic variables and inflammatory marker concentrations. This study assessed the effects of two hypocaloric diets (legume-restricted- vs. legume-based diet) on metabolic and inflammatory changes, accompanying weight loss. Thirty obese subjects (17 M/13F; BMI: 32.5 ± 4.5 kg/m(2); 36 ± 8 years) were randomly assigned to one of the following hypocaloric treatments (8 weeks): Calorie-restricted legume-free diet (Control: C-diet) or calorie-restricted legume-based diet (L-diet), prescribing 4 weekly different cooked-servings (160-235 g) of lentils, chickpeas, peas or beans. Body composition, blood pressure (BP), blood biochemical and inflammatory marker concentrations as well as dietary intake were measured at baseline and after the nutritional intervention. The L-diet achieved a greater body weight loss, when compared to the C-diet (-7.8 ± 2.9% vs. -5.3 ± 2.7%; p = 0.024). Total and LDL cholesterol levels and systolic BP were improved only when consuming the L-diet (p diet also resulted in a significant higher reduction in C-reactive protein (CRP) and complement C3 (C3) concentrations (p diet values. Interestingly, the reduction in the concentrations of CRP and C3 remained significantly higher to L-diet group, after adjusting by weight loss (p diet group, independent from weight loss (p hypocaloric diet resulted in a specific reduction in proinflammatory markers, such as CRP and C3 and a clinically significant improvement of some metabolic features (lipid profile and BP) in overweight/ obese subjects, which were in some cases independent from weight loss.

Caloric restriction alters the metabolic response to a mixed-meal: results from a randomized, controlled trial.

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Kim M Huffman

Full Text Available To determine if caloric restriction (CR would cause changes in plasma metabolic intermediates in response to a mixed meal, suggestive of changes in the capacity to adapt fuel oxidation to fuel availability or metabolic flexibility, and to determine how any such changes relate to insulin sensitivity (S(I.Forty-six volunteers were randomized to a weight maintenance diet (Control, 25% CR, or 12.5% CR plus 12.5% energy deficit from structured aerobic exercise (CR+EX, or a liquid calorie diet (890 kcal/d until 15% reduction in body weightfor six months. Fasting and postprandial plasma samples were obtained at baseline, three, and six months. A targeted mass spectrometry-based platform was used to measure concentrations of individual free fatty acids (FFA, amino acids (AA, and acylcarnitines (AC. S(I was measured with an intravenous glucose tolerance test.Over three and six months, there were significantly larger differences in fasting-to-postprandial (FPP concentrations of medium and long chain AC (byproducts of FA oxidation in the CR relative to Control and a tendency for the same in CR+EX (CR-3 month P = 0.02; CR-6 month P = 0.002; CR+EX-3 month P = 0.09; CR+EX-6 month P = 0.08. After three months of CR, there was a trend towards a larger difference in FPP FFA concentrations (P = 0.07; CR-3 month P = 0.08. Time-varying differences in FPP concentrations of AC and AA were independently related to time-varying S(I (P<0.05 for both.Based on changes in intermediates of FA oxidation following a food challenge, CR imparted improvements in metabolic flexibility that correlated with improvements in S(I.ClinicalTrials.gov NCT00099151.

Effects of Tight Versus Non Tight Control of Metabolic Acidosis on Early Renal Function After Kidney Transplantation

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Farhad Etezadi

2012-09-01

Full Text Available Background Recently, several studies have been conducted to determine the optimal strategy for intraoperative fluid replacement therapy in renal transplantation surgery. Since infusion of sodium bicarbonate as a buffer seems to be safer than other buffer compounds (lactate, gluconate, acetatethat indirectly convert into it within the liver, We hypothesized tight control of metabolic acidosis by infusion of sodium bicarbonate may improve early post-operative renal function in renal transplant recipients. Methods:120 patients were randomly divided into two equal groups. In group A, bicarbonate was infused intra-operatively according to Base Excess (BE measurements to achieve the normal values of BE (5 to +5 mEq/L. In group B, infusion of bicarbonate was allowed only in case of severe metabolic acidosis (BE [less than or equal to] 15 mEq/L or bicarbonate [less than or equal to] 10 mEq/L or PH [less than or equal to] 7.15. Minute ventilation was adjusted to keep PaCO2 within the normal range. Primary end-point was sampling of serum creatinine level in first, second, third and seventh post-operative days for statistical comparison between groups. Secondary objectives were comparison of cumulative urine volumes in the first 24 h of post-operative period and serum BUN levels which were obtained in first, second, third and seventh post-operative days. Results:In group A, all of consecutive serum creatinine levels were significantly lower in comparison with group B. With regard to secondary outcomes, no significant difference between groups was observed. Conclusion:Intra-operative tight control of metabolic acidosis by infusion of Sodium Bicarbonate in renal transplant recipients may improve early post-operative renal function.

Effects of tight versus non tight control of metabolic acidosis on early renal function after kidney transplantation

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Etezadi Farhad

2012-09-01

Full Text Available Abstract Background Recently, several studies have been conducted to determine the optimal strategy for intra-operative fluid replacement therapy in renal transplantation surgery. Since infusion of sodium bicarbonate as a buffer seems to be safer than other buffer compounds (lactate, gluconate, acetatethat indirectly convert into it within the liver, We hypothesized tight control of metabolic acidosis by infusion of sodium bicarbonate may improve early post-operative renal function in renal transplant recipients. Methods 120 patients were randomly divided into two equal groups. In group A, bicarbonate was infused intra-operatively according to Base Excess (BE measurements to achieve the normal values of BE (−5 to +5 mEq/L. In group B, infusion of bicarbonate was allowed only in case of severe metabolic acidosis (BE ≤ −15 mEq/L or bicarbonate ≤ 10 mEq/L or PH ≤ 7.15. Minute ventilation was adjusted to keep PaCO2 within the normal range. Primary end-point was sampling of serum creatinine level in first, second, third and seventh post-operative days for statistical comparison between groups. Secondary objectives were comparison of cumulative urine volumes in the first 24 h of post-operative period and serum BUN levels which were obtained in first, second, third and seventh post-operative days. Results In group A, all of consecutive serum creatinine levels were significantly lower in comparison with group B. With regard to secondary outcomes, no significant difference between groups was observed. Conclusion Intra-operative tight control of metabolic acidosis by infusion of Sodium Bicarbonate in renal transplant recipients may improve early post-operative renal function.

Synthetic biology and regulatory networks: where metabolic systems biology meets control engineering.

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He, Fei; Murabito, Ettore; Westerhoff, Hans V

2016-04-01

Metabolic pathways can be engineered to maximize the synthesis of various products of interest. With the advent of computational systems biology, this endeavour is usually carried out through in silico theoretical studies with the aim to guide and complement further in vitro and in vivo experimental efforts. Clearly, what counts is the result in vivo, not only in terms of maximal productivity but also robustness against environmental perturbations. Engineering an organism towards an increased production flux, however, often compromises that robustness. In this contribution, we review and investigate how various analytical approaches used in metabolic engineering and synthetic biology are related to concepts developed by systems and control engineering. While trade-offs between production optimality and cellular robustness have already been studied diagnostically and statically, the dynamics also matter. Integration of the dynamic design aspects of control engineering with the more diagnostic aspects of metabolic, hierarchical control and regulation analysis is leading to the new, conceptual and operational framework required for the design of robust and productive dynamic pathways. © 2016 The Author(s).

Atorvastatin Improves Ventricular Remodeling after Myocardial Infarction by Interfering with Collagen Metabolism

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Reichert, Karla; Pereira do Carmo, Helison Rafael; Galluce Torina, Anali; Diógenes de Carvalho, Daniela; Carvalho Sposito, Andrei; de Souza Vilarinho, Karlos Alexandre; da Mota Silveira-Filho, Lindemberg; Martins de Oliveira, Pedro Paulo

2016-01-01

Purpose Therapeutic strategies that modulate ventricular remodeling can be useful after acute myocardial infarction (MI). In particular, statins may exert effects on molecular pathways involved in collagen metabolism. The aim of this study was to determine whether treatment with atorvastatin for 4 weeks would lead to changes in collagen metabolism and ventricular remodeling in a rat model of MI. Methods Male Wistar rats were used in this study. MI was induced in rats by ligation of the left anterior descending coronary artery (LAD). Animals were randomized into three groups, according to treatment: sham surgery without LAD ligation (sham group, n = 14), LAD ligation followed by 10mg atorvastatin/kg/day for 4 weeks (atorvastatin group, n = 24), or LAD ligation followed by saline solution for 4 weeks (control group, n = 27). After 4 weeks, hemodynamic characteristics were obtained by a pressure-volume catheter. Hearts were removed, and the left ventricles were subjected to histologic analysis of the extents of fibrosis and collagen deposition, as well as the myocyte cross-sectional area. Expression levels of mediators involved in collagen metabolism and inflammation were also assessed. Results End-diastolic volume, fibrotic content, and myocyte cross-sectional area were significantly reduced in the atorvastatin compared to the control group. Atorvastatin modulated expression levels of proteins related to collagen metabolism, including MMP1, TIMP1, COL I, PCPE, and SPARC, in remote infarct regions. Atorvastatin had anti-inflammatory effects, as indicated by lower expression levels of TLR4, IL-1, and NF-kB p50. Conclusion Treatment with atorvastatin for 4 weeks was able to attenuate ventricular dysfunction, fibrosis, and left ventricular hypertrophy after MI in rats, perhaps in part through effects on collagen metabolism and inflammation. Atorvastatin may be useful for limiting ventricular remodeling after myocardial ischemic events. PMID:27880844

Metabolic control in type 1 diabetes patients practicing combat sports: at least two-year follow-up study.

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Benbenek-Klupa, Teresa; Matejko, Bartlomiej; Klupa, Tomasz

2015-01-01

It is well recognized that physical activity should be an integral part of the management of diabetes. It remains controversial, however, whether combat sports, often preferred by young individuals type 1 diabetes mellitus (T1DM), may be performed without high risk of metabolic decompensation. The aim of this observational study was to summarize a two-year follow-up period of five young male patients with T1DM practicing combat sports under the care of a physical-activity oriented specialist diabetes outpatient clinic. Of the five patients, three mixed martial arts and two kick-boxing competitors were included in the study. To control glucose in each patient, an individual approach was used that took into consideration the type of training, the sequence of the exercises, and the relative proportion of different forms of exercise. During the follow-up, glycemic control was improved and maintained in all individuals. Neither an episode of hospitalization-requiring diabetic ketoacidosis nor severe hypoglycemia occurred in these patients during the follow-up. In conclusion, an individual approach for T1DM patients practicing combat sports may result in achieving and maintaining satisfactory glycemic control without increased risk of metabolic decompensation.

The Consumption of Bicarbonate-Rich Mineral Water Improves Glycemic Control

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Shinnosuke Murakami

2015-01-01

Full Text Available Hot spring water and natural mineral water have been therapeutically used to prevent or improve various diseases. Specifically, consumption of bicarbonate-rich mineral water (BMW has been reported to prevent or improve type 2 diabetes (T2D in humans. However, the molecular mechanisms of the beneficial effects behind mineral water consumption remain unclear. To elucidate the molecular level effects of BMW consumption on glycemic control, blood metabolome analysis and fecal microbiome analysis were applied to the BMW consumption test. During the study, 19 healthy volunteers drank 500 mL of commercially available tap water (TW or BMW daily. TW consumption periods and BMW consumption periods lasted for a week each and this cycle was repeated twice. Biochemical tests indicated that serum glycoalbumin levels, one of the indexes of glycemic controls, decreased significantly after BMW consumption. Metabolome analysis of blood samples revealed that 19 metabolites including glycolysis-related metabolites and 3 amino acids were significantly different between TW and BMW consumption periods. Additionally, microbiome analysis demonstrated that composition of lean-inducible bacteria was increased after BMW consumption. Our results suggested that consumption of BMW has the possible potential to prevent and/or improve T2D through the alterations of host metabolism and gut microbiota composition.

The efficiency of telemedicine to optimize metabolic control in patients with type 1 diabetes mellitus: Telemed study.

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Esmatjes, Enric; Jansà, Margarida; Roca, Daria; Pérez-Ferre, Natalia; del Valle, Laura; Martínez-Hervás, Sergio; Ruiz de Adana, Marisol; Linares, Francisca; Batanero, Ricardo; Vázquez, Federico; Gomis, Ramon; de Solà-Morales, Oriol

2014-07-01

This study evaluated the impact of an Internet-based telematic system on the economic and clinical management of patients with type 1 diabetes mellitus. This 6-month prospective, randomized, comparative, open, multicenter study included patients with type 1 diabetes >18 years old treated with multiple insulin doses and with a glycated hemoglobin (HbA1c) level of >8%. We compared an intervention group (IG) (two face-to-face and five telematic appointments) with a control group (CG) (seven face-to-face appointments). The variables studied were (1) patient and healthcare team costs, (2) metabolic control, (3) knowledge of diabetes, (4) quality of life, and (5) self-care treatment adherence. Of the 154 patients included, 118 (76.6%) completed the study (IG, 54; CG, 64). The time used by the CG to follow the program was 823±645 min versus 353±222 min in the IG (Pknowledge and self-care treatment adherence. The use of interactive telematic appointments in subjects with type 1 diabetes and inadequate metabolic control is an efficient strategy, providing results comparable to those of face-to-face appointments in relation to improvement in glycemic control, knowledge acquisition, and self-care treatment adherence, with a significant reduction in the time used, especially by patients.

Longitudinal Trajectories of Metabolic Control across Adolescence: Associations with Parental Involvement, Adolescents’ Psychosocial Maturity, and Health Care Utilization

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King, Pamela S.; Berg, Cynthia A.; Butner, Jonathan; Drew, Linda M.; Foster, Carol; Donaldson, David; Murray, Mary; Swinyard, Michael; Wiebe, Deborah J.

2012-01-01

Purpose To predict trajectories of metabolic control across adolescence from parental involvement and adolescent psychosocial maturity, and to link metabolic control trajectories to health care utilization. Methods 252 adolescents (M age at study initiation = 12.5, SD=1.5, range 10–14 years) with type 1 diabetes (54.4% female, 92.8% Caucasian, length of diagnosis M=4.7 years, SD=3.0, range 1–12) participated in a 2-year longitudinal study. Metabolic control was gathered from medical records every three months. Adolescents completed measures of self-reliance (functional autonomy and extreme peer orientation), self-control (self-control and externalizing behavior), and parental involvement in diabetes care (acceptance, monitoring, and frequency of help). At the end of the study, mothers reported health care utilization (diabetes-related emergency room visits and hospitalizations) over the past six months. Results Latent class growth analyses indicated two distinct trajectories of metabolic control across adolescence: moderate control with slight deterioration (92% of the sample; average HbA1c = 8.18%) and poor control with rapid deterioration (8% of the sample; average HbA1c of 12.09%). Adolescents with poor and rapidly deteriorating metabolic control reported lower paternal monitoring and frequency of help with diabetes management, lower functional autonomy, and lower self-control than others. Those with poor and rapidly deteriorating metabolic control were 6.4 times more likely to report diabetes-related emergency room visits, and 9.3 times more likely to report diabetes-related hospitalizations near the end of the study. Conclusions Parental involvement and adolescents’ psychosocial maturity predict patterns of deteriorating metabolic control across adolescence and could be targeted for intervention. PMID:22525113

Hypoxia in Combination With Muscle Contraction Improves Insulin Action and Glucose Metabolism in Human Skeletal Muscle via the HIF-1α Pathway.

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Görgens, Sven W; Benninghoff, Tim; Eckardt, Kristin; Springer, Christian; Chadt, Alexandra; Melior, Anita; Wefers, Jakob; Cramer, Andrea; Jensen, Jørgen; Birkeland, Kåre I; Drevon, Christian A; Al-Hasani, Hadi; Eckel, Jürgen

2017-11-01

Skeletal muscle insulin resistance is the hallmark of type 2 diabetes and develops long before the onset of the disease. It is well accepted that physical activity improves glycemic control, but the knowledge on underlying mechanisms mediating the beneficial effects remains incomplete. Exercise is accompanied by a decrease in intramuscular oxygen levels, resulting in induction of HIF-1α. HIF-1α is a master regulator of gene expression and might play an important role in skeletal muscle function and metabolism. Here we show that HIF-1α is important for glucose metabolism and insulin action in skeletal muscle. By using a genome-wide gene expression profiling approach, we identified RAB20 and TXNIP as two novel exercise/HIF-1α-regulated genes in skeletal muscle. Loss of Rab20 impairs insulin-stimulated glucose uptake in human and mouse skeletal muscle by blocking the translocation of GLUT4 to the cell surface. In addition, exercise/HIF-1α downregulates the expression of TXNIP , a well-known negative regulator of insulin action. In conclusion, we are the first to demonstrate that HIF-1α is a key regulator of glucose metabolism in skeletal muscle by directly controlling the transcription of RAB20 and TXNIP These results hint toward a novel function of HIF-1α as a potential pharmacological target to improve skeletal muscle insulin sensitivity. © 2017 by the American Diabetes Association.

Control of mitochondrial metabolism and systemic energy homeostasis by microRNAs 378 and 378*.

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Carrer, Michele; Liu, Ning; Grueter, Chad E; Williams, Andrew H; Frisard, Madlyn I; Hulver, Matthew W; Bassel-Duby, Rhonda; Olson, Eric N

2012-09-18

Obesity and metabolic syndrome are associated with mitochondrial dysfunction and deranged regulation of metabolic genes. Peroxisome proliferator-activated receptor γ coactivator 1β (PGC-1β) is a transcriptional coactivator that regulates metabolism and mitochondrial biogenesis through stimulation of nuclear hormone receptors and other transcription factors. We report that the PGC-1β gene encodes two microRNAs (miRNAs), miR-378 and miR-378*, which counterbalance the metabolic actions of PGC-1β. Mice genetically lacking miR-378 and miR-378* are resistant to high-fat diet-induced obesity and exhibit enhanced mitochondrial fatty acid metabolism and elevated oxidative capacity of insulin-target tissues. Among the many targets of these miRNAs, carnitine O-acetyltransferase, a mitochondrial enzyme involved in fatty acid metabolism, and MED13, a component of the Mediator complex that controls nuclear hormone receptor activity, are repressed by miR-378 and miR-378*, respectively, and are elevated in the livers of miR-378/378* KO mice. Consistent with these targets as contributors to the metabolic actions of miR-378 and miR-378*, previous studies have implicated carnitine O-acetyltransferase and MED13 in metabolic syndrome and obesity. Our findings identify miR-378 and miR-378* as integral components of a regulatory circuit that functions under conditions of metabolic stress to control systemic energy homeostasis and the overall oxidative capacity of insulin target tissues. Thus, these miRNAs provide potential targets for pharmacologic intervention in obesity and metabolic syndrome.

Can melatonin prevent or improve metabolic side effects during antipsychotic treatments?

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Porfirio MC

2017-08-01

Full Text Available Maria-Cristina Porfirio,1 Juliana Paula Gomes de Almeida,2 Maddalena Stornelli,1 Silvia Giovinazzo,1 Diane Purper-Ouakil,3 Gabriele Masi4 1Unit of Child Neurology and Psychiatry, “Tor Vergata” University of Rome, Italy; 2Unit of Child Neurology, Irmandade Santa Casa de Misericordia Hospital São Paulo, Brazil; 3Unit of Child and Adolescent Psychiatry, Saint Eloi Hospital, Montpellier, France; 4IRCCS Stella Maris, Scientific Institute of Child Neurology and Psychiatry, Calambrone, Pisa, Italy Abstract: In the last two decades, second-generation antipsychotics (SGAs were more frequently used than typical antipsychotics for treating both psychotic and nonpsychotic psychiatric disorders in both children and adolescents, because of their lower risk of adverse neurological effects, that is, extrapyramidal symptoms. Recent studies have pointed out their effect on weight gain and increased visceral adiposity as they induce metabolic syndrome. Patients receiving SGAs often need to be treated with other substances to counteract metabolic side effects. In this paper, we point out the possible protective effect of add-on melatonin treatment in preventing, mitigating, or even reversing SGAs metabolic effects, improving quality of life and providing safer long-term treatments in pediatric patients. Melatonin is an endogenous indolamine secreted during darkness by the pineal gland; it plays a key role in regulating the circadian rhythm, generated by the suprachiasmatic nuclei (SCN of the hypothalamus, and has many other biological functions, including chronobiotic, antioxidant and neuroprotective properties, anti-inflammatory and free radical scavenging effects, and diminishing oxidative injury and fat distribution. It has been hypothesized that SGAs cause adverse metabolic effects that may be restored by nightly administration of melatonin because of its influence on autonomic and hormonal outputs. Interestingly, atypical anti-psychotics (AAPs can cause

Liraglutide improves hypertension and metabolic perturbation in a rat model of polycystic ovarian syndrome.

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Vanessa Hoang

Full Text Available Polycystic ovarian syndrome (PCOS is the most common endocrine disorder in women of reproductive age, with a prevalence of 5-8%. Type 2 diabetes and cardiovascular disease (CVD are its long-term complications. Targeted therapies addressing both these complications together are lacking. Glucagon like peptide-1 (GLP-1 agonists that are used to treat type 2 diabetes mellitus have beneficial effects on the cardiovascular system. Hence we hypothesized that a GLP-1 agonist would improve both cardiovascular and metabolic outcomes in PCOS. To test this hypothesis, we used an established rat model of PCOS. Prepubertal female Sprague Dawley rats were sham-implanted or implanted s.c. with dihydrotestosterone (DHT pellets (90 day release; 83 μg/day. At 12 wks of age, sham implanted rats received saline injections and the DHT treated animals were administered either saline or liraglutide (0.2 mg/kg s.c twice daily for 4 weeks. Subgroups of rats were implanted with telemeters between 12-13 weeks of age to monitor blood pressure. DHT implanted rats had irregular estrus cycles and were significantly heavier than the control females at 12 weeks (mean± SEM 251.9±3.4 vs 216.8±3.4 respectively; p<0.05 and 4 weeks of treatment with liraglutide in DHT treated rats significantly decreased body weight (mean± SEM 294.75 ±3.2 in DHT+ saline vs 276.25±2.7 in DHT+ liraglutide group respectively; p<0.01. Liraglutide treatment in the DHT implanted rats significantly improved glucose excursion during oral glucose tolerance test (area under the curve: DHT+ saline 28674±310 vs 24990± 420 in DHT +liraglutide p <0.01. DHT rats were hypertensive and liraglutide treatment significantly improved mean arterial pressure. These results suggest that GLP-1 treatment could improve DHT-induced metabolic and blood pressure deficits associated with PCOS.

Increasing Winter Maximal Metabolic Rate Improves Intrawinter Survival in Small Birds.

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Petit, Magali; Clavijo-Baquet, Sabrina; Vézina, François

Small resident bird species living at northern latitudes increase their metabolism in winter, and this is widely assumed to improve their chances of survival. However, the relationship between winter metabolic performance and survival has yet to be demonstrated. Using capture-mark-recapture, we followed a population of free-living black-capped chickadees (Poecile atricapillus) over 3 yr and evaluated their survival probability within and among winters. We also measured the size-independent body mass (M s ), hematocrit (Hct), basal metabolic rate (BMR), and maximal thermogenic capacity (Msum) and investigated how these parameters influenced survival within and among winters. Results showed that survival probability was high and constant both within (0.92) and among (0.96) winters. They also showed that while M s , Hct, and BMR had no significant influence, survival was positively related to Msum-following a sigmoid relationship-within but not among winter. Birds expressing an Msum below 1.26 W (i.e., similar to summer levels) had a winter. Our data therefore suggest that black-capped chickadees that are either too slow or unable to adjust their phenotype from summer to winter have little chances of survival and thus that seasonal upregulation of metabolic performance is highly beneficial. This study is the first to document in an avian system the relationship between thermogenic capacity and winter survival, a proxy of fitness.

Exercise training improves in vivo endothelial repair capacity of early endothelial progenitor cells in subjects with metabolic syndrome.

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Sonnenschein, Kristina; Horváth, Tibor; Mueller, Maja; Markowski, Andrea; Siegmund, Tina; Jacob, Christian; Drexler, Helmut; Landmesser, Ulf

2011-06-01

Endothelial dysfunction and injury are considered to contribute considerably to the development and progression of atherosclerosis. It has been suggested that intense exercise training can increase the number and angiogenic properties of early endothelial progenitor cells (EPCs). However, whether exercise training stimulates the capacity of early EPCs to promote repair of endothelial damage and potential underlying mechanisms remain to be determined. The present study was designed to evaluate the effects of moderate exercise training on in vivo endothelial repair capacity of early EPCs, and their nitric oxide and superoxide production as characterized by electron spin resonance spectroscopy analysis in subjects with metabolic syndrome. Twenty-four subjects with metabolic syndrome were randomized to an 8 weeks exercise training or a control group. Superoxide production and nitric oxide (NO) availability of early EPCs were characterized by using electron spin resonance (ESR) spectroscopy analysis. In vivo endothelial repair capacity of EPCs was examined by transplantation into nude mice with defined carotid endothelial injury. Endothelium-dependent, flow-mediated vasodilation was analysed using high-resolution ultrasound. Importantly, exercise training resulted in a substantially improved in vivo endothelial repair capacity of early EPCs (24.0 vs 12.7%; p exercise training, but not in the control group. Moreover, exercise training reduced superoxide production of EPCs, which was not observed in the control group. The present study suggests for the first time that moderate exercise training increases nitric oxide production of early endothelial progenitor cells and reduces their superoxide production. Importantly, this is associated with a marked beneficial effect on the in vivo endothelial repair capacity of early EPCs in subjects with metabolic syndrome.

Metabolic Diet App Suite for inborn errors of amino acid metabolism.

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Ho, Gloria; Ueda, Keiko; Houben, Roderick F A; Joa, Jeff; Giezen, Alette; Cheng, Barbara; van Karnebeek, Clara D M

2016-03-01

An increasing number of rare inborn errors of metabolism (IEMs) are amenable to targeted metabolic nutrition therapy. Daily adherence is important to attain metabolic control and prevent organ damage. This is challenging however, given the lack of information of disorder specific nutrient content of foods, the limited availability and cost of specialty products as well as difficulties in reliable calculation and tracking of dietary intake and targets. To develop apps for all inborn errors of amino acid metabolism for which the mainstay of treatment is a medical diet, and obtain patient and family feedback throughout the process to incorporate this into subsequent versions. The Metabolic Diet App Suite was created with input from health care professionals as a free, user-friendly, online tool for both mobile devices and desktop computers (http://www.metabolicdietapp.org) for 15 different IEMs. General information is provided for each IEM with links to useful online resources. Nutrient information is based on the MetabolicPro™, a North American food database compiled by the Genetic Metabolic Dietitians International (GMDI) Technology committee. After user registration, a personalized dashboard and management plan including specific nutrient goals are created. Each Diet App has a user-friendly interface and the functions include: nutrient intake counts, adding your own foods and homemade recipes and, managing a daily food diary. Patient and family feedback was overall positive and specific suggestions were used to further improve the App Suite. The Metabolic Diet App Suite aids individuals affected by IEMs to track and plan their meals. Future research should evaluate its impact on patient adherence, metabolic control, quality of life and health-related outcomes. The Suite will be updated and expanded to Apps for other categories of IEMs. Finally, this Suite is a support tool only, and does not replace medical/metabolic nutrition professional advice. Copyright �

Improving metabolic parameters of antipsychotic child treatment (IMPACT) study: rationale, design, and methods

OpenAIRE

Reeves, Gloria M; Keeton, Courtney; Correll, Christoph U; Johnson, Jacqueline L; Hamer, Robert M; Sikich, Linmarie; Hazzard, Lindsey; Alderman, Cheryl; Scheer, Abigail; Mabe, Micah; Kapoor, Sandeep; Sheridan, Eva; Borner, Irmgard; Bussell, Kristin; Pirmohamed, Sara

2013-01-01

Background Youth with serious mental illness may experience improved psychiatric stability with second generation antipsychotic (SGA) medication treatment, but unfortunately may also experience unhealthy weight gain adverse events. Research on weight loss strategies for youth who require ongoing antipsychotic treatment is quite limited. The purpose of this paper is to present the design, methods, and rationale of the Improving Metabolic Parameters in Antipsychotic Child Treatment (IMPACT) stu...

Effect of periodontal therapy on metabolic control and an inflammatory mediator in type 2 diabetic subjects: a report on 17 consecutive cases.

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Serrano, Carlos; Pérez, Clara; Sabogal, Diego

2012-04-01

A reciprocal relationship between diabetes mellitus and chronic periodontitis has been described, whereby chronic periodontal infection could affect diabetic metabolic control. Therefore, periodontal therapy could influence metabolic control or systemic inflammation leading to diabetic complications. This case report series presents the effect of therapy on periodontal indices, glycated hemoglobin (HbA1c) and high-sensitivity C-reactive protein (hs-CRP) in a group of type 2 diabetic patients. Seventeen diabetic patients diagnosed with moderate to severe chronic periodontitis received periodontal therapy. All patients received a hygienic phase of treatment and were re-examined 3 months later. At re-examination, subjects judged to need periodontal surgery were treated and re-examined after a further 3 months. A complete clinical examination and measurements of HbA1c and hs-CRP were evaluated. Periodontal treatment led to a significant improvement in periodontal indices; only five patients required periodontal surgery. The percentage of bleeding on probing was reduced by nearly 40%; percentage of pockets > or = 5 mm was less than half baseline values; mean pocket depth reduction was 1.21 mm (0.58) and attachment level gain was 0.74 mm (0.69). Nevertheless, no changes were present for HbA1c; a reduction in hs-CRP of 1.37 mg/L (2.67) was present. Periodontal therapy in this case series group produced a significant improvement in the clinical condition, butdid not affect metabolic control. It led to a decrease in hs-CRP.

Metabolic control of vesicular glutamate transport and release.

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Juge, Narinobu; Gray, John A; Omote, Hiroshi; Miyaji, Takaaki; Inoue, Tsuyoshi; Hara, Chiaki; Uneyama, Hisayuki; Edwards, Robert H; Nicoll, Roger A; Moriyama, Yoshinori

2010-10-06

Fasting has been used to control epilepsy since antiquity, but the mechanism of coupling between metabolic state and excitatory neurotransmission remains unknown. Previous work has shown that the vesicular glutamate transporters (VGLUTs) required for exocytotic release of glutamate undergo an unusual form of regulation by Cl(-). Using functional reconstitution of the purified VGLUTs into proteoliposomes, we now show that Cl(-) acts as an allosteric activator, and the ketone bodies that increase with fasting inhibit glutamate release by competing with Cl(-) at the site of allosteric regulation. Consistent with these observations, acetoacetate reduced quantal size at hippocampal synapses and suppresses glutamate release and seizures evoked with 4-aminopyridine in the brain. The results indicate an unsuspected link between metabolic state and excitatory neurotransmission through anion-dependent regulation of VGLUT activity. Copyright © 2010 Elsevier Inc. All rights reserved.

A real-time control system of gene expression using ligand-bound nucleic acid aptamer for metabolic engineering.

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Wang, Jing; Cui, Xun; Yang, Le; Zhang, Zhe; Lv, Liping; Wang, Haoyuan; Zhao, Zhenmin; Guan, Ningzi; Dong, Lichun; Chen, Rachel

2017-07-01

Artificial control of bio-functions through regulating gene expression is one of the most important and attractive technologies to build novel living systems that are useful in the areas of chemical synthesis, nanotechnology, pharmacology, cell biology. Here, we present a novel real-time control system of gene regulation that includes an enhancement element by introducing duplex DNA aptamers upstream promoter and a repression element by introducing a RNA aptamer upstream ribosome binding site. With the presence of ligands corresponding to the DNA aptamers, the expression of the target gene can be potentially enhanced at the transcriptional level by strengthening the recognition capability of RNAP to the recognition region and speeding up the separation efficiency of the unwinding region due to the induced DNA bubble around the thrombin-bound aptamers; while with the presence of RNA aptamer ligand, the gene expression can be repressed at the translational level by weakening the recognition capability of ribosome to RBS due to the shielding of RBS by the formed aptamer-ligand complex upstream RBS. The effectiveness and potential utility of the developed gene regulation system were demonstrated by regulating the expression of ecaA gene in the cell-free systems. The realistic metabolic engineering application of the system has also tested by regulating the expression of mgtC gene and thrombin cDNA in Escherichia coli JD1021 for controlling metabolic flux and improving thrombin production, verifying that the real-time control system of gene regulation is able to realize the dynamic regulation of gene expression with potential applications in bacterial physiology studies and metabolic engineering. Copyright © 2017. Published by Elsevier Inc.

Molecular, metabolic, and genetic control: An introduction

Science.gov (United States)

Tyson, John J.; Mackey, Michael C.

2001-03-01

The living cell is a miniature, self-reproducing, biochemical machine. Like all machines, it has a power supply, a set of working components that carry out its necessary tasks, and control systems that ensure the proper coordination of these tasks. In this Special Issue, we focus on the molecular regulatory systems that control cell metabolism, gene expression, environmental responses, development, and reproduction. As for the control systems in human-engineered machines, these regulatory networks can be described by nonlinear dynamical equations, for example, ordinary differential equations, reaction-diffusion equations, stochastic differential equations, or cellular automata. The articles collected here illustrate (i) a range of theoretical problems presented by modern concepts of cellular regulation, (ii) some strategies for converting molecular mechanisms into dynamical systems, (iii) some useful mathematical tools for analyzing and simulating these systems, and (iv) the sort of results that derive from serious interplay between theory and experiment.

Control of fluxes towards antibiotics and the role of primary metabolism in production of antibiotics

DEFF Research Database (Denmark)

Gunnarsson, Nina; Eliasson Lantz, Anna; Nielsen, Jacob

2004-01-01

Yield improvements in antibiotic-producing strains have classically been obtained through random mutagenesis and screening. An attractive alternative to this strategy is the rational design of producer strains via metabolic engineering, an approach that offers the possibility to increase yields...... in the metabolic network. Here we describe and discuss available methods for identification of these steps, both in antibiotic biosynthesis pathways and in the primary metabolism, which serves as the supplier of precursors and cofactors for the secondary metabolism. Finally, the importance of precursor...... and cofactor supply from primary metabolism in the biosynthesis of different types of antibiotics is discussed and recent developments in metabolic engineering towards increased product yields in antibiotic producing strains are reviewed....

Lycium barbarum Reduces Abdominal Fat and Improves Lipid Profile and Antioxidant Status in Patients with Metabolic Syndrome

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Mayara Zagonel de Souza Zanchet

2017-01-01

Full Text Available Natural antioxidants present in fruits have attracted considerable interest due to their presumed safety and potential nutritional value. Even though antioxidant activities of many fruits have been reported, the effects of phytochemicals of goji berry (GB in patients with metabolic syndrome have not been investigated. In this study, we examined anthropometric and biochemical parameters in patients with metabolic syndrome after the consumption of GB. The patients were divided into two groups, control (C and supplemented (S, and followed up for 45 days. Participants were individually instructed to carry out a healthy diet, but additionally, an inclusion of 14 g of the natural form of goji berry in the diet during 45 days for the S group was proposed. After 45 days of study, a significant reduction in transaminases as well as an improvement in lipid profile in the S group was observed. Likewise, a significant reduction in the waist circumference of the S group was observed when compared with that of the C group, and increased glutathione and catalase levels associated with a reduction of lipid peroxidation. These results suggest that this is an effective dietary supplement for the prevention of cardiovascular diseases in individuals with metabolic syndrome.

Urea and Ammonia Metabolism and the Control of Renal Nitrogen Excretion

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Mitch, William E.; Sands, Jeff M.

2015-01-01

Renal nitrogen metabolism primarily involves urea and ammonia metabolism, and is essential to normal health. Urea is the largest circulating pool of nitrogen, excluding nitrogen in circulating proteins, and its production changes in parallel to the degradation of dietary and endogenous proteins. In addition to serving as a way to excrete nitrogen, urea transport, mediated through specific urea transport proteins, mediates a central role in the urine concentrating mechanism. Renal ammonia excretion, although often considered only in the context of acid-base homeostasis, accounts for approximately 10% of total renal nitrogen excretion under basal conditions, but can increase substantially in a variety of clinical conditions. Because renal ammonia metabolism requires intrarenal ammoniagenesis from glutamine, changes in factors regulating renal ammonia metabolism can have important effects on glutamine in addition to nitrogen balance. This review covers aspects of protein metabolism and the control of the two major molecules involved in renal nitrogen excretion: urea and ammonia. Both urea and ammonia transport can be altered by glucocorticoids and hypokalemia, two conditions that also affect protein metabolism. Clinical conditions associated with altered urine concentrating ability or water homeostasis can result in changes in urea excretion and urea transporters. Clinical conditions associated with altered ammonia excretion can have important effects on nitrogen balance. PMID:25078422

Exogenous trehalose improves growth under limiting nitrogen through upregulation of nitrogen metabolism.

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Lin, Yingchao; Zhang, Jie; Gao, Weichang; Chen, Yi; Li, Hongxun; Lawlor, David W; Paul, Matthew J; Pan, Wenjie

2017-12-19

The trehalose (Tre) pathway has strong effects on growth and development in plants through regulation of carbon metabolism. Altering either Tre or trehalose 6-phosphate (T6P) can improve growth and productivity of plants as observed under different water availability. As yet, there are no reports of the effects of modification of Tre orT6P on plant performance under limiting nutrition. Here we report that nitrogen (N) metabolism is positively affected by exogenous application of Tre in nitrogen-deficient growing conditions. Spraying foliage of tobacco (Nicotiana tabacum) with trehalose partially alleviated symptoms of nitrogen deficiency through upregulation of nitrate and ammonia assimilation and increasing activities of nitrate reductase (NR), glycolate oxidase (GO), glutamine synthetase (GS) and glutamine oxoglutarate aminotransferase (GOGAT) with concomitant changes in ammonium (NH 4 + ) and nitrate (NO 3 - ) concentrations, glutamine and amino acids. Chlorophyll and total nitrogen content of leaves and rates of photosynthesis were increased compared to nitrogen-deficient plants without applied Tre. Total plant biomass accumulation was also higher in Tre -fed nitrogen-deficient plants, with a smaller proportion of dry weight partitioned to roots, compared to nitrogen-deficient plants without applied Tre. Consistent with higher nitrogen assimilation and growth, Tre application reduced foliar starch. Minimal effects of Tre feeding were observed on nitrogen-sufficient plants. The data show, for the first time, significant stimulatory effects of exogenous Tre on nitrogen metabolism and growth in plants growing under deficient nitrogen. Under such adverse conditions metabolism is regulated for survival rather than productivity. Application of Tre can alter this regulation towards maintenance of productive functions under low nitrogen. This has implications for considering approaches to modifying the Tre pathway for to improve crop nitrogen-use efficiency and

Moringa oleifera Lam. improves lipid metabolism during adipogenic differentiation of human stem cells.

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Barbagallo, I; Vanella, L; Distefano, A; Nicolosi, D; Maravigna, A; Lazzarino, G; Di Rosa, M; Tibullo, D; Acquaviva, R; Li Volti, G

2016-12-01

Moringa oleifera Lam., a multipurpose tree, is used traditionally for its nutritional and medicinal properties. It has been used for the treatment of a variety of conditions, including inflammation, cancer and metabolic disorders. We investigated the effect of Moringa oleifera Lam. on adipogenic differentiation of human adipose-derived mesenchymal stem cells and its impact on lipid metabolism and cellular antioxidant systems. We showed that Moringa oleifera Lam. treatment during adipogenic differentiation reduces inflammation, lipid accumulation and induces thermogenesis by activation of uncoupling protein 1 (UCP1), sirtuin 1 (SIRT1), peroxisome proliferator-activated receptor alpha (PPARα), and coactivator 1 alpha (PGC1α). In addition, Moringa oleifera Lam. induces heme oxygenase-1 (HO-1), a well established protective and antioxidant enzyme. Finally Moringa oleifera Lam. significantly decreases the expression of molecules involved in adipogenesis and upregulates the expression of mediators involved in thermogenesis and lipid metabolism. Our results suggest that Moringa oleifera Lam. may promote the brown remodeling of white adipose tissue inducing thermogenesis and improving metabolic homeostasis.

Diabetes self-management, depressive symptoms, quality of life and metabolic control in youth with type 1 diabetes in China.

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Guo, Jia; Whittemore, Robin; Grey, Margaret; Wang, Jing; Zhou, Zhi-Guang; He, Guo-Ping

2013-01-01

To assess diabetes self-management, depressive symptoms, quality of life and metabolic control in a cohort of youth with type 1 diabetes in mainland China. Predictors of self-management and depressive symptoms were also explored. Studies have shown that adaptation to childhood chronic illness is important in determining outcomes. Few studies have been reported on the behavioural, psychosocial and physiological adaptation processes and outcomes in Chinese youth with type 1 diabetes. This is a cross-sectional study as part of a multi-site longitudinal descriptive study. Data for this report were collected at baseline. A convenience sample of 136 eligible youth was recruited during follow-up visits in hospitals in 14 major cities of Hunan Province (located in central southern mainland China) from July 2009-October 2010. Data were collected on socio-demographic background, clinical characteristics, diabetes self-management, depressive symptoms, quality of life and metabolic control. Diabetes self-management was lower in Chinese youth compared with a US cohort and was associated with insulin treatment regimen, treatment location, depressive symptoms and gender. A total of 17·6% of youth reported high depressive symptoms, and depressive symptoms were correlated with family annual revenue, school attendance, peer relationship and parent-child relationship. The mean score of global satisfaction with quality of life was 17·14 ± 3·58. The mean HbA1c was 9·68%. Living with type 1 diabetes poses considerable challenges, and Chinese youth report lower self-management than US youth and high depressive symptoms. Metabolic control and quality of life were sub-optimal. More clinic visits, treatment for high depressive symptoms and an intensive insulin regimen may improve diabetes self-management for youth with type 1 diabetes in China. Culturally appropriate interventions aimed at helping them adapt to living with the disease and improving outcomes are urgently needed. © 2012

Concentrating carbohydrates before sleep improves feeding regulation and metabolic and inflammatory parameters in mice.

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Sofer, Sigal; Eliraz, Abraham; Madar, Zecharia; Froy, Oren

2015-10-15

New evidance highlights the importance of food timing. Recently, we showed that a low-calorie diet with carbohydrates eaten mostly at dinner changed diurnal hormone secretion and led to greater weight loss and improved metabolic status in obese people. Herein, we set out to test whether concentrated-carbohydrates diet (CCD), in which carbohydrates are fed only before sleep, leads to an improved metabolic status in mouse hypothalamus and peripheral tissues. Diet-induced obese mice were given concentrated or distributed carbohydrate diet for 6 weeks. Obese mice fed CCD ate 8.3% less, were 9.3% leaner and had 39.7% less fat mass. Leptin, ghrelin and adiponectin displayed altered secretion. In addition, these mice exhibited an improved biochemical and inflammatory status. In the hypothalamus, anorexigenic signals were up-regulated and orexigenic signals were down-regulated. In peripheral tissues, CCD promoted adiponectin signaling, repressed gluconeogenesis, enhanced lipid oxidation and lowered inflammation, thus ameliorating the major risk factors of obesity. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Improving Bioenergy Crops through Dynamic Metabolic Modeling

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Mojdeh Faraji

2017-10-01

Full Text Available Enormous advances in genetics and metabolic engineering have made it possible, in principle, to create new plants and crops with improved yield through targeted molecular alterations. However, while the potential is beyond doubt, the actual implementation of envisioned new strains is often difficult, due to the diverse and complex nature of plants. Indeed, the intrinsic complexity of plants makes intuitive predictions difficult and often unreliable. The hope for overcoming this challenge is that methods of data mining and computational systems biology may become powerful enough that they could serve as beneficial tools for guiding future experimentation. In the first part of this article, we review the complexities of plants, as well as some of the mathematical and computational methods that have been used in the recent past to deepen our understanding of crops and their potential yield improvements. In the second part, we present a specific case study that indicates how robust models may be employed for crop improvements. This case study focuses on the biosynthesis of lignin in switchgrass (Panicum virgatum. Switchgrass is considered one of the most promising candidates for the second generation of bioenergy production, which does not use edible plant parts. Lignin is important in this context, because it impedes the use of cellulose in such inedible plant materials. The dynamic model offers a platform for investigating the pathway behavior in transgenic lines. In particular, it allows predictions of lignin content and composition in numerous genetic perturbation scenarios.

A metabolic switch controls intestinal differentiation downstream of Adenomatous polyposis coli (APC).

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Sandoval, Imelda T; Delacruz, Richard Glenn C; Miller, Braden N; Hill, Shauna; Olson, Kristofor A; Gabriel, Ana E; Boyd, Kevin; Satterfield, Christeena; Remmen, Holly Van; Rutter, Jared; Jones, David A

2017-04-11

Elucidating signaling pathways that regulate cellular metabolism is essential for a better understanding of normal development and tumorigenesis. Recent studies have shown that mitochondrial pyruvate carrier 1 (MPC1) , a crucial player in pyruvate metabolism, is downregulated in colon adenocarcinomas. Utilizing zebrafish to examine the genetic relationship between MPC1 and Adenomatous polyposis coli (APC), a key tumor suppressor in colorectal cancer, we found that apc controls the levels of mpc1 and that knock down of mpc1 recapitulates phenotypes of impaired apc function including failed intestinal differentiation. Exogenous human MPC1 RNA rescued failed intestinal differentiation in zebrafish models of apc deficiency. Our data demonstrate a novel role for apc in pyruvate metabolism and that pyruvate metabolism dictates intestinal cell fate and differentiation decisions downstream of apc .

Deletion of genes involved in glutamate metabolism to improve poly-gamma-glutamic acid production in B. amyloliquefaciens LL3.

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Zhang, Wei; He, Yulian; Gao, Weixia; Feng, Jun; Cao, Mingfeng; Yang, Chao; Song, Cunjiang; Wang, Shufang

2015-02-01

Here, we attempted to elevate poly-gamma-glutamic acid (γ-PGA) production by modifying genes involved in glutamate metabolism in Bacillus amyloliquefaciens LL3. Products of rocR, rocG and gudB facilitate the conversion from glutamate to 2-oxoglutarate in Bacillus subtillis. The gene odhA is responsible for the synthesis of a component of the 2-oxoglutarate dehydrogenase complex that catalyzes the oxidative decarboxylation of 2-oxoglutarate to succinyl coenzyme A. In-frame deletions of these four genes were performed. In shake flask experiments the gudB/rocG double mutant presented enhanced production of γ-PGA, a 38 % increase compared with wild type. When fermented in a 5-L fermenter with pH control, the γ-PGA yield of the rocR mutant was increased to 5.83 g/L from 4.55 g/L for shake flask experiments. The gudB/rocG double mutant produced 5.68 g/L γ-PGA compared with that of 4.03 g/L for the wild type, a 40 % increase. Those results indicated the possibility of improving γ-PGA production by modifying glutamate metabolism, and identified potential genetic targets to improve γ-PGA production.

Improvement in cardiac function and free fatty acid metabolism in a case of dilated cardiomyopathy with CD36 deficiency.

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Hirooka, K; Yasumura, Y; Ishida, Y; Komamura, K; Hanatani, A; Nakatani, S; Yamagishi, M; Miyatake, K

2000-09-01

A 27-year-old man diagnosed as having dilated cardiomyopathy (DCM) without myocardial accumulation of 123I-beta-methyl-iodophenylpentadecanoic acid, and he was found to have type I CD36 deficiency. This abnormality of cardiac free fatty acid metabolism was also confirmed by other methods: 18F-fluoro-2-deoxyglucose positron emission tomography, measurements of myocardial respiratory quotient and cardiac fatty acid uptake. Although the type I CD36 deficiency was reconfirmed after 3 months, the abnormal free fatty acid metabolism improved after carvedilol therapy and was accompanied by improved cardiac function. Apart from a cause-and-effect relationship, carvedilol can improve cardiac function and increase free fatty acid metabolism in patients with both DCM and CD36 deficiency.

The CD36-PPARγ Pathway in Metabolic Disorders

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Loïze Maréchal

2018-05-01

Full Text Available Uncovering the biological role of nuclear receptor peroxisome proliferator-activated receptors (PPARs has greatly advanced our knowledge of the transcriptional control of glucose and energy metabolism. As such, pharmacological activation of PPARγ has emerged as an efficient approach for treating metabolic disorders with the current use of thiazolidinediones to improve insulin resistance in diabetic patients. The recent identification of growth hormone releasing peptides (GHRP as potent inducers of PPARγ through activation of the scavenger receptor CD36 has defined a novel alternative to regulate essential aspects of lipid and energy metabolism. Recent advances on the emerging role of CD36 and GHRP hexarelin in regulating PPARγ downstream actions with benefits on atherosclerosis, hepatic cholesterol biosynthesis and fat mitochondrial biogenesis are summarized here. The response of PPARγ coactivator PGC-1 is also discussed in these effects. The identification of the GHRP-CD36-PPARγ pathway in controlling various tissue metabolic functions provides an interesting option for metabolic disorders.

Self-Efficacy, Self-Care, and Metabolic Control in Persons with Type 2, Diet and Exercised Controlled Diabetes

National Research Council Canada - National Science Library

Randall, Lisa

1998-01-01

.... psychological determinants of self-care and metabolic control must be explored. Self-efficacy (Bandura, 1977) has demonstrated its importance in behavioral modification but has been minimally investigated in diabetes...

Berberine improves glucose metabolism in diabetic rats by inhibition of hepatic gluconeogenesis.

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Xuan Xia

2011-02-01

Full Text Available Berberine (BBR is a compound originally identified in a Chinese herbal medicine Huanglian (Coptis chinensis French. It improves glucose metabolism in type 2 diabetic patients. The mechanisms involve in activation of adenosine monophosphate activated protein kinase (AMPK and improvement of insulin sensitivity. However, it is not clear if BBR reduces blood glucose through other mechanism. In this study, we addressed this issue by examining liver response to BBR in diabetic rats, in which hyperglycemia was induced in Sprague-Dawley rats by high fat diet. We observed that BBR decreased fasting glucose significantly. Gluconeogenic genes, Phosphoenolpyruvate carboxykinase (PEPCK and Glucose-6-phosphatase (G6Pase, were decreased in liver by BBR. Hepatic steatosis was also reduced by BBR and expression of fatty acid synthase (FAS was inhibited in liver. Activities of transcription factors including Forkhead transcription factor O1 (FoxO1, sterol regulatory element-binding protein 1c (SREBP1 and carbohydrate responsive element-binding protein (ChREBP were decreased. Insulin signaling pathway was not altered in the liver. In cultured hepatocytes, BBR inhibited oxygen consumption and reduced intracellular adenosine triphosphate (ATP level. The data suggest that BBR improves fasting blood glucose by direct inhibition of gluconeogenesis in liver. This activity is not dependent on insulin action. The gluconeogenic inhibition is likely a result of mitochondria inhibition by BBR. The observation supports that BBR improves glucose metabolism through an insulin-independent pathway.

Effects of short- and long-term Mediterranean-based dietary treatment on plasma LC-QTOF/MS metabolic profiling of subjects with metabolic syndrome features: The Metabolic Syndrome Reduction in Navarra (RESMENA) randomized controlled trial.

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Bondia-Pons, Isabel; Martinez, José Alfredo; de la Iglesia, Rocio; Lopez-Legarrea, Patricia; Poutanen, Kaisa; Hanhineva, Kati; Zulet, Maria de los Ángeles

2015-04-01

Adherence to the Mediterranean diet has been associated with a reduced risk of metabolic syndrome (MetS). Metabolomics approach may contribute to identify beneficial associations of metabolic changes affected by Mediterranean diet-based interventions with inflammatory and oxidative-stress markers related to the etiology and development of the MetS. Liquid chromatography coupled to quadrupole-time of flight-MS metabolic profiling was applied to plasma from a 6-month randomized intervention with two sequential periods, a 2-month nutritional-learning intervention period, and a 4-month self-control period, with two energy-restricted diets; the RESMENA diet (based on the Mediterranean dietary pattern) and the Control diet (based on the American Heart Association guidelines), in 72 subjects with a high BMI and at least two features of MetS. The major contributing biomarkers of each sequential period were lipids, mainly phospholipids and lysophospholipids. Dependency network analysis showed a different pattern of associations between metabolic changes and clinical variables after 2 and 6 month of intervention, with a highly interconnected network during the nutritional-learning intervention period of the study. The 2-month RESMENA diet produced significant changes in the plasma metabolic profile of subjects with MetS features. However, at the end of the 6-month study, most of the associations between metabolic and clinical variables disappeared; suggesting that adherence to healthy dietary habits had declined during the self-control period. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Restoration of muscle mitochondrial function and metabolic flexibility in type 2 diabetes by exercise training is paralleled by increased myocellular fat storage and improved insulin sensitivity.

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Meex, Ruth C R; Schrauwen-Hinderling, Vera B; Moonen-Kornips, Esther; Schaart, Gert; Mensink, Marco; Phielix, Esther; van de Weijer, Tineke; Sels, Jean-Pierre; Schrauwen, Patrick; Hesselink, Matthijs K C

2010-03-01

Mitochondrial dysfunction and fat accumulation in skeletal muscle (increased intramyocellular lipid [IMCL]) have been linked to development of type 2 diabetes. We examined whether exercise training could restore mitochondrial function and insulin sensitivity in patients with type 2 diabetes. Eighteen male type 2 diabetic and 20 healthy male control subjects of comparable body weight, BMI, age, and VO2max participated in a 12-week combined progressive training program (three times per week and 45 min per session). In vivo mitochondrial function (assessed via magnetic resonance spectroscopy), insulin sensitivity (clamp), metabolic flexibility (indirect calorimetry), and IMCL content (histochemically) were measured before and after training. Mitochondrial function was lower in type 2 diabetic compared with control subjects (P = 0.03), improved by training in control subjects (28% increase; P = 0.02), and restored to control values in type 2 diabetic subjects (48% increase; P type 2 diabetic subjects (delta Rd 63% increase; P type 2 diabetic subjects was restored (delta respiratory exchange ratio 63% increase; P = 0.01) but was unchanged in control subjects (delta respiratory exchange ratio 7% increase; P = 0.22). Starting with comparable pretraining IMCL levels, training tended to increase IMCL content in type 2 diabetic subjects (27% increase; P = 0.10), especially in type 2 muscle fibers. Exercise training restored in vivo mitochondrial function in type 2 diabetic subjects. Insulin-mediated glucose disposal and metabolic flexibility improved in type 2 diabetic subjects in the face of near-significantly increased IMCL content. This indicates that increased capacity to store IMCL and restoration of improved mitochondrial function contribute to improved muscle insulin sensitivity.

Recent applications of synthetic biology tools for yeast metabolic engineering

DEFF Research Database (Denmark)

Jensen, Michael Krogh; Keasling, Jay

2015-01-01

to engineer microbial chemical factories has steadily decreased, improvement is still needed. Through the development of synthetic biology tools for key microbial hosts, it should be possible to further decrease the development times and improve the reliability of the resulting microorganism. Together...... with continuous decreases in price and improvements in DNA synthesis, assembly and sequencing, synthetic biology tools will rationalize time-consuming strain engineering, improve control of metabolic fluxes, and diversify screening assays for cellular metabolism. This review outlines some recently developed...... synthetic biology tools and their application to improve production of chemicals and fuels in yeast. Finally, we provide a perspective for the challenges that lie ahead....

The radical scavenger edaravone improves neurologic function and perihematomal glucose metabolism after acute intracerebral hemorrhage.

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Shang, Hanbing; Cui, Derong; Yang, Dehua; Liang, Sheng; Zhang, Weifeng; Zhao, Weiguo

2015-01-01

Oxidative injury caused by reactive oxygen species plays an important role in the progression of intracerebral hemorrhage (ICH)-induced secondary brain injury. Previous studies have demonstrated that the free radical scavenger edaravone may prevent neuronal injury and brain edema after ICH. However, the influence of edaravone on cerebral metabolism in the early stages after ICH and the underlying mechanism have not been fully investigated. In the present study, we investigated the effect of edaravone on perihematomal glucose metabolism using (18)F-fluorordeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). Additionally, the neurologic deficits, brain edemas, and cell death that followed ICH were quantitatively analyzed. After blood infusion, the rats treated with edaravone showed significant improvement in both forelimb placing and corner turn tests compared with those treated with vehicle. Moreover, the brain water content of the edaravone-treated group was significantly decreased compared with that of the vehicle group on day 3 after ICH. PET/CT images of ICH rats exhibited obvious decreases in FDG standardized uptake values in perihematomal region on day 3, and the lesion-to-normal ratio of the edaravone-treated ICH rats was significantly increased compared with that of the control rats. Calculation of the brain injury volumes from the PET/CT images revealed that the volumes of the blood-induced injuries were significantly smaller in the edaravone group compared with the vehicle group. Terminal Deoxynucleotidyl Transferase-mediated dUTP Nick End Labeling assays performed 3 days after ICH revealed that the numbers of apoptotic cells in perihematomal region of edaravone-treated ICH rats were decreased relative to the vehicle group. Thus, the present study demonstrates that edaravone has scavenging properties that attenuate neurologic behavioral deficits and brain edema in the early period of ICH. Additionally, edaravone may improve

Effects of Aerobic and Resistance Exercise on Metabolic Syndrome, Sarcopenic Obesity, and Circulating Biomarkers in Overweight or Obese Survivors of Breast Cancer: A Randomized Controlled Trial.

Science.gov (United States)

Dieli-Conwright, Christina M; Courneya, Kerry S; Demark-Wahnefried, Wendy; Sami, Nathalie; Lee, Kyuwan; Buchanan, Thomas A; Spicer, Darcy V; Tripathy, Debu; Bernstein, Leslie; Mortimer, Joanne E

2018-03-20

Purpose Metabolic syndrome is associated with an increased risk of cardiovascular disease, type 2 diabetes, and breast cancer recurrence in survivors of breast cancer. This randomized controlled trial assessed the effects of a 16-week combined aerobic and resistance exercise intervention on metabolic syndrome, sarcopenic obesity, and serum biomarkers among ethnically diverse, sedentary, overweight, or obese survivors of breast cancer. Methods Eligible survivors of breast cancer (N = 100) were randomly assigned to exercise (n = 50) or usual care (n = 50). The exercise group participated in supervised moderate-to-vigorous-65% to 85% of heart rate maximum-aerobic and resistance exercise three times per week for 16 weeks. Metabolic syndrome z-score (primary outcome), sarcopenic obesity, and serum biomarkers were measured at baseline, postintervention (4 months), and 3-month follow-up (exercise only). Results Participants were age 53 ± 10.4 years, 46% were obese, and 74% were ethnic minorities. Adherence to the intervention was 95%, and postintervention assessments were available in 91% of participants. Postintervention metabolic syndrome z-score was significantly improved in exercise versus usual care (between-group difference, -4.4; 95% CI, -5.9 to -2.7; P metabolic syndrome variables remained significantly improved compared with baseline in the exercise group ( P exercise effectively attenuated metabolic syndrome, sarcopenic obesity, and relevant biomarkers in an ethnically diverse sample of sedentary, overweight, or obese survivors of breast cancer. Our findings suggest a targeted exercise prescription for improving metabolic syndrome in survivors of breast cancer and support the incorporation of supervised clinical exercise programs into breast cancer treatment and survivorship care plans.

Sustained exercise-trained juvenile black carp (Mylopharyngodon piceus at a moderate water velocity exhibit improved aerobic swimming performance and increased postprandial metabolic responses

Directory of Open Access Journals (Sweden)

Xiuming Li

2018-02-01

Full Text Available The objectives of this study were to examine whether sustained exercise training at four water velocities, i.e. nearly still water (control, 1 body length (BL s−1, 2 BL s−1 and 4 BL s−1, has effects on swimming performance and digestive metabolism in juvenile black carp (Mylopharyngodon piceus. The results demonstrated that fish subjected to sustained training at 2 and 4 BL s−1 showed significantly higher critical swimming speed (Ucrit and maximum metabolic rate (MMR over the control group. Fish subjected to sustained training at 1 and 2 BL s−1 showed a significantly (30 and 54% prolonged duration, 14 and 17% higher postprandial ṀO2 increment (i.e. ṀO2peak, and 62 and 92% more energy expended on specific dynamic action (SDA, respectively, after consuming a similar meal over fish kept in nearly still water. These results suggest that (1 sustained exercise training at a higher speed (2 or 4 BL s−1 had a positive influence on the aerobic swimming performance of juvenile M. piceus, which may be associated with improved aerobic metabolism; and (2 sustained exercise training at a lower speed (1 or 2 BL s−1 resulted in elevated postprandial metabolic responses in juvenile M. piceus.

Vulnerability to stress, anxiety and depressive symptoms and metabolic control in Type 2 diabetes

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Gois Carlos

2012-06-01

Full Text Available Abstract Background Vulnerability to stress has been associated to distress, emotional distress symptoms and metabolic control in type 2 diabetes mellitus (T2DM patients as well. Furthermore some conflicting results were noticed. We aimed to evaluate the effect over metabolic control in what concerns vulnerability to stress beyond depressive and anxiety symptoms. Findings This cross-sectional study assessed 273 T2DM patients with depressive and anxiety symptoms using the Hospital Anxiety Depression Scale (HADS and the 23 Questions to assess Vulnerability to Stress (23QVS, along with demographic and clinical diabetes-related variables. Hierarchical logistic regression models were used to investigate predictors of poor glycemic control. The results showed an association of depressive symptoms (odds ratio = 1.12, 95%CI = 1.01-1.24, P = 0.030 with increased risk of poor glycemic control. Anxiety symptoms and vulnerability to stress on their own were not predictive of metabolic control, respectively (odds ratio = 0.92, 95%CI = 0.84-1.00, P = 0.187 and odds ratio = 0.98, 95%CI = 0.95-1.01, P = 0.282. Conclusions Our data suggested that vulnerability to stress was not predictive of poor glycemic control in T2DM, but depressive symptoms were.

Perspectives in metabolic engineering: understanding cellular regulation towards the control of metabolic routes.

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Zadran, Sohila; Levine, Raphael D

2013-01-01

Metabolic engineering seeks to redirect metabolic pathways through the modification of specific biochemical reactions or the introduction of new ones with the use of recombinant technology. Many of the chemicals synthesized via introduction of product-specific enzymes or the reconstruction of entire metabolic pathways into engineered hosts that can sustain production and can synthesize high yields of the desired product as yields of natural product-derived compounds are frequently low, and chemical processes can be both energy and material expensive; current endeavors have focused on using biologically derived processes as alternatives to chemical synthesis. Such economically favorable manufacturing processes pursue goals related to sustainable development and "green chemistry". Metabolic engineering is a multidisciplinary approach, involving chemical engineering, molecular biology, biochemistry, and analytical chemistry. Recent advances in molecular biology, genome-scale models, theoretical understanding, and kinetic modeling has increased interest in using metabolic engineering to redirect metabolic fluxes for industrial and therapeutic purposes. The use of metabolic engineering has increased the productivity of industrially pertinent small molecules, alcohol-based biofuels, and biodiesel. Here, we highlight developments in the practical and theoretical strategies and technologies available for the metabolic engineering of simple systems and address current limitations.

Complications of acromegaly: cardiovascular, respiratory and metabolic comorbidities.

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Pivonello, Rosario; Auriemma, Renata S; Grasso, Ludovica F S; Pivonello, Claudia; Simeoli, Chiara; Patalano, Roberta; Galdiero, Mariano; Colao, Annamaria

2017-02-01

Acromegaly is associated with an enhanced mortality, with cardiovascular and respiratory complications representing not only the most frequent comorbidities but also two of the main causes of deaths, whereas a minor role is played by metabolic complications, and particularly diabetes mellitus. The most prevalent cardiovascular complications of acromegaly include a cardiomyopathy, characterized by cardiac hypertrophy and diastolic and systolic dysfunction together with arterial hypertension, cardiac rhythm disorders and valve diseases, as well as vascular endothelial dysfunction. Biochemical control of acromegaly significantly improves cardiovascular disease, albeit completely recovering to normal mainly in young patients with short disease duration. Respiratory complications, represented mainly by sleep-breathing disorders, particularly sleep apnea, and respiratory insufficiency, frequently occur at the early stage of the disease and, although their severity decreases with disease control, this improvement does not often change the indication for a specific therapy directed to improve respiratory function. Metabolic complications, including glucose and lipid disorders, are variably reported in acromegaly. Treatments of acromegaly may influence glucose metabolism, and the presence of diabetes mellitus in acromegaly may affect the choice of treatments, so that glucose homeostasis is worth being monitored during the entire course of the disease. Early diagnosis and prompt treatment of acromegaly, aimed at obtaining a strict control of hormone excess, are the best strategy to limit the development or reverse the complications and prevent the premature mortality.

Brain Ceramide Metabolism in the Control of Energy Balance

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Céline Cruciani-Guglielmacci

2017-10-01

Full Text Available The regulation of energy balance by the central nervous system (CNS is a key actor of energy homeostasis in mammals, and deregulations of the fine mechanisms of nutrient sensing in the brain could lead to several metabolic diseases such as obesity and type 2 diabetes (T2D. Indeed, while neuronal activity primarily relies on glucose (lactate, pyruvate, the brain expresses at high level enzymes responsible for the transport, utilization and storage of lipids. It has been demonstrated that discrete neuronal networks in the hypothalamus have the ability to detect variation of circulating long chain fatty acids (FA to regulate food intake and peripheral glucose metabolism. During a chronic lipid excess situation, this physiological lipid sensing is impaired contributing to type 2 diabetes in predisposed subjects. Recently, different studies suggested that ceramides levels could be involved in the regulation of energy balance in both hypothalamic and extra-hypothalamic areas. Moreover, under lipotoxic conditions, these ceramides could play a role in the dysregulation of glucose homeostasis. In this review we aimed at describing the potential role of ceramides metabolism in the brain in the physiological and pathophysiological control of energy balance.

Anti-IL-17 Antibody Improves Hepatic Steatosis by Suppressing Interleukin-17-Related Fatty Acid Synthesis and Metabolism

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Weidong Shi

2013-01-01

Full Text Available To investigate the relationship between interleukin-17 and proteins involved in fatty acid metabolism with respect to alcoholic liver disease, male ICR mice were randomized into five groups: control, alcoholic liver disease (ALD at 4 weeks, 8 weeks, and 12 weeks, and anti-IL-17 antibody treated ALD. A proteomic approach was adopted to investigate changes in liver proteins between control and ALD groups. The proteomic analysis was performed by two-dimensional difference gel electrophoresis. Spots of interest were subsequently subjected to nanospray ionization tandem mass spectrometry (MS/MS for protein identification. Additionally, expression levels of selected proteins were confirmed by western blot. Transcriptional levels of some selected proteins were determined by RT-PCR. Expression levels of 95 protein spots changed significantly (ratio >1.5, P<0.05 during the development of ALD. Sterol regulatory element-binding protein-lc (SREBP-1c, carbohydrate response element binding protein (ChREBP, enoyl-coenzyme A hydratase (ECHS1, and peroxisome proliferator-activated receptor alpha (PPAR-α were identified by MS/MS among the proteins shown to vary the most; increased IL-17 elevated the transcription of SREBP-1c and ChREBP but suppressed ECHS1 and PPAR-α. The interleukin-17 signaling pathway is involved in ALD development; anti-IL-17 antibody improved hepatic steatosis by suppressing interleukin-17-related fatty acid metabolism.

It must be my metabolism: Metabolic control of mind

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Dana M Small

2014-07-01

relationship between the reinforcing potency of sugared solutions and the metabolic effects that follow their consumption (16, also see the abstract of I. de Araujo. We therefore hypothesized that metabolic response provides the critical signal necessary to condition preference. To test this prediction in humans we designed a flavor nutrient conditioning study in which participants first rated their liking for novel flavored beverages and then, over a three week-long conditioning protocol, alternately ingested one of the flavored beverages with 112.5 kcal from maltodextrin, a tasteless and odorless polysaccharide that breaks down into glucose, and another flavored beverage with no calories added. Plasma glucose was measured before and after each of the drinks’ consumption as a proxy measure of metabolic response, assuming that glucose oxidation depends upon the level of circulating glucose. For each participant flavor-calorie pairings were held constant but the identity of the conditioned flavors were counterbalanced across participants. Following the exposure phase, participants’ liking of, and brain responses to, non-caloric versions of the flavors were assessed. We predicted that change in plasma glucose produced by beverage consumption during the exposure sessions would be associated with neural responses in dopamine source and target regions to the calorie predictive flavor. As predicted, response in the ventral striatum and hypothalamus to the calorie-predictive flavor (CS+ vs. non the noncaloric-predictive flavor (CS- was strongly associated with the changes in plasma glucose levels produced by ingestion of these same beverages when consumed previously either with (CS+ or without (CS- calories (17. Specifically, the greater the increase in circulating glucose occurring post ingestion of the beverage containing 112.5 kcal from maltodextrin versus the noncaloric drink, the stronger was the brain response to the CS+ compared to the CS- flavor. Importantly, because each

How to determine control of growth rate in a chemostat. Using metabolic control analysis to resolve the paradox

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Snoep, Jacky L.; Jensen, Peter Ruhdal; Groeneveld, Philip

1994-01-01

how, paradoxically, one can determine control of growth rate, of growth yield and of other fluxes in a chemostat. We develop metabolic control analysis for the chemostat. this analysis does not depend on the particular way in which specific growth rate varies with the concentration of the growth...

IGOB131, a novel seed extract of the West African plant Irvingia gabonensis, significantly reduces body weight and improves metabolic parameters in overweight humans in a randomized double-blind placebo controlled investigation

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Mbofung Carl MF

2009-03-01

Full Text Available Abstract Background A recent in vitro study indicates that IGOB131, a novel seed extract of the traditional West African food plant Irvingia gabonensis, favorably impacts adipogenesis through a variety of critical metabolic pathways including PPAR gamma, leptin, adiponectin, and glycerol-3 phosphate dehydrogenase. This study was therefore aimed at evaluating the effects of IGOB131, an extract of Irvingia gabonensis, on body weight and associated metabolic parameters in overweight human volunteers. Methods The study participants comprised of 102 healthy, overweight and/or obese volunteers (defined as BMI > 25 kg/m2 randomly divided into two groups. The groups received on a daily basis, either 150 mg of IGOB131 or matching placebo in a double blinded fashion, 30–60 minutes before lunch and dinner. At baseline, 4, 8 and 10 weeks of the study, subjects were evaluated for changes in anthropometrics and metabolic parameters to include fasting lipids, blood glucose, C-reactive protein, adiponectin, and leptin. Results Significant improvements in body weight, body fat, and waist circumference as well as plasma total cholesterol, LDL cholesterol, blood glucose, C-reactive protein, adiponectin and leptin levels were observed in the IGOB131 group compared with the placebo group. Conclusion Irvingia gabonensis administered 150 mg twice daily before meals to overweight and/or obese human volunteers favorably impacts body weight and a variety of parameters characteristic of the metabolic syndrome. This is the first double blind randomized placebo controlled clinical trial regarding the anti-obesity and lipid profile modulating effects of an Irvingia gabonensis extract. The positive clinical results, together with our previously published mechanisms of gene expression modulation related to key metabolic pathways in lipid metabolism, provide impetus for much larger clinical studies. Irvingia gabonensis extract may prove to be a useful tool in dealing with the

Mitochondrial metabolism and the control of vascular smooth muscle cell proliferation

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Mario eChiong

2014-12-01

Full Text Available Differentiation and dedifferentiation of vascular smooth muscle cells (VSMCs are essential processes of vascular development. VSMCs have biosynthetic, proliferative and contractile roles in the vessel wall. Alterations in the differentiated state of the VSMCs play a critical role in the pathogenesis of a variety of cardiovascular diseases, including atherosclerosis, hypertension and vascular stenosis. This review provides an overview of the current state of knowledge of molecular mechanisms involved in the control of VSMC proliferation, with particular focus on mitochondrial metabolism. Mitochondrial activity can be controlled by regulating mitochondrial dynamics, i.e. mitochondrial fusion and fission, and by regulating mitochondrial calcium handling through the interaction with the endoplasmic reticulum (ER. Alterations in both VSMC proliferation and mitochondrial function can be triggered by dysregulation of mitofusin-2, a small GTPase associated with mitochondrial fusion and mitochondrial-ER interaction. Several lines of evidence highlight the relevance of mitochondrial metabolism in the control of VSMC proliferation, indicating a new area to be explored in the treatment of vascular diseases.

Metabolic Agents that Enhance ATP can Improve Cognitive Functioning: A Review of the Evidence for Glucose, Oxygen, Pyruvate, Creatine, and l-Carnitine

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Lauren Owen

2011-08-01

Full Text Available Over the past four or five decades, there has been increasing interest in the neurochemical regulation of cognition. This field received considerable attention in the 1980s, with the identification of possible cognition enhancing agents or “smart drugs”. Even though many of the optimistic claims for some agents have proven premature, evidence suggests that several metabolic agents may prove to be effective in improving and preserving cognitive performance and may lead to better cognitive aging through the lifespan. Aging is characterized by a progressive deterioration in physiological functions and metabolic processes. There are a number of agents with the potential to improve metabolic activity. Research is now beginning to identify these various agents and delineate their potential usefulness for improving cognition in health and disease. This review provides a brief overview of the metabolic agents glucose, oxygen, pyruvate, creatine, and l-carnitine and their beneficial effects on cognitive function. These agents are directly responsible for generating ATP (adenosine triphosphate the main cellular currency of energy. The brain is the most metabolically active organ in the body and as such is particularly vulnerable to disruption of energy resources. Therefore interventions that sustain adenosine triphosphate (ATP levels may have importance for improving neuronal dysfunction and loss. Moreover, recently, it has been observed that environmental conditions and diet can affect transgenerational gene expression via epigenetic mechanisms. Metabolic agents might play a role in regulation of nutritional epigenetic effects. In summary, the reviewed metabolic agents represent a promising strategy for improving cognitive function and possibly slowing or preventing cognitive decline.

Guava leaf extracts promote glucose metabolism in SHRSP.Z-Leprfa/Izm rats by improving insulin resistance in skeletal muscle.

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Guo, Xiangyu; Yoshitomi, Hisae; Gao, Ming; Qin, Lingling; Duan, Ying; Sun, Wen; Xu, Tunhai; Xie, Peifeng; Zhou, Jingxin; Huang, Liansha; Liu, Tonghua

2013-03-01

Metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM) have been associated with insulin-resistance; however, the effective therapies in improving insulin sensitivity are limited. This study is aimed at investigating the effect of Guava Leaf (GL) extracts on glucose tolerance and insulin resistance in SHRSP.Z-Leprfa/Izm rats (SHRSP/ZF), a model of spontaneously metabolic syndrome. Male rats at 7 weeks of age were administered with vehicle water or treated by gavage with 2 g/kg GL extracts daily for six weeks, and their body weights, water and food consumption, glucose tolerance, and insulin resistance were measured. Compared with the controls, treatment with GL extracts did not modulate the amounts of water and food consumption, but significantly reduced the body weights at six weeks post treatment. Treatment with GL extracts did not alter the levels of fasting plasma glucose and insulin, but significantly reduced the levels of plasma glucose at 60 and 120 min post glucose challenge, also reduced the values of AUC and quantitative insulin sensitivity check index (QUICKI) at 42 days post treatment. Furthermore, treatment with GL extracts promoted IRS-1, AKT, PI3Kp85 expression, then IRS-1, AMKP, and AKT308, but not AKT473, phosphorylation, accompanied by increasing the ratios of membrane to total Glut 4 expression and adiponectin receptor 1 transcription in the skeletal muscles. These data indicated that GL extracts improved glucose metabolism and insulin sensitivity in the skeletal muscles of rats by modulating the insulin-related signaling.

[Aging and metabolism: changes and regulation].

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Ortiz, Genaro Gabriel; Arias-Merino, Elva D; Velázquez-Brizuela, Irma E; Pacheco-Moisés, Fermín P; Flores-Alvarado, Luis J; Torres-Sánchez, Erandis D; Cortés-Enríquez, Fernando; González-Renovato, Erika D; Ortiz-Velázquez, Irma G

2012-09-01

Studies about the effects of aging in the physiology and metabolism are increasingly, one of its objectives is to help implement programs to improve the quality of life and prevent disability in elderly. It is relevant to mention that, during aging, there is a natural metabolic deceleration, a series of changes in the regulation of energy are produced, which contributes to loss of weight and fat; the changes in the regulation of caloric intake contribute to increase the susceptibility to energy imbalance both positive and negative, which is associated with a deterioration in health. However, to grow old, is not a death sentence for metabolism, on the other hand, it can be controlled by maintaining an active lifestyle, coupled with this, research has shown that the metabolism'can be regulated by a synchronized clock (circadian rhythms), which is mediated by regulatory proteins, this relationship ensures the proper functioning of the cells and therefore good health. The aim of this review is to provide updated information on the energy- metabolism-regulation and its relationship with the great variety of components involved in energy expenditure that accompany aging, to analyze the regulation of this system to improve the quality of life and maintenance of health in old age.

Diabetes in children and adolescents from ethnic minorities: barriers to education, treatment and good metabolic control

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Povlsen, Lene; Olsen, Birthe; Ladelund, Steen

2005-01-01

AIM: This paper reports an investigation to establish whether metabolic control is different in children and adolescents from ethnic minorities with type 1 diabetes compared with young Danish patients, and to learn about factors affecting their opportunities to achieve good metabolic control....... BACKGROUND: The prevalence of diabetes in children and adolescents from ethnic minorities in Denmark is increasing. Having a different ethnic background has frequently been described as a risk factor for poor metabolic control, but whether the risk is represented by the ethnicity and immigration itself...... the centres provided limited specialized knowledge and support. The questionnaires completed by the parents revealed limited schooling, lack of professional education and a major need for interpreters; these characteristics were especially prevalent among the mothers. CONCLUSIONS: Young patients from ethnic...

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

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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 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.

Beneficial effects of viscous dietary fiber from Konjac-mannan in subjects with the insulin resistance syndrome: results of a controlled metabolic trial.

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Vuksan, V; Sievenpiper, J L; Owen, R; Swilley, J A; Spadafora, P; Jenkins, D J; Vidgen, E; Brighenti, F; Josse, R G; Leiter, L A; Xu, Z; Novokmet, R

2000-01-01

Dietary fiber has recently received recognition for reducing the risk of developing diabetes and heart disease. The implication is that it may have therapeutic benefit in prediabetic metabolic conditions. To test this hypothesis, we investigated the effect of supplementing a high-carbohydrate diet with fiber from Konjac-mannan (KJM) on metabolic control in subjects with the insulin resistance syndrome. We screened 278 free-living subjects between the ages of 45 and 65 years from the Canadian-Maltese Diabetes Study. A total of 11 (age 55+/-4 years, BMI 28+/-1.5 kg/m2) were recruited who satisfied the inclusion criteria: impaired glucose tolerance, reduced HDL cholesterol, elevated serum triglycerides, and moderate hypertension. After an 8-week baseline, they were randomly assigned to take either KJM fiber-enriched test biscuits (0.5 g of glucomannan per 100 kcal of dietary intake or 8-13 g/day) or wheat bran fiber (WB) control biscuits for two 3-week treatment periods separated by a 2-week washout. The diets were isoenergetic, metabolically controlled, and conformed to National Cholesterol Education Program Step 2 guidelines. Serum lipids, glycemic control, and blood pressure were the outcome measures. Decreases in serum cholesterol (total, 12.4+/-3.1%, PFasting blood glucose, insulin, triglycerides, HDL cholesterol, and body weight remained unchanged. A diet rich in high-viscosity KJM improves glycemic control and lipid profile, suggesting a therapeutic potential in the treatment of the insulin resistance syndrome.

Prevalence of chronic complications, metabolic control and nutritional intake in type 1 diabetes

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Toeller, M; Buyken, A E; Heitkamp, G

1999-01-01

and proliferative retinopathy were more common. Persons from the eastern European and the German centres consumed undesirably high amounts of cholesterol, total and saturated fat. Overall, improvements in the prevention, detection and management of diabetes complications in persons with type 1 diabetes......) and chronic diabetes complications (retinopathy, nephropathy, neuropathy, cardiovascular disease) were all considerably more frequent in the eastern European centres. HbA1c was lower in the German centres than in the total EURODIAB cohort or in the north-western European centres, but severe hypoglycaemia......This study compares the prevalence of chronic complications, the quality of metabolic control and the nutritional intake in people with type 1 diabetes in different European regions. The EURODIAB Complications Study included a sample of 3250 European patients with type 1 diabetes stratified...

Vitamin K2 Improves Anxiety and Depression but not Cognition in Rats with Metabolic Syndrome: a Role of Blood Glucose?

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Gancheva, Silvia M; Zhelyazkova-Savova, Maria D

2016-12-01

The metabolic syndrome is a socially important disorder of energy utilization and storage, recognized as a factor predisposing to the development of depression, anxiety and cognitive impairment in humans. In the present study we examined the effects of vitamin K2 on the behavior of rats with metabolic syndrome and looked for relationships with the effects on blood sugar. Male Wistar rats were divided in four groups: a control group on a regular rat chow, a metabolic syndrome (MS) group fed a high-fat high-fructose diet, a control group treated with vitamin K2 and a MS group treated with vitamin K2. Vitamin K2 was given by gavage. At the end of the study (after 10 weeks) behavioral tests were performed and fasting blood glucose was measured. Anxiety was determined using the social interaction test and depression was assessed by the Porsolt test. Memory effects were estimated by the object recognition test. Correlations between fasting blood glucose and behavioral performance were analyzed. The rats from the MS group had elevated blood glucose. They had anxiety, depression and memory deficit. Vitamin K2 normalized blood glucose, reduced anxiety and depression, but did not improve memory. Time of social interaction (inverse index of anxiety) and memory recognition were negatively correlated with blood glucose in the untreated rats but the immobility time (measure of depression) was not. When vitamin K2-treated rats were added, the correlation of blood glucose with the time of social interaction was kept, but the one with the recognition memory was lost. It might be that the anxiolytic effect of vitamin K2 in this setting is at least partly due to its effects on blood glucose, while the anti-depressant effect is glucose-independent. The present study demonstrated that vitamin K2 prevented the development of anxiety and depression, but did not improve the memory deficit caused by the dietary manipulation in an experimental model of metabolic syndrome. It might be that

Improving clustering with metabolic pathway data.

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Milone, Diego H; Stegmayer, Georgina; López, Mariana; Kamenetzky, Laura; Carrari, Fernando

2014-04-10

It is a common practice in bioinformatics to validate each group returned by a clustering algorithm through manual analysis, according to a-priori biological knowledge. This procedure helps finding functionally related patterns to propose hypotheses for their behavior and the biological processes involved. Therefore, this knowledge is used only as a second step, after data are just clustered according to their expression patterns. Thus, it could be very useful to be able to improve the clustering of biological data by incorporating prior knowledge into the cluster formation itself, in order to enhance the biological value of the clusters. A novel training algorithm for clustering is presented, which evaluates the biological internal connections of the data points while the clusters are being formed. Within this training algorithm, the calculation of distances among data points and neurons centroids includes a new term based on information from well-known metabolic pathways. The standard self-organizing map (SOM) training versus the biologically-inspired SOM (bSOM) training were tested with two real data sets of transcripts and metabolites from Solanum lycopersicum and Arabidopsis thaliana species. Classical data mining validation measures were used to evaluate the clustering solutions obtained by both algorithms. Moreover, a new measure that takes into account the biological connectivity of the clusters was applied. The results of bSOM show important improvements in the convergence and performance for the proposed clustering method in comparison to standard SOM training, in particular, from the application point of view. Analyses of the clusters obtained with bSOM indicate that including biological information during training can certainly increase the biological value of the clusters found with the proposed method. It is worth to highlight that this fact has effectively improved the results, which can simplify their further analysis.The algorithm is available as a

Metabolic control, self-care behaviors, and parenting in adolescents with type 1 diabetes: a correlational study.

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Greene, Maia Stoker; Mandleco, Barbara; Roper, Susanne Olsen; Marshall, Elaine S; Dyches, Tina

2010-01-01

The purpose of this pilot study was to explore relationships among metabolic control, self-care behaviors, and parenting in adolescents with type 1 diabetes. Twenty-nine adolescents (mean age, 14.1 years) and their parents participated. Metabolic control was determined by an average of 4 A1C values taken prior to study enrollment; self-care behaviors were measured with a 12-item self-report questionnaire; parenting style was evaluated using the Parenting Practices Report. The mean for A1C values was 8.5%; the mean for overall self-care behaviors was 4.93 (5 = usually). Participants rated themselves highest on the self-care behaviors of giving insulin shots when indicated and adjusting insulin when eating a lot. They ranked themselves lowest on eating a low-fat diet and testing urine for ketones. Parents tended to be more authoritative in their approaches to parenting than either authoritarian or permissive. A significant relationship was found between authoritative mothering and adolescent self-care behaviors and metabolic control. Regression analyses controlling for age and length of time with diabetes confirmed the significance of these relationships. Authoritative fathering positively correlated with the self-care behaviors of monitoring blood glucose, taking insulin, and not skipping meals. A relationship was also noted between permissive parenting by mothers/fathers and poorer metabolic outcomes. However, the permissive parenting correlations did not remain significant when controlling for age and length of time with diabetes. Clinicians may help prevent declining participation in self-care behaviors and metabolic control in adolescents with type 1 diabetes by working with parents, particularly mothers, and encouraging authoritative parenting.

EnzDP: improved enzyme annotation for metabolic network reconstruction based on domain composition profiles.

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Nguyen, Nam-Ninh; Srihari, Sriganesh; Leong, Hon Wai; Chong, Ket-Fah

2015-10-01

Determining the entire complement of enzymes and their enzymatic functions is a fundamental step for reconstructing the metabolic network of cells. High quality enzyme annotation helps in enhancing metabolic networks reconstructed from the genome, especially by reducing gaps and increasing the enzyme coverage. Currently, structure-based and network-based approaches can only cover a limited number of enzyme families, and the accuracy of homology-based approaches can be further improved. Bottom-up homology-based approach improves the coverage by rebuilding Hidden Markov Model (HMM) profiles for all known enzymes. However, its clustering procedure relies firmly on BLAST similarity score, ignoring protein domains/patterns, and is sensitive to changes in cut-off thresholds. Here, we use functional domain architecture to score the association between domain families and enzyme families (Domain-Enzyme Association Scoring, DEAS). The DEAS score is used to calculate the similarity between proteins, which is then used in clustering procedure, instead of using sequence similarity score. We improve the enzyme annotation protocol using a stringent classification procedure, and by choosing optimal threshold settings and checking for active sites. Our analysis shows that our stringent protocol EnzDP can cover up to 90% of enzyme families available in Swiss-Prot. It achieves a high accuracy of 94.5% based on five-fold cross-validation. EnzDP outperforms existing methods across several testing scenarios. Thus, EnzDP serves as a reliable automated tool for enzyme annotation and metabolic network reconstruction. Available at: www.comp.nus.edu.sg/~nguyennn/EnzDP .

High intensity aerobic interval training improves peak oxygen consumption in patients with metabolic syndrome: CAT

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Alexis Espinoza Salinas

2014-06-01

Full Text Available Introduction A number of cardiovascular risk factors characterizes the metabolic syndrome: insulin resistance (IR, low HDL cholesterol and high triglycerides. The aforementioned risk factors lead to elevated levels of abdominal adipose tissue, resulting in oxygen consumption deficiency. Purpose To verify the validity and applicability of using high intensity interval training (HIIT in subjects with metabolic syndrome and to answer the following question: Can HIIT improve peak oxygen consumption? Method The systematic review "Effects of aerobic interval training on exercise capacity and metabolic risk factors in individuals with cardiometabolic disorders" was analyzed. Results Data suggests high intensity aerobic interval training increases peak oxygen consumption by a standardized mean difference of 3.60 mL/kg-1/min-1 (95% confidence interval, 0.28-4.91. Conclusion In spite of the methodological shortcomings of the primary studies included in the systematic review, we reasonably conclude that implementation of high intensity aerobic interval training in subjects with metabolic syndrome, leads to increases in peak oxygen consumption.

Obeticholic Acid Improves Adipose Morphometry and Inflammation and Reduces Steatosis in Dietary but not Metabolic Obesity in Mice

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Haczeyni, Fahrettin; Poekes, Laurence; Wang, Hans; Mridha, Auvro R.; Barn, Vanessa; Haigh, W. Geoffrey; Ioannou, George N.; Yeh, Matthew M; Leclercq, Isabelle A.; Teoh, Narcissus C.; Farrell, Geoffrey C.

2018-01-01

Objective Non-alcoholic steatohepatitis (NASH) is the outcome of interactions between overnutrition, energy metabolism, and adipose function. Obeticholic acid (OCA) improves steatosis in patients, but for unknown reason does not resolve NASH pathology. We therefore investigated OCA effects in Wt mice which develop obesity with atherogenic dietary feeding, and appetite-dysregulated, Alms1 mutant foz/foz mice fed the same diet which develop metabolic obesity and diabetes. Methods OCA (1mg/kg) was administered orally to female foz/foz mice and Wt littermates from weaning until 28 weeks. We studied adipose indices, glucose tolerance and fatty liver pathology. Experiments were repeated with OCA 10mg/kg. Results OCA reduced body weight and hepatic lipids and improved glucose disposal only in Wt mice. OCA limited Wt adipose expansion, altered morphometry in favour of small adipocytes, enhanced expression of genes indicating adipose browning, and reduced crown-like structure (CLS) number in visceral adipose. foz/foz mice showed more CLSs in all compartments; OCA failed to alter adipose morphometry, browning, inflammation, or improve NASH severity, even at 10mg/kg. Conclusion OCA improves adipose indices, glucose tolerance and steatosis in milder metabolic phenotype, but fails to improve these factors in morbidly obese diabetic mice. These results help explain OCA’s limited efficacy to reverse human NASH. PMID:27804232

Transcriptional and metabolic effects of glucose on Streptococcus pneumoniae sugar metabolism

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Laura ePaixão

2015-10-01

Full Text Available Streptococcus pneumoniae is a strictly fermentative human pathogen that relies on carbohydrate metabolism to generate energy for growth. The nasopharynx colonised 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 colonisation 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 towards 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.

Transcriptional and metabolic effects of glucose on Streptococcus pneumoniae sugar metabolism.

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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.

Fasting-induced liver GADD45β restrains hepatic fatty acid uptake and improves metabolic health.

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Fuhrmeister, Jessica; Zota, Annika; Sijmonsma, Tjeerd P; Seibert, Oksana; Cıngır, Şahika; Schmidt, Kathrin; Vallon, Nicola; de Guia, Roldan M; Niopek, Katharina; Berriel Diaz, Mauricio; Maida, Adriano; Blüher, Matthias; Okun, Jürgen G; Herzig, Stephan; Rose, Adam J

2016-06-01

Recent studies have demonstrated that repeated short-term nutrient withdrawal (i.e. fasting) has pleiotropic actions to promote organismal health and longevity. Despite this, the molecular physiological mechanisms by which fasting is protective against metabolic disease are largely unknown. Here, we show that, metabolic control, particularly systemic and liver lipid metabolism, is aberrantly regulated in the fasted state in mouse models of metabolic dysfunction. Liver transcript assays between lean/healthy and obese/diabetic mice in fasted and fed states uncovered "growth arrest and DNA damage-inducible" GADD45β as a dysregulated gene transcript during fasting in several models of metabolic dysfunction including ageing, obesity/pre-diabetes and type 2 diabetes, in both mice and humans. Using whole-body knockout mice as well as liver/hepatocyte-specific gain- and loss-of-function strategies, we revealed a role for liver GADD45β in the coordination of liver fatty acid uptake, through cytoplasmic retention of FABP1, ultimately impacting obesity-driven hyperglycaemia. In summary, fasting stress-induced GADD45β represents a liver-specific molecular event promoting adaptive metabolic function. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

Metabolism and the Control of Cell Fate Decisions and Stem Cell Renewal

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Ito, Kyoko; Ito, Keisuke

2016-01-01

Although the stem cells of various tissues remain in the quiescent state to maintain their undifferentiated state, they also undergo cell divisions as required, and if necessary, even a single stem cell is able to provide for lifelong tissue homeostasis. Stem cell populations are precisely controlled by the balance between their symmetric and asymmetric divisions, with their division patterns determined by whether the daughter cells involved retain their self-renewal capacities. Recent studies have reported that metabolic pathways and the distribution of mitochondria are regulators of the division balance of stem cells and that metabolic defects can shift division balance toward symmetric commitment, which leads to stem cell exhaustion. It has also been observed that in asymmetric division, old mitochondria, which are central metabolic organelles, are segregated to the daughter cell fated to cell differentiation, whereas in symmetric division, young and old mitochondria are equally distributed between both daughter cells. Thus, metabolism and mitochondrial biology play important roles in stem cell fate decisions. As these decisions directly affect tissue homeostasis, understanding their regulatory mechanisms in the context of cellular metabolism is critical. PMID:27482603

[Blood-sugar self control. A means for the diabetic of controlling his metabolic management. Quality control of a battery-run pocket size reflectometer (glucose-meter)].

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Leidinger, F; Jörgens, V; Chantelau, E; Berchtold, P; Berger, M

1980-07-26

Home blood glucose monitoring by diabetic patients has recently been advocated as an effective means to improve metabolic control. The Glucocheck apparatus, a pocket-size battery-driven reflectance-meter (in Germany commercially available under the name Glucose-meter), has been evaluated for accuracy and practicability. In 450 blood glucose measurements, the variance between the values obtained using the Glucocheck apparatus and routine clinical laboratory procedures was +/- 11.7%. Especially in the low range of blood glucose concentrations, the Glucocheck method was very reliable. The quantitative precision of the Glucocheck method depends, however, quite considerably on the ability of the patient to use the apparatus correctly. In order to profit from Glucocheck in clinical practice, particular efforts to educate the patients in its use are necessary.

The relative contribution of insulin secretory capacity, insulin action, and incretins to metabolic control after islet transplantation in dogs

NARCIS (Netherlands)

van der Burg, MPM; van Suylichem, PTR; Guicherit, OR; Frolich, M; Lemkes, HHPJ; Gooszen, HG

Adequate metabolic control is central to the concept of islet transplantation, but has received limited attention. We studied metabolic control in 8 dogs at 6-9 months after intrasplenic autografting of similar to 25% of the normal mass islets - as compared to 30 controls. A similar posttransplant

A method for accounting for maintenance costs in flux balance analysis improves the prediction of plant cell metabolic phenotypes under stress conditions.

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Cheung, C Y Maurice; Williams, Thomas C R; Poolman, Mark G; Fell, David A; Ratcliffe, R George; Sweetlove, Lee J

2013-09-01

Flux balance models of metabolism generally utilize synthesis of biomass as the main determinant of intracellular fluxes. However, the biomass constraint alone is not sufficient to predict realistic fluxes in central heterotrophic metabolism of plant cells because of the major demand on the energy budget due to transport costs and cell maintenance. This major limitation can be addressed by incorporating transport steps into the metabolic model and by implementing a procedure that uses Pareto optimality analysis to explore the trade-off between ATP and NADPH production for maintenance. This leads to a method for predicting cell maintenance costs on the basis of the measured flux ratio between the oxidative steps of the oxidative pentose phosphate pathway and glycolysis. We show that accounting for transport and maintenance costs substantially improves the accuracy of fluxes predicted from a flux balance model of heterotrophic Arabidopsis cells in culture, irrespective of the objective function used in the analysis. Moreover, when the new method was applied to cells under control, elevated temperature and hyper-osmotic conditions, only elevated temperature led to a substantial increase in cell maintenance costs. It is concluded that the hyper-osmotic conditions tested did not impose a metabolic stress, in as much as the metabolic network is not forced to devote more resources to cell maintenance. © 2013 The Authors The Plant Journal © 2013 John Wiley & Sons Ltd.

A randomized controlled trial: branched-chain amino acid levels and glucose metabolism in patients with obesity and sleep apnea.

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Barceló, Antonia; Morell-Garcia, Daniel; Salord, Neus; Esquinas, Cristina; Pérez, Gerardo; Pérez, Antonio; Monasterio, Carmen; Gasa, Merce; Fortuna, Ana Maria; Montserrat, Josep Maria; Mayos, Mercedes

2017-12-01

There is evidence that changes in branched-chain amino acid (BCAA) levels may correlate with the efficacy of therapeutic interventions for affecting improvement in metabolic control. The objective of this study was to evaluate whether serum concentrations of BCAAs (leucine, isoleucine, valine) could mediate in insulin sensitivity and glucose tolerance after continuous positive airway pressure (CPAP) treatment in patients with obstructive sleep apnea (OSA). A prospective randomized controlled trial of OSA patients with morbid obesity was conducted. Eighty patients were randomized into two groups: 38 received conservative treatment and 42 received CPAP treatment for 12 weeks. Plasma levels of BCAA, glucose tolerance and insulin resistance were evaluated at baseline and after treatment. After treatment, significant decreases of leucine levels were observed in both groups when compared with baseline levels (P fasting plasma glucose and glycosylated haemoglobin values only in the conservative group (P < 0.05). In summary, we found that the treatment with CPAP for 12 weeks caused similar changes in circulating BCAAs concentrations to conservative treatment and a differential metabolic response of CPAP and conservative treatment was observed between the relationship of BCAAs and glucose homeostasis. Additional studies are needed to determine the interplay between branched-chain amino acids and glucose metabolism in patients with sleep apnea. © 2017 European Sleep Research Society.

FGF-dependent metabolic control of vascular development

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Yu, Pengchun; Alves, Tiago C.; Fang, Jennifer S.; Xie, Yi; Zhu, Jie; Chen, Zehua; De Smet, Frederik; Zhang, Jiasheng; Jin, Suk-Won; Sun, Lele; Sun, Hongye; Kibbey, Richard G.; Hirschi, Karen K.; Hay, Nissim; Carmeliet, Peter; Chittenden, Thomas W.; Eichmann, Anne; Potente, Michael; Simons, Michael

2017-01-01

Blood and lymphatic vasculatures are intimately involved in tissue oxygenation and fluid homeostasis maintenance. Assembly of these vascular networks involves sprouting, migration and proliferation of endothelial cells. Recent studies have suggested that changes in cellular metabolism are of importance to these processes1. While much is known about vascular endothelial growth factor (VEGF)-dependent regulation of vascular development and metabolism2,3, little is understood about the role of fibroblast growth factors (FGFs) in this context4. Here we identify FGF receptor (FGFR) signaling as a critical regulator of vascular development. This is achieved by FGF-dependent control of c-MYC (MYC) expression that, in turn, regulates expression of the glycolytic enzyme hexokinase 2 (HK2). A decrease in HK2 levels in the absence of FGF signaling inputs results in decreased glycolysis leading to impaired endothelial cell proliferation and migration. Pan-endothelial- and lymphatic-specific Hk2 knockouts phenocopy blood and/or lymphatic vascular defects seen in Fgfr1/r3 double mutant mice while HK2 overexpression partially rescues the defects caused by suppression of FGF signaling. Thus, FGF-dependent regulation of endothelial glycolysis is a pivotal process in developmental and adult vascular growth and development. PMID:28467822

NAD+ metabolism and the control of energy homeostasis - a balancing act between mitochondria and the nucleus

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Cantó, Carles; Menzies, Keir; Auwerx, Johan

2015-01-01

NAD+ has emerged as a vital cofactor that can rewire metabolism, activate sirtuins and maintain mitochondrial fitness through mechanisms such as the mitochondrial unfolded protein response. This improved understanding of NAD+ metabolism revived interest in NAD+ boosting strategies to manage a wide spectrum of diseases, ranging from diabetes to cancer. In this review, we summarize how NAD+ metabolism links energy status with adaptive cellular and organismal responses and how this knowledge can be therapeutically exploited. PMID:26118927

Adaptive Activation of a Stress Response Pathway Improves Learning and Memory Through Gs and β-Arrestin-1-Regulated Lactate Metabolism.

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Dong, Jun-Hong; Wang, Yi-Jing; Cui, Min; Wang, Xiao-Jing; Zheng, Wen-Shuai; Ma, Ming-Liang; Yang, Fan; He, Dong-Fang; Hu, Qiao-Xia; Zhang, Dao-Lai; Ning, Shang-Lei; Liu, Chun-Hua; Wang, Chuan; Wang, Yue; Li, Xiang-Yao; Yi, Fan; Lin, Amy; Kahsai, Alem W; Cahill, Thomas Joseph; Chen, Zhe-Yu; Yu, Xiao; Sun, Jin-Peng

2017-04-15

Stress is a conserved physiological response in mammals. Whereas moderate stress strengthens memory to improve reactions to previously experienced difficult situations, too much stress is harmful. We used specific β-adrenergic agonists, as well as β 2 -adrenergic receptor (β2AR) and arrestin knockout models, to study the effects of adaptive β2AR activation on cognitive function using Morris water maze and object recognition experiments. We used molecular and cell biological approaches to elucidate the signaling subnetworks. We observed that the duration of the adaptive β2AR activation determines its consequences on learning and memory. Short-term formoterol treatment, for 3 to 5 days, improved cognitive function; however, prolonged β2AR activation, for more than 6 days, produced harmful effects. We identified the activation of several signaling networks downstream of β2AR, as well as an essential role for arrestin and lactate metabolism in promoting cognitive ability. Whereas Gs-protein kinase A-cyclic adenosine monophosphate response element binding protein signaling modulated monocarboxylate transporter 1 expression, β-arrestin-1 controlled expression levels of monocarboxylate transporter 4 and lactate dehydrogenase A through the formation of a β-arrestin-1/phospho-mitogen-activated protein kinase/hypoxia-inducible factor-1α ternary complex to upregulate lactate metabolism in astrocyte-derived U251 cells. Conversely, long-term treatment with formoterol led to the desensitization of β2ARs, which was responsible for its decreased beneficial effects. Our results not only revealed that β-arrestin-1 regulated lactate metabolism to contribute to β2AR functions in improved memory formation, but also indicated that the appropriate management of one specific stress pathway, such as through the clinical drug formoterol, may exert beneficial effects on cognitive abilities. Copyright © 2016 Society of Biological Psychiatry. All rights reserved.

Impact of hypothalamic reactive oxygen species in the control of energy metabolism and food intake

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Anne eDrougard

2015-02-01

Full Text Available Hypothalamus is a key area involved in the control of metabolism and food intake via the integrations of numerous signals (hormones, neurotransmitters, metabolites from various origins. These factors modify hypothalamic neurons activity and generate adequate molecular and behavioral responses to control energy balance. In this complex integrative system, a new concept has been developed in recent years, that includes reactive oxygen species (ROS as a critical player in energy balance. ROS are known to act in many signaling pathways in different peripheral organs, but also in hypothalamus where they regulate food intake and metabolism by acting on different types of neurons, including proopiomelanocortin (POMC and agouti-related protein (AgRP/neuropeptide Y (NPY neurons. Hypothalamic ROS release is under the influence of different factors such as pancreatic and gut hormones, adipokines (leptin, apelin,..., neurotransmitters and nutrients (glucose, lipids,.... The sources of ROS production are multiple including NADPH oxidase, but also the mitochondria which is considered as the main ROS producer in the brain. ROS are considered as signaling molecules, but conversely impairment of this neuronal signaling ROS pathway contributes to alterations of autonomic nervous system and neuroendocrine function, leading to metabolic diseases such as obesity and type 2 diabetes.In this review we focus our attention on factors that are able to modulate hypothalamic ROS release in order to control food intake and energy metabolism, and whose deregulations could participate to the development of pathological conditions. This novel insight reveals an original mechanism in the hypothalamus that controls energy balance and identify hypothalamic ROS signaling as a potential therapeutic strategy to treat metabolic disorders.

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

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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.

Metabolic control and bone health in adolescents with type 1 diabetes

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Mohan Subburaman

2011-10-01

Full Text Available Abstract Background Adults with type 1 diabetes (T1D have decreased bone mineral density (BMD and increased fracture risk, yet the etiologies remain elusive. Early detection of derangements in bone biomarkers during adolescence could lead to timely recognition. In adolescents with T1D, we evaluated the relationships between metabolic control, BMD, and bone anabolic and turnover markers. Methods Cross-sectional study of 57 adolescent subjects with T1D who had HbA1c consistently ≥ 9% (Poor Control, PC n = 27 or Results There were no differences between HbA1c groups in BMD, components of the IGF system, or 25-hydroxyvitamin D status. The prevalence of 25-hydroxyvitamin D abnormalities was similar to that seen in the general adolescent population. Few patients met the recommended dietary allowance (RDA for vitamin D or calcium. Conclusions These data provide no evidence of association between degree of metabolic control and BMD in adolescents with T1D. Adolescents with T1D have a high prevalence of serum 25-hydroxyvitamin D abnormalities. Longitudinal studies are needed to evaluate the predictive value of vitamin D abnormalities on fracture risk.

Consumption of extra-virgin olive oil rich in phenolic compounds improves metabolic control in patients with type 2 diabetes mellitus: a possible involvement of reduced levels of circulating visfatin.

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Santangelo, C; Filesi, C; Varì, R; Scazzocchio, B; Filardi, T; Fogliano, V; D'Archivio, M; Giovannini, C; Lenzi, A; Morano, S; Masella, R

2016-11-01

Phenolic compounds naturally contained in extra-virgin olive oil (EVOO) have demonstrated anti-inflammatory and antioxidant properties. The present study aimed at evaluating the effects of a polyphenol-rich extra-virgin olive oil (EVOO) (high-polyphenol EVOO, HP-EVOO) on the metabolic control and the production of specific pro-/anti-inflammatory adipokines in overweight patients with type 2 diabetes mellitus (T2D). Eleven overweight T2D patients not in treatment with insulin were invited to follow their habitual diet for a total of 8 weeks. During the first 4 weeks (wash-out period), they were asked to consume refined olive oil (ROO, polyphenols not detectable) and then to replace ROO with HP-EVOO (25 mL/day, 577 mg of phenolic compounds/kg) for the remaining 4 weeks. Anthropometric parameters, fasting glycaemia, glycated haemoglobin (HbA1c), high-sensitive C-reactive protein, plasma lipid profile, liver function and serum levels of TNF-α, IL-6, adiponectin, visfatin and apelin were assessed at the end of each 4-week period. HP-EVOO consumption significantly reduced fasting plasma glucose (P = 0.023) and HbA1c (P = 0.039) levels as well as BMI (P = 0.012) and body weight (P = 0.012). HP-EVOO ingestion determined a reduction in serum level of aspartate aminotransferase (AST, P = 0.0056) and alanine aminotransferase (ALT, P = 0.024). Serum visfatin levels strongly decreased after HP-EVOO ingestion (P = 0.0021). Daily consumption of polyphenol-rich EVOO might improve metabolic control and circulating inflammatory adipokines profile in overweight T2D patients.

Effects of Low-Carbohydrate Diets Versus Low-Fat Diets on Metabolic Risk Factors: A Meta-Analysis of Randomized Controlled Clinical Trials

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Hu, Tian; Mills, Katherine T.; Yao, Lu; Demanelis, Kathryn; Eloustaz, Mohamed; Yancy, William S.; Kelly, Tanika N.; He, Jiang; Bazzano, Lydia A.

2012-01-01

The effects of low-carbohydrate diets (≤45% of energy from carbohydrates) versus low-fat diets (≤30% of energy from fat) on metabolic risk factors were compared in a meta-analysis of randomized controlled trials. Twenty-three trials from multiple countries with a total of 2,788 participants met the predetermined eligibility criteria (from January 1, 1966 to June 20, 2011) and were included in the analyses. Data abstraction was conducted in duplicate by independent investigators. Both low-carbohydrate and low-fat diets lowered weight and improved metabolic risk factors. Compared with participants on low-fat diets, persons on low-carbohydrate diets experienced a slightly but statistically significantly lower reduction in total cholesterol (2.7 mg/dL; 95% confidence interval: 0.8, 4.6), and low density lipoprotein cholesterol (3.7 mg/dL; 95% confidence interval: 1.0, 6.4), but a greater increase in high density lipoprotein cholesterol (3.3 mg/dL; 95% confidence interval: 1.9, 4.7) and a greater decrease in triglycerides (−14.0 mg/dL; 95% confidence interval: −19.4, −8.7). Reductions in body weight, waist circumference and other metabolic risk factors were not significantly different between the 2 diets. These findings suggest that low-carbohydrate diets are at least as effective as low-fat diets at reducing weight and improving metabolic risk factors. Low-carbohydrate diets could be recommended to obese persons with abnormal metabolic risk factors for the purpose of weight loss. Studies demonstrating long-term effects of low-carbohydrate diets on cardiovascular events were warranted. PMID:23035144

Metabolic Control of Dendritic Cell Activation and Function: Recent Advances and Clinical Implications

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Bart eEverts

2014-05-01

Full Text Available Dendritic cells (DCs are key regulators of both immunity and tolerance by controlling activation and polarization of effector T helper cell and regulatory T cell responses. Therefore, there is a major focus on developing approaches to manipulate DC function for immunotherapy. It is well known that changes in cellular activation are coupled to profound changes in cellular metabolism. Over the past decade there is a growing appreciation that these metabolic changes also underlie the capacity of immune cells to perform particular functions. This has led to the concept that the manipulation of cellular metabolism can be used to shape innate and adaptive immune responses. While most of our understanding in this area has been gained from studies with T cells and macrophages, evidence is emerging that the activation and function of DCs are also dictated by the type of metabolism these cells commit to. We here discuss these new insights and explore whether targeting of metabolic pathways in DCs could hold promise as a novel approach to manipulate the functional properties of DCs for clinical purposes.

The effects of improved metabolic risk factors on bone turnover markers after 12 weeks of simvastatin treatment with or without exercise.

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Jiang, Jun; Boyle, Leryn J; Mikus, Catherine R; Oberlin, Douglas J; Fletcher, Justin A; Thyfault, John P; Hinton, Pamela S

2014-11-01

Emerging evidence supports an association between metabolic risk factors and bone turnover. Statins and exercise independently improve metabolic risk factors; however whether improvements in metabolic risk factor affects bone turnover is unknown. The purpose of the present study was to: 1) evaluate the relationship between metabolic risk factors and bone turnover; and 2) determine if improvements in metabolic risk factors after 12 weeks of statin treatment, exercise or the combination affect bone turnover. Fifty participants with ≥2 metabolic syndrome defining characteristics were randomly assigned to one of three groups: statin (STAT: simvastatin, 40 mg/day), exercise (EX: brisk walking and/or slow jogging, 45 minutes/day, 5 days/week), or the combination (STAT+EX). Body composition and whole body bone mineral density were measured with dual energy X-ray absorptiometry. Serum markers of bone formation (bone specific alkaline phosphatase, BAP; osteocalcin, OC), resorption (C-terminal peptide of type I collagen, CTX) and metabolic risk factors were determined. Two-factor (time, group) repeated-measures ANCOVA was used to examine changes of metabolic risk factors and bone turnover. General linear models were used to determine the effect of pre-treatment metabolic risk factors on post-treatment bone turnover marker outcomes. Participants with ≥4 metabolic syndrome defining characteristics had lower pre-treatment OC than those with 3 or fewer. OC was negatively correlated with glucose, and CTX was positively correlated with cholesterol. STAT or STAT+EX lowered total and LDL cholesterol. The OC to CTX ratio decreased in all groups with no other significant changes in bone turnover. Higher pre-treatment insulin or body fat predicted a greater CTX reduction and a greater BAP/CTX increase. Metabolic risk factors were negatively associated with bone turnover markers. Short-term statin treatment with or without exercise lowered cholesterol and all treatments had a small

Nutrigenetics, metabolic syndrome risk and personalized nutrition.

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Perez-Martinez, Pablo; Phillips, Catherine M; Delgado-Lista, Javier; Garcia-Rios, Antonio; Lopez-Miranda, Jose; Perez-Jimenez, Francisco

2013-11-01

The metabolic syndrome (MetS) is a constellation of metabolic risk factors reflecting overnutrition and sedentary lifestyle and its increasing prevalence is reaching epidemic proportions. The importance of MetS lies in its close association with the risk of cardiometabolic disease. In this scenario, the principal goals of pharmacological therapy for these patients are to achieve and maintain an optimal cardiometabolic control, including lipids, blood glucose and blood pressure; in order to prevent and treat potential complications. Moreover nutrition has commonly been accepted as a cornerstone of treatment for MetS, with the expectation that an appropriate intake of energy and nutrients will improve its control. However the question arises as to whether dietary therapy may require a more personalised approach. In this regard improvements in genetic analysis have enhanced our understanding of the role of genetics in this dietrelated condition. In this review we will present recent data highlighting the importance of gene-nutrient interactions in the context of MetS risk.

Defining a novel leptin–melanocortin–kisspeptin pathway involved in the metabolic control of puberty

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Maria Manfredi-Lozano

2016-10-01

Full Text Available Objective: Puberty is a key developmental phenomenon highly sensitive to metabolic modulation. Worrying trends of changes in the timing of puberty have been reported in humans. These might be linked to the escalating prevalence of childhood obesity and could have deleterious impacts on later (cardio-metabolic health, but their underlying mechanisms remain unsolved. The neuropeptide α-MSH, made by POMC neurons, plays a key role in energy homeostasis by mediating the actions of leptin and likely participates in the control of reproduction. However, its role in the metabolic regulation of puberty and interplay with kisspeptin, an essential puberty-regulating neuropeptide encoded by Kiss1, remain largely unknown. We aim here to unveil the potential contribution of central α-MSH signaling in the metabolic control of puberty by addressing its role in mediating the pubertal effects of leptin and its potential interaction with kisspeptin. Methods: Using wild type and genetically modified rodent models, we implemented pharmacological studies, expression analyses, electrophysiological recordings, and virogenetic approaches involving DREADD technology to selectively inhibit Kiss1 neurons, in order to interrogate the physiological role of a putative leptin→α-MSH→kisspeptin pathway in the metabolic control of puberty. Results: Stimulation of central α-MSH signaling robustly activated the reproductive axis in pubertal rats, whereas chronic inhibition of melanocortin receptors MC3/4R, delayed puberty, and prevented the permissive effect of leptin on puberty onset. Central blockade of MC3/4R or genetic elimination of kisspeptin receptors from POMC neurons did not affect kisspeptin effects. Conversely, congenital ablation of kisspeptin receptors or inducible, DREADD-mediated inhibition of arcuate nucleus (ARC Kiss1 neurons resulted in markedly attenuated gonadotropic responses to MC3/4R activation. Furthermore, close appositions were observed between

Does bariatric surgery improve adipose tissue function?

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Frikke-Schmidt, H.; O’Rourke, R. W.; Lumeng, C. N.; Sandoval, D. A.; Seeley, R. J.

2017-01-01

Summary Bariatric surgery is currently the most effective treatment for obesity. Not only do these types of surgeries produce significant weight loss but also they improve insulin sensitivity and whole body metabolic function. The aim of this review is to explore how altered physiology of adipose tissue may contribute to the potent metabolic effects of some of these procedures. This includes specific effects on various fat depots, the function of individual adipocytes and the interaction between adipose tissue and other key metabolic tissues. Besides a dramatic loss of fat mass, bariatric surgery shifts the distribution of fat from visceral to the subcutaneous compartment favoring metabolic improvement. The sensitivity towards lipolysis controlled by insulin and catecholamines is improved, adipokine secretion is altered and local adipose inflammation as well as systemic inflammatory markers decreases. Some of these changes have been shown to be weight loss independent, and novel hypothesis for these effects includes include changes in bile acid metabolism, gut microbiota and central regulation of metabolism. In conclusion bariatric surgery is capable of improving aspects of adipose tissue function and do so in some cases in ways that are not entirely explained by the potent effect of surgery. PMID:27272117

Engineering of metabolic pathways by artificial enzyme channels

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Marlene ePröschel

2015-10-01

Full Text Available Application of industrial enzymes for production of valuable chemical compounds has greatly benefited from recent developments in Systems and Synthetic Biology. Both, in vivo and in vitro systems have been established, allowing conversion of simple into complex compounds. Metabolic engineering in living cells needs to be balanced which is achieved by controlling gene expression levels, translation, scaffolding, compartmentation and flux control. In vitro applications are often hampered by limited protein stability/half-life and insufficient rates of substrate conversion. To improve stability and catalytic activity, proteins are post-translationally modified and arranged in artificial metabolic channels. Within the review article we will first discuss the supramolecular organization of enzymes in living systems and secondly summarize current and future approaches to design artificial metabolic channels by additive manufacturing for the efficient production of desired products.

Pyruvate Kinase Triggers a Metabolic Feedback Loop that Controls Redox Metabolism in Respiring Cells

NARCIS (Netherlands)

Grüning, N.M.; Rinnerthaler, M.; Bluemlein, K.; Mulleder, M.; Wamelink, M.M.C.; Lehrach, H.; Jakobs, C.A.J.M.; Breitenbach, M.; Ralser, M.

2011-01-01

In proliferating cells, a transition from aerobic to anaerobic metabolism is known as the Warburg effect, whose reversal inhibits cancer cell proliferation. Studying its regulator pyruvate kinase (PYK) in yeast, we discovered that central metabolism is self-adapting to synchronize redox metabolism

Current progress of targetron technology: development, improvement and application in metabolic engineering.

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Liu, Ya-Jun; Zhang, Jie; Cui, Gu-Zhen; Cui, Qiu

2015-06-01

Targetrons are mobile group II introns that can recognize their DNA target sites by base-pairing RNA-DNA interactions with the aid of site-specific binding reverse transcriptases. Targetron technology stands out from recently developed gene targeting methods because of the flexibility, feasibility, and efficiency, and is particularly suitable for the genetic engineering of difficult microorganisms, including cellulolytic bacteria that are considered promising candidates for biomass conversion via consolidated bioprocessing. Along with the development of the thermotargetron method for thermophiles, targetron technology becomes increasingly important for the metabolic engineering of industrial microorganisms aiming at biofuel/chemical production. To summarize the current progress of targetron technology and provide new insights on the use of the technology, this paper reviews the retrohoming mechanisms of both mesophilic and thermophilic targetron methods based on various group II introns, investigates the improvement of targetron tools for high target efficiency and specificity, and discusses the current applications in the metabolic engineering for bacterial producers. Although there are still intellectual property and technical restrictions in targetron applications, we propose that targetron technology will contribute to both biochemistry research and the metabolic engineering for industrial productions. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Effects of Breakfast Consumption and Composition on Metabolic Wellness with a Focus on Carbohydrate Metabolism.

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Maki, Kevin C; Phillips-Eakley, Alyssa K; Smith, Kristen N

2016-05-01

Findings from epidemiologic studies indicate that there are associations between breakfast consumption and a lower risk of type 2 diabetes mellitus (T2DM) and metabolic syndrome, prompting interest in the influence of breakfast on carbohydrate metabolism and indicators of T2DM risk. The objective of this review was to summarize the available evidence from randomized controlled trials assessing the impact of breakfast on variables related to carbohydrate metabolism and metabolic wellness. Consuming compared with skipping breakfast appeared to improve glucose and insulin responses throughout the day. Breakfast composition may also be important. Dietary patterns high in rapidly available carbohydrate were associated with elevated T2DM risk. Therefore, partial replacement of rapidly available carbohydrate with other dietary components, such as whole grains and cereal fibers, proteins, and unsaturated fatty acids (UFAs), at breakfast may be a useful strategy for producing favorable metabolic outcomes. Consumption of fermentable and viscous dietary fibers at breakfast lowers glycemia and insulinemia. Fermentable fibers likely act through enhancing insulin sensitivity later in the day, and viscous fibers have an acute effect to slow the rate of carbohydrate absorption. Partially substituting protein for rapidly available carbohydrate enhances satiety and diet-induced thermogenesis, and also favorably affects lipoprotein lipids and blood pressure. Partially substituting UFA for carbohydrate has been associated with improved insulin sensitivity, lipoprotein lipids, and blood pressure. Overall, the available evidence suggests that consuming breakfast foods high in whole grains and cereal fiber, while limiting rapidly available carbohydrate, is a promising strategy for metabolic health promotion. © 2016 American Society for Nutrition.

Aerobic interval exercise improves parameters of nonalcoholic fatty liver disease (NAFLD) and other alterations of metabolic syndrome in obese Zucker rats.

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Kapravelou, Garyfallia; Martínez, Rosario; Andrade, Ana M; Nebot, Elena; Camiletti-Moirón, Daniel; Aparicio, Virginia A; Lopez-Jurado, Maria; Aranda, Pilar; Arrebola, Francisco; Fernandez-Segura, Eduardo; Bermano, Giovanna; Goua, Marie; Galisteo, Milagros; Porres, Jesus M

2015-12-01

Metabolic syndrome (MS) is a group of metabolic alterations that increase the susceptibility to cardiovascular disease and type 2 diabetes. Nonalcoholic fatty liver disease has been described as the liver manifestation of MS. We aimed to test the beneficial effects of an aerobic interval training (AIT) protocol on different biochemical, microscopic, and functional liver alterations related to the MS in the experimental model of obese Zucker rat. Two groups of lean and obese animals (6 weeks old) followed a protocol of AIT (4 min at 65%-80% of maximal oxygen uptake, followed by 3 min at 50%-65% of maximal oxygen uptake for 45-60 min, 5 days/week, 8 weeks of experimental period), whereas 2 control groups remained sedentary. Obese rats had higher food intake and body weight (P metabolism and increased the liver protein expression of PPARγ, as well as the gene expression of glutathione peroxidase 4 (P < 0.001). The training protocol also showed significant effects on the activity of hepatic antioxidant enzymes, although this action was greatly influenced by rat phenotype. The present data suggest that AIT protocol is a feasible strategy to improve some of the plasma and liver alterations featured by the MS.

Changes in the isozymic pattern of phosphoenolpyruvate : An early step in photoperiodic control of crassulacean acid metabolism level.

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Brulfert, J; Arrabaça, M C; Guerrier, D; Queiroz, O

1979-01-01

Two major isofunctional forms of phosphoenolpyruvate carboxylase (EC 4.1.1.31) have been separated from the leaves of Kalanchoe blossfeldiana Poelln. Tom Thumb by acrylamide gel electrophoresis and diethylaminoethyl cellulose techniques: one of the forms prevails under long-day treatment (low crassulacean acid metabolism level), the other develops under short-day treatment (high Crassulacean acid metabolism level). Molecular weights are significantly different: 175·10(3) and 186·10(3), respectively. These results indicate that two populations of phosphoenolyruvate carboxylase are present in the plant, one of which is responsible for Crassulacean acid metabolism activity under the control of photoperiod.The Crassulacean acid metabolism appears to depend on the same endogenous clock that governs other photoperiodically controlled events (e.g. flowering). The metabolic and energetic significance of this feature is discussed. It is suggested that modification in isozymic composition could be an early step in the response to photoperiodism at the metabolic level.

Improvement of pustulosis palmaris et plantaris by periodontal infection control in a patient with chronic periodontitis.

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Murai, Osamu; Sasaki, Daisuke; Ando, Yoshinori; Fujimura, Akira; Oikawa, Hiromi; Suwa, Nagisa; Watabe, Daisuke; Maeda, Fumihiko; Endo, Kohki; Yaegashi, Takashi; Akasaka, Toshihide; Naruishi, Koji

2012-01-01

Pustulosis palmaris et plantaris (PPP) is a chronic, inflammatory, autoimmune-type disease characterized by sterile pustules of skin. The skin inflammation is influenced by several factors such as drugs, sunlight, metabolic and psychogenic factors as well as metal allergy. Here, we report a rare case that intensive periodontal treatment might have contributed to the improvement of skin inflammation. Skin inflammation regressed 1 month after intensive periodontal treatment. Both CD4/CD8 ratio and % of B cells in the blood sample were slightly decreased corresponding to the improvement of periodontal inflammation. Infection control of periodontal lesions might be one of attractive therapeutic targets in management of PPP.

Carbohydrate-Restriction with High-Intensity Interval Training: An Optimal Combination for Treating Metabolic Diseases?

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Monique E. Francois

2017-10-01

Full Text Available Lifestyle interventions incorporating both diet and exercise strategies remain cornerstone therapies for treating metabolic disease. Carbohydrate-restriction and high-intensity interval training (HIIT have independently been shown to improve cardiovascular and metabolic health. Carbohydrate-restriction reduces postprandial hyperglycemia, thereby limiting potential deleterious metabolic and cardiovascular consequences of excessive glucose excursions. Additionally, carbohydrate-restriction has been shown to improve body composition and blood lipids. The benefits of exercise for improving insulin sensitivity are well known. In this regard, HIIT has been shown to rapidly improve glucose control, endothelial function, and cardiorespiratory fitness. Here, we report the available evidence for each strategy and speculate that the combination of carbohydrate-restriction and HIIT will synergistically maximize the benefits of both approaches. We hypothesize that this lifestyle strategy represents an optimal intervention to treat metabolic disease; however, further research is warranted in order to harness the potential benefits of carbohydrate-restriction and HIIT for improving cardiometabolic health.

Carbohydrate-Restriction with High-Intensity Interval Training: An Optimal Combination for Treating Metabolic Diseases?

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Francois, Monique E; Gillen, Jenna B; Little, Jonathan P

2017-01-01

Lifestyle interventions incorporating both diet and exercise strategies remain cornerstone therapies for treating metabolic disease. Carbohydrate-restriction and high-intensity interval training (HIIT) have independently been shown to improve cardiovascular and metabolic health. Carbohydrate-restriction reduces postprandial hyperglycemia, thereby limiting potential deleterious metabolic and cardiovascular consequences of excessive glucose excursions. Additionally, carbohydrate-restriction has been shown to improve body composition and blood lipids. The benefits of exercise for improving insulin sensitivity are well known. In this regard, HIIT has been shown to rapidly improve glucose control, endothelial function, and cardiorespiratory fitness. Here, we report the available evidence for each strategy and speculate that the combination of carbohydrate-restriction and HIIT will synergistically maximize the benefits of both approaches. We hypothesize that this lifestyle strategy represents an optimal intervention to treat metabolic disease; however, further research is warranted in order to harness the potential benefits of carbohydrate-restriction and HIIT for improving cardiometabolic health.

Oral cancer cells may rewire alternative metabolic pathways to survive from siRNA silencing of metabolic enzymes

International Nuclear Information System (INIS)

Zhang, Min; Chai, Yang D; Brumbaugh, Jeffrey; Liu, Xiaojun; Rabii, Ramin; Feng, Sizhe; Misuno, Kaori; Messadi, Diana; Hu, Shen

2014-01-01

Cancer cells may undergo metabolic adaptations that support their growth as well as drug resistance properties. The purpose of this study is to test if oral cancer cells can overcome the metabolic defects introduced by using small interfering RNA (siRNA) to knock down their expression of important metabolic enzymes. UM1 and UM2 oral cancer cells were transfected with siRNA to transketolase (TKT) or siRNA to adenylate kinase (AK2), and Western blotting was used to confirm the knockdown. Cellular uptake of glucose and glutamine and production of lactate were compared between the cancer cells with either TKT or AK2 knockdown and those transfected with control siRNA. Statistical analysis was performed with student T-test. Despite the defect in the pentose phosphate pathway caused by siRNA knockdown of TKT, the survived UM1 or UM2 cells utilized more glucose and glutamine and secreted a significantly higher amount of lactate than the cells transferred with control siRNA. We also demonstrated that siRNA knockdown of AK2 constrained the proliferation of UM1 and UM2 cells but similarly led to an increased uptake of glucose/glutamine and production of lactate by the UM1 or UM2 cells survived from siRNA silencing of AK2. Our results indicate that the metabolic defects introduced by siRNA silencing of metabolic enzymes TKT or AK2 may be compensated by alternative feedback metabolic mechanisms, suggesting that cancer cells may overcome single defective pathways through secondary metabolic network adaptations. The highly robust nature of oral cancer cell metabolism implies that a systematic medical approach targeting multiple metabolic pathways may be needed to accomplish the continued improvement of cancer treatment

Leptin and the central nervous system control of glucose metabolism.

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Morton, Gregory J; Schwartz, Michael W

2011-04-01

The regulation of body fat stores and blood glucose levels is critical for survival. This review highlights growing evidence that leptin action in the central nervous system plays a key role in both processes. Investigation into underlying mechanisms has begun to clarify the physiological role of leptin in the control of glucose metabolism and raises interesting new possibilities for the treatment of diabetes and related disorders.

Metabolic and Electrophysiological Changes Associated to Clinical Improvement in Two Severely Traumatized Subjects Treated With EMDR—A Pilot Study

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Marco Pagani

2018-04-01

Full Text Available Neuroimaging represents a powerful tool to investigate the neurobiological correlates of Eye Movements Desensitization and Reprocessing (EMDR. The impact of EMDR on cortical and sub-cortical brain regions has been proven by several investigations demonstrating a clear association between symptoms disappearance and changes in cortical structure and functionality. The aim of this study was to assess by electroencephalography (EEG and for the first time by positron emission tomography (PET the changes occurring after EMDR therapy in two cases of psychological trauma following brain concussion and comatose state due to traffic accident. A 28 and a 29 years old men underwent extensive neuropsychological examination, which investigated: (i categorical and phonological verbal fluency; (ii episodic verbal memory; (iii executive functions; (iv visuospatial abilities; (v attention and working memory as well as clinical assessment by means of psychopathological tests (CAPS, IES, BDI, SCL90R, and DES. They were then treated by eight sessions of EMDR. During the first session EEG monitoring was continuously performed and 18F-FDG PET scans, depicting brain metabolism, were acquired at rest within a week (T0. After the last session, in which the two clients were considered to be symptoms-free, neuropsychological, clinical, and PET assessment were repeated (T1. PET data were semi-quantitatively compared to a group of 18 normal controls, as for EEG the preferential cortical activations were disclosed by thresholding the individual z-score to a p < 0.05. There was a significant improvement in clinical condition for both clients associated with a significant decrease in CAPS scores. IES and BDI were found to be pathological at T0 and improved at T1 in only one subject. Visuo-constructive abilities and abstract reasoning improved after EMDR in both subjects. As for EEG, the most striking changes occurred in fronto-temporal-parietal cortex in subject 1 while subject

Sleep Control, GPCRs, and Glucose Metabolism.

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Tsuneki, Hiroshi; Sasaoka, Toshiyasu; Sakurai, Takeshi

2016-09-01

Modern lifestyles prolong daily activities into the nighttime, disrupting circadian rhythms, which may cause sleep disturbances. Sleep disturbances have been implicated in the dysregulation of blood glucose levels and reported to increase the risk of type 2 diabetes (T2D) and diabetic complications. Sleep disorders are treated using anti-insomnia drugs that target ionotropic and G protein-coupled receptors (GPCRs), including γ-aminobutyric acid (GABA) agonists, melatonin agonists, and orexin receptor antagonists. A deeper understanding of the effects of these medications on glucose metabolism and their underlying mechanisms of action is crucial for the treatment of diabetic patients with sleep disorders. In this review we focus on the beneficial impact of sleep on glucose metabolism and suggest a possible strategy for therapeutic intervention against sleep-related metabolic disorders. Copyright © 2016. Published by Elsevier Ltd.

The Role of Monoaminergic Neurotransmission for Metabolic Control in the Fruit Fly Drosophila Melanogaster

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Yong Li

2017-08-01

Full Text Available Hormones control various metabolic traits comprising fat deposition or starvation resistance. Here we show that two invertebrate neurohormones, octopamine (OA and tyramine (TA as well as their associated receptors, had a major impact on these metabolic traits. Animals devoid of the monoamine OA develop a severe obesity phenotype. Using flies defective in the expression of receptors for OA and TA, we aimed to decipher the contributions of single receptors for these metabolic phenotypes. Whereas those animals impaired in octß1r, octß2r and tar1 share the obesity phenotype of OA-deficient (tβh-deficient animals, the octß1r, octß2r deficient flies showed reduced insulin release, which is opposed to the situation found in tβh-deficient animals. On the other hand, OAMB deficient flies were leaner than controls, implying that the regulation of this phenotype is more complex than anticipated. Other phenotypes seen in tβh-deficient animals, such as the reduced ability to perform complex movements tasks can mainly be attributed to the octß2r. Tissue-specific RNAi experiments revealed a very complex interorgan communication leading to the different metabolic phenotypes observed in OA or OA and TA-deficient flies.

Role of a critical visceral adipose tissue threshold (CVATT) in metabolic syndrome: implications for controlling dietary carbohydrates: a review

OpenAIRE

Freedland Eric S

2004-01-01

Abstract There are likely many scenarios and pathways that can lead to metabolic syndrome. This paper reviews mechanisms by which the accumulation of visceral adipose tissue (VAT) may contribute to the metabolic syndrome, and explores the paradigm of a critical VAT threshold (CVATT). Exceeding the CVATT may result in a number of metabolic disturbances such as insulin resistance to glucose uptake by cells. Metabolic profiles of patients with visceral obesity may substantially improve after onl...

Acetazolamide improves oxygenation in patients with respiratory failure and metabolic alkalosis.

Science.gov (United States)

Gulsvik, Ragnhild; Skjørten, Ingunn; Undhjem, Kenneth; Holø, Lars; Frostad, Anne; Saure, Eirunn Waatevik; Lejlic, Vasvija; Humerfelt, Sjur; Hansen, Gunnar; Bruun Wyller, Torgeir

2013-10-01

Coexistent respiratory failure and metabolic alkalosis is a common finding. Acidotic diuretics cause a fall in pH that may stimulate respiration. The purpose of the study was to evaluate the effectiveness of short-term treatment with acetazolamide for combined respiratory failure and metabolic alkalosis. A randomised, placebo-controlled and double-blind parallel group trial where oral acetazolamide 250 mg three times a day for 5 days were administered to patients hospitalised for respiratory failure because of a pulmonary disease (Pa O2 ≤ 8 kPa and/or Pa CO2 ≥ 7 kPa) who had concurrent metabolic alkalosis [base excess (BE) ≥ 8 mmol/L]. Pa O2 after 5 days was the primary effect variable. Secondary effect variables were Pa CO2 , BE and pH on day 5, and the total number of days in hospital. Of 70 patients enrolled (35 in each group), data from 54 were analysed per protocol, while last observation carried forward was used for the remaining 16. During the 5-day treatment, Pa O2 increased on average 0.81 kPa in the placebo group and 1.41 kPa in the acetazolamide group. After adjustment for baseline skewness, the difference was statistically significant (adjusted mean difference 0.55 kPa, 95% confidence interval 0.03-1.06). Pa CO2 decreased in both groups, but the difference was not statistically significant. As expected, pH and BE decreased markedly in the acetazolamide group. Acetazolamide may constitute a useful adjuvant treatment mainly to be considered in selected patients with respiratory failure combined with prominent metabolic alkalosis or where non-invasive ventilation is insufficient or infeasible. © 2013 John Wiley & Sons Ltd.

Therapeutic role of ursolic acid on ameliorating hepatic steatosis and improving metabolic disorders in high-fat diet-induced non-alcoholic fatty liver disease rats.

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Li, Songtao; Liao, Xilu; Meng, Fanyu; Wang, Yemei; Sun, Zongxiang; Guo, Fuchuan; Li, Xiaoxia; Meng, Man; Li, Ying; Sun, Changhao

2014-01-01

Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases around the world, and is closely associated with obesity, diabetes, and insulin resistance. Ursolic acid (UA), an ubiquitous triterpenoid with multifold biological roles, is distributed in various plants. This study was conducted to investigate the therapeutic effect and potential mechanisms of UA against hepatic steatosis in a high-fat diet (HFD)-induced obese non-alcoholic fatty liver disease (NAFLD) rat model. Obese NAFLD model was established in Sprague-Dawley rats by 8-week HFD feeding. Therapeutic role of UA was evaluated using 0.125%, 0.25%, 0.5% UA-supplemented diet for another 6 weeks. The results from both morphologic and histological detections indicated that UA significantly reversed HFD-induced hepatic steatosis and liver injury. Besides, hepatic peroxisome proliferator-activated receptor (PPAR)-α was markedly up-regulated at both mRNA and protein levels by UA. Knocking down PPAR-α significantly inhibited the anti-steatosis role of UA in vitro. HFD-induced adverse changes in the key genes, which participated in hepatic lipid metabolism, were also alleviated by UA treatment. Furthermore, UA significantly ameliorated HFD-induced metabolic disorders, including insulin resistance, inflammation and oxidative stress. These results demonstrated that UA effectively ameliorated HFD-induced hepatic steatosis through a PPAR-α involved pathway, via improving key enzymes in the controlling of lipids metabolism. The metabolic disorders were accordingly improved with the decrease of hepatic steatosis. Thereby, UA could be a promising candidate for the treatment of NAFLD.

Therapeutic role of ursolic acid on ameliorating hepatic steatosis and improving metabolic disorders in high-fat diet-induced non-alcoholic fatty liver disease rats.

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Songtao Li

Full Text Available BACKGROUND: Non-alcoholic fatty liver disease (NAFLD is one of the most prevalent liver diseases around the world, and is closely associated with obesity, diabetes, and insulin resistance. Ursolic acid (UA, an ubiquitous triterpenoid with multifold biological roles, is distributed in various plants. This study was conducted to investigate the therapeutic effect and potential mechanisms of UA against hepatic steatosis in a high-fat diet (HFD-induced obese non-alcoholic fatty liver disease (NAFLD rat model. METHODOLOGY/PRINCIPAL FINDINGS: Obese NAFLD model was established in Sprague-Dawley rats by 8-week HFD feeding. Therapeutic role of UA was evaluated using 0.125%, 0.25%, 0.5% UA-supplemented diet for another 6 weeks. The results from both morphologic and histological detections indicated that UA significantly reversed HFD-induced hepatic steatosis and liver injury. Besides, hepatic peroxisome proliferator-activated receptor (PPAR-α was markedly up-regulated at both mRNA and protein levels by UA. Knocking down PPAR-α significantly inhibited the anti-steatosis role of UA in vitro. HFD-induced adverse changes in the key genes, which participated in hepatic lipid metabolism, were also alleviated by UA treatment. Furthermore, UA significantly ameliorated HFD-induced metabolic disorders, including insulin resistance, inflammation and oxidative stress. CONCLUSIONS/SIGNIFICANCE: These results demonstrated that UA effectively ameliorated HFD-induced hepatic steatosis through a PPAR-α involved pathway, via improving key enzymes in the controlling of lipids metabolism. The metabolic disorders were accordingly improved with the decrease of hepatic steatosis. Thereby, UA could be a promising candidate for the treatment of NAFLD.

Metabolic effects of low glycaemic index diets

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Rusu Emilia

2009-01-01

Full Text Available Abstract The persistence of an epidemic of obesity and type 2 diabetes suggests that new nutritional strategies are needed if the epidemic is to be overcome. A promising nutritional approach suggested by this thematic review is metabolic effect of low glycaemic-index diet. The currently available scientific literature shows that low glycaemic-index diets acutely induce a number of favorable effects, such as a rapid weight loss, decrease of fasting glucose and insulin levels, reduction of circulating triglyceride levels and improvement of blood pressure. The long-term effect of the combination of these changes is at present not known. Based on associations between these metabolic parameters and risk of cardiovascular disease, further controlled studies on low-GI diet and metabolic disease are needed.

Nutritional regulation of bile acid metabolism is associated with improved pathological characteristics of the metabolic syndrome

DEFF Research Database (Denmark)

Liaset, Bjørn; Hao, Qin; Jørgensen, Henry Johs. Høgh

2011-01-01

Bile acids (BAs) are powerful regulators of metabolism, and mice treated orally with cholic acid are protected from diet-induced obesity, hepatic lipid accumulation, and increased plasma triacylglycerol (TAG) and glucose levels. Here, we show that plasma BA concentration in rats was elevated by e...... metabolism can be modulated by diet and that such modulation may prevent/ameliorate the characteristic features of the metabolic syndrome.......Bile acids (BAs) are powerful regulators of metabolism, and mice treated orally with cholic acid are protected from diet-induced obesity, hepatic lipid accumulation, and increased plasma triacylglycerol (TAG) and glucose levels. Here, we show that plasma BA concentration in rats was elevated...... with induction of genes involved in energy metabolism and uncoupling, Dio2, Pgc-1a, and Ucp1, in interscapular brown adipose tissue. Interestingly, the same transcriptional pattern was found in white adipose tissue depots of both abdominal and subcutaneous origin. Accordingly, rats fed SPH-based diet exhibited...

Individual and family strengths: an examination of the relation to disease management and metabolic control in youth with type 1 diabetes.

Science.gov (United States)

Mackey, Eleanor Race; Hilliard, Marisa E; Berger, Sarah Shafer; Streisand, Randi; Chen, Rusan; Holmes, Clarissa

2011-12-01

We examined the association of youths' positive qualities, family cohesion, disease management, and metabolic control in Type 1 diabetes. Two-hundred fifty-seven youth-parent dyads completed the Family Cohesion subscale of the Family Environment Scale, the Diabetes Behavior Rating Scale, 24-hour diabetes interview, and youth completed the Positive Qualities subscale of the Youth Self Report (YSR-PQ). Structural equation modeling demonstrated that YSR-PQ scores were associated with metabolic control mediated by associations with more family cohesion and better disease management. That is, youth with higher YSR-PQ scores had more cohesive families, better disease management, and, indirectly, better metabolic control. Family cohesion was indirectly associated with better metabolic control mediated by its association with better disease management, but not mediated by its association with YSR-PQ scores. Youth who reported more positive qualities, as measured by the YSR-PQ subscale, had better disease management and metabolic control through the association with more family cohesion. However, the current results did not support an alternative hypothesis that cohesive families display better diabetes management mediated by higher YSR-PQ scores.

Space Station CMIF extended duration metabolic control test

Science.gov (United States)

Schunk, Richard G.; Bagdigian, Robert M.; Carrasquillo, Robyn L.; Ogle, Kathryn Y.; Wieland, Paul O.

1989-01-01

The Space Station Extended Duration Metabolic Control Test (EMCT) was conducted at the MSFC Core Module Integration Facility. The primary objective of the EMCT was to gather performance data from a partially-closed regenerative Environmental Control and Life Support (ECLS) system functioning under steady-state conditions. Included is a description of the EMCT configuration, a summary of events, a discussion of anomalies that occurred during the test, and detailed results and analysis from individual measurements of water and gas samples taken during the test. A comparison of the physical, chemical, and microbiological methods used in the post test laboratory analyses of the water samples is included. The preprototype ECLS hardware used in the test, providing an overall process description and theory of operation for each hardware item. Analytical results pertaining to a system level mass balance and selected system power estimates are also included.

Global metabolic rewiring for improved CO2 fixation and chemical production in cyanobacteria

Science.gov (United States)

Kanno, Masahiro; Carroll, Austin L.; Atsumi, Shota

2017-03-01

Cyanobacteria have attracted much attention as hosts to recycle CO2 into valuable chemicals. Although cyanobacteria have been engineered to produce various compounds, production efficiencies are too low for commercialization. Here we engineer the carbon metabolism of Synechococcus elongatus PCC 7942 to improve glucose utilization, enhance CO2 fixation and increase chemical production. We introduce modifications in glycolytic pathways and the Calvin Benson cycle to increase carbon flux and redirect it towards carbon fixation. The engineered strain efficiently uses both CO2 and glucose, and produces 12.6 g l-1 of 2,3-butanediol with a rate of 1.1 g l-1 d-1 under continuous light conditions. Removal of native regulation enables carbon fixation and 2,3-butanediol production in the absence of light. This represents a significant step towards industrial viability and an excellent example of carbon metabolism plasticity.

Effect of dietary regime on metabolic control in phenylketonuria: Is exact calculation of phenylalanine intake really necessary?

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Carmen Rohde

2015-12-01

Conclusion: Exact calculation of Phe content of all food is not necessary to achieve good metabolic control in children and adolescents with PKU. Excluding special low protein food, as well as fruit and vegetables from calculation of Phe-intake has no impact on metabolic control. However including protein rich food into the diet and simply estimating all Phe-intake appears insufficient. The simplification of dietary regime may be helpful in enhancing acceptability and feasibility.

Combined Effects of Ezetimibe and Phytosterols on Cholesterol Metabolism: A Randomized, Controlled Feeding Study in Humans

Science.gov (United States)

Lin, Xiaobo; Racette, Susan B.; Lefevre, Michael; Ma, Lina; Spearie, Catherine Anderson; Steger-May, Karen; Ostlund, Richard E.

2011-01-01

Background Both ezetimibe and phytosterols inhibit cholesterol absorption. We tested the hypothesis that ezetimibe combined with phytosterols is more effective than ezetimibe alone in altering cholesterol metabolism. Methods and Results Twenty-one mildly hypercholesterolemic subjects completed a randomized, double-blind, placebo-controlled, triple crossover study. Each subject received a phytosterol-controlled diet plus (1) ezetimibe placebo + phytosterol placebo, (2) 10 mg ezetimibe/day + phytosterol placebo, and (3) 10 mg ezetimibe/day + 2.5 g phytosterols/day, for 3 weeks each. All meals were prepared in a metabolic kitchen. Primary outcomes were intestinal cholesterol absorption, fecal cholesterol excretion, and LDL cholesterol levels. The combined treatment resulted in significantly lower intestinal cholesterol absorption (598 mg/day, 95% CI 368 to 828) relative to control (2161 mg/day, 1112 to 3209) and ezetimibe alone (1054 mg/day, 546 to 1561, both P phytosterols averaged 129 (95% CI: 116 to 142), 108 (97 to 119), and 101 (90 to 112) mg/dL (P phytosterols to ezetimibe significantly enhanced the effects of ezetimibe on whole-body cholesterol metabolism and plasma LDL cholesterol. The large cumulative action of combined dietary and pharmacologic treatment on cholesterol metabolism emphasizes the potential importance of dietary phytosterols as adjunctive therapy for the treatment of hypercholesterolemia. PMID:21768544

Weight loss after bariatric surgery reverses insulin-induced increases in brain glucose metabolism of the morbidly obese.

Science.gov (United States)

Tuulari, Jetro J; Karlsson, Henry K; Hirvonen, Jussi; Hannukainen, Jarna C; Bucci, Marco; Helmiö, Mika; Ovaska, Jari; Soinio, Minna; Salminen, Paulina; Savisto, Nina; Nummenmaa, Lauri; Nuutila, Pirjo

2013-08-01

Obesity and insulin resistance are associated with altered brain glucose metabolism. Here, we studied brain glucose metabolism in 22 morbidly obese patients before and 6 months after bariatric surgery. Seven healthy subjects served as control subjects. Brain glucose metabolism was measured twice per imaging session: with and without insulin stimulation (hyperinsulinemic-euglycemic clamp) using [18F]fluorodeoxyglucose scanning. We found that during fasting, brain glucose metabolism was not different between groups. However, the hyperinsulinemic clamp increased brain glucose metabolism in a widespread manner in the obese but not control subjects, and brain glucose metabolism was significantly higher during clamp in obese than in control subjects. After follow-up, 6 months postoperatively, the increase in glucose metabolism was no longer observed, and this attenuation was coupled with improved peripheral insulin sensitivity after weight loss. We conclude that obesity is associated with increased insulin-stimulated glucose metabolism in the brain and that this abnormality can be reversed by bariatric surgery.

Brain glucose sensing, glucokinase and neural control of metabolism and islet function.

Science.gov (United States)

Ogunnowo-Bada, E O; Heeley, N; Brochard, L; Evans, M L

2014-09-01

It is increasingly apparent that the brain plays a central role in metabolic homeostasis, including the maintenance of blood glucose. This is achieved by various efferent pathways from the brain to periphery, which help control hepatic glucose flux and perhaps insulin-stimulated insulin secretion. Also, critically important for the brain given its dependence on a constant supply of glucose as a fuel--emergency counter-regulatory responses are triggered by the brain if blood glucose starts to fall. To exert these control functions, the brain needs to detect rapidly and accurately changes in blood glucose. In this review, we summarize some of the mechanisms postulated to play a role in this and examine the potential role of the low-affinity hexokinase, glucokinase, in the brain as a key part of some of this sensing. We also discuss how these processes may become altered in diabetes and related metabolic diseases. © 2014 John Wiley & Sons Ltd.

Central nervous system control of triglyceride metabolism

NARCIS (Netherlands)

Geerling, Johanna Janetta (Janine)

2013-01-01

This thesis describes the role of the brain in the regulation of peripheral triglyceride metabolism, in the context of the metabolic syndrome. Based on various pharmacological studies we described the role of two hormones, insulin and glucagon-like peptide-1, in the production and clearance of

Improving the precision of lake ecosystem metabolism estimates by identifying predictors of model uncertainty

Science.gov (United States)

Rose, Kevin C.; Winslow, Luke A.; Read, Jordan S.; Read, Emily K.; Solomon, Christopher T.; Adrian, Rita; Hanson, Paul C.

2014-01-01

Diel changes in dissolved oxygen are often used to estimate gross primary production (GPP) and ecosystem respiration (ER) in aquatic ecosystems. Despite the widespread use of this approach to understand ecosystem metabolism, we are only beginning to understand the degree and underlying causes of uncertainty for metabolism model parameter estimates. Here, we present a novel approach to improve the precision and accuracy of ecosystem metabolism estimates by identifying physical metrics that indicate when metabolism estimates are highly uncertain. Using datasets from seventeen instrumented GLEON (Global Lake Ecological Observatory Network) lakes, we discovered that many physical characteristics correlated with uncertainty, including PAR (photosynthetically active radiation, 400-700 nm), daily variance in Schmidt stability, and wind speed. Low PAR was a consistent predictor of high variance in GPP model parameters, but also corresponded with low ER model parameter variance. We identified a threshold (30% of clear sky PAR) below which GPP parameter variance increased rapidly and was significantly greater in nearly all lakes compared with variance on days with PAR levels above this threshold. The relationship between daily variance in Schmidt stability and GPP model parameter variance depended on trophic status, whereas daily variance in Schmidt stability was consistently positively related to ER model parameter variance. Wind speeds in the range of ~0.8-3 m s–1 were consistent predictors of high variance for both GPP and ER model parameters, with greater uncertainty in eutrophic lakes. Our findings can be used to reduce ecosystem metabolism model parameter uncertainty and identify potential sources of that uncertainty.

Mice with chimeric livers are an improved model for human lipoprotein metabolism.

Science.gov (United States)

Ellis, Ewa C S; Naugler, Willscott Edward; Nauglers, Scott; Parini, Paolo; Mörk, Lisa-Mari; Jorns, Carl; Zemack, Helen; Sandblom, Anita Lövgren; Björkhem, Ingemar; Ericzon, Bo-Göran; Wilson, Elizabeth M; Strom, Stephen C; Grompe, Markus

2013-01-01

Rodents are poor model for human hyperlipidemias because total cholesterol and low density lipoprotein levels are very low on a normal diet. Lipoprotein metabolism is primarily regulated by hepatocytes and we therefore assessed whether chimeric mice extensively repopulated with human cells can model human lipid and bile acid metabolism. FRG [ F ah(-/-) R ag2(-/-)Il2r g (-/-)]) mice were repopulated with primary human hepatocytes. Serum lipoprotein lipid composition and distribution (VLDL, LDL, and HDL) was analyzed by size exclusion chromatography. Bile was analyzed by LC-MS or by GC-MS. RNA expression levels were measured by quantitative RT-PCR. Chimeric mice displayed increased LDL and VLDL fractions and a lower HDL fraction compared to wild type, thus significantly shifting the ratio of LDL/HDL towards a human profile. Bile acid analysis revealed a human-like pattern with high amounts of cholic acid and deoxycholic acid (DCA). Control mice had only taurine-conjugated bile acids as expcted, but highly repopulated mice had glycine-conjugated cholic acid as found in human bile. RNA levels of human genes involved in bile acid synthesis including CYP7A1, and CYP27A1 were significantly upregulated as compared to human control liver. However, administration of recombinant hFGF19 restored human CYP7A1 levels to normal. Humanized-liver mice showed a typical human lipoprotein profile with LDL as the predominant lipoprotein fraction even on a normal diet. The bile acid profile confirmed presence of an intact enterohepatic circulation. Although bile acid synthesis was deregulated in this model, this could be fully normalized by FGF19 administration. Taken together these data indicate that chimeric FRG-mice are a useful new model for human lipoprotein and bile-acid metabolism.

Impact of a structured multicomponent educational intervention program on metabolic control of patients with type 2 diabetes.

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do Rosário Pinto, Maria; Parreira, Pedro Miguel Dinis Santos; Basto, Marta Lima; Dos Santos Mendes Mónico, Lisete

2017-12-15

Diabetes is one of the most common metabolic disorders, with a high prevalence of patients with poor metabolic control. Worldwide, evidence highlights the importance of developing and implementing educational interventions that can reduce this burden. The main objective of this study was to analyse the impact of a lifestyle centred intervention on glycaemic control of poorly controlled type 2 diabetic patients, followed in a Community Care Centre. A type 2 experimental design was conducted over 6 months, including 122 adults with HbA1c ≥ 7.5%, randomly allocated into Experimental group (EG) or Control Group (CG). EG patients attended a specific Educational Program while CG patients frequented usual care. Personal and health characterization variables, clinical metrics and self-care activities were measured before and after the implementation of the intervention. Analysis was done by comparing gains between groups (CG vs EG) through differential calculations (post minus pre-test results) and Longitudinal analysis. Statistical differences were obtained between groups for HbA1c and BMI: EG had a decrease in 11% more (effect-size r2 = .11) than CG for HbA1c (p values [Wilks' ʎ = .900; F(1,59) = 6.57; p = .013; ηp2 = .100; observed power = .713]; systolic Blood pressure [Wilks' ʎ = .735; F(1,61) = 21.94; p educational intervention program by itself, beyond standard educational approach alone, supported in a Longitudinal analysis that controlled variables statistically associated with clinical metrics in pre-test measures, has demonstrated its effectiveness in improving HbA1c, BMI and Blood pressure values. RBR-8ns8pb . (Retrospectively registered: October 30,2017).

Relationship between the Peroxidation of Leukocytes Index Ratio and the Improvement of Postprandial Metabolic Stress by a Functional Food.

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Peluso, Ilaria; Manafikhi, Husseen; Reggi, Raffaella; Longhitano, Yaroslava; Zanza, Christian; Palmery, Maura

2016-01-01

For the first time, we investigated the relationship between postprandial dysmetabolism and the Peroxidation of Leukocytes Index Ratio (PLIR), a test that measures the resistance of leukocytes to exogenous oxidative stress and their functional capacity of oxidative burst upon activation. Following a blind, placebo controlled, randomized, crossover design, ten healthy subjects ingested, in two different occasions, a high fat and high carbohydrates meal with Snello cookie (HFHCM-S) or with control cookies (HFHCM-C). Snello cookie, a functional food covered by dark chocolate and containing glucomannan, inulin, fructooligosaccharides, and Bacillus coagulans strain GanedenBC30, significantly improved postprandial metabolic stress (insulin, glucose, and triglycerides) and reduced the postprandial increase of uric acid. HFHCM-S improved PLIR of lymphocytes, but not of monocytes and granulocytes. Both meals increased granulocytes' count and reduced the lipoperoxidation induced by both exogenous free radicals and reactive oxygen species (ROS) produced by oxidative burst. Our results suggest that the healthy status of the subjects could be a limitation of this pilot study for PLIR evaluation on cells that produce ROS by oxidative burst. In conclusion, the relationship between PLIR and postprandial dysmetabolism requires further investigations.

Relationship between the Peroxidation of Leukocytes Index Ratio and the Improvement of Postprandial Metabolic Stress by a Functional Food

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Ilaria Peluso

2016-01-01

Full Text Available For the first time, we investigated the relationship between postprandial dysmetabolism and the Peroxidation of Leukocytes Index Ratio (PLIR, a test that measures the resistance of leukocytes to exogenous oxidative stress and their functional capacity of oxidative burst upon activation. Following a blind, placebo controlled, randomized, crossover design, ten healthy subjects ingested, in two different occasions, a high fat and high carbohydrates meal with Snello cookie (HFHCM-S or with control cookies (HFHCM-C. Snello cookie, a functional food covered by dark chocolate and containing glucomannan, inulin, fructooligosaccharides, and Bacillus coagulans strain GanedenBC30, significantly improved postprandial metabolic stress (insulin, glucose, and triglycerides and reduced the postprandial increase of uric acid. HFHCM-S improved PLIR of lymphocytes, but not of monocytes and granulocytes. Both meals increased granulocytes’ count and reduced the lipoperoxidation induced by both exogenous free radicals and reactive oxygen species (ROS produced by oxidative burst. Our results suggest that the healthy status of the subjects could be a limitation of this pilot study for PLIR evaluation on cells that produce ROS by oxidative burst. In conclusion, the relationship between PLIR and postprandial dysmetabolism requires further investigations.

Cancer treatment induced metabolic syndrome : Improving outcome with lifestyle

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Westerink, M. D. N. L.; Nuver, J.; Lefrandt, J. D.; Vrieling, A. H.; Gietema, J. A.; Walenkamp, A. M. E.

2016-01-01

Increasing numbers of long-term cancer survivors face important treatment related adverse effects. Cancer treatment induced metabolic syndrome (CTIMetS) is an especially prevalent and harmful condition. The aetiology of CTIMetS likely differs from metabolic syndrome in the general population, but

Sodium bicarbonate on severe metabolic acidosis during prolonged cardiopulmonary resuscitation: a double-blind, randomized, placebo-controlled pilot study.

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Ahn, Shin; Kim, Youn-Jung; Sohn, Chang Hwan; Seo, Dong Woo; Lim, Kyoung Soo; Donnino, Michael W; Kim, Won Young

2018-04-01

Sodium bicarbonate administration during cardiopulmonary resuscitation (CPR) is controversial. Current guidelines recommend sodium bicarbonate injection in patients with existing metabolic acidosis, but clinical trials, particularly, those involving patients with acidosis, are limited. We aimed to evaluate the efficacy of sodium bicarbonate administration in out-of-hospital cardiac arrest (OHCA) patients with severe metabolic acidosis during prolonged CPR. Prospective, double-blind, randomized placebo-controlled pilot trial was conducted between January 2015 and December 2015, at a single center emergency department (ED). After 10 minutes of CPR, patients who failed to achieve return of spontaneous circulation (ROSC) and with severe metabolic acidosis (pH<7.1 or bicarbonate <10 mEq/L) were enrolled. Sodium bicarbonate (n=25) or normal saline (n=25) were administered. The primary end point was sustained ROSC. The secondary end points were the change of acidosis and good neurologic survival. Sodium bicarbonate group had significant effect on pH (6.99 vs. 6.90, P=0.038) and bicarbonate levels (21.0 vs. 8.0 mEq/L, P=0.007). However, no significant differences showed between sodium bicarbonate and placebo groups in sustained ROSC (4.0% vs. 16.0%, P=0.349) or good neurologic survival at 1 month (0.0% vs. 4.0%, P=1.000). The use of sodium bicarbonate improved acid-base status, but did not improve the rate of ROSC and good neurologic survival. We could not draw a conclusion, but our pilot data could be used to design a larger trial to verify the efficacy of sodium bicarbonate. NCT02303548 (http://www.ClinicalTrials.gov).

Metabolic effects of lifestyle intervention in obese pregnant women. Results from the randomized controlled trial 'Lifestyle in Pregnancy' (LiP)

DEFF Research Database (Denmark)

Vinter, C A; Jørgensen, J S; Ovesen, Per Glud

2014-01-01

weight gain in the intervention group, there was no difference between the groups with respect to total cholesterol, HDL, LDL or triglycerides. CONCLUSIONS: Lifestyle intervention in obese pregnant women resulted in attenuation of the physiologic pregnancy-induced insulin resistance. Despite restricted......AIMS: The Lifestyle in Pregnancy intervention in obese pregnant women resulted in significantly lower gestational weight gain compared with the control group, but without improvement in rates of clinical pregnancy complications. The impact of the lifestyle intervention on metabolic measurements...... in the study participants is now reported. METHODS: The Lifestyle in Pregnancy study was a randomized controlled trial among 360 obese women (BMI 30-45 kg/m(2) ) who were allocated in early pregnancy to lifestyle interventions with diet counselling and physical activities or to the control group. Fasting blood...

Managing uncertainty in metabolic network structure and improving predictions using EnsembleFBA.

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Matthew B Biggs

2017-03-01

Full Text Available Genome-scale metabolic network reconstructions (GENREs are repositories of knowledge about the metabolic processes that occur in an organism. GENREs have been used to discover and interpret metabolic functions, and to engineer novel network structures. A major barrier preventing more widespread use of GENREs, particularly to study non-model organisms, is the extensive time required to produce a high-quality GENRE. Many automated approaches have been developed which reduce this time requirement, but automatically-reconstructed draft GENREs still require curation before useful predictions can be made. We present a novel approach to the analysis of GENREs which improves the predictive capabilities of draft GENREs by representing many alternative network structures, all equally consistent with available data, and generating predictions from this ensemble. This ensemble approach is compatible with many reconstruction methods. We refer to this new approach as Ensemble Flux Balance Analysis (EnsembleFBA. We validate EnsembleFBA by predicting growth and gene essentiality in the model organism Pseudomonas aeruginosa UCBPP-PA14. We demonstrate how EnsembleFBA can be included in a systems biology workflow by predicting essential genes in six Streptococcus species and mapping the essential genes to small molecule ligands from DrugBank. We found that some metabolic subsystems contributed disproportionately to the set of predicted essential reactions in a way that was unique to each Streptococcus species, leading to species-specific outcomes from small molecule interactions. Through our analyses of P. aeruginosa and six Streptococci, we show that ensembles increase the quality of predictions without drastically increasing reconstruction time, thus making GENRE approaches more practical for applications which require predictions for many non-model organisms. All of our functions and accompanying example code are available in an open online repository.

Novel benzimidazole derivatives as phosphodiesterase 10A (PDE10A) inhibitors with improved metabolic stability.

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Chino, Ayaka; Masuda, Naoyuki; Amano, Yasushi; Honbou, Kazuya; Mihara, Takuma; Yamazaki, Mayako; Tomishima, Masaki

2014-07-01

In this study, we report the identification of potent benzimidazoles as PDE10A inhibitors. We first identified imidazopyridine 1 as a high-throughput screening hit compound from an in-house library. Next, optimization of the imidazopyridine moiety to improve inhibitory activity gave imidazopyridinone 10b. Following further structure-activity relationship development by reducing lipophilicity and introducing substituents, we acquired 35, which exhibited both improved metabolic stability and reduced CYP3A4 time-dependent inhibition. Copyright © 2014. Published by Elsevier Ltd.

Metabolic Response to Four Weeks of Muscular Endurance Resistance Training

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John W. Farrell III

2017-10-01

Full Text Available Background: Previous investigations have shown that muscular endurance resistance training (MERT is conducive in improving the onset of blood lactate accumulation (OBLA. However, the metabolic response and time course for adaption is still unclear. Objective: The aims of the current study were to evaluate and track the metabolic response to an individual session of MERT as well as to assess performance adaptations of supplementing an aerobic exercise training program with four weeks of MERT. Methods: Seventeen aerobically active men were randomly assigned to either the experimental (EX or control group (CON, 9 EX and 8 CON. Baseline measures included a graded exercise test (GXT and 1-repetition maximum (1RM testing for leg press (LP, leg curl (LC, and leg extension (LE. CON continued their regular aerobic activity while the EX supplemented their regular aerobic exercise with 4 weeks of MERT. Results: No significant group differences were observed for all pre-training variables. Following four weeks of training no significant differences in cardiorespiratory or metabolic variables were observed for either group. However, significant improvements in LC and LE 1-RM were observed in EX compared to CON. Substantial accumulations in blood lactate were observed following each MERT session. Conclusion: Four weeks of MERT did not improve cardiorespiratory or metabolic variables, but did significantly improve LC and LE. MERT was also observed to induce a blood lactate response similar to that of HIIT. These findings suggest greater than four weeks is need to see metabolic adaptations conducive for improved aerobic performance using MERT.

BEYOND GLYCEMIC CONTROL IN DIABETES MELLITUS: EFFECTS OF INCRETIN-BASED THERAPY ON BONE METABOLISM

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ELENA eCECCARELLI

2013-06-01

Full Text Available Diabetes mellitus (DM and osteoporosis (OP are common disorders with a significant health burden, and an increase in fracture risk has been described both in type 1 (T1DM and in type 2 (T2DM diabetes. The pathogenic mechanisms of impaired skeletal strength in diabetes remain to be clarified in details and they are only in part reflected by a variation in bone mineral density (BMD. In T2DM, the occurrence of low bone turnover together with a decreased osteoblast activity and compromised bone quality has been shown. Of note, some antidiabetic drugs (e.g. tiazolidinediones, insulin may deeply affect bone metabolism. In addition, the recently introduced class of incretin-based drugs (i.e. GLP-1 receptor agonists and DPP-4 inhibitors is expected to exert potentially beneficial effects on bone health, possibly due to a bone anabolic activity of GLP-1, that can be either direct or indirect through the involvement of thyroid C cells.Here we will review the established as well as the putative effects of incretin hormones and of incretin-based drugs on bone metabolism, both in preclinical models and in man, taking into account that such therapeutic strategy may be effective not only to achieve a good glycemic control, but also to improve bone health in diabetic patients.

The effect of exercise training on clinical outcomes in patients with the metabolic syndrome: a systematic review and meta-analysis.

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Ostman, C; Smart, N A; Morcos, D; Duller, A; Ridley, W; Jewiss, D

2017-08-30

Purpose: to establish if exercise training improves clinical outcomes in people with metabolic syndrome (MetS). Registered with PROSPERO international prospective register of systematic reviews ( https://www.crd.york.ac.uk/PROSPERO/Identifier:CRD42017055491 ). studies were identified through a MEDLINE search strategy (1985 to Jan 12, 2017), Cochrane controlled trials registry, CINAHL and SPORTDiscus. prospective randomized or controlled trials of exercise training in humans with metabolic syndrome, lasting 12 weeks or more. We included 16 studies with 23 intervention groups; 77,000 patient-hours of exercise training. In analyses of aerobic exercise studies versus control: body mass index was significantly reduced, mean difference (MD) -0.29 (kg m -2 ) (95% CI -0.44, -0.15, p exercise versus control: waist circumference, MD -3.80 cm (95% CI -5.65, -1.95, p exercise interventions. Exercise training improves body composition, cardiovascular, and, metabolic outcomes in people with metabolic syndrome. For some outcome measures, isolated aerobic exercise appears optimal.

[Metabolic control in the critically ill patient an update: hyperglycemia, glucose variability hypoglycemia and relative hypoglycemia].

Science.gov (United States)

Pérez-Calatayud, Ángel Augusto; Guillén-Vidaña, Ariadna; Fraire-Félix, Irving Santiago; Anica-Malagón, Eduardo Daniel; Briones Garduño, Jesús Carlos; Carrillo-Esper, Raúl

Metabolic changes of glucose in critically ill patients increase morbidity and mortality. The appropriate level of blood glucose has not been established so far and should be adjusted for different populations. However concepts such as glucose variability and relative hypoglycemia of critically ill patients are concepts that are changing management methods and achieving closer monitoring. The purpose of this review is to present new data about the management and metabolic control of patients in critical areas. Currently glucose can no longer be regarded as an innocent element in critical patients; both hyperglycemia and hypoglycemia increase morbidity and mortality of patients. Protocols and better instruments for continuous measurement are necessary to achieve the metabolic control of our patients. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

Cardio-Metabolic Benefits of Plant-Based Diets

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Hana Kahleova

2017-08-01

Full Text Available Cardio-metabolic disease, namely ischemic heart disease, stroke, obesity, and type 2 diabetes, represent substantial health and economic burdens. Almost one half of cardio-metabolic deaths in the U.S. might be prevented through proper nutrition. Plant-based (vegetarian and vegan diets are an effective strategy for improving nutrient intake. At the same time, they are associated with decreased all-cause mortality and decreased risk of obesity, type 2 diabetes, and coronary heart disease. Evidence suggests that plant-based diets may reduce the risk of coronary heart disease events by an estimated 40% and the risk of cerebral vascular disease events by 29%. These diets also reduce the risk of developing metabolic syndrome and type 2 diabetes by about one half. Properly planned vegetarian diets are healthful, effective for weight and glycemic control, and provide metabolic and cardiovascular benefits, including reversing atherosclerosis and decreasing blood lipids and blood pressure. The use of plant-based diets as a means of prevention and treatment of cardio-metabolic disease should be promoted through dietary guidelines and recommendations.

Effects and mechanisms of caffeine to improve immunological and metabolic abnormalities in diet-induced obese rats.

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Liu, Chih-Wei; Tsai, Hung-Cheng; Huang, Chia-Chang; Tsai, Chang-Youh; Su, Yen-Bo; Lin, Ming-Wei; Lee, Kuei-Chuan; Hsieh, Yun-Cheng; Li, Tzu-Hao; Huang, Shiang-Fen; Yang, Ying-Ying; Hou, Ming-Chih; Lin, Han-Chieh; Lee, Fa-Yauh; Lee, Shou-Dong

2018-05-01

In obesity, there are no effective therapies for parallel immune and metabolic abnormalities, including systemic/tissue insulin-resistance/inflammation, adiposity and hepatic steatosis. Caffeine has anti-inflammation, antihepatic steatosis, and anti-insulin resistance effects. In this study, we evaluated the effects and molecular mechanisms of 6 wk of caffeine treatment (HFD-caf) on immunological and metabolic abnormalities of high-fat diet (HFD)-induced obese rats. Compared with HFD vehicle (HFD-V) rats, in HFD-caf rats the suppressed circulating immune cell inflammatory [TNFα, MCP-1, IL-6, intercellular adhesion molecule 1 (ICAM-1), and nitrite] profiles were accompanied by decreased liver, white adipose tissue (WAT), and muscle macrophages and their intracellular cytokine levels. Metabolically, the increase in metabolic rates reduced lipid accumulation in various tissues, resulting in reduced adiposity, lower fat mass, decreased body weight, amelioration of hepatic steatosis, and improved systemic/muscle insulin resistance. Further mechanistic approaches revealed an upregulation of tissue lipogenic [(SREBP1c, fatty acid synthase, acetyl-CoA carboxylase)/insulin-sensitizing (GLUT4 and p-IRS1)] markers in HFD-caf rats. Significantly, ex vivo experiments revealed that the cytokine release by the cocultured peripheral blood mononuclear cell (monocyte) and WAT (adipocyte), which are known to stimulate macrophage migration and hepatocyte lipogenesis, were lower in HFD-V groups than HFD-caf groups. Caffeine treatment simultaneously ameliorates immune and metabolic pathogenic signals present in tissue to normalize immunolgical and metabolic abnormalities found in HFD-induced obese rats.

Delayed sodium (18)F-fluoride PET/CT imaging does not improve quantification of vascular calcification metabolism

DEFF Research Database (Denmark)

Blomberg, Björn Alexander; Thomassen, Anders; Takx, Richard A P

2014-01-01

This study aimed to determine if delayed sodium (18)F-fluoride (Na(18)F) PET/CT imaging improves quantification of vascular calcification metabolism. Blood-pool activity can disturb the arterial Na(18)F signal. With time, blood-pool activity declines. Therefore, delayed imaging can potentially...

Interaction of Pubertal Development and Metabolic Control in Adolescents with Type 1 Diabetes Mellitus

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M. Plamper

2017-01-01

Full Text Available Background. In T1DM, delayed pubertal development and reduced final height are associated with inadequate metabolic control. Objective. To assess whether T1DM affects pubertal growth spurt and whether metabolic control during puberty is gender-related. Methods. Using a large multicentre database, longitudinal data from 1294 patients were analysed. Inclusion criteria: complete records of height and HbA1c from the age of seven to 16 years. Exclusion criteria: other significant chronic diseases and medications, T1DM duration less than three months, and initial BMI 97th percentile. Results. Growth velocity (GV was impaired with a significant reduction of peak GV by 1.2 cm in boys. HbA1c increase during male puberty was lower except for a period of 1.5 years. The highest HbA1c increase in boys coincided with maximum growth spurt. In girls, the highest HbA1c increase was observed during late puberty. Even though there is impaired GV, both sexes reach a height at 16 years of age which corresponds to the background population height. Conclusion. Worsening of metabolic control is sex-discordant and associated with gender-specific alterations of GV. However, the vast majority of boys and girls with T1DM seems to reach normal height at the age of 16 years.

Effectiveness of physical activity intervention among government employees with metabolic syndrome.

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Huei Phing, Chee; Abu Saad, Hazizi; Barakatun Nisak, M Y; Mohd Nasir, M T

2017-12-01

Our study aimed to assess the effects of physical activity interventions via standing banners (point-of-decision prompt) and aerobics classes to promote physical activity among individuals with metabolic syndrome. We conducted a cluster randomized controlled intervention trial (16-week intervention and 8-week follow-up). Malaysian government employees in Putrajaya, Malaysia, with metabolic syndrome were randomly assigned by cluster to a point-of-decision prompt group (n = 44), an aerobics group (n = 42) or a control group (n = 103) based on sample size calculation formula. Step counts were evaluated by Lifecorder e-STEP accelerometers for all participants. Metabolic syndrome was defined according to the 'harmonizing' definition, in which individuals who have at least three of the five metabolic risk factors (waist circumference, high-density lipoprotein cholesterol, triglycerides, fasting glucose levels, systolic and diastolic blood pressure) will be classified as having metabolic syndrome. A total of 80% of the enrolled government employees with metabolic syndrome completed the programme. Data were analyzed using SPSS for Windows (version 20, SPSS, Chicago, IL). There were significantly higher step counts on average in the aerobics group compared to the control group over assessments. Assessments at baseline, post-intervention and follow-up showed a significant difference in step counts between the intervention and control groups. The greatest reductions in the proportions of individuals with metabolic syndrome were observed in the aerobics group with a reduction of 79.4% in the post-intervention assessment compared to the assessment at baseline. The findings of this study suggest that physical activity intervention via aerobics classes is an effective strategy for improving step counts and reducing the prevalence of metabolic syndrome.

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

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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.

Linking metabolic QTLs with network and cis-eQTLs controlling biosynthetic pathways.

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Adam M Wentzell

2007-09-01

Full Text Available Phenotypic variation between individuals of a species is often under quantitative genetic control. Genomic analysis of gene expression polymorphisms between individuals is rapidly gaining popularity as a way to query the underlying mechanistic causes of variation between individuals. However, there is little direct evidence of a linkage between global gene expression polymorphisms and phenotypic consequences. In this report, we have mapped quantitative trait loci (QTLs-controlling glucosinolate content in a population of 403 Arabidopsis Bay x Sha recombinant inbred lines, 211 of which were previously used to identify expression QTLs controlling the transcript levels of biosynthetic genes. In a comparative study, we have directly tested two plant biosynthetic pathways for association between polymorphisms controlling biosynthetic gene transcripts and the resulting metabolites within the Arabidopsis Bay x Sha recombinant inbred line population. In this analysis, all loci controlling expression variation also affected the accumulation of the resulting metabolites. In addition, epistasis was detected more frequently for metabolic traits compared to transcript traits, even when both traits showed similar distributions. An analysis of candidate genes for QTL-controlling networks of transcripts and metabolites suggested that the controlling factors are a mix of enzymes and regulatory factors. This analysis showed that regulatory connections can feedback from metabolism to transcripts. Surprisingly, the most likely major regulator of both transcript level for nearly the entire pathway and aliphatic glucosinolate accumulation is variation in the last enzyme in the biosynthetic pathway, AOP2. This suggests that natural variation in transcripts may significantly impact phenotypic variation, but that natural variation in metabolites or their enzymatic loci can feed back to affect the transcripts.

Fasting the Microbiota to Improve Metabolism?

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Haas, Joel T; Staels, Bart

2017-10-03

While intermittent or periodic fasting provides a variety of favorable health benefits, the molecular mediators of these effects are poorly understood. In this issue of Cell Metabolism, Li and colleagues (2017) highlight the role of gut microbiota in mediating benefits of intermittent fasting through activation of adipose tissue beiging. Copyright © 2017. Published by Elsevier Inc.

Assessment of metabolic control in patients with diabetes treated with insulin using Contour USB and A1cNow+ devices (COMET study).

Science.gov (United States)

Vinagre, Irene; Álvarez, Pilar; García, Nicolás; Roura, Guillem; Conget, Ignacio

2015-10-01

The self-determination of blood glucose is relevant for diabetes mellitus (DM) insulin-treated patients. The use of glucometers with advanced features and measuring glycated haemoglobin (HbA1c) may help improve metabolic control. The main objective of this study was to determine the percentage of insulin treated patients who reduced HbA1c by at least 0.4% after 6 months of using Contour and A1CNow+. Observational, prospective, multicentre study in adult DM insulin treated patients, with HbA1c> 8%. Of the 454 recruited patients analysed, a total of 333 were evaluable. After 6 months the HbA1c decreased (P 8% was observed, with this reaching: 41% for all, 45% in type 1 DM, and 25% in type 2 DM. In the glycaemic profile, a reduction (P<.05) was observed in pre- and post-prandial glycaemia in both groups (-20.7±36.4 and -37.1±47.1mg/dL, respectively), with 23% pre-prandial glucose < 130mg/dL and post-prandial < 180mg/dL CONCLUSION: The use of glucometers with advanced features, and measuring glycated haemoglobin (HbA1c) may help improve metabolic control and to monitor insulin treated DM patients more closely. Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

Thyroid peroxidase antibodies in pregnant women with type 1 diabetes: impact on thyroid function, metabolic control and pregnancy outcome

DEFF Research Database (Denmark)

Vestgaard, Marianne; Nielsen, Lene Ringholm; Rasmussen, Åse Krogh

2008-01-01

In pregnant women with type 1 diabetes, we evaluated whether the presence of thyroid peroxidase autoantibodies (anti-TPO) was associated with changes in thyroid function, metabolic control and pregnancy outcome.......In pregnant women with type 1 diabetes, we evaluated whether the presence of thyroid peroxidase autoantibodies (anti-TPO) was associated with changes in thyroid function, metabolic control and pregnancy outcome....

The Impact of a Cultural Lifestyle Intervention on Metabolic Parameters After Gestational Diabetes Mellitus A Randomized Controlled Trial.

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Zilberman-Kravits, Dana; Meyerstein, Naomi; Abu-Rabia, Yones; Wiznitzer, Arnon; Harman-Boehm, Ilana

2018-06-01

The prevalence of type 2 diabetes in Israel is increasing in all ethnic groups but most markedly in the Bedouin population. We aimed to assess the effects of a lifestyle change intervention on risk markers for type 2 diabetes after gestational diabetes mellitus (GDM). One hundred eighty Jewish and Bedouin post-GDM women were randomly assigned to a lifestyle intervention group (IG) or a control group (CG) starting 3-4 months after delivery. The IG participated in healthy lifestyle sessions led by a dietician and a sports instructor for 24 months after delivery. The IG participants had three individual 45-min counseling sessions and four 90-min group meetings (10 women each). The dietary and exercise recommendations were culturally adapted. The primary outcome of the study was HOMA-IR. We monitored clinical and chemical biomarkers 1 and 2 years after delivery. After 1 and 2 years of intervention, the metabolic measures improved substantially. The intervention reduced the insulin, glucose and HOMA-IR levels in the IG compared with those in the CG (p < 0.001). This novel culturally tailored lifestyle intervention program significantly improved the metabolic and morphometric indices measured 1 and 2 years after delivery. These results highlight and underscore the importance of effective lifestyle change education following GDM.

Identification of microRNAs controlling hepatic mRNA levels for metabolic genes during the metabolic transition from embryonic to posthatch development in the chicken.

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Hicks, Julie A; Porter, Tom E; Liu, Hsiao-Ching

2017-09-05

The transition from embryonic to posthatch development in the chicken represents a massive metabolic switch from primarily lipolytic to primarily lipogenic metabolism. This metabolic switch is essential for the chick to successfully transition from the metabolism of stored egg yolk to the utilization of carbohydrate-based feed. However, regulation of this metabolic switch is not well understood. We hypothesized that microRNAs (miRNAs) play an important role in the metabolic switch that is essential to efficient growth of chickens. We used high-throughput RNA sequencing to characterize expression profiles of mRNA and miRNA in liver during late embryonic and early posthatch development of the chicken. This extensive data set was used to define the contributions of microRNAs to the metabolic switch during development that is critical to growth and nutrient utilization in chickens. We found that expression of over 800 mRNAs and 30 miRNAs was altered in the embryonic liver between embryonic day 18 and posthatch day 3, and many of these differentially expressed mRNAs and miRNAs are associated with metabolic processes. We confirmed the regulation of some of these mRNAs by miRNAs expressed in a reciprocal pattern using luciferase reporter assays. Finally, through the use of yeast one-hybrid screens, we identified several proteins that likely regulate expression of one of these important miRNAs. Integration of the upstream regulatory mechanisms governing miRNA expression along with monitoring the downstream effects of this expression will ultimately allow for the construction of complete miRNA regulatory networks associated with the hepatic metabolic switch in chickens. Our findings support a key role for miRNAs in controlling the metabolic switch that occurs between embryonic and posthatch development in the chicken.

Clinical and Metabolic Response to Selenium Supplementation in Pregnant Women at Risk for Intrauterine Growth Restriction: Randomized, Double-Blind, Placebo-Controlled Trial.

Science.gov (United States)

Mesdaghinia, Elaheh; Rahavi, Azam; Bahmani, Fereshteh; Sharifi, Nasrin; Asemi, Zatollah

2017-07-01

Data on the effects of selenium supplementation on clinical signs and metabolic profiles in women at risk for intrauterine growth restriction (IUGR) are scarce. This study was designed to assess the effects of selenium supplementation on clinical signs and metabolic status in pregnant women at risk for IUGR. This randomized double-blind placebo-controlled clinical trial was performed among 60 women at risk for IUGR according to abnormal uterine artery Doppler waveform. Participants were randomly assigned to intake either 100 μg selenium supplements as tablet (n = 30) or placebo (n = 30) for 10 weeks between 17 and 27 weeks of gestation. After 10 weeks of selenium administration, a higher percentage of women in the selenium group had pulsatility index (PI) of women at risk for IUGR resulted in improved PI, TAC, GSH, hs-CRP, and markers of insulin metabolism and HDL-C levels, but it did not affect MDA, NO, FPG, and other lipid profiles.Clinical trial registration number http://www.irct.ir : IRCT201601045623N64.

Construction of a Genome-Scale Metabolic Model of Arthrospira platensis NIES-39 and Metabolic Design for Cyanobacterial Bioproduction.

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Katsunori Yoshikawa

Full Text Available Arthrospira (Spirulina platensis is a promising feedstock and host strain for bioproduction because of its high accumulation of glycogen and superior characteristics for industrial production. Metabolic simulation using a genome-scale metabolic model and flux balance analysis is a powerful method that can be used to design metabolic engineering strategies for the improvement of target molecule production. In this study, we constructed a genome-scale metabolic model of A. platensis NIES-39 including 746 metabolic reactions and 673 metabolites, and developed novel strategies to improve the production of valuable metabolites, such as glycogen and ethanol. The simulation results obtained using the metabolic model showed high consistency with experimental results for growth rates under several trophic conditions and growth capabilities on various organic substrates. The metabolic model was further applied to design a metabolic network to improve the autotrophic production of glycogen and ethanol. Decreased flux of reactions related to the TCA cycle and phosphoenolpyruvate reaction were found to improve glycogen production. Furthermore, in silico knockout simulation indicated that deletion of genes related to the respiratory chain, such as NAD(PH dehydrogenase and cytochrome-c oxidase, could enhance ethanol production by using ammonium as a nitrogen source.

Hypoglycemia in pregnant women with type 1 diabetes - Predictors and role of metabolic control

DEFF Research Database (Denmark)

Nielsen, L.R.; Johansen, M.; Pedersen-Bjergaard, U.

2008-01-01

OBJECTIVE- In pregnancy with type 1 diabetes, we evaluated occurrence of mild and severe hypoglycemia and analyzed the influence of strict metabolic control, nausea, Vomiting, and other potential predictors of occurrence of severe hypoglycemia. RESEARCH DESIGN AND METHODS- A prospective...... awareness or unawareness (3.2 [1.2-8.2]) as independent predictors for severe hypoglycemia. CONCLUSIONS - In pregnancy with type 1 diabetes, the incidence of mild and severe hypoglycemia was highest in early pregnancy, although metabolic control was tighter in the last part of pregnancy. Predictors...... observational study of 108 consecutive pregnant women with type 1 diabetes was conducted. At 8, 14, 21, 27, and 33 weeks of gestation, patients performed self-monitored plasma glucose (SMPG) (eight/day) for 3 days and completed a questionnaire on nausea, vomiting, hypoglycemia awareness, and history of mild...

Hepatic Expression of Adenovirus 36 E4ORF1 Improves Glycemic Control and Promotes Glucose Metabolism Through AKT Activation.

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McMurphy, Travis B; Huang, Wei; Xiao, Run; Liu, Xianglan; Dhurandhar, Nikhil V; Cao, Lei

2017-02-01

Considering that impaired proximal insulin signaling is linked with diabetes, approaches that enhance glucose disposal independent of insulin signaling are attractive. In vitro data indicate that the E4ORF1 peptide derived from human adenovirus 36 (Ad36) interacts with cells from adipose tissue, skeletal muscle, and liver to enhance glucose disposal, independent of proximal insulin signaling. Adipocyte-specific expression of Ad36E4ORF1 improves hyperglycemia in mice. To determine the hepatic interaction of Ad36E4ORF1 in enhancing glycemic control, we expressed E4ORF1 of Ad36 or Ad5 or fluorescent tag alone by using recombinant adeno-associated viral vector in the liver of three mouse models. In db/db or diet-induced obesity (DIO) mice, hepatic expression of Ad36E4ORF1 but not Ad5E4ORF1 robustly improved glycemic control. In normoglycemic wild-type mice, hepatic expression of Ad36E4ORF1 lowered nonfasting blood glucose at a high dose of expression. Of note, Ad36E4ORF1 significantly reduced insulin levels in db/db and DIO mice. The improvement in glycemic control was observed without stimulation of the proximal insulin signaling pathway. Collectively, these data indicate that Ad36E4ORF1 is not a typical sensitizer, mimetic, or secretagogue of insulin. Instead, it may have insulin-sparing action, which seems to reduce the need for insulin and, hence, to reduce insulin levels. © 2017 by the American Diabetes Association.

Monitoring and robust adaptive control of fed-batch cultures of microorganisms exhibiting overflow metabolism [abstract

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Vande Wouwer, A.

2010-01-01

Full Text Available Overflow metabolism characterizes cells strains that are likely to produce inhibiting by-products resulting from an excess of substrate feeding and a saturated respiratory capacity. The critical substrate level separating the two different metabolic pathways is generally not well defined. Monitoring of this kind of cultures, going from model identification to state estimation, is first discussed. Then, a review of control techniques which all aim at maximizing the cell productivity of fed-batch fermentations is presented. Two main adaptive control strategies, one using an estimation of the critical substrate level as set-point and another regulating the by-product concentration, are proposed. Finally, experimental investigations of an adaptive RST control scheme using the observer polynomial for the regulation of the ethanol concentration in Saccharomyces cerevisiae fed-batch cultures ranging from laboratory to industrial scales, are also presented.

Metabolic Syndrome Increases the Risk of Sudden Sensorineural Hearing Loss in Taiwan: A Case-Control Study.

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Chien, Chen-Yu; Tai, Shu-Yu; Wang, Ling-Feng; Hsi, Edward; Chang, Ning-Chia; Wu, Ming-Tsang; Ho, Kuen-Yao

2015-07-01

Sudden sensorineural hearing loss has been reported to be associated with diabetes mellitus, hypertension, and hyperlipidemia in previous studies. The aim of this study was to examine whether metabolic syndrome increases the risk of sudden sensorineural hearing loss in Taiwan. A case-control study. Tertiary university hospital. We retrospectively investigated 181 cases of sudden sensorineural hearing loss and 181 controls from the Department of Otorhinolaryngology, Kaohsiung Medical University Hospital, in southern Taiwan from 2010 to 2012, comparing their clinical variables. We analyzed the relationship between metabolic syndrome and sudden sensorineural hearing loss. Metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III with Asian modifications. The demographic and clinical characteristics, audiometry results, and outcome were reviewed. Subjects with metabolic syndrome had a 3.54-fold increased risk (95% confidence interval [CI] = 2.00-6.43, P diabetes mellitus, hypertension, and hyperlipidemia. With increases in the number of metabolic syndrome components, the risk of sudden sensorineural hearing loss increased (P for trend Vertigo was associated with a poor outcome (P = .02; 95% CI = 1.13~5.13, adjusted odds ratio = 2.39). The hearing loss pattern may influence the outcome of sudden sensorineural hearing loss (P Vertigo and total hearing loss were indicators of a poor outcome in sudden sensorineural hearing loss. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

Antenatal exercise in overweight and obese women and its effects on offspring and maternal health: design and rationale of the IMPROVE (Improving Maternal and Progeny Obesity Via Exercise) randomised controlled trial.

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Seneviratne, Sumudu N; Parry, Graham K; McCowan, Lesley Me; Ekeroma, Alec; Jiang, Yannan; Gusso, Silmara; Peres, Geovana; Rodrigues, Raquel O; Craigie, Susan; Cutfield, Wayne S; Hofman, Paul L

2014-04-26

Obesity during pregnancy is associated with adverse outcomes for the offspring and mother. Lifestyle interventions in pregnancy such as antenatal exercise, are proposed to improve both short- and long-term health of mother and child. We hypothesise that regular moderate-intensity exercise during the second half of pregnancy will result in improved maternal and offspring outcomes, including a reduction in birth weight and adiposity in the offspring, which may be protective against obesity in later life. The IMPROVE (Improving Maternal and Progeny Risks of Obesity Via Exercise) study is a two-arm parallel randomised controlled clinical trial being conducted in Auckland, New Zealand. Overweight and obese women (BMI ≥25 kg/m2) aged 18-40 years, with a singleton pregnancy of exercise.Participants are randomised with 1:1 allocation ratio to either intervention or control group, using computer-generated randomisation sequences in variable block sizes, stratified on ethnicity and parity, after completion of baseline assessments. The intervention consists of a 16-week structured home-based moderate-intensity exercise programme utilising stationary cycles and heart rate monitors, commencing at 20 weeks of gestation. The control group do not receive any exercise intervention. Both groups undergo regular fetal ultrasonography and receive standard antenatal care. Due to the nature of the intervention, participants are un-blinded to group assignment during the trial.The primary outcome is offspring birth weight. Secondary offspring outcomes include fetal and neonatal body composition and anthropometry, neonatal complications and cord blood metabolic markers. Maternal outcomes include weight gain, pregnancy and delivery complications, aerobic fitness, quality of life, metabolic markers and post-partum body composition. The results of this trial will provide valuable insights on the effects of antenatal exercise on health outcomes in overweight and obese mothers and their

Exercise improves glycaemic control in women diagnosed with gestational diabetes mellitus: a systematic review.

Science.gov (United States)

Harrison, Anne L; Shields, Nora; Taylor, Nicholas F; Frawley, Helena C

2016-10-01

Does exercise improve postprandial glycaemic control in women diagnosed with gestational diabetes mellitus? A systematic review of randomised trials. Pregnant women diagnosed with gestational diabetes mellitus. Exercise, performed more than once a week, sufficient to achieve an aerobic effect or changes in muscle metabolism. Postprandial blood glucose, fasting blood glucose, glycated haemoglobin, requirement for insulin, adverse events and adherence. This systematic review identified eight randomised, controlled trials involving 588 participants; seven trials (544 participants) had data that were suitable for meta-analysis. Five trials scored ≥ 6 on the PEDro scale, indicating a relatively low risk of bias. Meta-analysis showed that exercise, as an adjunct to standard care, significantly improved postprandial glycaemic control (MD -0.33mmol/L, 95% CI -0.49 to -0.17) and lowered fasting blood glucose (MD -0.31 mmol/L, 95% CI -0.56 to -0.05) when compared with standard care alone, with no increase in adverse events. Effects of similar magnitude were found for aerobic and resistance exercise programs, if performed at a moderate intensity or greater, for 20 to 30minutes, three to four times per week. Meta-analysis did not show that exercise significantly reduced the requirement for insulin. All studies reported that complications or other adverse events were either similar or reduced with exercise. Aerobic or resistance exercise, performed at a moderate intensity at least three times per week, safely helps to control postprandial blood glucose levels and other measures of glycaemic control in women diagnosed with gestational diabetes mellitus. PROSPERO CRD42015019106. [Harrison AL, Shields N, Taylor NF, Frawley HC (2016) Exercise improves glycaemic control in women diagnosed with gestational diabetes mellitus: a systematic review.Journal of Physiotherapy62: 188-196]. Copyright © 2016 Australian Physiotherapy Association. Published by Elsevier B.V. All rights

Insulin Sensitivity and Glucose Homeostasis Can Be Influenced by Metabolic Acid Load

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Lucio Della Guardia

2018-05-01

Full Text Available Recent epidemiological findings suggest that high levels of dietary acid load can affect insulin sensitivity and glucose metabolism. Consumption of high protein diets results in the over-production of metabolic acids which has been associated with the development of chronic metabolic disturbances. Mild metabolic acidosis has been shown to impair peripheral insulin action and several epidemiological findings suggest that metabolic acid load markers are associated with insulin resistance and impaired glycemic control through an interference intracellular insulin signaling pathways and translocation. In addition, higher incidence of diabetes, insulin resistance, or impaired glucose control have been found in subjects with elevated metabolic acid load markers. Hence, lowering dietary acid load may be relevant for improving glucose homeostasis and prevention of type 2 diabetes development on a long-term basis. However, limitations related to patient acid load estimation, nutritional determinants, and metabolic status considerably flaws available findings, and the lack of solid data on the background physiopathology contributes to the questionability of results. Furthermore, evidence from interventional studies is very limited and the trials carried out report no beneficial results following alkali supplementation. Available literature suggests that poor acid load control may contribute to impaired insulin sensitivity and glucose homeostasis, but it is not sufficiently supportive to fully elucidate the issue and additional well-designed studies are clearly needed.

Physical Activity Enhances Metabolic Fitness Independently of Cardiorespiratory Fitness in Marathon Runners

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M. J. Laye

2015-01-01

Full Text Available High levels of cardiovascular fitness (CRF and physical activity (PA are associated with decreased mortality and risk to develop metabolic diseases. The independent contributions of CRF and PA to metabolic disease risk factors are unknown. We tested the hypothesis that runners who run consistently >50 km/wk and/or >2 marathons/yr for the last 5 years have superior metabolic fitness compared to matched sedentary subjects (CRF, age, gender, and BMI. Case-control recruitment of 31 pairs of runner-sedentary subjects identified 10 matched pairs with similar VO2max (mL/min/kg (similar-VO2max. The similar-VO2max group was compared with a group of age, gender, and BMI matched pairs who had the largest difference in VO2max (different-VO2max. Primary outcomes that defined metabolic fitness including insulin response to an oral glucose tolerance test, fasting lipids, and fasting insulin were superior in runners versus sedentary controls despite similar VO2max. Furthermore, performance (velocity at VO2max, running economy, improved exercise metabolism (lactate threshold, and skeletal muscle levels of mitochondrial proteins were superior in runners versus sedentary controls with similar VO2max. In conclusion subjects with a high amount of PA have more positive metabolic health parameters independent of CRF. PA is thus a good marker against metabolic diseases.

miR-182 Regulates Metabolic Homeostasis by Modulating Glucose Utilization in Muscle

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Duo Zhang

2016-07-01

Full Text Available Understanding the fiber-type specification and metabolic switch in skeletal muscle provides insights into energy metabolism in physiology and diseases. Here, we show that miR-182 is highly expressed in fast-twitch muscle and negatively correlates with blood glucose level. miR-182 knockout mice display muscle loss, fast-to-slow fiber-type switching, and impaired glucose metabolism. Mechanistic studies reveal that miR-182 modulates glucose utilization in muscle by targeting FoxO1 and PDK4, which control fuel selection via the pyruvate dehydrogenase complex (PDHC. Short-term high-fat diet (HFD feeding reduces muscle miR-182 levels by tumor necrosis factor α (TNFα, which contributes to the upregulation of FoxO1/PDK4. Restoration of miR-182 expression in HFD-fed mice induces a faster muscle phenotype, decreases muscle FoxO1/PDK4 levels, and improves glucose metabolism. Together, our work establishes miR-182 as a critical regulator that confers robust and precise controls on fuel usage and glucose homeostasis. Our study suggests that a metabolic shift toward a faster and more glycolytic phenotype is beneficial for glucose control.

Role of Parenting Style in Achieving Metabolic Control in Adolescents With Type 1 Diabetes

OpenAIRE

Shorer, Maayan; David, Ravit; Schoenberg-Taz, Michal; Levavi-Lavi, Ifat; Phillip, Moshe; Meyerovitch, Joseph

2011-01-01

OBJECTIVE To examine the role of parenting style in achieving metabolic control and treatment adherence in adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS Parents of 100 adolescents with type 1 diabetes completed assessments of their parenting style and sense of helplessness. Parents and patients rated patient adherence to the treatment regimen. Glycemic control was evaluated by HbA1c values. RESULTS An authoritative paternal parenting style predicted better glycemic control and...

Muscle insulin sensitivity and glucose metabolism are controlled by the intrinsic muscle clock

DEFF Research Database (Denmark)

Dyar, Kenneth A.; Ciciliot, Stefano; Wright, Lauren E.

2014-01-01

Circadian rhythms control metabolism and energy homeostasis, but the role of the skeletal muscle clock has never been explored. We generated conditional and inducible mouse lines with muscle-specific ablation of the core clock gene Bmal1. Skeletal muscles from these mice showed impaired insulin-s...

The effect of a novel probiotic on metabolic biomarkers in adults with prediabetes and recently diagnosed type 2 diabetes mellitus: study protocol for a randomized controlled trial.

Science.gov (United States)

Palacios, Talia; Vitetta, Luis; Coulson, Samantha; Madigan, Claire D; Denyer, Gareth S; Caterson, Ian D

2017-01-09

Shifts in the gastrointestinal microbiome have been shown to contribute to the progression of metabolic diseases including prediabetes and type 2 diabetes mellitus. Research suggests that in-vivo modulation of the gut microbiome by specific probiotic microorganisms may improve insulin sensitivity and blood sugar management, preventing or delaying the development of type 2 diabetes mellitus. However, further research is needed to understand the effect of probiotics as a therapy for the treatment of metabolic diseases. An evidence-based multi-species probiotic was developed to encourage a shift in the gastrointestinal bacterial cohort from a disease-prone to a balanced state with the aim of improving metabolic markers associated with type 2 diabetes mellitus. Sixty adults with a body mass index ≥25 kg/m 2 with prediabetes or type 2 diabetes mellitus (diagnosed within the previous 12 months) will be enrolled in a double-blind, placebo-controlled pilot study. Participants will be randomized to a multi-species probiotic or placebo for 12 weeks. Both groups will receive lifestyle and nutritional advice. The primary outcome measure is the change between groups in fasting plasma glucose levels from baseline to 12 weeks. Secondary outcome measures include, but are not limited to, the change in lipid profile, systemic inflammation, gut permeability, and faecal microbial and metabolomic profiles. Blood and stool samples are collected at baseline and 12 weeks after treatment. Intentional manipulation of gastrointestinal microbial profiles may be useful for preventing and controlling type 2 diabetes mellitus and its associated metabolic complications. Australian New Zealand Clinical Trials Registry, ACTRN12613001378718 . Registered on 16 December 2013.

FDG PET in non-pharmacological therapy in Alzheimer's disease; cerebral metabolic increase correlates with clinical improvement after cognitive therapy

International Nuclear Information System (INIS)

Na, Hae Ri; Kim, Yu Kyeong; Park, Seong Min; Lee, Seung Hyun; Park, Eun Kyung; Lee, Jung Seok; Kim, Sang Yun; Kim, Sang Eun

2007-01-01

In management of AD, pharmacological treatment alone using acetylcholinesterase inhibitor (AChEI) is general consensus, and provides beneficial effect to prolong their progression. Combined non-pharmacological therapy, especially cognitive therapy is recently having attention with expectation of improvement in cognitive ability. This study examined the effect of combined cognitive therapy in AD patients who were maintaining AChEI using FDG PET. Four patients (689 yrs) who diagnosed as probable Alzheimer's disease based on the NINCDS-ADRDA criteria participated in this study. 12-week cognitive therapy comprised seven fields to enhance orientation, memory, recall, visuo-motor organization, categorization and behavior modification/sequencing. They received 45-minute sessions twice per week with maintaining their previous medication. Clinical improvement was assessed by comprehensive neuropsychological tests. Two FDG PET studies were performed before cognitive therapy and in the middle of the therapy, and compared to evaluate the effect of cognitive therapy to cerebral metabolism. Two of 4 patients whose initial cognitive impairment was milder had clinical improvement after 12 weeks, the rest who were more severely impaired failed to have clinical improvement. Regional cerebral hypometabolism on initial PET was correlated with their functional status. Follow up PET of two responders demonstrated the increases in regional metabolism in the temporal and/or frontal cortex, which was associated their functional improvement. Cerebral metabolism in poor responders were minimally increased or no changed. This preliminary data suggests that cognitive therapy is potentially useful to stabilize or improve cognitive and functional performance in AD patients with relatively mild cognitive dysfunction. And FDG PET could demonstrate possible candidates for cognitive therapy and the effect of the therapy

Dose effects of dietary phytosterols on cholesterol metabolism: a controlled feeding study.

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Racette, Susan B; Lin, Xiaobo; Lefevre, Michael; Spearie, Catherine Anderson; Most, Marlene M; Ma, Lina; Ostlund, Richard E

2010-01-01

Phytosterol supplementation of 2 g/d is recommended by the National Cholesterol Education Program to reduce LDL cholesterol. However, the effects of different intakes of phytosterol on cholesterol metabolism are uncertain. We evaluated the effects of 3 phytosterol intakes on whole-body cholesterol metabolism. In this placebo-controlled, crossover feeding trial, 18 adults received a phytosterol-deficient diet (50 mg phytosterols/2000 kcal) plus beverages supplemented with 0, 400, or 2000 mg phytosterols/d for 4 wk each, in random order. All meals were prepared in a metabolic kitchen; breakfast and dinner on weekdays were eaten on site. Primary outcomes were fecal cholesterol excretion and intestinal cholesterol absorption measured with stable-isotope tracers and serum lipoprotein concentrations. Phytosterol intakes (diet plus supplements) averaged 59, 459, and 2059 mg/d during the 3 diet periods. Relative to the 59-mg diet, the 459- and 2059-mg phytosterol intakes significantly (P phytosterol dose (-8.9 +/- 2.3%); a trend was observed with the 459-mg/d dose (-5.0 +/- 2.1%; P = 0.077). Dietary phytosterols in moderate and high doses favorably alter whole-body cholesterol metabolism in a dose-dependent manner. A moderate phytosterol intake (459 mg/d) can be obtained in a healthy diet without supplementation. This trial was registered at clinicaltrials.gov as NCT00860054.

Shikimic acid production in Escherichia coli: From classical metabolic engineering strategies to omics applied to improve its production

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Juan Andrés Martínez

2015-09-01

Full Text Available Shikimic acid (SA is an intermediate of the SA pathway that is present in bacteria and plants. SA has gained great interest because it is a precursor in the synthesis of the drug oseltamivir phosphate (OSF, an efficient inhibitor of the neuraminidase enzyme of diverse seasonal influenza viruses, the avian influenza virus H5N1, and the human influenza virus H1N1. For the purposes of OSF production, SA is extracted from the pods of Chinese star anise plants (Illicium spp., yielding up to 17% of SA (dry basis content. The high demand for OSF necessary to manage a major influenza outbreak is not adequately met by industrial production using SA from plants sources. As the SA pathway is present in the model bacteria Escherichia coli, several intuitive metabolically engineered strains have been applied for its successful overproduction by biotechnological processes, resulting in strains producing up to 71 g/L of SA, with high conversion yields of up to 0.42 (mol SA/mol Glc, in both batch and fed-batch cultures using complex fermentation broths, including glucose as a carbon source and yeast extract. Global transcriptomic analyses have been performed in SA producing strains, resulting in the identification of possible key target genes for the design of a rational strain improvement strategy. Because possible target genes are involved in the transport, catabolism and interconversion of different carbon sources and metabolic intermediates outside the central carbon metabolism and SA pathways, as genes involved in diverse cellular stress responses, the development of rational cellular strain improvement strategies based on omics data constitutes a challenging task to improve SA production in currently overproducing engineered strains. In this review, we discuss the main metabolic engineering strategies that have been applied for the development of efficient SA producing strains, as the perspective of omics analysis has focused on further strain improvement

Lipoprotein metabolism indicators improve cardiovascular risk prediction

NARCIS (Netherlands)

Schalkwijk, D.B. van; Graaf, A.A. de; Tsivtsivadze, E.; Parnell, L.D.; Werff-van der Vat, B.J.C. van der; Ommen, B. van; Greef, J. van der; Ordovás, J.M.

2014-01-01

Background: Cardiovascular disease risk increases when lipoprotein metabolism is dysfunctional. We have developed a computational model able to derive indicators of lipoprotein production, lipolysis, and uptake processes from a single lipoprotein profile measurement. This is the first study to

How does 'metabolic surgery' work its magic? New evidence for gut microbiota.

Science.gov (United States)

Peck, Bailey C E; Seeley, Randy J

2018-04-01

Metabolic surgery is recommended for the treatment of type 2 diabetes for its potent ability to improve glycemic control. However, the mechanisms underlying the beneficial effects of metabolic surgery are still under investigation. We provide an updated review of recent studies into the molecular underpinnings of metabolic surgery, focusing in on what is known about the role of gut microbiota. Over the last 7 years several reports have been published on the topic, however the field is expanding rapidly. Studies have now linked the regulation of glucose and lipid metabolism, neuronal and intestinal adaptations, and hormonal and nutrient signaling pathways to gut microbiota. Given that the composition of gut microbiota is altered by metabolic surgery, investigating the potential mechanism and outcomes of this change are now a priority to the field. As evidence for a role for microbiota builds, we expect future patients may receive microbe-based therapeutics to improve surgical outcomes and perhaps one day preclude the need for surgical therapies all together. In this review and perspective, we evaluate the current state of the field and its future.

Improving control of the coal industry

Energy Technology Data Exchange (ETDEWEB)

Valkovyy, V I; Ignatyev, B N

1982-01-01

Questions of organizing control of the coal industry based on the use of ACS are examined. Improvement of control of the sector is done in the following main trends: pinpointing the distribution of rights; duties and responsibilities within the associations; more complete calculation of the positions; standard structures of the mines, open pits and other production units of the specific operating conditions; improvement in the forms and methods of controlling specialized production units; formation of style and methods of leadership corresponding to the modern conditions of production.

Engineering Cellular Metabolism

DEFF Research Database (Denmark)

Nielsen, Jens; Keasling, Jay

2016-01-01

Metabolic engineering is the science of rewiring the metabolism of cells to enhance production of native metabolites or to endow cells with the ability to produce new products. The potential applications of such efforts are wide ranging, including the generation of fuels, chemicals, foods, feeds...... of metabolic engineering and will discuss how new technologies can enable metabolic engineering to be scaled up to the industrial level, either by cutting off the lines of control for endogenous metabolism or by infiltrating the system with disruptive, heterologous pathways that overcome cellular regulation....

Clinical study on the prevalence and comparative analysis of metabolic syndrome and its components among Chinese breast cancer women and control population.

Science.gov (United States)

Wu, Yu-Tuan; Luo, Qing-Qing; Li, Xin; Arshad, Bilal; Xu, Zhou; Ran, Liang; Zhao, Chun-Xia; Wu, He; Shi, Yan-Ling; Chen, Hao-Ran; Li, Hao; Li, Hong-Yuan; Wu, Kai-Nan; Kong, Ling-Quan

2018-01-01

Metabolic syndrome has been previously identified as a risk factor for breast cancer and is increasingly a public health concern. This study aims to investigate the prevalence of metabolic syndrome and its components among primary breast cancer and control population. The clinical data of metabolic syndrome and its components in the breast cancer (605 cases) and control population (3212 cases), from Breast Cancer Center and Physical Examination Center of Chongqing, China, from July 2015 to February 2017, were collected for comparative analysis. This study was prospectively registered in Chinese Clinical Trial Registry (http://www.chictr.org.cn/, number: ChiCTR-OOB-15007543). The prevalence of metabolic syndrome in breast cancer (32.6%) was obviously higher than that in control population (18.2%) (pmetabolic syndrome in breast cancer group aged below 60 years (24.9%, pmetabolic syndrome and its components in Chinese breast cancer women, and metabolic syndrome is closely related with breast cancer. Therefore, screening and prevention strategy of metabolic syndrome should be carried out in the management of breast cancer.

Analysis of clock-regulated genes in Neurospora reveals widespread posttranscriptional control of metabolic potential

Science.gov (United States)

Hurley, Jennifer M.; Dasgupta, Arko; Emerson, Jillian M.; Zhou, Xiaoying; Ringelberg, Carol S.; Knabe, Nicole; Lipzen, Anna M.; Lindquist, Erika A.; Daum, Christopher G.; Barry, Kerrie W.; Grigoriev, Igor V.; Smith, Kristina M.; Galagan, James E.; Bell-Pedersen, Deborah; Freitag, Michael; Cheng, Chao; Loros, Jennifer J.; Dunlap, Jay C.

2014-01-01

Neurospora crassa has been for decades a principal model for filamentous fungal genetics and physiology as well as for understanding the mechanism of circadian clocks. Eukaryotic fungal and animal clocks comprise transcription-translation–based feedback loops that control rhythmic transcription of a substantial fraction of these transcriptomes, yielding the changes in protein abundance that mediate circadian regulation of physiology and metabolism: Understanding circadian control of gene expression is key to understanding eukaryotic, including fungal, physiology. Indeed, the isolation of clock-controlled genes (ccgs) was pioneered in Neurospora where circadian output begins with binding of the core circadian transcription factor WCC to a subset of ccg promoters, including those of many transcription factors. High temporal resolution (2-h) sampling over 48 h using RNA sequencing (RNA-Seq) identified circadianly expressed genes in Neurospora, revealing that from ∼10% to as much 40% of the transcriptome can be expressed under circadian control. Functional classifications of these genes revealed strong enrichment in pathways involving metabolism, protein synthesis, and stress responses; in broad terms, daytime metabolic potential favors catabolism, energy production, and precursor assembly, whereas night activities favor biosynthesis of cellular components and growth. Discriminative regular expression motif elicitation (DREME) identified key promoter motifs highly correlated with the temporal regulation of ccgs. Correlations between ccg abundance from RNA-Seq, the degree of ccg-promoter activation as reported by ccg-promoter–luciferase fusions, and binding of WCC as measured by ChIP-Seq, are not strong. Therefore, although circadian activation is critical to ccg rhythmicity, posttranscriptional regulation plays a major role in determining rhythmicity at the mRNA level. PMID:25362047

Improving Accuracy of Processing Through Active Control

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N. N. Barbashov

2016-01-01

Full Text Available An important task of modern mathematical statistics with its methods based on the theory of probability is a scientific estimate of measurement results. There are certain costs under control, and under ineffective control when a customer has got defective products these costs are significantly higher because of parts recall.When machining the parts, under the influence of errors a range scatter of part dimensions is offset towards the tolerance limit. To improve a processing accuracy and avoid defective products involves reducing components of error in machining, i.e. to improve the accuracy of machine and tool, tool life, rigidity of the system, accuracy of the adjustment. In a given time it is also necessary to adapt machine.To improve an accuracy and a machining rate there, currently  become extensively popular various the in-process gaging devices and controlled machining that uses adaptive control systems for the process monitoring. Improving the accuracy in this case is compensation of a majority of technological errors. The in-cycle measuring sensors (sensors of active control allow processing accuracy improvement by one or two quality and provide a capability for simultaneous operation of several machines.Efficient use of in-cycle measuring sensors requires development of methods to control the accuracy through providing the appropriate adjustments. Methods based on the moving average, appear to be the most promising for accuracy control since they include data on the change in some last measured values of the parameter under control.

The effects of nocturnal compared with conventional hemodialysis on mineral metabolism: A randomized-controlled trial.

Science.gov (United States)

Walsh, Michael; Manns, Braden J; Klarenbach, Scott; Tonelli, Marcello; Hemmelgarn, Brenda; Culleton, Bruce

2010-04-01

Hyperphosphatemia is common among patients receiving dialysis and is associated with increased mortality. Nocturnal hemodialysis (NHD) is a long, slow dialytic modality that may improve hyperphosphatemia and disorders of mineral metabolism. We performed a randomized-controlled trial of NHD compared with conventional hemodialysis (CvHD); in this paper, we report detailed results of mineral metabolism outcomes. Prevalent patients were randomized to receive NHD 5 to 6 nights per week for 6to 10 hours per night or to continue CvHD thrice weekly for 6 months. Oral phosphate binders and vitamin D analogs were adjusted to maintain phosphate, calcium and parathyroid hormone (PTH) levels within recommended targets. Compared with CvHD patients, patients in the NHD group had a significant decrease in serum phosphate over the course of the study (0.49 mmol/L, 95% confidence interval 0.24-0.74; P=0.002) despite a significant reduction in the use of phosphate binders. Sixty-one percent of patients in the NHD group compared with 20% in the CvHD group had a decline in intact PTH (P=0.003). Nocturnal hemodialysis lowers serum phosphate, calcium-phosphate product and requirement for phosphate binders. The effects of NHD on PTH are variable. The impact of these changes on long-term cardiovascular and bone-related outcomes requires further investigation.

Playing Action Video Games Improves Visuomotor Control.

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Li, Li; Chen, Rongrong; Chen, Jing

2016-08-01

Can playing action video games improve visuomotor control? If so, can these games be used in training people to perform daily visuomotor-control tasks, such as driving? We found that action gamers have better lane-keeping and visuomotor-control skills than do non-action gamers. We then trained non-action gamers with action or nonaction video games. After they played a driving or first-person-shooter video game for 5 or 10 hr, their visuomotor control improved significantly. In contrast, non-action gamers showed no such improvement after they played a nonaction video game. Our model-driven analysis revealed that although different action video games have different effects on the sensorimotor system underlying visuomotor control, action gaming in general improves the responsiveness of the sensorimotor system to input error signals. The findings support a causal link between action gaming (for as little as 5 hr) and enhancement in visuomotor control, and suggest that action video games can be beneficial training tools for driving. © The Author(s) 2016.

Health effect of vegetable-based diet: lettuce consumption improves cholesterol metabolism and antioxidant status in the rat.

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Nicolle, Catherine; Cardinault, Nicolas; Gueux, Elyett; Jaffrelo, Lydia; Rock, Edmond; Mazur, Andrzej; Amouroux, Pierre; Rémésy, Christian

2004-08-01

It is often assumed that fruits and vegetables contribute to protect against degenerative pathologies such as cardiovascular diseases. Besides epidemiological observations, scientific evidences for their mechanism of action are scarce. In the present study, we investigated the mean term and post-prandial effects of lettuce ingestion on lipid metabolism and antioxidant protection in the rat. Feeding rats a 20% lettuce diet for 3 weeks resulted in a decrease cholesterol LDL/HDL ratio and a marked decrease of liver cholesterol levels (-41%). Concurrently, fecal total steroid excretion increased (+44%) and apparent absorption of dietary cholesterol was significantly depressed (-37%) by the lettuce diet. Lettuce diet also displayed an improvement of vitamin E/TG ratio in plasma and limited lipid peroxidation in heart as evidenced by TBARS. In post-prandial experiment, lettuce intake significantly increased both ascorbic acid and alpha-tocopherol plasma levels which contribute to improve plasma antioxidant capacity within 2 h of consumption. Other lipid-soluble antioxidants (lutein and vitamin E) may also improve the plasma antioxidant capacity. Lettuce consumption increases the total cholesterol end-products excretion and improves antioxidant status due to the richness in antioxidants (vitamins C, E and carotenoids). In our model, lettuce clearly shows a beneficial effect on lipid metabolism and on tissue oxidation. Therefore regular consumption of lettuce should contribute to improve protection against cardiovascular diseases. Copyright 2003 Elsevier Ltd.

Fear of Hypoglycemia, Parenting Stress, and Metabolic Control for Children with Type 1 Diabetes and Their Parents.

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Viaene, Ann-Sofie; Van Daele, Tom; Bleys, Dries; Faust, Kelly; Massa, Guy G

2017-03-01

This study sets out to extend current knowledge of parenting stress and fear of hypoglycemia (FoH) in parents of children with type 1 diabetes mellitus (T1DM). We examined if the relationship between parental and children's FoH and metabolic control, as reflected by HbA1c, is mediated by parenting stress. A total of 63 parents and children with T1DM were recruited during their routine physician's appointment. Parents completed questionnaires on parenting stress and FoH. Children eight years and older also completed a questionnaire on FoH. HbA1c values were obtained from all children. Mediation analysis revealed an indirect association between parental FoH and HbA1c values through parenting stress (Sobel's z = 2.42, p = .02), but no indirect association between children's FoH and HbA1c. We concluded that parental FOH has an indirect association with the child's metabolic control that is mediated by parenting stress. More simply, fear of hypoglycemia predicts parent stress, which in turn, predicts metabolic control.

Influence of revascularization on myocardial perfusion, metabolism and function

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Kropp, Joachim; Krois, Markus; Eichhorn, Bernd; Fehske, Wolfgang; Likungu, James; Kirchhoff, P.G.; Luederitz, Berndt; Biersack, Hans-Juergen; Knapp, F.F. Jr.

1993-01-01

Thirty-nine patients with coronary artery disease (CAD) were investigated with sequential SPECT-scintigraphy after administration of 200 MBq of 15-(p-[I-123]iodophenyl)pentadecanoic acid (IPPA) at peak submaximal exercise. Twenty patients underwent coronary angioplasty (PTCA) from which 14 had control coronary arteriography (CA) and left ventricular cineventriculography (LVCV). Nineteen patients underwent bypass graft surgery (ACB) and stress sonography. Semi-quantification of uptake (Up, related to perfusion) and turnover (Tr, linked to metabolism) was obtained by segmental comparison of oblique slices. About 90% of the reperfused myocardial segments in the PTCA-group and 76% in the ACB-group showed an improvement of uptake after therapy (RUp). Out of these, 50% and 66% exhibited increased turnover (RTr) after PTCA or ACB, respectively. The remaining segments had persistingly pathologic RTr indicating a dissociation of improvement of perfusion and metabolism after therapy. Pathologic RTr was highly correlated with regional wall motion abnormalities (RWMA) after therapy in both groups. In the ACB-group improvement in RTr was correlated with improved RWM at rest and stress in 86% and 92%, respectively, whereas no improvement in RTr was correlated with impared function in 100% and 52%, respectively. IPPA-studies show potential to provide information about changes of perfusion and metabolism after reperfusion and IPPA-turnover is a good predictor of the pattern of contractile function. (author)

Exercise improves quality of life in androgen deprivation therapy-treated prostate cancer: systematic review of randomised controlled trials.

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Teleni, Laisa; Chan, Raymond J; Chan, Alexandre; Isenring, Elisabeth A; Vela, Ian; Inder, Warrick J; McCarthy, Alexandra L

2016-02-01

Men receiving androgen deprivation therapy (ADT) for prostate cancer (PCa) are likely to develop metabolic conditions such as diabetes, cardiovascular disease, abdominal obesity and osteoporosis. Other treatment-related side effects adversely influence quality of life (QoL) including vasomotor distress, depression, anxiety, mood swings, poor sleep quality and compromised sexual function. The objective of this study was to systematically review the nature and effects of dietary and exercise interventions on QoL, androgen deprivation symptoms and metabolic risk factors in men with PCa undergoing ADT. An electronic search of CINAHL, CENTRAL, Medline, PsychINFO and reference lists was performed to identify peer-reviewed articles published between January 2004 and December 2014 in English. Eligible study designs included randomised controlled trials (RCTs) with pre- and post-intervention data. Data extraction and assessment of methodological quality with the Cochrane approach was conducted by two independent reviewers. Seven exercise studies were identified. Exercise significantly improved QoL, but showed no effect on metabolic risk factors (weight, waist circumference, lean or fat mass, blood pressure and lipid profile). Two dietary studies were identified, both of which tested soy supplements. Soy supplementation did not improve any outcomes. No dietary counselling studies were identified. No studies evaluated androgen-deficiency symptoms (libido, erectile function, sleep quality, mood swings, depression, anxiety and bone mineral density). Evidence from RCTs indicates that exercise enhances health- and disease-specific QoL in men with PCa undergoing ADT. Further studies are required to evaluate the effect of exercise and dietary interventions on QoL, androgen deprivation symptoms and metabolic risk factors in this cohort. © 2016 Society for Endocrinology.

The effect of diabetes self-management education on body weight, glycemic control, and other metabolic markers in patients with type 2 diabetes mellitus.

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Yuan, Chuang; Lai, Christopher W K; Chan, Lawrence W C; Chow, Meyrick; Law, Helen K W; Ying, Michael

2014-01-01

To comprehensively evaluate the effect of a short-term diabetes self-management education (DSME) on metabolic markers and atherosclerotic parameters in patients with type 2 diabetes. 76 patients with type 2 diabetes were recruited in this study. They were divided into the intervention group (n = 36) and control group (n = 40). The patients in the intervention group received a 3-month intervention, including an 8-week education on self-management of diabetes mellitus and subsequent 4 weeks of practice of the self-management guidelines. The patients in the control group received standard advice on medical nutrition therapy. Metabolic markers, carotid intima-media thickness (CIMT), and carotid arterial stiffness (CAS) of the patients in both groups were assessed before and after the 3-month intervention. There was a significant reduction in hemoglobin A1c (HbA1c, -0.2 ± 0.56% versus 0.08 ± 0.741%; P 0.05). DSME can improve HbA1c and body weight in patients with type 2 diabetes.

The Effect of Diabetes Self-Management Education on Body Weight, Glycemic Control, and Other Metabolic Markers in Patients with Type 2 Diabetes Mellitus

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Chuang Yuan

2014-01-01

Full Text Available Aims. To comprehensively evaluate the effect of a short-term diabetes self-management education (DSME on metabolic markers and atherosclerotic parameters in patients with type 2 diabetes. Methods. 76 patients with type 2 diabetes were recruited in this study. They were divided into the intervention group (n=36 and control group (n=40. The patients in the intervention group received a 3-month intervention, including an 8-week education on self-management of diabetes mellitus and subsequent 4 weeks of practice of the self-management guidelines. The patients in the control group received standard advice on medical nutrition therapy. Metabolic markers, carotid intima-media thickness (CIMT, and carotid arterial stiffness (CAS of the patients in both groups were assessed before and after the 3-month intervention. Results. There was a significant reduction in hemoglobin A1c (HbA1c, -0.2±0.56% versus 0.08±0.741%; P0.05. Conclusions. DSME can improve HbA1c and body weight in patients with type 2 diabetes.

Liver-Specific Deletion of Protein-Tyrosine Phosphatase 1B (PTP1B) Improves Metabolic Syndrome and Attenuates Diet-Induced Endoplasmic Reticulum Stress

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Delibegovic, Mirela; Zimmer, Derek; Kauffman, Caitlin; Rak, Kimberly; Hong, Eun-Gyoung; Cho, You-Ree; Kim, Jason K.; Kahn, Barbara B.; Neel, Benjamin G.; Bence, Kendra K.

2009-01-01

OBJECTIVE—The protein tyrosine phosphatase PTP1B is a negative regulator of insulin signaling; consequently, mice deficient in PTP1B are hypersensitive to insulin. Because PTP1B−/− mice have diminished fat stores, the extent to which PTP1B directly regulates glucose homeostasis is unclear. Previously, we showed that brain-specific PTP1B−/− mice are protected against high-fat diet–induced obesity and glucose intolerance, whereas muscle-specific PTP1B−/− mice have increased insulin sensitivity independent of changes in adiposity. Here we studied the role of liver PTP1B in glucose homeostasis and lipid metabolism. RESEARCH DESIGN AND METHODS—We analyzed body mass/adiposity, insulin sensitivity, glucose tolerance, and lipid metabolism in liver-specific PTP1B−/− and PTP1Bfl/fl control mice, fed a chow or high-fat diet. RESULTS—Compared with normal littermates, liver-specific PTP1B−/− mice exhibit improved glucose homeostasis and lipid profiles, independent of changes in adiposity. Liver-specific PTP1B−/− mice have increased hepatic insulin signaling, decreased expression of gluconeogenic genes PEPCK and G-6-Pase, enhanced insulin-induced suppression of hepatic glucose production, and improved glucose tolerance. Liver-specific PTP1B−/− mice exhibit decreased triglyceride and cholesterol levels and diminished expression of lipogenic genes SREBPs, FAS, and ACC. Liver-specific PTP1B deletion also protects against high-fat diet–induced endoplasmic reticulum stress response in vivo, as evidenced by decreased phosphorylation of p38MAPK, JNK, PERK, and eIF2α and lower expression of the transcription factors C/EBP homologous protein and spliced X box-binding protein 1. CONCLUSIONS—Liver PTP1B plays an important role in glucose and lipid metabolism, independent of alterations in adiposity. Inhibition of PTP1B in peripheral tissues may be useful for the treatment of metabolic syndrome and reduction of cardiovascular risk in addition to

Innovative dairy cow management to improve resistance to metabolic and infectious diseases during the transition period.

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Lacasse, P; Vanacker, N; Ollier, S; Ster, C

2018-02-01

The incidence of metabolic and infectious diseases varies greatly during the lactation cycle. Most new cases of clinical mastitis appear at the beginning of lactation, and the incidence increases with the level of milk production. In addition to mastitis, many other infectious diseases become clinically apparent during the first 2weeks of lactation. During this time, cows are in a negative energy balance and must mobilize body reserves to balance the deficit between food energy intake and energy required for milk production. The relationships between energy deficit and metabolic diseases, such as ketosis and hepatic lipidosis, are well known. Furthermore, cows in energy deficit have a weakened immune system and are therefore more susceptible to infections. There is now good evidence that the increase in circulating non-esterified fatty acids impairs immune cell functions. Therefore, management approaches that reduce the negative energy balance and the increase in non-esterified fatty acids at the beginning of lactation are likely to improve resistance to infection. Improving the nutrient supply through periparturient nutritional management has been the subject of considerable research. However, another way to reduce the imbalance between nutrient supply and demand is to temporarily decrease the latter. In this review, we examine how management strategies such as conjugated linoleic acid feeding, prepartum milking, or limiting postpartum milk production could be used to reduce metabolic perturbations and immunosuppression during the transition period. At this stage, it appears that reducing the amount of milk harvested postpartum by means of partial milking in the first days after calving is the most promising approach to reduce metabolic stress and immunosuppression without compromising the productivity of high-yielding dairy cows. Copyright © 2017. Published by Elsevier Ltd.

Gut microbiota metabolites, amino acid metabolites and improvements in insulin sensitivity and glucose metabolism: the POUNDS Lost trial.

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Heianza, Yoriko; Sun, Dianjianyi; Li, Xiang; DiDonato, Joseph A; Bray, George A; Sacks, Frank M; Qi, Lu

2018-06-02

Alterations in gut microbiota have been linked to host insulin resistance, diabetes and impaired amino acid metabolism. We investigated whether changes in gut microbiota-dependent metabolite of trimethylamine N-oxide (TMAO) and its nutrient precursors (choline and L-carnitine) were associated with improvements in glucose metabolism and diabetes-related amino acids in a weight-loss diet intervention. We included 504 overweight and obese adults who were randomly assigned to one of four energy-reduced diets varying in macronutrient intake. The 6-month changes (Δ) in TMAO, choline and L-carnitine levels after the intervention were calculated. Greater decreases in choline and L-carnitine were significantly (p<0.05) associated with greater improvements in fasting insulin concentrations and homeostasis model assessment of insulin resistance (HOMA-IR) at 6 months. The reduction of choline was significantly related to 2-year improvements in glucose and insulin resistance. We found significant linkages between dietary fat intake and ΔTMAO for changes in fasting glucose, insulin and HOMA-IR (p interaction <0.05); a greater increase in TMAO was related to lesser improvements in the outcomes among participants who consumed a high-fat diet. In addition, ΔL-carnitine and Δcholine were significantly related to changes in amino acids (including branched-chain and aromatic amino acids). Interestingly, the associations of ΔTMAO, Δcholine and ΔL-carnitine with diabetes-related traits were independent of the changes in amino acids. Our findings underscore the importance of changes in TMAO, choline and L-carnitine in improving insulin sensitivity during a weight-loss intervention for obese patients. Dietary fat intake may modify the associations of TMAO with insulin sensitivity and glucose metabolism. NCT00072995. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless

Rodent Models for Metabolic Syndrome Research

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Sunil K. Panchal

2011-01-01

Full Text Available Rodents are widely used to mimic human diseases to improve understanding of the causes and progression of disease symptoms and to test potential therapeutic interventions. Chronic diseases such as obesity, diabetes and hypertension, together known as the metabolic syndrome, are causing increasing morbidity and mortality. To control these diseases, research in rodent models that closely mimic the changes in humans is essential. This review will examine the adequacy of the many rodent models of metabolic syndrome to mimic the causes and progression of the disease in humans. The primary criterion will be whether a rodent model initiates all of the signs, especially obesity, diabetes, hypertension and dysfunction of the heart, blood vessels, liver and kidney, primarily by diet since these are the diet-induced signs in humans with metabolic syndrome. We conclude that the model that comes closest to fulfilling this criterion is the high carbohydrate, high fat-fed male rodent.

Metabolic disorders of the vestibular system.

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Rybak, L P

1995-01-01

This article reviews the impact of metabolic disorders on vestibular function. Diabetes mellitus is a disorder of glucose metabolism that can be associated with vestibular dysfunction. Vertigo can be alleviated by diet management in many cases. Elevated levels of blood lipids have been implicated in cochleovestibular disorders. Treatment with a lipid-lowering drug has resulted in improved auditory and vestibular function in a placebo-controlled trial. Hypothyroidism may affect different parts of the vestibular system depending on the severity and duration of thyroid deficiency. Severe congenital hypothyroidism can cause central vestibular disorders affecting the cerebellum, whereas mild hypothyroidism may result in peripheral vestibulopathy. Endogenous alterations in concentrations of estrogen and progesterone in the premenstrual syndrome or with the use of exogenous hormones such as oral contraceptives may trigger vertigo. Metabolic evaluations for unexplained vertigo should include a lipoprotein profile, with cholesterol and triglyceride levels, glucose tolerance test, and thyroid hormone measurements. Nutritional and drug therapy may be useful to reverse the vestibular dysfunction.

Dynamic optimal control of homeostasis: an integrative system approach for modeling of the central nitrogen metabolism in Saccharomyces cerevisiae.

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van Riel, N A; Giuseppin, M L; Verrips, C T

2000-01-01

The theory of dynamic optimal metabolic control (DOMC), as developed by Giuseppin and Van Riel (Metab. Eng., 2000), is applied to model the central nitrogen metabolism (CNM) in Saccharomyces cerevisiae. The CNM represents a typical system encountered in advanced metabolic engineering. The CNM is the source of the cellular amino acids and proteins, including flavors and potentially valuable biomolecules; therefore, it is also of industrial interest. In the DOMC approach the cell is regarded as an optimally controlled system. Given the metabolic genotype, the cell faces a control problem to maintain an optimal flux distribution in a changing environment. The regulation is based on strategies and balances feedback control of homeostasis and feedforward regulation for adaptation. The DOMC approach is an integrative, holistic approach, not based on mechanistic descriptions and (therefore) not biased by the variation present in biochemical and molecular biological data. It is an effective tool to structure the rapidly increasing amount of data on the function of genes and pathways. The DOMC model is used successfully to predict the responses of pulses of ammonia and glutamine to nitrogen-limited continuous cultures of a wild-type strain and a glutamine synthetase-negative mutant. The simulation results are validated with experimental data.

Metabolic regulation of yeast

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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.

Computational Modelling of the Metabolic States Regulated by the Kinase Akt

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Ettore eMosca

2012-11-01

Full Text Available Signal transduction pathways and gene regulation determine a major reorganization of metabolic activities in order to support cell proliferation. Protein Kinase B (PKB, also known as Akt, participates in the PI3K/Akt/mTOR pathway, a master regulator of aerobic glycolysis and cellular biosynthesis, two activities shown by both normal and cancer proliferating cells. Not surprisingly considering its relevance for cellular metabolism, Akt/PKB is often found hyperactive in cancer cells. In the last decade, many efforts have been made to improve the understanding of the control of glucose metabolism and the identification of a therapeutic window between proliferating cancer cells and proliferating normal cells. In this context, we have modelled the link between the PI3K/Akt/mTOR pathway, glycolysis, lactic acid production and nucleotide biosynthesis. We used a computational model in order to compare two metabolic states generated by the specific variation of the metabolic fluxes regulated by the activity of the PI3K/Akt/mTOR pathway. One of the two states represented the metabolism of a growing cancer cell characterised by aerobic glycolysis and cellular biosynthesis, while the other state represented the same metabolic network with a reduced glycolytic rate and a higher mitochondrial pyruvate metabolism, as reported in literature in relation to the activity of the PI3K/Akt/mTOR. Some steps that link glycolysis and pentose phosphate pathway revealed their importance for controlling the dynamics of cancer glucose metabolism.

Proprietary tomato extract improves metabolic response to high-fat meal in healthy normal weight subjects

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Xavier Deplanque

2016-10-01

Full Text Available Background: Low-density lipoprotein (LDL oxidation is a risk factor for atherosclerosis. Lycopene and tomato-based products have been described as potent inhibitors of LDL oxidation. Objectives: To evaluate the effect of a 2-week supplementation with a carotenoid-rich tomato extract (CRTE standardized for a 1:1 ratio of lycopene and phytosterols, on post-prandial LDL oxidation after a high-fat meal. Design: In a randomized, double-blind, parallel-groups, placebo-controlled study, 146 healthy normal weight individuals were randomly assigned to a daily dose of CRTE standardized for tomato phytonutrients or placebo during 2 weeks. Oxidized LDL (OxLDL, glucose, insulin, and triglyceride (TG responses were measured for 8 h after ingestion of a high-fat meal before and at the end of intervention. Results: Plasma lycopene, phytofluene, and phytoene were increased throughout the study period in the CRTE group compared to placebo. CRTE ingestion significantly improved changes in OxLDL response to high-fat meal compared to placebo after 2 weeks (p<0.0001. Changes observed in glucose, insulin, and TG responses were not statistically significant after 2 weeks of supplementation, although together they may suggest a trend of favorable effect on metabolic outcomes after a high-fat meal. Conclusions: Two-week supplementation with CRTE increased carotenoids levels in plasma and improved oxidized LDL response to a high-fat meal in healthy normal weight individuals.

A soft sensor for bioprocess control based on sequential filtering of metabolic heat signals.

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Paulsson, Dan; Gustavsson, Robert; Mandenius, Carl-Fredrik

2014-09-26

Soft sensors are the combination of robust on-line sensor signals with mathematical models for deriving additional process information. Here, we apply this principle to a microbial recombinant protein production process in a bioreactor by exploiting bio-calorimetric methodology. Temperature sensor signals from the cooling system of the bioreactor were used for estimating the metabolic heat of the microbial culture and from that the specific growth rate and active biomass concentration were derived. By applying sequential digital signal filtering, the soft sensor was made more robust for industrial practice with cultures generating low metabolic heat in environments with high noise level. The estimated specific growth rate signal obtained from the three stage sequential filter allowed controlled feeding of substrate during the fed-batch phase of the production process. The biomass and growth rate estimates from the soft sensor were also compared with an alternative sensor probe and a capacitance on-line sensor, for the same variables. The comparison showed similar or better sensitivity and lower variability for the metabolic heat soft sensor suggesting that using permanent temperature sensors of a bioreactor is a realistic and inexpensive alternative for monitoring and control. However, both alternatives are easy to implement in a soft sensor, alone or in parallel.

A Soft Sensor for Bioprocess Control Based on Sequential Filtering of Metabolic Heat Signals

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Dan Paulsson

2014-09-01

Full Text Available Soft sensors are the combination of robust on-line sensor signals with mathematical models for deriving additional process information. Here, we apply this principle to a microbial recombinant protein production process in a bioreactor by exploiting bio-calorimetric methodology. Temperature sensor signals from the cooling system of the bioreactor were used for estimating the metabolic heat of the microbial culture and from that the specific growth rate and active biomass concentration were derived. By applying sequential digital signal filtering, the soft sensor was made more robust for industrial practice with cultures generating low metabolic heat in environments with high noise level. The estimated specific growth rate signal obtained from the three stage sequential filter allowed controlled feeding of substrate during the fed-batch phase of the production process. The biomass and growth rate estimates from the soft sensor were also compared with an alternative sensor probe and a capacitance on-line sensor, for the same variables. The comparison showed similar or better sensitivity and lower variability for the metabolic heat soft sensor suggesting that using permanent temperature sensors of a bioreactor is a realistic and inexpensive alternative for monitoring and control. However, both alternatives are easy to implement in a soft sensor, alone or in parallel.

Reduction of liver fructokinase expression and improved hepatic inflammation and metabolism in liquid fructose-fed rats after atorvastatin treatment

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Vila, Laia; Rebollo, Alba; Adalsteisson, Gunnar S [Pharmacology Unit, Department of Pharmacology and Therapeutic Chemistry, School of Pharmacy, University of Barcelona, Barcelona (Spain); Alegret, Marta; Merlos, Manuel; Roglans, Nuria [Pharmacology Unit, Department of Pharmacology and Therapeutic Chemistry, School of Pharmacy, University of Barcelona, Barcelona (Spain); IBUB - Institute of Biomedicine, University of Barcelona, Barcelona (Spain); CIBERobn, [Center for Biomedical Investigation Network in Obesity and Nutrition Physiopathology; Spain; Laguna, Juan C., E-mail: jclagunae@ub.edu [Pharmacology Unit, Department of Pharmacology and Therapeutic Chemistry, School of Pharmacy, University of Barcelona, Barcelona (Spain); IBUB -Institute of Biomedicine, University of Barcelona, Barcelona (Spain); CIBERobn, [Center for Biomedical Investigation Network in Obesity and Nutrition Physiopathology; Spain

2011-02-15

Consumption of beverages that contain fructose favors the increasing prevalence of metabolic syndrome alterations in humans, including non-alcoholic fatty liver disease (NAFLD). Although the only effective treatment for NAFLD is caloric restriction and weight loss, existing data show that atorvastatin, a hydroxymethyl-glutaryl-CoA reductase inhibitor, can be used safely in patients with NAFLD and improves hepatic histology. To gain further insight into the molecular mechanisms of atorvastatin's therapeutic effect on NAFLD, we used an experimental model that mimics human consumption of fructose-sweetened beverages. Control, fructose (10% w/v solution) and fructose + atorvastatin (30 mg/kg/day) Sprague-Dawley rats were sacrificed after 14 days. Plasma and liver tissue samples were obtained to determine plasma analytes, liver histology, and the expression of liver proteins that are related to fatty acid synthesis and catabolism, and inflammatory processes. Fructose supplementation induced hypertriglyceridemia and hyperleptinemia, hepatic steatosis and necroinflammation, increased the expression of genes related to fatty acid synthesis and decreased fatty acid {beta}-oxidation activity. Atorvastatin treatment completely abolished histological signs of necroinflammation, reducing the hepatic expression of metallothionein-1 and nuclear factor kappa B binding. Furthermore, atorvastatin reduced plasma (x 0.74) and liver triglyceride (x 0.62) concentrations, decreased the liver expression of carbohydrate response element binding protein transcription factor (x0.45) and its target genes, and increased the hepatic activity of the fatty acid {beta}-oxidation system (x 1.15). These effects may be related to the fact that atorvastatin decreased the expression of fructokinase (x 0.6) in livers of fructose-supplemented rats, reducing the metabolic burden on the liver that is imposed by continuous fructose ingestion. - Graphical Abstract: Display Omitted Research Highlights

Reduction of liver fructokinase expression and improved hepatic inflammation and metabolism in liquid fructose-fed rats after atorvastatin treatment

International Nuclear Information System (INIS)

Vila, Laia; Rebollo, Alba; Adalsteisson, Gunnar S.; Alegret, Marta; Merlos, Manuel; Roglans, Nuria; Laguna, Juan C.

2011-01-01

Consumption of beverages that contain fructose favors the increasing prevalence of metabolic syndrome alterations in humans, including non-alcoholic fatty liver disease (NAFLD). Although the only effective treatment for NAFLD is caloric restriction and weight loss, existing data show that atorvastatin, a hydroxymethyl-glutaryl-CoA reductase inhibitor, can be used safely in patients with NAFLD and improves hepatic histology. To gain further insight into the molecular mechanisms of atorvastatin's therapeutic effect on NAFLD, we used an experimental model that mimics human consumption of fructose-sweetened beverages. Control, fructose (10% w/v solution) and fructose + atorvastatin (30 mg/kg/day) Sprague-Dawley rats were sacrificed after 14 days. Plasma and liver tissue samples were obtained to determine plasma analytes, liver histology, and the expression of liver proteins that are related to fatty acid synthesis and catabolism, and inflammatory processes. Fructose supplementation induced hypertriglyceridemia and hyperleptinemia, hepatic steatosis and necroinflammation, increased the expression of genes related to fatty acid synthesis and decreased fatty acid β-oxidation activity. Atorvastatin treatment completely abolished histological signs of necroinflammation, reducing the hepatic expression of metallothionein-1 and nuclear factor kappa B binding. Furthermore, atorvastatin reduced plasma (x 0.74) and liver triglyceride (x 0.62) concentrations, decreased the liver expression of carbohydrate response element binding protein transcription factor (x0.45) and its target genes, and increased the hepatic activity of the fatty acid β-oxidation system (x 1.15). These effects may be related to the fact that atorvastatin decreased the expression of fructokinase (x 0.6) in livers of fructose-supplemented rats, reducing the metabolic burden on the liver that is imposed by continuous fructose ingestion. - Graphical Abstract: Display Omitted Research Highlights: �

Hepatic mTORC1 controls locomotor activity, body temperature, and lipid metabolism through FGF21

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Cornu, Marion; Oppliger, Wolfgang; Albert, Verena; Robitaille, Aaron M.; Trapani, Francesca; Quagliata, Luca; Fuhrer, Tobias; Sauer, Uwe; Terracciano, Luigi; Hall, Michael N.

2014-01-01

The liver is a key metabolic organ that controls whole-body physiology in response to nutrient availability. Mammalian target of rapamycin (mTOR) is a nutrient-activated kinase and central controller of growth and metabolism that is negatively regulated by the tumor suppressor tuberous sclerosis complex 1 (TSC1). To investigate the role of hepatic mTOR complex 1 (mTORC1) in whole-body physiology, we generated liver-specific Tsc1 (L-Tsc1 KO) knockout mice. L-Tsc1 KO mice displayed reduced locomotor activity, body temperature, and hepatic triglyceride content in a rapamycin-sensitive manner. Ectopic activation of mTORC1 also caused depletion of hepatic and plasma glutamine, leading to peroxisome proliferator–activated receptor γ coactivator-1α (PGC-1α)–dependent fibroblast growth factor 21 (FGF21) expression in the liver. Injection of glutamine or knockdown of PGC-1α or FGF21 in the liver suppressed the behavioral and metabolic defects due to mTORC1 activation. Thus, mTORC1 in the liver controls whole-body physiology through PGC-1α and FGF21. Finally, mTORC1 signaling correlated with FGF21 expression in human liver tumors, suggesting that treatment of glutamine-addicted cancers with mTOR inhibitors might have beneficial effects at both the tumor and whole-body level. PMID:25082895

Low fish oil intake improves insulin sensitivity, lipid profile and muscle metabolism on insulin resistant MSG-obese rats.

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Yamazaki, Ricardo K; Brito, Gleisson A P; Coelho, Isabela; Pequitto, Danielle C T; Yamaguchi, Adriana A; Borghetti, Gina; Schiessel, Dalton Luiz; Kryczyk, Marcelo; Machado, Juliano; Rocha, Ricelli E R; Aikawa, Julia; Iagher, Fabiola; Naliwaiko, Katya; Tanhoffer, Ricardo A; Nunes, Everson A; Fernandes, Luiz Claudio

2011-04-28

Obesity is commonly associated with diabetes, cardiovascular diseases and cancer. The purpose of this study was to determinate the effect of a lower dose of fish oil supplementation on insulin sensitivity, lipid profile, and muscle metabolism in obese rats. Monosodium glutamate (MSG) (4 mg/g body weight) was injected in neonatal Wistar male rats. Three-month-old rats were divided in normal-weight control group (C), coconut fat-treated normal weight group (CO), fish oil-treated normal weight group (FO), obese control group (Ob), coconut fat-treated obese group (ObCO) and fish oil-treated obese group (ObFO). Obese insulin-resistant rats were supplemented with fish oil or coconut fat (1 g/kg/day) for 4 weeks. Insulin sensitivity, fasting blood biochemicals parameters, and skeletal muscle glucose metabolism were analyzed. Obese animals (Ob) presented higher Index Lee and 2.5 fold epididymal and retroperitoneal adipose tissue than C. Insulin sensitivity test (Kitt) showed that fish oil supplementation was able to maintain insulin sensitivity of obese rats (ObFO) similar to C. There were no changes in glucose and HDL-cholesterol levels amongst groups. Yet, ObFO revealed lower levels of total cholesterol (TC; 30%) and triacylglycerol (TG; 33%) compared to Ob. Finally, since exposed to insulin, ObFO skeletal muscle revealed an increase of 10% in lactate production, 38% in glycogen synthesis and 39% in oxidation of glucose compared to Ob. Low dose of fish oil supplementation (1 g/kg/day) was able to reduce TC and TG levels, in addition to improved systemic and muscle insulin sensitivity. These results lend credence to the benefits of n-3 fatty acids upon the deleterious effects of insulin resistance mechanisms.

Serum Bile Acids Are Higher in Humans With Prior Gastric Bypass: Potential Contribution to Improved Glucose and Lipid Metabolism

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Patti, Mary-Elizabeth; Houten, Sander M.; Bianco, Antonio C.; Bernier, Raquel; Larsen, P. Reed; Holst, Jens J.; Badman, Michael K.; Maratos-Flier, Eleftheria; Mun, Edward C.; Pihlajamaki, Jussi; Auwerx, Johan; Goldfine, Allison B.

2015-01-01

The multifactorial mechanisms promoting weight loss and improved metabolism following Roux-en-Y gastric bypass (GB) surgery remain incompletely understood. Recent rodent studies suggest that bile acids can mediate energy homeostasis by activating the G-protein coupled receptor TGR5 and the type 2 thyroid hormone deiodinase. Altered gastrointestinal anatomy following GB could affect enterohepatic recirculation of bile acids. We assessed whether circulating bile acid concentrations differ in patients who previously underwent GB, which might then contribute to improved metabolic homeostasis. We performed cross-sectional analysis of fasting serum bile acid composition and both fasting and post-meal metabolic variables, in three subject groups: (i) post-GB surgery (n = 9), (ii) without GB matched to preoperative BMI of the index cohort (n = 5), and (iii) without GB matched to current BMI of the index cohort (n = 10). Total serum bile acid concentrations were higher in GB (8.90 ± 4.84 µmol/l) than in both overweight (3.59 ± 1.95, P = 0.005, Ov) and severely obese (3.86 ± 1.51, P = 0.045, MOb). Bile acid subfractions taurochenodeoxycholic, taurodeoxycholic, glycocholic, glycochenodeoxycholic, and glycodeoxycholic acids were all significantly higher in GB compared to Ov (P fasting triglycerides (r = −0.40, P = 0.05), and positively correlated with adiponectin (r = −0.48, P < 0.02) and peak glucagon-like peptide-1 (GLP-1) (r = 0.58, P < 0.003). Total bile acids strongly correlated inversely with thyrotropic hormone (TSH) (r = −0.57, P = 0.004). Together, our data suggest that altered bile acid levels and composition may contribute to improved glucose and lipid metabolism in patients who have had GB. PMID:19360006

Female fibromyalgia patients: lower resting metabolic rates than matched healthy controls.

Science.gov (United States)

Lowe, John C; Yellin, Jackie; Honeyman-Lowe, Gina

2006-07-01

Many features of fibromyalgia and hypothyroidism are virtually the same, and thyroid hormone treatment trials have reduced or eliminated fibromyalgia symptoms. These findings led the authors to test the hypothesis that fibromyalgia patients are hypometabolic compared to matched controls. Resting metabolic rate (RMR) was measured by indirect calorimetry and body composition by bioelectrical impedance for 15 fibromyalgia patients and 15 healthy matched controls. Measured resting metabolic rate (mRMR) was compared to percentages of predicted RMR (pRMR) by fat-free weight (FFW) (Sterling-Passmore: SP) and by sex, age, height, and weight (Harris-Benedict: HB). Patients had a lower mRMR (4,306.31+/-1077.66 kJ vs 5,411.59+/-695.95 kJ, p=0.0028) and lower percentages of pRMRs (SP: -28.42+/-15.82% vs -6.83+/-12.55%, pBMI) best accounted for variability in controls' RMRs, age and fat weight (FW) did for patients. In the patient group, TSH level accounted for 28% of the variance in pain distribution, and free T3 (FT3) accounted for 30% of the variance in pressure-pain threshold. Patients had lower mRMR and percentages of pRMRs. The lower RMRs were not due to calorie restriction or low FFW. Patients' normal FFW argues against low physical activity as the mechanism. TSH, FT4, and FT3 levels did not correlate with RMRs in either group. This does not rule out inadequate thyroid hormone regulation because studies show these laboratory values do not reliably predict RMR.

The role of the autonomic nervous liver innervation in the control of energy metabolism

NARCIS (Netherlands)

Yi, Chun-Xia; la Fleur, Susanne E.; Fliers, Eric; Kalsbeek, Andries

2010-01-01

Despite a longstanding research interest ever since the early work by Claude Bernard, the functional significance of autonomic liver innervation, either sympathetic or parasympathetic, is still ill defined. This scarcity of information not only holds for the brain control of hepatic metabolism, but

Braking Control for Improving Ride Comfort

Directory of Open Access Journals (Sweden)

Lee Jonghyup

2018-01-01

Full Text Available While many vehicle control systems focus on vehicle safety and vehicle performance at high speeds, most driving conditions are very low risk situations. In such a driving situation, the ride comfort of the vehicle is the most important performance index of the vehicle. Electro mechanical brake (EMB and other brake-by-wire (BBW systems have been actively researched. As a result, braking actuators in vehicles are more freely controllable, and research on improving ride comfort is also possible. In this study, we develop a control algorithm that dramatically improves ride comfort in low risk braking situations. A method for minimizing the inconvenience of a passenger due to a suddenly changing acceleration at the moment when the vehicle is stopped is presented. For this purpose, an acceleration trajectory is generated that minimizes the discomfort index defined by the change in acceleration, jerk. A controller is also designed to track this trajectory. The algorithm that updates the trajectory is designed considering the error due to the phase lag occurring in the controller and the plant. In order to verify the performance of this controller, simulation verification is completed using a car simulator, Carsim. As a result, it is confirmed that the ride comfort is dramatically improved.

Preoperative overnight parenteral nutrition (TPN) improves skeletal muscle protein metabolism indicated by microarray algorithm analyses in a randomized trial.

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Iresjö, Britt-Marie; Engström, Cecilia; Lundholm, Kent

2016-06-01

Loss of muscle mass is associated with increased risk of morbidity and mortality in hospitalized patients. Uncertainties of treatment efficiency by short-term artificial nutrition remain, specifically improvement of protein balance in skeletal muscles. In this study, algorithmic microarray analysis was applied to map cellular changes related to muscle protein metabolism in human skeletal muscle tissue during provision of overnight preoperative total parenteral nutrition (TPN). Twenty-two patients (11/group) scheduled for upper GI surgery due to malignant or benign disease received a continuous peripheral all-in-one TPN infusion (30 kcal/kg/day, 0.16 gN/kg/day) or saline infusion for 12 h prior operation. Biopsies from the rectus abdominis muscle were taken at the start of operation for isolation of muscle RNA RNA expression microarray analyses were performed with Agilent Sureprint G3, 8 × 60K arrays using one-color labeling. 447 mRNAs were differently expressed between study and control patients (P nutrition; particularly anabolic signaling S6K1 (P parenteral nutrition is effective to promote muscle protein metabolism. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

SIRT4 Is a Lysine Deacylase that Controls Leucine Metabolism and Insulin Secretion

DEFF Research Database (Denmark)

Anderson, Kristin A; Huynh, Frank K; Fisher-Wellman, Kelsey

2017-01-01

in leucine oxidation, and we show a primary role for SIRT4 in controlling this pathway in mice. Furthermore, we find that dysregulated leucine metabolism in SIRT4KO mice leads to elevated basal and stimulated insulin secretion, which progressively develops into glucose intolerance and insulin resistance....... These findings identify a robust enzymatic activity for SIRT4, uncover a mechanism controlling branched-chain amino acid flux, and position SIRT4 as a crucial player maintaining insulin secretion and glucose homeostasis during aging....

Improved Production of a Heterologous Amylase in Saccharomyces cerevisiae by Inverse Metabolic Engineering

DEFF Research Database (Denmark)

Liu, Zihe; Liu, Lifang; Osterlund, Tobias

2014-01-01

this modification alone, the amylase secretion could be improved by 35%. As a complement to the identification of genomic variants, transcriptome analysis was also performed in order to understand on a global level the transcriptional changes associated with the improved amylase production caused by UV mutagenesis.......The increasing demand for industrial enzymes and biopharmaceutical proteins relies on robust production hosts with high protein yield and productivity. Being one of the best-studied model organisms and capable of performing posttranslational modifications, the yeast Saccharomyces cerevisiae...... is widely used as a cell factory for recombinant protein production. However, many recombinant proteins are produced at only 1% (or less) of the theoretical capacity due to the complexity of the secretory pathway, which has not been fully exploited. In this study, we applied the concept of inverse metabolic...

Improvement of metabolic disorders by an EP2 receptor agonist via restoration of the subcutaneous adipose tissue in pulmonary emphysema.

Science.gov (United States)

Tsuji, Takao; Yamaguchi, Kazuhiro; Kikuchi, Ryota; Nakamura, Hiroyuki; Misaka, Ryoichi; Nagai, Atsushi; Aoshiba, Kazutetsu

2017-05-01

Chronic obstructive pulmonary disease (COPD) is often associated with co-morbidities. Metabolic disorders like hyperlipidemia and diabetes occur also in underweight COPD patients, although the mechanism is uncertain. Subcutaneous adipose tissue (SAT) plays an important role in energy homeostasis, since restricted capacity to increase fat cell number with increase in fat cell size occurring instead, is associated with lipotoxicity and metabolic disorders. The aim of this study is to show the protective role of SAT for the metabolic disorders in pulmonary emphysema of a murine model. We found ectopic fat accumulation and impaired glucose homeostasis with wasting of SAT in a murine model of elastase-induced pulmonary emphysema (EIE mice) reared on a high-fat diet. ONO-AE1-259, a selective E-prostanoid (EP) 2 receptor agonist, improved angiogenesis and subsequently adipogenesis, and finally improved ectopic fat accumulation and glucose homeostasis with restoration of the capacity for storage of surplus energy in SAT. These results suggest that metabolic disorders like hyperlipidemia and diabetes occured in underweight COPD is partially due to the less capacity for storage of surplus energy in SAT, though the precise mechanism is uncertained. Our data pave the way for the development of therapeutic interventions for metabolic disorders in emphysema patients, e.g., use of pro-angiogenic agents targeting the capacity for storage of surplus energy in the subcutaneous adipose tissue. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of metabolic syndrome on the functional outcomes of corticosteroid injection for De Quervain tenosynovitis.

Science.gov (United States)

Roh, Y H; Noh, J H; Gong, H S; Baek, G H

2017-06-01

Metabolic syndrome is a constellation of medical conditions that arise from insulin resistance and abnormal adipose deposition and function. In patients with metabolic syndrome and De Quervain tenosynovitis this might affect the outcome of treatment by local corticosteroid injection. A total of 64 consecutive patients with De Quervain tenosynovitis and metabolic syndrome treated with corticosteroid injection were age- and sex-matched with 64 control patients without metabolic syndrome. The response to treatment, including visual analogue scale score for pain, objective findings consistent with De Quervain tenosynovitis (tenderness at first dorsal compartment, Finkelstein test result), and Disability of the Arm, Shoulder, and Hand score were assessed at 6, 12, and 24 weeks follow-up. Treatment failure was defined as persistence of symptoms or surgical intervention. Prior to treatment, patients with metabolic syndrome had mean initial pain visual analogue scale and Disability of the Arm, Shoulder, and Hand scores similar to those in the control group. The proportion of treatment failure in the metabolic syndrome group (43%) was significantly higher than that in the control group (20%) at 6 months follow-up. The pain visual analogue scale scores in the metabolic syndrome group were higher than the scores in the control group at the 12- and 24-week follow-ups. The Disability of the Arm, Shoulder, and Hand scores of the metabolic syndrome group were higher (more severe symptoms) than those of the control group at the 12- and 24-week follow-ups. Although considerable improvements in symptom severity and hand function will likely occur in patients with metabolic syndrome, corticosteroid injection for De Quervain tenosynovitis is not as effective in these patients compared with age- and sex-matched controls in terms of functional outcomes and treatment failure. III.

Robotic excavator trajectory control using an improved GA based PID controller

Science.gov (United States)

Feng, Hao; Yin, Chen-Bo; Weng, Wen-wen; Ma, Wei; Zhou, Jun-jing; Jia, Wen-hua; Zhang, Zi-li

2018-05-01

In order to achieve excellent trajectory tracking performances, an improved genetic algorithm (IGA) is presented to search for the optimal proportional-integral-derivative (PID) controller parameters for the robotic excavator. Firstly, the mathematical model of kinematic and electro-hydraulic proportional control system of the excavator are analyzed based on the mechanism modeling method. On this basis, the actual model of the electro-hydraulic proportional system are established by the identification experiment. Furthermore, the population, the fitness function, the crossover probability and mutation probability of the SGA are improved: the initial PID parameters are calculated by the Ziegler-Nichols (Z-N) tuning method and the initial population is generated near it; the fitness function is transformed to maintain the diversity of the population; the probability of crossover and mutation are adjusted automatically to avoid premature convergence. Moreover, a simulation study is carried out to evaluate the time response performance of the proposed controller, i.e., IGA based PID against the SGA and Z-N based PID controllers with a step signal. It was shown from the simulation study that the proposed controller provides the least rise time and settling time of 1.23 s and 1.81 s, respectively against the other tested controllers. Finally, two types of trajectories are designed to validate the performances of the control algorithms, and experiments are performed on the excavator trajectory control experimental platform. It was demonstrated from the experimental work that the proposed IGA based PID controller improves the trajectory accuracy of the horizontal line and slope line trajectories by 23.98% and 23.64%, respectively in comparison to the SGA tuned PID controller. The results further indicate that the proposed IGA tuning based PID controller is effective for improving the tracking accuracy, which may be employed in the trajectory control of an actual excavator.

PPAR ligands improve impaired metabolic pathways in fetal hearts of diabetic rats.

Science.gov (United States)

Kurtz, Melisa; Capobianco, Evangelina; Martinez, Nora; Roberti, Sabrina Lorena; Arany, Edith; Jawerbaum, Alicia

2014-10-01

In maternal diabetes, the fetal heart can be structurally and functionally affected. Maternal diets enriched in certain unsaturated fatty acids can activate the nuclear receptors peroxisome proliferator-activated receptors (PPARs) and regulate metabolic and anti-inflammatory pathways during development. Our aim was to investigate whether PPARα expression, lipid metabolism, lipoperoxidation, and nitric oxide (NO) production are altered in the fetal hearts of diabetic rats, and to analyze the putative effects of in vivo PPAR activation on these parameters. We found decreased PPARα expression in the hearts of male but not female fetuses of diabetic rats when compared with controls. Fetal treatments with the PPARα ligand leukotriene B4 upregulated the expression of PPARα and target genes involved in fatty acid oxidation in the fetal hearts. Increased concentrations of triglycerides, cholesterol, and phospholipids were found in the hearts of fetuses of diabetic rats. Maternal treatments with diets supplemented with 6% olive oil or 6% safflower oil, enriched in unsaturated fatty acids that can activate PPARs, led to few changes in lipid concentrations, but up-regulated PPARα expression in fetal hearts. NO production, which was increased in the hearts of male and female fetuses in the diabetic group, and lipoperoxidation, which was increased in the hearts of male fetuses in the diabetic group, was reduced by the maternal treatments supplemented with safflower oil. In conclusion, impaired PPARα expression, altered lipid metabolism, and increased oxidative and nitridergic pathways were evidenced in hearts of fetuses of diabetic rats and were regulated in a gender-dependent manner by treatments enriched with PPAR ligands. © 2014 Society for Endocrinology.

Update on Mycoplasma hyopneumoniae infections in pigs: Knowledge gaps for improved disease control.

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Maes, D; Sibila, M; Kuhnert, P; Segalés, J; Haesebrouck, F; Pieters, M

2017-08-23

Mycoplasma hyopneumoniae (M. hyopneumoniae) is the primary pathogen of enzootic pneumonia, a chronic respiratory disease in pigs. Infections occur worldwide and cause major economic losses to the pig industry. The present paper reviews the current knowledge on M. hyopneumoniae infections, with emphasis on identification and analysis of knowledge gaps for optimizing control of the disease. Close contact between infected and susceptible pigs is the main route of M. hyopneumoniae transmission. Management and housing conditions predisposing for infection or disease are known, but further research is needed to better understand M. hyopneumoniae transmission patterns in modern pig production systems, and to assess the importance of the breeding population for downstream disease control. The organism is primarily found on the mucosal surface of the trachea, bronchi and bronchioles. Different adhesins and lipoproteins are involved in the adherence process. However, a clear picture of the virulence and pathogenicity of M. hyopneumoniae is still missing. The role of glycerol metabolism, myoinositol metabolism and the Mycoplasma Ig binding protein-Mycoplasma Ig protease system should be further investigated for their contribution to virulence. The destruction of the mucociliary apparatus, together with modulating the immune response, enhances the susceptibility of infected pigs to secondary pathogens. Clinical signs and severity of lesions depend on different factors, such as management, environmental conditions and likely also M. hyopneumoniae strain. The potential impact of strain variability on disease severity is not well defined. Diagnostics could be improved by developing tests that may detect virulent strains, by improving sampling in live animals and by designing ELISAs allowing discrimination between infected and vaccinated pigs. The currently available vaccines are often cost-efficient, but the ongoing research on developing new vaccines that confer protective

The effect of metabolic control on hemodynamics in short-term insulin-dependent diabetic patients

DEFF Research Database (Denmark)

Mathiesen, E R; Hilsted, J; Feldt-Rasmussen, B

1985-01-01

Hemodynamics variables (heart rate, arterial blood pressure, cardiac output, hepato-splanchnic blood flow, forearm blood flow, and plasma catecholamines) were measured during good (median blood glucose 4.7 mmol/L) and poor (median blood glucose 16.3 mmol/L) metabolic control in eight young, short...

Improvement of Insulin Sensitivity after Lean Donor Feces in Metabolic Syndrome Is Driven by Baseline Intestinal Microbiota Composition

DEFF Research Database (Denmark)

Kootte, Ruud S.; Levin, Evgeni; Salojärvi, Jarkko

2017-01-01

be predicted based on baseline fecal microbiota composition. Kootte et al. show that fecal microbiota transplantation from lean donors to obese patients with metabolic syndrome improves insulin sensitivity, a transient effect associated with changes in microbiota composition and fasting plasma metabolites...

Probiotics and Probiotic Metabolic Product Improved Intestinal Function and Ameliorated LPS-Induced Injury in Rats.

Science.gov (United States)

Deng, Bo; Wu, Jie; Li, Xiaohui; Men, Xiaoming; Xu, Ziwei

2017-11-01

In the present study, we sought to determine the effects of Bacillus subtilis (BAS) and Bacillus licheniformis (BAL) in rats after lipopolysaccharide (LPS)-induced acute intestinal inflammation. We also determined whether the B. subtilis metabolic product (BASM) is as effective as the live-cell probiotic. 60 male SD rats were randomly assigned to five groups and administered a diet containing 0.05% B. licheniformis (BAL group), 0.05% B. subtilis (BAS group), 0.5% B. subtilis metabolic product (BASM group), or a basic diet (PC group and NC group) for 40 days. On day 40, BAL, BAS, BASM, and NC groups were injected with 4 mg/kg body weight LPS. 4 h later, all rats were anesthetized and sacrificed. The results showed that the administration of B. licheniformis and B. subtilis improved intestinal function as evidenced by histology, increased enzyme activity, and mucosal thickness. They also increased the number of intraepithelial lymphocytes and decreased mucosal myeloperoxidase activity and plasma TNF-α. In addition, the cecal content of B. subtilis-treated rats had significantly increased microbial diversity, decreased numbers of Firmicutes, and increased numbers of Bacteroidetes as compared to rats fed basic diets. Similar to BAS group, the cecal content of B. licheniformis-treated rats decreased the number of Firmicutes. Administration of B. subtilis metabolic product had similar effects on intestinal function, inflammation response, and microbial diversity as B. subtilis but these effects were attenuated. In conclusion, administration of probiotic strains B. licheniformis or B. subtilis improved intestinal function, ameliorated the inflammation response, and modulated microflora after LPS-induced acute inflammation in rats. Non-living cells also exerted probiotic properties but live cells tended to function better.

Bariatric Surgery Improves Hyperandrogenism, Menstrual Irregularities, and Metabolic Dysfunction Among Women with Polycystic Ovary Syndrome (PCOS).

Science.gov (United States)

Christ, Jacob P; Falcone, Tommaso

2018-03-02

To characterize the impact of bariatric surgery on reproductive and metabolic features common to polycystic ovary syndrome (PCOS) and to assess the relevance of preoperative evaluations in predicting likelihood of benefit from surgery. A retrospective chart review of records from 930 women who had undergone bariatric surgery at the Cleveland Clinic Foundation from 2009 to 2014 was completed. Cases of PCOS were identified from ICD coding and healthy women with pelvic ultrasound evaluations were identified using Healthcare Common Procedure Coding System coding. Pre- and postoperative anthropometric evaluations, menstrual cyclicity, ovarian volume (OV) as well as markers of hyperandrogenism, dyslipidemia, and dysglycemia were evaluated. Forty-four women with PCOS and 65 controls were evaluated. Both PCOS and non-PCOS had significant reductions in body mass index (BMI) and markers of dyslipidemia postoperatively (p PCOS had significant reductions in androgen levels (p irregular menses (p PCOS, independent of preoperative BMI and age, preoperative OV associated with change in hemoglobin A1c (β 95% (confidence interval) 0.202 (0.011-0.393), p = 0.04) and change in triglycerides (6.681 (1.028-12.334), p = 0.03), and preoperative free testosterone associated with change in total cholesterol (3.744 (0.906-6.583), p = 0.02) and change in non-HDL-C (3.125 (0.453-5.796), p = 0.03). Bariatric surgery improves key diagnostic features seen in women with PCOS and ovarian volume, and free testosterone may have utility in predicting likelihood of metabolic benefit from surgery.

A qualitative study of young people's perspectives of living with type 1 diabetes: do perceptions vary by levels of metabolic control?

Science.gov (United States)

Scholes, Cheryl; Mandleco, Barbara; Roper, Susanne; Dearing, Karen; Dyches, Tina; Freeborn, Donna

2013-06-01

To explore if young people with higher and lower levels of metabolic control of type 1 diabetes have different perceptions about their lives and illness. Adolescence through emerging adulthood is a developmental stage made more challenging when the person has type 1 diabetes. Little research has investigated if individuals with high and low levels of metabolic control in this age group perceive their disease differently. Qualitative descriptive. In this study, 14 participants, ages 11-22 years were interviewed in 2008 about their perceptions of living with type 1 diabetes. Through a process of induction, major themes were identified. Participants with high and low metabolic control levels reported similar themes related to reactions of others, knowledge about type 1 diabetes, and believed healthcare providers used authoritarian interactions. However, high metabolic control level participants believed type 1 diabetes would be cured; had negative initial responses to being diagnosed; rarely received parental support in managing their diabetes; and were negligent in self-care activities. Participants with low metabolic control levels did not believe a cure was imminent or have negative responses to being diagnosed; received parental support in managing diabetes; and were diligent in self-care activities. Nurses should give information to young people with type 1 diabetes beyond initial diagnosis and help and support this age group learn appropriate ways to manage their disease, develop positive relationships with healthcare professionals, and participate in interactions with others their age successfully managing type 1 diabetes. © 2012 Blackwell Publishing Ltd.

What change in body mass index is needed to improve metabolic health status in childhood obesity: protocol for a systematic review.

Science.gov (United States)

Birch, Laura; Perry, Rachel; Penfold, Chris; Beynon, Rhona; Hamilton-Shield, Julian

2016-07-26

Childhood obesity is one of the most serious, global, public health challenges and has adverse health consequences in both the short-and long-term. The purpose of this study is to establish the change in body mass index (BMI) needed to achieve improvements in metabolic health status in obese children and adolescents attending lifestyle treatment interventions. The following electronic databases will be searched from their inception: AMED, Embase, MEDLINE via OVID, Web of Science and CENTRAL via Cochrane library. Randomised controlled trials (RCTs) or cohort studies of lifestyle interventions (i.e. dietary, physical activity and/or behavioural therapy) for treating obesity in children and adolescents (4-18 years) will be included. Interventions that last less than 2 weeks and trials that include overweight participants or those with a secondary or syndromic cause of obesity will not be included. No language restrictions will be applied. Titles and abstracts will be assessed for eligibility by two reviewers, and data from full-text articles will be extracted using a standardised data extraction template. Reference lists of all included articles will be hand-searched for additional publications. A narrative synthesis of the findings will be presented, and meta-analysis will be conducted if considered appropriate. This will be the first systematic review of studies to establish the change in BMI required to improve metabolic health status in obese children and adolescents. PROSPERO CRD42016025317.

α/β-Hydrolase Domain 6 in the Ventromedial Hypothalamus Controls Energy Metabolism Flexibility

Directory of Open Access Journals (Sweden)

Alexandre Fisette

2016-10-01

Full Text Available α/β-Hydrolase domain 6 (ABHD6 is a monoacylglycerol hydrolase that degrades the endocannabinoid 2-arachidonoylglycerol (2-AG. Although complete or peripheral ABHD6 loss of function is protective against diet-induced obesity and insulin resistance, the role of ABHD6 in the central control of energy balance is unknown. Using a viral-mediated knockout approach, targeted endocannabinoid measures, and pharmacology, we discovered that mice lacking ABHD6 from neurons of the ventromedial hypothalamus (VMHKO have higher VMH 2-AG levels in conditions of endocannabinoid recruitment and fail to physiologically adapt to key metabolic challenges. VMHKO mice exhibited blunted fasting-induced feeding and reduced food intake, energy expenditure, and adaptive thermogenesis in response to cold exposure, high-fat feeding, and dieting (transition to a low-fat diet. Our findings identify ABHD6 as a regulator of the counter-regulatory responses to major metabolic shifts, including fasting, nutrient excess, cold, and dieting, thereby highlighting the importance of ABHD6 in the VMH in mediating energy metabolism flexibility.

Muscle insulin sensitivity and glucose metabolism are controlled by the intrinsic muscle clock★

Science.gov (United States)

Dyar, Kenneth A.; Ciciliot, Stefano; Wright, Lauren E.; Biensø, Rasmus S.; Tagliazucchi, Guidantonio M.; Patel, Vishal R.; Forcato, Mattia; Paz, Marcia I.P.; Gudiksen, Anders; Solagna, Francesca; Albiero, Mattia; Moretti, Irene; Eckel-Mahan, Kristin L.; Baldi, Pierre; Sassone-Corsi, Paolo; Rizzuto, Rosario; Bicciato, Silvio; Pilegaard, Henriette; Blaauw, Bert; Schiaffino, Stefano

2013-01-01

Circadian rhythms control metabolism and energy homeostasis, but the role of the skeletal muscle clock has never been explored. We generated conditional and inducible mouse lines with muscle-specific ablation of the core clock gene Bmal1. Skeletal muscles from these mice showed impaired insulin-stimulated glucose uptake with reduced protein levels of GLUT4, the insulin-dependent glucose transporter, and TBC1D1, a Rab-GTPase involved in GLUT4 translocation. Pyruvate dehydrogenase (PDH) activity was also reduced due to altered expression of circadian genes Pdk4 and Pdp1, coding for PDH kinase and phosphatase, respectively. PDH inhibition leads to reduced glucose oxidation and diversion of glycolytic intermediates to alternative metabolic pathways, as revealed by metabolome analysis. The impaired glucose metabolism induced by muscle-specific Bmal1 knockout suggests that a major physiological role of the muscle clock is to prepare for the transition from the rest/fasting phase to the active/feeding phase, when glucose becomes the predominant fuel for skeletal muscle. PMID:24567902

A High-Protein Diet Reduces Weight Gain, Decreases Food Intake, Decreases Liver Fat Deposition, and Improves Markers of Muscle Metabolism in Obese Zucker Rats.

Science.gov (United States)

French, William W; Dridi, Sami; Shouse, Stephanie A; Wu, Hexirui; Hawley, Aubree; Lee, Sun-Ok; Gu, Xuan; Baum, Jamie I

2017-06-08

A primary factor in controlling and preventing obesity is through dietary manipulation. Diets higher in protein have been shown to improve body composition and metabolic health during weight loss. The objective of this study was to examine the effects of a high-protein diet versus a moderate-protein diet on muscle, liver and fat metabolism and glucose regulation using the obese Zucker rat. Twelve-week old, male, Zucker (fa/fa) and lean control (Fa/fa) rats were randomly assigned to either a high-protein (40% energy) or moderate-protein (20% energy) diet for 12 weeks, with a total of four groups: lean 20% protein (L20; n = 8), lean 40% protein (L40; n = 10), obese 20% protein (O20; n = 8), and obese 40% protein (O40; n = 10). At the end of 12 weeks, animals were fasted and euthanized. There was no difference in food intake between L20 and L40. O40 rats gained less weight and had lower food intake ( p diet rats, respectively. O40 had decreased skeletal muscle mechanistic target of rapamycin complex 1 (mTORC1) phosphorylation and peroxisome proliferator-activated receptor gamma (PPARγ) mRNA expression compared to O20 ( p protein kinase (AMPK), eukaryotic translation initiation factor 4E binding protein 1 (4EBP1), protein kinase B (Akt) or p70 ribosomal S6 kinase (p70S6K) phosphorylation. The data suggest that high-protein diets have the potential to reduce weight gain and alter metabolism, possibly through regulation of an mTORC1-dependent pathway in skeletal muscle.

A randomized controlled trial of an exercise intervention targeting cardiovascular and metabolic risk factors for prostate cancer patients from the RADAR trial

International Nuclear Information System (INIS)

Galvão, Daniel A; Spry, Nigel; Taaffe, Dennis R; Denham, James; Joseph, David; Lamb, David S; Levin, Greg; Duchesne, Gillian; Newton, Robert U

2009-01-01

Androgen deprivation therapy leads to a number of adverse effects including deterioration of the musculoskeletal system and increased risk factors for cardiovascular and metabolic complications. The purpose of this study is to determine the effects, efficacy, retention and compliance of a physical exercise intervention in a large established cohort of prostate cancer patients from the Randomised Androgen Deprivation and Radiotherapy (RADAR) study. Specifically, we aim to compare short- and long-term effects of a prostate cancer-specific supervised exercise program to a standard public health physical activity strategy utilizing printed resources on cardiovascular and metabolic risk factors. Our primary outcomes are cardiorespiratory capacity, abdominal obesity, and lipid and glycemic control, while secondary outcomes include self-reported physical activity, quality of life and psychological distress. Multi-site randomized controlled trial of 370 men from the RADAR study cohort undergoing treatment or previously treated for prostate cancer involving androgen deprivation therapy in the cities of Perth and Newcastle (Australia), and Wellington (New Zealand). Participants will be randomized to (1) supervised resistance/aerobic exercise or (2) printed material comprising general physical activity recommendations. Participants will then undergo progressive training for 6 months. Measurements for primary and secondary endpoints will take place at baseline, 6 months (end of intervention), and at 6 months follow-up. This study uses a large existent cohort of patients and will generate valuable information as to the continuing effects of exercise specifically targeting cardiovascular function and disease risk, insulin metabolism, abdominal obesity, physical function, quality of life and psychological distress. We expect dissemination of the knowledge gained from this project to reduce risk factors for the development of co-morbid diseases commonly associated with androgen

Improvement of internal book-keeping control at company "Balttranslaine"

OpenAIRE

Kolodinska, Aļona

2012-01-01

Master's thesis "Internal Accounting Control Improvement in Ltd."Balttranslaine"" is designed to determine the potential and directions for improving accounting controls Ltd. "Balttranslaine". The paper assesses Ltd. "Balttranslaine" internal accounting control system and develops proposals for its improvement, based on research on accounting control nature and its place in the overall company's internal control system, as well as the Latvian laws and regulations for construction and maint...

The metabolic costs of improving ethanol yield by reducing glycerol formation capacity under anaerobic conditions in Saccharomyces cerevisiae.

Science.gov (United States)

Pagliardini, Julien; Hubmann, Georg; Alfenore, Sandrine; Nevoigt, Elke; Bideaux, Carine; Guillouet, Stephane E

2013-03-28

Finely regulating the carbon flux through the glycerol pathway by regulating the expression of the rate controlling enzyme, glycerol-3-phosphate dehydrogenase (GPDH), has been a promising approach to redirect carbon from glycerol to ethanol and thereby increasing the ethanol yield in ethanol production. Here, strains engineered in the promoter of GPD1 and deleted in GPD2 were used to investigate the possibility of reducing glycerol production of Saccharomyces cerevisiae without jeopardising its ability to cope with process stress during ethanol production. For this purpose, the mutant strains TEFmut7 and TEFmut2 with different GPD1 residual expression were studied in Very High Ethanol Performance (VHEP) fed-batch process under anaerobic conditions. Both strains showed a drastic reduction of the glycerol yield by 44 and 61% while the ethanol yield improved by 2 and 7% respectively. TEFmut2 strain showing the highest ethanol yield was accompanied by a 28% reduction of the biomass yield. The modulation of the glycerol formation led to profound redox and energetic changes resulting in a reduction of the ATP yield (YATP) and a modulation of the production of organic acids (acetate, pyruvate and succinate). Those metabolic rearrangements resulted in a loss of ethanol and stress tolerance of the mutants, contrarily to what was previously observed under aerobiosis. This work demonstrates the potential of fine-tuned pathway engineering, particularly when a compromise has to be found between high product yield on one hand and acceptable growth, productivity and stress resistance on the other hand. Previous study showed that, contrarily to anaerobiosis, the resulting gain in ethanol yield was accompanied with no loss of ethanol tolerance under aerobiosis. Moreover those mutants were still able to produce up to 90 gl-1 ethanol in an anaerobic SSF process. Fine tuning metabolic strategy may then open encouraging possibilities for further developing robust strains with improved

Orphan Nuclear Receptor ERRα Controls Macrophage Metabolic Signaling and A20 Expression to Negatively Regulate TLR-Induced Inflammation.

Science.gov (United States)

Yuk, Jae-Min; Kim, Tae Sung; Kim, Soo Yeon; Lee, Hye-Mi; Han, Jeongsu; Dufour, Catherine Rosa; Kim, Jin Kyung; Jin, Hyo Sun; Yang, Chul-Su; Park, Ki-Sun; Lee, Chul-Ho; Kim, Jin-Man; Kweon, Gi Ryang; Choi, Hueng-Sik; Vanacker, Jean-Marc; Moore, David D; Giguère, Vincent; Jo, Eun-Kyeong

2015-07-21

The orphan nuclear receptor estrogen-related receptor α (ERRα; NR3B1) is a key metabolic regulator, but its function in regulating inflammation remains largely unknown. Here, we demonstrate that ERRα negatively regulates Toll-like receptor (TLR)-induced inflammation by promoting Tnfaip3 transcription and fine-tuning of metabolic reprogramming in macrophages. ERRα-deficient (Esrra(-/-)) mice showed increased susceptibility to endotoxin-induced septic shock, leading to more severe pro-inflammatory responses than control mice. ERRα regulated macrophage inflammatory responses by directly binding the promoter region of Tnfaip3, a deubiquitinating enzyme in TLR signaling. In addition, Esrra(-/-) macrophages showed an increased glycolysis, but impaired mitochondrial respiratory function and biogenesis. Further, ERRα was required for the regulation of NF-κB signaling by controlling p65 acetylation via maintenance of NAD(+) levels and sirtuin 1 activation. These findings unravel a previously unappreciated role for ERRα as a negative regulator of TLR-induced inflammatory responses through inducing Tnfaip3 transcription and controlling the metabolic reprogramming. Copyright © 2015 Elsevier Inc. All rights reserved.

Dose effects of dietary phytosterols on cholesterol metabolism: a controlled feeding study123

Science.gov (United States)

Lin, Xiaobo; Lefevre, Michael; Spearie, Catherine Anderson; Most, Marlene M; Ma, Lina; Ostlund, Richard E

2010-01-01

Background: Phytosterol supplementation of 2 g/d is recommended by the National Cholesterol Education Program to reduce LDL cholesterol. However, the effects of different intakes of phytosterol on cholesterol metabolism are uncertain. Objective: We evaluated the effects of 3 phytosterol intakes on whole-body cholesterol metabolism. Design: In this placebo-controlled, crossover feeding trial, 18 adults received a phytosterol-deficient diet (50 mg phytosterols/2000 kcal) plus beverages supplemented with 0, 400, or 2000 mg phytosterols/d for 4 wk each, in random order. All meals were prepared in a metabolic kitchen; breakfast and dinner on weekdays were eaten on site. Primary outcomes were fecal cholesterol excretion and intestinal cholesterol absorption measured with stable-isotope tracers and serum lipoprotein concentrations. Results: Phytosterol intakes (diet plus supplements) averaged 59, 459, and 2059 mg/d during the 3 diet periods. Relative to the 59-mg diet, the 459- and 2059-mg phytosterol intakes significantly (P phytosterol dose (−8.9 ± 2.3%); a trend was observed with the 459-mg/d dose (−5.0 ± 2.1%; P = 0.077). Conclusions: Dietary phytosterols in moderate and high doses favorably alter whole-body cholesterol metabolism in a dose-dependent manner. A moderate phytosterol intake (459 mg/d) can be obtained in a healthy diet without supplementation. This trial was registered at clinicaltrials.gov as NCT00860054. PMID:19889819

Metabolic control of muscle blood flow during exercise in humans

DEFF Research Database (Denmark)

Boushel, Robert Christopher

2003-01-01

that combined blockade of NOS and PGI2, and NOS and cytochrome P450, both attenuate exercise-induced hyperemia in humans. Combined vasodilator blockade studies offer the potential to uncover important interactions and compensatory vasodilator responses. The signaling pathways that link metabolic events evoked...... to exert control of muscle vasodilation. Adenosine, nitric oxide (NO), prostacyclin (PGI2), and endothelial-derived hyperpolarization factor (EDHF) are possible mediators of muscle vasodilation during exercise. In humans, adenosine has been shown to contribute to functional hyperemia as blood flow...... by muscle contraction to vasodilatory signals in the local vascular bed remains an important area of study....

KUDESAN EFFICACY IN ADOLESCENTS WITH METABOLIC SYNDROME

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M.B. Kolesnikova

2011-01-01

Full Text Available Metabolic abnormalities in metabolic syndrome affect the functioning of practically all organs and systems, and most seriously — cardio-vascular system. Cardio-vascular abnormalities in metabolic syndrome manifest as arterial hypertension, Riley-Day syndrome and endothelial dysfunction that can lead to decrease of adaptive and reserve capabilities. Co-enzyme Q10 possesses cardioprotective,  stress-protective and anti-ischaemic activity. Clinical study performed on 40 children aged 10 to 17 years with constitutive obesity, complicated metabolic syndrome, has proven validity of co-enzyme Q10 treatment in patients with metabolic syndrome. The use of co-enzyme Q10 15 mg/day during 30 days has lead to improvement of psycho-emotional condition, decrease in anxiety complaints, sleep improvement, decrease in asthenic syndrome symptoms, improvement in electrophysiological heart indices Key words: metabolic syndrome, co-enzyme Q10. (Voprosy sovremennoi pediatrii — Current Pediatrics. — 2011; 10 (5: 102–106.

Improved Xylose Metabolism by a CYC8 Mutant of Saccharomyces cerevisiae.

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Nijland, Jeroen G; Shin, Hyun Yong; Boender, Leonie G M; de Waal, Paul P; Klaassen, Paul; Driessen, Arnold J M

2017-06-01

Engineering Saccharomyces cerevisiae for the utilization of pentose sugars is an important goal for the production of second-generation bioethanol and biochemicals. However, S. cerevisiae lacks specific pentose transporters, and in the presence of glucose, pentoses enter the cell inefficiently via endogenous hexose transporters (HXTs). By means of in vivo engineering, we have developed a quadruple hexokinase deletion mutant of S. cerevisiae that evolved into a strain that efficiently utilizes d-xylose in the presence of high d-glucose concentrations. A genome sequence analysis revealed a mutation (Y353C) in the general corepressor CYC8 , or SSN6 , which was found to be responsible for the phenotype when introduced individually in the nonevolved strain. A transcriptome analysis revealed altered expression of 95 genes in total, including genes involved in (i) hexose transport, (ii) maltose metabolism, (iii) cell wall function (mannoprotein family), and (iv) unknown functions (seripauperin multigene family). Of the 18 known HXTs, genes for 9 were upregulated, especially the low or nonexpressed HXT10 , HXT13 , HXT15 , and HXT16 Mutant cells showed increased uptake rates of d-xylose in the presence of d-glucose, as well as elevated maximum rates of metabolism ( V max ) for both d-glucose and d-xylose transport. The data suggest that the increased expression of multiple hexose transporters renders d-xylose metabolism less sensitive to d-glucose inhibition due to an elevated transport rate of d-xylose into the cell. IMPORTANCE The yeast Saccharomyces cerevisiae is used for second-generation bioethanol formation. However, growth on xylose is limited by pentose transport through the endogenous hexose transporters (HXTs), as uptake is outcompeted by the preferred substrate, glucose. Mutant strains were obtained with improved growth characteristics on xylose in the presence of glucose, and the mutations mapped to the regulator Cyc8. The inactivation of Cyc8 caused increased

Prevalence and characteristics of metabolic syndrome in adults from the French childhood leukemia survivors’ cohort: a comparison with controls from the French population

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Oudin, Claire; Berbis, Julie; Bertrand, Yves; Vercasson, Camille; Thomas, Frédérique; Chastagner, Pascal; Ducassou, Stéphane; Kanold, Justyna; Tabone, Marie-Dominique; Paillard, Catherine; Poirée, Marilyne; Plantaz, Dominique; Dalle, Jean-Hugues; Gandemer, Virginie; Thouvenin, Sandrine; Sirvent, Nicolas; Saultier, Paul; Béliard, Sophie; Leverger, Guy; Baruchel, André; Auquier, Pascal; Pannier, Bruno; Michel, Gérard

2018-01-01

The prevalence of the metabolic syndrome among adults from the French LEA childhood acute leukemia survivors’ cohort was prospectively evaluated considering the type of anti-leukemic treatment received, and compared with that of controls. The metabolic profile of these patients was compared with that of controls. A total of 3203 patients from a French volunteer cohort were age- and sex-matched 3:1 to 1025 leukemia survivors (in both cohorts, mean age: 24.4 years; females: 51%). Metabolic syndrome was defined according to the National Cholesterol Education Program’s Adult Treatment Panel III criteria. Metabolic syndrome was found in 10.3% of patients (mean follow-up duration: 16.3±0.2 years) and 4.5% of controls, (OR=2.49; Pmetabolic syndrome displayed a unique profile compared with controls: smaller waist circumference (91 vs. 99.6 cm; P=0.01), and increased triglyceride levels (3.99 vs. 1.5 mmol/L; Pmetabolic syndrome had a larger waist circumference (109 vs. 99.6 cm; P=0.007) than controls. Regardless of the anti-leukemic treatment, metabolic syndrome risk was higher among childhood leukemia survivors. Its presentation differed depending on the treatment type, thus suggesting a divergent pathophysiology. This study is registered at clinicaltrials.gov identifier: 01756599. PMID:29351982

Pathophysiology and therapeutics of cardiovascular disease in metabolic syndrome.

Science.gov (United States)

Wang, Yabin; Yu, Qiujun; Chen, Yundai; Cao, Feng

2013-01-01

The metabolic syndrome (MetS) is characterized by a cluster of cardiovascular risk factors, including central obesity, hyperglycemia, dyslipidemia and hypertension, which are highly associated with increased morbidity and mortality of cardiovascular diseases (CVD). The association between these metabolic disorders and the development of CVD is believed to be multifactorial, where insulin resistance, oxidative stress, low-grade inflammation and vascular maladaptation act as the major contributors. Therefore, multipronged therapeutic strategies should be taken for the management of patients with MetS. Lifestyle changes including weight control, healthy heart diet and regular exercises have been proposed as first line treatment to decrease CVD risks in MetS individuals. In addition, improving insulin resistance and glucose metabolism, controlling blood pressure as well as modulating dyslipidemia can also delay or reverse the progression of CVD in MetS. This review will first address the complicated interactions between MetS and CVD¸ followed by discussion about the optimal strategy in the prevention and treatment of CVD in MetS patients and the updated results from newly released clinical trials.

Overexpression of a water-forming NADH oxidase improves the metabolism and stress tolerance of Saccharmyces cerevisiae in aerobic fermenation

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Xinchi Shi

2016-09-01

Full Text Available Redox homeostasis is fundamental to the maintenance of metabolism. Redox imbalance can cause oxidative stress, which affects metabolism and growth. Water-forming NADH oxidase regulates the redox balance by oxidizing cytosolic NADH to NAD+, which relieves cytosolic NADH accumulation through rapid glucose consumption in Saccharomyces cerevisiae, thus decreasing the production of the byproduct glycerol in industrial ethanol production. Here, we studied the effects of overexpression of a water-forming NADH oxidase from Lactococcus lactis on the stress response of S. cerevisiae in aerobic batch fermentation, and we constructed an interaction network of transcriptional regulation and metabolic networks to study the effects of and mechanisms underlying NADH oxidase regulation. The oxidase-overexpressing strain (NOX showed increased glucose consumption, growth, and ethanol production, while glycerol production was remarkably lower. Glucose was exhausted by NOX at 26 h, while 18.92 ± 0.94 g/L residual glucose was left in the fermentation broth of the control strain (CON at this time point. At 29.5 h, the ethanol concentration for NOX peaked at 35.25 ± 1.76 g/L, which was 14.37 % higher than that for CON (30.82 ± 1.54 g/L. Gene expression involved in the synthesis of thiamine, which is associated with stress responses in various organisms, was increased in NOX. The transcription factor HAP4 was significantly upregulated in NOX at the late-exponential phase, indicating a diauxic shift in response to starvation. The apoptosis-inducing factor Nuc1 was downregulated while the transcription factor Sok2, which regulates the production of the small signaling molecule ammonia, was upregulated at the late-exponential phase, benefiting young cells on the rim. Reactive oxygen species production was decreased by 10% in NOX, supporting a decrease in apoptosis. The HOG pathway was not activated, although the osmotic stress was truly higher, indicating improved

Deranged Cardiac Metabolism and the Pathogenesis of Heart Failure

Science.gov (United States)

2016-01-01

Activation of the neuro-hormonal system is a pathophysiological consequence of heart failure. Neuro-hormonal activation promotes metabolic changes, such as insulin resistance, and determines an increased use of non-carbohydrate substrates for energy production. Fasting blood ketone bodies as well as fat oxidation are increased in patients with heart failure, yielding a state of metabolic inefficiency. The net result is additional depletion of myocardial adenosine triphosphate, phosphocreatine and creatine kinase levels with further decreased efficiency of mechanical work. In this context, manipulation of cardiac energy metabolism by modification of substrate use by the failing heart has produced positive clinical results. The results of current research support the concept that shifting the energy substrate preference away from fatty acid metabolism and towards glucose metabolism could be an effective adjunctive treatment in patients with heart failure. The additional use of drugs able to partially inhibit fatty acids oxidation in patients with heart failure may therefore yield a significant protective effect for clinical symptoms and cardiac function improvement, and simultaneously ameliorate left ventricular remodelling. Certainly, to clarify the exact therapeutic role of metabolic therapy in heart failure, a large multicentre, randomised controlled trial should be performed. PMID:28785448

The medical food Souvenaid affects brain phospholipid metabolism in mild Alzheimer's disease: results from a randomized controlled trial.

Science.gov (United States)

Rijpma, Anne; van der Graaf, Marinette; Lansbergen, Marieke M; Meulenbroek, Olga; Cetinyurek-Yavuz, Aysun; Sijben, John W; Heerschap, Arend; Olde Rikkert, Marcel G M

2017-07-26

Synaptic dysfunction contributes to cognitive impairment in Alzheimer's disease and may be countered by increased intake of nutrients that target brain phospholipid metabolism. In this study, we explored whether the medical food Souvenaid affects brain phospholipid metabolism in patients with Alzheimer's disease. Thirty-four drug-naive patients with mild Alzheimer's disease (Mini Mental State Examination score ≥20) were enrolled in this exploratory, double-blind, randomized controlled study. Before and after 4-week intervention with Souvenaid or an isocaloric control product, phosphorus and proton magnetic resonance spectroscopy (MRS) was performed to assess surrogate measures of phospholipid synthesis and breakdown (phosphomonoesters [PME] and phosphodiesters [PDEs]), neural integrity (N-acetyl aspartate), gliosis (myo-inositol), and choline metabolism (choline-containing compounds [tCho]). The main outcome parameters were PME and PDE signal intensities and the PME/PDE ratio. MRS data from 33 patients (60-86 years old; 42% males; Souvenaid arm n = 16; control arm n = 17) were analyzed. PME/PDE and tCho were higher after 4 weeks of Souvenaid compared with control (PME/PDE least squares [LS] mean difference [95% CI] 0.18 [0.06-0.30], p = 0.005; tCho LS mean difference [95% CI] 0.01 [0.00-0.02], p = 0.019). No significant differences were observed in the other MRS outcome parameters. MRS reveals that Souvenaid affects brain phospholipid metabolism in mild Alzheimer's disease, in line with findings in preclinical studies. Netherlands Trial Register, NTR3346 . Registered on 13 March 2012.

Continued improvement of cardiovascular mortality in Hungary - impact of increased cardio-metabolic prescriptions

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Jozan Peter

2010-07-01

Full Text Available Abstract Background During the last 35 years the poor ranking of Hungary on the list of life expectancy at birth among European countries, has not changed. In 1970 our lag behind the leading European countries was the smallest. The gap was growing between 1970 and 1993 but from 1994 onwards the life expectancy at birth in Hungary has increased continuously and somewhat faster than in other European countries. The aim of this study was to analyze the association between decreasing cardiovascular mortality rates, as a main cause of death and the increase in cardio-metabolic prescriptions and possible changes in lifestyle behavior. Methods Analyses were conducted on national data concerning cardiovascular mortality and the number of cardio-metabolic drug prescription per capita. The association between yearly rates of cardiovascular events and changes in antihypertensive, antilipidemic and antidiabetic prescription rates was analyzed. The changes in other cardiovascular risk factors, like lifestyle were also considered. Results We observed a remarkable decline of mortality due to stroke and acute myocardial infarction (AMI. The fall was significantly associated with all prescription rates. The proportion of each treatment type responsible for suppression of specific mortality rates is different. All treatment types comparably improved stroke mortality, while antilipidemic therapy improved AMI outcome. Conclusions These results emphasize the importance of a comprehensive strategy that maximizes the population coverage of effective treatments. Hungary appears to be at the beginning of the fourth stage of epidemiologic transition, i.e. it has entered the stage of delayed chronic noninfectious diseases.

Cancer metabolism meets systems biology: Pyruvate kinase isoform PKM2 is a metabolic master regulator

OpenAIRE

Fabian V Filipp

2013-01-01

Pyruvate kinase activity is controlled by a tightly woven regulatory network. The oncofetal isoform of pyruvate kinase (PKM2) is a master regulator of cancer metabolism. PKM2 engages in parallel, feed-forward, positive and negative feedback control contributing to cancer progression. Besides its metabolic role, non-metabolic functions of PKM2 as protein kinase and transcriptional coactivator for c-MYC and hypoxia-inducible factor 1-alpha are essential for epidermal growth factor receptor acti...

Improved growth rate in Clostridium thermocellum hydrogenase mutant via perturbed sulfur metabolism.

Science.gov (United States)

Biswas, Ranjita; Wilson, Charlotte M; Giannone, Richard J; Klingeman, Dawn M; Rydzak, Thomas; Shah, Manesh B; Hettich, Robert L; Brown, Steven D; Guss, Adam M

2017-01-01

Metabolic engineering is a commonly used approach to develop organisms for an industrial function, but engineering aimed at improving one phenotype can negatively impact other phenotypes. This lack of robustness can prove problematic. Cellulolytic bacterium Clostridium thermocellum is able to rapidly ferment cellulose to ethanol and other products. Recently, genes involved in H 2 production, including the hydrogenase maturase hydG and NiFe hydrogenase ech , were deleted from the chromosome of C. thermocellum . While ethanol yield increased, the growth rate of Δ hydG decreased substantially compared to wild type. Addition of 5 mM acetate to the growth medium improved the growth rate in C. thermocellum ∆hydG , whereas wild type remained unaffected. Transcriptomic analysis of the wild type showed essentially no response to the addition of acetate. However, in C. thermocellum ΔhydG , 204 and 56 genes were significantly differentially regulated relative to wild type in the absence and presence of acetate, respectively. Genes, Clo1313_0108-0125, which are predicted to encode a sulfate transport system and sulfate assimilatory pathway, were drastically upregulated in C. thermocellum ΔhydG in the presence of added acetate. A similar pattern was seen with proteomics. Further physiological characterization demonstrated an increase in sulfide synthesis and elimination of cysteine consumption in C. thermocellum ΔhydG . Clostridium thermocellum ΔhydGΔech had a higher growth rate than ΔhydG in the absence of added acetate, and a similar but less pronounced transcriptional and physiological effect was seen in this strain upon addition of acetate. Sulfur metabolism is perturbed in C. thermocellum ΔhydG strains, likely to increase flux through sulfate reduction to act either as an electron sink to balance redox reactions or to offset an unknown deficiency in sulfur assimilation.

Control of (pre-analytical aspects in immunoassay measurements of metabolic hormones in rodents

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Maximilian Bielohuby

2018-04-01

Full Text Available The measurement of circulating hormones by immunoassay remains a cornerstone in preclinical endocrine research. For scientists conducting and interpreting immunoassay measurements of rodent samples, the paramount aim usually is to obtain reliable and meaningful measurement data in order to draw conclusions on biological processes. However, the biological variability between samples is not the only variable affecting the readout of an immunoassay measurement and a considerable amount of unwanted or unintended variability can be quickly introduced during the pre-analytical and analytical phase. This review aims to increase the awareness for the factors ‘pre-analytical’ and ‘analytical’ variability particularly in the context of immunoassay measurement of circulating metabolic hormones in rodent samples. In addition, guidance is provided how to gain control over these variables and how to avoid common pitfalls associated with sample collection, processing, storage and measurement. Furthermore, recommendations are given on how to perform a basic validation of novel single and multiplex immunoassays for the measurement of metabolic hormones in rodents. Finally, practical examples from immunoassay measurements of plasma insulin in mice address the factors ‘sampling site and inhalation anesthesia’ as frequent sources of introducing an unwanted variability during the pre-analytical phase. The knowledge about the influence of both types of variability on the immunoassay measurement of circulating hormones as well as strategies to control these variables are crucial, on the one hand, for planning and realization of metabolic rodent studies and, on the other hand, for the generation and interpretation of meaningful immunoassay data from rodent samples.

Negative Affectivity Predicts Lower Quality of Life and Metabolic Control in Type 2 Diabetes Patients: A Structural Equation Modeling Approach

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Chiara Conti

2017-05-01

Full Text Available Introduction: It is essential to consider the clinical assessment of psychological aspects in patients with Diabetes Mellitus (DM, in order to prevent potentially adverse self-management care behaviors leading to diabetes-related complications, including declining levels of Quality of Life (QoL and negative metabolic control.Purpose: In the framework of Structural Equation Modeling (SEM, the specific aim of this study is to evaluate the influence of distressed personality factors as Negative Affectivity (NA and Social Inhibition (SI on diabetes-related clinical variables (i.e., QoL and glycemic control.Methods: The total sample consists of a clinical sample, including 159 outpatients with Type 2 Diabetes Mellitus (T2DM, and a control group composed of 102 healthy respondents. All participants completed the following self- rating scales: The Type D Scale (DS14 and the World Health Organization QoL Scale (WHOQOLBREF. Furthermore, the participants of the clinical group were assessed for HbA1c, disease duration, and BMI. The observed covariates were BMI, gender, and disease duration, while HbA1c was considered an observed variable.Results: SEM analysis revealed significant differences between groups in regards to the latent construct of NA and the Environmental dimension of QoL. For the clinical sample, SEM showed that NA had a negative impact on both QoL dimensions and metabolic control.Conclusions: Clinical interventions aiming to improve medication adherence in patients with T2DM should include the psychological evaluation of Type D Personality traits, by focusing especially on its component of NA as a significant risk factor leading to negative health outcomes.

Low fish oil intake improves insulin sensitivity, lipid profile and muscle metabolism on insulin resistant MSG-obese rats

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Iagher Fabiola

2011-04-01

Full Text Available Abstract Background Obesity is commonly associated with diabetes, cardiovascular diseases and cancer. The purpose of this study was to determinate the effect of a lower dose of fish oil supplementation on insulin sensitivity, lipid profile, and muscle metabolism in obese rats. Methods Monosodium glutamate (MSG (4 mg/g body weight was injected in neonatal Wistar male rats. Three-month-old rats were divided in normal-weight control group (C, coconut fat-treated normal weight group (CO, fish oil-treated normal weight group (FO, obese control group (Ob, coconut fat-treated obese group (ObCO and fish oil-treated obese group (ObFO. Obese insulin-resistant rats were supplemented with fish oil or coconut fat (1 g/kg/day for 4 weeks. Insulin sensitivity, fasting blood biochemicals parameters, and skeletal muscle glucose metabolism were analyzed. Results Obese animals (Ob presented higher Index Lee and 2.5 fold epididymal and retroperitoneal adipose tissue than C. Insulin sensitivity test (Kitt showed that fish oil supplementation was able to maintain insulin sensitivity of obese rats (ObFO similar to C. There were no changes in glucose and HDL-cholesterol levels amongst groups. Yet, ObFO revealed lower levels of total cholesterol (TC; 30% and triacylglycerol (TG; 33% compared to Ob. Finally, since exposed to insulin, ObFO skeletal muscle revealed an increase of 10% in lactate production, 38% in glycogen synthesis and 39% in oxidation of glucose compared to Ob. Conclusions Low dose of fish oil supplementation (1 g/kg/day was able to reduce TC and TG levels, in addition to improved systemic and muscle insulin sensitivity. These results lend credence to the benefits of n-3 fatty acids upon the deleterious effects of insulin resistance mechanisms.

Effect of a fermented dietary supplement containing chromium and zinc on metabolic control in patients with type 2 diabetes: a randomized, placebo-controlled, double-blind cross-over study

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Yu-Mi Lee

2016-06-01

Full Text Available Background: For the increasing development of type 2 diabetes dietary habits play an important role. In this regard, dietary supplements are of growing interest to influence the progression of this disease. Objective: The aim of this study was to investigate the effect of a cascade-fermented dietary supplement based on fruits, nuts, and vegetables fortified with chromium and zinc on metabolic control in patients with type 2 diabetes mellitus. Methods: This was a randomized, placebo-controlled, double-blind, intervention study under free-living conditions using a cross-over design. Thirty-six patients with type 2 diabetes mellitus were enrolled and randomized either to receive a cascade-fermented dietary supplement enriched with chromium (100 µg/d and zinc (15 mg/d or a placebo similar in taste but without supplements, over a period of 12 weeks. After a wash-out period of 12 weeks, the patients received the other test product. The main outcome variable was the levels of glycated hemoglobin (HbA1c. Other outcome variables were fasting blood glucose, fructosamine, and lipid parameters. Results: Thirty-one patients completed the study. HbA1c showed no relevant changes during both treatment periods, nor was there a relevant difference between the two treatments (HbA1c: p=0.48. The same results were found for fructosamine and fasting glucose (fructosamine: p=0.9; fasting glucose: p=0.31. In addition, there was no effect on lipid metabolism. Conclusion: This intervention study does not provide evidence that a cascade-fermented plant-based dietary supplement enriched with a combination of chromium and zinc improves glucose metabolism in patients with type 2 diabetes mellitus under free-living conditions.

Interplay between FGF21 and insulin action in the liver regulates metabolism

DEFF Research Database (Denmark)

Emanuelli, Brice; Vienberg, Sara G; Smyth, Graham

2014-01-01

gluconeogenesis in these animals. Improvements in blood sugar were due in part to increased glucose uptake in brown fat, browning of white fat, and overall increased energy expenditure. These effects were preserved even after removal of the main interscapular brown fat pad. In contrast to its retained effects...... of insulin action in the liver by increasing energy metabolism via activation of brown fat and browning of white fat, but intact liver insulin action is required for FGF21 to control hepatic lipid metabolism....

EFFECT OF DANCE EXERCISE ON COGNITIVE FUNCTION IN ELDERLY PATIENTS WITH METABOLIC SYNDROME: A PILOT STUDY

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Sang-Wook Song

2011-12-01

Full Text Available Metabolic syndrome is associated with an increased risk of cognitive impairment. The purpose of this prospective pilot study was to examine the effects of dance exercise on cognitive function in elderly patients with metabolic syndrome. The participants included 38 elderly metabolic syndrome patients with normal cognitive function (26 exercise group and 12 control group. The exercise group performed dance exercise twice a week for 6 months. Cognitive function was assessed in all participants using the Korean version of the Consortium to Establish a Registry for Alzheimer's disease (CERAD-K. Repeated-measures ANCOVA was used to assess the effect of dance exercise on cognitive function and cardiometabolic risk factors. Compared with the control group, the exercise group significantly improved in verbal fluency (p = 0.048, word list delayed recall (p = 0.038, word list recognition (p = 0.007, and total CERAD-K score (p = 0.037. However, no significance difference was found in body mass index, blood pressure, waist circumference, fasting plasma glucose, triglyceride, and HDL cholesterol between groups over the 6-month period. In the present study, six months of dance exercise improved cognitive function in older adults with metabolic syndrome. Thus, dance exercise may reduce the risk for cognitive disorders in elderly people with metabolic syndrome.

Exploitation of dietary tannins to improve rumen metabolism and ruminant nutrition.

Science.gov (United States)

Patra, Amlan K; Saxena, Jyotisna

2011-01-15

Tannins (hydrolysable and condensed tannin) are polyphenolic polymers of relatively high molecular weight with the capacity to form complexes mainly with proteins due to the presence of a large number of phenolic hydroxyl groups. They are widely distributed in nutritionally important forage trees, shrubs and legumes, cereals and grains, which are considered as anti-nutritional compounds due to their adverse effects on intake and animal performance. However, tannins have been recognised to modulate rumen fermentation favourably such as reducing protein degradation in the rumen, prevention of bloat, inhibition of methanogenesis and increasing conjugated linoleic acid concentrations in ruminant-derived foods. The inclusion of tannins in diets has been shown to improve body weight and wool growth, milk yields and reproductive performance. However, the beneficial effects on rumen modulation and animal performance have not been consistently observed. This review discusses the effects of tannins on nitrogen metabolism in the rumen and intestine, and microbial populations (bacteria, protozoa, fungi and archaea), metabolism of tannins, microbial tolerance mechanisms to tannins, inhibition of methanogenesis, ruminal biohydrogenation processes and performance of animals. The discrepancies of responses of tannins among different studies are attributed to the different chemical structures (degree of polymerisation, procyanidins to propdelphinidins, stereochemistry and C-C bonding) and concentrations of tannins, and type of diets. An establishment of structure-activity relationship would be required to explain differences among studies and obtain consistent beneficial tannin effects. Copyright © 2010 Society of Chemical Industry.

Coconut Products Improve Signs of Diet-Induced Metabolic Syndrome in Rats.

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Panchal, Sunil K; Carnahan, Sharyn; Brown, Lindsay

2017-12-01

Increasing prevalence of obesity and metabolic syndrome warrants identification of potential therapeutic options for intervention. This study tested commercially available Virgin Coconut Oil and Coconut Nourish, as coconuts are rich sources of lauric and myristic acids. Male Wistar rats were fed either corn starch diet (C); high-carbohydrate, high-fat diet (H); high-carbohydrate, high-virgin coconut oil diet (HV); or high-carbohydrate, high-coconut Nourish diet (HN) for 16 weeks. Metabolic, liver, and cardiovascular health parameters were measured during and at the end of the study. Virgin coconut oil lowered body weight (C 386±8g, H 516±13g, HV 459±10g), blood glucose concentrations (C 4.2±0.1 mmol/L, H 5.4±0.2 mmol/L, HV 4.6±0.2 mmol/L), systolic blood pressure (C 127±5mmHg, H 149±4mmHg, HV 133±3mmHg,) and diastolic stiffness (C 25.0±1.7, H 31.4±1.2, HV 25.2±2.3,) with improved structure and function of the heart and liver. Coconut Nourish increased total body lean mass (C 255±10g, H 270±16g, HN 303±15g) and lowered plasma total cholesterol concentrations (C 1.6±0.2 mmol/L, H 1.7±0.1 mmol/L, HN 1.0±0.0 mmol/L), systolic blood pressure (C 127±5mmHg, H 149±4mmHg, HN 130±3mmHg) and diastolic stiffness (C 25.0±1.7, H 31.4±1.2, HN 26.5±1.0), improved structure and function of the heart and liver but increased plasma concentrations of triglycerides (C 0.3±0.1 mmol/L, H 1.1±0.4 mmol/L, HN 1.8±0.2 mmol/L) and non-esterified fatty acids (C 1.2±0.3 mmol/L, H 3.3±0.8 mmol/L, HN 5.6±0.4 mmol/L). Thus, the fiber and protein in coconut Nourish and the medium-chain saturated fatty acids in virgin coconut oil may improve cardiovascular and liver complications in obesity.

Repletion of branched chain amino acids reverses mTORC1 signaling but not improved metabolism during dietary protein dilution

DEFF Research Database (Denmark)

Maida, Adriano; Chan, Jessica S K; Sjøberg, Kim Anker

2017-01-01

OBJECTIVE: Dietary protein dilution (PD) has been associated with metabolic advantages such as improved glucose homeostasis and increased energy expenditure. This phenotype involves liver-induced release of FGF21 in response to amino acid insufficiency; however, it has remained unclear whether...... dietary dilution of specific amino acids (AAs) is also required. Circulating branched chain amino acids (BCAAs) are sensitive to protein intake, elevated in the serum of obese humans and mice and thought to promote insulin resistance. We tested whether replenishment of dietary BCAAs to an AA-diluted (AAD......) diet is sufficient to reverse the glucoregulatory benefits of dietary PD. METHODS: We conducted AA profiling of serum from healthy humans and lean and high fat-fed or New Zealand obese (NZO) mice following dietary PD. We fed wildtype and NZO mice one of three amino acid defined diets: control, total...

Metabolic cartography: experimental quantification of metabolic fluxes from isotopic labelling studies.

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O'Grady, John; Schwender, Jörg; Shachar-Hill, Yair; Morgan, John A

2012-03-01

For the past decade, flux maps have provided researchers with an in-depth perspective on plant metabolism. As a rapidly developing field, significant headway has been made recently in computation, experimentation, and overall understanding of metabolic flux analysis. These advances are particularly applicable to the study of plant metabolism. New dynamic computational methods such as non-stationary metabolic flux analysis are finding their place in the toolbox of metabolic engineering, allowing more organisms to be studied and decreasing the time necessary for experimentation, thereby opening new avenues by which to explore the vast diversity of plant metabolism. Also, improved methods of metabolite detection and measurement have been developed, enabling increasingly greater resolution of flux measurements and the analysis of a greater number of the multitude of plant metabolic pathways. Methods to deconvolute organelle-specific metabolism are employed with increasing effectiveness, elucidating the compartmental specificity inherent in plant metabolism. Advances in metabolite measurements have also enabled new types of experiments, such as the calculation of metabolic fluxes based on (13)CO(2) dynamic labelling data, and will continue to direct plant metabolic engineering. Newly calculated metabolic flux maps reveal surprising and useful information about plant metabolism, guiding future genetic engineering of crops to higher yields. Due to the significant level of complexity in plants, these methods in combination with other systems biology measurements are necessary to guide plant metabolic engineering in the future.

The post-transcriptional regulatory system CSR controls the balance of metabolic pools in upper glycolysis of Escherichia coli.

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Morin, Manon; Ropers, Delphine; Letisse, Fabien; Laguerre, Sandrine; Portais, Jean-Charles; Cocaign-Bousquet, Muriel; Enjalbert, Brice

2016-05-01

Metabolic control in Escherichia coli is a complex process involving multilevel regulatory systems but the involvement of post-transcriptional regulation is uncertain. The post-transcriptional factor CsrA is stated as being the only regulator essential for the use of glycolytic substrates. A dozen enzymes in the central carbon metabolism (CCM) have been reported as potentially controlled by CsrA, but its impact on the CCM functioning has not been demonstrated. Here, a multiscale analysis was performed in a wild-type strain and its isogenic mutant attenuated for CsrA (including growth parameters, gene expression levels, metabolite pools, abundance of enzymes and fluxes). Data integration and regulation analysis showed a coordinated control of the expression of glycolytic enzymes. This also revealed the imbalance of metabolite pools in the csrA mutant upper glycolysis, before the phosphofructokinase PfkA step. This imbalance is associated with a glucose-phosphate stress. Restoring PfkA activity in the csrA mutant strain suppressed this stress and increased the mutant growth rate on glucose. Thus, the carbon storage regulator system is essential for the effective functioning of the upper glycolysis mainly through its control of PfkA. This work demonstrates the pivotal role of post-transcriptional regulation to shape the carbon metabolism. © 2016 John Wiley & Sons Ltd.

Instrument ampersand controls section (IA) improvements

International Nuclear Information System (INIS)

Kramer, C.; Paul, J.

1993-01-01

This portion of the panel session briefly delineates improvements in the Instrument and Controls (IA) Section over the past few years. These improvements are listed briefly in summary form. The status of publication of the IA Section of AG-1 is reviewed

Natto and viscous vegetables in a Japanese-style breakfast improved insulin sensitivity, lipid metabolism and oxidative stress in overweight subjects with impaired glucose tolerance.

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Taniguchi-Fukatsu, Akiko; Yamanaka-Okumura, Hisami; Naniwa-Kuroki, Yuko; Nishida, Yuka; Yamamoto, Hironori; Taketani, Yutaka; Takeda, Eiji

2012-04-01

We previously suggested that the consumption of natto and viscous vegetables as part of a Japanese-style meal based on white rice (WR) reduced postprandial glucose and insulin levels in healthy subjects. The aim of the present study was to assess whether a single breakfast of natto and viscous vegetables or the same breakfast consumed for 2 weeks could improve glucose control, insulin sensitivity, lipid metabolism and oxidative stress in overweight subjects with impaired glucose tolerance (IGT). A total of eleven free-living subjects with IGT followed a randomised, crossover breakfast intervention for 2 weeks. The test meal included boiled WR with natto (viscous fermented soyabeans), Japanese yam and okra. The control meal included WR with non-viscous boiled soyabeans, potatoes and broccoli. Both meals contained comparable amounts of carbohydrate, fat, protein and fibre. The test meal reduced acute glucose and insulin responses compared to the control meal in the study participants. Insulin sensitivity was assessed using the composite insulin sensitivity index (CISI) after both the test and control meal periods. The test meal resulted in improvements in CISI compared to the baseline, whereas no significant changes were observed after the control meal period. Serum levels of both total and LDL-cholesterol were assessed before and after the test meal period and found to decrease significantly. There was also a tendency towards reduced serum malondialdehyde-modified LDL and N(ɛ)-carboxymethyllysine. No differences were observed in the measures of chronic glycaemic control. Thus, we conclude that a breakfast of natto and viscous vegetables consumed for 2 weeks improves insulin sensitivity, serum lipid and oxidative stress.

Topiramate improves neurovascular function, epidermal nerve fiber morphology, and metabolism in patients with type 2 diabetes mellitus

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Boyd A

2010-12-01

Full Text Available Amanda L Boyd, Patricia M Barlow, Gary L Pittenger, Kathryn F Simmons, Aaron I VinikDepartment of Internal Medicine, Eastern Virginia Medical School, Norfolk, VA, USAPurpose: To assess the effects of topiramate on C-fiber function, nerve fiber morphology, and metabolism (including insulin sensitivity, obesity, and dyslipidemia in type 2 diabetes.Patients and methods: We conducted an 18-week, open-label trial treating patients with topiramate. Twenty subjects with type 2 diabetes and neuropathy (61.5 ± 1.29 years; 15 male, 5 female were enrolled and completed the trial. Neuropathy was evaluated by total neuropathy scores, nerve conduction studies, quantitative sensory tests, laser Doppler skin blood flow, and intraepidermal nerve fibers in skin biopsies.Results: Topiramate treatment improved symptoms compatible with C-fiber dysfunction. Weight, blood pressure, and hemoglobin A1c also improved. Laser Doppler skin blood flow improved significantly after 12 weeks of treatment, but returned to baseline at 18 weeks. After 18 weeks of treatment there was a significant increase in intraepidermal nerve fiber length at the forearm, thigh, and proximal leg. Intraepidermal nerve fiber density was significantly increased by topiramate in the proximal leg.Conclusion: This study is the first to demonstrate that it is possible to induce skin intraepidermal nerve fiber regeneration accompanied by enhancement of neurovascular function, translating into improved symptoms as well as sensory nerve function. The simultaneous improvement of selective metabolic indices may play a role in this effect, but this remains to be determined.Keywords: diabetic neuropathy, skin blood flow, skin biopsy, diabetes

Randomized placebo control study of metformin in psoriasis patients with metabolic syndrome (systemic treatment cohort

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Surjit Singh

2017-01-01

Full Text Available Background: Psoriasis has been found to be associated with obesity, metabolic syndrome (MS, diabetes, and cardiovascular risk factors. Metformin treatment showed improvement in cardiovascular risk factors and hyperinsulinemia. Objective: To evaluate the efficacy and safety of metformin in psoriasis patients with MS. Materials and Methods: This was a single-center, parallel-group, randomized, open-label study with blinded end point assessment of metformin (1000 mg once daily for 12 weeks; n = 20 and placebo (n = 18 in psoriasis patients with MS. Total sample size was 38 participants. Results: Statistically significant improvement was observed in mean percentage change in erythema, scaling, and induration (ESI (P = 0.048 in metformin as compared to placebo while mean percentage change in psoriasis area and severity index (PASI and physician global assessment (PGA scores was not significant (PASI - P = 0.215, PGA - P = 0.070. There was a statistically significant difference in percentage of parameters of MS improved following 12 weeks of treatment in metformin (19% as compared to placebo (8.9% group (P = 0.046. Statistically significant difference in percentage of patients achieving 75% reduction in ESI scores (P = 0.024. Significant improvement was observed in mean weight, body mass index (BMI, total cholesterol, and low-density lipoprotein (LDL cholesterol in metformin group as compared to placebo. Improvement in BMI, fasting plasma glucose, serum triglycerides, high-density lipoprotein, LDL, systolic blood pressure, diastolic blood pressure, and total cholesterol was statistically significant in metformin group over the period of 12 weeks. There was no significant difference in adverse events in two groups except weight gain. Conclusion: Metformin has shown improvement in psoriasis and parameters of MS, hence can be used for the benefit of psoriasis patients having MS. Large, controlled studies are needed to confirm.

Does Self-Control Training Improve Self-Control? A Meta-Analysis.

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Friese, Malte; Frankenbach, Julius; Job, Veronika; Loschelder, David D

2017-11-01

Self-control is positively associated with a host of beneficial outcomes. Therefore, psychological interventions that reliably improve self-control are of great societal value. A prominent idea suggests that training self-control by repeatedly overriding dominant responses should lead to broad improvements in self-control over time. Here, we conducted a random-effects meta-analysis based on robust variance estimation of the published and unpublished literature on self-control training effects. Results based on 33 studies and 158 effect sizes revealed a small-to-medium effect of g = 0.30, confidence interval (CI 95 ) [0.17, 0.42]. Moderator analyses found that training effects tended to be larger for (a) self-control stamina rather than strength, (b) studies with inactive compared to active control groups, (c) males than females, and (d) when proponents of the strength model of self-control were (co)authors of a study. Bias-correction techniques suggested the presence of small-study effects and/or publication bias and arrived at smaller effect size estimates (range: g corrected = .13 to .24). The mechanisms underlying the effect are poorly understood. There is not enough evidence to conclude that the repeated control of dominant responses is the critical element driving training effects.

Energy Metabolism in the Liver

Science.gov (United States)

Rui, Liangyou

2014-01-01

The liver is an essential metabolic organ, and its metabolic activity is tightly controlled by insulin and other metabolic hormones. Glucose is metabolized into pyruvate through glycolysis in the cytoplasm, and pyruvate is completely oxidized to generate ATP through the TCA cycle and oxidative phosphorylation in the mitochondria. In the fed state, glycolytic products are used to synthesize fatty acids through de novo lipogenesis. Long-chain fatty acids are incorporated into triacylglycerol, phospholipids, and cholesterol esters in hepatocytes, and these complex lipids are stored in lipid droplets and membrane structures, or secreted into the circulation as VLDL particles. In the fasted state, the liver secretes glucose through both breakdown of glycogen (glycogenolysis) and de novo glucose synthesis (gluconeogenesis). During pronged fasting, hepatic gluconeogenesis is the primary source of endogenous glucose production. Fasting also promotes lipolysis in adipose tissue to release nonesterified fatty acids which are converted into ketone bodies in the liver though mitochondrial β oxidation and ketogenesis. Ketone bodies provide a metabolic fuel for extrahepatic tissues. Liver metabolic processes are tightly regulated by neuronal and hormonal systems. The sympathetic system stimulates, whereas the parasympathetic system suppresses, hepatic gluconeogenesis. Insulin stimulates glycolysis and lipogenesis, but suppresses gluconeogenesis; glucagon counteracts insulin action. Numerous transcription factors and coactivators, including CREB, FOXO1, ChREBP, SREBP, PGC-1α, and CRTC2, control the expression of the enzymes which catalyze the rate-limiting steps of liver metabolic processes, thus controlling liver energy metabolism. Aberrant energy metabolism in the liver promotes insulin resistance, diabetes, and nonalcoholic fatty liver diseases (NAFLD). PMID:24692138

Metabolic pathways regulated by abscisic acid, salicylic acid and γ-aminobutyric acid in association with improved drought tolerance in creeping bentgrass (Agrostis stolonifera).

Science.gov (United States)

Li, Zhou; Yu, Jingjin; Peng, Yan; Huang, Bingru

2017-01-01

Abscisic acid (ABA), salicylic acid (SA) and γ-aminobutyric acid (GABA) are known to play roles in regulating plant stress responses. This study was conducted to determine metabolites and associated pathways regulated by ABA, SA and GABA that could contribute to drought tolerance in creeping bentgrass (Agrostis stolonifera). Plants were foliar sprayed with ABA (5 μM), GABA (0.5 mM) and SA (10 μM) or water (untreated control) prior to 25 days drought stress in controlled growth chambers. Application of ABA, GABA or SA had similar positive effects on alleviating drought damages, as manifested by the maintenance of lower electrolyte leakage and greater relative water content in leaves of treated plants relative to the untreated control. Metabolic profiling showed that ABA, GABA and SA induced differential metabolic changes under drought stress. ABA mainly promoted the accumulation of organic acids associated with tricarboxylic acid cycle (aconitic acid, succinic acid, lactic acid and malic acid). SA strongly stimulated the accumulation of amino acids (proline, serine, threonine and alanine) and carbohydrates (glucose, mannose, fructose and cellobiose). GABA enhanced the accumulation of amino acids (GABA, glycine, valine, proline, 5-oxoproline, serine, threonine, aspartic acid and glutamic acid) and organic acids (malic acid, lactic acid, gluconic acid, malonic acid and ribonic acid). The enhanced drought tolerance could be mainly due to the enhanced respiration metabolism by ABA, amino acids and carbohydrates involved in osmotic adjustment (OA) and energy metabolism by SA, and amino acid metabolism related to OA and stress-defense secondary metabolism by GABA. © 2016 Scandinavian Plant Physiology Society.

Hypothalamic control of energy and glucose metabolism.

Science.gov (United States)

Sisley, Stephanie; Sandoval, Darleen

2011-09-01

The central nervous system (CNS), generally accepted to regulate energy homeostasis, has been implicated in the metabolic perturbations that either cause or are associated with obesity. Normally, the CNS receives hormonal, metabolic, and neuronal input to assure adequate energy levels and maintain stable energy homeostasis. Recent evidence also supports that the CNS uses these same inputs to regulate glucose homeostasis and this aspect of CNS regulation also becomes impaired in the face of dietary-induced obesity. This review focuses on the literature surrounding hypothalamic regulation of energy and glucose homeostasis and discusses how dysregulation of this system may contribute to obesity and T2DM.

Meal replacement based on Human Ration modulates metabolic risk factors during body weight loss: a randomized controlled trial.

Science.gov (United States)

Alves, Natalia Elizabeth Galdino; Enes, Bárbara Nery; Martino, Hércia Stampini Duarte; Alfenas, Rita de Cássia Gonçalves; Ribeiro, Sônia Machado Rocha

2014-04-01

A meal replacement may be an effective strategy in the management of obesity to increase antioxidant intake, attenuating oxidative stress and inflammation. In the present study, we investigated the efficacy of a new nutritional supplement to reduce metabolic risk parameters in obese women. In a randomized controlled crossover study (2 × 2), 22 women (percentage body fat 40.52 ± 3.75%; body mass index-BMI 28.72 ± 2.87 kg/m²; 35.04 ± 5.6 years old) were allocated into two treatments: hypocaloric diet and drink containing "Human Ration" (HR) consumption (CRHR), and hypocaloric diet and control drink consumption (CR). The study consisted of 2 periods of 5 weeks with 1 week of washout in two orders (CR → CRHR and CRHR → CR). Caloric restriction was 15%, based on estimated energy requirement. Anthropometric, clinical and metabolic risk parameters were assessed at baseline and at the end of each period. Some metabolic risk factors were favorably modulated in both interventions: reduction in body weight (CR -0.74 ± 1.27 kg; p = 0.01; CRHR -0.77 ± 1.3 kg; p = 0.02), body mass index (BMI) (CR -0.27 ± 0.51 kg/m²; p = 0.02; CRHR -0.30 ± 0.52 kg/m²; p = 0.01) and HOMA-IR (CR -0.35 ± 0.82; p = 0.02, CRHR -0.41 ± 0.83; p = 0.03). However, CRHR reduced waist circumference (-2.54 ± 2.74 cm; p < 0.01) and gynoid fat (-0.264 ± 0.28 g; p < 0.01), and increased HDL-c levels (0.08 ± 0.15 mmol/l; p = 0.04). Associated with hypocaloric diet, the intake of a nutritional supplement rich in phytochemicals as a breakfast substitute for 5 weeks had no additional effect on weight reduction than caloric restriction alone, but increased central lipolysis and improved the lipoprotein profile.

LakeMetabolizer: An R package for estimating lake metabolism from free-water oxygen using diverse statistical models

Science.gov (United States)

Winslow, Luke; Zwart, Jacob A.; Batt, Ryan D.; Dugan, Hilary; Woolway, R. Iestyn; Corman, Jessica; Hanson, Paul C.; Read, Jordan S.

2016-01-01

Metabolism is a fundamental process in ecosystems that crosses multiple scales of organization from individual organisms to whole ecosystems. To improve sharing and reuse of published metabolism models, we developed LakeMetabolizer, an R package for estimating lake metabolism from in situ time series of dissolved oxygen, water temperature, and, optionally, additional environmental variables. LakeMetabolizer implements 5 different metabolism models with diverse statistical underpinnings: bookkeeping, ordinary least squares, maximum likelihood, Kalman filter, and Bayesian. Each of these 5 metabolism models can be combined with 1 of 7 models for computing the coefficient of gas exchange across the air–water interface (k). LakeMetabolizer also features a variety of supporting functions that compute conversions and implement calculations commonly applied to raw data prior to estimating metabolism (e.g., oxygen saturation and optical conversion models). These tools have been organized into an R package that contains example data, example use-cases, and function documentation. The release package version is available on the Comprehensive R Archive Network (CRAN), and the full open-source GPL-licensed code is freely available for examination and extension online. With this unified, open-source, and freely available package, we hope to improve access and facilitate the application of metabolism in studies and management of lentic ecosystems.

Improvement on reliability of control system in power plant

International Nuclear Information System (INIS)

Taguchi, S.; Mizumoto, T.; Hirose, Y.; Kashiwai, J.; Takami, I.; Shono, M.; Roji, Y.; Kizaki, S.

1985-01-01

Studies made of Japanese PWR operating experiences have revealed that failures in the control system are the primary causes of unscheduled shutdowns. An attempt has, therefore, been made to improve the reliability of the control system in order to raise the plant reliability. The following are the procedures applied to solve the issue; study of operating experiences, fault tree analysis and failure mode and effects analysis. Improvement measures are developed for the control system whose failure threatens to cause the plant trip during the plant life. These systems are the main feedwater control system, rod control system, pressurizer control system and main steam control system in the primary control system. As a result, the plant unavailability is expected to be reduced significantly by applying the improvements. The improvements are applied to the plants under construction and the operating plants in co-operation with utilities and vendors. (author)

A Randomized Controlled Trial of Two Different Macronutrient Profiles on Weight, Body Composition and Metabolic Parameters in Obese Adolescents Seeking Weight Loss.

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Helen Truby

Full Text Available Adolescent obesity is difficult to treat and the optimal dietary pattern, particularly in relation to macronutrient composition, remains controversial. This study tested the effect of two structured diets with differing macronutrient composition versus control, on weight, body composition and metabolic parameters in obese adolescents.A randomized controlled trial conducted in a children's hospital.Eighty seven obese youth (means: age 13.6 years, BMI z-score 2.2, waist: height ratio 0.65, 69% female completed a psychological preparedness program and were then randomized to a short term 'structured modified carbohydrate' (SMC, 35% carbohydrate; 30% protein; 35% fat, n = 37 or a 'structured low fat' (SLF, 55% carbohydrate; 20% protein; 25% fat, n = 36 or a wait listed control group (n = 14. Anthropometric, body composition and biochemical parameters were measured at randomization and after 12 weeks, and analyzed under the intention to treat principle using analysis of variance models.After 12 weeks, data was collected from 79 (91% participants. BMI z-scores were significantly lower in both intervention groups compared to control after adjusting for baseline values, SLF vs. control, mean difference = -0.13 (95%CI = -0.18, -0.07, P<0.001; SMC vs. control, -0.14 (-0.19, -0.09, P<0.001, but there was no difference between the two intervention diet groups: SLF vs. SMC, 0.00 (-0.05, 0.04, P = 0.83.Both dietary patterns resulted in similar changes in weight, body composition and metabolic improvements compared to control. The use of a structured eating system which allows flexibility but limited choices can assist in weight change and the rigid application of a low fat eating pattern is not exclusive in its efficacy.International Clinical Trials Registry ISRCTN49438757.

Effects of yam dioscorin interventions on improvements of the metabolic syndrome in high-fat diet-induced obese rats.

Science.gov (United States)

Shih, Shen-Liang; Lin, Yin-Shiou; Lin, Shyr-Yi; Hou, Wen-Chi

2015-12-01

The metabolic syndrome (MS) is termed a cluster of multiple metabolic risk criteria which is positively correlated with cardiovascular disease and type 2 diabetes mellitus (DM). Yam dioscorins have been reported to exhibit biological activities, however, little is known their preventive effects on the MS. Therefore, a high-fat (HF) diet was used to induce Wistar rat obesity and then yam dioscorin (50 mg/kg, dio50) was intervened daily concurrent HF diet (HF diet + dio50) for five weeks to check the changes of weights of body and tissues, blood pressures, and impaired glucose tolerances. The in vitro peptic hydrolysates of dioscorin with molecular mass between 3 kDa and 10 kDa and less than 3 kDa were used to determine dipeptidyl peptidase IV (DPP IV) inhibitory activities which DPP IV inhibitor has been reported to prevent and treat type 2 DM. There were no significant difference in body weights, feed intakes, feed conversion, and weights of adipose tissues of obese rats in groups of HF and (HF diet + dio50). However, the systolic blood pressures in obese rats of 2-, 3- and 4-week dioscorin interventions were showed significantly lower (P dioscorin intervention (HF+ dio50) was showed significantly different (P dioscorin peptic hydrolysates (5 mg/ml) showed inhibitory activities against DPP IV using sitagliptin phosphate as positive controls. Yam dioscorins exhibit improved MS activities in obese rats which the related mechanisms may need further investigations.

Effect of Acarbose on Control of Metabolic Parameters in Patients with Diabetes Type 1

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A. Ziaee

2012-07-01

Full Text Available Introduction & Objective: Acarbose is an intestinal alpha-glucosidase inhibitor that delays absorption of carbohydrates. Findings of some studies show that it has been effective in better control of blood glucose in patients with diabetes type 1. The goal of this study is to investigate the effect of administration of acarbose on glycemic & lipid parameters and daily insulin requirements and tolerability in type 1 diabetic patient.Materials & Methods: This was a clinical trial randomized double blind placebo controlled study. Performed on patients with history of at least 1 year diabetes type 1 and had HbA1c≥7.5%. Patients with Cr≥2, partial GI obstruction or IBD were excluded from the study. 45 patients were randomized to be administered acarbose or placebo for 12 weeks. Initial dose of acarbose was 25 mg T.D.S for 2 weeks, and then it was increased to 50 mg T.D.S for 10 weeks. BMI, FBS, 2hpp, HbA1c, Total cholesterol, HDL, LDL, TG and Insulin dosage were investigated monthly.Results: The values of BMI, FBS, 2hpp, HbA1c, Total cholesterol, and TG & Insulin requirements decreased significantly in the case group compared to the controls (P=0.003, P=0.005, P<0.001, P=0.001, P=0.003, P<0.001, P<0.001, respectively; but no significant changes were observed in HDL &LDL levels. Conclusion: Administration of acarbose together with insulin to type 1 diabetic patient can be valuable in improving metabolic control (BMI, FBS, 2hpp, HbA1c, Total cholesterol and TG.(Sci J Hamadan Univ Med Sci 2012;19(2:5-10

Improving the description of metabolic networks: the TCA cycle as example

NARCIS (Netherlands)

Stobbe, Miranda D.; Houten, Sander M.; van Kampen, Antoine H. C.; Wanders, Ronald J. A.; Moerland, Perry D.

2012-01-01

To collect the ever-increasing yet scattered knowledge on metabolism, multiple pathway databases like the Kyoto Encyclopedia of Genes and Genomes have been created. A complete and accurate description of the metabolic network for human and other organisms is essential to foster new biological

Exogenous Application of GABA Improves PEG-Induced Drought Tolerance Positively Associated with GABA-Shunt, Polyamines, and Proline Metabolism in White Clover.

Science.gov (United States)

Yong, Bin; Xie, Huan; Li, Zhou; Li, Ya-Ping; Zhang, Yan; Nie, Gang; Zhang, Xin-Quan; Ma, Xiao; Huang, Lin-Kai; Yan, Yan-Hong; Peng, Yan

2017-01-01

In order to investigate the physiological effects of exogenous γ-aminobutyric acid (GABA) on drought tolerance in white clover (Trifolium repens), GABA shunt, polyamines (PAs), and proline (Pro) metabolism were examined after plants pretreated with or without GABA (8 mM) and then exposed to water or 15% PEG-induced drought stress in growth chamber. In this study, exogenous application of GABA effectively alleviated drought-induced damage in leaves, as reflected by significantly higher relative water content, lower electrolyte leakage, lipid peroxidation, and leaf wilt. Exogenous GABA further promoted drought-induced increases in GABA transaminase and alpha ketone glutarate dehydrogenase activities, but inhibited glutamate decarboxylase activity under both control and drought conditions, resulting in an increase in endogenous glutamate (Glu) and GABA content. Besides, exogenous GABA could well accelerated PAs synthesis and suppressed PAs catabolism, which lead to the extremely enhanced different types of PAs content (free Put and Spd, insoluble bound Spd and Spm, soluble conjugated Spd and Spm, and total Put, Spd and Spm) under drought stress. In addition, exogenous GABA application further activated drought-induced Δ 1 -pyrroline-5-carboxylate synthetase and proline dehydrogenase activities, but suppressed drought-facilitated ornithine -δ-amino transferase activities, leading to a higher Pro accumulation and metabolism in GABA-pretreated plants in the middle and last period of drought. The results suggested that increased endogenous GABA by exogenous GABA treatment could improve drought tolerance of white clover associated with a positive regulation in the GABA-shunt, PAs and Pro metabolism.

Training Attentional Control Improves Cognitive and Motor Task Performance.

Science.gov (United States)

Ducrocq, Emmanuel; Wilson, Mark; Vine, Sam; Derakshan, Nazanin

2016-10-01

Attentional control is a necessary function for the regulation of goal-directed behavior. In three experiments we investigated whether training inhibitory control using a visual search task could improve task-specific measures of attentional control and performance. In Experiment 1 results revealed that training elicited a near-transfer effect, improving performance on a cognitive (antisaccade) task assessing inhibitory control. In Experiment 2 an initial far-transfer effect of training was observed on an index of attentional control validated for tennis. The principal aim of Experiment 3 was to expand on these findings by assessing objective gaze measures of inhibitory control during the performance of a tennis task. Training improved inhibitory control and performance when pressure was elevated, confirming the mechanisms by which cognitive anxiety impacts performance. These results suggest that attentional control training can improve inhibition and reduce taskspecific distractibility with promise of transfer to more efficient sporting performance in competitive contexts.

Tilting Plant Metabolism for Improved Metabolite Biosynthesis and Enhanced Human Benefit

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Bhekumthetho Ncube

2015-07-01

Full Text Available The immense chemical diversity of plant-derived secondary metabolites coupled with their vast array of biological functions has seen this group of compounds attract considerable research interest across a range of research disciplines. Medicinal and aromatic plants, in particular, have been exploited for this biogenic pool of phytochemicals for products such as pharmaceuticals, fragrances, dyes, and insecticides, among others. With consumers showing increasing interests in these products, innovative biotechnological techniques are being developed and employed to alter plant secondary metabolism in efforts to improve on the quality and quantity of specific metabolites of interest. This review provides an overview of the biosynthesis for phytochemical compounds with medicinal and other related properties and their associated biological activities. It also provides an insight into how their biosynthesis/biosynthetic pathways have been modified/altered to enhance production.

Metabolic effects of testosterone replacement therapy on hypogonadal men with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials

Directory of Open Access Journals (Sweden)

Xiang Cai

2014-02-01

Full Text Available This systematic review was aimed at assessing the metabolic effects of testosterone replacement therapy (TRT on hypogonadal men with type 2 diabetes mellitus (T2DM. A literature search was performed using the Cochrane Library, EMBASE and PubMed. Only randomized controlled trials (RCTs were included in the meta-analysis. Two reviewers retrieved articles and evaluated the study quality using an appropriate scoring method. Outcomes including glucose metabolism, lipid parameters, body fat and blood pressure were pooled using a random effects model and tested for heterogeneity. We used the Cochrane Collaboration's Review Manager 5.2 software for statistical analysis. Five RCTs including 351 participants with a mean follow-up time of 6.5-months were identified that strictly met our eligibility criteria. A meta-analysis of the extractable data showed that testosterone reduced fasting plasma glucose levels (mean difference (MD: −1.10; 95% confidence interval (CI (−1.88, −0.31, fasting serum insulin levels (MD: −2.73; 95% CI (−3.62, −1.84, HbA1c % (MD: −0.87; 95% CI (−1.32, −0.42 and triglyceride levels (MD: −0.35; 95% CI (−0.62, −0.07. The testosterone and control groups demonstrated no significant difference for other outcomes. In conclusion, we found that TRT can improve glycemic control and decrease triglyceride levels of hypogonadal men with T2DM. Considering the limited number of participants and the confounding factors in our systematic review; additional large, well-designed RCTs are needed to address the metabolic effects of TRT and its long-term influence on hypogonadal men with T2DM.

Association of neural tube defects in children of mothers with MTHFR 677TT genotype and abnormal carbohydrate metabolism risk: a case-control study.

Science.gov (United States)

Cadenas-Benitez, N M; Yanes-Sosa, F; Gonzalez-Meneses, A; Cerrillos, L; Acosta, D; Praena-Fernandez, J M; Neth, O; Gomez de Terreros, I; Ybot-González, P

2014-03-26

Abnormalities in maternal folate and carbohydrate metabolism have both been shown to induce neural tube defects (NTD) in humans and animal models. However, the relationship between these two factors in the development of NTDs remains unclear. Data from mothers of children with spina bifida seen at the Unidad de Espina Bífida del Hospital Infantil Virgen del Rocío (case group) were compared to mothers of healthy children with no NTD (control group) who were randomly selected from patients seen at the outpatient ward in the same hospital. There were 25 individuals in the case group and 41 in the control group. Analysis of genotypes for the methylenetetrahydrofolate reductase (MTHFR) 677CT polymorphism in women with or without risk factors for abnormal carbohydrate metabolism revealed that mothers who were homozygous for the MTHFR 677TT polymorphism and at risk of abnormal carbohydrate metabolism were more likely to have offspring with spina bifida and high levels of homocysteine, compared to the control group. The increased incidence of NTDs in mothers homozygous for the MTHFR 677TT polymorphism and at risk of abnormal carbohydrate metabolism stresses the need for careful metabolic screening in pregnant women, and, if necessary, determination of the MTHFR 677CT genotype in those mothers at risk of developing abnormal carbohydrate metabolism.

Long-lived hypopituitary Ames dwarf mice are resistant to the detrimental effects of high-fat diet on metabolic function and energy expenditure.

Science.gov (United States)

Hill, Cristal M; Fang, Yimin; Miquet, Johanna G; Sun, Liou Y; Masternak, Michal M; Bartke, Andrzej

2016-06-01

Growth hormone (GH) signaling stimulates the production of IGF-1; however, increased GH signaling may induce insulin resistance and can reduce life expectancy in both mice and humans. Interestingly, disruption of GH signaling by reducing plasma GH levels significantly improves health span and extends lifespan in mice, as observed in Ames dwarf mice. In addition, these mice have increased adiposity, yet are more insulin sensitive compared to control mice. Metabolic stressors such as high-fat diet (HFD) promote obesity and may alter longevity through the GH signaling pathway. Therefore, our objective was to investigate the effects of a HFD (metabolic stressor) on genetic mechanisms that regulate metabolism during aging. We show that Ames dwarf mice fed HFD for 12 weeks had an increase in subcutaneous and visceral adiposity as a result of diet-induced obesity, yet are more insulin sensitive and have higher levels of adiponectin compared to control mice fed HFD. Furthermore, energy expenditure was higher in Ames dwarf mice fed HFD than in control mice fed HFD. Additionally, we show that transplant of epididymal white adipose tissue (eWAT) from Ames dwarf mice fed HFD into control mice fed HFD improves their insulin sensitivity. We conclude that Ames dwarf mice are resistant to the detrimental metabolic effects of HFD and that visceral adipose tissue of Ames dwarf mice improves insulin sensitivity in control mice fed HFD. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Metabolic learning and memory formation by the brain influence systemic metabolic homeostasis