Effect of L-ascorbic acid on nickel-induced alterations in serum lipid profiles and liver histopathology in rats.

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Das, Kusal K; Gupta, Amrita Das; Dhundasi, Salim A; Patil, Ashok M; Das, Swastika N; Ambekar, Jeevan G

2006-01-01

Nickel exposure greatly depletes intracellular ascorbate and alters ascorbate-cholesterol metabolism. We studied the effect of the simultaneous oral treatment with L-ascorbic acid (50 mg/100 g body weight (BW) and nickel sulfate (2.0 mg/100 g BW, i.p) on nickelinduced changes in serum lipid profiles and liver histopathology. Nickel-treated rats showed a significant increase in serum low-density lipoprotein-cholesterol, total cholesterol, triglycerides, and a significant decrease in serum high-density lipoprotein-cholesterol. In the liver, nickel sulfate caused a loss of normal architecture, fatty changes, extensive vacuolization in hepatocytes, eccentric nuclei, and Kupffer cell hypertrophy. Simultaneous administration of L-ascorbic acid with nickel sulfate improved both the lipid profile and liver impairments when compared with rats receiving nickel sulfate only. The results indicate that L-ascorbic acid is beneficial in preventing nickel-induced lipid alterations and hepatocellular damage.

High salt diet induces metabolic alterations in multiple biological processes of Dahl salt-sensitive rats.

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Wang, Yanjun; Liu, Xiangyang; Zhang, Chen; Wang, Zhengjun

2018-06-01

High salt induced renal disease is a condition resulting from the interactions of genetic and dietary factors causing multiple complications. To understand the metabolic alterations associated with renal disease, we comprehensively analyzed the metabonomic changes induced by high salt intake in Dahl salt-sensitive (SS) rats using GC-MS technology and biochemical analyses. Physiological features, serum chemistry, and histopathological data were obtained as complementary information. Our results showed that high salt (HS) intake for 16 weeks caused significant metabolic alterations in both the renal medulla and cortex involving a variety pathways involved in the metabolism of organic acids, amino acids, fatty acids, and purines. In addition, HS enhanced glycolysis (hexokinase, phosphofructokinase and pyruvate kinase) and amino acid metabolism and suppressed the TCA (citrate synthase and aconitase) cycle. Finally, HS intake caused up-regulation of the pentose phosphate pathway (glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase), the ratio of NADPH/NADP + , NADPH oxidase activity and ROS production, suggesting that increased oxidative stress was associated with an altered PPP pathway. The metabolic pathways identified may serve as potential targets for the treatment of renal damage. Our findings provide comprehensive biochemical details about the metabolic responses to a high salt diet, which may contribute to the understanding of renal disease and salt-induced hypertension in SS rats. Copyright © 2018. Published by Elsevier Inc.

Alteration in metabolic signature and lipid metabolism in patients with angina pectoris and myocardial infarction.

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Park, Ju Yeon; Lee, Sang-Hak; Shin, Min-Jeong; Hwang, Geum-Sook

2015-01-01

Lipid metabolites are indispensable regulators of physiological and pathological processes, including atherosclerosis and coronary artery disease (CAD). However, the complex changes in lipid metabolites and metabolism that occur in patients with these conditions are incompletely understood. We performed lipid profiling to identify alterations in lipid metabolism in patients with angina and myocardial infarction (MI). Global lipid profiling was applied to serum samples from patients with CAD (angina and MI) and age-, sex-, and body mass index-matched healthy subjects using ultra-performance liquid chromatography/quadruple time-of-flight mass spectrometry and multivariate statistical analysis. A multivariate analysis showed a clear separation between the patients with CAD and normal controls. Lysophosphatidylcholine (lysoPC) and lysophosphatidylethanolamine (lysoPE) species containing unsaturated fatty acids and free fatty acids were associated with an increased risk of CAD, whereas species of lysoPC and lyso-alkyl PC containing saturated fatty acids were associated with a decreased risk. Additionally, PC species containing palmitic acid, diacylglycerol, sphingomyelin, and ceramide were associated with an increased risk of MI, whereas PE-plasmalogen and phosphatidylinositol species were associated with a decreased risk. In MI patients, we found strong positive correlation between lipid metabolites related to the sphingolipid pathway, sphingomyelin, and ceramide and acute inflammatory markers (high-sensitivity C-reactive protein). The results of this study demonstrate altered signatures in lipid metabolism in patients with angina or MI. Lipidomic profiling could provide the information to identity the specific lipid metabolites under the presence of disturbed metabolic pathways in patients with CAD.

Serum Progranulin Levels in Type 2 Diabetic Patients with Metabolic Syndrome.

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Shafaei, Azam; Marjani, Abdoljalal; Khoshnia, Masoud

2016-12-01

The role of progranulin in individuals with metabolic syndrome is not exactly clear.We aimed to assess the serum level of progranulin in type 2 diabetic patients with and without metabolic syndrome and compare them with healthy controls. The study included 60 patients with type 2 diabetes and 30 healthy individuals as control groups. Biochemical parameters and progranulin levels were determined. Subjects with metabolic syndrome showed significantly higher levels of triglyceride, waist circumference, BMI, systolic and diastolic blood pressure than subjects without metabolic syndrome and the control groups, while HDL-cholesterol level was significantly lower in subjects with metabolic syndrome. Fasting blood sugar was significantly higher in type 2 diabetic patients than in the control groups. Serum level of progranulin was slightly increased in subjects with metabolic syndrome. Serum progranulin level had no significant relationship with metabolic syndrome components. Serum progranulin was also not dependent on cardiometabolic risk factors for subjects with metabolic syndrome, but it could be considered for the management of type 2 diabetes mellitus. Further studies are recommended to explain the effect of progranulin on the pathogenesis of metabolic risk factors.

Serum Myostatin Is Reduced in Individuals with Metabolic Syndrome

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Chiang, Chih-Kang; Tseng, Fen-Yu; Tseng, Ping-Huei; Chen, Chi-Ling; Wu, Kwan-Dun; Yang, Wei-Shiung

2014-01-01

Aims Myostatin is a negative regulator of skeletal muscle mass and may also modulate energy metabolism secondarily. We aim to investigate the relationship between serum myostatin and the metabolic variables in diabetic (DM) and non-diabetic subjects. Materials and Methods A cross-sectional study recruiting 246 consecutive DM patients and 82 age- and gender-matched non-diabetic individuals at a medical center was conducted. The variables of anthropometry and blood chemistry were obtained. Serum myostatin level was measured with enzyme immunoassay. Results DM group had lower serum myostatin compared with non-diabetics (7.82 versus 9.28 ng/ml, pmyostatin than those without (7.39 versus 9.49 ng/ml, pmyostatin level decreased with increasing numbers of the MetS components (p for trendmyostatin than those without. The serum myostatin level was independently negatively related to larger abdominal girth, higher triglycerides, and lower HDL-C after adjustment. The odds ratios for MetS, central obesity, low HDL-C, high triglycerides, and DM were 0.85, 0.88, 0.89, 0.85, and 0.92, respectively, when serum myostatin increased per 1 ng/mL, in the binary logistic regression models. Conclusions Lower serum myostatin independently associated with MetS, central obesity, low HDL-C, and high triglycerides after adjustment. Higher serum myostatin is associated with favorable metabolic profiles. PMID:25254550

Altered drug metabolism during pregnancy: hormonal regulation of drug-metabolizing enzymes.

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Jeong, Hyunyoung

2010-06-01

Medication use during pregnancy is prevalent, but pharmacokinetic information of most drugs used during pregnancy is lacking in spite of known effects of pregnancy on drug disposition. Accurate pharmacokinetic information is essential for optimal drug therapy in mother and fetus. Thus, understanding how pregnancy influences drug disposition is important for better prediction of pharmacokinetic changes of drugs in pregnant women. Pregnancy is known to affect hepatic drug metabolism, but the underlying mechanisms remain unknown. Physiological changes accompanying pregnancy are probably responsible for the reported alteration in drug metabolism during pregnancy. These include elevated concentrations of various hormones such as estrogen, progesterone, placental growth hormones and prolactin. This review covers how these hormones influence expression of drug-metabolizing enzymes (DMEs), thus potentially responsible for altered drug metabolism during pregnancy. The reader will gain a greater understanding of the altered drug metabolism in pregnant women and the regulatory effects of pregnancy hormones on expression of DMEs. In-depth studies in hormonal regulatory mechanisms as well as confirmatory studies in pregnant women are warranted for systematic understanding and prediction of the changes in hepatic drug metabolism during pregnancy.

Alteration of serum adropin level in preeclampsia.

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Wang, Huihua; Gao, Bo; Wu, Zaigui; Wang, Hanzhi; Dong, Minyue

2017-04-01

To clarify the alterations in serum adropin and preptin concentrations in preeclampsia, we determined serum adropin and preptin levels in 29 women with normal pregnancy and 32 women with preeclampsia. We found that maternal age, body mass index and fetal gender were not significantly different between two groups; however, blood pressure, gestational age and neonatal birth weight were significantly different. Serum adropin levels were significantly increased in women with preeclampsia compared with those with normal pregnancy but there were no significant differences in preptin levels. An increase in maternal serum adropin level was found in preeclampsia, and this may be a compensation for pregnancy complicated with preeclampsia. Copyright © 2017 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

Obesogenic diets alter metabolism in mice.

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Megan R Showalter

Full Text Available Obesity and accompanying metabolic disease is negatively correlated with lung health yet the exact mechanisms by which obesity affects the lung are not well characterized. Since obesity is associated with lung diseases as chronic bronchitis and asthma, we designed a series of experiments to measure changes in lung metabolism in mice fed obesogenic diets. Mice were fed either control or high fat/sugar diet (45%kcal fat/17%kcal sucrose, or very high fat diet (60%kcal fat/7% sucrose for 150 days. We performed untargeted metabolomics by GC-TOFMS and HILIC-QTOFMS and lipidomics by RPLC-QTOFMS to reveal global changes in lung metabolism resulting from obesity and diet composition. From a total of 447 detected metabolites, we found 91 metabolite and lipid species significantly altered in mouse lung tissues upon dietary treatments. Significantly altered metabolites included complex lipids, free fatty acids, energy metabolites, amino acids and adenosine and NAD pathway members. While some metabolites were altered in both obese groups compared to control, others were different between obesogenic diet groups. Furthermore, a comparison of changes between lung, kidney and liver tissues indicated few metabolic changes were shared across organs, suggesting the lung is an independent metabolic organ. These results indicate obesity and diet composition have direct mechanistic effects on composition of the lung metabolome, which may contribute to disease progression by lung-specific pathways.

Obesogenic diets alter metabolism in mice.

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Showalter, Megan R; Nonnecke, Eric B; Linderholm, A L; Cajka, Tomas; Sa, Michael R; Lönnerdal, Bo; Kenyon, Nicholas J; Fiehn, Oliver

2018-01-01

Obesity and accompanying metabolic disease is negatively correlated with lung health yet the exact mechanisms by which obesity affects the lung are not well characterized. Since obesity is associated with lung diseases as chronic bronchitis and asthma, we designed a series of experiments to measure changes in lung metabolism in mice fed obesogenic diets. Mice were fed either control or high fat/sugar diet (45%kcal fat/17%kcal sucrose), or very high fat diet (60%kcal fat/7% sucrose) for 150 days. We performed untargeted metabolomics by GC-TOFMS and HILIC-QTOFMS and lipidomics by RPLC-QTOFMS to reveal global changes in lung metabolism resulting from obesity and diet composition. From a total of 447 detected metabolites, we found 91 metabolite and lipid species significantly altered in mouse lung tissues upon dietary treatments. Significantly altered metabolites included complex lipids, free fatty acids, energy metabolites, amino acids and adenosine and NAD pathway members. While some metabolites were altered in both obese groups compared to control, others were different between obesogenic diet groups. Furthermore, a comparison of changes between lung, kidney and liver tissues indicated few metabolic changes were shared across organs, suggesting the lung is an independent metabolic organ. These results indicate obesity and diet composition have direct mechanistic effects on composition of the lung metabolome, which may contribute to disease progression by lung-specific pathways.

Relationship of serum resistin level to traits of metabolic syndrome and serum paraoxonase 1 activity in a population with a broad range of body mass index.

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Bajnok, L; Seres, I; Varga, Z; Jeges, S; Peti, A; Karanyi, Z; Juhasz, A; Csongradi, E; Mezosi, E; Nagy, E V; Paragh, G

2008-11-01

The relationship between resistin, one of the adipokines, and metabolic syndrome is not fully elucidated. Altered activity of the HDL-associated antioxidant enzyme paraoxonase 1 (PON1) that participates in the antioxidant defense mechanisms of HDL may have an important role in the obesity-related accelerated atherosclerosis. Inverse associations of PON1 with obesity and serum levels of leptin have been demonstrated. Our aim was to investigate the association of serum levels of resistin with (i) PON1 activity, and (ii) parameters of metabolic syndrome, including some that are additional for research. A total of 74 Caucasian subjects were recruited into the study and divided into 3 age and sex-matched groups. Group 1, 25 non-diabetic overweight/obese subjects with BMI of 28-39.9 kg/m (2); group 2, 25 non-diabetic obese patients with BMI >or=40 kg/m (2); and the control group 3, 24 healthy, normal-weight control subjects. Serum levels of resistin were correlated negatively with BMI (r=-0.27, Pcorrelated positively with PON1 (r=0.24, PHDL-C. During multiple regression analyses BMI and TBARS were independent predictors of PON1, while age, gender, blood pressure, HOMA-IR, LDL-C, HDL-C, and resistin were not. Among the study subjects, serum levels of resistin showed a positive, although not independent correlation with serum PON1, and a negative correlation with numerous parameters of the metabolic syndrome (i.e. adiposity, blood pressure, levels of leptin, free fatty acid, glycosylated hemoglobin, and lipid peroxidation). BMI and TBARS are independent predictors of PON1 activity.

L-Arginine Availability and Metabolism Is Altered in Ulcerative Colitis.

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Coburn, Lori A; Horst, Sara N; Allaman, Margaret M; Brown, Caroline T; Williams, Christopher S; Hodges, Mallary E; Druce, Jennifer P; Beaulieu, Dawn B; Schwartz, David A; Wilson, Keith T

2016-08-01

L-arginine (L-Arg) is the substrate for both inducible nitric oxide (NO) synthase (NOS2) and arginase (ARG) enzymes. L-Arg is actively transported into cells by means of cationic amino acid transporter (SLC7) proteins. We have linked L-Arg and arginase 1 activity to epithelial restitution. Our aim was to determine if L-Arg, related amino acids, and metabolic enzymes are altered in ulcerative colitis (UC). Serum and colonic tissues were prospectively collected from 38 control subjects and 137 UC patients. Dietary intake, histologic injury, and clinical disease activity were assessed. Amino acid levels were measured by high-performance liquid chromatography. Messenger RNA (mRNA) levels were measured by real-time PCR. Colon tissue samples from 12 Crohn's disease patients were obtained for comparison. Dietary intake of arginine and serum L-Arg levels were not different in UC patients versus control subjects. In active UC, tissue L-Arg was decreased, whereas L-citrulline (L-Cit) and the L-Cit/L-Arg ratio were increased. This pattern was also seen when paired involved (left) versus uninvolved (right) colon tissues in UC were assessed. In active UC, SLC7A2 and ARG1 mRNA levels were decreased, whereas ARG2 and NOS2 were increased. Similar alterations in mRNA expression occurred in tissues from Crohn's disease patients. In involved UC, SLC7A2 and ARG1 mRNA levels were decreased, and NOS2 and ARG2 increased, when compared with uninvolved tissues. Patients with UC exhibit diminished tissue L-Arg, likely attributable to decreased cellular uptake and increased consumption by NOS2. These findings combined with decreased ARG1 expression indicate a pattern of dysregulated L-Arg availability and metabolism in UC.

Potential serum biomarkers and metabonomic profiling of serum in ischemic stroke patients using UPLC/Q-TOF MS/MS.

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Hongxue Sun

Full Text Available Stroke still has a high incidence with a tremendous public health burden and it is a leading cause of mortality and disability. However, biomarkers for early diagnosis are absent and the metabolic alterations associated with ischemic stroke are not clearly understood. The objectives of this case-control study are to identify serum biomarkers and explore the metabolic alterations of ischemic stroke.Metabonomic analysis was performed using ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry and multivariate statistical analysis was employed to study 60 patients with or without ischemic stroke (30 cases and 30 controls.Serum metabolic profiling identified a series of 12 metabolites with significant alterations, and the related metabolic pathways involved glycerophospholipid, sphingolipid, phospholipid, fat acid, acylcarnitine, heme, and purine metabolism. Subsequently, multiple logistic regression analyses of these metabolites showed uric acid, sphinganine and adrenoyl ethanolamide were potential biomarkers of ischemic stroke with an area under the receiver operating characteristic curve of 0.941.These findings provide insights into the early diagnosis and potential pathophysiology of ischemic stroke.

Serum Ferritin Is Associated with Metabolic Syndrome and Red Meat Consumption

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Avila Felipe

2015-01-01

Full Text Available Background and Aims. Hyperferritinemia has been related with a wide spectrum of pathologies, including diabetes, cardiovascular disease, neurodegenerative disorders, and metabolic syndrome. The aim of this study was to investigate the association between hyperferritinemia and iron consumption. Methods and Results. Serum ferritin concentration was evaluated in 66 presumed healthy men, along with other clinical and biochemical markers of chronic diseases. A three-day food questionnaire was applied for nutrition information. Hyperferritinemia was a condition found in 13.4% of the volunteers analyzed. Significant correlations were found between serum ferritin concentration and metabolic syndrome parameters (HDL cholesterol, triglycerides, and fasting glucose as well as an increase of the serum ferritin mean value with the number of risk factors of metabolic syndrome. Also, oxidative stress markers (carbonyl groups, AOPP, and glycated hemoglobin, hepatic damage markers (GGT, SGOT, and parameters related to insulin resistance (HOMA, blood insulin, and blood glucose correlate significantly with serum ferritin. Volunteers had an excessive iron intake, principally by bread consumption. Analyses of food intake showed that red meat consumption correlates significantly with serum ferritin. Conclusion. Red meat consumption, metabolic syndrome, and chronic disease markers are associated with hyperferritinemia in a population of Chilean men.

Association of Serum Ferritin Levels with Metabolic Syndrome and Insulin Resistance.

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Padwal, Meghana K; Murshid, Mohsin; Nirmale, Prachee; Melinkeri, R R

2015-09-01

The impact of CVDs and Type II DM is increasing over the last decade. It has been estimated that by 2025 their incidence will double. Ferritin is one of the key proteins regulating iron homeostasis and is a widely available clinical biomarker of iron status. Some studies suggest that prevalence of atherosclerosis and insulin resistance increases significantly with increasing serum ferritin. Metabolic syndrome is known to be associated with increased risk of atherosclerosis as well as insulin resistance. The present study was designed to explore the association of serum ferritin levels with metabolic syndrome and insulin resistance. The present study was prospective, cross sectional. The study protocol was approved by IEC. The study group consisted of 90 participants (50 cases of metabolic syndrome and 40 age and sex matched controls). Diagnosis of metabolic syndrome was done as per NCEP ATP III criteria. Estimation of serum Ferritin and Insulin was done by Chemiluminescence Immunoassay (CLIA) while Glucose by Glucose Oxidase and Peroxidase (GOD-POD) method. Insulin Resistance was calculated by HOMA IR score. Data obtained was statistically analysed by using student t-test. We found statistically significant rise in the levels of serum ferritin (p=syndrome as compared with controls. High serum ferritin levels though within normal range are significantly associated with both metabolic syndrome and insulin resistance.

Early Stress History Alters Serum Insulin-Like Growth Factor-1 and Impairs Muscle Mitochondrial Function in Adult Male Rats.

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Ghosh, S; Banerjee, K K; Vaidya, V A; Kolthur-Seetharam, U

2016-09-01

Early-life adversity is associated with an enhanced risk for adult psychopathology. Psychiatric disorders such as depression exhibit comorbidity for metabolic dysfunction, including obesity and diabetes. However, it is poorly understood whether, besides altering anxiety and depression-like behaviour, early stress also evokes dysregulation of metabolic pathways and enhances vulnerability for metabolic disorders. We used the rodent model of the early stress of maternal separation (ES) to examine the effects of early stress on serum metabolites, insulin-like growth factor (IGF)-1 signalling, and muscle mitochondrial content. Adult ES animals exhibited dyslipidaemia, decreased serum IGF1 levels, increased expression of liver IGF binding proteins, and a decline in the expression of specific metabolic genes in the liver and muscle, including Pck1, Lpl, Pdk4 and Hmox1. These changes occurred in the absence of alterations in body weight, food intake, glucose tolerance, insulin tolerance or insulin levels. ES animals also exhibited a decline in markers of muscle mitochondrial content, such as mitochondrial DNA levels and expression of TFAM (transcription factor A, mitochondrial). Furthermore, the expression of several genes involved in mitochondrial function, such as Ppargc1a, Nrf1, Tfam, Cat, Sesn3 and Ucp3, was reduced in skeletal muscle. Adult-onset chronic unpredictable stress resulted in overlapping and distinct consequences from ES, including increased circulating triglyceride levels, and a decline in the expression of specific metabolic genes in the liver and muscle, with no change in the expression of genes involved in muscle mitochondrial function. Taken together, our results indicate that a history of early adversity can evoke persistent changes in circulating IGF-1 and muscle mitochondrial function and content, which could serve to enhance predisposition for metabolic dysfunction in adulthood. © 2016 British Society for Neuroendocrinology.

Association between serum CA 19-9 and metabolic syndrome: A cross-sectional study.

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Du, Rui; Cheng, Di; Lin, Lin; Sun, Jichao; Peng, Kui; Xu, Yu; Xu, Min; Chen, Yuhong; Bi, Yufang; Wang, Weiqing; Lu, Jieli; Ning, Guang

2017-11-01

Increasing evidence suggests that serum CA 19-9 is associated with abnormal glucose metabolism. However, data on the association between CA 19-9 and metabolic syndrome is limited. The aim of the present study was to investigate the association between serum CA 19-9 and metabolic syndrome. A cross-sectional study was conducted on 3641 participants aged ≥40 years from the Songnan Community, Baoshan District in Shanghai, China. Logistic regression analysis was used to evaluate the association between serum CA 19-9 and metabolic syndrome. Multivariate logistic regression analysis showed that compared with participants in the first tertile of serum CA 19-9, those in the second and third tertiles had increased odds ratios (OR) for prevalent metabolic syndrome (multivariate adjusted OR 1.46 [95% confidence interval {CI} 1.11-1.92] and 1.51 [95% CI 1.14-1.98]; P trend  = 0.005). In addition, participants with elevated serum CA 19-9 (≥37 U/mL) had an increased risk of prevalent metabolic syndrome compared with those with serum CA 19-9 metabolic syndrome. In order to confirm this association and identify potential mechanisms, prospective cohort and mechanic studies should be performed. © 2017 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Metabolic syndrome, alcohol consumption and genetic factors are associated with serum uric acid concentration.

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Blanka Stibůrková

Full Text Available Uric acid is the end product of purine metabolism in humans, and increased serum uric acid concentrations lead to gout. The objective of the current study was to identify factors that are independently associated with serum uric acid concentrations in a cohort of Czech control individuals.The cohort consisted of 589 healthy subjects aged 18-65 years. We studied the associations between the serum uric acid concentration and the following: (i demographic, anthropometric and other variables previously reported to be associated with serum uric acid concentrations; (ii the presence of metabolic syndrome and the levels of metabolic syndrome components; and (iii selected genetic variants of the MTHFR (c.665C>T, c.1286A>C, SLC2A9 (c.844G>A, c.881G>A and ABCG2 genes (c.421C>A. A backward model selection procedure was used to build two multiple linear regression models; in the second model, the number of metabolic syndrome criteria that were met replaced the metabolic syndrome-related variables.The models had coefficients of determination of 0.59 and 0.53. The serum uric acid concentration strongly correlated with conventional determinants including male sex, and with metabolic syndrome-related variables. In the simplified second model, the serum uric acid concentration positively correlated with the number of metabolic syndrome criteria that were met, and this model retained the explanatory power of the first model. Moderate wine drinking did not increase serum uric acid concentrations, and the urate transporter ABCG2, unlike MTHFR, was a genetic determinant of serum uric acid concentrations.Metabolic syndrome, moderate wine drinking and the c.421C>A variant in the ABCG gene are independently associated with the serum uric acid concentration. Our model indicates that uric acid should be clinically monitored in persons with metabolic syndrome.

Metabolism of homologous and heterologous serum proteins in garter snakes (Thamnophis ordinoides)

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Leong, D.; Coe, J.E.

1978-01-01

The half-life (Tsub(1/2) of serum immunoglobulin (Ig) and albumin from snakes and mammals were determined in both garter snakes (Thamnophis ordinoides) and mice (Mus musculus). Metabolism of serum proteins in snakes was similar to mammalian protein metabolism in that homologous serum albumin had shorter Tsub(1/2) (16 days) than IgG (38 days). Also, reptilian and mammalian serum proteins had a relatively longer Tsub(1/2) when injected into closely related species. Thus mammalian serum Ig (rabbit gamma globulin (RGG)) had a shorter Tsub(1/2) (6.3 days) in snake than did homologous snake IgG (38 days), whereas in mice, RGG had a longer Tsub(1/2) (3.8 days) than snake Ig (0.9 days). Differences between metabolism of homologous and heterologous albumins were apparent only in snakes in which the Tsub(1/2) of homologous albumin was approximately 8-fold greater than mammalian albumin. These results indicate that metabolism of both Ig and albumin in snakes is regulated by specific receptors whereas albumin receptors have been difficult to demonstrate in mammals. The results of this study suggest that one of the factors determining the metabolism of a protein is its foreignness to the host perhaps because of receptor cross reactions. (author)

Glucose metabolism during fasting is altered in experimental porphobilinogen deaminase deficiency.

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Collantes, María; Serrano-Mendioroz, Irantzu; Benito, Marina; Molinet-Dronda, Francisco; Delgado, Mercedes; Vinaixa, María; Sampedro, Ana; Enríquez de Salamanca, Rafael; Prieto, Elena; Pozo, Miguel A; Peñuelas, Iván; Corrales, Fernando J; Barajas, Miguel; Fontanellas, Antonio

2016-04-01

Porphobilinogen deaminase (PBGD) haploinsufficiency (acute intermittent porphyria, AIP) is characterized by neurovisceral attacks when hepatic heme synthesis is activated by endogenous or environmental factors including fasting. While the molecular mechanisms underlying the nutritional regulation of hepatic heme synthesis have been described, glucose homeostasis during fasting is poorly understood in porphyria. Our study aimed to analyse glucose homeostasis and hepatic carbohydrate metabolism during fasting in PBGD-deficient mice. To determine the contribution of hepatic PBGD deficiency to carbohydrate metabolism, AIP mice injected with a PBGD-liver gene delivery vector were included. After a 14 h fasting period, serum and liver metabolomics analyses showed that wild-type mice stimulated hepatic glycogen degradation to maintain glucose homeostasis while AIP livers activated gluconeogenesis and ketogenesis due to their inability to use stored glycogen. The serum of fasted AIP mice showed increased concentrations of insulin and reduced glucagon levels. Specific over-expression of the PBGD protein in the liver tended to normalize circulating insulin and glucagon levels, stimulated hepatic glycogen catabolism and blocked ketone body production. Reduced glucose uptake was observed in the primary somatosensorial brain cortex of fasted AIP mice, which could be reversed by PBGD-liver gene delivery. In conclusion, AIP mice showed a different response to fasting as measured by altered carbohydrate metabolism in the liver and modified glucose consumption in the brain cortex. Glucose homeostasis in fasted AIP mice was efficiently normalized after restoration of PBGD gene expression in the liver. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Dairy cows affected by ketosis show alterations in innate immunity and lipid and carbohydrate metabolism during the dry off period and postpartum.

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Zhang, Guanshi; Hailemariam, Dagnachew; Dervishi, Elda; Goldansaz, Seyed Ali; Deng, Qilan; Dunn, Suzanna M; Ametaj, Burim N

2016-08-01

The objective of this investigation was to search for alterations in blood variables related to innate immunity and carbohydrate and lipid metabolism during the transition period in cows affected by ketosis. One hundred multiparous Holstein dairy cows were involved in the study. Blood samples were collected at -8, -4, week of disease diagnosis (+1 to +3weeks), and +4weeks relative to parturition from 6 healthy cows (CON) and 6 cows with ketosis and were analyzed for serum variables. Results showed that cows with ketosis had greater concentrations of serum β-hydroxybutyric acid (BHBA), interleukin (IL)-6, tumor necrosis factor (TNF), serum amyloid A (SAA), and lactate in comparison with the CON animals. Serum concentrations of BHBA, IL-6, TNF, and lactate were greater starting at -8 and -4weeks prior to parturition in cows with ketosis vs those of CON group. Cows with ketosis also had lower DMI and milk production vs CON cows. Milk fat also was lower in ketotic cows at diagnosis of disease. Cows affected by ketosis showed an activated innate immunity and altered carbohydrate and lipid metabolism several weeks prior to diagnosis of disease. Serum IL-6 and lactate were the strongest discriminators between ketosis cows and CON ones before the occurrence of ketosis, which might be useful as predictive biomarkers of the disease state. Copyright © 2016 Elsevier Ltd. All rights reserved.

Altered Cellular Metabolism Drives Trained Immunity.

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Sohrabi, Yahya; Godfrey, Rinesh; Findeisen, Hannes M

2018-04-04

Exposing innate immune cells to an initial insult induces a long-term proinflammatory response due to metabolic and epigenetic alterations which encompass an emerging new concept called trained immunity. Recent studies provide novel insights into mechanisms centered on metabolic reprogramming which induce innate immune memory in hematopoietic stem cells and monocytes. Copyright © 2018 Elsevier Ltd. All rights reserved.

Adipose Tissue Dysfunction and Altered Systemic Amino Acid Metabolism Are Associated with Non-Alcoholic Fatty Liver Disease.

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Sulin Cheng

Full Text Available Fatty liver is a major cause of obesity-related morbidity and mortality. The aim of this study was to identify early metabolic alterations associated with liver fat accumulation in 50- to 55-year-old men (n = 49 and women (n = 52 with and without NAFLD.Hepatic fat content was measured using proton magnetic resonance spectroscopy (1H MRS. Serum samples were analyzed using a nuclear magnetic resonance (NMR metabolomics platform. Global gene expression profiles of adipose tissues and skeletal muscle were analyzed using Affymetrix microarrays and quantitative PCR. Muscle protein expression was analyzed by Western blot.Increased branched-chain amino acid (BCAA, aromatic amino acid (AAA and orosomucoid were associated with liver fat accumulation already in its early stage, independent of sex, obesity or insulin resistance (p<0.05 for all. Significant down-regulation of BCAA catabolism and fatty acid and energy metabolism was observed in the adipose tissue of the NAFLD group (p<0.001for all, whereas no aberrant gene expression in the skeletal muscle was found. Reduced BCAA catabolic activity was inversely associated with serum BCAA and liver fat content (p<0.05 for all.Liver fat accumulation, already in its early stage, is associated with increased serum branched-chain and aromatic amino acids. The observed associations of decreased BCAA catabolism activity, mitochondrial energy metabolism and serum BCAA concentration with liver fat content suggest that adipose tissue dysfunction may have a key role in the systemic nature of NAFLD pathogenesis.

Interaction between valproic acid and aspirin in epileptic children: serum protein binding and metabolic effects.

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Orr, J M; Abbott, F S; Farrell, K; Ferguson, S; Sheppard, I; Godolphin, W

1982-05-01

In five of six epileptic children who were taking 18 to 49 mg/kg/day valproic acid (VPA), the steady-state serum free fractions of VPA rose from 12% to 43% when antipyretic doses of aspirin were also taken. Mean total VPA half-life (t1/2) rose from 10.4 +/- 2.7 to 12.9 +/- 1.8 hr and mean free VPA t1/2 rose from 6.7 +/- to 2.1 to 8.9 +2- 3.0 hr when salicylate was present in the serum. The in vitro albumin binding association constant (ka) for VPA was decreased by salicylate, but the in vivo ka value was not affected. The 12-hr (trough) concentrations of both free and total VPA were higher in the presence of serum salicylate in five of six patients. Renal excretion of unchanged VPA decreased in five of six patients, but the VPA carboxyl conjugate metabolite-excretion patterns were not consistently affected. Salicylate appeared to displace VPA from serum albumin in vivo, but the increased VPA t1/2 and changes in VPA elimination patterns suggest that serum salicylate also altered VPA metabolism.

Tributyltin Exposure Alters Cytokine Levels in Mouse Serum

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Lawrence, Shanieek; Pellom, Samuel T.; Shanker, Anil; Whalen, Margaret M.

2016-01-01

Tributyltin (TBT), a toxic environmental contaminant, has been widely utilized for various industrial, agricultural and household purposes. Its usage has led to a global contamination and its bioaccumulation in aquatic organisms and terrestrial mammals. Previous studies suggest that TBT has debilitating effects on the overall immune function of animals, rendering them more vulnerable to diseases. TBT (at concentrations that have been detected in human blood) alters secretion of inflammatory cytokines from human lymphocytes ex vivo. Thus, it is important to determine if specified levels of TBT can alter levels of cytokines in an in vivo system. Mice were exposed to biologically relevant concentrations of TBT (200, 100 or 25 nM final concentrations). The quantitative determination of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL2, IL5, IL7, IL12βp40, IL13, IL15, KC, MIP1β, MIP2 and RANTES was performed in mouse sera by MAGPIX analysis and Western blot. Results indicated alterations (both decreases and increases) in several cytokines. The pro-inflammatory cytokines IFNγ, TNFα, IL-1β, IL-2, IL5, IL12βp40, and IL-15 were altered as were the chemokines MIP-1 and RANTES and the anti-inflammatory cytokine IL-13. Increases in IFNγ and TNFα were seen in serum of mice exposed to TBT for less than 24 hr. IL1-β, IL-12βp40, IL-5 and IL-15 were also modulated in mouse serum depending on the specific experiment and the exposure concentration. IL-2 was consistently decreased in mouse serum when animals were exposed to TBT. There were also TBT-induced increases in MIP-1β, RANTES, and IL-13. These results from human and murine samples clearly suggest that TBT exposures modulate the secretion inflammatory cytokines. PMID:27602597

Hemodialysis does not alter in vitro hepatic CYP3A4 and CYP2D6 metabolic activity in uremic serum

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Decker BS

2013-12-01

Full Text Available Brian S Decker,1,2 Kalisha D O'Neill,1,2 Mary A Chambers,1,2 James E Slaven,3 Zhangsheng Yu,3 David R Jones,2,4 Sharon M Moe1,21Division of Nephrology, 2Department of Medicine, 3Department of Biostatistics, 4Division of Clinical Pharmacology, Department of Medicine, School of Medicine, Indiana University, Indianapolis, IN, USAAbstract: There is a paucity of studies evaluating the change in liver metabolism in subjects receiving hemodialysis. The purpose of this study was to compare the effect of uremic toxins on hepatic cytochrome P450 (CYP3A4 and CYP2D6 metabolism before and after a 4-hour hemodialysis session. Midazolam and dextromethorphan were incubated with uremic serum collected from subjects before and after the 4-hour hemodialysis session. Analysis and quantification of the 1'-OH-midazolam and 4-OH-midazolam and dextrorphan metabolites were performed by high-pressure liquid chromatography/mass spectrometry. Statistical analysis using the Student's t-test (paired was used to compare the amount of metabolite formed. The mean amount of 1'-OH-midazolam, 4-OH-midazolam, and dextrorphan metabolites formed before and after hemodialysis did not significantly differ. There was no significant difference in CYP3A4 and CYP2D6 metabolic activity in uremic serum before and after hemodialysis.Keywords: hemodialysis, uremia, CYP3A4, CYP2D6, metabolism

Alteration in Bone Mineral Metabolism in Children with Acute Lymphoblastic Leukemia (ALL: A Review

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Chowdhury Yakub Jamal

2009-11-01

Full Text Available In recent years there has been a significant increase in event free survival (EFS and overall survival in children with cancer. As survival rates for childhood cancer have radically improved, late effects associated with the successful but highly intensive chemotherapy and/or radiotherapy have dramatically increased. Many possible late effects of cancer treatment are recognized in pediatric cancer patients as infertility, endocrine deficiency, renal failure, pulmonary and cardiac toxicity, obesity and osteopenia/osteoporosis. Decreased bone mineral density (BMD and bone metabolism disturbances have been recognized and reported in literature. Osteopenia/osteoporosis skeletal abnormalities, osteonecrosis and pathological fractures are known to occur frequently in childhood acute lymphoblastic leukemia (ALL at diagnosis, during and after treatment with chemotherapy. Various studies have revealed different metabolic alterations related to ALL. Some suggestions have been made about their relationship with the disease process. Various metabolic abnormalities may be encountered in the newly diagnosed ALL patients. It includes decreased and increased serum levels of calcium and phosphate. Hypercalcemia may result from leukemic infiltrations of bone and release of parathormone like substance from lymphoblast. Elevated serum phosphate can occur as a result of leukemic cell lysis and may induce hypocalcemia. It has been postulated by other authors that leukemic cells may directly infiltrate bone and produce parathroid hormone related peptides, prostaglandin E and osteoblast inhibiting factors. Hypomagnesemia, hypocalcaemia and hypothyroidisum have been demonstrated in patients with ALL. Some patients may have poor nutrition and decreased physical activities during treatment. However postulations have also been made that chemotherapy may play a role in creating metabolic alterations in children with ALL. Corticosteroid, methotraxate and cranial irradiations

Whole Blood Reveals More Metabolic Detail of the Human Metabolome than Serum as Measured by 1H-NMR Spectroscopy: Implications for Sepsis Metabolomics

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Stringer, Kathleen A.; Younger, John G.; McHugh, Cora; Yeomans, Larisa; Finkel, Michael A.; Puskarich, Michael A.; Jones, Alan E.; Trexel, Julie; Karnovsky, Alla

2015-01-01

Serum is a common sample of convenience for metabolomics studies. Its processing time can be lengthy and may result in the loss of metabolites including those of red blood cells (RBC). Unlike serum, whole blood (WB) is quickly processed, minimizing the influence of variable hemolysis while including RBC metabolites. To determine differences between serum and WB metabolomes, both sample types, collected from healthy volunteers, were assayed by 1H-NMR spectroscopy. A total of 34 and 50 aqueous metabolites were quantified from serum and WB, respectively. Free hemoglobin (Hgb) levels in serum were measured and the correlation between Hgb and metabolite concentrations was determined. All metabolites detected in serum were at higher concentrations in WB with the exception of acetoacetate and propylene glycol. The 18 unique metabolites of WB included adenosine, AMP, ADP and ATP, which are associated with RBC metabolism. The use of serum results in the underrepresentation of a number of metabolic pathways including branched chain amino acid degradation and glycolysis and gluconeogenesis. The range of free Hgb in serum was 0.03-0.01 g/dL and 8 metabolites were associated (p ≤ 0.05) with free Hgb. The range of free Hgb in serum samples from 18 sepsis patients was 0.02-0.46 g/dL. WB and serum have unique aqueous metabolite profiles but the use of serum may introduce potential pathway bias. Use of WB for metabolomics may be particularly important for studies in diseases like sepsis in which RBC metabolism is altered and mechanical and sepsis-induced hemolysis contributes to variance in the metabolome. PMID:26009817

Dietary taurine alters ascorbic acid metabolism in rats fed diets containing polychlorinated biphenyls.

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Mochizuki, H; Oda, H; Yokogoshi, H

2000-04-01

The effect of dietary taurine on ascorbic acid metabolism and hepatic drug-metabolizing enzymes was investigated in rats fed diets containing polychlorinated biphenyls (PCB) to determine whether taurine has an adaptive and protective function in xenobiotic-treated animals. Young male Wistar rats (60 g) were fed diets containing 0 or 0.2 g/kg diet PCB with or without 30 g/kg diet of taurine for 14 d. The rats fed the PCB-containing diets had greater liver weight, higher ascorbic acid concentrations in the liver and spleen and greater hepatic cytochrome P-450 contents than control rats that were not treated with PCB (P ascorbic acid excretion was enhanced, and serum cholesterol concentration (especially HDL-cholesterol) was significantly elevated compared with those in control rats. Dietary taurine significantly potentiated the increases in the urinary excretion of ascorbic acid and the rise in the levels of cytochrome P-450 which were caused by PCB treatment. On the other hand, the supplementation of taurine to control diet did not alter these variables. Taurine may enhance the hepatic drug-metabolizing systems, leading to the stimulation of the ascorbic acid metabolism in rats fed diets containing PCB.

Altered brain arginine metabolism in schizophrenia.

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Liu, P; Jing, Y; Collie, N D; Dean, B; Bilkey, D K; Zhang, H

2016-08-16

Previous research implicates altered metabolism of l-arginine, a versatile amino acid with a number of bioactive metabolites, in the pathogenesis of schizophrenia. The present study, for we believe the first time, systematically compared the metabolic profile of l-arginine in the frontal cortex (Brodmann's area 8) obtained post-mortem from schizophrenic individuals and age- and gender-matched non-psychiatric controls (n=20 per group). The enzyme assays revealed no change in total nitric oxide synthase (NOS) activity, but significantly increased arginase activity in the schizophrenia group. Western blot showed reduced endothelial NOS protein expression and increased arginase II protein level in the disease group. High-performance liquid chromatography and liquid chromatography/mass spectrometric assays confirmed significantly reduced levels of γ-aminobutyric acid (GABA), but increased agmatine concentration and glutamate/GABA ratio in the schizophrenia cases. Regression analysis indicated positive correlations between arginase activity and the age of disease onset and between l-ornithine level and the duration of illness. Moreover, cluster analyses revealed that l-arginine and its main metabolites l-citrulline, l-ornithine and agmatine formed distinct groups, which were altered in the schizophrenia group. The present study provides further evidence of altered brain arginine metabolism in schizophrenia, which enhances our understanding of the pathogenesis of schizophrenia and may lead to the future development of novel preventions and/or therapeutics for the disease.

Changes in serum metabolic hormone levels after glucose infusion during lactation cycles in Holstein cows

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Aliasghar Chalmeh

2015-02-01

Full Text Available Negative energy balance can impair the metabolism of high producing dairy cows and supplying the glucose, as an energy source; can prevent the metabolic disorders in these animals. Hence, we hypothesized that bolus intravenous glucose administration may change the concentrations of metabolic hormones in order to prevent and control of metabolic dysfunctions of dairy cows. Twenty five multiparous Holstein dairy cows were divided to 5 equal groups containing early, mid and late lactations, far-off and close-up dry periods. All cows were received dextrose 50% intravenously at 500 mg/kg, 10 mL/kg/h. Blood samples were collected from all animals prior to and 1, 2, 3 and 4 after dextrose 50% infusion and sera were separated to determine glucose, triiodothyronine (T3, thyroxine (T4, serum free T3 (fT3, free T4 (fT4, cortisol and insulin like growth factor-1 (IGF-1. The decreasing pattern of T3 concentration was detected in all studied animals following intravenous glucose infusion (P<0.05. The significant increasing pattern of T4 levels was seen in early and mid lactation cows after glucose administration (P<0.05. The significant decreasing pattern of IGF-1 was detected in mid and late lactations and far-off dry groups (P<0.05. There were no significant alterations in fT3, fT4 and cortisol concentrations following glucose infusion in all experimental groups. In conclusion, bolus intravenous glucose infusion could influence the metabolic hormones in high producing Holstein dairy cows. Alterations of metabolic hormones following bolus intravenous glucose administration indicated that glucose is an important direct controller of metabolic interactions and responses in dairy cows during different physiological states.

Tributyltin exposure alters cytokine levels in mouse serum.

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Lawrence, Shanieek; Pellom, Samuel T; Shanker, Anil; Whalen, Margaret M

2016-11-01

Tributyltin (TBT), a toxic environmental contaminant, has been widely utilized for various industrial, agricultural and household purposes. Its usage has led to a global contamination and its bioaccumulation in aquatic organisms and terrestrial mammals. Previous studies suggest that TBT has debilitating effects on the overall immune function of animals, rendering them more vulnerable to diseases. TBT (at concentrations that have been detected in human blood) alters secretion of inflammatory cytokines from human lymphocytes ex vivo. Thus, it is important to determine if specified levels of TBT can alter levels of cytokines in an in vivo system. Mice were exposed to biologically relevant concentrations of TBT (200, 100 or 25 nM final concentrations). The quantitative determination of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL2, IL5, IL7, IL12βp40, IL13, IL15, keratinocyte chemoattractant (KC), macrophage inflammatory protein 1β (MIP), MIP2 and regulated on activation normal T-cell-expressed and secreted (RANTES) was performed in mouse sera by MAGPIX analysis and Western blot. Results indicated alterations (both decreases and increases) in several cytokines. The pro-inflammatory cytokines IFNγ, TNFα, IL-1β, IL-2, IL5, IL12βp40 and IL-15 were altered as were the chemokines MIP-1 and RANTES and the anti-inflammatory cytokine IL-13. Increases in IFNγ and TNFα were seen in the serum of mice exposed to TBT for less than 24 h. Levels of IL1β, IL-12 βp40, IL-5 and IL-15 were also modulated in mouse serum, depending on the specific experiment and exposure level. IL-2 was consistently decreased in mouse serum when animals were exposed to TBT. There were also TBT-induced increases in MIP-1β, RANTES and IL-13. These results from human and murine samples clearly suggest that TBT exposures modulate the secretion inflammatory cytokines.

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

Elevated serum tartrate-resistant acid phosphatase isoform 5a levels in metabolic syndrome.

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Huang, Yi-Jhih; Huang, Tsai-Wang; Chao, Tsu-Yi; Sun, Yu-Shan; Chen, Shyi-Jou; Chu, Der-Ming; Chen, Wei-Liang; Wu, Li-Wei

2017-09-29

Tartrate-resistant phosphatase isoform 5a is expressed in tumor-associated macrophages and is a biomarker of chronic inflammation. Herein, we correlated serum tartrate-resistant phosphatase isoform 5a levels with metabolic syndrome status and made comparisons with traditional markers of inflammation, including c-reactive protein and interleukin-6. One hundred healthy volunteers were randomly selected, and cut-off points for metabolic syndrome related inflammatory biomarkers were determined using receiver operating characteristic curves. Linear and logistic regression models were subsequently used to correlate inflammatory markers with the risk of metabolic syndrome. Twenty-two participants met the criteria for metabolic syndrome, and serum tartrate-resistant phosphatase isoform 5a levels of >5.8 μg/L were associated with metabolic syndrome (c-statistics, 0.730; p = 0.001; 95% confidence interval, 0.618-0.842). In addition, 1 μg/L increases in tartrate-resistant phosphatase isoform 5a levels were indicative of a 1.860 fold increase in the risk of metabolic syndrome (p = 0.012). Elevated serum tartrate-resistant phosphatase isoform 5a levels are associated with the risk of metabolic syndrome, with a cut-off level of 5.8 μg/L.

Muscular Dystrophies at Different Ages: Metabolic and Endocrine Alterations

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Oriana del Rocío Cruz Guzmán

2012-01-01

Full Text Available Common metabolic and endocrine alterations exist across a wide range of muscular dystrophies. Skeletal muscle plays an important role in glucose metabolism and is a major participant in different signaling pathways. Therefore, its damage may lead to different metabolic disruptions. Two of the most important metabolic alterations in muscular dystrophies may be insulin resistance and obesity. However, only insulin resistance has been demonstrated in myotonic dystrophy. In addition, endocrine disturbances such as hypogonadism, low levels of testosterone, and growth hormone have been reported. This eventually will result in consequences such as growth failure and delayed puberty in the case of childhood dystrophies. Other consequences may be reduced male fertility, reduced spermatogenesis, and oligospermia, both in childhood as well as in adult muscular dystrophies. These facts all suggest that there is a need for better comprehension of metabolic and endocrine implications for muscular dystrophies with the purpose of developing improved clinical treatments and/or improvements in the quality of life of patients with dystrophy. Therefore, the aim of this paper is to describe the current knowledge about of metabolic and endocrine alterations in diverse types of dystrophinopathies, which will be divided into two groups: childhood and adult dystrophies which have different age of onset.

Altered metabolic signature in pre-diabetic NOD mice.

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Rasmus Madsen

Full Text Available Altered metabolism proceeding seroconversion in children progressing to Type 1 diabetes has previously been demonstrated. We tested the hypothesis that non-obese diabetic (NOD mice show a similarly altered metabolic profile compared to C57BL/6 mice. Blood samples from NOD and C57BL/6 female mice was collected at 0, 1, 2, 3, 4, 5, 6, 7, 9, 11, 13 and 15 weeks and the metabolite content was analyzed using GC-MS. Based on the data of 89 identified metabolites OPLS-DA analysis was employed to determine the most discriminative metabolites. In silico analysis of potential involved metabolic enzymes was performed using the dbSNP data base. Already at 0 weeks NOD mice displayed a unique metabolic signature compared to C57BL/6. A shift in the metabolism was observed for both strains the first weeks of life, a pattern that stabilized after 5 weeks of age. Multivariate analysis revealed the most discriminative metabolites, which included inosine and glutamic acid. In silico analysis of the genes in the involved metabolic pathways revealed several SNPs in either regulatory or coding regions, some in previously defined insulin dependent diabetes (Idd regions. Our result shows that NOD mice display an altered metabolic profile that is partly resembling the previously observation made in children progressing to Type 1 diabetes. The level of glutamic acid was one of the most discriminative metabolites in addition to several metabolites in the TCA cycle and nucleic acid components. The in silico analysis indicated that the genes responsible for this reside within previously defined Idd regions.

Hormone-metabolic parameters of blood serum at revealing the metabolic syndrome at liquidators on Chernobyl disaster

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Chirkin, A.A.; Stepanova, N.A.; Danchenko, E.O.; Orekhova, D.S.

2006-01-01

The purpose of research was the definition of the maintenance leptin, other hormones and some metabolic parameters in liquidators blood serum of group 1.1. Under supervision was 30 healthy persons who were not treat to action of radiation-ecological factors, and 154 liquidators. It is established, that in blood serum of liquidators with body mass index > 25 kg/m 2 leptin concentration is authentically raised and cortisol concentration is lowered. Following most important results are received: 1) hyperleptinemia and hypo-alpha-cholesterolemia can be markers of a radiating influence available in the past; 2) the strict algorithm of revealing of metabolic syndrome X allows to generate adequate groups of risk of the diseases interfaced with an insulin resistance and an atherosclerosis development; 3) the strict algorithm of metabolic syndrome X revealing allows to define concrete directions of metabolic preventive maintenance and therapy at the persons who have entered into risk-groups of diseases development. (authors)

Hyperandrogenemia predicts metabolic phenotype in polycystic ovary syndrome: the utility of serum androstenedione.

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O'Reilly, Michael W; Taylor, Angela E; Crabtree, Nicola J; Hughes, Beverly A; Capper, Farfia; Crowley, Rachel K; Stewart, Paul M; Tomlinson, Jeremy W; Arlt, Wiebke

2014-03-01

Polycystic ovary syndrome (PCOS) is a triad of anovulation, insulin resistance, and hyperandrogenism. Androgen excess may correlate with metabolic risk and PCOS consensus criteria define androgen excess on the basis of serum T. Here we studied the utility of the androgen precursor serum androstenedione (A) in conjunction with serum T for predicting metabolic dysfunction in PCOS. Eighty-six PCOS patients fulfilling Rotterdam diagnostic consensus criteria and 43 age- and body mass index-matched controls underwent measurement of serum androgens by tandem mass spectrometry and an oral glucose tolerance test with homeostatic model assessment of insulin resistance and insulin sensitivity index calculation. We analyzed 24-hour urine androgen excretion by gas chromatography/mass spectrometry. PCOS patients had higher levels of serum androgens and urinary androgen metabolites than controls (all P PCOS cohort, both serum A and T were positively correlated with the free androgen index (T × 100/SHBG) and total androgen metabolite excretion (all P androgen excretion than NA/NT (P androgen phenotype (NA/NT, 0%; HA/NT, 14%; HA/HT, 25%, P = .03). Simultaneous measurement of serum T and A represents a useful tool for predicting metabolic risk in PCOS women. HA levels are a sensitive indicator of PCOS-related androgen excess.

Relationship of serum adipocytokine levels with glucolipid metabolism and micro-inflammatory state in obese children

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Shen Zhao

2016-10-01

Full Text Available Objective: To analyze the relationship of serum adipocytokine levels with glucolipid metabolism and micro-inflammatory state in obese children. Methods: A total of 299 obese children and 264 normal children were included in the study, fasting peripheral venous blood was extracted to determine serum levels of adipocytokines, glucolipid metabolism and microinflammation-related indexes, and the correlation between the levels of adipocytokines and the levels of glucolipid metabolism and micro-inflammation-related indexes was further analyzed. Results: Serum leptin and Vaspin levels of observation group were higher than those of control group, and APN level was lower than that of control group (P<0.05; serum FINS, C-P, Cor, TG and LDL-C levels were higher than those of control group, and HDL-C level was lower than that of control group (P<0.05; serum hs-CRP, IL-8, IL-6 and TNF-α levels were higher than those of control group (P<0.05; serum Leptin, APN and Vaspin levels were directly correlated with the levels of above glucolipid metabolism and micro-micro-inflammatory state indexes. Conclusions: There are high expression levels of inflammatory factors and glucolipid metabolism disorder in obese children, and excessively expressed adipocytokines may be the important factors of persist and worsened obesity.

The Choice of Euthanasia Method Affects Metabolic Serum Biomarkers.

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Pierozan, Paula; Jernerén, Fredrik; Ransome, Yusuf; Karlsson, Oskar

2017-08-01

The impact of euthanasia methods on endocrine and metabolic parameters in rodent tissues and biological fluids is highly relevant for the accuracy and reliability of the data collected. However, few studies concerning this issue are found in the literature. We compared the effects of three euthanasia methods currently used in animal experimentation (i.e. decapitation, CO 2 inhalation and pentobarbital injection) on the serum levels of corticosterone, insulin, glucose, triglycerides, cholesterol and a range of free fatty acids in rats. The corticosterone and insulin levels were not significantly affected by the euthanasia protocol used. However, euthanasia by an overdose of pentobarbital (120 mg/kg intraperitoneal injection) increased the serum levels of glucose, and decreased cholesterol, stearic and arachidonic acids levels compared with euthanasia by CO 2 inhalation and decapitation. CO 2 inhalation appears to increase the serum levels of triglycerides, while euthanasia by decapitation induced no individual discrepant biomarker level. We conclude that choice of the euthanasia methods is critical for the reliability of serum biomarkers and indicate the importance of selecting adequate euthanasia methods for metabolic analysis in rodents. Decapitation without anaesthesia may be the most adequate method of euthanasia when taking both animal welfare and data quality in consideration. © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Identification of the Consistently Altered Metabolic Targets in Human Hepatocellular Carcinoma.

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Nwosu, Zeribe Chike; Megger, Dominik Andre; Hammad, Seddik; Sitek, Barbara; Roessler, Stephanie; Ebert, Matthias Philip; Meyer, Christoph; Dooley, Steven

2017-09-01

Cancer cells rely on metabolic alterations to enhance proliferation and survival. Metabolic gene alterations that repeatedly occur in liver cancer are largely unknown. We aimed to identify metabolic genes that are consistently deregulated, and are of potential clinical significance in human hepatocellular carcinoma (HCC). We studied the expression of 2,761 metabolic genes in 8 microarray datasets comprising 521 human HCC tissues. Genes exclusively up-regulated or down-regulated in 6 or more datasets were defined as consistently deregulated. The consistent genes that correlated with tumor progression markers ( ECM2 and MMP9) (Pearson correlation P < .05) were used for Kaplan-Meier overall survival analysis in a patient cohort. We further compared proteomic expression of metabolic genes in 19 tumors vs adjacent normal liver tissues. We identified 634 consistent metabolic genes, ∼60% of which are not yet described in HCC. The down-regulated genes (n = 350) are mostly involved in physiologic hepatocyte metabolic functions (eg, xenobiotic, fatty acid, and amino acid metabolism). In contrast, among consistently up-regulated metabolic genes (n = 284) are those involved in glycolysis, pentose phosphate pathway, nucleotide biosynthesis, tricarboxylic acid cycle, oxidative phosphorylation, proton transport, membrane lipid, and glycan metabolism. Several metabolic genes (n = 434) correlated with progression markers, and of these, 201 predicted overall survival outcome in the patient cohort analyzed. Over 90% of the metabolic targets significantly altered at the protein level were similarly up- or down-regulated as in genomic profile. We provide the first exposition of the consistently altered metabolic genes in HCC and show that these genes are potentially relevant targets for onward studies in preclinical and clinical contexts.

Serum Progranulin Levels in Type 2 Diabetic Patients with Metabolic Syndrome

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Shafaei Azam

2016-12-01

Full Text Available Introduction. The role of progranulin in individuals with metabolic syndrome is not exactly clear.We aimed to assess the serum level of progranulin in type 2 diabetic patients with and without metabolic syndrome and compare them with healthy controls.

Alterations in urine, serum and brain metabolomic profiles exhibit sexual dimorphism during malaria disease progression

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Sharma Shobhona

2010-04-01

Full Text Available Abstract Background Metabolic changes in the host in response to Plasmodium infection play a crucial role in the pathogenesis of malaria. Alterations in metabolism of male and female mice infected with Plasmodium berghei ANKA are reported here. Methods 1H NMR spectra of urine, sera and brain extracts of these mice were analysed over disease progression using Principle Component Analysis and Orthogonal Partial Least Square Discriminant Analysis. Results Analyses of overall changes in urinary profiles during disease progression demonstrate that females show a significant early post-infection shift in metabolism as compared to males. In contrast, serum profiles of female mice remain unaltered in the early infection stages; whereas that of the male mice changed. Brain metabolite profiles do not show global changes in the early stages of infection in either sex. By the late stages urine, serum and brain profiles of both sexes are severely affected. Analyses of individual metabolites show significant increase in lactate, alanine and lysine, kynurenic acid and quinolinic acid in sera of both males and females at this stage. Early changes in female urine are marked by an increase of ureidopropionate, lowering of carnitine and transient enhancement of asparagine and dimethylglycine. Several metabolites when analysed individually in sera and brain reveal significant changes in their levels in the early phase of infection mainly in female mice. Asparagine and dimethylglycine levels decrease and quinolinic acid increases early in sera of infected females. In brain extracts of females, an early rise in levels is also observed for lactate, alanine and glycerol, kynurenic acid, ureidopropionate and 2-hydroxy-2-methylbutyrate. Conclusions These results suggest that P. berghei infection leads to impairment of glycolysis, lipid metabolism, metabolism of tryptophan and degradation of uracil. Characterization of early changes along these pathways may be crucial for

Subtle metabolic alterations in adolescents with obesity and polycystic ovarian syndrome.

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Vital-Reyes, Víctor Saúl; Lopez-Alarcón, Mardia Guadalupe; Inda-Icaza, Patricia; Márquez-Maldonado, Concepción

2017-01-01

To evaluate the frequency of some subtle metabolic alterations in a group of adolescents with obesity and polycystic ovary syndrome (PCOS). A cross-sectional, comparative study was conducted in a group of adolescents with obesity, and characterized as with or without PCOS according with the Rotterdam Consensus. Medical history, anthropometry, gynecologic pelvic ultrasound (to evaluate ovarian volumes, number of antral follicles and endometrial width), as well as serum glucose, insulin, lipoproteins, interleukin-6, tumor necrosis factor alpha, total testosterone, dehydroepiandrosterone, sexual hormones binding globulin, leptin, adiponectin and insulin-like growth factor 1, the free-androgen index, free and available testosterone, and homeostatic model assessment index were calculated. For statistics, mean and standard deviation, or median and ranges were used for description as appropriate. Likewise, Student t-test or Mann-Whitney test were used for comparisons. From a sample of 180 adolescents, 47 attached to selection criteria. Mean age was 13.5 year and Z-score 2.5. Eighty percent of adolescents presented central distribution of body fat and 95% hyperinsulinemia. The more frequent dyslipidemias were hypertriglyceridemia in 57% and hypercholesterolemia in 12.8%; 25.5% of adolescents presented two out of three criteria for polycystic ovary syndrome (PCOS). Body mass index and insulin were correlated with free testosterone, but the multivariate analysis demonstrated that the magnitude of the association was significantly higher in SOP patients. The metabolic alterations detected in obese adolescents with SOP suggest that the clinical manifestations that accompany the syndrome characterize the PCOS as a metabolic disease, which carry important health risks at short, medium and long term. Therefore, they merit intervening actions to prevent, diagnose and provide timing treatment in order to limit the damage in the course of the natural history of PCOS. Copyright: �

Serum Compounds of Energy Metabolism Impairment Are Related to Disability, Disease Course and Neuroimaging in Multiple Sclerosis.

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Lazzarino, Giacomo; Amorini, Angela M; Petzold, Axel; Gasperini, Claudio; Ruggieri, Serena; Quartuccio, Maria Esmeralda; Lazzarino, Giuseppe; Di Stasio, Enrico; Tavazzi, Barbara

2017-11-01

Multiple sclerosis (MS) is characterized by primary inflammation, demyelination, and progressive neurodegeneration. A biochemical MS feature is neuronal mitochondrial dysfunction, compensated by anaerobic metabolism increase, likely aggravating progression of neurodegeneration. Here, we characterized a pragmatic serum profile of compounds related to mitochondrial energy metabolism of potential clinical use. Blood samples of 518 well characterized (disability, disease course) MS patients and 167 healthy controls were analyzed for serum purines, pyrimidines, creatinine, and lactate. Nine of the 15 compounds assayed, hypoxanthine, xanthine, uric acid, inosine, uracil, β-pseudouridine, uridine, creatinine, and lactate, differed significantly between MS patients and controls (p < 0.0001). Using these nine compounds, a unifying Biomarker Score was calculated. Controls and MS patients had mean Biomarker Scores of 0.4 ± 0.7 and 4.4 ± 1.9, respectively (p < 0.00001). The Biomarker Score was higher in patients with progressive (6.0 ± 1.8 than with relapsing remitting disease course (3.6 ± 1.5, p < 0.00001). High association between the Biomarker Score and increase in disability (EDSS) was also observed. Additionally, in 50 patients who underwent magnetic resonance imaging (MRI), increase in the Biomarker Score correlated to neuroanatomical alterations. These results, obtained in a large cohort of MS patients evaluated for serum metabolic compounds connected to energy metabolism, demonstrated that the Biomarker Score might represent a pragmatic, resource saving, easy to obtain, laboratory tool useful to monitor MS patients and predict at an early stage who will switch from an RR to a progressive disease course. For the first time, it was also clearly shown a link between mitochondrial dysfunction and MRI lesions characteristic of MS.

Citrate metabolism and its complications in non-massive blood transfusions: association with decompensated metabolic alkalosis+respiratory acidosis and serum electrolyte levels.

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Bıçakçı, Zafer; Olcay, Lale

2014-06-01

Metabolic alkalosis, which is a non-massive blood transfusion complication, is not reported in the literature although metabolic alkalosis dependent on citrate metabolism is reported to be a massive blood transfusion complication. The aim of this study was to investigate the effect of elevated carbon dioxide production due to citrate metabolism and serum electrolyte imbalance in patients who received frequent non-massive blood transfusions. Fifteen inpatients who were diagnosed with different conditions and who received frequent blood transfusions (10-30 ml/kg/day) were prospectively evaluated. Patients who had initial metabolic alkalosis (bicarbonate>26 mmol/l), who needed at least one intensive blood transfusion in one-to-three days for a period of at least 15 days, and whose total transfusion amount did not fit the massive blood transfusion definition (alkalosis+respiratory acidosis developed as a result of citrate metabolism. There was a positive correlation between cumulative amount of citrate and the use of fresh frozen plasma, venous blood pH, ionized calcium, serum-blood gas sodium and mortality, whereas there was a negative correlation between cumulative amount of citrate and serum calcium levels, serum phosphorus levels and amount of urine chloride. In non-massive, but frequent blood transfusions, elevated carbon dioxide production due to citrate metabolism causes intracellular acidosis. As a result of intracellular acidosis compensation, decompensated metabolic alkalosis+respiratory acidosis and electrolyte imbalance may develop. This situation may contribute to the increase in mortality. In conclusion, it should be noted that non-massive, but frequent blood transfusions may result in certain complications. Copyright © 2014 Elsevier Ltd. All rights reserved.

5-HT2A receptor deficiency alters the metabolic and transcriptional, but not the behavioral, consequences of chronic unpredictable stress

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Minal Jaggar

2017-12-01

Full Text Available Chronic stress enhances risk for psychiatric disorders, and in animal models is known to evoke depression-like behavior accompanied by perturbed neurohormonal, metabolic, neuroarchitectural and transcriptional changes. Serotonergic neurotransmission, including serotonin2A (5-HT2A receptors, have been implicated in mediating specific aspects of stress-induced responses. Here we investigated the influence of chronic unpredictable stress (CUS on depression-like behavior, serum metabolic measures, and gene expression in stress-associated neurocircuitry of the prefrontal cortex (PFC and hippocampus in 5-HT2A receptor knockout (5-HT2A−/− and wild-type mice of both sexes. While 5-HT2A−/− male and female mice exhibited a baseline reduced anxiety-like state, this did not alter the onset or severity of behavioral despair during and at the cessation of CUS, indicating that these mice can develop stress-evoked depressive behavior. Analysis of metabolic parameters in serum revealed a CUS-evoked dyslipidemia, which was abrogated in 5-HT2A−/− female mice with a hyperlipidemic baseline phenotype. 5-HT2A−/− male mice in contrast did not exhibit such a baseline shift in their serum lipid profile. Specific stress-responsive genes (Crh, Crhr1, Nr3c1, and Nr3c2, trophic factors (Bdnf, Igf1 and immediate early genes (IEGs (Arc, Fos, Fosb, Egr1-4 in the PFC and hippocampus were altered in 5-HT2A−/− mice both under baseline and CUS conditions. Our results support a role for the 5-HT2A receptor in specific metabolic and transcriptional, but not behavioral, consequences of CUS, and highlight that the contribution of the 5-HT2A receptor to stress-evoked changes is sexually dimorphic. Keywords: 5-HT2A−/− mice, Prefrontal cortex, Hippocampus, Gene expression, Sexual dimorphism, Despair

Rice Bran and Probiotics Alter the Porcine Large Intestine and Serum Metabolomes for Protection against Human Rotavirus Diarrhea

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Elizabeth P. Ryan

2017-04-01

Full Text Available Human rotavirus (HRV is a leading cause of severe childhood diarrhea, and there is limited vaccine efficacy in the developing world. Neonatal gnotobiotic pigs consuming a prophylactic synbiotic combination of probiotics and rice bran (Pro+RB did not exhibit HRV diarrhea after challenge. Multiple immune, gut barrier protective, and anti-diarrheal mechanisms contributed to the prophylactic efficacy of Pro+RB when compared to probiotics (Pro alone. In order to understand the molecular signature associated with diarrheal protection by Pro+RB, a global non-targeted metabolomics approach was applied to investigate the large intestinal contents and serum of neonatal gnotobiotic pigs. The ultra-high performance liquid chromatography-tandem mass spectrometry platform revealed significantly different metabolites (293 in LIC and 84 in serum in the pigs fed Pro+RB compared to Pro, and many of these metabolites were lipids and amino acid/peptides. Lipid metabolites included 2-oleoylglycerol (increased 293.40-fold in LIC of Pro+RB, p = 3.04E-10, which can modulate gastric emptying, andhyodeoxycholate (decreased 0.054-fold in the LIC of Pro+RB, p = 0.0040 that can increase colonic mucus production to improve intestinal barrier function. Amino acid metabolites included cysteine (decreased 0.40-fold in LIC, p = 0.033, and 0.62-fold in serum, p = 0.014 of Pro+RB, which has been found to reduce inflammation, lower oxidative stress and modulate mucosal immunity, and histamine (decreased 0.18-fold in LIC, p = 0.00030, of Pro+RB and 1.57-fold in serum, p = 0.043, which modulates local and systemic inflammatory responses as well as influences the enteric nervous system. Alterations to entire LIC and serum metabolic pathways further contributed to the anti-diarrheal and anti-viral activities of Pro+RB such as sphingolipid, mono/diacylglycerol, fatty acid, secondary bile acid, and polyamine metabolism. Sphingolipid and long chain fatty acid profiles influenced the

Altered erythropoiesis and iron metabolism in carriers of thalassemia

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

2014-01-01

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

Higher levels of serum lycopene are associated with reduced mortality in individuals with metabolic syndrome.

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Han, Guang-Ming; Meza, Jane L; Soliman, Ghada A; Islam, K M Monirul; Watanabe-Galloway, Shinobu

2016-05-01

Metabolic syndrome increases the risk of mortality. Increased oxidative stress and inflammation may play an important role in the high mortality of individuals with metabolic syndrome. Previous studies have suggested that lycopene intake might be related to the reduced oxidative stress and decreased inflammation. Using data from the National Health and Nutrition Examination Survey, we examined the hypothesis that lycopene is associated with mortality among individuals with metabolic syndrome. A total of 2499 participants 20 years and older with metabolic syndrome were divided into 3 groups based on their serum concentration of lycopene using the tertile rank method. The National Health and Nutrition Examination Survey from years 2001 to 2006 was linked to the mortality file for mortality follow-up data through December 31, 2011, to determine the mortality rate and hazard ratios (HR) for the 3 serum lycopene concentration groups. The mean survival time was significantly higher in the group with the highest serum lycopene concentration (120.6 months; 95% confidence interval [CI], 118.8-122.3) and the medium group (116.3 months; 95% CI, 115.2-117.4), compared with the group with lowest serum lycopene concentration (107.4 months; 95% CI, 106.5-108.3). After adjusting for possible confounding factors, participants in the highest (HR, 0.61; P = .0113) and in the second highest (HR, 0.67; P = .0497) serum lycopene concentration groups showed significantly lower HRs of mortality when compared with participants in the lower serum lycopene concentration. The data suggest that higher serum lycopene concentration has a significant association with the reduced risk of mortality among individuals with metabolic syndrome. Copyright © 2016 Elsevier Inc. All rights reserved.

Association of Serum Adiponectin Levels with Metabolic Syndrome Risk Factors in Malay Adults

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Nur Firdaus Isa

2017-09-01

Full Text Available Introduction: This study aimed to investigate the relationship between serum adiponectin and metabolic syndrome in adults living in rural Malaysia. Methods: A total of 299 Malay adults (men=124; women = 175 with a mean age 48.8 (11.7 years were recruited. Measurements for waist circumference and blood pressure were taken before drawing an overnight fasting blood samples. Biochemical tests for triglycerides, HDL cholesterol, glucose and serum adiponectin concentration were measured. Results: Our results show that the adiponectin level in the subjects with metabolic syndrome was significantly lower than those without metabolic syndrome (p < 0.05. Among the metabolic syndrome risk factors, adiponectin level was significantly associated with hypertriglyceridemia and reduced HDL cholesterol (p < 0.001. Conclusion: The outcome from this study which highlights the association of hypoadiponectinemia with risk factors of metabolic syndrome in Malay adults, suggests that the reduced level of adiponectin may play a pivotal role in the development of metabolic syndrome in this ethnic group.

Identification of the Consistently Altered Metabolic Targets in Human Hepatocellular CarcinomaSummary

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Zeribe Chike Nwosu

2017-09-01

Full Text Available Background & Aims: Cancer cells rely on metabolic alterations to enhance proliferation and survival. Metabolic gene alterations that repeatedly occur in liver cancer are largely unknown. We aimed to identify metabolic genes that are consistently deregulated, and are of potential clinical significance in human hepatocellular carcinoma (HCC. Methods: We studied the expression of 2,761 metabolic genes in 8 microarray datasets comprising 521 human HCC tissues. Genes exclusively up-regulated or down-regulated in 6 or more datasets were defined as consistently deregulated. The consistent genes that correlated with tumor progression markers (ECM2 and MMP9 (Pearson correlation P < .05 were used for Kaplan-Meier overall survival analysis in a patient cohort. We further compared proteomic expression of metabolic genes in 19 tumors vs adjacent normal liver tissues. Results: We identified 634 consistent metabolic genes, ∼60% of which are not yet described in HCC. The down-regulated genes (n = 350 are mostly involved in physiologic hepatocyte metabolic functions (eg, xenobiotic, fatty acid, and amino acid metabolism. In contrast, among consistently up-regulated metabolic genes (n = 284 are those involved in glycolysis, pentose phosphate pathway, nucleotide biosynthesis, tricarboxylic acid cycle, oxidative phosphorylation, proton transport, membrane lipid, and glycan metabolism. Several metabolic genes (n = 434 correlated with progression markers, and of these, 201 predicted overall survival outcome in the patient cohort analyzed. Over 90% of the metabolic targets significantly altered at the protein level were similarly up- or down-regulated as in genomic profile. Conclusions: We provide the first exposition of the consistently altered metabolic genes in HCC and show that these genes are potentially relevant targets for onward studies in preclinical and clinical contexts. Keywords: Liver Cancer, HCC, Tumor Metabolism

Characteristics of Endotoxin-Altering Fractions Derived from Normal Serum III. Isolation and Properties of Horse Serum alpha(2)-Macroglobulin.

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Yoshioka, M; Konno, S

1970-05-01

The endotoxin-altering activity of fractions isolated from normal horse serum was examined by incubation of Salmonella typhosa strain 0-901 endotoxin (Boivin) in a solution of the fraction, and subsequent quantitation of any diminution in the capacity of endotoxin to be precipitated by specific anti-endotoxin antiserum. The horse serum fraction isolated by precipitation with ammonium sulfate at a concentration between 1.6 and 2.7 m was incubated with Pronase PA and then with trypsin. When this partly digested fraction was passed twice through a Sephadex G-200 column and eluted with 0.2 m tris(hydroxymethyl)aminomethane buffer, most of the endotoxinaltering activity was found in the first protein peak designated F-1a. F-1a was found to be homogeneous and corresponded to an alpha(2)-macroglobulin by the techniques of electrophoresis, immunodiffusion, and ultracentrifugation. Approximately 100-fold more F-1a than endotoxin was needed to reduce the antigenicity of the endotoxin by one-half. Alteration was increased when F-1a was incubated with the endotoxin at acid pH or at 45 C rather than at 37 C and was lost after heating F-1a at 56 C for 30 min. N-ethylmaleimide increased the endotoxin-altering activity of horse serum, F-1a, and human plasma fraction III(0), whereas p-chloromercuribenzoate did not. On the other hand, diazonium-1-H-tetrazole, iodoacetic acid, and benzylchloride suppressed the activity of F-1a. When the interaction of endotoxin and F-1a was examined by immunodiffusion techniques, depolymerization of the endotoxin molecule was indicated. The endotoxin-altering factor of horse serum is discussed in relation to the mechanisms of other known reagents, such as deoxycholate and sodium lauryl sulfate.

Characteristics of Endotoxin-Altering Fractions Derived from Normal Serum III. Isolation and Properties of Horse Serum α2-Macroglobulin

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Yoshioka, Morimasa; Konno, Seishi

1970-01-01

The endotoxin-altering activity of fractions isolated from normal horse serum was examined by incubation of Salmonella typhosa strain 0-901 endotoxin (Boivin) in a solution of the fraction, and subsequent quantitation of any diminution in the capacity of endotoxin to be precipitated by specific anti-endotoxin antiserum. The horse serum fraction isolated by precipitation with ammonium sulfate at a concentration between 1.6 and 2.7 m was incubated with Pronase PA and then with trypsin. When this partly digested fraction was passed twice through a Sephadex G-200 column and eluted with 0.2 m tris(hydroxymethyl)aminomethane buffer, most of the endotoxinaltering activity was found in the first protein peak designated F-1a. F-1a was found to be homogeneous and corresponded to an α2-macroglobulin by the techniques of electrophoresis, immunodiffusion, and ultracentrifugation. Approximately 100-fold more F-1a than endotoxin was needed to reduce the antigenicity of the endotoxin by one-half. Alteration was increased when F-1a was incubated with the endotoxin at acid pH or at 45 C rather than at 37 C and was lost after heating F-1a at 56 C for 30 min. N-ethylmaleimide increased the endotoxin-altering activity of horse serum, F-1a, and human plasma fraction III0, whereas p-chloromercuribenzoate did not. On the other hand, diazonium-1-H-tetrazole, iodoacetic acid, and benzylchloride suppressed the activity of F-1a. When the interaction of endotoxin and F-1a was examined by immunodiffusion techniques, depolymerization of the endotoxin molecule was indicated. The endotoxin-altering factor of horse serum is discussed in relation to the mechanisms of other known reagents, such as deoxycholate and sodium lauryl sulfate. Images PMID:16557754

Reduced brain/serum glucose ratios predict cerebral metabolic distress and mortality after severe brain injury.

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Kurtz, Pedro; Claassen, Jan; Schmidt, J Michael; Helbok, Raimund; Hanafy, Khalid A; Presciutti, Mary; Lantigua, Hector; Connolly, E Sander; Lee, Kiwon; Badjatia, Neeraj; Mayer, Stephan A

2013-12-01

The brain is dependent on glucose to meet its energy demands. We sought to evaluate the potential importance of impaired glucose transport by assessing the relationship between brain/serum glucose ratios, cerebral metabolic distress, and mortality after severe brain injury. We studied 46 consecutive comatose patients with subarachnoid or intracerebral hemorrhage, traumatic brain injury, or cardiac arrest who underwent cerebral microdialysis and intracranial pressure monitoring. Continuous insulin infusion was used to maintain target serum glucose levels of 80-120 mg/dL (4.4-6.7 mmol/L). General linear models of logistic function utilizing generalized estimating equations were used to relate predictors of cerebral metabolic distress (defined as a lactate/pyruvate ratio [LPR] ≥ 40) and mortality. A total of 5,187 neuromonitoring hours over 300 days were analyzed. Mean serum glucose was 133 mg/dL (7.4 mmol/L). The median brain/serum glucose ratio, calculated hourly, was substantially lower (0.12) than the expected normal ratio of 0.40 (brain 2.0 and serum 5.0 mmol/L). In addition to low cerebral perfusion pressure (P = 0.05) and baseline Glasgow Coma Scale score (P brain/serum glucose ratios below the median of 0.12 were independently associated with an increased risk of metabolic distress (adjusted OR = 1.4 [1.2-1.7], P brain/serum glucose ratios were also independently associated with in-hospital mortality (adjusted OR = 6.7 [1.2-38.9], P brain/serum glucose ratios, consistent with impaired glucose transport across the blood brain barrier, are associated with cerebral metabolic distress and increased mortality after severe brain injury.

Some metabolic and anthropometric variables in obes children by measuring serum insulin, and leptin

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Nour Eldin, A.M.

2004-01-01

The present study aimed to assess serum leptin level in obese children to study its correlation with some metabolic variables as serum insulin and serum glucose. The study was conducted on 30 obese children of age from 9-14 years with body mass index (BMI) > 27.8 Kg/m 2 . All children were subjected to history taking, clinical examination, anthropometric measurements and laboratory investigations including fasting serum leptin, insulin and blood glucose. Serum leptin was significantly higher in obese children (102.3± 56.2 ng/ml) compared to non-obese ones (48.15±26.1 ng/ml). The relation between serum leptin and anthropometric measurements and laboratory investigations including fasting serum insulin and blood glucose. Serum leptin was significantly higher in obese children (102.3± 56.2 ng/ml)compared to non-obese ones (48.15±26.1 ng/ml). The relation between serum leptin and anthropometric variables was positively correlated with BMI r s = 0.68, (p s = 0.59.(p<0.01). It is concluded that serum leptin is increased in obesity and its concentration effects the size of the body. Moreover, the relation of leptin and insulin suggests a positive role of leptin in insulin resistance, which are common metabolic disorders associated with obesity

Urinary deoxypyridinoline (DPD), serum bone glia protein (BGP) and bone metabolism change in hyperthyroidism

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Zeng Yun; Ding Jianzhong; Xiang Hong

2002-01-01

Objective: To study the effect of thyroid function on bone metabolism. Methods: Urinary DPD, Serum FT 3 , FT 4 and BGP levels were determined with chemiluminescence assay and RIA in 41 patients with hyperthyroidism and 47 healthy controls. Results: Urinary DPD and serum FT 3 , FT 4 , BGP levels were significantly higher in patients with hyperthyroidism than those in healthy controls (p < 0.01). Conclusion: The data showed that hyperthyroidism was correlated with bone metabolism

Increased intestinal permeability, measured by serum zonulin, is associated with metabolic risk markers in overweight pregnant women.

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Mokkala, Kati; Pellonperä, Outi; Röytiö, Henna; Pussinen, Pirkko; Rönnemaa, Tapani; Laitinen, Kirsi

2017-04-01

Increased intestinal permeability with subsequent metabolic endotoxemia, i.e., elevated circulating levels of bacterial lipopolysaccharide, LPS, has been introduced as a novel initiator of obesity related metabolic disturbances in non-pregnant individuals. The objective was to investigate the extent to which intestinal permeability, measured by serum zonulin concentration, is related to metabolic endotoxemia and metabolic risk markers in overweight pregnant women. This was a cross-sectional study including 100 pregnant overweight women in early pregnancy. Serum zonulin was analyzed using ELISA, and markers for metabolic endotoxemia (LPS), inflammation (high-sensitive C-reactive protein and glycoprotein acetylation GlyA), glucose metabolism (fasting glucose and insulin), and lipid metabolism were measured. Higher serum zonulin concentration associated positively with LPS (P=0.02), inflammatory markers (Pzonulin quartiles). All the observed associations were confirmed (Pzonulin concentration, i.e., increased intestinal permeability, contributes to metabolic endotoxemia, systemic inflammation, and insulin resistance in overweight pregnant women. By reinforcing intestinal barrier, it may be possible to manipulate maternal metabolism during pregnancy with subsequent health benefits. Copyright © 2017 Elsevier Inc. All rights reserved.

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

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

2017-04-01

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

GC-MS-Based metabolomics discovers a shared serum metabolic characteristic among three types of epileptic seizures.

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Wang, Dian; Wang, Xingxing; Kong, Jing; Wu, Jiayan; Lai, Minchao

2016-10-01

Understanding the overall and common metabolic changes of seizures can provide novel clues for their control and prevention. Here, we aim to investigate the global metabolic feature of serum for three types of seizures. We recruited 27 patients who had experienced a seizure within 48h (including 11 who had a generalized seizure, nine who had a generalized seizure secondary to partial seizure and seven who had a partial seizure) and 23 healthy controls. We analyzed the global metabolic changes of serum after seizures using gas chromatography-mass spectrometry-based metabolomics. Based on differential metabolites, the metabolic pathways and their potential to diagnose seizures were analyzed, and metabolic differences among three types of seizures were compared. The metabolic profiles of serum were distinctive between the seizure group and the controls but were not different among the three types of seizures. Compared to the controls, patients with seizures had higher levels of lactate, butanoic acid, proline and glutamate and lower levels of palmitic acid, linoleic acid, elaidic acid, trans-13-octadecenoic acid, stearic acid, citrate, cysteine, glutamine, asparagine, and glyceraldehyde in the serum. Furthermore, these differential metabolites had common change trends among the three types of seizures. Related pathophysiological processes reflected by these metabolites are energy deficit, inflammation, nervous excitation and neurotoxicity. Importantly, transamination inhibition is suspected to occur in seizures. Lactate, glyceraldehyde and trans-13-octadecenoic acid in serum jointly enabled a precision of 92.9% for diagnosing seizures. There is a common metabolic feature in three types of seizures. Lactate, glyceraldehyde and trans-13-octadecenoic acid levels jointly enable high-precision seizure diagnosis. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparison of Serum Adipocytokine Levels according to Metabolic Health and Obesity Status

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Tae Hoon Lee

2015-06-01

Full Text Available BackgroundMetabolic health is an emerging concept that is highly correlated with various metabolic complications, and adipocytokines have been causally linked to a wide range of metabolic diseases. Thus, this study compared serum adipocytokine levels according to metabolic health and obesity status.MethodsFour hundred and fifty-six nondiabetic subjects (mean age, 40.5 years were categorized into four groups according to metabolic health and obesity status: metabolically healthy nonobese (MHNO, metabolically healthy obese (MHO, metabolically unhealthy nonobese (MUHNO, and metabolically unhealthy obese (MUHO. Being metabolically healthy was defined as the presence of fewer than two of the following five metabolic abnormalities: high blood pressure, high fasting blood glucose, high triglyceride, low high density lipoprotein cholesterol, and being in the highest decile of the homeostatic model assessment of insulin resistance index. Obesity status was assessed using body mass index (BMI, with obesity defined as a BMI higher than 25 kg/m2. Levels of serum interleukin-6 (IL-6, monocyte chemoattractant protein-1 (MCP-1, tumor necrosis factor α (TNF-α, and adipocyte fatty acid binding protein (A-FABP were also evaluated.ResultsOf the 456 subjects, 247 (54.2% were in the MHNO group, 66 (14.5% were in the MHO group, 66 (14.5% were in the MUHNO group, and 77 (16.9% were in the MUHO group. There were no significant differences in IL-6 or MCP-1 levels among the groups, but levels of TNF-α and A-FABP were significantly higher in the MUHNO group compared to the MHNO group.ConclusionHigh TNF-α and A-FABP levels are significantly associated with metabolically unhealthiness in nonobese Korean individuals.

Deciphering the Differential Effective and Toxic Responses of Bupleuri Radix following the Induction of Chronic Unpredictable Mild Stress and in Healthy Rats Based on Serum Metabolic Profiles

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Xiaoxia Gao

2018-01-01

Full Text Available The petroleum ether fraction of Bupleuri Radix which is contained in the traditional Chinese medicine prescription of Xiaoyaosan (XYS may have a therapeutic effect in depressed subjects based on the results of our previous study. It has been reported that Bupleuri Radix can cause liver toxicity following overdosing or long-term use. Therefore, this study aimed to decipher the differential effective and toxic responses of Bupleuri Radix in chronic unpredictable mild stress (CUMS (with depression and healthy rats based on serum metabolic profiles. Serum metabolic profiles were obtained using the UHPLC- Q Exactive Orbitrap-MS technique. Our results demonstrated that the petroleum ether fraction of Bupleuri Radix (PBR produces an antidepressant effect through regulating glycometabolism, amino acid metabolism, sphingolipid metabolism, glycerophospholipid metabolism, and fatty acid metabolism. It also induces more severe toxic reactions in the liver or kidney in healthy rats than in CUMS rats, which exhibited a comparatively mild drug-induced toxic reaction. The altered lysine degradation, sphingolipid metabolism, glycerophospholipid metabolism, fatty acid metabolism, and bile acid metabolism could be at least partly responsible for the PBR toxic responses in healthy rats. The differential effective and toxic response of PBR in CUMS rats and healthy rats provide a new standard for the more rational and safer application of clinical drugs in the future.

Alterations of polyunsaturated fatty acid metabolism in ovarian tissues of polycystic ovary syndrome rats.

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Huang, Rong; Xue, Xinli; Li, Shengxian; Wang, Yuying; Sun, Yun; Liu, Wei; Yin, Huiyong; Tao, Tao

2018-03-30

The metabolism of polyunsaturated fatty acids (PUFAs) remains poorly characterized in ovarian tissues of patients with polycystic ovary syndrome (PCOS). This study aimed to explore alterations in the levels of PUFAs and their metabolites in serum and ovarian tissues in a PCOS rat model treated with a high-fat diet and andronate. Levels of PUFAs and their metabolites were measured using gas/liquid chromatography-mass spectrometry after the establishment of a PCOS rat model. Only 3 kinds of PUFAs [linoleic acid, arachidonic acid (AA) and docosahexaenoic acid] were detected in both the circulation and ovarian tissues of the rats, and their concentrations were lower in ovarian tissues than in serum. Moreover, significant differences in the ovarian levels of AA were observed between control, high-fat diet-fed and PCOS rats. The levels of prostaglandins, AA metabolites via the cyclooxygenase (COX) pathway, in ovarian tissues of the PCOS group were significantly increased compared to those in the controls. Further studies on the mechanism underlying this phenomenon showed a correlation between decreased expression of phosphorylated cytosolic phospholipase A2 (p-cPLA2) and increased mRNA and protein expression of COX2, potentially leading to a deeper understanding of altered AA and prostaglandin levels in ovarian tissues of PCOS rats. © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Altered serum copper homeostasis suggests higher oxidative stress and lower antioxidant capability in patients with chronic hepatitis B.

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Huang, Yansong; Zhang, Yuan; Lin, Zhexuan; Han, Ming; Cheng, Hongqiu

2018-06-01

Copper homeostasis can be altered by inflammation. This study aimed to investigate the alteration of serum copper homeostasis and to explore its clinical significance in patients with chronic hepatitis B (CHB).Thirty-two patients with CHB and 10 aged- and sex-matched healthy controls were recruited. Analyses included serum levels of total copper (TCu), copper ions (Cu), small molecule copper (SMC), ceruloplasmin (CP), Cu/Zn superoxide dismutase 1 (SOD1), urinary copper, and the activities of serum CP and SOD1.The serum TCu and urinary copper levels in patients with CHB were significantly higher than the controls (P = .04 and .003), while the serum Cu was lower than the controls (P = .0002). CP and SOD1 activities in the serum were significantly lower in patients with CHB compared to controls (P = .005) despite higher serum concentrations. In addition, serum alanine aminotransferase inversely correlated with serum CP activity (P = .0318, r = -0.4065).Serum copper homeostasis was altered in this cohort of patients with CHB. The results suggest increased oxidative stress and impaired antioxidant capability in patients with CHB, in addition to necroinflammation. These results may provide novel insights into the diagnosis and treatment of patients with CHB.

The relationship between metabolic presbycusis and serum paraoxonase/arylesterase activity.

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Keleş, Erol; Kapusuz, Zeliha; Gürsu, Mehmet Ferit; Karlıdag, Turgut; Kaygusuz, Irfan; Bulmuş, Funda Gülcü; Yalcın, Sinasi

2014-01-01

To determine the presence of a relationship between metabolic presbycusis and serum paraoxonase/arylesterase activity. A total of 30 patients who had been admitted to the Ear, Nose, and Throat (ENT) Clinic of Fırat University Medical Faculty and diagnosed as metabolic presbycusis were included in the study. The control group was composed of 30 healthy volunteers. Pure tone audiometry and impedencemeter were performed on all subjects included in the study at the audiometry laboratory of the ENT clinic. The presence of a regular hearing curve, a symmetrical sensorineural hearing loss more than 25 dB with preserved speech discrimination were accepted as criteria for metabolic presbycusis. Blood samples were drawn from the patients prior to the hearing tests. The sera were separated for measurements of total cholesterol, triglyceride, high-density lipoprotein, very low-density lipoprotein, low-density lipoprotein, human serum paraoxonase and arylesterase levels, respectively. No statistically significant difference was found between the patient and the control groups in terms of age and gender. Paraoxonase, arylesterase and paraoxonase/arylesterase, high-density lipoprotein levels were found to decrease in the study group and the difference was found to be statistically significant compared to the control group (P presbycusis. Furthermore, the results of this study make us think that there could be a relationship between metabolic presbycusis and cardiovascular diseases. In this case, metabolic presbycusis may be a determining parameter in the early diagnosis of cardiovascular diseases. We consider that this study may be the pioneer for further studies conducted with larger patient numbers.

Effects of Walker 256 carcinoma on metabolic alterations during the evolution of pregnancy.

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Cintra-Gomes, M C; Cury, L; Parreira, M R; Elias, C F; Areas, M A

1990-01-01

The control of pregnant cancer patients is difficult because it involves both mother and fetus, and the metabolic alterations in the cancer host induce a massive mobilization of nutrients diverted to the neoplastic cells. The purpose of the present study was to determine the evolution of the Walker 256 carcinoma in pregnant rats and its consequences on fetal development. The results showed that the tumors displayed a very rapid rate of growth and induced a reduction in fetal weights in the pregnant tumor-bearing rats. The tumor-bearing and pregnant tumor-bearing groups showed a decrease in blood glucose and total serum protein, suggesting an increase in energy utilization of these substrates and synthetic activity by the tumoral cells. An imbalance between protein synthesis and catabolism may occur in the tumor-bearing rats which may be related to the degree of nutritional depletion.

Serum uric acid concentration and metabolic syndrome among elderly Koreans: The Korean Urban Rural Elderly (KURE) study.

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Choi, Hansol; Kim, Hyeon Chang; Song, Bo Mi; Park, Ji Hye; Lee, Ju-Mi; Yoon, Da-Lim; Yoon, Young Mi; Rhee, Yumie; Youm, Yousik; Kim, Chang Oh

2016-01-01

Epidemiologic studies have demonstrated that elevated serum uric acid concentration is an independent risk factor for metabolic syndrome. However, few studies have focused on elderly populations. Thus, we investigated the association of serum uric acid concentration with metabolic syndrome in community-dwelling elderly Koreans. This cross-sectional analysis included 2940 participants (986 men and 1954 women) aged 65 years or older who participated in a baseline health assessment for the Korean Urban Rural Elderly cohort study from 2012 to 2014. Serum uric acid concentration was analyzed using both continuous and dichotomous variables. Hyperuricemia was defined as a uric acid concentration ≥7.0 mg/dL in men and ≥6.0 mg/dL in women. Metabolic syndrome was defined according to the 2009 harmonizing definition. Multiple logistic regression models were used to investigate independent association between serum uric acid and metabolic syndrome, after adjusting for age, body mass index, LDL cholesterol, glycated hemoglobin, blood urea nitrogen, estimated glomerular filtration rate health behaviors, and medications. Prevalence of metabolic syndrome and its components increased significantly according to uric acid concentration in both sexes. The adjusted odds ratios for having metabolic syndrome per 1.0mg/dL higher uric acid concentration were 1.16 (95% CI: 1.03-1.31) in men and 1.27 (95% CI: 1.13-1.42) in women. Hyperuricemia was also associated with metabolic syndrome, with adjusted odds ratios of 1.71 (95% CI: 1.11-2.63) in men and 1.55 (95% CI: 1.05-2.29) in women. Elevated serum uric acid concentration was independently associated with an increased prevalence of metabolic syndrome in community-dwelling elderly Koreans. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Serum metabolic profiling of human gastric cancer based on gas chromatography/mass spectrometry

International Nuclear Information System (INIS)

Song, Hu; Peng, Jun-Sheng; Yao, Dong-Sheng; Yang, Zu-Li; Liu, Huan-Liang; Zeng, Yi-Ke; Shi, Xian-Ping; Lu, Bi-Yan

2011-01-01

Research on molecular mechanisms of carcinogenesis plays an important role in diagnosing and treating gastric cancer. Metabolic profiling may offer the opportunity to understand the molecular mechanism of carcinogenesis and help to non-invasively identify the potential biomarkers for the early diagnosis of human gastric cancer. The aims of this study were to explore the underlying metabolic mechanisms of gastric cancer and to identify biomarkers associated with morbidity. Gas chromatography/mass spectrometry (GC/MS) was used to analyze the serum metabolites of 30 Chinese gastric cancer patients and 30 healthy controls. Diagnostic models for gastric cancer were constructed using orthogonal partial least squares discriminant analysis (OPLS-DA). Acquired metabolomic data were analyzed by the nonparametric Wilcoxon test to find serum metabolic biomarkers for gastric cancer. The OPLS-DA model showed adequate discrimination between cancer and non-cancer cohorts while the model failed to discriminate different pathological stages (I-IV) of gastric cancer patients. A total of 44 endogenous metabolites such as amino acids, organic acids, carbohydrates, fatty acids, and steroids were detected, of which 18 differential metabolites were identified with significant differences. A total of 13 variables were obtained for their greatest contribution in the discriminating OPLS-DA model [variable importance in the projection (VIP) value >1.0], among which 11 metabolites were identified using both VIP values (VIP >1) and the Wilcoxon test. These metabolites potentially revealed perturbations of glycolysis and of amino acid, fatty acid, cholesterol, and nucleotide metabolism of gastric cancer patients. These results suggest that gastric cancer serum metabolic profiling has great potential in detecting this disease and helping to understand its metabolic mechanisms

Sclerostin alters serum vitamin D metabolite and fibroblast growth factor 23 concentrations and the urinary excretion of calcium

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Ryan, Zachary C.; Ketha, Hemamalini; McNulty, Melissa S.; McGee-Lawrence, Meghan; Craig, Theodore A.; Grande, Joseph P.; Westendorf, Jennifer J.; Singh, Ravinder J.; Kumar, Rajiv

2013-01-01

Inactivating mutations of the SOST (sclerostin) gene are associated with overgrowth and sclerosis of the skeleton. To determine mechanisms by which increased amounts of calcium and phosphorus are accreted to enable enhanced bone mineralization in the absence of sclerostin, we measured concentrations of calciotropic and phosphaturic hormones, and urine and serum calcium and inorganic phosphorus in mice in which the sclerostin (sost) gene was replaced by the β-D-galactosidase (lacZ) gene in the germ line. Knockout (KO) (sost−/−) mice had increased bone mineral density and content, increased cortical and trabecular bone thickness, and greater net bone formation as a result of increased osteoblast and decreased osteoclast surfaces compared with wild-type (WT) mice. β-Galactosidase activity was detected in osteocytes of sost KO mice but was undetectable in WT mice. Eight-week-old, male sost KO mice had increased serum 1α,25-dihydroxyvitamin D, decreased 24,25-dihydroxyvitamin D, decreased intact fibroblast growth factor 23, and elevated inorganic phosphorus concentrations compared with age-matched WT mice. 25-Hydroxyvitamin D 1α-hydroxylase cytochrome P450 (cyp27B1) mRNA was increased in kidneys of sost KO mice compared with WT mice. Treatment of cultured proximal tubule cells with mouse recombinant sclerostin decreased cyp27B1 mRNA transcripts. Urinary calcium and renal fractional excretion of calcium were decreased in sost KO mice compared with WT mice. Sost KO and WT mice had similar serum calcium and parathyroid hormone concentrations. The data show that sclerostin not only alters bone mineralization, but also influences mineral metabolism by altering concentrations of hormones that regulate mineral accretion. PMID:23530237

Altered fatty acid metabolism and reduced stearoyl-coenzyme a desaturase activity in asthma.

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Rodriguez-Perez, N; Schiavi, E; Frei, R; Ferstl, R; Wawrzyniak, P; Smolinska, S; Sokolowska, M; Sievi, N A; Kohler, M; Schmid-Grendelmeier, P; Michalovich, D; Simpson, K D; Hessel, E M; Jutel, M; Martin-Fontecha, M; Palomares, O; Akdis, C A; O'Mahony, L

2017-11-01

Fatty acids and lipid mediator signaling play an important role in the pathogenesis of asthma, yet this area remains largely underexplored. The aims of this study were (i) to examine fatty acid levels and their metabolism in obese and nonobese asthma patients and (ii) to determine the functional effects of altered fatty acid metabolism in experimental models. Medium- and long-chain fatty acid levels were quantified in serum from 161 human volunteers by LC/MS. Changes in stearoyl-coenzyme A desaturase (SCD) expression and activity were evaluated in the ovalbumin (OVA) and house dust mite (HDM) murine models. Primary human bronchial epithelial cells from asthma patients and controls were evaluated for SCD expression and activity. The serum desaturation index (an indirect measure of SCD) was significantly reduced in nonobese asthma patients and in the OVA murine model. SCD1 gene expression was significantly reduced within the lungs following OVA or HDM challenge. Inhibition of SCD in mice promoted airway hyper-responsiveness. SCD1 expression was suppressed in bronchial epithelial cells from asthma patients. IL-4 and IL-13 reduced epithelial cell SCD1 expression. Inhibition of SCD reduced surfactant protein C expression and suppressed rhinovirus-induced IP-10 secretion, which was associated with increased viral titers. This is the first study to demonstrate decreased fatty acid desaturase activity in humans with asthma. Experimental models in mice and human epithelial cells suggest that inhibition of desaturase activity leads to airway hyper-responsiveness and reduced antiviral defense. SCD may represent a new target for therapeutic intervention in asthma patients. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Interferon-driven alterations of the host's amino acid metabolism in the pathogenesis of typhoid fever.

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Blohmke, Christoph J; Darton, Thomas C; Jones, Claire; Suarez, Nicolas M; Waddington, Claire S; Angus, Brian; Zhou, Liqing; Hill, Jennifer; Clare, Simon; Kane, Leanne; Mukhopadhyay, Subhankar; Schreiber, Fernanda; Duque-Correa, Maria A; Wright, James C; Roumeliotis, Theodoros I; Yu, Lu; Choudhary, Jyoti S; Mejias, Asuncion; Ramilo, Octavio; Shanyinde, Milensu; Sztein, Marcelo B; Kingsley, Robert A; Lockhart, Stephen; Levine, Myron M; Lynn, David J; Dougan, Gordon; Pollard, Andrew J

2016-05-30

Enteric fever, caused by Salmonella enterica serovar Typhi, is an important public health problem in resource-limited settings and, despite decades of research, human responses to the infection are poorly understood. In 41 healthy adults experimentally infected with wild-type S. Typhi, we detected significant cytokine responses within 12 h of bacterial ingestion. These early responses did not correlate with subsequent clinical disease outcomes and likely indicate initial host-pathogen interactions in the gut mucosa. In participants developing enteric fever after oral infection, marked transcriptional and cytokine responses during acute disease reflected dominant type I/II interferon signatures, which were significantly associated with bacteremia. Using a murine and macrophage infection model, we validated the pivotal role of this response in the expression of proteins of the host tryptophan metabolism during Salmonella infection. Corresponding alterations in tryptophan catabolites with immunomodulatory properties in serum of participants with typhoid fever confirmed the activity of this pathway, and implicate a central role of host tryptophan metabolism in the pathogenesis of typhoid fever. © 2016 Blohmke et al.

Alterations in fatty acid metabolism in response to obesity surgery combined with dietary counseling.

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Walle, P; Takkunen, M; Männistö, V; Vaittinen, M; Käkelä, P; Ågren, J; Schwab, U; Lindström, J; Tuomilehto, J; Uusitupa, M; Pihlajamäki, J

2017-09-04

The effects of obesity surgery on serum and adipose tissue fatty acid (FA) profile and FA metabolism may modify the risk of obesity-related diseases. We measured serum (n=122) and adipose tissue (n=24) FA composition and adipose tissue mRNA expression of genes regulating FA metabolism (n=100) in participants of the Kuopio Obesity Surgery Study (KOBS, age 47.2±8.7 years, BMI 44.6±6.0, 40 men, 82 women) before and one year after obesity surgery. As part of the surgery protocol, all the subjects were instructed to add sources of unsaturated fatty acids, such as rapeseed oil and fatty fish, into their diet. The results were compared with changes in serum FA composition in 122 subjects from the Finnish Diabetes Prevention study (DPS) (age 54.3±7.1 years, BMI 32.2±4.6, 28 men, 94 women). The proportion of saturated FAs decreased and the proportion of n-3 and n-6 FAs increased in serum triglycerides after obesity surgery (all Pobesity surgery in all lipid fractions (all Pobesity surgery and lifestyle intervention, except for the change in the absolute amounts of n-3 FAs between the two studies (P=0.044). Beneficial changes in serum and adipose tissue FAs after obesity surgery could be associated with changes in endogenous metabolism and diet.

Clinical significance of determination of serum leptin, insulin levels and blood sugar in pregnant women with glucose metabolism disturbances

International Nuclear Information System (INIS)

Yu Suqing; Li Yusheng; Wang Lin; Chu Kaiqiu

2006-01-01

Objective: To investigate the changes of serum leptin, insulin levels and blood sugar contents in pregnant women with gestational glucose metabolism disturbances. Methods: Fasting and 3h after oral 50g glucose serum levels of leptin were measured with RIA in 36 pregnant women with glucose metabolism disturbances (gestational diabetes mellitus or gestational impaired glucose tolerance) and 34 controls. Also, fasting serum insulin levels (with CLIA) and blood sugar contents 1h after oral 50 glucose (with glucose oxidase method) were determined in all these subjects. Results: 1. Serum levels of leptin in pregnant women with glucose metabolism disturbances were 14.9 ± 4.3 μg/L (vs controls 9.8 ± 1.7 μg/L, P<0.01). 2. The serum levels of insulin and 1 h post - 50g glucose blood sugar contents in pregnant women with glucose metabolism disturbances were 12.9±4.3mU/L and 11.0±1.4mmol/L respectively, which were both significantly positively correlated with the serum leptin levels (r=0.835, r=0.758 respectively) (vs levels in controls: 8.45±3.0mU/L and 7.84±1.3mmol/L). Conclusion: Elevation of fasting serum levels of leptin was demonstrated in pregnant women with glucose metabolism disturbances and the level of leptin was positively correlated with that of insulin and blood sugar. (authors)

Genetic Variation in Choline-Metabolizing Enzymes Alters Choline Metabolism in Young Women Consuming Choline Intakes Meeting Current Recommendations

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Ariel B. Ganz

2017-01-01

Full Text Available Single nucleotide polymorphisms (SNPs in choline metabolizing genes are associated with disease risk and greater susceptibility to organ dysfunction under conditions of dietary choline restriction. However, the underlying metabolic signatures of these variants are not well characterized and it is unknown whether genotypic differences persist at recommended choline intakes. Thus, we sought to determine if common genetic risk factors alter choline dynamics in pregnant, lactating, and non-pregnant women consuming choline intakes meeting and exceeding current recommendations. Women (n = 75 consumed 480 or 930 mg choline/day (22% as a metabolic tracer, choline-d9 for 10–12 weeks in a controlled feeding study. Genotyping was performed for eight variant SNPs and genetic differences in metabolic flux and partitioning of plasma choline metabolites were evaluated using stable isotope methodology. CHKA rs10791957, CHDH rs9001, CHDH rs12676, PEMT rs4646343, PEMT rs7946, FMO3 rs2266782, SLC44A1 rs7873937, and SLC44A1 rs3199966 altered the use of choline as a methyl donor; CHDH rs9001 and BHMT rs3733890 altered the partitioning of dietary choline between betaine and phosphatidylcholine synthesis via the cytidine diphosphate (CDP-choline pathway; and CHKA rs10791957, CHDH rs12676, PEMT rs4646343, PEMT rs7946 and SLC44A1 rs7873937 altered the distribution of dietary choline between the CDP-choline and phosphatidylethanolamine N-methyltransferase (PEMT denovo pathway. Such metabolic differences may contribute to disease pathogenesis and prognosis over the long-term.

Metabolite Profiling of Feces and Serum in Hemodialysis Patients and the Effect of Medicinal Charcoal Tablets.

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Liu, Sixiu; Liang, Shanshan; Liu, Hua; Chen, Lei; Sun, Lingshuang; Wei, Meng; Jiang, Hongli; Wang, Jing

2018-05-22

Recently, the colon has been recognized as an important source of various uremic toxins in patients with end stage renal disease. Medicinal charcoal tablets are an oral adsorbent that are widely used in patients with chronic kidney disease in China to remove creatinine and urea from the colon. A parallel fecal and serum metabolomics study was performed to determine comprehensive metabolic profiles of patients receiving hemodialysis (HD). The effects of medicinal charcoal tablets on the fecal and serum metabolomes of HD patients were also investigated. Ultra-performance liquid chromatography/mass spectrometry was used to investigate the fecal and serum metabolic profiles of 20 healthy controls and 31 HD patients before and after taking medicinal charcoal tablets for 3 months. There were distinct metabolic variations between the HD patients and healthy controls both in the feces and serum according to multivariate data analysis. Metabolic disturbances of alanine, aspartate and glutamate metabolism, arginine and proline metabolism figured prominently in the serum. However, in the feces, alterations of tryptophan metabolism, lysine degradation and beta-alanine metabolism were pronounced, and the levels of several amino acids (leucine, phenylalanine, lysine, histidine, methionine, tyrosine, and tryptophan) were increased dramatically. Nineteen fecal metabolites and 21 serum metabolites were also identified as biomarkers that contributed to the metabolic differences. Additionally, medicinal charcoal treatment generally enabled the serum and fecal metabolomes of the HD patients to draw close to those of the control subjects, especially the serum metabolic profile. Parallel fecal and serum metabolomics uncovered the systematic metabolic variations of HD patients, especially disturbances in amino acid metabolism in the colon. Medicinal charcoal tablets had an impact on the serum and fecal metabolomes of HD patients, but their exact effects still need to be studied further

The Effect of Changing Serum 25-Hydroxyvitamin D Concentrations on Metabolic Syndrome: A Longitudinal Analysis of Participants of a Preventive Health Program

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Truong-Minh Pham

2015-08-01

Full Text Available Several studies have shown that a poor vitamin D status may increase the risk of developing metabolic syndrome, which leaves the question whether improving one’s vitamin D status may reduce the risk for the syndrome. Here we investigate the effect of temporal changes in serum 25-hydroxyvitamin D (25(OHD concentrations on metabolic syndrome among Canadians enrolled in a preventive health program that promotes vitamin D supplementation. We accessed and analyzed data of 6682 volunteer participants with repeated observations on serum 25(OHD concentrations and metabolic syndrome. We applied logistic regression to quantify the independent contribution of baseline serum 25(OHD and temporal increases in serum 25(OHD to the development of metabolic syndrome. In the first year in the program, participants, on average, increased their serum 25(OHD concentrations by 37 nmol/L. We observed a statistical significant inverse relationship of increases in serum 25(OHD with risk for metabolic syndrome. Relative to those without improvements, those who improved their serum 25(OHD concentrations with less 25 nmol/L, 25 to 50 nmol/L, 50 to 75 nmol/L, and more 75 nmol/L had respectively 0.76, 0.64, 0.59, 0.56 times the risk for metabolic syndrome at follow up. These estimates were independent of the effect of baseline serum 25(OHD concentrations on metabolic syndrome. Improvement of vitamin D status may help reduce the public health burden of metabolic syndrome, and potential subsequent health conditions including type 2 diabetes and cardiovascular disease.

Alteration of human serum albumin binding properties induced by modifications: A review

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Maciążek-Jurczyk, Małgorzata; Szkudlarek, Agnieszka; Chudzik, Mariola; Pożycka, Jadwiga; Sułkowska, Anna

2018-01-01

Albumin, a major transporting protein in the blood, is the main target of modification that affects the binding of drugs to Sudlow's site I and II. These modification of serum protein moderates its physiological function, and works as a biomarker of some diseases. The main goal of the paper was to explain the possible alteration of human serum albumin binding properties induced by modifications such as glycation, oxidation and ageing, their origin, methods of evaluation and positive and negative meaning described by significant researchers.

Correlation of serum 25(OHVitD concentration with metabolism parameters in patients with type 2 diabetes

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Yuan-Qing Qu

2016-04-01

Full Text Available Objective: To explore the correlation of serum 25(OHVitD concentration with the metabolism parameters in patients with type 2 diabetes. Methods: A total of 80 patients with type 2 diabetes who were admitted in our hospital from January, 2014 to March, 2015 were included in the study and served as the observation group, while 80 healthy individuals who came our hospital for physical examination were served as the control group. The serum 25(OHVitD concentration and metabolism parameters in the two groups were detected. The correlation of serum 25(OHVitD concentration with the metabolism parameters was analyzed. Results: The body weight, height, and BMI in the observation group were significantly higher than those in the control group (P0.05. The serum 25(OHVitD and HDL-C levels in the observation group were significantly lower than those in the control group (P<0.05, while SBP, FBG, TG, and DBP levels were significantly higher than those in the control group (P<0.05. The serum 25(OHVitD was negatively correlated with body weight, BMI, abdominal circumference, SBP, DBP, FBG, LDL-C, TG, and HbAlc. Conclusions: The serum 25(OHVitD level is closely associated with TG, LDL-C, and HbAlc, providing a reference value for the study on type 2 diabetes.

Serum leptin and its relationship with metabolic variables in Arabs with type 2 diabetes mellitus

International Nuclear Information System (INIS)

Al-Shoumer, Kamal A.; Doi, Suhail A.; Vasanthy, Bagavathy A.; Al-Asousi, Adnan A.

2008-01-01

Most studies on serum leptin in type 2 diabetes mellitus have focused on white populations. We studied serum leptin concentrations and parameters related to glycemic control and the association between leptin levels and anthropometric and metabolic factors in Arab patients with type 2 diabetes and in Arab control subjects. Ninety-two patients (65 females and 27 males) with type 2 diabetes and 69 matched normal and control subjects (48 females and 21 males) were included. Anthropometric measures (including body mass index (BMI) and waist: hip ratio) were assessed in all subjects. After an overnight fast, blood was collected for serum leptin assay. Other metabolic parameters include glucose, insulin, C-peptide, intact proinsulin, insulin resistance index (HOMA-IR), insulin-like growth factor 1 (IGF-1), lipids and hemoglobin A 1c (HbA) were determined. Fasting serum leptin levels, IGF-1 and high-density lipoprotein (HDL) cholesterol were similar in patients with type 2 diabetes and control subjects. When obese subjects (BMI>-30kg/m2) were analyzed separately, serum levels of leptin were significantly lower in patients compared to controls. In contrast, patients had higher fasting glucose, insulin, C-peptide, intact proinsulin, insulin resistance, total cholesterol, triglycerides, HbA, and a larger waist circumference and waist-to-hip ratio than controls. Serum leptin correlated positively with BM, negatively with waist-to-hip ratio, and demonstrated no relationship to other parameters. Patients with type 2 diabetes in an Arab ethnic population showed evidence of an unfavorable metabolic profile despite having leptin levels similar to controls. Obesity influences serum leptin levels more significantly in type 2 diabetes, in which leptin levels tends to be low. (author)

Differential melatonin alterations in cerebrospinal fluid and serum of patients with major depressive disorder and bipolar disorder.

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Bumb, J M; Enning, F; Mueller, J K; van der List, Till; Rohleder, C; Findeisen, P; Noelte, I; Schwarz, E; Leweke, F M

2016-07-01

Melatonin, which plays an important role for regulation of circadian rhythms and the sleep/wake cycle has been linked to the pathophysiology of major depressive and bipolar disorder. Here we investigated melatonin levels in cerebrospinal fluid (CSF) and serum of depression and bipolar patients to elucidate potential differences and commonalities in melatonin alterations across the two disorders. Using enzyme-linked immunosorbent assays, CSF and serum melatonin levels were measured in 108 subjects (27 healthy volunteers, 44 depressed and 37 bipolar patients). Covariate adjusted multiple regression analysis was used to investigate group differences in melatonin levels. In CSF, melatonin levels were significantly decreased in bipolar (Pdepressive disorder. In serum, we observed a significant melatonin decrease in major depressive (P=0.003), but not bipolar disorder. No associations were found between serum and CSF melatonin levels or between melatonin and measures of symptom severity or sleep disruptions in either condition. This study suggests the presence of differential, body fluid specific alterations of melatonin levels in bipolar and major depressive disorder. Further, longitudinal studies are required to explore the disease phase dependency of melatonin alterations and to mechanistically explore the causes and consequences of site-specific alterations. Copyright © 2016 Elsevier Inc. All rights reserved.

High-dose supplementation with natural α-tocopherol does neither alter the pharmacodynamics of atorvastatin nor its phase I metabolism in guinea pigs

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Podszun, Maren C.; Grebenstein, Nadine; Hofmann, Ute; Frank, Jan

2013-01-01

It has been hypothesized in the literature that intake of high-dosage vitamin E supplements might alter the expression of cytochrome P 450 enzymes (CYP), particularly CYP3A4, which may lead to adverse nutrient–drug interactions. Because previously published studies reported conflicting findings, we investigated the pharmacodynamics of the lipid-lowering drug atorvastatin (ATV), a CYP3A4 substrate, in response to high-dose α-tocopherol (αT) feeding and determined protein expression and activities of relevant CYP. Groups of ten female Dunkin–Hartley guinea pigs were fed a control (5% fat) or a high-fat control diet (HFC; 21% fat, 0.15% cholesterol) or the HFC diet fortified with αT (250 mg/kg diet), ATV (300 mg/kg diet) or both ATV + αT for 6 weeks. Relative to control, HFC animals had increased serum cholesterol concentrations, which were significantly reduced by ATV. High-dose αT feeding in combination with ATV (ATV + αT), albeit not αT feeding alone (αT), significantly lowered serum cholesterol relative to HFC, but did not alter the cholesterol-lowering activity of the drug compared to the ATV treated guinea pigs. Protein expression of CYP3A4, CYP4F2, CYP20A1 and OATP C was similar in all groups. Accordingly, no differences in plasma concentrations of phase I metabolites of ATV were observed between the ATV and ATV + αT groups. In conclusion, feeding guinea pigs high-doses of αT for 6 weeks did neither alter the hepatic expression of CYP, nor the pharmacodynamics and metabolism of ATV. High-dose αT intake is thus unlikely to change the efficacy of drugs metabolized by CYP enzymes, particularly by CYP3A4. -- Highlights: ► Vitamin E-atorvastatin interactions were studied in hypercholesterolemic guinea pigs. ► High-dose α-tocopherol did not alter the lipid-lowering efficacy of atorvastatin. ► α-Tocopherol did not change the expression of CYP3A4, CYP4F2, CYP20A or OATP C. ► α-Tocopherol did not affect phase I metabolism of atorvastatin. �

High-dose supplementation with natural α-tocopherol does neither alter the pharmacodynamics of atorvastatin nor its phase I metabolism in guinea pigs

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Podszun, Maren C.; Grebenstein, Nadine [Institute of Biological Chemistry and Nutrition, University of Hohenheim, D-70599 Stuttgart (Germany); Hofmann, Ute [Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, D-70376 Stuttgart (Germany); Frank, Jan [Institute of Biological Chemistry and Nutrition, University of Hohenheim, D-70599 Stuttgart (Germany); Department of Nutrition and Food Science, University of Bonn, D-53115 Bonn (Germany)

2013-02-01

It has been hypothesized in the literature that intake of high-dosage vitamin E supplements might alter the expression of cytochrome P{sub 450} enzymes (CYP), particularly CYP3A4, which may lead to adverse nutrient–drug interactions. Because previously published studies reported conflicting findings, we investigated the pharmacodynamics of the lipid-lowering drug atorvastatin (ATV), a CYP3A4 substrate, in response to high-dose α-tocopherol (αT) feeding and determined protein expression and activities of relevant CYP. Groups of ten female Dunkin–Hartley guinea pigs were fed a control (5% fat) or a high-fat control diet (HFC; 21% fat, 0.15% cholesterol) or the HFC diet fortified with αT (250 mg/kg diet), ATV (300 mg/kg diet) or both ATV + αT for 6 weeks. Relative to control, HFC animals had increased serum cholesterol concentrations, which were significantly reduced by ATV. High-dose αT feeding in combination with ATV (ATV + αT), albeit not αT feeding alone (αT), significantly lowered serum cholesterol relative to HFC, but did not alter the cholesterol-lowering activity of the drug compared to the ATV treated guinea pigs. Protein expression of CYP3A4, CYP4F2, CYP20A1 and OATP C was similar in all groups. Accordingly, no differences in plasma concentrations of phase I metabolites of ATV were observed between the ATV and ATV + αT groups. In conclusion, feeding guinea pigs high-doses of αT for 6 weeks did neither alter the hepatic expression of CYP, nor the pharmacodynamics and metabolism of ATV. High-dose αT intake is thus unlikely to change the efficacy of drugs metabolized by CYP enzymes, particularly by CYP3A4. -- Highlights: ► Vitamin E-atorvastatin interactions were studied in hypercholesterolemic guinea pigs. ► High-dose α-tocopherol did not alter the lipid-lowering efficacy of atorvastatin. ► α-Tocopherol did not change the expression of CYP3A4, CYP4F2, CYP20A or OATP C. ► α-Tocopherol did not affect phase I metabolism of atorvastatin

Serum vitamin D levels, diabetes and cardio-metabolic risk factors in Aboriginal and Torres Strait Islander Australians.

Science.gov (United States)

Maple-Brown, Louise J; Hughes, Jaquelyne T; Lu, Zhong X; Jeyaraman, Kanakamani; Lawton, Paul; Jones, Graham Rd; Ellis, Andrew; Sinha, Ashim; Cass, Alan; MacIsaac, Richard J; Jerums, George; O'Dea, Kerin

2014-01-01

Low levels of serum 25-hydroxy vitamin D (25(OH)D), have been associated with development of type 2 diabetes and cardiovascular disease (CVD); however there are limited data on serum 25(OH)D in Indigenous Australians, a population at high risk for both diabetes and CVD. We aimed to assess levels of serum 25(OH)D in Aboriginal and Torres Strait Islander Australians and to explore relationships between 25(OH)D and cardio-metabolic risk factors and diabetes. 592 Aboriginal and/or Torres Strait Islander Australian participants of The eGFR (estimated glomerular filtration rate) Study, a cross-sectional analysis of a cohort study performed in 2007-2011, from urban and remote centres within communities, primary care and tertiary hospitals across Northern Territory, Far North Queensland and Western Australia. Assessment of serum 25(OH)D, cardio-metabolic risk factors (central obesity, diabetes, hypertension, history of cardiovascular disease, current smoker, low HDL-cholesterol), and diabetes (by history or HbA1c ≥6.5%) was performed. Associations were explored between 25(OH)D and outcome measures of diabetes and number of cardio-metabolic risk factors. The median (IQR) serum 25(OH)D was 60 (45-77) nmol/L, 31% had 25(OH)D 72 nmol/L, respectively) after adjusting for known cardio-metabolic risk factors. The percentage of 25(OH)D levels Aboriginal and Torres Strait Islander Australians from Northern and Central Australia. Low 25(OH)D level was associated with adverse cardio-metabolic risk profile and was independently associated with diabetes. These findings require exploration in longitudinal studies.

Soluble Fms-Like Tyrosine Kinase-1 Alters Cellular Metabolism and Mitochondrial Bioenergetics in Preeclampsia

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Lissette C. Sánchez-Aranguren

2018-03-01

Full Text Available Preeclampsia is a maternal hypertensive disorder that affects up to 1 out of 12 pregnancies worldwide. It is characterized by proteinuria, endothelial dysfunction, and elevated levels of the soluble form of the vascular endothelial growth factor receptor-1 (VEGFR-1, known as sFlt-1. sFlt-1 effects are mediated in part by decreasing VEGF signaling. The direct effects of sFlt-1 on cellular metabolism and bioenergetics in preeclampsia, have not been established. The goal of this study was to evaluate whether sFlt-1 causes mitochondrial dysfunction leading to disruption of normal functioning in endothelial and placental cells in preeclampsia. Endothelial cells (ECs and first-trimester trophoblast (HTR-8/SVneo were treated with serum from preeclamptic women rich in sFlt-1 or with the recombinant protein. sFlt-1, dose-dependently inhibited ECs respiration and acidification rates indicating a metabolic phenotype switch enhancing glycolytic flux. HTR-8/SVneo displayed a strong basal glycolytic metabolism, remaining less sensitive to sFlt-1-induced mitochondrial impairment. Moreover, results obtained in ECs exposed to serum from preeclamptic subjects demonstrated that increased sFlt-1 leads to metabolic perturbations accountable for mitochondrial dysfunction observed in preeclampsia. sFlt-1 exacerbated mitochondrial reactive oxygen species (ROS formation and mitochondrial membrane potential dissipation in ECs and trophoblasts exposed to serum from preeclamptic women. Forcing oxidative metabolism by culturing cells in galactose media, further sensitized cells to sFlt-1. This approach let us establish that sFlt-1 targets mitochondrial function in ECs. Effects of sFlt-1 on HTR-8/SVneo cells metabolism were amplified in galactose, demonstrating that sFlt-1 only target cells that rely mainly on oxidative metabolism. Together, our results establish the early metabolic perturbations induced by sFlt-1 and the resulting endothelial and mitochondrial dysfunction

Clinical significance of bone metabolic parameters and serum thyroid hormone levels in patients with hyperthyroidism

International Nuclear Information System (INIS)

Xiao Jinhua; Wang Yaping; Sun Junming; Hua Wenjing

2002-01-01

To study the changes in bone metabolic parameters and serum thyroid hormone levels in patients with hyperthyroidism, seventy patients with hyperthyroidism and sixty healthy controls were investigated by means of radioimmunoassay (RIA) for serum ICTP, chemiluminescent immunoassay for BAP and serum thyroid hormone and meanwhile bone mineral density was measured. The results showed that the levels of serum BAP, ICTP and thyroid hormone in patients with hyperthyroidism were dramatically higher than those in control group (all P<0.01), BMD was significantly decreased in the study group (P<0.01). The correlation analysis showed that both BAP and ICTP were negatively correlated with BMD (all P<0.05). The results from this investigation indicated that increased bone turnover is significantly associated with an increased thyroid hormone in patients with hyperthyroidism, and bone resorption is greater than formation resulting in a bone mass loss. Measurement of serum BAP and ICTP levels may be of help to judge the severity of bone metabolism, study the state of an illness in hyperthyroidism

Altered oxidative stress and carbohydrate metabolism in canine mammary tumors

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K. Jayasri

2016-12-01

Full Text Available Aim: Mammary tumors are the most prevalent type of neoplasms in canines. Even though cancer induced metabolic alterations are well established, the clinical data describing the metabolic profiles of animal tumors is not available. Hence, our present investigation was carried out with the aim of studying changes in carbohydrate metabolism along with the level of oxidative stress in canine mammary tumors. Materials and Methods: Fresh mammary tumor tissues along with the adjacent healthy tissues were collected from the college surgical ward. The levels of thiobarbituric acid reactive substances (TBARS, glutathione, protein, hexose, hexokinase, glucose-6-phosphatase, fructose-1, 6-bisphosphatase, and glucose-6-phosphate dehydrogenase (G6PD were analyzed in all the tissues. The results were analyzed statistically. Results: More than two-fold increase in TBARS and three-fold increase in glutathione levels were observed in neoplastic tissues. Hexokinase activity and hexose concentration (175% was found to be increased, whereas glucose-6-phosphatase (33%, fructose-1, 6-bisphosphatase (42%, and G6PD (5 fold activities were reduced in tumor mass compared to control. Conclusion: Finally, it was revealed that lipid peroxidation was increased with differentially altered carbohydrate metabolism in canine mammary tumors.

Omega-6 polyunsaturated fatty acids, serum zinc, delta-5- and delta-6-desaturase activities and incident metabolic syndrome.

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Yary, T; Voutilainen, S; Tuomainen, T-P; Ruusunen, A; Nurmi, T; Virtanen, J K

2017-08-01

The associations of n-6 polyunsaturated fatty acids (PUFA) with metabolic syndrome have been poorly explored. We investigated the associations of the serum n-6 PUFA and the activities of enzymes involved in the PUFA metabolism, delta-5-desaturase (D5D) and delta-6-desaturase (D6D) with risk of incident metabolic syndrome. We also investigated whether zinc, a cofactor for these enzymes, modifies these associations. A prospective follow-up study was conducted on 661 men who were aged 42-60 years old at baseline in 1984-1989 and who were re-examined in 1998-2001. Men in the highest versus the lowest serum total omega-6 PUFA tertile had a 70% lower multivariate-adjusted risk of incident metabolic syndrome [odds ratio (OR) = 0.30; 95% confidence interval (CI) = 0.18-0.51, P trend metabolic syndrome components at the re-examinations. Most associations were attenuated after adjustment for body mass index. Finally, the associations of D6D and LA were stronger among those with a higher serum zinc concentration. Higher serum total n-6 PUFA, linoleic acid and arachidonic acid concentrations and D5D activity were associated with a lower risk of developing metabolic syndrome and higher D6D activity was associated with a higher risk. The role of zinc also needs to be investigated in other populations. © 2016 The British Dietetic Association Ltd.

Interferon-driven alterations of the host’s amino acid metabolism in the pathogenesis of typhoid fever

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Jones, Claire; Waddington, Claire S.; Zhou, Liqing; Hill, Jennifer; Clare, Simon; Mukhopadhyay, Subhankar; Schreiber, Fernanda; Roumeliotis, Theodoros I.; Yu, Lu; Ramilo, Octavio; Sztein, Marcelo B.; Kingsley, Robert A.; Levine, Myron M.

2016-01-01

Enteric fever, caused by Salmonella enterica serovar Typhi, is an important public health problem in resource-limited settings and, despite decades of research, human responses to the infection are poorly understood. In 41 healthy adults experimentally infected with wild-type S. Typhi, we detected significant cytokine responses within 12 h of bacterial ingestion. These early responses did not correlate with subsequent clinical disease outcomes and likely indicate initial host–pathogen interactions in the gut mucosa. In participants developing enteric fever after oral infection, marked transcriptional and cytokine responses during acute disease reflected dominant type I/II interferon signatures, which were significantly associated with bacteremia. Using a murine and macrophage infection model, we validated the pivotal role of this response in the expression of proteins of the host tryptophan metabolism during Salmonella infection. Corresponding alterations in tryptophan catabolites with immunomodulatory properties in serum of participants with typhoid fever confirmed the activity of this pathway, and implicate a central role of host tryptophan metabolism in the pathogenesis of typhoid fever. PMID:27217537

Association of a Human FABP1 Gene Promoter Region Polymorphism with Altered Serum Triglyceride Levels.

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Xian-E Peng

Full Text Available Liver fatty acid-binding protein (L-FABP, also known as fatty acid-binding protein 1 (FABP1, is a key regulator of hepatic lipid metabolism. Elevated FABP1 levels are associated with an increased risk of cardiovascular disease (CVD and metabolic syndromes. In this study, we examine the association of FABP1 gene promoter variants with serum FABP1 and lipid levels in a Chinese population. Four promoter single-nucleotide polymorphisms (SNPs of FABP1 gene were genotyped in a cross-sectional survey of healthy volunteers (n = 1,182 from Fuzhou city of China. Results showed that only the rs2919872 G>A variant was significantly associated with serum TG concentration(P = 0.032.Compared with the rs2919872 G allele, rs2919872 A allele contributed significantly to reduced serum TG concentration, and this allele dramatically decreased the FABP1 promoter activity(P < 0.05. The rs2919872 A allele carriers had considerably lower serum FABP1 levels than G allele carriers (P < 0.01. In the multivariable linear regression analysis, the rs2919872 A allele was negatively associated with serum FABP1 levels (β = -0.320, P = 0.003, while serum TG levels were positively associated with serum FABP1 levels (β = 0.487, P = 0.014. Our data suggest that compared with the rs2919872 G allele, the rs2919872 A allele reduces the transcriptional activity of FABP1 promoter, and thereby may link FABP1 gene variation to TG level in humans.

Metabolic alterations and neurodevelopmental outcome of infants with transposition of the great arteries.

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Park, I Sook; Yoon, S Young; Min, J Yeon; Kim, Y Hwue; Ko, J Kok; Kim, K Soo; Seo, D Man; Lee, J Hee

2006-01-01

Abnormal neurodevelopment has been reported for infants who were born with transposition of the great arteries (TGA) and underwent arterial switch operation (ASO). This study evaluates the cerebral metabolism of TGA infants at birth and before ASO and neurodevelopment 1 year after ASO. Proton magnetic resonance spectroscopy (1H-MRS) was performed on 16 full-term TGA brains before ASO within 3-6 days after birth. The brain metabolite ratios of [NAA/Cr], [Cho/Cr], and [mI/Cr] evaluated measured. Ten infants were evaluated at 1 year using the Bayley Scales of Infants Development II (BSED II). Cerebral metabolism of infants with TGA was altered in parietal white matter (PWM) and occipital gray matter (OGM) at birth before ASO. One year after ASO, [Cho/Cr] in PWM remained altered, but all metabolic ratios in OGM were normal. The results of BSID II at 1 year showed delayed mental and psychomotor development. This delayed neurodevelopmental outcome may reflect consequences of the altered cerebral metabolism in PWM measured by 1H-MRS. It is speculated that the abnormal hemodynamics due to TGA in utero may be responsible for the impaired cerebral metabolism and the subsequent neurodevelopmental deficit.

Alterations of blood serum parameters in patients with chronic hematogenous osteomyelitis

Institute of Scientific and Technical Information of China (English)

Sadrudin Magomedov; Larisa Polishchuk

2015-01-01

Objective:To examine metabolic disorders of major components of organic basis of bone tissue in patients with chronic hematogenous osteomyelitis and response to surgical treatment. Methods: The cubital vein puncture was conducted to take blood for analysis in patients with chronic hematogenous osteomyelitis. The activity of collagenase and hyaluronidase, elastin, elastase and total content of glycosaminoglycans were measured in blood serum. Results: The study revealed an enhancement of catabolic phase of metabolism of the main components in bone organic matrix during the relapse of inflammation. It was evidenced by indicators reflecting the synthetic and catabolic phases of the main components of the connective tissue collagen and glycosaminoglycans. The effective therapeutic treatments led to the reduction and normalization of studied compounds. Conclusions: The initial development of hematogenous osteomyelitis happens in a background of metabolic disorders of the main components of organic matrix of bone tissue, and normalizes upon effective therapy.

Metabolic Footprinting of Fermented Milk Consumption in Serum of Healthy Men

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Pimentel, Grégory; Burton, Kathryn J; von Ah, Ueli; Bütikofer, Ueli; Pralong, François P; Vionnet, Nathalie; Portmann, Reto; Vergères, Guy

2018-01-01

Abstract Background Fermentation is a widely used method of natural food preservation that has consequences on the nutritional value of the transformed food. Fermented dairy products are increasingly investigated in view of their ability to exert health benefits beyond their nutritional qualities. Objective To explore the mechanisms underpinning the health benefits of fermented dairy intake, the present study followed the effects of milk fermentation, from changes in the product metabolome to consequences on the human serum metabolome after its ingestion. Methods A randomized crossover study design was conducted in 14 healthy men [mean age: 24.6 y; mean body mass index (in kg/m2): 21.8]. At the beginning of each test phase, serum samples were taken 6 h postprandially after the ingestion of 800 g of a nonfermented milk or a probiotic yogurt. During the 2-wk test phases, subjects consumed 400 g of the assigned test product daily (200 g, 2 times/d). Serum samples were taken from fasting participants at the end of each test phase. The serum metabolome was assessed through the use of LC-MS–based untargeted metabolomics. Results Postprandial serum metabolomes after milk or yogurt intake could be differentiated [orthogonal projections to latent structures discriminant analysis (OPLS-DA) Q2 = 0.74]. Yogurt intake was characterized by higher concentrations of 7 free amino acids (including proline, P = 0.03), reduced concentrations of 5 bile acids (including glycocholic acid, P = 0.04), and modulation of 4 indole derivative compounds (including indole lactic acid, P = 0.01). Fasting serum samples after 2 wk of daily intake of milk or yogurt could also be differentiated based on their metabolic profiles (OPLS-DA Q2 = 0.56) and were discussed in light of the postprandial results. Conclusion Metabolic pathways related to amino acids, indole derivatives, and bile acids were modulated in healthy men by the intake of yogurt. Further investigation to explore novel

Influence of common preanalytical variations on the metabolic profile of serum samples in biobanks

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Fliniaux, Ophélie; Gaillard, Gwenaelle; Lion, Antoine; Cailleu, Dominique; Mesnard, François; Betsou, Fotini

2011-01-01

A blood pre-centrifugation delay of 24 h at room temperature influenced the proton NMR spectroscopic profiles of human serum. A blood pre-centrifugation delay of 24 h at 4°C did not influence the spectroscopic profile as compared with 4 h delays at either room temperature or 4°C. Five or ten serum freeze–thaw cycles also influenced the proton NMR spectroscopic profiles. Certain common in vitro preanalytical variations occurring in biobanks may impact the metabolic profile of human serum.

Alteration of the fecal microbiota and serum metabolite profiles in dogs with idiopathic inflammatory bowel disease

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Minamoto, Yasushi; Otoni, Cristiane C; Steelman, Samantha M; Büyükleblebici, Olga; Steiner, Jörg M; Jergens, Albert E; Suchodolski, Jan S

2015-01-01

Idiopathic inflammatory bowel disease (IBD) is a common cause of chronic gastrointestinal (GI) disease in dogs. The combination of an underlying host genetic susceptibility, an intestinal dysbiosis, and dietary/environmental factors are suspected as main contributing factors in the pathogenesis of canine IBD. However, actual mechanisms of the host-microbe interactions remain elusive. The aim of this study was to compare the fecal microbiota and serum metabolite profiles between healthy dogs (n = 10) and dogs with IBD before and after 3 weeks of medical therapy (n = 12). Fecal microbiota and metabolite profiles were characterized by 454-pyrosequencing of 16 S rRNA genes and by an untargeted metabolomics approach, respectively. Significantly lower bacterial diversity and distinct microbial communities were observed in dogs with IBD compared to the healthy control dogs. While Gammaproteobacteria were overrepresented, Erysipelotrichia, Clostridia, and Bacteroidia were underrepresented in dogs with IBD. The functional gene content was predicted from the 16 S rRNA gene data using PICRUSt, and revealed overrepresented bacterial secretion system and transcription factors, and underrepresented amino acid metabolism in dogs with IBD. The serum metabolites 3-hydroxybutyrate, hexuronic acid, ribose, and gluconic acid lactone were significantly more abundant in dogs with IBD. Although a clinical improvement was observed after medical therapy in all dogs with IBD, this was not accompanied by significant changes in the fecal microbiota or in serum metabolite profiles. These results suggest the presence of oxidative stress and a functional alteration of the GI microbiota in dogs with IBD, which persisted even in the face of a clinical response to medical therapy. PMID:25531678

Alteration of the fecal microbiota and serum metabolite profiles in dogs with idiopathic inflammatory bowel disease.

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Minamoto, Yasushi; Otoni, Cristiane C; Steelman, Samantha M; Büyükleblebici, Olga; Steiner, Jörg M; Jergens, Albert E; Suchodolski, Jan S

2015-01-01

Idiopathic inflammatory bowel disease (IBD) is a common cause of chronic gastrointestinal (GI) disease in dogs. The combination of an underlying host genetic susceptibility, an intestinal dysbiosis, and dietary/environmental factors are suspected as main contributing factors in the pathogenesis of canine IBD. However, actual mechanisms of the host-microbe interactions remain elusive. The aim of this study was to compare the fecal microbiota and serum metabolite profiles between healthy dogs (n = 10) and dogs with IBD before and after 3 weeks of medical therapy (n = 12). Fecal microbiota and metabolite profiles were characterized by 454-pyrosequencing of 16 S rRNA genes and by an untargeted metabolomics approach, respectively. Significantly lower bacterial diversity and distinct microbial communities were observed in dogs with IBD compared to the healthy control dogs. While Gammaproteobacteria were overrepresented, Erysipelotrichia, Clostridia, and Bacteroidia were underrepresented in dogs with IBD. The functional gene content was predicted from the 16 S rRNA gene data using PICRUSt, and revealed overrepresented bacterial secretion system and transcription factors, and underrepresented amino acid metabolism in dogs with IBD. The serum metabolites 3-hydroxybutyrate, hexuronic acid, ribose, and gluconic acid lactone were significantly more abundant in dogs with IBD. Although a clinical improvement was observed after medical therapy in all dogs with IBD, this was not accompanied by significant changes in the fecal microbiota or in serum metabolite profiles. These results suggest the presence of oxidative stress and a functional alteration of the GI microbiota in dogs with IBD, which persisted even in the face of a clinical response to medical therapy.

Serum resistin level among healthy subjects: relationship to anthropometric and metabolic parameters.

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Chen, Ching-Chu; Li, Tsai-Chung; Li, Chia-Ing; Liu, Chiu-Shong; Wang, Hui-Ju; Lin, Cheng-Chieh

2005-04-01

Resistin is a novel adipocyte-secreted hormone that has been proposed to be the link between obesity and diabetes, although little appears to be known regarding the physiological role of resistin in human beings. We aimed to explore the relationship between serum resistin level and certain anthropometric and metabolic parameters. Seventy-one healthy subjects with a mean body mass index of 23 kg/m 2 or greater were recruited in this study. Anthropometric measurements including height, weight, body mass index, waist and hip circumferences, waist-to-hip ratio, and blood pressure were recorded. Insulin resistance was measured by homeostasis model assessment (HOMA). Fasting serum resistin, insulin and plasma glucose, lipid profiles, and uric acid levels were measured. The results revealed that serum resistin level did not correlate with any markers for adiposity, blood pressure, fasting plasma glucose, or uric acid level for either sex. Serum resistin level correlated negatively with fasting insulin level (gamma=-0.455, P=.006) and HOMA (gamma=-0.455, P=.006) in women but not in men. Serum resistin level only correlated negatively with high-density lipoprotein cholesterol (HDL-C) level in men (gamma=-0.347, P=.038); there was no correlation between serum resistin level and lipid profiles in women. Multiple linear regression analysis using the logarithm of resistin as a dependent variable revealed that only HDL-C level (beta=-.058, P=.019) was an independent significant predictor for resistin in men; however, the analysis revealed that HDL-C level (beta=-.044, P=.029) and HOMA (beta=-.719, P=.004) were independent significant predictors for resistin in women. In conclusion, resistin is not related to adiposity, blood pressure, insulin resistance, fasting plasma glucose level, and most lipid profiles. Resistin correlates negatively with HDL-C level for both sexes. The role of resistin in metabolic syndrome warrants further investigation.

Combined metabolomic and correlation networks analyses reveal fumarase insufficiency altered amino acid metabolism.

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Hou, Entai; Li, Xian; Liu, Zerong; Zhang, Fuchang; Tian, Zhongmin

2018-04-01

Fumarase catalyzes the interconversion of fumarate and l-malate in the tricarboxylic acid cycle. Fumarase insufficiencies were associated with increased levels of fumarate, decreased levels of malate and exacerbated salt-induced hypertension. To gain insights into the metabolism profiles induced by fumarase insufficiency and identify key regulatory metabolites, we applied a GC-MS based metabolomics platform coupled with a network approach to analyze fumarase insufficient human umbilical vein endothelial cells (HUVEC) and negative controls. A total of 24 altered metabolites involved in seven metabolic pathways were identified as significantly altered, and enriched for the biological module of amino acids metabolism. In addition, Pearson correlation network analysis revealed that fumaric acid, l-malic acid, l-aspartic acid, glycine and l-glutamic acid were hub metabolites according to Pagerank based on their three centrality indices. Alanine aminotransferase and glutamate dehydrogenase activities increased significantly in fumarase deficiency HUVEC. These results confirmed that fumarase insufficiency altered amino acid metabolism. The combination of metabolomics and network methods would provide another perspective on expounding the molecular mechanism at metabolomics level. Copyright © 2017 John Wiley & Sons, Ltd.

Impact of prebiotics on metabolic and behavioral alterations in a mouse model of metabolic syndrome.

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de Cossío, Lourdes Fernández; Fourrier, Célia; Sauvant, Julie; Everard, Amandine; Capuron, Lucile; Cani, Patrice D; Layé, Sophie; Castanon, Nathalie

2017-08-01

Mounting evidence shows that the gut microbiota, an important player within the gut-brain communication axis, can affect metabolism, inflammation, brain function and behavior. Interestingly, gut microbiota composition is known to be altered in patients with metabolic syndrome (MetS), who also often display neuropsychiatric symptoms. The use of prebiotics, which beneficially alters the microbiota, may therefore be a promising way to potentially improve physical and mental health in MetS patients. This hypothesis was tested in a mouse model of MetS, namely the obese and type-2 diabetic db/db mice, which display emotional and cognitive alterations associated with changes in gut microbiota composition and hippocampal inflammation compared to their lean db/+ littermates. We assessed the impact of chronic administration (8weeks) of prebiotics (oligofructose) on both metabolic (body weight, food intake, glucose homeostasis) and behavioral (increased anxiety-like behavior and impaired spatial memory) alterations characterizing db/db mice, as well as related neurobiological correlates, with particular attention to neuroinflammatory processes. Prebiotic administration improved excessive food intake and glycemic dysregulations (glucose tolerance and insulin resistance) in db/db mice. This was accompanied by an increase of plasma anti-inflammatory cytokine IL-10 levels and hypothalamic mRNA expression of the anorexigenic cytokine IL-1β, whereas unbalanced mRNA expression of hypothalamic orexigenic (NPY) and anorexigenic (CART, POMC) peptides was unchanged. We also detected signs of improved blood-brain-barrier integrity in the hypothalamus of oligofructose-treated db/db mice (normalized expression of tight junction proteins ZO-1 and occludin). On the contrary, prebiotic administration did not improve behavioral alterations and associated reduction of hippocampal neurogenesis displayed by db/db mice, despite normalization of increased hippocampal IL-6 mRNA expression. Of note

Influence of common preanalytical variations on the metabolic profile of serum samples in biobanks

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Fliniaux, Ophelie [University of Picardie Jules Verne, Laboratoire de Phytotechnologie EA 3900-BioPI (France); Gaillard, Gwenaelle [Biobanque de Picardie (France); Lion, Antoine [University of Picardie Jules Verne, Laboratoire de Phytotechnologie EA 3900-BioPI (France); Cailleu, Dominique [Batiment Serres-Transfert, rue de Mai/rue Dallery, Plateforme Analytique (France); Mesnard, Francois, E-mail: francois.mesnard@u-picardie.fr [University of Picardie Jules Verne, Laboratoire de Phytotechnologie EA 3900-BioPI (France); Betsou, Fotini [Integrated Biobank of Luxembourg (Luxembourg)

2011-12-15

A blood pre-centrifugation delay of 24 h at room temperature influenced the proton NMR spectroscopic profiles of human serum. A blood pre-centrifugation delay of 24 h at 4 Degree-Sign C did not influence the spectroscopic profile as compared with 4 h delays at either room temperature or 4 Degree-Sign C. Five or ten serum freeze-thaw cycles also influenced the proton NMR spectroscopic profiles. Certain common in vitro preanalytical variations occurring in biobanks may impact the metabolic profile of human serum.

High sensitive C-reactive protein and serum amyloid A are inversely related to serum bilirubin : effect-modification by metabolic syndrome

NARCIS (Netherlands)

Deetman, Petronella E.; Bakker, Stephan J. L.; Dullaart, Robin P. F.

2013-01-01

Background: Bilirubin has been implicated in cardiovascular protection by virtue of its anti-inflammatory and anti-oxidative properties. The metabolic syndrome is featured by enhanced low-grade systemic inflammation and oxidative stress. Serum amyloid A (SAA) impairs anti-oxidative properties of

Short-term fasting alters cytochrome P450-mediated drug metabolism in humans

NARCIS (Netherlands)

Lammers, Laureen A.; Achterbergh, Roos; de Vries, Emmely M.; van Nierop, F. Samuel; Klümpen, Heinz-Josef; Soeters, Maarten R.; Boelen, Anita; Romijn, Johannes A.; Mathôt, Ron A. A.

2015-01-01

Experimental studies indicate that short-term fasting alters drug metabolism. However, the effects of short-term fasting on drug metabolism in humans need further investigation. Therefore, the aim of this study was to evaluate the effects of short-term fasting (36 h) on P450-mediated drug

Dynamic Metabolic Disruption in Rats Perinatally Exposed to Low Doses of Bisphenol-A.

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Marie Tremblay-Franco

Full Text Available Along with the well-established effects on fertility and fecundity, perinatal exposure to endocrine disrupting chemicals, and notably to xeno-estrogens, is strongly suspected of modulating general metabolism. The metabolism of a perinatally exposed individual may be durably altered leading to a higher susceptibility of developing metabolic disorders such as obesity and diabetes; however, experimental designs involving the long term study of these dynamic changes in the metabolome raise novel challenges. 1H-NMR-based metabolomics was applied to study the effects of bisphenol-A (BPA, 0; 0.25; 2.5, 25 and 250 μg/kg BW/day in rats exposed perinatally. Serum and liver samples of exposed animals were analyzed on days 21, 50, 90, 140 and 200 in order to explore whether maternal exposure to BPA alters metabolism. Partial Least Squares-Discriminant Analysis (PLS-DA was independently applied to each time point, demonstrating a significant pair-wise discrimination for liver as well as serum samples at all time-points, and highlighting unequivocal metabolic shifts in rats perinatally exposed to BPA, including those exposed to lower doses. In BPA exposed animals, metabolism of glucose, lactate and fatty acids was modified over time. To further explore dynamic variation, ANOVA-Simultaneous Component Analysis (A-SCA was used to separate data into blocks corresponding to the different sources of variation (Time, Dose and Time*Dose interaction. A-SCA enabled the demonstration of a dynamic, time/age dependent shift of serum metabolome throughout the rats' lifetimes. Variables responsible for the discrimination between groups clearly indicate that BPA modulates energy metabolism, and suggest alterations of neurotransmitter signaling, the latter finding being compatible with the neurodevelopmental effect of this xenoestrogen. In conclusion, long lasting metabolic effects of BPA could be characterized over 200 days, despite physiological (and thus metabolic changes

Serum vitamin D and the metabolic syndrome among osteoporotic postmenopausal female patients of a family practice clinic in Jordan.

Science.gov (United States)

Yasein, Nada; Shroukh, Wejdan; Hijjawi, Razan

2015-01-01

Vitamin D deficiency and insufficiency and the metabolic syndrome are two common health issues worldwide. The association between these two health problems is subject to debate. This study aims to investigate the association between vitamin D deficiency or insufficiency and the metabolic syndrome in a sample of osteoporotic postmenopausal women attending a family practice clinic in Amman-Jordan. This was an observational cross sectional study. It was carried out in the family practice clinic in Jordan University Hospital. The study included all postmenopausal osteoporotic women attending the clinic between June 2011 and May 2012, yielding a total of 326 subjects. The association between metabolic syndrome and serum vitamin D levels was investigated. Waist circumference, body mass index, triglycerides and fasting blood sugar were significantly higher among postmenopausal women with metabolic syndrome, but HDL cholesterol was significantly lower (pmetabolic syndrome among all study participants was 42.9%. Triglycerides and LDL cholesterol were significantly higher among women deficiency or insufficiency (pmetabolic syndrome, the prevalence of vitamin D deficiency or insufficiency was 50.7%. Findings of the current study suggest a lack of relationship between serum vitamin D and metabolic syndrome. However, a significant inverse relationship was found between serum vitamin D levels and both serum triglycerides and LDL levels.

Traumatic brain injury alters methionine metabolism: implications for pathophysiology

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Pramod K Dash

2016-04-01

Full Text Available Methionine is an essential proteinogenic amino acid that is obtained from the diet. In addition to its requirement for protein biosynthesis, methionine is metabolized to generate metabolites that play key roles in a number of cellular functions. Metabolism of methionine via the transmethylation pathway generates S-adenosylmethionine (SAM that serves as the principal methyl (-CH3 donor for DNA and histone methyltransferases to regulate epigenetic changes in gene expression. SAM is also required for methylation of other cellular proteins that serve various functions and phosphatidylcholine synthesis that participate in cellular signaling.. Under conditions of oxidative stress, homocysteine (which is derived from SAM enters the transsulfuration pathway to generate glutathione, an important cytoprotective molecule against oxidative damage. As both experimental and clinical studies have shown that traumatic brain injury (TBI alters DNA and histone methylation and causes oxidative stress, we examined if TBI alters the plasma levels of methionine and its metabolites in human patients. Blood samples were collected from healthy volunteers (n = 20 and patients with mild TBI (GCS > 12; n = 20 or severe TBI (GCS < 8; n = 20 within the first 24 hours of injury. The levels of methionine and its metabolites in the plasma samples were analyzed by either liquid chromatography-mass spectrometry or gas chromatography-mass spectrometry (LC-MS or GC-MS. Severe TBI decreased the levels of methionine, SAM, betaine and 2-methylglycine as compared to healthy volunteers, indicating a decrease in metabolism through the transmethylation cycle. In addition, precursors for the generation of glutathione, cysteine and glycine were also found to be decreased as were intermediate metabolites of the gamma-glutamyl cycle (gamma-glutamyl amino acids and 5-oxoproline. Mild TBI also decreased the levels of methionine, α-ketobutyrate, 2 hydroxybutyrate and glycine, albeit to lesser

Cartap and carbofuran induced alterations in serum lipid profile of Wistar rats.

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Rai, Devendra K; Rai, Prashant Kumar; Gupta, Aradhna; Watal, Geeta; Sharma, Bechan

2009-04-01

Wistar rats of 6-8 weeks in age weighing between 120-150 g were exposed to the fixed doses of each of the carbamate pesticides such as cartap (50% LD(50)) and carbofuran (50% LD(50)) as well as a combination of these two with 25% LD(50) of each for one week. The effect of treatments was studied in terms of serum lipid parameters such as high-density lipoprotein, total cholesterol, triglyceride, low-density lipoprotein and very low-density lipoprotein. Treatment with individual doses of carbofuran (50% LD(50)) and cartap (50 % LD(50)) caused significant alterations in the levels of serum lipid parameters. The pesticides treatment resulted in marked decrease in the level of serum high-density lipoprotein where as that of other lipids got significantly elevated. Further, the rats exhibited relatively higher impact of pesticides when treated with the compounds in combination (25 % LD(50) of each). The results indicated that these compounds when used together may exert enhanced effect on the levels of serum lipids in rat.

Ovine placental steroid synthesis and metabolism in late gestation.

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Reynolds, Lawrence P; Legacki, Erin L; Corbin, C Jo; Caton, Joel S; Vonnahme, Kimberly A; Stanley, Scott; Conley, Alan J

2018-04-14

Steroid synthesis is required for pregnancy maintenance and for parturition but comparatively little is known about the major metabolic routes that influence circulating concentrations. Dietary intake changes progesterone and estradiol concentrations in pregnant ewes but whether this reflects placental synthesis is unknown. Progesterone metabolism by 5alpha-reduction is a major metabolic route in other species and can influence the onset of parturition. Therefore, studies were conducted to 1) determine placental enzyme activity, progesterone and estradiol measured by immuno-assay in late gestation ewes on low, moderate and high nutritional planes, 2) to assess the significance of 5alpha-reduction of progesterone in determining progesterone concentrations in late gestation ewes (gestation day 145) given finasteride to inhibit 5alpha-reductase metabolism. In the second experiment, steroid profiles were examined comprehensively in blood and tissues by liquid chromatography tandem mass spectrometry for the first time in this species. Dietary intake altered progesterone and estradiol serum concentrations but without correlated changes in placental 3beta-hydroxysteroid dehydrogenase, 17alpha-hydroxylase/17,20-lyase cytochrome P450 or aromatase activity. 5alpha-reduced pregnane metabolites were identified in ewes at 145 days of gestation, but concentrations were lower than those of progesterone. Finasteride inhibited 5alpha-reduced progesterone metabolism but did not impact serum progesterone concentrations in these ewes. We conclude 1) that diet-induced changes in serum progesterone and estradiol concentrations are not likely a result of altered placental synthesis of sex steroid but most likely by their metabolism, and 2) metabolism by 5α-reduction is not a major determinant of systemic progesterone concentrations in late gestation ewes.

Acute dim light at night increases body mass, alters metabolism, and shifts core body temperature circadian rhythms.

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Borniger, Jeremy C; Maurya, Santosh K; Periasamy, Muthu; Nelson, Randy J

2014-10-01

The circadian system is primarily entrained by the ambient light environment and is fundamentally linked to metabolism. Mounting evidence suggests a causal relationship among aberrant light exposure, shift work, and metabolic disease. Previous research has demonstrated deleterious metabolic phenotypes elicited by chronic (>4 weeks) exposure to dim light at night (DLAN) (∼ 5 lux). However, the metabolic effects of short-term (dim light would gain more body mass, alter whole body metabolism, and display altered body temperature (Tb) and activity rhythms compared to mice maintained in dark nights. Our data largely support these predictions; DLAN mice gained significantly more mass, reduced whole body energy expenditure, increased carbohydrate over fat oxidation, and altered temperature circadian rhythms. Importantly, these alterations occurred despite similar activity locomotor levels (and rhythms) and total food intake between groups. Peripheral clocks are potently entrained by body temperature rhythms, and the deregulation of body temperature we observed may contribute to metabolic problems due to "internal desynchrony" between the central circadian oscillator and temperature sensitive peripheral clocks. We conclude that even relatively short-term exposure to low levels of nighttime light can influence metabolism to increase mass gain.

Differential impact of serum glucose, triglycerides, and high-density lipoprotein cholesterol on cardiovascular risk factor burden in nondiabetic, obese African American women: implications for the prevalence of metabolic syndrome.

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Gaillard, Trudy; Schuster, Dara; Osei, Kwame

2010-08-01

summary, each of the metabolic components of MetS was associated with different degrees of the clustering of CVD risk factors in AAW. We found that alterations in serum glucose and HDL-C were more predictive of MetS, each yielding approximately 40% of the prevalence of MetS in our nondiabetic, obese AAW. We found that triglycerides had the least impact on MetS in our AAW. We propose (1) that the 3 metabolic parameters for MetS defined by ATP III should be weighted differently with respect to their potential for CVD risks and perhaps outcomes and (2) that nondiabetic AAW in our third tertile of serum glucose (>100 mg/dL) and/or first tertile of HDL-C (<40 mg/dL) should be targeted for screening for MetS. Copyright 2010 Elsevier Inc. All rights reserved.

Fetal rat metabonome alteration by prenatal caffeine ingestion probably due to the increased circulatory glucocorticoid level and altered peripheral glucose and lipid metabolic pathways

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Liu, Yansong; Xu, Dan; Feng, Jianghua; Kou, Hao; Liang, Gai; Yu, Hong; He, Xiaohua; Zhang, Baifang; Chen, Liaobin; Magdalou, Jacques; Wang, Hui

2012-01-01

The aims of this study were to clarify the metabonome alteration in fetal rats after prenatal caffeine ingestion and to explore the underlying mechanism pertaining to the increased fetal circulatory glucocorticoid (GC). Pregnant Wistar rats were daily intragastrically administered with different doses of caffeine (0, 20, 60 and 180 mg/kg) from gestational days (GD) 11 to 20. Metabonome of fetal plasma and amniotic fluid on GD20 were analyzed by 1 H nuclear magnetic resonance-based metabonomics. Gene and protein expressions involved in the GC metabolism, glucose and lipid metabolic pathways in fetal liver and gastrocnemius were measured by real-time RT-PCR and immunohistochemistry. Fetal plasma metabonome were significantly altered by caffeine, which presents as the elevated α- and β‐glucose, reduced multiple lipid contents, varied apolipoprotein contents and increased levels of a number of amino acids. The metabonome of amniotic fluids showed a similar change as that in fetal plasma. Furthermore, the expressions of 11β-hydroxysteroid dehydrogenase 2 (11β-HSD-2) were decreased, while the level of blood GC and the expressions of 11β-HSD-1 and glucocorticoid receptor (GR) were increased in fetal liver and gastrocnemius. Meanwhile, the expressions of insulin-like growth factor 1 (IGF-1), IGF-1 receptor and insulin receptor were decreased, while the expressions of adiponectin receptor 2, leptin receptors and AMP-activated protein kinase α2 were increased after caffeine treatment. Prenatal caffeine ingestion characteristically change the fetal metabonome, which is probably attributed to the alterations of glucose and lipid metabolic pathways induced by increased circulatory GC, activated GC metabolism and enhanced GR expression in peripheral metabolic tissues. -- Highlights: ► Prenatal caffeine ingestion altered the metabonome of IUGR fetal rats. ► Caffeine altered the glucose and lipid metabolic pathways of IUGR fetal rats. ► Prenatal caffeine ingestion

Increased serum phosphate concentrations in patients with advanced chronic kidney disease treated with diuretics.

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Caravaca, Francisco; García-Pino, Guadalupe; Martínez-Gallardo, Rocío; Ferreira-Morong, Flavio; Luna, Enrique; Alvarado, Raúl; Ruiz-Donoso, Enrique; Chávez, Edgar

2013-01-01

Serum phosphate concentrations usually show great variability in patients with advanced chronic kidney disease (ACKD) not on dialysis. Diuretics treatment can have an influence over the severity of mineral-bone metabolism alterations related to ACKD, but their effect on serum phosphate levels is less known. This study aims to determine whether diuretics are independently associated with serum phosphate levels, and to investigate the mechanisms by which diuretics may affect phosphate metabolism. 429 Caucasian patients with CKD not on dialysis were included in this cross-sectional study. In addition to conventional serum biochemical measures, the following parameters of renal phosphate excretion were assessed: 24-hours urinary phosphate excretion, tubular maximum phosphate reabsorption (TmP), and fractional excretion of phosphate (FEP). 58% of patients were on treatment with diuretics. Patients on diuretics showed significantly higher mean serum phosphate concentration (4.78 ± 1.23 vs. 4.24 ± 1.04 mg/dl; Pdiuretics. By multivariate linear and logistic regression, significant associations between diuretics and serum phosphate concentrations or hyperphosphataemia remained after adjustment for potential confounding variables. In patients with the highest phosphate load adjusted to kidney function, those treated with diuretics showed significantly lower FEP than those untreated with diuretics. Treatment with diuretics is associated with increased serum phosphate concentrations in patients with ACKD. Diuretics may indirectly interfere with the maximum renal compensatory capacity to excrete phosphate. Diuretics should be considered in the studies linking the relationship between serum phosphate concentrations and cardiovascular alterations in patients with CKD.

Metabolic Changes and Serum Ghrelin Level in Patients with Psoriasis

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Haydar Ucak

2014-01-01

Full Text Available Background. Serum ghrelin levels may be related to metabolic and clinical changes in patients with psoriasis. Objective. This study was performed to determine the possible effects of serum ghrelin in patients with psoriasis. Methods. The study population consisted of 25 patients with plaque psoriasis. The patients were questioned with regard to age, gender, age of onset, duration of disease, height, weight, and body mass index (BMI. In addition, fasting blood sugar, triglyceride, cholesterol levels, insulin, and ghrelin levels were measured. Results. The mean serum ghrelin level was 45.41 ± 22.41 in the psoriasis group and 29.92 ± 14.65 in the healthy control group. Serum ghrelin level was significantly higher in the psoriasis group compared with the controls (P=0.01. The mean ghrelin level in patients with a lower PASI score was significantly higher than in those with a higher PASI score (P=0.02. Conclusion. The present study was performed to determine the effects of ghrelin in psoriasis patients. We found a negative correlation between severity of psoriasis and ghrelin level. Larger and especially experimental studies focusing on correlation of immune system-ghrelin levels and severity of psoriasis may be valuable to clarify the etiopathogenesis of the disease.

Altered carbon dioxide metabolism and creatine abnormalities in rett syndrome

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Halbach, Nicky S J; Smeets, Eric E J; Bierau, Jörgen; Keularts, Irene M L W; Plasqui, Guy; Julu, Peter O O; Engerström, Ingegerd Witt; Bakker, Jaap A.; Curfs, Leopold M G

2012-01-01

Despite their good appetite, many females with Rett syndrome (RTT) meet the criteria for moderate to severe malnutrition. Although feeding difficulties may play a part in this, other constitutional factors such as altered metabolic processes are suspected. Irregular breathing is a common clinical

Loss of FTO in adipose tissue decreases Angptl4 translation and alters triglyceride metabolism.

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Wang, Chao-Yung; Shie, Shian-Sen; Wen, Ming-Shien; Hung, Kuo-Chun; Hsieh, I-Chang; Yeh, Ta-Sen; Wu, Delon

2015-12-15

A common variant of the FTO (fat mass- and obesity-associated) gene is a risk factor for obesity. We found that mice with an adipocyte-specific deletion of FTO gained more weight than control mice on a high-fat diet. Analysis of mice lacking FTO in adipocytes fed a normal diet or adipocytes from these mice revealed alterations in triglyceride metabolism that would be expected to favor increased fatty acid storage by adipose tissue. Mice lacking FTO in adipocytes showed increased serum triglyceride breakdown and clearance, which was associated with lower serum triglyceride concentrations. In addition, lipolysis in response to β-adrenergic stimulation was decreased in adipocytes and ex vivo adipose explants from the mutant mice. FTO is a nucleic acid demethylase that removes N(6)-methyladenosine (m(6)A) from mRNAs. We found that FTO bound to Angptl4, which encodes an adipokine that stimulates intracellular lipolysis in adipocytes. Unexpectedly, the adipose tissue of fasted or fed mice lacking FTO in adipocytes had greater Angptl4 mRNA abundance. However, after high-fat feeding, the mutant mice had less Angptl4 protein and more m(6)A-modified Angptl4 than control mice, suggesting that lack of FTO prevented the translation of Angptl4. Injection of Angptl4-encoding adenovirus into mice lacking FTO in adipocytes restored serum triglyceride concentrations and lipolysis to values similar to those in control mice and abolished excessive weight gain from a high-fat diet. These results reveal that FTO regulates fatty acid mobilization in adipocytes and thus body weight in part through posttranscriptional regulation of Angptl4. Copyright © 2015, American Association for the Advancement of Science.

The association of serum leptin levels with metabolic diseases

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Jen-Pi Tsai

2017-01-01

Full Text Available Leptin is a 167-amino-acid protein released by white adipose tissue and encoded by the obese gene. It has a role as a negative regulator of appetite control through sending a satiety signal to act on receptors within the hypothalamus. At normal levels, leptin can exert its effects on weight regulation according to white fat mass, induce sodium excretion, maintain vascular tone, and repair the myocardium. Beyond these effects, elevated serum leptin levels have been implicated in the pathogenesis of metabolic syndrome, diabetes mellitus, hypertension, and multiple cardiovascular diseases. In addition, hyperleptinemia had been reported to contribute to renal diseases through multiple mechanisms resulting in glomerulopathy presenting with a decreased glomerular filtration rate, increased albuminuria, and related clinical symptoms, which are pathophysiological features of chronic kidney disease. Because these cardiovascular and metabolic disorders are great challenges for physicians, understanding the related pathophysiological association with leptin might become a valuable aid in handling patients in daily clinical practice. This review will discuss the roles of leptin in the regulation of biological functions of multiple organs beyond the maintenance of feeding and metabolism.

Comparative Circadian Metabolomics Reveal Differential Effects of Nutritional Challenge in the Serum and Liver.

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Abbondante, Serena; Eckel-Mahan, Kristin L; Ceglia, Nicholas J; Baldi, Pierre; Sassone-Corsi, Paolo

2016-02-05

Diagnosis and therapeutic interventions in pathological conditions rely upon clinical monitoring of key metabolites in the serum. Recent studies show that a wide range of metabolic pathways are controlled by circadian rhythms whose oscillation is affected by nutritional challenges, underscoring the importance of assessing a temporal window for clinical testing and thereby questioning the accuracy of the reading of critical pathological markers in circulation. We have been interested in studying the communication between peripheral tissues under metabolic homeostasis perturbation. Here we present a comparative circadian metabolomic analysis on serum and liver in mice under high fat diet. Our data reveal that the nutritional challenge induces a loss of serum metabolite rhythmicity compared with liver, indicating a circadian misalignment between the tissues analyzed. Importantly, our results show that the levels of serum metabolites do not reflect the circadian liver metabolic signature or the effect of nutritional challenge. This notion reveals the possibility that misleading reads of metabolites in circulation may result in misdiagnosis and improper treatments. Our findings also demonstrate a tissue-specific and time-dependent disruption of metabolic homeostasis in response to altered nutrition. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Body composition and risk for metabolic alterations in female adolescents

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Eliane Rodrigues de Faria

2014-06-01

Full Text Available OBJECTIVE: To study anthropometrical and body composition variables as predictors of risk for metabolic alterations and metabolic syndrome in female adolescents.METHODS: Biochemical, clinical and corporal composition data of 100 adolescents from 14 to 17 years old, who attended public schools in Viçosa, Southeastern Brazil, were collected.RESULTS: Regarding nutritional status, 83, 11 and 6% showed eutrophia, overweight/obesity and low weight, respectively, and 61% presented high body fat percent. Total cholesterol presented the highest percentage of inadequacy (57%, followed by high-density lipoprotein (HDL - 50%, low-density lipoprotein (LDL - 47% and triacylglycerol (22%. Inadequacy was observed in 11, 9, 3 and 4% in relation to insulin resistance, fasting insulin, blood pressure and glycemia, respectively. The highest values of the fasting insulin and the Homeostasis Model Assessment-Insulin Resistance(HOMA-IR were verified at the highest quartiles of body mass index (BMI, waist perimeter, waist-to-height ratio and body fat percent. Body mass index, waist perimeter, and waist-to-height ratio were the better predictors for high levels of HOMA-IR, blood glucose and fasting insulin. Waist-to-hip ratio was associated to arterial hypertension diagnosis. All body composition variables were effective in metabolic syndrome diagnosis.CONCLUSIONS: Waist perimeter, BMI and waist-to-height ratio showed to be good predictors for metabolic alterations in female adolescents and then should be used together for the nutritional assessment in this age range.

Metabolic Profile and Inflammatory Responses in Dairy Cows with Left Displaced Abomasum Kept under Small-Scaled Farm Conditions

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Fenja Klevenhusen

2015-10-01

Full Text Available Left displaced abomasum (LDA is a severe metabolic disease of cattle with a strong negative impact on production efficiency of dairy farms. Metabolic and inflammatory alterations associated with this disease have been reported in earlier studies, conducted mostly in large dairy farms. This research aimed to: (1 evaluate metabolic and inflammatory responses in dairy cows affected by LDA in small-scaled dairy farms; and (2 establish an Animals 2015, 5 1022 association between lactation number and milk production with the outcome of metabolic variables. The cows with LDA had lower serum calcium (Ca, but greater concentrations of non-esterified fatty acids (NEFA and beta-hydroxy-butyrate (BHBA, in particular when lactation number was >2. Cows with LDA showed elevated levels of aspartate aminotransferase, glutamate dehydrogenase, and serum amyloid A (SAA, regardless of lactation number. In addition, this study revealed strong associations between milk yield and the alteration of metabolic profile but not with inflammation in the sick cows. Results indicate metabolic alterations, liver damage, and inflammation in LDA cows kept under small-scale farm conditions. Furthermore, the data suggest exacerbation of metabolic profile and Ca metabolism but not of inflammation and liver health with increasing lactation number and milk yield in cows affected by LDA.

Metabolic Profile and Inflammatory Responses in Dairy Cows with Left Displaced Abomasum Kept under Small-Scaled Farm Conditions.

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Klevenhusen, Fenja; Humer, Elke; Metzler-Zebeli, Barbara; Podstatzky-Lichtenstein, Leopold; Wittek, Thomas; Zebeli, Qendrim

2015-10-13

Left displaced abomasum (LDA) is a severe metabolic disease of cattle with a strong negative impact on production efficiency of dairy farms. Metabolic and inflammatory alterations associated with this disease have been reported in earlier studies, conducted mostly in large dairy farms. This research aimed to: (1) evaluate metabolic and inflammatory responses in dairy cows affected by LDA in small-scaled dairy farms; and (2) establish an Animals 2015, 5 1022 association between lactation number and milk production with the outcome of metabolic variables. The cows with LDA had lower serum calcium (Ca), but greater concentrations of non-esterified fatty acids (NEFA) and beta-hydroxy-butyrate (BHBA), in particular when lactation number was >2. Cows with LDA showed elevated levels of aspartate aminotransferase, glutamate dehydrogenase, and serum amyloid A (SAA), regardless of lactation number. In addition, this study revealed strong associations between milk yield and the alteration of metabolic profile but not with inflammation in the sick cows. Results indicate metabolic alterations, liver damage, and inflammation in LDA cows kept under small-scale farm conditions. Furthermore, the data suggest exacerbation of metabolic profile and Ca metabolism but not of inflammation and liver health with increasing lactation number and milk yield in cows affected by LDA.

Alterations of hippocampal glucose metabolism by even versus uneven medium chain triglycerides

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McDonald, Tanya S; Tan, Kah Ni; Hodson, Mark P; Borges, Karin

2014-01-01

Medium chain triglycerides (MCTs) are used to treat neurologic disorders with metabolic impairments, including childhood epilepsy and early Alzheimer's disease. However, the metabolic effects of MCTs in the brain are still unclear. Here, we studied the effects of feeding even and uneven MCTs on brain glucose metabolism in the mouse. Adult mice were fed 35% (calories) of trioctanoin or triheptanoin (the triglycerides of octanoate or heptanoate, respectively) or a matching control diet for 3 weeks. Enzymatic assays and targeted metabolomics by liquid chromatography tandem mass spectrometry were used to quantify metabolites in extracts from the hippocampal formations (HFs). Both oils increased the levels of β-hydroxybutyrate, but no other significant metabolic alterations were observed after triheptanoin feeding. The levels of glucose 6-phosphate and fructose 6-phosphate were increased in the HF of mice fed trioctanoin, whereas levels of metabolites further downstream in the glycolytic pathway and the pentose phosphate pathway were reduced. This indicates that trioctanoin reduces glucose utilization because of a decrease in phosphofructokinase activity. Trioctanoin and triheptanoin showed similar anticonvulsant effects in the 6 Hz seizure model, but it remains unknown to what extent the anticonvulsant mechanism(s) are shared. In conclusion, triheptanoin unlike trioctanoin appears to not alter glucose metabolism in the healthy brain. PMID:24169853

Serum cytokine contents in schizophrenia patient with metabolic syndrome and their correlation with nerve electrophysiology

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Li-Yong Chen

2016-07-01

Full Text Available Objective: To analyze serum cytokine contents in schizophrenia patient with metabolic syndrome (MS and their correlation with nerve electrophysiology. Methods: A total of 90 chizophrenia patient with MS, including 41 cases with simple schizophrenia and 39 cases with simple metabolic syndrome were included for study. The values of nerve electrophysiology indexes and serum illness-related indexes were compared among included patients, and the correlation between the two was further analyzed. Results: Compared with simple schizophrenia group and simple MS group, P300 latency of schizophrenia with MS group was longer, and the amplitude was shorter; N2-P3 latency and amplitude were shorter (P<0.05; serum SOD, S100b, BDNF, ABAb, PAI-1, 毩-HBDH, AST, cystatin c, TG, FBG and 2hPG values of schizophrenia with MS group were higher, IGF1, HMW-APN and HDL-C levels were lower, and compared with simple schizophrenia group and simple MS group, differences were significant (P<0.05; P300 latency, P300 amplitude, N2-P3 latency and N2- P3 amplitude of schizophrenia with MS group were directly correlated with serum cytokine contents (P<0.05. Conclusions: There are significantly abnormal serum cytokines and nerve electrophysiology indexes in schizophrenia patient with MS, and nerve electrophysiology detection can be used as the means to judge disease and guide treatment.

Metabolic alterations in patients who develop traumatic brain injury (TBI)-induced hypopituitarism.

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Prodam, F; Gasco, V; Caputo, M; Zavattaro, M; Pagano, L; Marzullo, P; Belcastro, S; Busti, A; Perino, C; Grottoli, S; Ghigo, E; Aimaretti, G

2013-08-01

Hypopituitarism is associated with metabolic alterations but in TBI-induced hypopituitarism data are scanty. The aim of our study was to evaluate the prevalence of naïve hypertension, dyslipidemia, and altered glucose metabolism in TBI-induced hypopituitarism patients. Cross-sectional retrospective study in a tertiary care endocrinology center. 54 adult patients encountering a moderate or severe TBI were evaluated in the chronic phase (at least 12 months after injury) after-trauma. Presence of hypopituitarism, BMI, hypertension, fasting blood glucose and insulin levels, oral glucose tolerance test (if available) and a lipid profile were evaluated. The 27.8% of patients showed various degrees of hypopituitarism. In particular, 9.3% had total, 7.4% multiple and 11.1% isolated hypopituitarism. GHD was present in 22.2% of patients. BMI was similar between the two groups. Hypopituitaric patients presented a higher prevalence of dyslipidemia (phypopituitaric patients. In particular, triglycerides (phypopituitaric TBI patients. We showed that long-lasting TBI patients who develop hypopituitarism frequently present metabolic alterations, in particular altered glucose levels, insulin resistance and hypertriglyceridemia. In view of the risk of premature cardiovascular death in hypopituitaric patients, major attention has to been paid in those who encountered a TBI, because they suffer from the same comorbidities and may present other deterioration factors due to complex pharmacological treatments and restriction in participation in life activities and healthy lifestyle. Copyright © 2013 Elsevier Ltd. All rights reserved.

[Serum glycosaminoglycans in Graves' disease patients].

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Winsz-Szczotka, Katarzyna B; Olczyk, Krystyna Z; Koźma, Ewa M; Komosińska-Vassev, Katarzyna B; Wisowski, Grzegorz R; Marcisz, Czesław

2006-01-01

The aim of the study was to determine the blood serum sulfated glycosaminoglycans (GAGs) and hyaluronic acid (HA) concentration of Graves' disease patients before treatment and after attainment of the euthyroid state. The study was carried out on the blood serum obtained from 17 patients with newly recognised Graves' disease and from the same patients after attainment of the euthyroid state. Graves' patients had not any clinical symptoms neither of ophthalmopathy nor pretibial myxedema. GAGs were isolated from the blood serum by the multistage extraction and purification using papaine hydrolysis, alkali elimination, as well as cetylpyridium chloride binding. Total amount of GAGs was quantified by the hexuronic acids assay. HA content in obtained GAGs sample was evaluated by the ELISA method. Increased serum concentration of sulfated GAGs in non-treated Graves' disease patients was found. Similarly, serum HA level in untreated patients was significantly elevated. The attainment of euthyroid state was accompanied by the decreased serum sulfated GAGs level and by normalization of serum HA concentration. In conclusion, the results obtained demonstrate that the alterations of GAGs metabolism connected with Graves' disease can lead to systemic changes of the extracellular matrix properties.

Fetal rat metabonome alteration by prenatal caffeine ingestion probably due to the increased circulatory glucocorticoid level and altered peripheral glucose and lipid metabolic pathways

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Liu, Yansong [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan University, Wuhan, 430071 (China); Xu, Dan [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan University, Wuhan, 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan, 430071 (China); Feng, Jianghua, E-mail: jianghua.feng@xmu.edu.cn [Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, 430071 (China); Department of Electronic Science, Fujian Provincial Key Laboratory of Plasma and Magnetic Resonance, Xiamen University, Xiamen, 361005 (China); Kou, Hao; Liang, Gai [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan University, Wuhan, 430071 (China); Yu, Hong; He, Xiaohua; Zhang, Baifang; Chen, Liaobin [Research Center of Food and Drug Evaluation, Wuhan University, Wuhan, 430071 (China); Magdalou, Jacques [UMR 7561 CNRS-Nancy Université, Faculté de Médicine, Vandoeuvre-lès-Nancy (France); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan University, Wuhan, 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan, 430071 (China)

2012-07-15

The aims of this study were to clarify the metabonome alteration in fetal rats after prenatal caffeine ingestion and to explore the underlying mechanism pertaining to the increased fetal circulatory glucocorticoid (GC). Pregnant Wistar rats were daily intragastrically administered with different doses of caffeine (0, 20, 60 and 180 mg/kg) from gestational days (GD) 11 to 20. Metabonome of fetal plasma and amniotic fluid on GD20 were analyzed by {sup 1}H nuclear magnetic resonance-based metabonomics. Gene and protein expressions involved in the GC metabolism, glucose and lipid metabolic pathways in fetal liver and gastrocnemius were measured by real-time RT-PCR and immunohistochemistry. Fetal plasma metabonome were significantly altered by caffeine, which presents as the elevated α- and β‐glucose, reduced multiple lipid contents, varied apolipoprotein contents and increased levels of a number of amino acids. The metabonome of amniotic fluids showed a similar change as that in fetal plasma. Furthermore, the expressions of 11β-hydroxysteroid dehydrogenase 2 (11β-HSD-2) were decreased, while the level of blood GC and the expressions of 11β-HSD-1 and glucocorticoid receptor (GR) were increased in fetal liver and gastrocnemius. Meanwhile, the expressions of insulin-like growth factor 1 (IGF-1), IGF-1 receptor and insulin receptor were decreased, while the expressions of adiponectin receptor 2, leptin receptors and AMP-activated protein kinase α2 were increased after caffeine treatment. Prenatal caffeine ingestion characteristically change the fetal metabonome, which is probably attributed to the alterations of glucose and lipid metabolic pathways induced by increased circulatory GC, activated GC metabolism and enhanced GR expression in peripheral metabolic tissues. -- Highlights: ► Prenatal caffeine ingestion altered the metabonome of IUGR fetal rats. ► Caffeine altered the glucose and lipid metabolic pathways of IUGR fetal rats. ► Prenatal caffeine

Serum selenium concentration is associated with metabolic factors in the elderly: a cross-sectional study

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Huang Hui-Ying

2010-05-01

Full Text Available Abstract Background Selenium is an essential micronutrient known for its antioxidant function. However, the association of serum selenium with lipid profiles and fasting glucose are inconsistent in populations with average intake of selenium. Furthermore, there were few studies conducted specifically for the elderly. This study examined the relationship of serum selenium concentration with serum lipids and fasting glucose in the Taiwanese elderly population. Methods This was a cross-sectional study of 200 males and females aged 65-85 years (mean 71.5 ± 4.6 years from Taipei, Taiwan. Serum selenium was measured by inductively coupled plasma-mass spectrometer. The association between serum selenium and metabolic factors was examined using a multivariate linear regression analysis after controlling several confounders. Results The mean serum selenium concentration was 1.14 μmol/L, without significant difference between sexes. Total cholesterol, triglycerides, and LDL cholesterol increased significantly with serum selenium concentration (P P P P Conclusions Total cholesterol, triglycerides, and LDL cholesterol, and fasting serum glucose concentrations increased significantly with serum selenium concentration in the Taiwanese elderly. The underlying mechanism warrants further research.

Elevated Serum Levels of Cysteine and Tyrosine: Early Biomarkers in Asymptomatic Adults at Increased Risk of Developing Metabolic Syndrome

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Nina Mohorko

2015-01-01

Full Text Available As there is effective intervention for delaying or preventing metabolic diseases, which are often present for years before becoming clinically apparent, novel biomarkers that would mark metabolic complications before the onset of metabolic disease should be identified. We investigated the role of fasting serum amino acids and their associations with inflammatory markers, adipokines, and metabolic syndrome (MetS components in subjects prior to the onset of insulin resistance (IR. Anthropometric measurements, food records, adipokines, biochemical markers, and serum levels of amino acids were determined in 96 asymptomatic subjects aged 25–49 years divided into three groups according to the number of MetS components present. Cysteine and tyrosine were significantly higher already in group with one component of MetS present compared to subjects without MetS components. Serum amino acid levels correlated with markers of inflammation and adipokines. Alanine and glycine explained 10% of insulin resistance variability. The role of tyrosine and cysteine, that were higher already with 1 component of MetS present, should be further investigated as they might point to future insulin disturbances.

Calcium homestasis markers of bone metabolism in feline hyperthyroidism - A review

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Cardoso, M. J L; Muniz, L. M R [UNESP; Gasparini, T. J.; Melussi, M.

2007-01-01

Hyperthyroidism is the most frequent endocrine disease in old-aged cats. It is a illness provoked by the excess of circulating thyroid hormones. Hyperthyroidism causes alteration in bone metabolism with predominance of activity resorption. The evaluation of bone metabolism can be made by measuring serum and urinary markers of bone metabolism or bone mineral densitometry. Osteoblasts are responsible cells for bone formation while the osteoclasts are for resorption. In physiological situation o...

Fluorescence lifetime microscopy of NADH distinguishes alterations in cerebral metabolism in vivo.

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Yaseen, Mohammad A; Sutin, Jason; Wu, Weicheng; Fu, Buyin; Uhlirova, Hana; Devor, Anna; Boas, David A; Sakadžić, Sava

2017-05-01

Evaluating cerebral energy metabolism at microscopic resolution is important for comprehensively understanding healthy brain function and its pathological alterations. Here, we resolve specific alterations in cerebral metabolism in vivo in Sprague Dawley rats utilizing minimally-invasive 2-photon fluorescence lifetime imaging (2P-FLIM) measurements of reduced nicotinamide adenine dinucleotide (NADH) fluorescence. Time-resolved fluorescence lifetime measurements enable distinction of different components contributing to NADH autofluorescence. Ostensibly, these components indicate different enzyme-bound formulations of NADH. We observed distinct variations in the relative proportions of these components before and after pharmacological-induced impairments to several reactions involved in glycolytic and oxidative metabolism. Classification models were developed with the experimental data and used to predict the metabolic impairments induced during separate experiments involving bicuculline-induced seizures. The models consistently predicted that prolonged focal seizure activity results in impaired activity in the electron transport chain, likely the consequence of inadequate oxygen supply. 2P-FLIM observations of cerebral NADH will help advance our understanding of cerebral energetics at a microscopic scale. Such knowledge will aid in our evaluation of healthy and diseased cerebral physiology and guide diagnostic and therapeutic strategies that target cerebral energetics.

Dietary diversity score is associated with cardiovascular risk factors and serum adiponectin concentrations in patients with metabolic syndrome.

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Farhangi, Mahdieh Abbasalizad; Jahangiry, Leila

2018-04-17

Metabolic syndrome is associated with cardio-metabolic risk factors and lipid abnormalities. Previous studies evaluated the dietary habits and nutrient intakes among patients with metabolic syndrome; however the association between metabolic risk factors and adiponectin with dietary diversity score (DDS) in patients with metabolic syndrome has not been evaluated yet. Therefore the aim of the current study was to evaluate these relationships among patients with metabolic syndrome. One hundred sixty patients with metabolic syndrome were recruited in the study. The anthropometric parameters including weight, height, waist circumference and hip circumference were measured. Serum adiponectin concentration was measured by enzyme- linked immunosorbent assay method (ELISA). Lipid profile and fasting serum glucose concentrations (FSG) were also measured with enzymatic colorimetric methods. Blood pressure was also measured and DDS was calculated using the data obtained from food frequency questionnaire (FFQ). Subjects in lower DDS categorizes had significantly lower energy and fiber intake; whereas mean protein intake of subjects in the highest quartile was significantly higher than second quartile. Higher prevalence of obesity was also observed in the top quartiles (P metabolic syndrome components among patients in lower DDS quartiles was significantly higher (P metabolic syndrome. However, for further confirming the findings, more studies are warranted.

Study of serum osteocalcin levels in patients with hyperthyroidism

International Nuclear Information System (INIS)

Qiu Ningyan; Zhang Jingxin; Li Huiping; Gong Yiming

2001-01-01

In order to study the serum osteocalcin (OC) level in hyperthyroidism, serum osteocalcin, FT 3 , FT 4 and TSH were measured by radioimmunoassay in 87 patients with hyperthyroidism and 52 healthy volunteers. The results indicated that the serum osteocalcin level was decreased with age increasing in healthy volunteers and there was no significant difference in sex (P > 0.05). Serum concentration of OC was significantly higher in untreated hyperthyroid patients than that in healthy volunteers (P 3 , FT 4 (FT 3 :r 0.84 - 0.27, P 4 :r = 0.58 - 0.29, P < 0.01), but not with TSH. Conclusion: Thyroid hormones might speed up bone turnover directly with increased bone resorption to induce bone mass loss. These results indicate that OC is a highly sensitive marker for altered bone metabolism in hyperthyroidism

Serum Calcium and the Risk of Incident Metabolic Syndrome: A 4.3-Year Retrospective Longitudinal Study

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Jong Ha Baek

2017-01-01

Full Text Available BackgroundAn association between serum calcium level and risk of metabolic syndrome (MetS has been suggested in cross-sectional studies. This study aimed to evaluate the association between baseline serum calcium level and risk of incident MetS in a longitudinal study.MethodsWe conducted a retrospective longitudinal study of 12,706 participants without MetS who participated in a health screening program, had normal range serum calcium level at baseline (mean age, 51 years, and were followed up for 4.3 years (18,925 person-years. The risk of developing MetS was analyzed according to the baseline serum calcium levels.ResultsA total of 3,448 incident cases (27.1% of MetS developed during the follow-up period. The hazard ratio (HR for incident MetS did not increase with increasing tertile of serum calcium level in an age- and sex-matched model (P for trend=0.915. The HRs (95% confidence interval [CI] for incident MetS comparing the second and the third tertiles to the first tertile of baseline serum calcium level were 0.91 (95% CI, 0.84 to 0.99 and 0.85 (95% CI, 0.78 to 0.92 in a fully adjusted model, respectively (P for trend=0.001. A decreased risk of incident MetS in higher tertiles of serum calcium level was observed in subjects with central obesity and/or a metabolically unhealthy state at baseline.ConclusionThere was no positive correlation between baseline serum calcium levels and incident risk of MetS in this longitudinal study. There was an association between higher serum calcium levels and decreased incident MetS in individuals with central obesity or two components of MetS at baseline.

Altered metabolism of growth hormone receptor mutant mice: a combined NMR metabonomics and microarray study.

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Horst Joachim Schirra

Full Text Available BACKGROUND: Growth hormone is an important regulator of post-natal growth and metabolism. We have investigated the metabolic consequences of altered growth hormone signalling in mutant mice that have truncations at position 569 and 391 of the intracellular domain of the growth hormone receptor, and thus exhibit either low (around 30% maximum or no growth hormone-dependent STAT5 signalling respectively. These mutations result in altered liver metabolism, obesity and insulin resistance. METHODOLOGY/PRINCIPAL FINDINGS: The analysis of metabolic changes was performed using microarray analysis of liver tissue and NMR metabonomics of urine and liver tissue. Data were analyzed using multivariate statistics and Gene Ontology tools. The metabolic profiles characteristic for each of the two mutant groups and wild-type mice were identified with NMR metabonomics. We found decreased urinary levels of taurine, citrate and 2-oxoglutarate, and increased levels of trimethylamine, creatine and creatinine when compared to wild-type mice. These results indicate significant changes in lipid and choline metabolism, and were coupled with increased fat deposition, leading to obesity. The microarray analysis identified changes in expression of metabolic enzymes correlating with alterations in metabolite concentration both in urine and liver. Similarity of mutant 569 to the wild-type was seen in young mice, but the pattern of metabolites shifted to that of the 391 mutant as the 569 mice became obese after six months age. CONCLUSIONS/SIGNIFICANCE: The metabonomic observations were consistent with the parallel analysis of gene expression and pathway mapping using microarray data, identifying metabolites and gene transcripts involved in hepatic metabolism, especially for taurine, choline and creatinine metabolism. The systems biology approach applied in this study provides a coherent picture of metabolic changes resulting from impaired STAT5 signalling by the growth hormone

Danazol alters mitochondria metabolism of fibrocystic breast Mcf10A cells.

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Irgebay, Zhazira; Yeszhan, Banu; Sen, Bhaswati; Tuleukhanov, Sultan; Brooks, Ari D; Sensenig, Richard; Orynbayeva, Zulfiya

2017-10-01

Fibrocystic Breast Disease (FBD) or Fibrocystic change (FC) affects about 60% of women at some time during their life. Although usually benign, it is often associated with pain and tenderness (mastalgia). The synthetic steroid danazol has been shown to be effective in reducing the pain associated with FBD, but the cellular and molecular mechanisms for its action have not been elucidated. We investigated the hypothesis that danazol acts by affecting energy metabolism. Effects of danazol on Mcf10A cells homeostasis, including mechanisms of oxidative phosphorylation, cytosolic calcium signaling and oxidative stress, were assessed by high-resolution respirometry and flow cytometry. In addition to fast physiological responses the associated genomic modulations were evaluated by Affimetrix microarray analysis. The alterations of mitochondria membrane potential and respiratory activity, downregulation of energy metabolism transcripts result in suppression of energy homeostasis and arrest of Mcf10A cells growth. The data obtained in this study impacts the recognition of direct control of mitochondria by cellular mechanisms associated with altered energy metabolism genes governing the breast tissue susceptibility and response to medication by danazol. Copyright © 2017 Elsevier Ltd. All rights reserved.

Metabolic and feeding behavior alterations provoked by prenatal exposure to aspartame.

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von Poser Toigo, E; Huffell, A P; Mota, C S; Bertolini, D; Pettenuzzo, L F; Dalmaz, C

2015-04-01

The use of artificial sweeteners has increased together with the epidemic growth of obesity. In addition to their widespread use in sodas, artificial sweeteners are added to nearly 6000 other products sold in the US, including baby foods, frozen dinners and even yogurts. It has been suggested that the use of nonnutritive sweeteners can lead to body weight gain and an altered metabolic profile. However, very few studies have evaluated the effects of maternal consumption of artificial non-caloric sweeteners on body weight, feeding behavior or the metabolism of offspring in adult life. In this study, we found that animals exposed to aspartame during the prenatal period presented a higher consumption of sweet foods during adulthood and a greater susceptibility to alterations in metabolic parameters, such as increased glucose, LDL and triglycerides. These effects were observed in both males and females, although they were more pronounced in males. Despite the preliminary nature of this study, and the need for further confirmation of these effects, our data suggest that the consumption of sweeteners during gestation may have deleterious long-term effects and should be used with caution. Copyright © 2014 Elsevier Ltd. All rights reserved.

Alterations of serum macro-minerals and trace elements are associated with major depressive disorder: a case-control study.

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Islam, Md Rabiul; Islam, Md Reazul; Shalahuddin Qusar, M M A; Islam, Mohammad Safiqul; Kabir, Md Humayun; Mustafizur Rahman, G K M; Islam, Md Saiful; Hasnat, Abul

2018-04-10

Major depressive disorder (MDD) is a mixed disorder with the highly irregular course, inconsistent response to treatment and has no well-known mechanism for the pathophysiology. Major causes of depression are genetic, neurobiological, and environmental. However, over the past few years, altered serum levels of macro-minerals (MM) and trace elements (TE) have been recognized as major causative factors to the pathogenesis of many mental disorders. The purpose of this study was to determine the serum levels of MM (calcium and magnesium) and TE (copper, iron, manganese, selenium, and zinc) in MDD patients and find out their associations with depression risk. This prospective case-control study recruited 247 patients and 248 healthy volunteers matched by age and sex. The serum levels of MM and TE were analyzed by atomic absorption spectroscopy (AAS). Statistical analysis was performed with independent sample t-tests and Pearson's correlation test. We found significantly decreased concentrations of calcium and magnesium, iron, manganese, selenium, and zinc in MDD patients compared with control subjects (p < 0.05). But the concentration of copper was significantly increased in the patients than control subjects (p < 0.05). Data obtained from different inter-element relations in MDD patients and control subjects strongly suggest that there is a disturbance in the element homeostasis. Our study suggests that altered serum concentrations of MM and TE are major contributing factors for the pathogenesis of MDD. Alterations of these elements in serum levels of MDD patients arise independently and they may provide a prognostic tool for the assessment of depression risk.

Alterations of serum antioxidant trace elements (Se, Zn and Cu status in patients with cutaneous leishmaniasis

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Leila Farzin

2014-02-01

Full Text Available Objective: To assess the serum antioxidant trace elements selenium (Se, zinc (Zn and copper (Cu in cutaneous leishmaniasis patients. Methods: In this study, serum Se, Zn and Cu was determined by using atomic absorption spectrometry in patients with cutaneous leishmaniasis (n=95. The values were statistically compared between patients and control group (n=100 using One-way analysis of variance (ANOVA. Results: Our results showed that there was a significant difference in the values of Se and Zn between two groups (P0.05. Se and Zn levels were found to be (4.33依1.06 and (70.23依19.12 µg/dL in cutaneous leishmaniasis cases, and these values were found statistically lower compared to the controls (11.10依2.37 and (119.61依26.18 µg/dL, respectively. Conclusions: The observations that host products are released from stimulated leukocytes and could induce metabolic changes similar to an acute-phase response revealed an endocrine role for the immune system. Characteristic changes in trace-mineral metabolism are an integral part of the acute-phase response. The changes are usually reflected in decreased serum Se and Zn concentrations.

Alterations in the brain adenosine metabolism cause behavioral and neurological impairment in ADA-deficient mice and patients

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Sauer, Aisha V.; Hernandez, Raisa Jofra; Fumagalli, Francesca; Bianchi, Veronica; Poliani, Pietro L.; Dallatomasina, Chiara; Riboni, Elisa; Politi, Letterio S.; Tabucchi, Antonella; Carlucci, Filippo; Casiraghi, Miriam; Carriglio, Nicola; Cominelli, Manuela; Forcellini, Carlo Alberto; Barzaghi, Federica; Ferrua, Francesca; Minicucci, Fabio; Medaglini, Stefania; Leocani, Letizia; la Marca, Giancarlo; Notarangelo, Lucia D.; Azzari, Chiara; Comi, Giancarlo; Baldoli, Cristina; Canale, Sabrina; Sessa, Maria; D’Adamo, Patrizia; Aiuti, Alessandro

2017-01-01

Adenosine Deaminase (ADA) deficiency is an autosomal recessive variant of severe combined immunodeficiency (SCID) caused by systemic accumulation of ADA substrates. Neurological and behavioral abnormalities observed in ADA-SCID patients surviving after stem cell transplantation or gene therapy represent an unresolved enigma in the field. We found significant neurological and cognitive alterations in untreated ADA-SCID patients as well as in two groups of patients after short- and long-term enzyme replacement therapy with PEG-ADA. These included motor dysfunction, EEG alterations, sensorineural hypoacusia, white matter and ventricular alterations in MRI as well as a low mental development index or IQ. Ada-deficient mice were significantly less active and showed anxiety-like behavior. Molecular and metabolic analyses showed that this phenotype coincides with metabolic alterations and aberrant adenosine receptor signaling. PEG-ADA treatment corrected metabolic adenosine-based alterations, but not cellular and signaling defects, indicating an intrinsic nature of the neurological and behavioral phenotype in ADA deficiency. PMID:28074903

Long-term exposure to xenoestrogens alters some brain monoamines and both serum thyroid hormones and cortisol levels in adult male rats

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Nashwa M. Saied

2014-10-01

Full Text Available The present study was designed to examine the effect of long-term treatment with the phytoestrogen soy isoflavone [(SIF; 43 mg/kg body weight/day] and/or the plastics component bisphenol-A [(BPA; 3 mg/kg body weight/day] on some monoamines in the forebrain and both serum thyroid hormones and cortisol levels of adult rats. Significant increases in serotonin (5-HT and norepinephrine (NE level, and significant decreases in 5-hydroxyindoleacetic acid (5-HIAA level and 5-HIAA/5-HT ratio, were observed after treatment with SIF or BPA. Level of dopamine (DA was increased in SIF-treated group and decreased in BPA-treated group. Activity of monoamine oxidase (MAO was decreased in all treated groups. The level of serum thyroid hormones (fT3 and fT4 was increased after treatment with SIF and decreased after exposure to BPA, while cortisol level was increased in all treated groups. It may be concluded that long-term exposure to SIF or BPA disrupts monoamine levels in the forebrain of adult rats through alteration in the metabolic pathways of amines and disorders of thyroid hormones and cortisol levels.

The Association of Elevated Serum Alanine Aminotransferase with Metabolic Syndrome in A Military Population in Southern Iran

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B Sabayan

2010-06-01

Full Text Available Background: Metabolic syndrome (MetS is rapidly rising at an alarming rate through all parts of the world. Elevated serum aminotransferase was proposed as a marker for early detection of MetS. In this investigation we primarily aimed to evaluate the prevalence of MetS and its components among army and secondly to explore the association between elevated serum aminotransferase and the components of metabolic syndrome. Methods: A total of 380 army personnel from a military camp in Southern Iran participated in this cross-sectional study. Life style related characteristics, anthropometric features, serum aminotransferase and components of MetS, based on National Cholesterol Education Program—Adult Treatment Panel III, were measured. Statistical significant was set as p value less than 0.05. Results: The mean age of participants was 35.0± 7.5 year-old and the prevalence of metabolic syndrome was 8.1%. The prevalence of the components of MetS including; central obesity, abnormal fasting blood glucose, hypertension, hypertriglycridemia and low HDL cholesterol level was 8.6%, 10.4%, 18.5%, 31%, and 45.5% respectively. MetS had significant relationship with obesity (P<0.001 and abnormal Waist Circumferance/Hip Circumference ratio (P<0.001. Twenty-six percent of subjects had ALT ≥ 41 U/L and 4.9% of them had ALT ≥ 81. Elevated serum aminotransferase had significant association with presence of MetS (P= 0.007. Conclusion: Although prevalence of metabolic syndrome among the studied army population was not high, life style modification of army members is recommended. Liver function tests should be included in routine health checkup of military personnel.

The role of serum non-cholesterol sterols as surrogate markers of absolute cholesterol synthesis and absorption.

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Miettinen, T A; Gylling, H; Nissinen, M J

2011-10-01

To study the whole-body cholesterol metabolism in man, cholesterol synthesis and absorption need to be measured. Because of the complicated methods of the measurements, new approaches were developed including the analysis of serum non-cholesterol sterols. In current lipidologic papers and even in intervention studies, serum non-cholesterol sterols are frequently used as surrogate markers of cholesterol metabolism without any validation to the absolute metabolic variables. The present review compares serum non-cholesterol sterols with absolute measurements of cholesterol synthesis and absorption in published papers to find out whether the serum markers are valid indicators of cholesterol metabolism in various conditions. During statin treatment, during interventions of dietary fat, and in type 2 diabetes the relative and absolute variables of cholesterol synthesis and absorption were frequently but not constantly correlated with each other. In some occasions, especially in subjects with apolipoprotein E3/4 and E4/4 phenotypes, the relative metabolic markers were even more sensitive than the absolute ones to reflect changes in cholesterol metabolism during dietary interventions. Even in general population at very high absorption the homeostasis of cholesterol metabolism is disturbed damaging the validity of the serum markers. It is worth using several instead of only one precursor and absorption sterol marker for making conclusions of altered synthesis or absorption of cholesterol, and even then the presence of at least some absolute measurement is valuable. During consumption of plant sterol-enriched diets and in situations of interfered cholesterol homeostasis the relative markers do not adequately reflect cholesterol metabolism. Accordingly, the validity of the relative markers of cholesterol metabolism should not be considered as self-evident. Copyright © 2011 Elsevier B.V. All rights reserved.

The effect of serum from obese and normal weight men on glucose metabolism in leucocytes

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Myking, O.; Kjoesen, B.; Bassoee, H.H.

1980-01-01

The influence of pooled serum from either obese or normal weight males on glucose metabolism in human leucocytes has been studied. Leucocytes from normal weight males were incubated with 10-90% pooled serum and either [U- 14 C], or [1- 14 C]glucose. Compared to serum from the normal weight males, serum from the obese group had a more stimulating effect on the 14 CO 2 and [ 14 C]lactate production from [U- 14 C]glucose and on the 14 CO 2 production from [1- 14 C]glucose. The two serum pools had the same stimulating effect on the Embden-Meyerhof pathway as indicated by the formation of [ 14 C]lactate from [l- 14 C]glucose. Calculations revealed that the activity in the pentose phosphate pathway was stimulated more by serum from obese, than from normal weight males. It is a possibility that increased stimulation of the pentose phosphate pathway may contribute to the development of overweight. (author)

Hemodynamics alter arterial low-density lipoprotein metabolism

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Warty, V.S.; Calvo, W.J.; Berceli, S.A.; Pham, S.M.; Durham, S.J.; Tanksale, S.K.; Klein, E.C.; Herman, I.M.; Borovetz, H.S.

1989-01-01

We have investigated the role of hemodynamic factors on low-density lipoprotein transport and metabolism in the intact arterial wall. Freshly excised canine carotid blood vessels were exposed to well-defined pulsatile flow in vitro for continuous periods up to 20 hours. We chose to impose the following hemodynamic conditions on our test carotid arteries: normotension, hypertension (at physiologic flow conditions), and hypertension coupled with elevated flow of canine serum perfusate. In several experiments the effect of endothelial denudation was examined in carotid arteries exposed to normotensive pulsatile flow. A trapped ligand method was used for quantitating low-density lipoprotein uptake and metabolism in the arterial wall. The distribution of both intact and degraded low-density lipoprotein fractions was determined from measurements of radiolabelled low-density lipoprotein activity within thin radial sections of perfused arteries. Our results suggest that both hypertensive hemodynamic simulations exacerbate the uptake of low-density lipoprotein within the arterial wall (by a factor of three to nine). The percentage of low-density lipoprotein that undergoes irreversible degradation falls from 41% under normotensive conditions to below 30% when hypertensive conditions are imposed, indicating that degradative processes are not proportionally elevated with the accelerated influx. A similar pattern is observed for deendothelialized vessels

Dietary patterns in men and women are simultaneously determinants of altered glucose metabolism and bone metabolism.

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Langsetmo, Lisa; Barr, Susan I; Dasgupta, Kaberi; Berger, Claudie; Kovacs, Christopher S; Josse, Robert G; Adachi, Jonathan D; Hanley, David A; Prior, Jerilynn C; Brown, Jacques P; Morin, Suzanne N; Davison, Kenneth S; Goltzman, David; Kreiger, Nancy

2016-04-01

We hypothesized that diet would have direct effects on glucose metabolism with direct and indirect effects on bone metabolism in a cohort of Canadian adults. We assessed dietary patterns (Prudent [fruit, vegetables, whole grains, fish, and legumes] and Western [soft drinks, potato chips, French fries, meats, and desserts]) from a semiquantitative food frequency questionnaire. We used fasting blood samples to measure glucose, insulin, homeostatic model assessment insulin resistance (HOMA-IR), 25-hydroxyvitamin D (25OHD), parathyroid hormone, bone-specific alkaline phosphatase (a bone formation marker), and serum C-terminal telopeptide (CTX; a bone resorption marker). We used multivariate regression models adjusted for confounders and including/excluding body mass index. In a secondary analysis, we examined relationships through structural equations models. The Prudent diet was associated with favorable effects on glucose metabolism (lower insulin and HOMA-IR) and bone metabolism (lower CTX in women; higher 25OHD and lower parathyroid hormone in men). The Western diet was associated with deleterious effects on glucose metabolism (higher glucose, insulin, and HOMA-IR) and bone metabolism (higher bone-specific alkaline phosphatase and lower 25OHD in women; higher CTX in men). Body mass index adjustment moved point estimates toward the null, indicating partial mediation. The structural equation model confirmed the hypothesized linkage with strong effects of Prudent and Western diet on metabolic risk, and both direct and indirect effects of a Prudent diet on bone turnover. In summary, a Prudent diet was associated with lower metabolic risk with both primary and mediated effects on bone turnover, suggesting that it is a potential target for reducing fracture risk. Copyright © 2016 Elsevier Inc. All rights reserved.

Novel cell-based assay reveals associations of circulating serum AhR-ligands with metabolic syndrome and mitochondrial dysfunction.

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Park, Wook-Ha; Jun, Dae Won; Kim, Jin Taek; Jeong, Jae Hoon; Park, Hyokeun; Chang, Yoon-Seok; Park, Kyong Soo; Lee, Hong Kyu; Pak, Youngmi Kim

2013-01-01

Serum concentrations of environmental pollutants have been positively correlated with diabetes and metabolic syndrome in epidemiologic studies. In turn, abnormal mitochondrial function has been associated with the diseases. The relationships between these variables, however, have not been studied. We developed novel cell-based aryl hydrocarbon receptor (AhR) agonist bioassay system without solvent extraction process and analyzed whether low-dose circulating AhR ligands in human serum are associated with parameters of metabolic syndrome and mitochondrial function. Serum AhR ligand activities were measured as serum 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalent (sTCDDeq) in pM using 10 μL human sera from 97 Korean participants (47 with glucose intolerance and 50 matched controls, average age of 46.6 ± 9.9 years, 53 male and 45 female). sTCDDeq were higher in participants with glucose intolerance than normal controls and were positively associated (P fasting glucose, but not with HDL-cholesterol. Body mass index was in a positive linear relationship with serum AhR ligands in healthy participants. When myoblast cells were incubated with human sera, ATP generating power of mitochondria became impaired in an AhR ligand concentration-dependent manner. Our results support that circulating AhR ligands may directly reduce mitochondrial function in tissues, leading to weight gain, glucose intolerance, and metabolic syndrome. Our rapid cell-based assay using minute volume of human serum may provide one of the best monitoring systems for circulating AhR ligands, good clinical biomarkers for the progress of disease and therapeutic efficacy. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.

Polyunsaturated fatty acids effect on serum triglycerides concentration in presence of metabolic syndrome components. The Alaska-Siberia Project

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Lopez-Alvarenga, Juan C.; Ebbesson, Sven O E; Ebbesson, Lars O E; Tejero, M Elizabeth; Voruganti, V. Saroja; Comuzzie, Anthony G

2009-01-01

Serum fatty acids (FA) have wide effects on metabolism: Serum saturated fatty acids (SFA) increase triglyceride (TG) levels in plasma while polyunsaturated fatty acids (PUFA) reduce them. Traditionally, Eskimos have a high consumption of omega -3 fatty acids (ω–3 FA), but the westernization of their food habits have increased their dietary SFAs, partly reflected in their serum concentrations. We studied the joint effect of serum SFAs and PUFAs on circulating levels of TG in the presence of metabolic syndrome components. We included 212 men and 240 women (age 47.9±15.7 y, BMI 26.9±5.3) from four villages located in Alaska for a cross sectional study. Generalized linear models were employed to build surface responses of TG as in functions of SFAs and PUFAs measured in blood samples adjusting by sex, BMI and village. The effects of individual FAs were assessed by multiple linear regression analysis and partial correlations (r) were calculated. The most important predictors for TG levels were glucose tolerance (r = 0.116, p = 0.018) and BMI (r = 0.42, pstructure. The long chain ω-3, even in presence of high levels of SF, was associated with lower triglyceride levels. Eicosapentanoic acid (20:5ω3) had the strongest effect against palmitic acid on TG. The total FA showed moderate association with levels of TG, while SFA was positively associated, and large chain PUFA negatively. The westernized dietary habits among Eskimos are likely to change their metabolic profile and increase comorbidities related to metabolic disease. PMID:19766268

Alert for bone alterations and low serum concentrations of vitamin D in patients with intestinal inflammatory disease

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Lorete Maria da Silva Kotze

Full Text Available Summary Background: Inflammatory bowel diseases (IBD, including Crohn's disease (CD and ulcerative colitis (UC, are characterized by chronic inflammation of the intestine that can reduce the absorption of nutrients such as vitamin D and calcium. Objective: To investigate bone alterations and serum levels of vitamin D in patients with IBD. Method: This was a cross-sectional study based on a review of medical records of patients from a private office in Curitiba, PR, Brazil. Serum levels of vitamin D and bone densitometry were measured at diagnosis of IBD. A total of 105 patients were included; 38 (58.4% with CD; 27 (41.6% with UC and 40 with irritable bowel syndrome (IBS as comparison group. Results: When compared to patients with UC, CD patients showed a higher prevalence of bone alterations, being 15.8% with osteoporosis and 36.8% with osteopenia. In UC, bone alterations occurred in 29.6% of cases, 3.7% with osteoporosis and 25.9% with osteopenia. As for vitamin D levels, among CD patients, 10.5% had vitamin deficiency, 65.8% insufficiency and 23.7% were sufficient. In UC, 7.4% of cases had deficiency, 74.1% insufficiency and 18.5% had sufficient serum levels of vitamin D. In the group with IBS, deficiency was observed in 17.5% of cases, insufficiency in 55% and sufficiency in 27.5% of them. There was no significant difference between groups. Conclusion: IBD patients have a high prevalence of bone changes, especially those with CD. Serum levels of vitamin D are below the recommended in all the evaluated groups.

Tissue and serum samples of patients with papillary thyroid cancer with and without benign background demonstrate different altered expression of proteins

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Mardiaty Iryani Abdullah

2016-09-01

Full Text Available Background Papillary thyroid cancer (PTC is mainly diagnosed using fine-needle aspiration biopsy. This most common form of well-differentiated thyroid cancer occurs with or without a background of benign thyroid goiter (BTG. Methods In the present study, a gel-based proteomics analysis was performed to analyse the expression of proteins in tissue and serum samples of PTC patients with (PTCb; n = 6 and without a history of BTG (PTCa; n = 8 relative to patients with BTG (n = 20. This was followed by confirmation of the levels of proteins which showed significant altered abundances of more than two-fold difference (p < 0.01 in the tissue and serum samples of the same subjects using ELISA. Results The data of our study showed that PTCa and PTCb distinguish themselves from BTG in the types of tissue and serum proteins of altered abundance. While higher levels of alpha-1 antitrypsin (A1AT and heat shock 70 kDa protein were associated with PTCa, lower levels of A1AT, protein disulfide isomerase and ubiquitin-conjugating enzyme E2 N seemed apparent in the PTCb. In case of the serum proteins, higher abundances of A1AT and alpha 1-beta glycoprotein were detected in PTCa, while PTCb was associated with enhanced apolipoprotein A-IV and alpha 2-HS glycoprotein (AHSG. The different altered expression of tissue and serum A1AT as well as serum AHSG between PTCa and PTCb patients were also validated by ELISA. Discussion The distinctive altered abundances of the tissue and serum proteins form preliminary indications that PTCa and PTCb are two distinct cancers of the thyroid that are etiologically and mechanistically different although it is currently not possible to rule out that they may also be due other reasons such as the different stages of the malignant disease. These proteins stand to have a potential use as tissue or serum biomarkers to discriminate the three different thyroid neoplasms although this requires further validation in clinically

Myostatin induces mitochondrial metabolic alteration and typical apoptosis in cancer cells

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Liu, Y; Cheng, H; Zhou, Y; Zhu, Y; Bian, R; Chen, Y; Li, C; Ma, Q; Zheng, Q; Zhang, Y; Jin, H; Wang, X; Chen, Q; Zhu, D

2013-01-01

Myostatin, a member of the transforming growth factor-β superfamily, regulates the glucose metabolism of muscle cells, while dysregulated myostatin activity is associated with a number of metabolic disorders, including muscle cachexia, obesity and type II diabetes. We observed that myostatin induced significant mitochondrial metabolic alterations and prolonged exposure of myostatin induced mitochondria-dependent apoptosis in cancer cells addicted to glycolysis. To address the underlying mechanism, we found that the protein levels of Hexokinase II (HKII) and voltage-dependent anion channel 1 (VDAC1), two key regulators of glucose metabolisms as well as metabolic stress-induced apoptosis, were negatively correlated. In particular, VDAC1 was dramatically upregulated in cells that are sensitive to myostatin treatment whereas HKII was downregulated and dissociated from mitochondria. Myostatin promoted the translocation of Bax from cytosol to mitochondria, and knockdown of VDAC1 inhibited myostatin-induced Bax translocation and apoptosis. These apoptotic changes can be partially rescued by repletion of ATP, or by ectopic expression of HKII, suggesting that perturbation of mitochondrial metabolism is causally linked with subsequent apoptosis. Our findings reveal novel function of myostatin in regulating mitochondrial metabolism and apoptosis in cancer cells. PMID:23412387

Multiplatform serum metabolic phenotyping combined with pathway mapping to identify biochemical differences in smokers.

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Kaluarachchi, Manuja R; Boulangé, Claire L; Garcia-Perez, Isabel; Lindon, John C; Minet, Emmanuel F

2016-10-01

Determining perturbed biochemical functions associated with tobacco smoking should be helpful for establishing causal relationships between exposure and adverse events. A multiplatform comparison of serum of smokers (n = 55) and never-smokers (n = 57) using nuclear magnetic resonance spectroscopy, UPLC-MS and statistical modeling revealed clustering of the classes, distinguished by metabolic biomarkers. The identified metabolites were subjected to metabolic pathway enrichment, modeling adverse biological events using available databases. Perturbation of metabolites involved in chronic obstructive pulmonary disease, cardiovascular diseases and cancer were identified and discussed. Combining multiplatform metabolic phenotyping with knowledge-based mapping gives mechanistic insights into disease development, which can be applied to next-generation tobacco and nicotine products for comparative risk assessment.

Visible light alters yeast metabolic rhythms by inhibiting respiration

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Robertson, James Brian; Davis, Chris R.; Johnson, Carl Hirschie

2013-01-01

In some organisms, respiration fluctuates cyclically, and these rhythms can be a sensitive gauge of metabolism. Constant or pulsatile exposure of yeast to visible wavelengths of light significantly alters and/or initiates these respiratory oscillations, revealing a further dimension of the challenges to yeast living in natural environments. Our results also have implications for the use of light as research tools—e.g., for excitation of fluorescence microscopically—even in organisms such as y...

Serum 25(OHD is inversely associated with metabolic syndrome risk profile among urban middle-aged Chinese population

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Yin Xiao

2012-09-01

Full Text Available Abstract Background Vitamin D deficiency is associated with a variety of chronic metabolic diseases. Limited evidence regarding vitamin D deficiency exists within the Chinese population. The present study aims to examine the association between serum vitamin D concentrations and cardiometabolic risk factors in the young and middle-aged, urban Chinese population Methods The cross-sectional relationships between serum 25-hydroxyvitamin D [25(OHD] concentrations and indices of adiposity and cardiometabolic risk factors (e.g., body mass index, waist circumference, fasting plasma glucose, etc. were evaluated in 601 non-diabetic adults. Result Vitamin D deficiency or insufficiency was present in 66% of the tested population, and serum 25(OHD levels were lower in patients who were overweight/obese or suffered metabolic syndrome when compared to individuals of healthy weight without metabolic syndrome (24.08 ± 8.08 vs 31.70 ± 11.77 ng/ml, 21.52 ± 6.9 vs 31.74 ± 10.21 ng/ml respectively. 25(OHD was inversely associated with waist circumference, fasting glucose, fasting insulin, triglycerides and LDL-cholesterol, and it was positively associated with HDL-cholesterol in a multivariable-adjusted regression model. Conclusion Vitamin D deficiency is common in the young and middle-aged, urban Chinese population, with high prevalence in overweight/obese individuals and patients with metabolic syndrome. Low vitamin D concentration was associated with indices of adiposity and cardiometabolic risk factors. Further studies are warranted to elucidate the cause-effect relation between vitamin D status, obesity and related metabolic disorders. Trial registration Current Controlled Trials (ISRCTN21527585

SERUM ELECTROLYTES AND OUTCOME IN PATIENTS UNDERGOING ENDOSCOPIC GASTROSTOMY

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Joana VIEIRA

Full Text Available ABSTRACT BACKGROUND: Percutaneous endoscopic gastrostomy (PEG is a gold standard for long term enteral feeding. Neurologic dysphagia and head/neck cancer are the most common indications for PEG as they can lead to protein-energy malnutrition and serum electrolyte abnormalities, with potential negative impact on metabolic balance. Refeeding syndrome may also be related with severe electrolyte changes in PEG-fed patients and contribute to poor prognosis. OBJECTIVE: This study aims to evaluate the changes in serum concentrations of the main electrolytes and its possible association with the outcome. METHODS: Retrospective study of patients followed in our Artificial Nutrition Clinic, submitted to PEG from 2010 to 2016, having head/neck cancer or neurologic dysphagia, who died under PEG feeding. Serum electrolytes (sodium, potassium, chlorine, magnesium, calcium and phosphorus were evaluated immediately before the gastrostomy procedure. Survival after PEG until death was recorded in months. RESULTS: We evaluated 101 patients, 59 with electrolyte alterations at the moment of the gastrostomy. Sodium was altered in 32 (31.7%, magnesium in 21 (20.8%, chlorine in 21 (20.8%, potassium in 14 (13.8%, calcium in 11 (10.9 % and phosphorus in 11 (10.9%. The survival of patients with low sodium (<135 mmol/L was significantly lower when compared to patients with normal/high values, 2.76 months vs 7.80 months, respectively (P=0.007. CONCLUSION: Changes in serum electrolytes of patients undergoing PEG were very common. More than half showed at least one abnormality, at the time of the procedure. The most frequent was hyponatremia, which was associated with significantly shorter survival, probably reflecting severe systemic metabolic distress.

1H NMR-based serum metabolomics reveals erythromycin-induced liver toxicity in albino Wistar rats

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Atul Rawat

2016-01-01

Full Text Available Introduction: Erythromycin (ERY is known to induce hepatic toxicity which mimics other liver diseases. Thus, ERY is often used to produce experimental models of drug-induced liver-toxicity. The serum metabolic profiles can be used to evaluate the liver-toxicity and to further improve the understanding of underlying mechanism. Objective: To establish the serum metabolic patterns of Erythromycin induced hepatotoxicity in albino wistar rats using 1H NMR based serum metabolomics. Experimental: Fourteen male rats were randomly divided into two groups (n = 7 in each group: control and ERY treated. After 28 days of intervention, the metabolic profiles of sera obtained from ERY and control groups were analyzed using high-resolution 1D 1H CPMG and diffusion-edited nuclear magnetic resonance (NMR spectra. The histopathological and SEM examinations were employed to evaluate the liver toxicity in ERY treated group. Results: The serum metabolic profiles of control and ERY treated rats were compared using multivariate statistical analysis and the metabolic patterns specific to ERY-induced liver toxicity were established. The toxic response of ERY was characterized with: (a increased serum levels of Glucose, glutamine, dimethylamine, malonate, choline, phosphocholine and phospholipids and (b decreased levels of isoleucine, leucine, valine, alanine, glutamate, citrate, glycerol, lactate, threonine, circulating lipoproteins, N-acetyl glycoproteins, and poly-unsaturated lipids. These metabolic alterations were found to be associated with (a decreased TCA cycle activity and enhanced fatty acid oxidation, (b dysfunction of lipid and amino acid metabolism and (c oxidative stress. Conclusion and Recommendations: Erythromycin is often used to produce experimental models of liver toxicity; therefore, the established NMR-based metabolic patterns will form the basis for future studies aiming to evaluate the efficacy of anti-hepatotoxic agents or the hepatotoxicity of new

Biomarker Identification and Pathway Analysis by Serum Metabolomics of Lung Cancer

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Yingrong Chen

2015-01-01

Full Text Available Lung cancer is one of the most common causes of cancer death, for which no validated tumor biomarker is sufficiently accurate to be useful for diagnosis. Additionally, the metabolic alterations associated with the disease are unclear. In this study, we investigated the construction, interaction, and pathways of potential lung cancer biomarkers using metabolomics pathway analysis based on the Kyoto Encyclopedia of Genes and Genomes database and the Human Metabolome Database to identify the top altered pathways for analysis and visualization. We constructed a diagnostic model using potential serum biomarkers from patients with lung cancer. We assessed their specificity and sensitivity according to the area under the curve of the receiver operator characteristic (ROC curves, which could be used to distinguish patients with lung cancer from normal subjects. The pathway analysis indicated that sphingolipid metabolism was the top altered pathway in lung cancer. ROC curve analysis indicated that glycerophospho-N-arachidonoyl ethanolamine (GpAEA and sphingosine were potential sensitive and specific biomarkers for lung cancer diagnosis and prognosis. Compared with the traditional lung cancer diagnostic biomarkers carcinoembryonic antigen and cytokeratin 19 fragment, GpAEA and sphingosine were as good or more appropriate for detecting lung cancer. We report our identification of potential metabolic diagnostic and prognostic biomarkers of lung cancer and clarify the metabolic alterations in lung cancer.

Correlation of Diffusion and Metabolic Alterations in Different Clinical Forms of Multiple Sclerosis

Science.gov (United States)

Hannoun, Salem; Bagory, Matthieu; Durand-Dubief, Francoise; Ibarrola, Danielle; Comte, Jean-Christophe; Confavreux, Christian; Cotton, Francois; Sappey-Marinier, Dominique

2012-01-01

Diffusion tensor imaging (DTI) and MR spectroscopic imaging (MRSI) provide greater sensitivity than conventional MRI to detect diffuse alterations in normal appearing white matter (NAWM) of Multiple Sclerosis (MS) patients with different clinical forms. Therefore, the goal of this study is to combine DTI and MRSI measurements to analyze the relation between diffusion and metabolic markers, T2-weighted lesion load (T2-LL) and the patients clinical status. The sensitivity and specificity of both methods were then compared in terms of MS clinical forms differentiation. MR examination was performed on 71 MS patients (27 relapsing remitting (RR), 26 secondary progressive (SP) and 18 primary progressive (PP)) and 24 control subjects. DTI and MRSI measurements were obtained from two identical regions of interest selected in left and right centrum semioval (CSO) WM. DTI metrics and metabolic contents were significantly altered in MS patients with the exception of N-acetyl-aspartate (NAA) and NAA/Choline (Cho) ratio in RR patients. Significant correlations were observed between diffusion and metabolic measures to various degrees in every MS patients group. Most DTI metrics were significantly correlated with the T2-LL while only NAA/Cr ratio was correlated in RR patients. A comparison analysis of MR methods efficiency demonstrated a better sensitivity/specificity of DTI over MRSI. Nevertheless, NAA/Cr ratio could distinguish all MS and SP patients groups from controls, while NAA/Cho ratio differentiated PP patients from controls. This study demonstrated that diffusivity changes related to microstructural alterations were correlated with metabolic changes and provided a better sensitivity to detect early changes, particularly in RR patients who are more subject to inflammatory processes. In contrast, the better specificity of metabolic ratios to detect axonal damage and demyelination may provide a better index for identification of PP patients. PMID:22479330

Anti-inflammatory salicylate treatment alters the metabolic adaptations to lactation in dairy cattle

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Farney, Jaymelynn K.; Mamedova, Laman K.; Coetzee, Johann F.; KuKanich, Butch; Sordillo, Lorraine M.; Stoakes, Sara K.; Minton, J. Ernest; Hollis, Larry C.

2013-01-01

Adapting to the lactating state requires metabolic adjustments in multiple tissues, especially in the dairy cow, which must meet glucose demands that can exceed 5 kg/day in the face of negligible gastrointestinal glucose absorption. These challenges are met through the process of homeorhesis, the alteration of metabolic setpoints to adapt to a shift in physiological state. To investigate the role of inflammation-associated pathways in these homeorhetic adaptations, we treated cows with the nonsteroidal anti-inflammatory drug sodium salicylate (SS) for the first 7 days of lactation. Administration of SS decreased liver TNF-α mRNA and marginally decreased plasma TNF-α concentration, but plasma eicosanoids and liver NF-κB activity were unaltered during treatment. Despite the mild impact on these inflammatory markers, SS clearly altered metabolic function. Plasma glucose concentration was decreased by SS, but this was not explained by a shift in hepatic gluconeogenic gene expression or by altered milk lactose secretion. Insulin concentrations decreased in SS-treated cows on day 7 compared with controls, which was consistent with the decline in plasma glucose concentration. The revised quantitative insulin sensitivity check index (RQUICKI) was then used to assess whether altered insulin sensitivity may have influenced glucose utilization rate with SS. The RQUICKI estimate of insulin sensitivity was significantly elevated by SS on day 7, coincident with the decline in plasma glucose concentration. Salicylate prevented postpartum insulin resistance, likely causing excessive glucose utilization in peripheral tissues and hypoglycemia. These results represent the first evidence that inflammation-associated pathways are involved in homeorhetic adaptations to lactation. PMID:23678026

Body mass index for predicting hyperglycemia and serum lipid changes in Brazilian adolescents.

Science.gov (United States)

Vieira, Ana Carolina R; Alvarez, Marlene M; Kanaan, Salim; Sichieri, Rosely; Veiga, Gloria V

2009-02-01

To determine the best cut-offs of body mass index for identifying alterations of blood lipids and glucose in adolescents. A probabilistic sample including 577 adolescent students aged 12-19 years in 2003 (210 males and 367 females) from state public schools in the city of Niterói, Southeastern Brazil, was studied. The Receiver Operating Characteristic curve was used to identify the best age-adjusted BMI cut-off for predicting high levels of serum total cholesterol (> or =150 mg/dL), LDL-C (> or =100 mg/dL), serum triglycerides (> or =100 mg/dL), plasma glucose (> 100 mg/dL) and low levels of HDL-C (international and two American. The most prevalent metabolic alterations (>50%) were: high total cholesterol and low HDL-C. BMI predicted high levels of triglycerides in males, high LDL-C in females, and high total cholesterol and the occurrence of three or more metabolic alterations in both males and females (areas under the curve range: 0.59 to 0.67), with low sensitivity (57%-66%) and low specificity (58%-66%). The best BMI cut-offs for this sample (20.3 kg/m(2) to 21.0 kg/m(2)) were lower than those proposed in the references studied. Although BMI values lower than the International cut-offs were better predictor of some metabolic abnormalities in Brazilian adolescents, overall BMI is not a good predictor of these abnormalities in this population.

Metabolic tumour burden assessed by 18F-FDG PET/CT associated with serum CA19-9 predicts pancreatic cancer outcome after resection

International Nuclear Information System (INIS)

Xu, Hua-Xiang; Chen, Tao; Wang, Wen-Quan; Wu, Chun-Tao; Liu, Chen; Long, Jiang; Xu, Jin; Liu, Liang; Yu, Xian-Jun; Zhang, Ying-Jian; Chen, Run-Hao

2014-01-01

Tumour burden is one of the most important prognosticators for pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to investigate the predictive significance of metabolic tumour burden measured by 18 F-FDG PET/CT in patients with resectable PDAC. Included in the study were 122 PDAC patients who received preoperative 18 F-FDG PET/CT examination and radical pancreatectomy. Metabolic tumour burden in terms of metabolic tumour volume (MTV) and total lesion glycolysis (TLG), pathological tumour burden (tumour size), serum tumour burden (baseline serum CA19-9 level), and metabolic activity (maximum standard uptake value, SUVmax) were determined, and compared for their performance in predicting overall survival (OS) and recurrence-free survival (RFS). MTV and TLG were significantly associated with baseline serum CA19-9 level (P = 0.001 for MTV, P < 0.001 for TLG) and tumour size (P < 0.001 for MTV, P = 0.001 for TLG). Multivariate analysis showed that MTV, TLG and baseline serum CA19-9 level as either categorical or continuous variables, but not tumour size or SUVmax, were independent risk predictors for both OS and RFS. Time-dependent receiving operating characteristics analysis further indicated that better predictive performances for OS and RFS were achieved by MTV and TLG compared to baseline serum CA19-9 level, SUVmax and tumour size (P < 0.001 for all). MTV and TLG showed strong consistency with baseline serum CA19-9 level in better predicting OS and RFS, and might serve as surrogate markers for prediction of outcome in patients with resectable PDAC. (orig.)

Serum metabolomic profiling in acute alcoholic hepatitis identifies multiple dysregulated pathways.

Science.gov (United States)

Rachakonda, Vikrant; Gabbert, Charles; Raina, Amit; Bell, Lauren N; Cooper, Sara; Malik, Shahid; Behari, Jaideep

2014-01-01

While animal studies have implicated derangements of global energy homeostasis in the pathogenesis of acute alcoholic hepatitis (AAH), the relevance of these findings to the development of human AAH remains unclear. Using global, unbiased serum metabolomics analysis, we sought to characterize alterations in metabolic pathways associated with severe AAH and identify potential biomarkers for disease prognosis. This prospective, case-control study design included 25 patients with severe AAH and 25 ambulatory patients with alcoholic cirrhosis. Serum samples were collected within 24 hours of the index clinical encounter. Global, unbiased metabolomics profiling was performed. Patients were followed for 180 days after enrollment to determine survival. Levels of 234 biochemicals were altered in subjects with severe AAH. Random-forest analysis, principal component analysis, and integrated hierarchical clustering methods demonstrated that metabolomics profiles separated the two cohorts with 100% accuracy. Severe AAH was associated with enhanced triglyceride lipolysis, impaired mitochondrial fatty acid beta oxidation, and upregulated omega oxidation. Low levels of multiple lysolipids and related metabolites suggested decreased plasma membrane remodeling in severe AAH. While most measured bile acids were increased in severe AAH, low deoxycholate and glycodeoxycholate levels indicated intestinal dysbiosis. Several changes in substrate utilization for energy homeostasis were identified in severe AAH, including increased glucose consumption by the pentose phosphate pathway, altered tricarboxylic acid (TCA) cycle activity, and enhanced peptide catabolism. Finally, altered levels of small molecules related to glutathione metabolism and antioxidant vitamin depletion were observed in patients with severe AAH. Univariable logistic regression revealed 15 metabolites associated with 180-day survival in severe AAH. Severe AAH is characterized by a distinct metabolic phenotype spanning

Intraerythrocyte and serum electrolytes in diabetic patients hypertension

International Nuclear Information System (INIS)

Yasmin, F.; Haleem, D.J.; Haleem, M. A.

2006-01-01

To determine the serum and intraerythrocyte concentrations of vasoactive ions in patients of diabetes mellitus of either gender with hypertension. The study was conducted on 48 volunteers. Out of 48, 24(12 men and 12 women) were hypertensive patients with diabetes mellitus. Remaining (12 men and 12 women) were normal healthy subjects. Biochemical estimations were done by flame photometry and spectrophotometry. Data were analyzed by Two-way ANOVA followed by Newman-Keuls test. A decrease in serum concentrations of sodium, calcium, magnesium, phosphorus, chloride and intraerythrocyte potassium and an increase in the levels of glucose, haematocrit and intraerythrocyte sodium was observed in both male and female patients with diabetes mellitus and hypertension. No significant changes were observed in serum potassium levels. The results suggest that dysregulations of electrolyte balance caused by hyperinsulinemia or altered glucose metabolism may lead to hypertension. (author)

Farnesoid X Receptor Agonist Treatment Alters Bile Acid Metabolism but Exacerbates Liver Damage in a Piglet Model of Short-Bowel Syndrome.

Science.gov (United States)

Pereira-Fantini, Prue M; Lapthorne, Susan; Gahan, Cormac G M; Joyce, Susan A; Charles, Jenny; Fuller, Peter J; Bines, Julie E

2017-07-01

Options for the prevention of short-bowel syndrome-associated liver disease (SBS-ALDs) are limited and often ineffective. The farnesoid X receptor (FXR) is a newly emerging pharmaceutical target and FXR agonists have been shown to ameliorate cholestasis and metabolic disorders. The aim of this study was to assess the efficacy of obeticholic acid (OCA) treatment in preventing SBS-ALDs. Piglets underwent 75% small-bowel resection (SBS) or sham surgery (sham) and were assigned to either a daily dose of OCA (2.4 mg/kg/day) or were untreated. Clinical measures included weight gain and stool studies. Histologic features were assessed. Ultraperformance liquid chromatography tandem mass spectrometry was used to determine bile acid composition in end point bile and portal serum samples. Gene expression of key FXR targets was assessed in intestinal and hepatic tissues via quantitative polymerase chain reaction. OCA-treated SBS piglets showed decreased stool fat and altered liver histology when compared with nontreated SBS piglets. OCA prevented SBS-associated taurine depletion, however, further analysis of bile and portal serum samples indicated that OCA did not prevent SBS-associated alterations in bile acid composition. The expression of FXR target genes involved in bile acid transport and synthesis increased within the liver of SBS piglets after OCA administration whereas, paradoxically, intestinal expression of FXR target genes were decreased by OCA administration. Administration of OCA in SBS reduced fat malabsorption and altered bile acid composition, but did not prevent the development of SBS-ALDs. We postulate that extensive small resection impacts the ability of the remnant intestine to respond to FXR activation.

Rescue of Metabolic Alterations in AR113Q Skeletal Muscle by Peripheral Androgen Receptor Gene Silencing

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Elisa Giorgetti

2016-09-01

Full Text Available Spinal and bulbar muscular atrophy (SBMA, a progressive degenerative disorder, is caused by a CAG/glutamine expansion in the androgen receptor (polyQ AR. Recent studies demonstrate that skeletal muscle is an important site of toxicity that contributes to the SBMA phenotype. Here, we sought to identify critical pathways altered in muscle that underlie disease manifestations in AR113Q mice. This led to the unanticipated identification of gene expression changes affecting regulators of carbohydrate metabolism, similar to those triggered by denervation. AR113Q muscle exhibits diminished glycolysis, altered mitochondria, and an impaired response to exercise. Strikingly, the expression of genes regulating muscle energy metabolism is rescued following peripheral polyQ AR gene silencing by antisense oligonucleotides (ASO, a therapeutic strategy that alleviates disease. Our data establish the occurrence of a metabolic imbalance in SBMA muscle triggered by peripheral expression of the polyQ AR and indicate that alterations in energy utilization contribute to non-neuronal disease manifestations.

Bioinformatical Analysis of Organ-Related (Heart, Brain, Liver, and Kidney and Serum Proteomic Data to Identify Protein Regulation Patterns and Potential Sepsis Biomarkers

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Andreas Hohn

2018-01-01

Full Text Available During the last years, proteomic studies have revealed several interesting findings in experimental sepsis models and septic patients. However, most studies investigated protein alterations only in single organs or in whole blood. To identify possible sepsis biomarkers and to evaluate the relationship between protein alteration in sepsis affected organs and blood, proteomics data from the heart, brain, liver, kidney, and serum were analysed. Using functional network analyses in combination with hierarchical cluster analysis, we found that protein regulation patterns in organ tissues as well as in serum are highly dynamic. In the tissue proteome, the main functions and pathways affected were the oxidoreductive activity, cell energy generation, or metabolism, whereas in the serum proteome, functions were associated with lipoproteins metabolism and, to a minor extent, with coagulation, inflammatory response, and organ regeneration. Proteins from network analyses of organ tissue did not correlate with statistically significantly regulated serum proteins or with predicted proteins of serum functions. In this study, the combination of proteomic network analyses with cluster analyses is introduced as an approach to deal with high-throughput proteomics data to evaluate the dynamics of protein regulation during sepsis.

Heritable IUGR and adult metabolic syndrome are reversible and associated with alterations in the metabolome following dietary supplementation of 1-carbon intermediates.

Science.gov (United States)

Seferovic, Maxim D; Goodspeed, Danielle M; Chu, Derrick M; Krannich, Laura A; Gonzalez-Rodriguez, Pablo J; Cox, James E; Aagaard, Kjersti M

2015-06-01

Metabolic syndrome (MetS), following intrauterine growth restriction (IUGR), is epigenetically heritable. Recently, we abrogated the F2 adult phenotype with essential nutrient supplementation (ENS) of intermediates along the 1-carbon pathway. With the use of the same grandparental uterine artery ligation model, we profiled the F2 serum metabolome at weaning [postnatal day (d)21; n = 76] and adulthood (d160; n = 12) to test if MetS is preceded by alterations in the metabolome. Indicative of developmentally programmed MetS, adult F2, formerly IUGR rats, were obese (621 vs. 461 g; P metabolome at weaning (randomForest analysis; class error metabolome accompany heritable IUGR, precede adult-onset MetS, and are partially amenable to dietary intervention. © FASEB.

Anti-inflammatory salicylate treatment alters the metabolic adaptations to lactation in dairy cattle

OpenAIRE

Farney, Jaymelynn K.; Mamedova, Laman K.; Coetzee, Johann F.; KuKanich, Butch; Sordillo, Lorraine M.; Stoakes, Sara K.; Minton, J. Ernest; Hollis, Larry C.; Bradford, Barry J.

2013-01-01

Adapting to the lactating state requires metabolic adjustments in multiple tissues, especially in the dairy cow, which must meet glucose demands that can exceed 5 kg/day in the face of negligible gastrointestinal glucose absorption. These challenges are met through the process of homeorhesis, the alteration of metabolic setpoints to adapt to a shift in physiological state. To investigate the role of inflammation-associated pathways in these homeorhetic adaptations, we treated cows with the no...

DI/LC-MS/MS-Based Metabolic Profiling for Identification of Early Predictive Serum Biomarkers of Metritis in Transition Dairy Cows.

Science.gov (United States)

Zhang, Guanshi; Deng, Qilan; Mandal, Rupasri; Wishart, David S; Ametaj, Burim N

2017-09-27

The objectives of this study were to evaluate alterations of metabolites in the blood of dairy cows before, during, and after diagnosis of metritis and identify predictive serum metabolite biomarkers for metritis. DI/LC-MS/MS was used to analyze serum samples collected from both healthy and metritic cows during -8, -4, disease diagnosis, +4, and +8 wks relative to parturition. Results indicated that cows with metritis experienced altered concentrations of serum amino acids, glycerophospholipids, sphingolipids, acylcarnitines, and biogenic amines during the entire experimental period. Moreover, two sets of predictive biomarker models and one set of diagnostic biomarker models for metritis were developed, and all of them showed high sensitivity and specificity (e.g., high AUC values by the ROC curve evaluation), which indicate that serum metabolites identified have pretty accurate predictive, diagnostic, and prognostic abilities for metritis in transition dairy cows.

Metabolic tumour burden assessed by {sup 18}F-FDG PET/CT associated with serum CA19-9 predicts pancreatic cancer outcome after resection

Energy Technology Data Exchange (ETDEWEB)

Xu, Hua-Xiang; Chen, Tao; Wang, Wen-Quan; Wu, Chun-Tao; Liu, Chen; Long, Jiang; Xu, Jin; Liu, Liang; Yu, Xian-Jun [Fudan University, Shanghai Cancer Center, Pancreatic Cancer Institute and Department of Pancreatic and Hepatobiliary Surgery, Shanghai (China); Fudan University, Department of Oncology, Shanghai Medical College, Shanghai (China); Zhang, Ying-Jian [Fudan University, Shanghai Cancer Center, Department of Nuclear Medicine, Shanghai (China); Fudan University, Department of Oncology, Shanghai Medical College, Shanghai (China); Chen, Run-Hao [Fudan University, Department of General Surgery, Jinshan Hospital, Shanghai (China)

2014-06-15

Tumour burden is one of the most important prognosticators for pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to investigate the predictive significance of metabolic tumour burden measured by {sup 18}F-FDG PET/CT in patients with resectable PDAC. Included in the study were 122 PDAC patients who received preoperative {sup 18}F-FDG PET/CT examination and radical pancreatectomy. Metabolic tumour burden in terms of metabolic tumour volume (MTV) and total lesion glycolysis (TLG), pathological tumour burden (tumour size), serum tumour burden (baseline serum CA19-9 level), and metabolic activity (maximum standard uptake value, SUVmax) were determined, and compared for their performance in predicting overall survival (OS) and recurrence-free survival (RFS). MTV and TLG were significantly associated with baseline serum CA19-9 level (P = 0.001 for MTV, P < 0.001 for TLG) and tumour size (P < 0.001 for MTV, P = 0.001 for TLG). Multivariate analysis showed that MTV, TLG and baseline serum CA19-9 level as either categorical or continuous variables, but not tumour size or SUVmax, were independent risk predictors for both OS and RFS. Time-dependent receiving operating characteristics analysis further indicated that better predictive performances for OS and RFS were achieved by MTV and TLG compared to baseline serum CA19-9 level, SUVmax and tumour size (P < 0.001 for all). MTV and TLG showed strong consistency with baseline serum CA19-9 level in better predicting OS and RFS, and might serve as surrogate markers for prediction of outcome in patients with resectable PDAC. (orig.)

Trehalose Alters Subcellular Trafficking and the Metabolism of the Alzheimer-associated Amyloid Precursor Protein.

Science.gov (United States)

Tien, Nguyen T; Karaca, Ilker; Tamboli, Irfan Y; Walter, Jochen

2016-05-13

The disaccharide trehalose is commonly considered to stimulate autophagy. Cell treatment with trehalose could decrease cytosolic aggregates of potentially pathogenic proteins, including mutant huntingtin, α-synuclein, and phosphorylated tau that are associated with neurodegenerative diseases. Here, we demonstrate that trehalose also alters the metabolism of the Alzheimer disease-related amyloid precursor protein (APP). Cell treatment with trehalose decreased the degradation of full-length APP and its C-terminal fragments. Trehalose also reduced the secretion of the amyloid-β peptide. Biochemical and cell biological experiments revealed that trehalose alters the subcellular distribution and decreases the degradation of APP C-terminal fragments in endolysosomal compartments. Trehalose also led to strong accumulation of the autophagic marker proteins LC3-II and p62, and decreased the proteolytic activation of the lysosomal hydrolase cathepsin D. The combined data indicate that trehalose decreases the lysosomal metabolism of APP by altering its endocytic vesicular transport. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Heart and bile acids - Clinical consequences of altered bile acid metabolism.

Science.gov (United States)

Vasavan, Tharni; Ferraro, Elisa; Ibrahim, Effendi; Dixon, Peter; Gorelik, Julia; Williamson, Catherine

2018-04-01

Cardiac dysfunction has an increased prevalence in diseases complicated by liver cirrhosis such as primary biliary cholangitis and primary sclerosing cholangitis. This observation has led to research into the association between abnormalities in bile acid metabolism and cardiac pathology. Approximately 50% of liver cirrhosis cases develop cirrhotic cardiomyopathy. Bile acids are directly implicated in this, causing QT interval prolongation, cardiac hypertrophy, cardiomyocyte apoptosis and abnormal haemodynamics of the heart. Elevated maternal serum bile acids in intrahepatic cholestasis of pregnancy, a disorder which causes an impaired feto-maternal bile acid gradient, have been associated with fatal fetal arrhythmias. The hydrophobicity of individual bile acids in the serum bile acid pool is of relevance, with relatively lipophilic bile acids having a more harmful effect on the heart. Ursodeoxycholic acid can reverse or protect against these detrimental cardiac effects of elevated bile acids. Copyright © 2018 Elsevier B.V. All rights reserved.

Mineral metabolism in European children living with a renal transplant

DEFF Research Database (Denmark)

Bonthuis, Marjolein; Busutti, Marco; van Stralen, Karlijn J

2015-01-01

BACKGROUND AND OBJECTIVES: Data on mineral metabolism in pediatric renal transplant recipients largely arise from small single-center studies. In adult patients, abnormal mineral levels are related to a higher risk of graft failure. This study used data from the European Society for Paediatric...... on prevention and treatment of renal osteodystrophy in children on chronic renal failure. RESULTS: Abnormal serum phosphorus levels were observed in 25% (14% hypophosphatemia and 11% hyperphosphatemia), altered serum calcium in 30% (19% hypocalcemia, 11% hypercalcemia), and hyperparathyroidism in 41...

Relationship Between Serum Zinc Level and Metabolic Syndrome: A Meta-Analysis of Observational Studies.

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Zhang, Yi; Zhang, Dian-Zhong

2018-05-10

This research sought to summarize the evidence regarding the relationship between serum zinc level and metabolic syndrome (MetS). The electronic databases of PubMed, Web of Science, and Embase were searched up to October 2017 for observational studies on the association between serum zinc level and MetS. The standard mean difference (SMD) and its corresponding 95% confidence interval (CI) of the serum zinc level for MetS versus control participants were calculated. In addition, the pooled odds ratio (OR) and relative risk (RR) of MetS for the highest versus lowest category of serum zinc level, as well as their corresponding 95% CI, were also calculated. A total of 11 observational studies (8 cross-sectional, 1 case-control, and 2 cohort studies) were included in this meta-analysis. The combined SMD demonstrated that the serum zinc level in MetS was higher than that in control participants (SMD = 0.11; 95% CI, 0.03-0.19; p = 0.009). Moreover, the overall multivariable-adjusted RR showed that the increased serum zinc level was associated with a higher risk of MetS (RR = 1.82; 95% CI, 1.33-2.50; p level and MetS (OR = 1.00; 95% CI, 0.99-1.01; p = 0.841). Although the serum zinc level in participants with MetS was significantly higher than that in control ones, the existing evidence was still insufficient to conclude a definite relationship between serum zinc level and MetS. More well-designed prospective cohort studies are needed to elaborate the concerned issues further.

Saharan dust inputs and high UVR levels jointly alter the metabolic balance of marine oligotrophic ecosystems

Science.gov (United States)

Cabrerizo, Marco J.; Medina-Sánchez, Juan Manuel; González-Olalla, Juan Manuel; Villar-Argaiz, Manuel; Carrillo, Presentación

2016-10-01

The metabolic balance of the most extensive bioma on the Earth is a controversial topic of the global-change research. High ultraviolet radiation (UVR) levels by the shoaling of upper mixed layers and increasing atmospheric dust deposition from arid regions may unpredictably alter the metabolic state of marine oligotrophic ecosystems. We performed an observational study across the south-western (SW) Mediterranean Sea to assess the planktonic metabolic balance and a microcosm experiment in two contrasting areas, heterotrophic nearshore and autotrophic open sea, to test whether a combined UVR × dust impact could alter their metabolic balance at mid-term scales. We show that the metabolic state of oligotrophic areas geographically varies and that the joint impact of UVR and dust inputs prompted a strong change towards autotrophic metabolism. We propose that this metabolic response could be accentuated with the global change as remote-sensing evidence shows increasing intensities, frequencies and number of dust events together with variations in the surface UVR fluxes on SW Mediterranean Sea. Overall, these findings suggest that the enhancement of the net carbon budget under a combined UVR and dust inputs impact could contribute to boost the biological pump, reinforcing the role of the oligotrophic marine ecosystems as CO2 sinks.

Alterations in cerebral metabolism observed in living rodents using fluorescence lifetime microscopy of intrinsic NADH (Conference Presentation)

Science.gov (United States)

Yaseen, Mohammad A.; Sakadžić, Sava; Sutin, Jason; Wu, Weicheng; Fu, Buyin; Boas, David A.

2017-02-01

Monitoring cerebral energy metabolism at a cellular level is essential to improve our understanding of healthy brain function and its pathological alterations. In this study, we resolve specific alterations in cerebral metabolism utilizing minimally-invasive 2-Photon fluorescence lifetime imaging (2P-FLIM) measurements of reduced nicotinamide adenine dinucleotide (NADH) fluorescence, collected in vivo from anesthetized rats and mice. Time-resolved lifetime measurements enables distinction of different components contributing to NADH autofluorescence. These components reportedly represent different enzyme-bound formulations of NADH. Our observations from this study confirm the hypothesis that NADH FLIM can identify specific alterations in cerebral metabolism. Using time-correlated single photon counting (TCSPC) equipment and a custom-built multimodal imaging system, 2-photon fluorescence lifetime imaging (FLIM) was performed in cerebral tissue with high spatial and temporal resolution. Multi-exponential fits for NADH fluorescence lifetimes indicate 4 distinct components, or 'species.' We observed distinct variations in the relative proportions of these components before and after pharmacological-induced impairments to several reactions involved in anaerobic glycolysis and aerobic oxidative metabolism. Classification models developed with experimental data correctly predict the metabolic impairments associated with bicuculline-induced focal seizures in separate experiments. Compared to traditional intensity-based NADH measurements, lifetime imaging of NADH is less susceptible to the adverse effects of overlying blood vessels. Evaluating NADH measurements will ultimately lead to a deeper understanding of cerebral energetics and its pathology-related alterations. Such knowledge will likely aid development of therapeutic strategies for neurodegenerative diseases such as Alzheimer's Disease, Parkinson's disease, and stroke.

Altered Mitochondria, Protein Synthesis Machinery, and Purine Metabolism Are Molecular Contributors to the Pathogenesis of Creutzfeldt-Jakob Disease.

Science.gov (United States)

Ansoleaga, Belén; Garcia-Esparcia, Paula; Llorens, Franc; Hernández-Ortega, Karina; Carmona Tech, Margarita; Antonio Del Rio, José; Zerr, Inga; Ferrer, Isidro

2016-06-12

Neuron loss, synaptic decline, and spongiform change are the hallmarks of sporadic Creutzfeldt-Jakob disease (sCJD), and may be related to deficiencies in mitochondria, energy metabolism, and protein synthesis. To investigate these relationships, we determined the expression levels of genes encoding subunits of the 5 protein complexes of the electron transport chain, proteins involved in energy metabolism, nucleolar and ribosomal proteins, and enzymes of purine metabolism in frontal cortex samples from 15 cases of sCJD MM1 and age-matched controls. We also assessed the protein expression levels of subunits of the respiratory chain, initiation and elongation translation factors of protein synthesis, and localization of selected mitochondrial components. We identified marked, generalized alterations of mRNA and protein expression of most subunits of all 5 mitochondrial respiratory chain complexes in sCJD cases. Expression of molecules involved in protein synthesis and purine metabolism were also altered in sCJD. These findings point to altered mRNA and protein expression of components of mitochondria, protein synthesis machinery, and purine metabolism as components of the pathogenesis of CJD. © 2016 American Association of Neuropathologists, Inc. All rights reserved.

A role for heme in Alzheimer's disease: Heme binds amyloid β and has altered metabolism

OpenAIRE

Atamna, Hani; Frey, William H.

2004-01-01

Heme is a common factor linking several metabolic perturbations in Alzheimer's disease (AD), including iron metabolism, mitochondrial complex IV, heme oxygenase, and bilirubin. Therefore, we determined whether heme metabolism was altered in temporal lobes obtained at autopsy from AD patients and age-matched nondemented subjects. AD brain demonstrated 2.5-fold more heme-b (P < 0.01) and 26% less heme-a (P = 0.16) compared with controls, resulting in a highly significant 2.9-fold decrease in he...

Altered Mycobacterium tuberculosis Cell Wall Metabolism and Physiology Associated With RpoB Mutation H526D

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Victoria L. Campodónico

2018-03-01

Full Text Available Background:Mycobacterium tuberculosis (Mtb rpoB mutations are associated with global metabolic remodeling. However, the net effects of rpoB mutations on Mtb physiology, metabolism and function are not completely understood. Based on previous work, we hypothesized that changes in the expression of cell wall molecules in Mtb mutant RpoB 526D lead to changes in cell wall permeability and to altered resistance to environmental stresses and drugs.Methods: The phenotypes of a fully drug-susceptible clinical strain of Mtb and its paired rifampin-monoresistant, RpoB H526D mutant progeny strain were compared.Results: The rpoB mutant showed altered colony morphology, bacillary length and cell wall thickness, which were associated with increased cell wall permeability and susceptibility to the cell wall detergent sodium dodecyl sulfate (SDS after exposure to nutrient starvation. Relative to the isogenic rifampin-susceptible strain, the RpoB H526D mutant showed altered bacterial cellular metabolic activity and an eightfold increase in susceptibility to the cell-wall acting drug vancomycin.Conclusion: Our data suggest that RpoB mutation H526D is associated with altered cell wall physiology and resistance to cell wall-related stress. These findings are expected to contribute to an improved understanding of the pathogenesis of drug-resistant M. tuberculosis infections.

GC/TOFMS analysis of metabolites in serum and urine reveals metabolic perturbation of TCA cycle in db/db mice involved in diabetic nephropathy.

Science.gov (United States)

Li, Mengjie; Wang, Xufang; Aa, Jiye; Qin, Weisong; Zha, Weibin; Ge, Yongchun; Liu, Linsheng; Zheng, Tian; Cao, Bei; Shi, Jian; Zhao, Chunyan; Wang, Xinwen; Yu, Xiaoyi; Wang, Guangji; Liu, Zhihong

2013-06-01

Early diagnosis of diabetic nephropathy (DN) is difficult although it is of crucial importance to prevent its development. To probe potential markers and the underlying mechanism of DN, an animal model of DN, the db/db mice, was used and serum and urine metabolites were profiled using gas chromatography/time-of-flight mass spectrometry. Metabolic patterns were evaluated based on serum and urine data. Principal component analysis of the data revealed an obvious metabonomic difference between db/db mice and controls, and db/db mice showed distinctly different metabolic patterns during the progression from diabetes to early, medium, and later DN. The identified metabolites discriminating between db/db mice and controls suggested that db/db mice have perturbations in the tricarboxylic acid cycle (TCA, citrate, malate, succinate, and aconitate), lipid metabolism, glycolysis, and amino acid turnover. The db/db mice were characterized by acidic urine, high TCA intermediates in serum at week 6 and a sharp decline thereafter, and gradual elevation of free fatty acids in the serum. The sharp drop of serum TCA intermediates from week 6 to 8 indicated the downregulated glycolysis and insulin resistance. However, urinary TCA intermediates did not decrease in parallel with those in the serum from week 6 to 10, and an increased portion of TCA intermediates in the serum was excreted into the urine at 8, 10, and 12 wk than at 6 wk, indicating kidney dysfunction occurred. The relative abundances of TCA intermediates in urine relative to those in serum were suggested as an index of renal damage.

Pressure sores and blood and serum dysmetabolism in spinal cord injury patients.

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Scivoletto, G; Fuoco, U; Morganti, B; Cosentino, E; Molinari, M

2004-08-01

Spinal cord injury (SCI) patients with pressure sores were studied before and after surgical intervention for ulcer healing and compared with matched SCI patients without sores and with patients with pressure sores and other diseases. To analyse the relationship between pressure sores and anaemia and serum protein alteration in SCI patients. To study the pathogenesis of these alterations and suggest appropriate therapy. Spinal cord unit in Rome, Italy. A total of 13 SCI patients with pressure sores, 13 comparable patients without pressure sores and four patients with other diseases and pressure sores. Haematochemical parameters. Patients with pressure sore showed significant decreased red cells, decreased haemoglobin and haematocrit, increased white cells and ferritin and decreased transferrin and transferrin saturation; total hypoproteinemia and hypoalbuminemia with increased Alfa-1 and gamma globulins increased erythrocyte sedimentation rate and C-reactive protein were also present. The alterations returned to normal after surgical intervention for pressure sore healing. Patients with pressure sores suffer from anaemia and serum protein alteration that fells within the range of metabolic alteration of chronic disorders and neoplastic diseases. The alterations depend on a decreased utilisation of iron stores in the reticuloendothelial system and on inhibition of the hepatic synthesis of albumin. With regard to treatment, iron treatment should be avoided because of the risk of haemochromatosis.

Serum microRNA miR-206 is decreased in hyperthyroidism and mediates thyroid hormone regulation of lipid metabolism in HepG2 human hepatoblastoma cells.

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Zheng, Yingjuan; Zhao, Chao; Zhang, Naijian; Kang, Wenqin; Lu, Rongrong; Wu, Huadong; Geng, Yingxue; Zhao, Yaping; Xu, Xiaoyan

2018-04-01

The actions of thyroid hormone (TH) on lipid metabolism in the liver are associated with a number of genes involved in lipogenesis and lipid metabolism; however, the underlying mechanisms through which TH impacts on lipid metabolism remain to be elucidated. The present study aimed to investigate the effects of hyperthyroidism on the serum levels of the microRNA (miR) miR‑206 and the role of miR‑206 on TH‑regulated lipid metabolism in liver cells. Serum was obtained from 12 patients diagnosed with hyperthyroidism and 10 healthy control subjects. Human hepatoblastoma (HepG2) cells were used to study the effects of triiodothyronine (T3) and miR‑206 on lipid metabolism. Expression of miR‑206 in serum and cells was determined by reverse transcription‑quantitative polymerase chain reaction analysis. Lipid accumulation in HepG2 cells was assessed with Oil Red O staining. Suppression or overexpression of miR‑206 was performed via transfection with a miR‑206 mimic or miR‑206 inhibitor. Serum miR‑206 was significantly decreased in patients with hyperthyroidism compared with euthyroid controls. Treatment of HepG2 cells with T3 led to reduced total cholesterol (TC) and triglyceride (TG) content, accompanied by reduced miR‑206 expression. Inhibition of endogenous miR‑206 expression decreased intracellular TG and TC content in HepG2 cells. By contrast, overexpression of miR‑206 in HepG2 partially prevented the reduction in TG content induced by treatment with T3. In conclusion, serum miR‑206 expression is reduced in patients with hyperthyroidism. In addition, miR‑206 is involved in T3‑mediated regulation of lipid metabolism in HepG2 cells, indicating a role for miR‑206 in thyroid hormone‑induced disorders of lipid metabolism in the liver.

Physiological Aldosterone Concentrations Are Associated with Alterations of Lipid Metabolism: Observations from the General Population.

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Hannich, M; Wallaschofski, H; Nauck, M; Reincke, M; Adolf, C; Völzke, H; Rettig, R; Hannemann, A

2018-01-01

Aldosterone and high-density lipoprotein cholesterol (HDL-C) are involved in many pathophysiological processes that contribute to the development of cardiovascular diseases. Previously, associations between the concentrations of aldosterone and certain components of the lipid metabolism in the peripheral circulation were suggested, but data from the general population is sparse. We therefore aimed to assess the associations between aldosterone and HDL-C, low-density lipoprotein cholesterol (LDL-C), total cholesterol, triglycerides, or non-HDL-C in the general adult population. Data from 793 men and 938 women aged 25-85 years who participated in the first follow-up of the Study of Health in Pomerania were obtained. The associations of aldosterone with serum lipid concentrations were assessed in multivariable linear regression models adjusted for sex, age, body mass index (BMI), estimated glomerular filtration rate (eGFR), and HbA1c. The linear regression models showed statistically significant positive associations of aldosterone with LDL-C ( β -coefficient = 0.022, standard error = 0.010, p = 0.03) and non-HDL-C ( β -coefficient = 0.023, standard error = 0.009, p = 0.01) as well as an inverse association of aldosterone with HDL-C ( β -coefficient = -0.022, standard error = 0.011, p = 0.04). The present data show that plasma aldosterone is positively associated with LDL-C and non-HDL-C and inversely associated with HDL-C in the general population. Our data thus suggests that aldosterone concentrations within the physiological range may be related to alterations of lipid metabolism.

Fasting serum blood measures of bone and lipid metabolism in children with myelomeningocele for early detection of cardiovascular and bone fragility risk factors.

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Van Speybroeck, Alexander; Mueske, Nicole M; Mittelman, Steven D; Kremer, Richard K; Ryan, Deirdre D; Wren, Tishya A L

2017-03-01

This study examined serum levels in children with myelomeningocele to identify the prevalence of pre-clinical signs of disease. A prospective, cross-sectional study. Patients were actively recruited from multidisciplinary care clinics at tertiary children's hospitals from 2010-2012. The control comparison group was recruited by word-of-mouth. Twenty-eight children with myelomeningocele (93% Hispanic; 17 males; 10.0 ± 2.1 years) and 58 controls (84% Hispanic; 30 males; 10.4 ± 2.4 years) provided ≥ 8-hour fasting blood samples with concomitant dual-energy x-ray absorptiometry measurements of body fat. Not applicable. The serum analysis included a lipid panel (cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein), insulin, glucose, leptin, aspartate aminotransferase, alanine transaminase, alkaline phosphatase, albumin, creatinine, calcium, phosphatase, parathyroid hormone, and vitamin D. Children with myelomeningocele had higher body fat (35.2% versus 29.9%, p=0.01) and altered lipid profiles (lower high-density lipoprotein levels, 43.9 mg/dL versus 51.6 mg/dL, P = 0.03) suggesting elevated risk of metabolic syndrome. They also had a higher prevalence of vitamin D deficiency (43% versus 17%, p=0.02) and significantly lower levels of calcium (9.4 mg/dL versus 9.7 mg/dL, P = 0.003) and alkaline phosphatase (187.0 U/L versus 237.0 U/L, P = 0.003). Unexpectedly children with myelomeningocele had lower parathyroid hormone levels (14.5 pg/mL versus 18.4 pg/mL, P = 0.02) than controls despite lower calcium, vitamin D and alkaline phosphatase levels. This suggests an alteration in the sensing mechanism or response of the parathyroid gland to normal physiological stimuli in patients with myelomeningocele. Children with myelomeningocele have abnormal biochemical markers for cardiovascular disease, insulin resistance and bone and mineral metabolism. Early recognition and monitoring of these risk factors in patients with

New insights into uremia-induced alterations in metabolic pathways.

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Rhee, Eugene P; Thadhani, Ravi

2011-11-01

This article summarizes recent studies on uremia-induced alterations in metabolism, with particular emphasis on the application of emerging metabolomics technologies. The plasma metabolome is estimated to include more than 4000 distinct metabolites. Because these metabolites can vary dramatically in size and polarity and are distributed across several orders of magnitude in relative abundance, no single analytical method is capable of comprehensive metabolomic profiling. Instead, a variety of analytical techniques, including targeted and nontargeted liquid chromatography-mass spectrometry, have been employed for metabolomic analysis of human plasma. Recent efforts to apply this technology to study uremia have reinforced the common view that end-stage renal disease is a state of generalized small molecule excess. However, the identification of precursor depletion and downstream metabolite excess - for example, with tryptophan and downstream kynurenine metabolites, with low molecular weight triglycerides and dicarboxylic acids, and with phosphatidylcholines, choline, and trimethylamine-N-oxide - suggest that uremia may directly modulate these metabolic pathways. Metabolomic studies have also begun to expand some of these findings to individuals with chronic kidney disease and in model systems. Uremia is associated with diverse, but incompletely understood metabolic disturbances. Metabolomic approaches permit higher resolution phenotyping of these disturbances, but significant efforts will be required to understand the functional significance of select findings.

Human longevity is characterised by high thyroid stimulating hormone secretion without altered energy metabolism

DEFF Research Database (Denmark)

Jansen, S W; Akintola, A A; Roelfsema, F

2015-01-01

hormone (TH) in an inverse relationship. Greater longevity has been associated with higher TSH and lower TH levels, but mechanisms underlying TSH/TH differences and longevity remain unknown. The HPT axis plays a pivotal role in growth, development and energy metabolism. We report that offspring...... of nonagenarians with at least one nonagenarian sibling have increased TSH secretion but similar bioactivity of TSH and similar TH levels compared to controls. Healthy offspring and spousal controls had similar resting metabolic rate and core body temperature. We propose that pleiotropic effects of the HPT axis...... may favour longevity without altering energy metabolism....

INTERRELATION AMONG SERUM LITHIUM LEVELS AND BONE METABOLISM AND SOME BIOCHEMICAL PARAMETERS IN PRE AND POST-MENAUPOSAL WOMEN

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Ruken Esra Demirdöğen

2016-08-01

Full Text Available The target of this study is to determine the interrelation among serum Li level on bone metabolism (Ca, P, Parathormon, and Vitamin-D, sex and metabolic hormones (estrogen, FSH, LH and TSH, and some biochemical parameters in premenopausal and postmenopausal women. The study is carried out with 10 women: 5 premenopausal and 5 postmenopausal women. The serum Li levels, bone metabolism indicators (i.e., ALP, Ca, P, Mg, Cu, Zn and some biochemical parameters such as serum tryglyceride, alkalene phosphatase, total cholesterol, HDL, LDL and cholesterol levels were determined. The estrogen blood level of women in menopause period was found to be lower than that of women in pre-menopause period (p<0.01 and the FSH level was found to be higher (p<0.01. In the lipid profile the triglyceride level in the post-menopause period was found to be low (p<0.05 and HDL (p<0.001, LDL (p<0.001 and the cholesterol levels were found to be high (p<0.001. The alkalene phosphatase (p<0.001 and Vitamin-D levels (p<0.001 were found to decrease. When the mineral levels were investigated no meaningful difference was observed in the serum magnesium and copper levels while zinc (p<0.01 and phosphorus (p<0.005 levels were observed to increase, the calcium levels (p<0.05 decreased and Li levels considerably decreased (p<0.0001. According to the results obtained it was determined for the first time that Li defficiency can be related with menopause and the related diseases and thus Li therapy can be used in developing new treatment protocols of menopause as an alternative method.

Metabolic state alters economic decision making under risk in humans.

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Mkael Symmonds

2010-06-01

Full Text Available Animals' attitudes to risk are profoundly influenced by metabolic state (hunger and baseline energy stores. Specifically, animals often express a preference for risky (more variable food sources when below a metabolic reference point (hungry, and safe (less variable food sources when sated. Circulating hormones report the status of energy reserves and acute nutrient intake to widespread targets in the central nervous system that regulate feeding behaviour, including brain regions strongly implicated in risk and reward based decision-making in humans. Despite this, physiological influences per se have not been considered previously to influence economic decisions in humans. We hypothesised that baseline metabolic reserves and alterations in metabolic state would systematically modulate decision-making and financial risk-taking in humans.We used a controlled feeding manipulation and assayed decision-making preferences across different metabolic states following a meal. To elicit risk-preference, we presented a sequence of 200 paired lotteries, subjects' task being to select their preferred option from each pair. We also measured prandial suppression of circulating acyl-ghrelin (a centrally-acting orexigenic hormone signalling acute nutrient intake, and circulating leptin levels (providing an assay of energy reserves. We show both immediate and delayed effects on risky decision-making following a meal, and that these changes correlate with an individual's baseline leptin and changes in acyl-ghrelin levels respectively.We show that human risk preferences are exquisitely sensitive to current metabolic state, in a direction consistent with ecological models of feeding behaviour but not predicted by normative economic theory. These substantive effects of state changes on economic decisions perhaps reflect shared evolutionarily conserved neurobiological mechanisms. We suggest that this sensitivity in human risk-preference to current metabolic state has

The gut hormone ghrelin partially reverses energy substrate metabolic alterations in the failing heart.

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Mitacchione, Gianfranco; Powers, Jeffrey C; Grifoni, Gino; Woitek, Felix; Lam, Amy; Ly, Lien; Settanni, Fabio; Makarewich, Catherine A; McCormick, Ryan; Trovato, Letizia; Houser, Steven R; Granata, Riccarda; Recchia, Fabio A

2014-07-01

The gut-derived hormone ghrelin, especially its acylated form, plays a major role in the regulation of systemic metabolism and exerts also relevant cardioprotective effects; hence, it has been proposed for the treatment of heart failure (HF). We tested the hypothesis that ghrelin can directly modulate cardiac energy substrate metabolism. We used chronically instrumented dogs, 8 with pacing-induced HF and 6 normal controls. Human des-acyl ghrelin [1.2 nmol/kg per hour] was infused intravenously for 15 minutes, followed by washout (rebaseline) and infusion of acyl ghrelin at the same dose. (3)H-oleate and (14)C-glucose were coinfused and arterial and coronary sinus blood sampled to measure cardiac free fatty acid and glucose oxidation and lactate uptake. As expected, cardiac substrate metabolism was profoundly altered in HF because baseline oxidation levels of free fatty acids and glucose were, respectively, >70% lower and >160% higher compared with control. Neither des-acyl ghrelin nor acyl ghrelin significantly affected function and metabolism in normal hearts. However, in HF, des-acyl and acyl ghrelin enhanced myocardial oxygen consumption by 10.2±3.5% and 9.9±3.7%, respectively (Pmetabolism in normal dogs, whereas they enhance free fatty acid oxidation and reduce glucose oxidation in HF dogs, thus partially correcting metabolic alterations in HF. This novel mechanism might contribute to the cardioprotective effects of ghrelin in HF. © 2014 American Heart Association, Inc.

Genetic Variant in Flavin-Containing Monooxygenase 3 Alters Lipid Metabolism in Laying Hens in a Diet-Specific Manner

OpenAIRE

Wang, Jing; Long, Cheng; Zhang, Haijun; Zhang, Yanan; Wang, Hao; Yue, Hongyuan; Wang, Xiaocui; Wu, Shugeng; Qi, Guanghai

2016-01-01

Genetic variant T329S in flavin-containing monooxygenase 3 (FMO3) impairs trimethylamine (TMA) metabolism in birds. The TMA metabolism that under complex genetic and dietary regulation, closely linked to cardiovascular disease risk. We determined whether the genetic defects in TMA metabolism may change other metabolic traits in birds, determined whether the genetic effects depend on diets, and to identify genes or gene pathways that underlie the metabolic alteration induced by genetic and die...

Does altered protein metabolism interfere with postmortem degradation analysis for PMI estimation?

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Zissler, A; Ehrenfellner, B; Foditsch, E E; Monticelli, F C; Pittner, S

2018-03-02

An accurate estimation of the postmortem interval (PMI) is a central aspect in forensic routine. Recently, a novel approach based on the analysis of postmortem muscle protein degradation has been proposed. However, a number of questions remain to be answered until sensible application of this method to a broad variety of forensic cases is possible. To evaluate whether altered in vivo protein metabolism interferes with postmortem degradation patterns, we conducted a comparative study. We developed a standardized animal degradation model in rats, and collected additional muscle samples from animals recovering from muscle injury and from rats with developed disuse muscle atrophy after induced spinal cord injury. All samples were analyzed by SDS-PAGE and Western blot, labeling well-characterized muscle proteins. Tropomyosin was found to be stable throughout the investigated PMI and no alterations were detected in regenerating and atrophic muscles. In contrast, significant predictable postmortem changes occurred in desmin and vinculin protein band patterns. While no significant deviations from native patterns were detected in at-death samples of disuse muscle atrophy, interestingly, samples of rats recovering from muscle injury revealed additional desmin and vinculin degradation bands that did not occur in this form in any of the examined postmortem samples regardless of PMI. It remains to be investigated whether in vivo-altered metabolism influences postmortem degradation kinetics or if such muscle samples undergo postmortem degradation in a regular fashion.

The effects of wet cupping on serum high-sensitivity C-reactive protein and heat shock protein 27 antibody titers in patients with metabolic syndrome.

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Farahmand, Seyed Kazem; Gang, Li Zhi; Saghebi, Seyed Ahmad; Mohammadi, Maryam; Mohammadi, Shabnam; Mohammadi, Ghazaleh; Ferns, Gordan A; Ghanbarzadeh, Majid; Razmgah, Gholamreza Ghayour; Ramazani, Zahra; Ghayour-Mobarhan, Majid; Esmaily, Habibollah; Bahrami Taghanaki, Hamidreza; Azizi, Hoda

2014-08-01

It has previously been reported that increased level of serum heat shock proteins (Hsps) antibody in patients with metabolic syndrome. It is possible that the expression of Hsp and inflammatory markers can be affected by cupping and traditional Chinese medicine. There is a little data investigating the effects of cupping on markers of inflammation and Hsp proteins, hence, the objective of this study was evaluation of the effects of wet cupping on serum high-sensitivity C-reactive protein (hs-CRP) and Hsp27 antibody titers in patients with metabolic syndrome. Serum Hs-CRP and Hsp27 antibody titers were assessed in samples from 126 patients with metabolic syndrome (18-65 years of age) at baseline, and after 6 and 12 weeks after treatment. One hundred and twenty-six patients were randomly divided into the experimental group treated with wet cupping combined with dietary advice, and the control group treated with dietary advice alone using a random number table. Eight patients in case group and five subjects in control groups were excluded from the study. Data were analyzed using SPSS 15.0 software and a repeated measure ANCOVA. Serum hs-CRP titers did not change significantly between groups (p>0.05) and times (p=0.27). The same result was found for Hsp27 titers (p>0.05). Wet-cupping on the interscapular region has no effect on serum hs-CRP and Hsp27 patients with metabolic syndrome. Copyright © 2014 Elsevier Ltd. All rights reserved.

Hepatitis C, human immunodeficiency virus and metabolic syndrome: interactions.

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Kotler, Donald P

2009-03-01

Significant concerns have been raised about the metabolic effects of antiretroviral medication, including the classic triad of dyslipidaemia, insulin resistance (IR) and characteristic alterations in fat distribution (lipoatrophy and lipohypertrophy). Co-infection with hepatitis C appears to exacerbate IR, reduce serum lipids and induce prothrombotic changes in the treated human immunodeficiency virus patient. The effects of co-infection are complex. While combination antiretroviral therapy has been shown to be associated with an increased risk of cardiovascular events through promotion of dyslipidaemia, IR and fat redistribution, co-infection exacerbates IR while reducing serum lipids. Co-infection also promotes a prothrombotic state characterized by endothelial dysfunction and platelet activation, which may enhance risk for cardiovascular disease. Consideration must be given to selection of appropriate treatment regimens and timing of therapy in co-infected patients to minimize metabolic derangements and, ultimately, reduce cardiovascular risk.

Cholesterol metabolism and serum non-cholesterol sterols: summary of 13 plant stanol ester interventions.

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Hallikainen, Maarit; Simonen, Piia; Gylling, Helena

2014-04-27

The efficacy and safety of plant stanols added to food products as serum cholesterol lowering agents have been demonstrated convincingly, but their effects on cholesterol metabolism and on serum non-cholesterol sterols is less evaluated. The aim of this study was to assess the validity of serum non-cholesterol sterols and squalene as bioindices of cholesterol synthesis and absorption, and to examine how the individual serum non-cholesterol sterols respond to consumption of plant stanols. We collected all randomized, controlled plant stanol ester (STAEST) interventions in which serum cholestanol, plant sterols campesterol and sitosterol, and at least two serum cholesterol precursors had been analysed. According to these criteria, there was a total of 13 studies (total 868 subjects without lipid-lowering medication; plant stanol doses varied from 0.8 to 8.8 g/d added in esterified form; the duration of the studies varied from 4 to 52 weeks). Serum non-cholesterol sterols were assayed with gas-liquid chromatography, cholesterol synthesis with the sterol balance technique, and fractional cholesterol absorption with the dual continuous isotope feeding method. The results demonstrated that during the control and the STAEST periods, the serum plant sterol/cholesterol- and the cholestanol/cholesterol-ratios reflected fractional cholesterol absorption, and the precursor sterol/cholesterol-ratios reflected cholesterol synthesis. Plant sterol levels were dose-dependently reduced by STAEST so that 2 g of plant stanols reduced serum campesterol/cholesterol-ratio on average by 32%. Serum cholestanol/cholesterol-ratio was reduced less frequently than those of the plant sterols by STAEST, and the cholesterol precursor sterol ratios did not change consistently in the individual studies emphasizing the importance of monitoring more than one surrogate serum marker. Serum non-cholesterol sterols are valid markers of cholesterol absorption and synthesis even during cholesterol

Inhibited Carnitine Synthesis Causes Systemic Alteration of Nutrient Metabolism in Zebrafish.

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Li, Jia-Min; Li, Ling-Yu; Qin, Xuan; Degrace, Pascal; Demizieux, Laurent; Limbu, Samwel M; Wang, Xin; Zhang, Mei-Ling; Li, Dong-Liang; Du, Zhen-Yu

2018-01-01

Impaired mitochondrial fatty acid β-oxidation has been correlated with many metabolic syndromes, and the metabolic characteristics of the mammalian models of mitochondrial dysfunction have also been intensively studied. However, the effects of the impaired mitochondrial fatty acid β-oxidation on systemic metabolism in teleost have never been investigated. In the present study, we established a low-carnitine zebrafish model by feeding fish with mildronate as a specific carnitine synthesis inhibitor [0.05% body weight (BW)/d] for 7 weeks, and the systemically changed nutrient metabolism, including carnitine and triglyceride (TG) concentrations, fatty acid (FA) β-oxidation capability, and other molecular and biochemical assays of lipid, glucose, and protein metabolism, were measured. The results indicated that mildronate markedly decreased hepatic carnitine concentrations while it had no effect in muscle. Liver TG concentrations increased by more than 50% in mildronate-treated fish. Mildronate decreased the efficiency of liver mitochondrial β-oxidation, increased the hepatic mRNA expression of genes related to FA β-oxidation and lipolysis, and decreased the expression of lipogenesis genes. Mildronate decreased whole body glycogen content, increased glucose metabolism rate, and upregulated the expression of glucose uptake and glycolysis genes. Mildronate also increased whole body protein content and hepatic mRNA expression of mechanistic target of rapamycin ( mtor ), and decreased the expression of a protein catabolism-related gene. Liver, rather than muscle, was the primary organ targeted by mildronate. In short, mildronate-induced hepatic inhibited carnitine synthesis in zebrafish caused decreased mitochondrial FA β-oxidation efficiency, greater lipid accumulation, and altered glucose and protein metabolism. This reveals the key roles of mitochondrial fatty acid β-oxidation in nutrient metabolism in fish, and this low-carnitine zebrafish model could also be

Inhibited Carnitine Synthesis Causes Systemic Alteration of Nutrient Metabolism in Zebrafish

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Jia-Min Li

2018-05-01

Full Text Available Impaired mitochondrial fatty acid β-oxidation has been correlated with many metabolic syndromes, and the metabolic characteristics of the mammalian models of mitochondrial dysfunction have also been intensively studied. However, the effects of the impaired mitochondrial fatty acid β-oxidation on systemic metabolism in teleost have never been investigated. In the present study, we established a low-carnitine zebrafish model by feeding fish with mildronate as a specific carnitine synthesis inhibitor [0.05% body weight (BW/d] for 7 weeks, and the systemically changed nutrient metabolism, including carnitine and triglyceride (TG concentrations, fatty acid (FA β-oxidation capability, and other molecular and biochemical assays of lipid, glucose, and protein metabolism, were measured. The results indicated that mildronate markedly decreased hepatic carnitine concentrations while it had no effect in muscle. Liver TG concentrations increased by more than 50% in mildronate-treated fish. Mildronate decreased the efficiency of liver mitochondrial β-oxidation, increased the hepatic mRNA expression of genes related to FA β-oxidation and lipolysis, and decreased the expression of lipogenesis genes. Mildronate decreased whole body glycogen content, increased glucose metabolism rate, and upregulated the expression of glucose uptake and glycolysis genes. Mildronate also increased whole body protein content and hepatic mRNA expression of mechanistic target of rapamycin (mtor, and decreased the expression of a protein catabolism-related gene. Liver, rather than muscle, was the primary organ targeted by mildronate. In short, mildronate-induced hepatic inhibited carnitine synthesis in zebrafish caused decreased mitochondrial FA β-oxidation efficiency, greater lipid accumulation, and altered glucose and protein metabolism. This reveals the key roles of mitochondrial fatty acid β-oxidation in nutrient metabolism in fish, and this low-carnitine zebrafish model

Independent and supra-additive effects of alcohol consumption, cigarette smoking, and metabolic syndrome on the elevation of serum liver enzyme levels.

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Eun Young Park

Full Text Available We investigated the independent and combined effects of alcohol consumption, cigarette smoking and metabolic syndrome on abnormal liver function, i.e., the elevation of serum liver enzyme levels. Participants of a Korean population-based prospective cohort aged ≥30 years without liver disease, diabetes, or cardiovascular diseases were included. Information on alcohol consumption, smoking status, and metabolic syndrome, defined as per the criteria of the Adult Treatment Panel III, were applied to evaluate their impact on serum levels of aspartate aminotransferase (AST, alanine aminotransferase (ALT, and gamma-glutamyl transferase (GGT. Alcohol consumption, cigarette smoking and metabolic syndrome were the significant individual factors that elevated serum liver enzyme levels. Supra-additive effects of metabolic syndrome and either alcohol consumption or cigarette smoking were also identified. The combination of heavy drinking (≥24 g/day and metabolic syndrome conferred an effect that was higher than the sum of the two individual effects (Synergic Index (SI: AST, 2.37 [1.20-4.67]; GGT, 1.91 [1.17-3.13]. Only GGT level (odds ratio 6.04 [3.68-9.94], SI 2.33 [1.24-4.41] was significantly elevated when the effect of moderate drinking (20 pack years, 1.80 for ≥24 g/day and ≤20 pack years, 2.03 for ≥24 g/day and >20 pack years, while only the combined effect of drinking ≥24 g/day and smoking >20 pack years elevated the AST level (SI 4.55 [3.12-6.61]. The combined effect of cigarette smoking and metabolic syndrome was not supra-additive. To prevent fatty liver disease and other related diseases, a multifactorial prevention strategy that includes limited alcohol consumption, smoking cessation and rectification of adverse metabolic profiles is required.

Serum Metabolic Alterations upon Zika Infection

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Carlos Fernando O. R. Melo

2017-10-01

Full Text Available Zika virus (ZIKV infection has recently emerged as a major concern worldwide due to its strong association with nervous system malformation (microcephaly of fetuses in pregnant women infected by the virus. Signs and symptoms of ZIKV infection are often mistaken with other common viral infections. Since transmission may occur through biological fluids exchange and coitus, in addition to mosquito bite, this condition is an important infectious disease. Thus, understanding the mechanism of viral infection has become an important research focus, as well as providing potential targets for assertive clinical diagnosis and quality screening for hemoderivatives. Within this context, the present work analyzed blood plasma from 79 subjects, divided as a control group and a ZIKV-infected group. Samples underwent direct-infusion mass spectrometry and statistical analysis, where eight markers related to the pathophysiological process of ZIKV infection were elected and characterized. Among these, Angiotensin (1-7 and Angiotensin I were upregulated under infection, showing an attempt to induce autophagy of the infected cells. However, this finding is concerning about hypertensive individuals under treatment with inhibitors of the Renin-Angiotensin System (RAS, which could reduce this response against the virus and exacerbate the symptoms of the infection. Moreover, one of the most abundant glycosphingolipids in the nervous tissue, Ganglioside GM2, was also elected in the present study as an infection biomarker. Considered an important pathogen receptor at membrane's outer layer, this finding represents the importance of gangliosides for ZIKV infection and its association with brain tropism. Furthermore, a series of phosphatidylinositols were also identified as biomarkers, implying a significant role of the PI3K-AKT-mTOR Pathway in this mechanism. Finally, these pathways may also be understood as potential targets to be considered in pharmacological intervention studies on ZIKV infection management.

Alterations in adipokines in feline hepatic lipidosis.

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Mazaki-Tovi, M; Abood, S K; Segev, G; Schenck, P A

2013-01-01

Feline hepatic lipidosis (HL) is associated with alterations in lipid and carbohydrate metabolism. The adipokines, adiponectin, and leptin have lipid-lowering and insulin-sensitizing effects. Serum concentrations of adiponectin and leptin are altered in feline HL. Client-owned cats: 55 healthy and 45 with liver disease. Cats with liver disease were categorized as having HL (n = 20), HL and concurrent disease (n = 19), or other liver disease (n = 6), based on clinical signs, laboratory findings, abdominal ultrasound examination as well as liver cytopathology, histopathology, or both. Serum samples were collected and body condition score determined. Mean serum concentrations of adiponectin were higher in overweight cats with HL (4.5 μg/mL), HL and concurrent disease (4.4 μg/mL), or other liver disease (6.1 μg/mL), as compared with healthy cats (1.5 μg/mL; P < .001, P < .001, and P = .04, respectively). Mean serum concentration of leptin was higher in cats with HL (9.8 ng/mL) or HL and concurrent disease (10.7 ng/mL) than healthy cats (4.9 ng/mL, P < .001 and P < .001, respectively). Cats with other liver disease had leptin concentration (4.9 ng/mL) similar to healthy cats. Concentrations of adiponectin were correlated with alanine aminotransferase activity (r = 0.40, P = .0069), and concentrations of leptin were correlated with alkaline phosphatase activity (r = 0.42, P = .0051) in cats with liver disease. Adipokine concentrations are altered in feline HL. Increased concentrations of adiponectin are related to liver disease, whereas increased concentrations of leptin are specifically related to HL. Copyright © 2013 by the American College of Veterinary Internal Medicine.

Serum metabolome biomarkers associate low-level environmental perfluorinated compound exposure with oxidative /nitrosative stress in humans.

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Wang, Xiaofei; Liu, Liangpo; Zhang, Weibing; Zhang, Jie; Du, Xiaoyan; Huang, Qingyu; Tian, Meiping; Shen, Heqing

2017-10-01

Previous in vivo and in vitro studies have linked perfluorinated compound (PFC) exposure with metabolic interruption, but the inter-species difference and high treatment doses usually make the results difficult to be extrapolated to humans directly. The best strategy for identifying the metabolic interruption may be to establish the direct correlations between monitored PFCs data and metabolic data on human samples. In this study, serum metabolome data and PFC concentrations were acquired for a Chinese adult male cohort. The most abundant PFCs are PFOA and PFOS with concentration medians 7.56 and 12.78 nM, respectively; in together they count around 81.6% of the total PFCs. PFC concentration-related serum metabolic profile changes and the related metabolic biomarkers were explored by using partial least squares-discriminant analysis (PLS-DA). Respectively taking PFOS, PFOA and total PFC as the classifiers, serum metabolome can be differentiated between the lowest dose group (1st quartile PFCs) and the highest PFC dose group (4th quartile PFCs). Ten potential PFC biomarkers were identified, mainly involving in pollutant detoxification, antioxidation and nitric oxide (NO) signal pathways. These suggested that low-level environmental PFC exposure has significantly adverse impacts on glutathione (GSH) cycle, Krebs cycle, nitric oxide (NO) generation and purine oxidation in humans. To the best of our knowledge, this is the first report investigating the association of environmental PFC exposure with human serum metabolome alteration. Given the important biological functions of the identified biomarkers, we suggest that PFC could increase the metabolism syndromes risk including diabetes and cardiovascular diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Osteopontin regulates the cross-talk between phosphatidylcholine and cholesterol metabolism in mouse liver.

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Nuñez-Garcia, Maitane; Gomez-Santos, Beatriz; Buqué, Xabier; García-Rodriguez, Juan L; Romero, Marta R; Marin, Jose J G; Arteta, Beatriz; García-Monzón, Carmelo; Castaño, Luis; Syn, Wing-Kin; Fresnedo, Olatz; Aspichueta, Patricia

2017-09-01

Osteopontin (OPN) is involved in different liver pathologies in which metabolic dysregulation is a hallmark. Here, we investigated whether OPN could alter liver, and more specifically hepatocyte, lipid metabolism and the mechanism involved. In mice, lack of OPN enhanced cholesterol 7α-hydroxylase (CYP7A1) levels and promoted loss of phosphatidylcholine (PC) content in liver; in vivo treatment with recombinant (r)OPN caused opposite effects. rOPN directly decreased CYP7A1 levels through activation of focal adhesion kinase-AKT signaling in hepatocytes. PC content was also decreased in OPN-deficient (OPN-KO) hepatocytes in which de novo FA and PC synthesis was lower, whereas cholesterol (CHOL) synthesis was higher, than in WT hepatocytes. In vivo inhibition of cholesterogenesis normalized liver PC content in OPN-KO mice, demonstrating that OPN regulates the cross-talk between liver CHOL and PC metabolism. Matched liver and serum samples showed a positive correlation between serum OPN levels and liver PC and CHOL concentration in nonobese patients with nonalcoholic fatty liver. In conclusion, OPN regulates CYP7A1 levels and the metabolic fate of liver acetyl-CoA as a result of CHOL and PC metabolism interplay. The results suggest that CYP7A1 is a main axis and that serum OPN could disrupt liver PC and CHOL metabolism, contributing to nonalcoholic fatty liver disease progression in nonobese patients.

Serum metabolomics of slow vs. rapid motor progression Parkinson's disease: a pilot study.

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Roede, James R; Uppal, Karan; Park, Youngja; Lee, Kichun; Tran, Vilinh; Walker, Douglas; Strobel, Frederick H; Rhodes, Shannon L; Ritz, Beate; Jones, Dean P

2013-01-01

Progression of Parkinson's disease (PD) is highly variable, indicating that differences between slow and rapid progression forms could provide valuable information for improved early detection and management. Unfortunately, this represents a complex problem due to the heterogeneous nature of humans in regards to demographic characteristics, genetics, diet, environmental exposures and health behaviors. In this pilot study, we employed high resolution mass spectrometry-based metabolic profiling to investigate the metabolic signatures of slow versus rapidly progressing PD present in human serum. Archival serum samples from PD patients obtained within 3 years of disease onset were analyzed via dual chromatography-high resolution mass spectrometry, with data extraction by xMSanalyzer and used to predict rapid or slow motor progression of these patients during follow-up. Statistical analyses, such as false discovery rate analysis and partial least squares discriminant analysis, yielded a list of statistically significant metabolic features and further investigation revealed potential biomarkers. In particular, N8-acetyl spermidine was found to be significantly elevated in the rapid progressors compared to both control subjects and slow progressors. Our exploratory data indicate that a fast motor progression disease phenotype can be distinguished early in disease using high resolution mass spectrometry-based metabolic profiling and that altered polyamine metabolism may be a predictive marker of rapidly progressing PD.

Serum vitamin d levels and the components of metabolic syndrome: an analytical cross-sectional study

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Roomi, M.A.; Farooq, A.; Ullah, E.; Lone, K.P.

2015-01-01

The present study was planned to determine the serum vitamin D levels and its relation with the various components of metabolic syndrome (MetS) in MetS positive and MetS negative subjects. Methods: This analytical cross-sectional study on 88 subjects who were divided into two groups based on whether they fulfill the diagnostic criteria for MetS or not. Fasting serum glucose, lipid profile, insulin, HOMA-IR and vitamin D levels were measured. Two sample-t test and Mann-Whitney U tests were used to compare the differences. Pearson and Spearman correlation tests were used to observe the correlations. Results: BMI (p=0.001), waist/hip ratio (p=0.001), systolic blood pressure (p=0.010), diastolic blood pressure (p=0.010), fasting serum TGs (p = 0.001), TG/HDL ratio (p=0.001), fasting blood sugar (p=0.010), fasting serum insulin (p = 0.001) and HOMA-IR (p=0.001) were significantly high in MetS positive than MetS negative subjects. In MetS Positive subjects, serum vitamin D levels were found to have negative correlation with serum LDL (r= -0.485, p=0.001), total cholesterol (r= -0.408, p=0.007) and total cholesterol/HDL ratio (r= -0.355, p=0.019). Moreover, serum vitamin D levels were found to have positive correlation with HDL/LDL ratio (r= 0.443, p=0.003). Other components of MetS did not show significant correlation with serum vitamin D levels in MetS positive subjects. In MetS negative subjects, serum vitamin D levels did not show any significant correlation with any of the study parameters. Conclusions: Serum vitamin D levels were correlated with a number of MetS components which may be controlled by optimizing vitamin D levels. (author)

Caffeine raises the serum melatonin level in healthy subjects: an indication of melatonin metabolism by cytochrome P450(CYP)1A2.

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Ursing, C; Wikner, J; Brismar, K; Röjdmark, S

2003-05-01

Caffeine is metabolized in the liver by cytochrome P450(CYP)1A2. Recent findings imply that this enzyme may also be of importance for the metabolism of human melatonin (MT). If caffeine and MT are metabolized by the same enzyme, one may expect to find different serum MT levels after ingestion of coffee compared with placebo. Although coffee is consumed by people all over the world, few studies have focused on whether caffeine actually affects serum MT levels in normal subjects. We decided to study that particular topic. For that purpose 12 healthy individuals were tested on two occasions, one week apart. On one of these occasions they were given a capsule containing 200 mg caffeine in the evening. On the other, they received placebo. The experimental order was randomized. Serum MT levels were determined every second hour between 22:00 h and 08:00 h, and the melatonin areas under the curve (MT-AUCs) were calculated. After caffeine the serum MT level rose from 0.09 +/- 0.03 nmol/l at 22:00 h to 0.48 +/- 0.07 nmol/l at 04:00 h. The corresponding rise after placebo was less prominent (from 0.06 +/- 0.01 to 0.35 +/- 0.06 nmol/l). This was reflected by the MT-AUC which was 32% larger after ingestion of caffeine compared with placebo (MT-AUC(caffeine) 3.16 +/- 0.44 nmol/l x h vs MT-AUC(placebo) 2.39 +/- 0.40 nmol/l x h; p coffee, augments the nocturnal serum MT level, which in turn supports the notion that cytochrome P450(CYP)1A2 is involved in the hepatic metabolism of human MT.

Positive Correlation of Serum Adiponectin with Lipid Profile in Patients with Type 2 Diabetes Mellitus is Affected by Metabolic Syndrome Status.

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Eslamian, Mohammad; Mohammadinejad, Payam; Aryan, Zahra; Nakhjavani, Manouchehr; Esteghamati, Alireza

2016-04-01

Type-2 diabetes mellitus (DM) and Metabolic syndrome (MetS) are both associated with dyslipidemia which may lead to development of vascular complications. Adiponectin is an anti-inflammatory protein synthesized by the adipose tissue. There is controversy regarding the association of adiponectin with lipid profile. To evaluate the correlation between serum adiponectin concentration and metabolic profile in patients with type-2 DM. A single center cross-sectional study was conducted on 173 patients with type-2 DM (82 males and 91 females). Plasma adiponectin concentration, lipid profile, glucose profile, and anthropometric features were investigated. Insulin resistance was determined using Homeostasis model assessment (HOMA). Correlation of serum adiponectin with lipid profile of patients with type-2 DM was assessed. Adiponectin was negatively correlated with waist circumference (r = -0.16, P = 0.06) and positively with HbA1c (r = 0.19, P = 0.032), total cholesterol (r = 0.23, P = 0.017), LDL (r = 0.30, P = 0.001), SD-LDL (r = 0.41, P < 0.001), and SD-LDL/LDL (r = 0.22, P = 0.023). We found a positive correlation between adiponectin and total cholesterol (r = 0.27, P = 0.055), LDL (r = 0.34, P = 0.026) and SD-LDL (r = 0.41, P = 0.006) in patients with at least 3 components of MetS criteria. Correlation of adiponectin with LDL and SD-LDL remained positively significant with increasing the number of MetS components. In patients with 5 components of MetS, serum adiponectin was significantly correlated with serum triglyceride (r = 0.89). Significant interaction was observed between adiponectin and metabolic syndrome in relation to serum lipid profile. The results of the present study suggest that in patients with type-2 DM and MetS, lipid profile is strongly correlated with blood concentration of adiponectin. The strongest association was observed between serum adiponectin and LDL.

Altered protein expression in serum from endometrial hyperplasia and carcinoma patients

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Cong Qing

2011-04-01

Full Text Available Abstract Background Endometrial carcinoma is one of the most common gynecological malignancies in women. The diagnosis of the disease at early or premalignant stages is crucial for the patient's prognosis. To date, diagnosis and follow-up of endometrial carcinoma and hyperplasia require invasive procedures. Therefore, there is considerable demand for the identification of biomarkers to allow non-invasive detection of these conditions. Methods In this study, we performed a quantitative proteomics analysis on serum samples from simple endometrial hyperplasia, complex endometrial hyperplasia, atypical endometrial hyperplasia, and endometrial carcinoma patients, as well as healthy women. Serum samples were first depleted of high-abundance proteins, labeled with isobaric tags (iTRAQ™, and then analyzed via two-dimensional liquid chromatography and tandem mass spectrometry. Protein identification and quantitation information were acquired by comparing the mass spectrometry data against the International Protein Index Database using ProteinPilot software. Bioinformatics annotation of identified proteins was performed by searching against the PANTHER database. Results In total, 74 proteins were identified and quantified in serum samples from endometrial lesion patients and healthy women. Using a 1.6-fold change as the benchmark, 12 proteins showed significantly altered expression levels in at least one disease group compared with healthy women. Among them, 7 proteins were found, for the first time, to be differentially expressed in atypical endometrial hyperplasia. These proteins are orosomucoid 1, haptoglobin, SERPINC 1, alpha-1-antichymotrypsin, apolipoprotein A-IV, inter-alpha-trypsin inhibitor heavy chain H4, and histidine-rich glycoprotein. Conclusions The differentially expressed proteins we discovered in this study may serve as biomarkers in the diagnosis and follow-up of endometrial hyperplasia and endometrial carcinoma.

Changes of serum bone metabolic biochemical markers in elderly subjects with subclinical hypothyroidism

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Dai Yaozong; Li Liren

2005-01-01

Objective: To explore the clinical significance of changes of serum bone metabolic biochemical markers levels in elderly subjects with subclinical hypothyroidism. Methods: Serum S-BGP (with RIA), TSH, FT 4 (with ECLIA), total cholesterol (TC), triglyceride (TG), HDL, LDL, ApoA 1 , ApoB and Ca 2+ (with biochemical methods) were measured in 30 elderly subjects with subclinical hypothyroidism and 30 controls. Results: The serum levels of S-BGP and calcium in elderly subjects with subclinical hypothyroidism (2.78 ± 0.96 μg/L and 2.16 ± 0.17 mmol/L respectively) were significantly lower than those in controls (3.9 ± 1.48 μg/L and 2.31 ± 0.21 mmol/L respectively, both P<0.01). TC and LDL levels in the subclinical hypothyroid subjects (5.58 ± 0.41 mmol/L and 3.67 ± 0.36 mmol/L) were significantly higher than those in controls (P<0.01). Conclusion: The lowering of calcium levels in subjects with subclinical hypothyroidism would lead to loss of bone mass. Decreased S-BGP contents might be the chief cause of osteoporosis in these subjects. (authors)

Metabolomic profiles of lipid metabolism, arterial stiffness and hemodynamics in male coronary artery disease patients

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Kaido Paapstel

2016-06-01

Conclusions: We demonstrated an independent association between the serum medium- and long-chain acylcarnitine profile and aortic stiffness for the CAD patients. In addition to the lipid-related classical CVD risk markers, the intermediates of lipid metabolism may serve as novel indicators for altered vascular function.

D-psicose, an epimer of D-fructose, favorably alters lipid metabolism in Sprague-Dawley rats.

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Nagata, Yasuo; Kanasaki, Akane; Tamaru, Shizuka; Tanaka, Kazunari

2015-04-01

D-Psicose, a C3 epimer of D-fructose, is known to lower body weight and adipose tissue weight and affect lipid metabolism. The precise mechanism remains unknown. It has been reported that D-psicose has a short half-life and is not metabolized in the body. To determine how D-psicose modifies lipid metabolism, rats were fed diets with or without 3% D-psicose for 4 weeks. Rats were decapitated without fasting every 6 h over a period of 24 h. Changes in serum and liver lipid levels, liver enzyme activity, and gene expression were quantified in experiment 1. Rats fed D-psicose had significantly lower serum insulin and leptin levels. Liver enzyme activities involved in lipogenesis were significantly lowered by the D-psicose diet, whereas gene expression of a transcriptional modulator of fatty acid oxidation was enhanced. In experiment 2, feeding the D-psicose diet gave significantly lower body weight (389 ± 3 vs 426 ± 6 g, p vs 25.7 ± 0.4 g/day, p energy expenditure in the light period and fat oxidation in the dark period compared to rats fed the control diet, whereas carbohydrate oxidation was lower. In summary, these results indicate that the D-psicose diet decreases lipogenesis, increases fatty acid oxidation, and enhances 24 h energy expenditure, leading to d-psicose's potential for weight management.

Comprehensive insights into microcystin-LR effects on hepatic lipid metabolism using cross-omics technologies

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Zhang, Zongyao; Zhang, Xu-Xiang; Wu, Bing; Yin, Jinbao; Yu, Yunjiang; Yang, Liuyan

2016-01-01

Highlights: • Use of cross-omics technologies to evaluate toxic effects of microcystin-LR. • Disturbance of hepatic lipid metabolism by oral exposure to microcystin-LR. • Crucial roles of gut microbial community shift in the metabolic disturbance induced by microcystin-LR. - Abstract: Microcystin-LR (MC-LR) can induce hepatic tissue damages and molecular toxicities, but its effects on lipid metabolism remain unknown. This study investigated the effects of MC-LR exposure on mice lipid metabolism and uncovered the underlying mechanism through metabonomic, transcriptomic and metagenomic analyses after administration of mice with MC-LR by gavage for 28 d. Increased liver weight and abdominal fat weight, and evident hepatic lipid vacuoles accumulation were observed in the mice fed with 0.2 mg/kg/d MC-LR. Serum nuclear magnetic resonance analysis showed that MC-LR treatment altered the levels of serum metabolites including triglyceride, unsaturated fatty acid (UFA) and very low density lipoprotein. Digital Gene Expression technology was used to reveal differential expression of hepatic transcriptomes, demonstrating that MC-LR treatment disturbed hepatic UFA biosynthesis and activated peroxisome proliferator-activated receptor (PPAR) signaling pathways via Pparγ, Fabp1 and Fabp2 over-expression. Metagenomic analyses of gut microbiota revealed that MC-LR exposure also increased abundant ratio of Firmicutes vs. Bacteroidetes in gut and altered biosynthetic pathways of various microbial metabolic and pro-inflammatory molecules. In conclusion, oral MC-LR exposure can induce hepatic lipid metabolism disorder mediated by UFA biosynthesis and PPAR activation, and gut microbial community shift may play an important role in the metabolic disturbance.

Comprehensive insights into microcystin-LR effects on hepatic lipid metabolism using cross-omics technologies

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Zhang, Zongyao [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023 (China); Center for Environmental Health Research, South China Institute of Environmental Sciences, The Ministry of Environmental Protection of PRC, Guangzhou 510655 (China); Zhang, Xu-Xiang, E-mail: zhangxx@nju.edu.cn [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023 (China); Wu, Bing; Yin, Jinbao [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023 (China); Yu, Yunjiang [Center for Environmental Health Research, South China Institute of Environmental Sciences, The Ministry of Environmental Protection of PRC, Guangzhou 510655 (China); Yang, Liuyan, E-mail: yangly@nju.edu.cn [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023 (China)

2016-09-05

Highlights: • Use of cross-omics technologies to evaluate toxic effects of microcystin-LR. • Disturbance of hepatic lipid metabolism by oral exposure to microcystin-LR. • Crucial roles of gut microbial community shift in the metabolic disturbance induced by microcystin-LR. - Abstract: Microcystin-LR (MC-LR) can induce hepatic tissue damages and molecular toxicities, but its effects on lipid metabolism remain unknown. This study investigated the effects of MC-LR exposure on mice lipid metabolism and uncovered the underlying mechanism through metabonomic, transcriptomic and metagenomic analyses after administration of mice with MC-LR by gavage for 28 d. Increased liver weight and abdominal fat weight, and evident hepatic lipid vacuoles accumulation were observed in the mice fed with 0.2 mg/kg/d MC-LR. Serum nuclear magnetic resonance analysis showed that MC-LR treatment altered the levels of serum metabolites including triglyceride, unsaturated fatty acid (UFA) and very low density lipoprotein. Digital Gene Expression technology was used to reveal differential expression of hepatic transcriptomes, demonstrating that MC-LR treatment disturbed hepatic UFA biosynthesis and activated peroxisome proliferator-activated receptor (PPAR) signaling pathways via Pparγ, Fabp1 and Fabp2 over-expression. Metagenomic analyses of gut microbiota revealed that MC-LR exposure also increased abundant ratio of Firmicutes vs. Bacteroidetes in gut and altered biosynthetic pathways of various microbial metabolic and pro-inflammatory molecules. In conclusion, oral MC-LR exposure can induce hepatic lipid metabolism disorder mediated by UFA biosynthesis and PPAR activation, and gut microbial community shift may play an important role in the metabolic disturbance.

Physiological Aldosterone Concentrations Are Associated with Alterations of Lipid Metabolism: Observations from the General Population

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M. Hannich

2018-01-01

Full Text Available Objective. Aldosterone and high-density lipoprotein cholesterol (HDL-C are involved in many pathophysiological processes that contribute to the development of cardiovascular diseases. Previously, associations between the concentrations of aldosterone and certain components of the lipid metabolism in the peripheral circulation were suggested, but data from the general population is sparse. We therefore aimed to assess the associations between aldosterone and HDL-C, low-density lipoprotein cholesterol (LDL-C, total cholesterol, triglycerides, or non-HDL-C in the general adult population. Methods. Data from 793 men and 938 women aged 25–85 years who participated in the first follow-up of the Study of Health in Pomerania were obtained. The associations of aldosterone with serum lipid concentrations were assessed in multivariable linear regression models adjusted for sex, age, body mass index (BMI, estimated glomerular filtration rate (eGFR, and HbA1c. Results. The linear regression models showed statistically significant positive associations of aldosterone with LDL-C (β-coefficient = 0.022, standard error = 0.010, p=0.03 and non-HDL-C (β-coefficient = 0.023, standard error = 0.009, p=0.01 as well as an inverse association of aldosterone with HDL-C (β-coefficient = −0.022, standard error = 0.011, p=0.04. Conclusions. The present data show that plasma aldosterone is positively associated with LDL-C and non-HDL-C and inversely associated with HDL-C in the general population. Our data thus suggests that aldosterone concentrations within the physiological range may be related to alterations of lipid metabolism.

Serum vaspin level as a predictive indicator in the amelioration of fatty liver and metabolic disturbance in patients with severe obesity after laparoscopic vertical banded gastroplasty.

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Wang, Yong; Yu, Zong-Fan; Cheng, Yun-Sheng; Jia, Ben-Li; Yu, Gang; Yin, Xiao-Qiang; Wang, Yang

2017-07-01

This study is all about predicting the value of serum vaspin level in the amelioration of fatty liver and metabolic disturbance in patients with severe obesity after laparoscopic vertical banded gastroplasty (LVBG). A total of 164 patients (from January 2012 to May 2015) with severe obesity were chosen and performed LVBG. Enzyme-linked immunosorbent assay was performed to detect the serum vaspin level. The patients were given a biochemical automatic analyzer to measure the biochemical indicators. Homeostasis model assessment (HOMA) helps in the calculation of fasting insulin level (FINS) and insulin resistance (IR). The changes in fatty liver were examined by computed tomography (CT). Receiver operating characteristic curve is used to increase the predictive value of serum vaspin level in the amelioration of liver function and disturbances in the metabolism. Weight, BMI, waist circumference, serum vaspin level, and triglyceride (TG) decreased, but CT value of liver increased at 4th, 7th, and 12th month after surgery. After the 7th and 12th month period of surgery, the alanine aminotransferase, aspartate aminotransferase, FINS, and HOMA-IR reduced in the patients (P fatty liver and metabolic disturbance. This study proves that the serum vaspin level serves as a predictive indicator in the amelioration of fatty liver and metabolic disturbance in patients with severe obesity after LVBG.

Qualitative metabolomics profiling of serum and bile from dogs with gallbladder mucocele formation

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Mathews, Kyle G.; Cullen, John; Seiler, Gabriela

2018-01-01

Mucocele formation is characterized by secretion of abnormally thick mucus by the gallbladder epithelium of dogs that may cause obstruction of the bile duct or rupture of the gallbladder. The disease is increasingly recognized and is associated with a high morbidity and mortality. The cause of gallbladder mucocele formation in dogs is unknown. There is a strong breed predisposition and affected dogs have a high incidence of concurrent endocrinopathy or hyperlipidemia. These observations suggest a significant influence of both genetic and metabolic factors on disease pathogenesis. In this study, we investigated a theory that mucocele formation is associated with a syndrome of metabolic disruption. We surmised that a global, untargeted metabolomics approach could provide unique insight into the systemic pathogenesis of gallbladder mucocele formation and identify specific compounds as candidate biomarkers or treatment targets. Moreover, concurrent examination of the serum and hepatic duct bile metabolome would enable the construction of mechanism-based theories or identification of specific compounds responsible for altered function of the gallbladder epithelium. Abnormalities observed in dogs with gallbladder mucocele formation, including a 33-fold decrease in serum adenosine 5’-monophosphate (AMP), lower quantities of precursors required for synthesis of energy transporting nucleotides, and increases in citric acid cycle intermediates, suggest excess metabolic energy and a carbon surplus. Altered quantities of compounds involved in protein translation and RNA turnover, together with accumulation of gamma-glutamylated and N-acetylated amino acids in serum suggest abnormal regulation of protein and amino acid metabolism. Increases in lathosterol and 7α-hydroxycholesterol suggest a primary increase in cholesterol synthesis and diversion to bile acid formation. A number of specific biomarker compounds were identified for their ability to distinguish between control

Increased serum free tryptophan in patients with diarrhea-predominant irritable bowel syndrome.

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Christmas, David M; Badawy, Abdulla A-B; Hince, Dana; Davies, Simon J C; Probert, Christopher; Creed, Tom; Smithson, John; Afzal, Muhammad; Nutt, David J; Potokar, John P

2010-10-01

Irregularities of serotonin function in irritable bowel syndrome (IBS) may be due to changes in the metabolism of the serotonin precursor l-tryptophan. Dietary alteration of tryptophan intake may impact upon the mood and bowel symptoms of IBS. We hypothesized that diarrhea-predominant irritable bowel syndrome (d-IBS) patients would exhibit an increase in plasma tryptophan due to alterations in tryptophan metabolism. We also hypothesized that a diet low in tryptophan would reverse this change and reduce symptoms. Thirteen patients with d-IBS had fasting serum free and total tryptophan, large neutral amino acids, and 6 kynurenine metabolites measured before and after 2 weeks of a strict dairy-free diet. Baseline tryptophan parameters were compared with an age- and sex-matched control group. Changes in the specific tryptophan parameters before and after dairy-free diet were correlated with symptoms of IBS and mood. Compared with the control group, d-IBS patients at baseline exhibited significantly higher free serum tryptophan (10.5 ± 4.35 vs 4.75 ± 2.43 μmol/L [means ± standard deviation], P = .006) and significantly lower tryptophan dioxygenase and total tryptophan oxidation as measured by the kynurenine to free tryptophan and total kynurenines to free tryptophan ratios (23.37 ± 10.12 vs 55.33 ± 16.02, P < .001 and 49.34 ± 17.84 vs 258.46 ± 98.67, P < .001, respectively). Dairy-free diet did not modulate metabolites of the kynurenine pathway or symptoms. Tryptophan metabolism along the kynurenine pathway is inhibited in d-IBS, and a dairy-free diet does not alter this. Our findings are consistent with possible enhanced serotonin activity in d-IBS. Copyright © 2010 Elsevier Inc. All rights reserved.

Inhaled ozone (O3)-induces changes in serum metabolomic and liver transcriptomic profiles in rats

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Miller, Desinia B.; Karoly, Edward D.; Jones, Jan C.; Ward, William O.; Vallanat, Beena D.; Andrews, Debora L.; Schladweiler, Mette C.; Snow, Samantha J.; Bass, Virginia L.; Richards, Judy E.; Ghio, Andrew J.; Cascio, Wayne E.; Ledbetter, Allen D.; Kodavanti, Urmila P.

2015-01-01

Air pollution has been linked to increased incidence of diabetes. Recently, we showed that ozone (O 3 ) induces glucose intolerance, and increases serum leptin and epinephrine in Brown Norway rats. In this study, we hypothesized that O 3 exposure will cause systemic changes in metabolic homeostasis and that serum metabolomic and liver transcriptomic profiling will provide mechanistic insights. In the first experiment, male Wistar Kyoto (WKY) rats were exposed to filtered air (FA) or O 3 at 0.25, 0.50, or 1.0 ppm, 6 h/day for two days to establish concentration-related effects on glucose tolerance and lung injury. In a second experiment, rats were exposed to FA or 1.0 ppm O 3 , 6 h/day for either one or two consecutive days, and systemic metabolic responses were determined immediately after or 18 h post-exposure. O 3 increased serum glucose and leptin on day 1. Glucose intolerance persisted through two days of exposure but reversed 18 h-post second exposure. O 3 increased circulating metabolites of glycolysis, long-chain free fatty acids, branched-chain amino acids and cholesterol, while 1,5-anhydroglucitol, bile acids and metabolites of TCA cycle were decreased, indicating impaired glycemic control, proteolysis and lipolysis. Liver gene expression increased for markers of glycolysis, TCA cycle and gluconeogenesis, and decreased for markers of steroid and fat biosynthesis. Genes involved in apoptosis and mitochondrial function were also impacted by O 3 . In conclusion, short-term O 3 exposure induces global metabolic derangement involving glucose, lipid, and amino acid metabolism, typical of a stress–response. It remains to be examined if these alterations contribute to insulin resistance upon chronic exposure. - Highlights: • Ozone, an ubiquitous air pollutant induces acute systemic metabolic derangement. • Serum metabolomic approach provides novel insights in ozone-induced changes. • Ozone exposure induces leptinemia, hyperglycemia, and glucose intolerance

Low levels of serum serotonin and amino acids identified in migraine patients.

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Ren, Caixia; Liu, Jia; Zhou, Juntuo; Liang, Hui; Wang, Yayun; Sun, Yinping; Ma, Bin; Yin, Yuxin

2018-02-05

Migraine is a highly disabling primary headache associated with a high socioeconomic burden and a generally high prevalence. The clinical management of migraine remains a challenge. This study was undertaken to identify potential serum biomarkers of migraine. Using Liquid Chromatography coupled to Mass Spectrometry (LC-MS), the metabolomic profile of migraine was compared with healthy individuals. Principal component analysis (PCA) and Orthogonal partial least squares-discriminant analysis (orthoPLS-DA) showed the metabolomic profile of migraine is distinguishable from controls. Volcano plot analysis identified 10 serum metabolites significantly decreased during migraine. One of these was serotonin, and the other 9 were amino acids. Pathway analysis and enrichment analysis showed tryptophan metabolism (serotonin metabolism), arginine and proline metabolism, and aminoacyl-tRNA biosynthesis are the three most prominently altered pathways in migraine. ROC curve analysis indicated Glycyl-l-proline, N-Methyl-dl-Alanine and l-Methionine are potential sensitive and specific biomarkers for migraine. Our results show Glycyl-l-proline, N-Methyl-dl-Alanine and l-Methionine may be as specific or more specific for migraine than serotonin which is the traditional biomarker of migraine. We propose that therapeutic manipulation of these metabolites or metabolic pathways may be helpful in the prevention and treatment of migraine. Copyright © 2018 Elsevier Inc. All rights reserved.

Metabolic syndrome in patients with morbid obesity, according to different levels of serum uric acid.

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Hordonho, Ana Adélia Cavalcante

2009-01-01

Although uric acid has a character antioxidant, when in increased serum levels, has been associated in several studies with various pathological conditions, particularly with obesity, cardiovascular disease, diabetes mellitus, dyslipidemia, hyperinsulinemia and insulin resistance, this being identified as the primary change of the metabolic syndrome. However, these studies were not performed on samples formed specifically for morbid obeses, where hyperuricemia is a common findi...

Natural Killer Cell Activity and Interleukin-12 in Metabolically Healthy versus Metabolically Unhealthy Overweight Individuals

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Kim, Minjoo; Kim, Minkyung; Yoo, Hye Jin; Lee, Jong Ho

2017-01-01

The purpose of this study was to determine whether the immune system is involved in the different metabolic circumstances in healthy and unhealthy overweight individuals. We examined the metabolic and immune characteristics of 117 overweight individuals. Subjects were classified as metabolically healthy overweight (MHO, n = 72) or metabolically unhealthy overweight (MUO, n = 45). The immune response was measured by circulating levels of natural killer (NK) cell activity and cytokines. Both groups were comparable with regards to age, sex distribution, smoking and drinking status, and body mass index. When compared to the MHO group, the MUO group showed higher systolic and diastolic blood pressure, serum levels of triglyceride, glucose, glucose-related markers, and lower levels of HDL cholesterol. Compared to the MHO group, the MUO group showed 39% lower interferon-γ levels (not significant) and 41% lower interleukin (IL)-12 levels (significant). The MUO group also showed lower NK cell activity at E:T ratios of 10:1, 5:1, 2.5:1, and 1.25:1 (all Ps < 0.05) than the MHO group. This study indicates that individuals displaying the MUO phenotype present an unfavorable immune system with lower NK cell activities under all assay conditions and lower serum levels of IL-12 than the activities and levels in similarly overweight MHO individuals. This result suggests that the immune system may be altered in overweight individuals who are at risk for overweight/obesity-related comorbidities. PMID:29238351

Natural Killer Cell Activity and Interleukin-12 in Metabolically Healthy versus Metabolically Unhealthy Overweight Individuals

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Minjoo Kim

2017-11-01

Full Text Available The purpose of this study was to determine whether the immune system is involved in the different metabolic circumstances in healthy and unhealthy overweight individuals. We examined the metabolic and immune characteristics of 117 overweight individuals. Subjects were classified as metabolically healthy overweight (MHO, n = 72 or metabolically unhealthy overweight (MUO, n = 45. The immune response was measured by circulating levels of natural killer (NK cell activity and cytokines. Both groups were comparable with regards to age, sex distribution, smoking and drinking status, and body mass index. When compared to the MHO group, the MUO group showed higher systolic and diastolic blood pressure, serum levels of triglyceride, glucose, glucose-related markers, and lower levels of HDL cholesterol. Compared to the MHO group, the MUO group showed 39% lower interferon-γ levels (not significant and 41% lower interleukin (IL-12 levels (significant. The MUO group also showed lower NK cell activity at E:T ratios of 10:1, 5:1, 2.5:1, and 1.25:1 (all Ps < 0.05 than the MHO group. This study indicates that individuals displaying the MUO phenotype present an unfavorable immune system with lower NK cell activities under all assay conditions and lower serum levels of IL-12 than the activities and levels in similarly overweight MHO individuals. This result suggests that the immune system may be altered in overweight individuals who are at risk for overweight/obesity-related comorbidities.

Genetic transformation of rare Verbascum eriophorum Godr. plants and metabolic alterations revealed by NMR-based metabolomics.

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Marchev, Andrey; Yordanova, Zhenya; Alipieva, Kalina; Zahmanov, Georgi; Rusinova-Videva, Snezhana; Kapchina-Toteva, Veneta; Simova, Svetlana; Popova, Milena; Georgiev, Milen I

2016-09-01

To develop a protocol to transform Verbascum eriophorum and to study the metabolic differences between mother plants and hairy root culture by applying NMR and processing the datasets with chemometric tools. Verbascum eriophorum is a rare species with restricted distribution, which is poorly studied. Agrobacterium rhizogenes-mediated genetic transformation of V. eriophorum and hairy root culture induction are reported for the first time. To determine metabolic alterations, V. eriophorum mother plants and relevant hairy root culture were subjected to comprehensive metabolomic analyses, using NMR (1D and 2D). Metabolomics data, processed using chemometric tools (and principal component analysis in particular) allowed exploration of V. eriophorum metabolome and have enabled identification of verbascoside (by means of 2D-TOCSY NMR) as the most abundant compound in hairy root culture. Metabolomics data contribute to the elucidation of metabolic alterations after T-DNA transfer to the host V. eriophorum genome and the development of hairy root culture for sustainable bioproduction of high value verbascoside.

Oleanolic acid alters bile acid metabolism and produces cholestatic liver injury in mice

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Liu, Jie, E-mail: JLiu@kumc.edu [University of Kansas Medical Center, Kansas City, KS 66160 (United States); Zunyi Medical College, Zunyi 563003 (China); Lu, Yuan-Fu [University of Kansas Medical Center, Kansas City, KS 66160 (United States); Zunyi Medical College, Zunyi 563003 (China); Zhang, Youcai; Wu, Kai Connie [University of Kansas Medical Center, Kansas City, KS 66160 (United States); Fan, Fang [Cytopathology, University of Kansas Medical Center, Kansas City, KS 66160 (United States); Klaassen, Curtis D. [University of Kansas Medical Center, Kansas City, KS 66160 (United States)

2013-11-01

Oleanolic acid (OA) is a triterpenoids that exists widely in plants. OA is effective in protecting against hepatotoxicants. Whereas a low dose of OA is hepatoprotective, higher doses and longer-term use of OA produce liver injury. This study characterized OA-induced liver injury in mice. Adult C57BL/6 mice were given OA at doses of 0, 22.5, 45, 90, and 135 mg/kg, s.c., daily for 5 days, and liver injury was observed at doses of 90 mg/kg and above, as evidenced by increases in serum activities of alanine aminotransferase and alkaline phosphatase, increases in serum total bilirubin, as well as by liver histopathology. OA-induced cholestatic liver injury was further evidenced by marked increases of both unconjugated and conjugated bile acids (BAs) in serum. Gene and protein expression analysis suggested that livers of OA-treated mice had adaptive responses to prevent BA accumulation by suppressing BA biosynthetic enzyme genes (Cyp7a1, 8b1, 27a1, and 7b1); lowering BA uptake transporters (Ntcp and Oatp1b2); and increasing a BA efflux transporter (Ostβ). OA increased the expression of Nrf2 and its target gene, Nqo1, but decreased the expression of AhR, CAR and PPARα along with their target genes, Cyp1a2, Cyp2b10 and Cyp4a10. OA had minimal effects on PXR and Cyp3a11. Taken together, the present study characterized OA-induced liver injury, which is associated with altered BA homeostasis, and alerts its toxicity potential. - Highlights: • Oleanolic acid at higher doses and long-term use may produce liver injury. • Oleanolic acid increased serum ALT, ALP, bilirubin and bile acid concentrations. • OA produced feathery degeneration, inflammation and cell death in the liver. • OA altered bile acid homeostasis, affecting bile acid synthesis and transport.

Association between Several Persistent Organic Pollutants in Serum and Adipokine Levels in Breast Milk among Lactating Women of Korea.

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Kim, Sunmi; Park, Jeongim; Kim, Hai-Joong; Lee, Jeong Jae; Choi, Gyuyeon; Choi, Sooran; Kim, Sungjoo; Kim, Su Young; Lee, Duk Hee; Moon, Hyo-Bang; Kim, Sungkyoon; Choi, Kyungho

2015-07-07

Exposure to several persistent organic pollutants (POPs) has been linked to alteration of lipid metabolism. Adipokines, such as leptin and adiponectin, are hormones that play roles in lipid metabolism, and have been suggested as markers of health effects that may lead to obesity. To date, only serum adipokines have been associated with POPs exposure. In the present study, for the first time, the associations between leptin and adiponectin in breast milk, and several POPs in serum were investigated among 82 lactating Korean women between 25 and 46 years of age. Breast milk adipokines are important because adipokine intake of infant through breastfeeding may influence the growth of infants. The median concentrations of leptin and adiponectin in skimmed milk of the Korean lactating women were 17.9 ng/L and 16.5 μg/L, respectively. Leptin concentrations in breast milk were negatively associated with ∑hexachlorohexane (HCH), oxychlordane, ∑chlordane, or 2,2',4,4',5,5'-hexachlorobiphenyl (CB 153) levels in maternal serum. Linear relationships between adiponectin and POPs concentrations were not observed, however, nonmonotonic relationship which showed generally positive associations was suggested for p,p'-dichlorodiphenyltrichloroethane (DDT) and ∑chlordane in quartile analysis. Our observations show that POPs at the current level of exposure may be associated with the alteration of lipid metabolism among lactating women. Implication of adipokine transfer to breastfed infants is of concern and deserves further investigation.

Elevated Serum Cyclophilin B Levels Are Associated with the Prevalence and Severity of Metabolic Syndrome

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Hang Zhang

2017-12-01

Full Text Available ObjectiveInflammation plays a central role in the pathogenesis of metabolic syndrome (MetS. Cyclophilin B (CypB can be constitutively secreted in response to inflammatory stimuli and oxidative stress, participating in tissue or systemic inflammation. We investigated the relationship between CypB and MetS in both humans and mice.MethodsSerum CypB levels were determined in 211 subjects with MetS and 292 subjects without MetS (non-MetS (133 healthy controls and 159 high-risk subjects with one to two MetS components. Additionally, CypB expression in metabolic organs was examined in mice fed with high-fat diet (HFD and genetically obese (ob/ob mice.ResultsSerum CypB level was significantly higher in MetS subjects compared with both groups of non-MetS subjects (193.80 ± 83.22 vs. 168.38 ± 65.01 vs. 124.26 ± 47.83 ng/mL, P < 0.001. Particularly, serum CypB level was significantly higher in subjects with hypertension, central obesity, diabetes mellitus or hyperglycemia, elevated levels of triglycerides, or reduced levels of high-density lipoprotein than in those without. Moreover, CypB was positively associated with the number of MetS components (r = 0.404, P < 0.001, indicating that a higher serum CypB level reflected more severe MetS. Multivariate regression revealed that a one SD increase in CypB was associated with an odds ratio of 1.506 (1.080–2.101, P = 0.016 for MetS prevalence after adjusting for age, gender, conventional risk factors, and medication. Stratified analyses by age and gender demonstrated that subjects >60 years old with higher CypB levels were more likely to have MetS, and the risk for MetS was higher and more significant in women compared with men. Additionally, CypB expression levels were lower at baseline and dramatically enhanced in metabolic organs (such as the liver and visceral and subcutaneous adipose tissue from HFD-induced obese mice and ob/ob mice.ConclusionIncreased CypB levels were

Metabolomics reveals metabolic alterations by intrauterine growth restriction in the fetal rabbit brain.

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Erwin van Vliet

Full Text Available Intrauterine Growth Restriction (IUGR due to placental insufficiency occurs in 5-10% of pregnancies and is a major risk factor for abnormal neurodevelopment. The perinatal diagnosis of IUGR related abnormal neurodevelopment represents a major challenge in fetal medicine. The development of clinical biomarkers is considered a promising approach, but requires the identification of biochemical/molecular alterations by IUGR in the fetal brain. This targeted metabolomics study in a rabbit IUGR model aimed to obtain mechanistic insight into the effects of IUGR on the fetal brain and identify metabolite candidates for biomarker development.At gestation day 25, IUGR was induced in two New Zealand rabbits by 40-50% uteroplacental vessel ligation in one horn and the contralateral horn was used as control. At day 30, fetuses were delivered by Cesarian section, weighed and brains collected for metabolomics analysis. Results showed that IUGR fetuses had a significantly lower birth and brain weight compared to controls. Metabolomics analysis using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS and database matching identified 78 metabolites. Comparison of metabolite intensities using a t-test demonstrated that 18 metabolites were significantly different between control and IUGR brain tissue, including neurotransmitters/peptides, amino acids, fatty acids, energy metabolism intermediates and oxidative stress metabolites. Principle component and hierarchical cluster analysis showed cluster formations that clearly separated control from IUGR brain tissue samples, revealing the potential to develop predictive biomarkers. Moreover birth weight and metabolite intensity correlations indicated that the extent of alterations was dependent on the severity of IUGR.IUGR leads to metabolic alterations in the fetal rabbit brain, involving neuronal viability, energy metabolism, amino acid levels, fatty acid profiles and oxidative stress

[Alterations in the metabolism of cornmeal epithelium during medium-term storage (author's transl)].

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Schmidt-Martens, F W; Hennighausen, U; Wirz, K; Teping, C

1977-08-08

Freshly prepared bovine corneas were stored in medium TC 199 with penicillin and fetal calf serum at +4 degrees C over a storage period of 168h. Every 24h, the levels of glucose, lactate, and pyruvate in the corneal epithelium were estimated. Also the glucose levels in the corneal epithelium and stroma were compared at the same time intervals. Furthermore, alterations in the enzyme pattern of the epithelial cells during storage were observed.

High altitude may alter oxygen availability and renal metabolism in diabetics as measured by hyperpolarized [1-1C]pyruvate magnetic resonance imaging

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Laustsen, Christoffer; Lycke, Sara; Palm, Fredrik

2014-01-01

inspired oxygen did not alter renal metabolism in the control group. Reduced oxygen availability in the diabetic kidney altered energy metabolism by increasing lactate and alanine formation by 23% and 34%, respectively, whereas the bicarbonate flux was unchanged. Thus, the increased prevalence and severity......The kidneys account for about 10% of the whole body oxygen consumption, whereas only 0.5% of the total body mass. It is known that intrarenal hypoxia is present in several diseases associated with development of kidney disease, including diabetes, and when renal blood flow is unaffected....... The importance of deranged oxygen metabolism is further supported by deterioration of kidney function in patients with diabetes living at high altitude. Thus, we argue that reduced oxygen availability alters renal energy metabolism. Here, we introduce a novel magnetic resonance imaging (MRI) approach to monitor...

Identification of altered metabolic pathways in plasma and CSF in mild cognitive impairment and Alzheimer's disease using metabolomics.

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Eugenia Trushina

Full Text Available Alzheimer's Disease (AD currently affects more than 5 million Americans, with numbers expected to grow dramatically as the population ages. The pathophysiological changes in AD patients begin decades before the onset of dementia, highlighting the urgent need for the development of early diagnostic methods. Compelling data demonstrate that increased levels of amyloid-beta compromise multiple cellular pathways; thus, the investigation of changes in various cellular networks is essential to advance our understanding of early disease mechanisms and to identify novel therapeutic targets. We applied a liquid chromatography/mass spectrometry-based non-targeted metabolomics approach to determine global metabolic changes in plasma and cerebrospinal fluid (CSF from the same individuals with different AD severity. Metabolic profiling detected a total of significantly altered 342 plasma and 351 CSF metabolites, of which 22% were identified. Based on the changes of >150 metabolites, we found 23 altered canonical pathways in plasma and 20 in CSF in mild cognitive impairment (MCI vs. cognitively normal (CN individuals with a false discovery rate <0.05. The number of affected pathways increased with disease severity in both fluids. Lysine metabolism in plasma and the Krebs cycle in CSF were significantly affected in MCI vs. CN. Cholesterol and sphingolipids transport was altered in both CSF and plasma of AD vs. CN. Other 30 canonical pathways significantly disturbed in MCI and AD patients included energy metabolism, Krebs cycle, mitochondrial function, neurotransmitter and amino acid metabolism, and lipid biosynthesis. Pathways in plasma that discriminated between all groups included polyamine, lysine, tryptophan metabolism, and aminoacyl-tRNA biosynthesis; and in CSF involved cortisone and prostaglandin 2 biosynthesis and metabolism. Our data suggest metabolomics could advance our understanding of the early disease mechanisms shared in progression from CN to

Toxicological effects of cinnabar in rats by NMR-based metabolic profiling of urine and serum

International Nuclear Information System (INIS)

Wei Lai; Liao Peiqiu; Wu Huifeng; Li Xiaojing; Pei Fengkui; Li Weisheng; Wu Yijie

2008-01-01

Cinnabar, an important traditional Chinese mineral medicine, has been widely used as a Chinese patent medicine ingredient for sedative therapy. However, the pharmaceutical and toxicological effects of cinnabar, especially in the whole organism, were subjected to few investigations. In this study, an NMR-based metabolomics approach has been applied to investigate the toxicological effects of cinnabar after intragastrical administration (dosed at 0.5, 2 and 5 g/kg body weight) on male Wistar rats. Liver and kidney histopathology examinations and serum clinical chemistry analyses were also performed. The 1 H NMR spectra were analyzed using multivariate pattern recognition techniques to show the time- and dose-dependent biochemical variations induced by cinnabar. The metabolic signature of urinalysis from cinnabar-treated animals exhibited an increase in the levels of creatinine, acetate, acetoacetate, taurine, hippurate and phenylacetylglycine, together with a decrease in the levels of trimethyl-N-oxide, dimethylglycine and Kreb's cycle intermediates (citrate, 2-oxoglutarate and succinate). The metabolomics analyses of serum showed elevated concentrations of ketone bodies (3-D-hydroxybutyrate and acetoacetate), branched-chain amino acids (valine, leucine and isoleucine), choline and creatine as well as decreased glucose, lipids and lipoproteins from cinnabar-treated animals. These findings indicated cinnabar induced disturbance in energy metabolism, amino acid metabolism and gut microflora environment as well as slight injury in liver and kidney, which might indirectly result from cinnabar induced oxidative stress. This work illustrated the high reliability of NMR-based metabolomic approach on the study of the biochemical effects induced by traditional Chinese medicine

REPEATED ACUTE STRESS INDUCED ALTERATIONS IN CARBOHYDRATE METABOLISM IN RAT

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Nirupama R.

2010-09-01

Full Text Available Acute stress induced alterations in the activity levels of rate limiting enzymes and concentration of intermediates of different pathways of carbohydrate metabolism have been studied. Adult male Wistar rats were restrained (RS for 1 h and after an interval of 4 h they were subjected to forced swimming (FS exercise and appropriate controls were maintained. Five rats were killed before the commencement of the experiment (initial controls, 5 control and equal number of stressed rats were killed 2 h after RS and remaining 5 rats in each group were killed 4 h after FS. There was a significant increase in the adrenal 3β- hydroxy steroid dehydrogenase activity following RS, which showed further increase after FS compared to controls and thereby indicated stress response of rats. There was a significant increase in the blood glucose levels following RS which showed further increase and reached hyperglycemic condition after FS. The hyperglycemic condition due to stress was accompanied by significant increases in the activities of glutamate- pyruvate transaminase, glutamate- oxaloacetate transaminase, glucose -6- phosphatase and lactate dehydrogenase and significant decrease in the glucose -6- phosphate dehydrogenase and pyruvate dehydrogenase activities, whereas pyruvate kinase activity did not show any alteration compared to controls. Further, the glycogen and total protein contents of the liver were decreased whereas those of pyruvate and lactate showed significant increase compared to controls after RS as well as FS.The results put together indicate that acute stress induced hyperglycemia results due to increased gluconeogenesis and glycogenolysis without alteration in glycolysis. The study first time reveals that after first acute stress exposure, the subsequent stressful experience augments metabolic stress response leading to hyperglycemia. The results have relevance to human health as human beings are exposed to several stressors in a day and

Alteration of tricarboxylic acid cycle metabolism in rat brain slices by halothane

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Cheng, S.C.; Brunner, E.A.

1978-01-01

Metabolism of [2- 14 C] pyruvate, [1- 14 C] acetate and [5- 14 C] citrate in rat cerebral cortex slices was studied in the presence of halothane. Metabolites assayed include acetylcholine (ACh), citrate, glutamate, glutamineγ-aminobutyrate (GABA) and aspartate. The trichloroacetic acid soluble extract, the trichloracetic acid insoluble precipitate and its lipid extract were also studied. In control experiments, pyruvate preferentially labelled ACh, citrate, glutamate, GABA and aspartate. Acetate labelled ACh, but to a lesser extent than pyruvate. Acetate also labelled lipids and glutamine. Citrate labelled lipids but not ACh and served as a preferential precursor for glutamine. These data support a three-compartment model for cerebral tricarboxylic acid cycle metabolism. Halothane caused increases in GABA and aspartate contents and a decrease in ACh content. It has no effect on the contents of citrate, glutamate and glutamine. Halothane preferentially inhibited the metabolic transfer of radioactivity from pyruvate into almost all metabolites, an effect probably not related to pyruvate permeability. This is interpreted as halothane depression of the large metabolic compartment which includes the nerve endings. Halothane increased the metabolic transfer of radioactivity from acetate into lipids but did not alter such a transfer into the trichloroacetic acid extract. Halothane increased the metabolic transfer of radioactivity from citrate into the trichloroacetic acid precipitate, lipids and especially glutamine. Transfer of citrate radioactivity into GABA was somewhat decreased. The differential effects of halothane on acetate and citrate utilization suggest that the small metabolic compartment should be subdivided. Therefore, at least three metabolic compartments are demonstrated. Halothane did not interfere with the dicarboxylic acid portion of the tricarboxylic acid cycle. (author)

Changes in serum markers of iron metabolism and their clinical significance in patients with nonalcoholic fatty liver disease

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OU Qiang

2016-12-01

Full Text Available ObjectiveTo investigate the changes in the serum markers of iron metabolism and their clinical significance in patients with nonalcoholic fatty liver disease (NAFLD. MethodsA total of 68 NAFLD patients who were admitted to The Eighth People′s Hospital of Shanghai from July 2014 to April 2016 were enrolled as NAFLD group, and 70 healthy persons who underwent physical examination were enrolled as healthy control group. Among the 68 patients in the NAFLD group, 24 had NAFLD alone and 44 were complicated by abnormal alanine aminotransferase (ALT level. The levels of aspartate aminotransferase (AST, ALT, total cholesterol (TC, triglyceride (TG, and serum markers of iron metabolism ［serum iron (SI, serum ferritin (SF, and serum hepcidin (HEPC］ were measured for all patients, and the correlations between abnormal ALT level and serum markers of iron metabolism were analyzed. The independent samples t-test was used for comparison of continuous data between groups, the chi-square test was used for comparison of categorical data between groups, and the Pearson correlation coefficient was used to investigate the correlation between two variables. ResultsThe NAFLD group had significantly higher body mass index and serum levels of ALT, AST, TC, and TG than the healthy control group (t=9.8, 8.6, 8.5, 9.2, and 2.7, all P＜0.05. Compared with the healthy control group, the NAFLD group had significantly higher levels of SI (21.7±7.1 μmol/L vs 187±6.9 μmol/L, t=2.3, P=0.02 and SF (340.2±257.6 μg/L vs 119.1±81.2 μg/L, t=6.7, P＜0.01 and a significantly lower level of HEPC (12.2±5.3 μg/L vs 22.2±6.5 μg/L, t=9.9, P＜0.01. Compared with those with NAFLD alone, the patients complicated by abnormal ALT level had significantly higher serum levels of ALT (89±58 U/L vs 26±8 U/L, t=7.1, P＜0.01, SI (23.4±6.2 μmol/L vs 19.6±7.9 μmol/L, t=2.2, P=0.03, and SF (406.2±290.0 μg/L vs 219.4±112.0 μg/L, t=3.7, P＜0.01, as well as a significantly

Inhaled ozone (O{sub 3})-induces changes in serum metabolomic and liver transcriptomic profiles in rats

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Miller, Desinia B. [Curriculum in Toxicology, University of North Carolina-Chapel Hill, Chapel Hill, NC (United States); Karoly, Edward D.; Jones, Jan C. [Metabolon Incorporation, Durham, NC (United States); Ward, William O.; Vallanat, Beena D.; Andrews, Debora L. [Research Cores Unit, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Schladweiler, Mette C.; Snow, Samantha J. [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Bass, Virginia L. [Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC (United States); Richards, Judy E.; Ghio, Andrew J.; Cascio, Wayne E.; Ledbetter, Allen D. [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Kodavanti, Urmila P., E-mail: kodavanti.urmila@epa.gov [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States)

2015-07-15

Air pollution has been linked to increased incidence of diabetes. Recently, we showed that ozone (O{sub 3}) induces glucose intolerance, and increases serum leptin and epinephrine in Brown Norway rats. In this study, we hypothesized that O{sub 3} exposure will cause systemic changes in metabolic homeostasis and that serum metabolomic and liver transcriptomic profiling will provide mechanistic insights. In the first experiment, male Wistar Kyoto (WKY) rats were exposed to filtered air (FA) or O{sub 3} at 0.25, 0.50, or 1.0 ppm, 6 h/day for two days to establish concentration-related effects on glucose tolerance and lung injury. In a second experiment, rats were exposed to FA or 1.0 ppm O{sub 3}, 6 h/day for either one or two consecutive days, and systemic metabolic responses were determined immediately after or 18 h post-exposure. O{sub 3} increased serum glucose and leptin on day 1. Glucose intolerance persisted through two days of exposure but reversed 18 h-post second exposure. O{sub 3} increased circulating metabolites of glycolysis, long-chain free fatty acids, branched-chain amino acids and cholesterol, while 1,5-anhydroglucitol, bile acids and metabolites of TCA cycle were decreased, indicating impaired glycemic control, proteolysis and lipolysis. Liver gene expression increased for markers of glycolysis, TCA cycle and gluconeogenesis, and decreased for markers of steroid and fat biosynthesis. Genes involved in apoptosis and mitochondrial function were also impacted by O{sub 3}. In conclusion, short-term O{sub 3} exposure induces global metabolic derangement involving glucose, lipid, and amino acid metabolism, typical of a stress–response. It remains to be examined if these alterations contribute to insulin resistance upon chronic exposure. - Highlights: • Ozone, an ubiquitous air pollutant induces acute systemic metabolic derangement. • Serum metabolomic approach provides novel insights in ozone-induced changes. • Ozone exposure induces leptinemia

Sleep apnea predicts distinct alterations in glucose homeostasis and biomarkers in obese adults with normal and impaired glucose metabolism

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Hill Nathan R

2010-12-01

Full Text Available Abstract Background Notwithstanding previous studies supporting independent associations between obstructive sleep apnea (OSA and prevalence of diabetes, the underlying pathogenesis of impaired glucose regulation in OSA remains unclear. We explored mechanisms linking OSA with prediabetes/diabetes and associated biomarker profiles. We hypothesized that OSA is associated with distinct alterations in glucose homeostasis and biomarker profiles in subjects with normal (NGM and impaired glucose metabolism (IGM. Methods Forty-five severely obese adults (36 women without certain comorbidities/medications underwent anthropometric measurements, polysomnography, and blood tests. We measured fasting serum glucose, insulin, selected cytokines, and calculated homeostasis model assessment estimates of insulin sensitivity (HOMA-IS and pancreatic beta-cell function (HOMA-B. Results Both increases in apnea-hypopnea index (AHI and the presence of prediabetes/diabetes were associated with reductions in HOMA-IS in the entire cohort even after adjustment for sex, race, age, and BMI (P = 0.003. In subjects with NGM (n = 30, OSA severity was associated with significantly increased HOMA-B (a trend towards decreased HOMA-IS independent of sex and adiposity. OSA-related oxyhemoglobin desaturations correlated with TNF-α (r=-0.76; P = 0.001 in women with NGM and with IL-6 (rho=-0.55; P = 0.035 in women with IGM (n = 15 matched individually for age, adiposity, and AHI. Conclusions OSA is independently associated with altered glucose homeostasis and increased basal beta-cell function in severely obese adults with NGM. The findings suggest that moderate to severe OSA imposes an excessive functional demand on pancreatic beta-cells, which may lead to their exhaustion and impaired secretory capacity over time. The two distinct biomarker profiles linking sleep apnea with NGM and IGM via TNF-α and IL-6 have been discerned in our study to suggest that sleep apnea and particularly

Deficiency of the GPR39 receptor is associated with obesity and altered adipocyte metabolism

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Petersen, Pia Steen; Jin, Chunyu; Madsen, Andreas Nygaard

2011-01-01

, conceivably due to decreased energy expenditure and adipocyte lipolytic activity.-Petersen, P. S., Jin, C., Madsen, A. N., Rasmussen, M., Kuhre, R., L. Egerod, K. L., Nielsen, L. B., Schwartz. T. W., Holst, B. Deficiency of the GPR39 receptor is associated with obesity and altered adipocyte metabolism....

Obesity and Hepatic Steatosis Are Associated with Elevated Serum Amyloid Beta in Metabolically Stressed APPswe/PS1dE9 Mice.

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Feng-Shiun Shie

Full Text Available Diabesity-associated metabolic stresses modulate the development of Alzheimer's disease (AD. For further insights into the underlying mechanisms, we examine whether the genetic background of APPswe/PS1dE9 at the prodromal stage of AD affects peripheral metabolism in the context of diabesity. We characterized APPswe/PS1dE9 transgenic mice treated with a combination of high-fat diet with streptozotocin (HFSTZ in the early stage of AD. HFSTZ-treated APPswe/PS1dE9 transgenic mice exhibited worse metabolic stresses related to diabesity, while serum β-amyloid levels were elevated and hepatic steatosis became apparent. Importantly, two-way analysis of variance shows a significant interaction between HFSTZ and genetic background of AD, indicating that APPswe/PS1dE9 transgenic mice are more vulnerable to HFSTZ treatment. In addition, body weight gain, high hepatic triglyceride, and hyperglycemia were positively associated with serum β-amyloid, as validated by Pearson's correlation analysis. Our data suggests that the interplay between genetic background of AD and HFSTZ-induced metabolic stresses contributes to the development of obesity and hepatic steatosis. Alleviating metabolic stresses including dysglycemia, obesity, and hepatic steatosis could be critical to prevent peripheral β-amyloid accumulation at the early stage of AD.

Serum metabolomics of slow vs. rapid motor progression Parkinson's disease: a pilot study.

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James R Roede

Full Text Available Progression of Parkinson's disease (PD is highly variable, indicating that differences between slow and rapid progression forms could provide valuable information for improved early detection and management. Unfortunately, this represents a complex problem due to the heterogeneous nature of humans in regards to demographic characteristics, genetics, diet, environmental exposures and health behaviors. In this pilot study, we employed high resolution mass spectrometry-based metabolic profiling to investigate the metabolic signatures of slow versus rapidly progressing PD present in human serum. Archival serum samples from PD patients obtained within 3 years of disease onset were analyzed via dual chromatography-high resolution mass spectrometry, with data extraction by xMSanalyzer and used to predict rapid or slow motor progression of these patients during follow-up. Statistical analyses, such as false discovery rate analysis and partial least squares discriminant analysis, yielded a list of statistically significant metabolic features and further investigation revealed potential biomarkers. In particular, N8-acetyl spermidine was found to be significantly elevated in the rapid progressors compared to both control subjects and slow progressors. Our exploratory data indicate that a fast motor progression disease phenotype can be distinguished early in disease using high resolution mass spectrometry-based metabolic profiling and that altered polyamine metabolism may be a predictive marker of rapidly progressing PD.

Metabolic development of the porcine placenta in response to alterations in maternal or fetal homeostasis

International Nuclear Information System (INIS)

Namsey, T.G.; kasser, T.R.; Hausman, G.J.; Martin, R.J.

1986-01-01

Porcine placenta has been utilized as a model for elucidating contributions of both fetal and maternal tissues to metabolic activity of the placenta in response to a variety of stresses. Alloxan diabetes, food restriction and genetic obesity all produced alterations in placental metablolism with differences in responses of fetal and maternal placentas. Further analysis of nutrient untilization by the placenta produced dramatic differences in the partitioning of substrates by fetal and maternal tissues during placental development. Metabolic activity of maternal tissue contributed to overall placental metabolic activity to a greater degree than fetal tissue. However, experiments with in utero fetal decapitation indicated that some of differences between fetal and maternal placental metabolic activity may be due to the influence of fetal regulatory mechanisms. Maternal endometrium plays a critical role in metabolic response of uteroplacenta and thus availability of nutrients to the fetus and fetal placenta. Differences in metabolic development of fetal and maternal tissues suggested that regulation of placental metabolism may originate from fetal as well as maternal sources

Serum biochemical responses under oxidative stress of aspartame in wistar albino rats

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Arbind Kumar Choudhary

2014-02-01

Full Text Available Objective: To study whether the oral administration of aspartame (40 mg/kg body weight for 15 d, 30 d and 90 d have any effect on marker enzymes, some selective liver and kidney function parameter, lipid peroxidation and antioxidant status in serum. To mimic human methanol metabolism, folate deficient animals were used. Method: Animal weight, complete hemogram, marker enzyme in serum, some selected serum profile reflect liver and kidney function, plasma corticosterone level, and in serum, lipid peroxidation, nitric oxide, enzymatic and non-enzymatic antioxidant level was measured . Result: After 15 d of aspartame administration animals showed a significant change in marker enzymes, and antioxidant level. However, after repeated long term administration (30 d and 90 d showed a significant change in some selected serum profile reflects liver and kidney function, along with marker enzymes, and antioxidant level. Conclusions: This study concludes that oral administration of aspartame (40 mg/kg body weight causes oxidative stress in Wistar albino rats by altering their oxidant/antioxidant balance.

Altered Methylation Profile of Lymphocytes Is Concordant with Perturbation of Lipids Metabolism and Inflammatory Response in Obesity

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Mette J. Jacobsen

2016-01-01

Full Text Available Obesity is associated with immunological perturbations that contribute to insulin resistance. Epigenetic mechanisms can control immune functions and have been linked to metabolic complications, although their contribution to insulin resistance still remains unclear. In this study, we investigated the link between metabolic dysfunction and immune alterations with the epigenetic signature in leukocytes in a porcine model of obesity. Global DNA methylation of circulating leukocytes, adipose tissue leukocyte trafficking, and macrophage polarisation were established by flow cytometry. Adipose tissue inflammation and metabolic function were further characterised by quantification of metabolites and expression levels of genes associated with obesity and inflammation. Here we show that obese pigs showed bigger visceral fat pads, higher levels of circulating LDL cholesterol, and impaired glucose tolerance. These changes coincided with impaired metabolism, sustained macrophages infiltration, and increased inflammation in the adipose tissue. Those immune alterations were linked to global DNA hypermethylation in both B-cells and T-cells. Our results provide novel insight into the possible contribution of immune cell epigenetics into the immunological disturbances observed in obesity. The dramatic changes in the transcriptomic and epigenetic signature of circulating lymphocytes reinforce the concept that epigenetic processes participate in the increased immune cell activation and impaired metabolic functions in obesity.

Metabolic and clinical effects of Ramadan fasting in patients with type II diabetes

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Yarahmadi, S.; Larijani, B.; Bastanhagh, M.H.; Pajouhi, M.; Bardar, J. R.; Zahedi, F.; Zendehdel, K.; Akrami, S.M.

2003-01-01

Objective: To evaluate the effects of fasting on anthropometric indices and carbohydrate and lipid metabolism in patients with type II diabetes. Results: Daily cholesterol intake increased in all subjects (p 0.01). Blood pressure, fasting blood glucose and serum fructosamine did not change during the study. Plasma insulin (p < 0.05), C-peptide (p < 0.01) and insulin resistance (p < 0.01) decreased only in men. Total and LDL cholesterol increased significantly in all subjects during the study. Conclusion: Ramadan fasting does not alter carbohydrate metabolism or tissue insulin sensitivity in patients with type II diabetes given appropriate dietary education and rescheduling of oral hypoglycaemic medication. Lipid profile is unfavorably altered due to changes in both diet and biochemical response to starvation. (author)

Antibiotic-Induced Changes to the Host Metabolic Environment Inhibit Drug Efficacy and Alter Immune Function

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Yang, Jason H.; Bhargava, Prerna; McCloskey, Douglas

2017-01-01

Bactericidal antibiotics alter microbial metabolism as part of their lethality and can damage mitochondria in mammalian cells. In addition, antibiotic susceptibility is sensitive to extracellular metabolites, but it remains unknown whether metabolites present at an infection site can affect eithe...

Altered Levels of Serum Zinc and Cadmium in Patients with Chronic Vesiculobullous Hand and Feet Dermatitis

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Swastika Suvirya

2016-01-01

Full Text Available Micronutrients serve many important functions in our body and altered levels of heavy and trace metals are associated with cutaneous and systemic disorders. Vesicular palmoplantar eczema is an entity whose etiopathogenesis is a mystery. In this prospective case-noncase study blood levels of Zinc and Cadmium in 37 patients of chronic vesiculobullous hand dermatitis were estimated and compared with 40 noncases with similar age and gender distributions. Low serum Zinc levels were found in patients as compared to noncases. The mean difference of serum Zinc between the case and noncase groups was 27.26; the mean value of serum Zinc between the two groups was statistically significant (p<0.0001. However, elevated Cadmium levels were detected in only 5 patients and in none of the noncases. The mean concentration of serum Cadmium was 2.32±0.38 μg/dL, with a range of 1.90–2.80 μg/dL for the five cases in whom Cadmium was detected. Various toxic and trace metals can interact by influencing each other’s absorption, retention, distribution, and bioavailability in the body. The clinical significance of this finding lies in the possible beneficial role of Zinc supplementation in the therapy of chronic vesiculobullous hand dermatitis.

Radiopharmaceuticals for Assessment of Altered Metabolism and Biometal Fluxes in Brain Aging and Alzheimer's Disease with Positron Emission Tomography.

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Xie, Fang; Peng, Fangyu

2017-01-01

Aging is a risk factor for Alzheimer's disease (AD). There are changes of brain metabolism and biometal fluxes due to brain aging, which may play a role in pathogenesis of AD. Positron emission tomography (PET) is a versatile tool for tracking alteration of metabolism and biometal fluxes due to brain aging and AD. Age-dependent changes in cerebral glucose metabolism can be tracked with PET using 2-deoxy-2-[18F]-fluoro-D-glucose (18F-FDG), a radiolabeled glucose analogue, as a radiotracer. Based on different patterns of altered cerebral glucose metabolism, 18F-FDG PET was clinically used for differential diagnosis of AD and Frontotemporal dementia (FTD). There are continued efforts to develop additional radiopharmaceuticals or radiotracers for assessment of age-dependent changes of various metabolic pathways and biometal fluxes due to brain aging and AD with PET. Elucidation of age-dependent changes of brain metabolism and altered biometal fluxes is not only significant for a better mechanistic understanding of brain aging and the pathophysiology of AD, but also significant for identification of new targets for the prevention, early diagnosis, and treatment of AD.

Decreased serum protein associated with Mycobacterium avium subspecies paratuberculosis shedding in German Holstein cows.

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Donat, K; Erhardt, G; Soschinka, A; Brandt, H R

2014-04-19

Using well established metabolic parameters, this study aimed to substantiate differences in protein and energy metabolism between Mycobacterium avium subspecies paratuberculosis (MAP) positive and negative dairy cows tested by faecal culture. A total of 227 MAP-positive and 239 MAP-negative German Holstein cows kept in 13 MAP-positive dairy herds were selected for metabolic testing. The serum concentrations of total protein (TP), bilirubin, cholesterol and betahydroxybutyrate were measured as well as the activities of Glutamate-Dehydrogenase (GLDH) and Aspartate-Aminotransferase. MAP-positive cows were characterised by a decreased mean TP (66.5 g/l) compared to the MAP-negative controls (73.2 g/l). Mean log10 GLDH activities tended to be higher in MAP-positive than MAP-negative cows. Concerning TP, there was a significant interaction between MAP status and farm. Within four farms, the difference between MAP-positive and MAP-negative animals differed significantly, while in the other farms this difference was not significant. It is concluded that a decreased TP and an increased GLDH indicate alterations in protein metabolism. These findings suggest an enhanced liver cell turnover in MAP-positive cows. The results contribute to an understanding of the metabolic alterations in MAP-positive dairy cows.

Alterations of Innate Immunity Reactants in Transition Dairy Cows before Clinical Signs of Lameness

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Zhang, Guanshi; Hailemariam, Dagnachew; Dervishi, Elda; Deng, Qilan; Goldansaz, Seyed A.; Dunn, Suzanna M.; Ametaj, Burim N.

2015-01-01

Simple Summary Lameness is prevalent in dairy cows and early diagnosis and timely treatment of the disease can lower animal suffering, improve recovery rate, increase longevity, and minimize cow loss. However, there are no indications of disease until it appears clinically, and presently the only approach to deal with the sick cow is intensive treatment or culling. The results suggest that lameness affected serum concentrations of the several parameters related to innate immunity and carbohydrate metabolism that might be used to monitor health status of transition dairy cows in the near future. Abstract The objectives of this study were to evaluate metabolic and innate immunity alterations in the blood of transition dairy cows before, during, and after diagnosis of lameness during periparturient period. Blood samples were collected from the coccygeal vain once per week before morning feeding from 100 multiparous Holstein dairy cows during −8, −4, disease diagnosis, and +4 weeks (wks) relative to parturition. Six healthy cows (CON) and six cows that showed clinical signs of lameness were selected for intensive serum analyses. Concentrations of interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor (TNF), haptoglobin (Hp), serum amyloid A (SAA), lipopolysaccharide binding protein (LBP), lactate, non-esterified fatty acids (NEFA), and β-hydroxybutyrate (BHBA) were measured in serum by ELISA or colorimetric methods. Health status, DMI, rectal temperature, milk yield, and milk composition also were monitored for each cow during the whole experimental period. Results showed that cows affected by lameness had greater concentrations of lactate, IL-6, and SAA in the serum vs. CON cows. Concentrations of TNF tended to be greater in cows with lameness compared with CON. In addition, there was a health status (Hs) by time (week) interaction for IL-1, TNF, and Hp in lameness cows vs. CON ones. Enhanced serum concentrations of lactate, IL-6, and SAA at −8 and �

Pulmonary Ozone Exposure Alters Essential Metabolic Pathways involved in Glucose Homeostasis in the Liver

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Pulmonary Ozone Exposure Alters Essential Metabolic Pathways involved in Glucose Homeostasis in the Liver D.B. Johnson, 1 W.O. Ward, 2 V.L. Bass, 2 M.C.J. Schladweiler, 2A.D. Ledbetter, 2 D. Andrews, and U.P. Kodavanti 2 1 Curriculum in Toxicology, UNC School of Medicine, Cha...

Relationship between serum anti-Mullerian hormone with vitamin D and metabolic syndrome risk factors in late reproductive-age women.

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Kim, Sunmie; Kim, Jin Ju; Kim, Min-Jeong; Han, Kyung Hee; Lee, Jung Ryeol; Suh, Chang Suk; Choi, Young Min; Kim, Seok Hyun

2018-04-01

The relationship between serum anti-Mullerian hormone (AMH) with vitamin D (25OH-D) and metabolic syndrome (MetS) risk was evaluated in healthy, late reproductive-age (35-49 years) women with regular menstrual cycles. Among the 291 participants (mean age = 42.5 years), most (76.6%, n = 223) were serum vitamin D insufficient (D were 2.04 ng/mL and 15.9 ng/mL, respectively. There was no correlation between AMH and 25OH-D after adjustment for age (r = -0.093, p = 0.113). Subjects with higher MetS score, higher waist circumference, and higher diastolic blood pressure had significantly higher serum AMH levels when adjusted for age, but the association attenuated when BMI was included. There was no significant correlation between MetS risk components with serum level of AMH or vitamin D. In conclusion, there was no association between AMH with serum 25OH-D or MetS risk factors in this population.

Metabolic alterations in dialysis patients

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Drechsler, Christiane

2010-01-01

Assessing metabolic risk in dialysis patients, three main aspects are important: a) the pathophysiologic effects of metabolic disturbances as known from the general population are unlikely to completely reverse once patients reach dialysis. b) Specific additional problems related to chronic kidney

Incremental Predictive Value of Serum AST-to-ALT Ratio for Incident Metabolic Syndrome: The ARIRANG Study

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Ahn, Song Vogue; Baik, Soon Koo; Cho, Youn zoo; Koh, Sang Baek; Huh, Ji Hye; Chang, Yoosoo; Sung, Ki-Chul; Kim, Jang Young

2016-01-01

Aims The ratio of aspartate aminotransferase (AST) to alanine aminotransferase (ALT) is of great interest as a possible novel marker of metabolic syndrome. However, longitudinal studies emphasizing the incremental predictive value of the AST-to-ALT ratio in diagnosing individuals at higher risk of developing metabolic syndrome are very scarce. Therefore, our study aimed to evaluate the AST-to-ALT ratio as an incremental predictor of new onset metabolic syndrome in a population-based cohort study. Material and Methods The population-based cohort study included 2276 adults (903 men and 1373 women) aged 40–70 years, who participated from 2005–2008 (baseline) without metabolic syndrome and were followed up from 2008–2011. Metabolic syndrome was defined according to the harmonized definition of metabolic syndrome. Serum concentrations of AST and ALT were determined by enzymatic methods. Results During an average follow-up period of 2.6-years, 395 individuals (17.4%) developed metabolic syndrome. In a multivariable adjusted model, the odds ratio (95% confidence interval) for new onset of metabolic syndrome, comparing the fourth quartile to the first quartile of the AST-to-ALT ratio, was 0.598 (0.422–0.853). The AST-to-ALT ratio also improved the area under the receiver operating characteristic curve (AUC) for predicting new cases of metabolic syndrome (0.715 vs. 0.732, P = 0.004). The net reclassification improvement of prediction models including the AST-to-ALT ratio was 0.23 (95% CI: 0.124–0.337, Pmetabolic syndrome and had incremental predictive value for incident metabolic syndrome. PMID:27560931

The Impact of Diabetes on Serum Osteocalcin in Egyptian Children

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Salem, E.S.; El-Maghraby, D.F.; Saeed, A.E.

2013-01-01

Diabetes may affect bone via bone structure, bone density, and biochemical markers of bone turnover. Lack of diagnosis and treatment of alterations of the bone tissue metabolism in type1diabetes (T1D) may lead to osteoporosis.T1D most often starts before achieving peak bone mass.Recent studies have revealed that, in T1D fracture risk is increased more than expected from the degree of decrease in bone mineral density (BMD).Osteocalcin (OC) is considered a useful biochemical marker of bone formation. As in T1D, there is absolute insulin deficiency but insulin sensitivity remains generally intact. Therefore, this study was conducted to evaluate the association between OC levels in relation the degree of residual β-cell function and other metabolic parameters in T1D In the present study, the impact of diabetes on serum OC in Egyptian children and adolescents was evaluated by comparing serum level of OC in T1D (30 subjects) and age-matched non-diabetic control (15 subjects). The present study showed that, patients with T1D had lower OC serum levels compared to the controls (7.67 ± 3.55, 21.82 ± 4.96 μg/ml respectively, p < 0.001) with a lower OC levels in diabetic females than in diabetic males (5.92 ± 3.12, 8.74 ± 2.84 μg/ml respectively, p < 0.001) and lower OC levels in pre-pubertal than pubertal diabetic patients in both genders with p < 0.05. Serum OC levels in T1D correlated with HbAIc (p < 0.001), BMI (p < 0.05), durations of T1D (p < 0.05) and total daily insulin dose (p < 0.05)and did not correlate with C-peptide levels . It may be concluded that serum OC levels in patients with T1D are regulated by a variety of developmental and metabolic pathways. Since OC levels correlated with exogenous insulin(daily insulin dose) and did not correlate with endogenous insulin (C-peptide levels), therefore, it is presumed that OC was regulated by insulin-mediated events, in presence of aggressive autoimmune destruction of pancreatic cell. These results proposed that

Altered phospholipid metabolism in schizophrenia: a phosphorus 31 nuclear magnetic resonance spectroscopy study.

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Weber-Fahr, Wolfgang; Englisch, Susanne; Esser, Andrea; Tunc-Skarka, Nuran; Meyer-Lindenberg, Andreas; Ende, Gabriele; Zink, Mathias

2013-12-30

Phospholipid (PL) metabolism is investigated by in vivo 31P magnetic resonance spectroscopy (MRS). Inconsistent alterations of phosphocholine (PC), phosphoethanolamine (PE), glycerophosphocholine (GPC) and glycerophosphoethanolamine (GPE) have been described in schizophrenia, which might be overcome by specific editing techniques. The selective refocused insensitive nuclei-enhanced polarization transfer (RINEPT) technique was applied in a cross-sectional study involving 11 schizophrenia spectrum disorder patients (SZP) on stable antipsychotic monotherapy and 15 matched control subjects. Metabolite signals were found to be modulated by cerebrospinal fluid (CSF) content and gray matter/brain matter ratio. Corrected metabolite concentrations of PC, GPC and PE differed between patients and controls in both subcortical and cortical regions, whereas antipsychotic medication exerted only small effects. Significant correlations were found between the severity of clinical symptoms and the assessed signals. In particular, psychotic symptoms correlated with PC levels in the cerebral cortex, depression with PC levels in the cerebellum and executive functioning with GPC in the insular and temporal cortices. In conclusion, after controlling for age and tissue composition, this investigation revealed alterations of metabolite levels in SZP and correlations with clinical properties. RINEPT 31P MRS should also be applied to at-risk-mental-state patients as well as drug-naïve and chronically treated schizophrenic patients in order to enhance the understanding of longitudinal alterations of PL metabolism in schizophrenia. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Membrane lipid alterations in the metabolic syndrome and the role of dietary oils.

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Perona, Javier S

2017-09-01

The metabolic syndrome is a cluster of pathological conditions, including hypertension, hyperglycemia, hypertriglyceridemia, obesity and low HDL levels that is of great concern worldwide, as individuals with metabolic syndrome have an increased risk of type-2 diabetes and cardiovascular disease. Insulin resistance, the key feature of the metabolic syndrome, might be at the same time cause and consequence of impaired lipid composition in plasma membranes of insulin-sensitive tissues like liver, muscle and adipose tissue. Diet intervention has been proposed as a powerful tool to prevent the development of the metabolic syndrome, since healthy diets have been shown to have a protective role against the components of the metabolic syndrome. Particularly, dietary fatty acids are capable of modulating the deleterious effects of these conditions, among other mechanisms, by modifications of the lipid composition of the membranes in insulin-sensitive tissues. However, there is still scarce data based of high-level evidence on the effects of dietary oils on the effects of the metabolic syndrome and its components. This review summarizes the current knowledge on the effects of dietary oils on improving alterations of the components of the metabolic syndrome. It also examines their influence in the modulation of plasma membrane lipid composition and in the functionality of membrane proteins involved in insulin activity, like the insulin receptor, GLUT-4, CD36/FAT and ABCA-1, and their effect in the metabolism of glucose, fatty acids and cholesterol, and, in turn, the key features of the metabolic syndrome. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá. Copyright © 2017 Elsevier B.V. All rights reserved.

Alterations in Hepatic FGF21, Co-Regulated Genes, and Upstream Metabolic Genes in Response to Nutrition, Ketosis and Inflammation in Peripartal Holstein Cows.

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Haji Akbar

Full Text Available In rodents, fibroblast growth factor 21 (FGF21 has emerged as a key metabolic regulator produced by liver. To gather preliminary data on the potential importance of FGF1, co-regulated genes, and upstream metabolic genes, we examined the hepatic mRNA expression in response to nutrition and inflammation in dairy cows. In experiment 1, induction of ketosis through feed restriction on d 5 postpartum upregulated FGF21, its co-receptor KLB, and PPARA but only elicited a numerical increase in serum FGF21 concentration. In experiment 2, cows in control (CON or receiving 50 g/d of L-carnitine (C50 from -14 through 21 d had increased FGF21, PPARA, and NFIL3 on d 10 compared with d 2 postpartum. In contrast, compared with CON and C50, 100 g/d L-carnitine (C100 resulted in lower FGF21, KLB, ANGPTL4, and ARNTL expression on d 10. In experiment 3, cows were fed during the dry period either a higher-energy (OVE; 1.62 Mcal/kg DM or lower-energy (CON; 1.34 Mcal/kg DM diet and received 0 (OVE:N, CON:N or 200 μg of LPS (OVE:Y, CON:Y into the mammary gland at d 7 postpartum. For FGF21 mRNA expression in CON, the LPS challenge (CON:Y prevented a decrease in expression between d 7 and 14 postpartum such that cows in CON:N had a 4-fold lower expression on d 14 compared with d 7. The inflammatory stimulus induced by LPS in CON:Y resulted in upregulation of PPARA on d 14 to a similar level as cows in OVE:N. In OVE:Y, expression of PPARA was lower than CON:N on d 7 and remained unchanged on d 14. On d 7, LPS led to a 4-fold greater serum FGF21 only in OVE but not in CON cows. In fact, OVE:Y reached the same serum FGF21 concentration as CON:N, suggesting a carryover effect of dietary energy level on signaling mechanisms within liver. Overall, results indicate that nutrition, ketosis, and inflammation during the peripartal period can alter hepatic FGF21, co-regulated genes, and upstream metabolic genes to various extents. The functional outcome of these changes merits

Alterations in Hepatic FGF21, Co-Regulated Genes, and Upstream Metabolic Genes in Response to Nutrition, Ketosis and Inflammation in Peripartal Holstein Cows.

Science.gov (United States)

Akbar, Haji; Batistel, Fernanda; Drackley, James K; Loor, Juan J

2015-01-01

In rodents, fibroblast growth factor 21 (FGF21) has emerged as a key metabolic regulator produced by liver. To gather preliminary data on the potential importance of FGF1, co-regulated genes, and upstream metabolic genes, we examined the hepatic mRNA expression in response to nutrition and inflammation in dairy cows. In experiment 1, induction of ketosis through feed restriction on d 5 postpartum upregulated FGF21, its co-receptor KLB, and PPARA but only elicited a numerical increase in serum FGF21 concentration. In experiment 2, cows in control (CON) or receiving 50 g/d of L-carnitine (C50) from -14 through 21 d had increased FGF21, PPARA, and NFIL3 on d 10 compared with d 2 postpartum. In contrast, compared with CON and C50, 100 g/d L-carnitine (C100) resulted in lower FGF21, KLB, ANGPTL4, and ARNTL expression on d 10. In experiment 3, cows were fed during the dry period either a higher-energy (OVE; 1.62 Mcal/kg DM) or lower-energy (CON; 1.34 Mcal/kg DM) diet and received 0 (OVE:N, CON:N) or 200 μg of LPS (OVE:Y, CON:Y) into the mammary gland at d 7 postpartum. For FGF21 mRNA expression in CON, the LPS challenge (CON:Y) prevented a decrease in expression between d 7 and 14 postpartum such that cows in CON:N had a 4-fold lower expression on d 14 compared with d 7. The inflammatory stimulus induced by LPS in CON:Y resulted in upregulation of PPARA on d 14 to a similar level as cows in OVE:N. In OVE:Y, expression of PPARA was lower than CON:N on d 7 and remained unchanged on d 14. On d 7, LPS led to a 4-fold greater serum FGF21 only in OVE but not in CON cows. In fact, OVE:Y reached the same serum FGF21 concentration as CON:N, suggesting a carryover effect of dietary energy level on signaling mechanisms within liver. Overall, results indicate that nutrition, ketosis, and inflammation during the peripartal period can alter hepatic FGF21, co-regulated genes, and upstream metabolic genes to various extents. The functional outcome of these changes merits further study

Aging and sarcopenia associate with specific interactions between gut microbes, serum biomarkers and host physiology in rats.

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Siddharth, Jay; Chakrabarti, Anirikh; Pannérec, Alice; Karaz, Sonia; Morin-Rivron, Delphine; Masoodi, Mojgan; Feige, Jerome N; Parkinson, Scott James

2017-07-17

The microbiome has been demonstrated to play an integral role in the maintenance of many aspects of health that are also associated with aging. In order to identify areas of potential exploration and intervention, we simultaneously characterized age-related alterations in gut microbiome, muscle physiology and serum proteomic and lipidomic profiles in aged rats to define an integrated signature of the aging phenotype. We demonstrate that aging skews the composition of the gut microbiome, in particular by altering the Sutterella to Barneseilla ratio, and alters the metabolic potential of intestinal bacteria. Age-related changes of the gut microbiome were associated with the physiological decline of musculoskeletal function, and with molecular markers of nutrient processing/availability, and inflammatory/immune status in aged versus adult rats. Altogether, our study highlights that aging leads to a complex interplay between the microbiome and host physiology, and provides candidate microbial species to target physical and metabolic decline during aging by modulating gut microbial ecology.

Hyperthyroidism alters excretion of dichloroethylene metabolites into serum and bile

International Nuclear Information System (INIS)

Kanz, M.F.; Moslen, M.T.

1990-01-01

Hepatotoxicity of 1,1-dichloroethylene (DCE) is enhanced in rats made hyperthyroid by excessive thryoxine (T 4 ). Our objective was to determine if the enhancement of DCE injury by T 4 was associated with alterations in the biologic fate of DCE, especially clearance of DCE metabolites into bile. Male SD rats (275 g) were injected with T 4 (40μg/100 g) 3 times at 48 hr intervals (hyperthyroid, HyperT) or sham injected (euthyroid, EuT). A 8 AM, all rats had jugular and biliary cannulas positioned under pentobarbital anesthesia. At 9:30 AM, all rats received 14 C-DCE (100 mg/kg) po in mineral oil. 14 C-DCE metabolite levels were measured serially in blood and bile for 4 hr and in liver at 4 hr. Major observations were: Rate of biliary excretion of 14 C by EuT was stable from 0.5 to 4 hr, while biliary 14 C in HyperT peaked at 1 hr at a level about 100% greater then EuT but then gradually declined by 4 hr to about 50% less than EuT. Serum 14 C was also stable from 2 to 4 hr in EuT, while serum 14 C in HyperT continued to rise and at 4 hr, was twice that of EuT. At 4 hr, HyperT had two times more 14 C covalently bound to total liver and liver mitochondria than EuT. Thus, enhancement of DCE injury by hyperthyroidism was associated with a temporal shift in DCE metabolite clearance from bile to blood and with more covalent binding of toxin to liver

Modulation of serum concentrations and hepatic metabolism of 17{beta}-estradiol and testosterone by amitraz in rats

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Chou, Chen-Ping [National Taiwan University, Institute of Toxicology, College of Medicine, Taipei (China); Taiwan Agricultural Chemicals and Toxic Substances Research Institute, Council of Agriculture, Taichung (China); Lu, Shui-Yuan [Taiwan Agricultural Chemicals and Toxic Substances Research Institute, Council of Agriculture, Taichung (China); Ueng, Tzuu-Huei [National Taiwan University, Institute of Toxicology, College of Medicine, Taipei (China)

2008-10-15

The present study has investigated the ability of amitraz, a widely used formamidine pesticide, to modulate serum concentrations and liver microsomal metabolism of 17{beta}-estradiol (E2) and testosterone in rats. Amitraz was administered intraperitoneally to male rats for 4 days and to intact female rats or ovariectomized (OVX) and 0.5 mg/kg E2-supplemented female rats for 7 days. E2 and metabolites were analyzed by gas chromatography-electron capture detection and testosterone and metabolites were analyzed by high-pressure liquid chromatography. In OVX and E2-supplemented females, 50 mg/kg amitraz caused an 85% decrease of serum E2 concentration and a marked increase of 2-OH-E2 concentration. Amitraz at 25 and 50 mg/kg produced 9.0-fold or greater increases of serum testosterone and 2{beta}-OH-testosterone levels in males. Amitraz at 25 mg/kg resulted in no or minimal increases of liver microsomal formation of E2 or testosterone metabolites. Amitraz at 50 mg/kg produced 1.4- to 3.6-fold increases of 2-OH-E2; estrone; 2{beta}-, 6{beta}-, and 16{alpha}-OH-testosterone; and androstenedione formation in males and intact females. Amitraz at 50 mg/kg preferentially increased intact female 16{beta}-OH-testosterone production by 8.6-fold. In OVX females, E2 supplement alone or cotreatment with E2 and 50 mg/kg amitraz produced 1.3- to several-fold increases of 2- and 4-OH-E2 formation and 2{beta}- and 16{alpha}-OH-testosterone production. The cotreatment increased 6{beta}- and 16{beta}-OH-testosterone formation by 1.8- and 1.6-fold, respectively. The present findings show that amitraz induces hepatic E2 and testosterone metabolism in male and female rats, decreases serum E2 concentration in OVX and E2-supplemented females, but increases serum testosterone in males. (orig.)

Nesting of colon and ovarian cancer cells in the endothelial niche is associated with alterations in glycan and lipid metabolism.

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Halama, Anna; Guerrouahen, Bella S; Pasquier, Jennifer; Satheesh, Noothan J; Suhre, Karsten; Rafii, Arash

2017-01-04

The metabolic phenotype of a cancer cell is determined by its genetic makeup and microenvironment, which dynamically modulates the tumor landscape. The endothelial cells provide both a promoting and protective microenvironment - a niche for cancer cells. Although metabolic alterations associated with cancer and its progression have been fairly defined, there is a significant gap in our understanding of cancer metabolism in context of its microenvironment. We deployed an in vitro co-culture system based on direct contact of cancer cells with endothelial cells (E4 + EC), mimicking the tumor microenvironment. Metabolism of colon (HTC15 and HTC116) and ovarian (OVCAR3 and SKOV3) cancer cell lines was profiled with non-targeted metabolic approaches at different time points in the first 48 hours after co-culture was established. We found significant, coherent and non-cell line specific changes in fatty acids, glycerophospholipids and carbohydrates over time, induced by endothelial cell contact. The metabolic patterns pinpoint alterations in hexosamine biosynthetic pathway, glycosylation and lipid metabolism as crucial for cancer - endothelial cells interaction. We demonstrated that "Warburg effect" is not modulated in the initial stage of nesting of cancer cell in the endothelial niche. Our study provides novel insight into cancer cell metabolism in the context of the endothelial microenvironment.

Exercise electrocardiographic responses and serum cystatin C levels among metabolic syndrome patients without overt diabetes mellitus

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Tanindi A

2011-02-01

Full Text Available Asli Tanindi1 Hilal Olgun1 Ayse Tuncel2 Bulent Celik3 Hatice Pasaoglu2 Bulent Boyaci11Department of Cardiology, 2Department of Medical Biochemistry, Faculty of Medicine, 3Department of Statistics, Faculty of Health Sciences, Gazi University, Ankara, TurkeyObjectives: An impaired heart rate response during exercise (chronotropic incompetence and an impaired heart rate recovery (HRR after exercise are predictors of cardiovascular risk and mortality. Cystatin C is a novel marker for cardiovascular disease. We aimed to investigate exercise electrocardiographic responses in patients with metabolic syndrome who were without overt diabetes mellitus, in addition to the association of serum cystatin C levels with the exercise electrocardiographic test results.Method: Forty-three consecutive patients admitted to a cardiology outpatient clinic without angina pectoris were recruited if they met criteria for metabolic syndrome but did not have overt diabetes mellitus. Serum cystatin C levels were measured, and all participants underwent exercise electrocardiographic testing. Patients who were found to have ischemia had a coronary angiography procedure.Results: The mean cystatin C level of patients was higher in metabolic syndrome group than healthy controls (610.1 ± 334.02 vs 337.3 ± 111.01 µg/L; P < 0.001. The percentage of patients with ischemia confirmed by coronary angiography was 13.9% in the metabolic syndrome group. Cystatin C levels in the ischemic patients of the metabolic syndrome group were higher than that in nonischemic patients (957.00 ± 375.6 vs 553.8 ± 295.3 µg /L; P = 0.005. Chronotropic incompetence was observed in 30.2% of the patients with metabolic syndrome compared with 16.7% in the control group (P = 0.186. Chronotropic response indices were 0.8 ± 0.18 versus 0.9 ± 0.10 for the two groups, respectively (P = 0.259. HRR was significantly lower in the metabolic syndrome patients compared with the controls (20.1 ± 8.01 vs 25.2 �

Metabolic markers in sports medicine.

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Banfi, Giuseppe; Colombini, Alessandra; Lombardi, Giovanni; Lubkowska, Anna

2012-01-01

Physical exercise induces adaptations in metabolism considered beneficial for health. Athletic performance is linked to adaptations, training, and correct nutrition in individuals with genetic traits that can facilitate such adaptations. Intense and continuous exercise, training, and competitions, however, can induce changes in the serum concentrations of numerous laboratory parameters. When these modifications, especially elevated laboratory levels, result outside the reference range, further examinations are ordered or participation in training and competition is discontinued or sports practice loses its appeal. In order to correctly interpret commonly used laboratory data, laboratory professionals and sport physicians need to know the behavior of laboratory parameters during and after practice and competition. We reviewed the literature on liver, kidney, muscle, heart, energy, and bone parameters in athletes with a view to increase the knowledge about clinical chemistry applied to sport and to stimulate studies in this field. In liver metabolism, the interpretation of serum aminotransferases concentration in athletes should consider the release of aspartate aminotransferase (AST) from muscle and of alanine aminotransferase (ALT) mainly from the liver, when bilirubin can be elevated because of continuous hemolysis, which is typical of exercise. Muscle metabolism parameters such as creatine kinase (CK) are typically increased after exercise. This parameter can be used to interpret the physiological release of CK from muscle, its altered release due to rhabdomyolysis, or incomplete recovery due to overreaching or trauma. Cardiac markers are released during exercise, and especially endurance training. Increases in these markers should not simply be interpreted as a signal of cardiac damage or wall stress but rather as a sign of regulation of myocardial adaptation. Renal function can be followed in athletes by measuring serum creatinine concentration, but it should

A Systematic Evaluation of Blood Serum and Plasma Pre-Analytics for Metabolomics Cohort Studies

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Elodie Jobard

2016-12-01

Full Text Available The recent thriving development of biobanks and associated high-throughput phenotyping studies requires the elaboration of large-scale approaches for monitoring biological sample quality and compliance with standard protocols. We present a metabolomic investigation of human blood samples that delineates pitfalls and guidelines for the collection, storage and handling procedures for serum and plasma. A series of eight pre-processing technical parameters is systematically investigated along variable ranges commonly encountered across clinical studies. While metabolic fingerprints, as assessed by nuclear magnetic resonance, are not significantly affected by altered centrifugation parameters or delays between sample pre-processing (blood centrifugation and storage, our metabolomic investigation highlights that both the delay and storage temperature between blood draw and centrifugation are the primary parameters impacting serum and plasma metabolic profiles. Storing the blood drawn at 4 °C is shown to be a reliable routine to confine variability associated with idle time prior to sample pre-processing. Based on their fine sensitivity to pre-analytical parameters and protocol variations, metabolic fingerprints could be exploited as valuable ways to determine compliance with standard procedures and quality assessment of blood samples within large multi-omic clinical and translational cohort studies.

Serum Fatty Acids Are Correlated with Inflammatory Cytokines in Ulcerative Colitis.

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Dawn M Wiese

Full Text Available Ulcerative colitis (UC is associated with increased dietary intake of fat and n-6 polyunsaturated fatty acids (PUFA. Modification of fat metabolism may alter inflammation and disease severity. Our aim was to assess differences in dietary and serum fatty acid levels between control and UC subjects and associations with disease activity and inflammatory cytokines.Dietary histories, serum, and colonic tissue samples were prospectively collected from 137 UC subjects and 38 controls. Both histologic injury and the Mayo Disease Activity Index were assessed. Serum and tissue cytokines were measured by Luminex assay. Serum fatty acids were obtained by gas chromatography.UC subjects had increased total fat and oleic acid (OA intake, but decreased arachidonic acid (AA intake vs controls. In serum, there was less percent saturated fatty acid (SFA and AA, with higher monounsaturated fatty acids (MUFA, linoleic acid, OA, eicosapentaenoic acid (EPA, and docosapentaenoic acid (DPA in UC. Tissue cytokine levels were directly correlated with SFA and inversely correlated with PUFA, EPA, and DPA in UC subjects, but not controls. 5-aminosalicylic acid therapy blunted these associations.In summary, we found differences in serum fatty acids in UC subjects that correlated with pro-inflammatory tissue cytokines. We propose that fatty acids may affect cytokine production and thus be immunomodulatory in UC.

Serum Fatty Acids Are Correlated with Inflammatory Cytokines in Ulcerative Colitis.

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Wiese, Dawn M; Horst, Sara N; Brown, Caroline T; Allaman, Margaret M; Hodges, Mallary E; Slaughter, James C; Druce, Jennifer P; Beaulieu, Dawn B; Schwartz, David A; Wilson, Keith T; Coburn, Lori A

2016-01-01

Ulcerative colitis (UC) is associated with increased dietary intake of fat and n-6 polyunsaturated fatty acids (PUFA). Modification of fat metabolism may alter inflammation and disease severity. Our aim was to assess differences in dietary and serum fatty acid levels between control and UC subjects and associations with disease activity and inflammatory cytokines. Dietary histories, serum, and colonic tissue samples were prospectively collected from 137 UC subjects and 38 controls. Both histologic injury and the Mayo Disease Activity Index were assessed. Serum and tissue cytokines were measured by Luminex assay. Serum fatty acids were obtained by gas chromatography. UC subjects had increased total fat and oleic acid (OA) intake, but decreased arachidonic acid (AA) intake vs controls. In serum, there was less percent saturated fatty acid (SFA) and AA, with higher monounsaturated fatty acids (MUFA), linoleic acid, OA, eicosapentaenoic acid (EPA), and docosapentaenoic acid (DPA) in UC. Tissue cytokine levels were directly correlated with SFA and inversely correlated with PUFA, EPA, and DPA in UC subjects, but not controls. 5-aminosalicylic acid therapy blunted these associations. In summary, we found differences in serum fatty acids in UC subjects that correlated with pro-inflammatory tissue cytokines. We propose that fatty acids may affect cytokine production and thus be immunomodulatory in UC.

Green tea polyphenols alter lipid metabolism in the livers of broiler chickens through increased phosphorylation of AMP-activated protein kinase.

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Jinbao Huang

Full Text Available Our previous results showed that green tea polyphenols (GTPs significantly altered the expression of lipid-metabolizing genes in the liver of chickens. However, the underlying mechanism was not elucidated. In this study, we further characterized how GTPs influence AMP-activated protein kinase (AMPK in the regulation of hepatic fat metabolism. Thirty-six male chickens were fed GTPs at a daily dose of 0, 80 or 160 mg/kg of body weight for 4 weeks. The results demonstrated that oral administration of GTPs significantly reduced hepatic lipid content and abdominal fat mass, enhanced the phosphorylation levels of AMPKα and ACACA, and altered the mRNA levels and enzymatic activities of lipid-metabolizing enzymes in the liver. These results suggested that the activation of AMPK is a potential mechanism by which GTPs regulate hepatic lipid metabolism in such a way that lipid synthesis is reduced and fat oxidation is stimulated.

Modulation by geraniol of gene expression involved in lipid metabolism leading to a reduction of serum-cholesterol and triglyceride levels.

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Galle, Marianela; Kladniew, Boris Rodenak; Castro, María Agustina; Villegas, Sandra Montero; Lacunza, Ezequiel; Polo, Mónica; de Bravo, Margarita García; Crespo, Rosana

2015-07-15

Geraniol (G) is a natural isoprenoid present in the essential oils of several aromatic plants, with various biochemical and pharmacologic properties. Nevertheless, the mechanisms of action of G on cellular metabolism are largely unknown. We propose that G could be a potential agent for the treatment of hyperlipidemia that could contribute to the prevention of cardiovascular disease. The aim of the present study was to advance our understanding of its mechanism of action on cholesterol and TG metabolism. NIH mice received supplemented diets containing 25, 50, and 75 mmol G/kg chow. After a 3-week treatment, serum total-cholesterol and triglyceride levels were measured by commercial kits and lipid biosynthesis determined by the [(14)C] acetate incorporated into fatty acids plus nonsaponifiable and total hepatic lipids of the mice. The activity of the mRNA encoding HMGCR-the rate-limiting step in cholesterol biosynthesis-along with the enzyme levels and catalysis were assessed by real-time RT-PCR, Western blotting, and HMG-CoA-conversion assays, respectively. In-silico analysis of several genes involved in lipid metabolism and regulated by G in cultured cells was also performed. Finally, the mRNA levels encoded by the genes for the low-density-lipoprotein receptor (LDLR), the sterol-regulatory-element-binding transcription factor (SREBF2), the very-low-density-lipoprotein receptor (VLDLR), and the acetyl-CoA carboxylase (ACACA) were determined by real-time RT-PCR. Plasma total-cholesterol and triglyceride levels plus hepatic fatty-acid, total-lipid, and nonsaponifiable-lipid biosynthesis were significantly reduced by feeding with G. Even though an up-regulation of the mRNA encoding HMGCR occurred in the G treated mouse livers, the protein levels and specific activity of the enzyme were both inhibited. G also enhanced the mRNAs encoding the LDL and VLDL receptors and reduced ACACA mRNA, without altering the transcription of the mRNA encoding the SREBF2. The following

Serum total bilirubin levels are negatively correlated with metabolic syndrome in aged Chinese women: a community-based study.

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Zhong, P; Sun, D M; Wu, D H; Li, T M; Liu, X Y; Liu, H Y

2017-01-26

We evaluated serum total bilirubin levels as a predictor for metabolic syndrome (MetS) and investigated the relationship between serum total bilirubin levels and MetS prevalence. This cross-sectional study included 1728 participants over 65 years of age from Eastern China. Anthropometric data, lifestyle information, and previous medical history were collected. We then measured serum levels of fasting blood-glucose, total cholesterol, triglycerides, and total bilirubin, as well as alanine aminotransferase activity. The prevalence of MetS and each of its individual component were calculated per quartile of total bilirubin level. Logistic regression was used to assess the correlation between serum total bilirubin levels and MetS. Total bilirubin level in the women who did not have MetS was significantly higher than in those who had MetS (Pbilirubin quartiles were linearly and negatively correlated with MetS prevalence and hypertriglyceridemia (HTG) in females (Pbilirubin was an independent predictor of MetS for females (OR: 0.910, 95%CI: 0.863-0.960; P=0.001). The present study suggests that physiological levels of serum total bilirubin might be an independent risk factor for aged Chinese women, and the prevalence of MetS and HTG are negatively correlated to serum total bilirubin levels.

Human longevity is characterised by high thyroid stimulating hormone secretion without altered energy metabolism.

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Jansen, S W; Akintola, A A; Roelfsema, F; van der Spoel, E; Cobbaert, C M; Ballieux, B E; Egri, P; Kvarta-Papp, Z; Gereben, B; Fekete, C; Slagboom, P E; van der Grond, J; Demeneix, B A; Pijl, H; Westendorp, R G J; van Heemst, D

2015-06-19

Few studies have included subjects with the propensity to reach old age in good health, with the aim to disentangle mechanisms contributing to staying healthier for longer. The hypothalamic-pituitary-thyroid (HPT) axis maintains circulating levels of thyroid stimulating hormone (TSH) and thyroid hormone (TH) in an inverse relationship. Greater longevity has been associated with higher TSH and lower TH levels, but mechanisms underlying TSH/TH differences and longevity remain unknown. The HPT axis plays a pivotal role in growth, development and energy metabolism. We report that offspring of nonagenarians with at least one nonagenarian sibling have increased TSH secretion but similar bioactivity of TSH and similar TH levels compared to controls. Healthy offspring and spousal controls had similar resting metabolic rate and core body temperature. We propose that pleiotropic effects of the HPT axis may favour longevity without altering energy metabolism.

Fluvoxamine alters the activity of energy metabolism enzymes in the brain

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Gabriela K. Ferreira

2014-09-01

Full Text Available Objective: Several studies support the hypothesis that metabolism impairment is involved in the pathophysiology of depression and that some antidepressants act by modulating brain energy metabolism. Thus, we evaluated the activity of Krebs cycle enzymes, the mitochondrial respiratory chain, and creatine kinase in the brain of rats subjected to prolonged administration of fluvoxamine. Methods: Wistar rats received daily administration of fluvoxamine in saline (10, 30, and 60 mg/kg for 14 days. Twelve hours after the last administration, rats were killed by decapitation and the prefrontal cortex, cerebral cortex, hippocampus, striatum, and cerebellum were rapidly isolated. Results: The activities of citrate synthase, malate dehydrogenase, and complexes I, II-III, and IV were decreased after prolonged administration of fluvoxamine in rats. However, the activities of complex II, succinate dehydrogenase, and creatine kinase were increased. Conclusions: Alterations in activity of energy metabolism enzymes were observed in most brain areas analyzed. Thus, we suggest that the decrease in citrate synthase, malate dehydrogenase, and complexes I, II-III, and IV can be related to adverse effects of pharmacotherapy, but long-term molecular adaptations cannot be ruled out. In addition, we demonstrated that these changes varied according to brain structure or biochemical analysis and were not dose-dependent.

Alterations in cellular metabolism modulate CD1d-mediated NKT-cell responses.

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Webb, Tonya J; Carey, Gregory B; East, James E; Sun, Wenji; Bollino, Dominique R; Kimball, Amy S; Brutkiewicz, Randy R

2016-08-01

Natural killer T (NKT) cells play a critical role in the host's innate immune response. CD1d-mediated presentation of glycolipid antigens to NKT cells has been established; however, the mechanisms by which NKT cells recognize infected or cancerous cells remain unclear. 5(')-AMP activated protein kinase (AMPK) is a master regulator of lipogenic pathways. We hypothesized that activation of AMPK during infection and malignancy could alter the repertoire of antigens presented by CD1d and serve as a danger signal to NKT cells. In this study, we examined the effect of alterations in metabolism on CD1d-mediated antigen presentation to NKT cells and found that an infection with lymphocytic choriomeningitis virus rapidly increased CD1d-mediated antigen presentation. Hypoxia inducible factors (HIF) enhance T-cell effector functions during infection, therefore antigen presenting cells pretreated with pharmacological agents that inhibit glycolysis, induce HIF and activate AMPK were assessed for their ability to induce NKT-cell responses. Pretreatment with 2-deoxyglucose, cobalt chloride, AICAR and metformin significantly enhanced CD1d-mediated NKT-cell activation. In addition, NKT cells preferentially respond to malignant B cells and B-cell lymphomas express HIF-1α. These data suggest that targeting cellular metabolism may serve as a novel means of inducing innate immune responses. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Adults with initial metabolic syndrome have altered muscle deoxygenation during incremental exercise.

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Machado, Alessandro da Costa; Barbosa, Thales Coelho; Kluser Sales, Allan Robson; de Souza, Marcio Nogueira; da Nóbrega, Antonio Claudio Lucas; Silva, Bruno Moreira

2017-02-01

Reduced aerobic power is independently associated with metabolic syndrome (MetS) incidence and prevalence in adults. This study investigated whether muscle deoxygenation (proxy of microvascular O 2 extraction) during incremental exercise is altered in MetS and associated with reduced oxygen consumption ( V˙O 2peak ). Twelve men with initial MetS (no overt diseases and medication-naive; mean ± SD, age 38 ± 7 years) and 12 healthy controls (HCs) (34 ± 7 years) completed an incremental cycling test to exhaustion, in which pulmonary ventilation and gas exchange (metabolic analyzer), as well as vastus lateralis deoxygenation (near infrared spectroscopy), were measured. Subjects with MetS, in contrast to HCs, showed lower V˙O 2peak normalized to total lean mass, similar V˙O 2 response to exercise, and earlier break point (BP) in muscle deoxygenation. Consequently, deoxygenation slope from BP to peak exercise was greater. Furthermore, absolute V˙O 2peak was positively associated with BP in correlations adjusted for total lean mass. MetS, without overt diseases, altered kinetics of muscle deoxygenation during incremental exercise, particularly at high-intensity exercise. Therefore, the balance between utilization and delivery of O 2 within skeletal muscle is impaired early in MetS natural history, which may contribute to the reduction in aerobic power. © 2017 The Obesity Society.

1H-NMR, 1H-NMR T2-edited, and 2D-NMR in bipolar disorder metabolic profiling.

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Sethi, Sumit; Pedrini, Mariana; Rizzo, Lucas B; Zeni-Graiff, Maiara; Mas, Caroline Dal; Cassinelli, Ana Cláudia; Noto, Mariane N; Asevedo, Elson; Cordeiro, Quirino; Pontes, João G M; Brasil, Antonio J M; Lacerda, Acioly; Hayashi, Mirian A F; Poppi, Ronei; Tasic, Ljubica; Brietzke, Elisa

2017-12-01

The objective of this study was to identify molecular alterations in the human blood serum related to bipolar disorder, using nuclear magnetic resonance (NMR) spectroscopy and chemometrics. Metabolomic profiling, employing 1 H-NMR, 1 H-NMR T 2 -edited, and 2D-NMR spectroscopy and chemometrics of human blood serum samples from patients with bipolar disorder (n = 26) compared with healthy volunteers (n = 50) was performed. The investigated groups presented distinct metabolic profiles, in which the main differential metabolites found in the serum sample of bipolar disorder patients compared with those from controls were lipids, lipid metabolism-related molecules (choline, myo-inositol), and some amino acids (N-acetyl-L-phenyl alanine, N-acetyl-L-aspartyl-L-glutamic acid, L-glutamine). In addition, amygdalin, α-ketoglutaric acid, and lipoamide, among other compounds, were also present or were significantly altered in the serum of bipolar disorder patients. The data presented herein suggest that some of these metabolites differentially distributed between the groups studied may be directly related to the bipolar disorder pathophysiology. The strategy employed here showed significant potential for exploring pathophysiological features and molecular pathways involved in bipolar disorder. Thus, our findings may contribute to pave the way for future studies aiming at identifying important potential biomarkers for bipolar disorder diagnosis or progression follow-up.

Chromium supplementation alters both glucose and lipid metabolism in feedlot cattle during the receiving period

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Crossbred steers (n = 20; 235 +/- 4 kg) were fed 53 days during a receiving period to determine if supplementing chromium (Cr; KemTRACE®brandChromium Propionate 0.04%, Kemin Industries) would alter the glucose or lipid metabolism of newly received cattle. Chromium premixes were supplemented to add 0...

Metabolic Characterization of Peripheral Host Responses to Drainage-Resistant Klebsiella pneumoniae Liver Abscesses by Serum 1H-NMR Spectroscopy

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Zhihui Chang

2018-06-01

Full Text Available Purpose: To explore the metabolic characterization of host responses to drainage-resistant Klebsiella pneumoniae liver abscesses (DRKPLAs with serum 1H-nuclear magnetic resonance (NMR spectroscopy.Materials and Methods: The hospital records of all patients with a diagnosis of a liver abscess between June 2015 and December 2016 were retrieved from an electronic hospital database. Eighty-six patients with Klebsiella pneumoniae (K. pneumoniae liver abscesses who underwent percutaneous drainage were identified. Twenty patients with confirmed DRKPLAs were studied. Moreover, we identified 20 consecutive patients with drainage-sensitive Klebsiella pneumoniae liver abscesses (DSKPLAs as controls. Serum samples from the two groups were analyzed with 1H NMR spectroscopy. Partial least squares discriminant analysis (PLS-DA was used to perform 1H NMR metabolic profiling. Metabolites were identified using the Human Metabolome Database, and pathway analysis was performed with MetaboAnalyst 3.0.Results: The PLS-DA test was able to discriminate between the two groups. Five key metabolites that contributed to their discrimination were identified. Glucose, lactate, and 3-hydroxybutyrate were found to be upregulated in DRKPLAs, whereas glutamine and alanine were downregulated compared with the DSKPLAs. Pathway analysis indicated that amino acid metabolisms were significantly different between the DRKPLAs and the DSKPLAs. The D-glutamine and D-glutamate metabolisms exhibited the greatest influences.Conclusions: The five key metabolites identified in our study may be potential targets for guiding novel therapeutics of DRKPLAs and are worthy of additional investigation.

Elevated Serum Cyclophilin B Levels Are Associated with the Prevalence and Severity of Metabolic Syndrome

OpenAIRE

Zhang, Hang; Fan, Qin; Xie, Hongyang; Lu, Lin; Tao, Rong; Wang, Fang; Xi, Rui; Hu, Jian; Chen, Qiujing; Shen, Weifeng; Zhang, Ruiyan; Yan, Xiaoxiang

2017-01-01

Objective Inflammation plays a central role in the pathogenesis of metabolic syndrome (MetS). Cyclophilin B (CypB) can be constitutively secreted in response to inflammatory stimuli and oxidative stress, participating in tissue or systemic inflammation. We investigated the relationship between CypB and MetS in both humans and mice. Methods Serum CypB levels were determined in 211 subjects with MetS and 292 subjects without MetS (non-MetS) (133 healthy controls and 159 high-risk subjects with ...

Elevated Serum Cyclophilin B Levels Are Associated with the Prevalence and Severity of Metabolic Syndrome

OpenAIRE

Hang Zhang; Hang Zhang; Qin Fan; Qin Fan; Hongyang Xie; Hongyang Xie; Lin Lu; Lin Lu; Rong Tao; Fang Wang; Rui Xi; Jian Hu; Qiujing Chen; Weifeng Shen; Ruiyan Zhang

2017-01-01

ObjectiveInflammation plays a central role in the pathogenesis of metabolic syndrome (MetS). Cyclophilin B (CypB) can be constitutively secreted in response to inflammatory stimuli and oxidative stress, participating in tissue or systemic inflammation. We investigated the relationship between CypB and MetS in both humans and mice.MethodsSerum CypB levels were determined in 211 subjects with MetS and 292 subjects without MetS (non-MetS) (133 healthy controls and 159 high-risk subjects with one...

Serum metabolic changes in rats after intragastric administration of dextromethorphan.

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Bao, Shihui; Zhang, Jing; Lin, Zixia; Su, Ke; Mo, Jingjing; Hong, Lin; Qian, Shuyi; Chen, Lianguo; Sun, Fa; Wen, Congcong; Wu, Qing; Hu, Lufeng; Lin, Guanyang; Wang, Xianqin

2017-03-01

Dextromethorphan is recognized as a substance of abuse around the world. An estimated 3.1 million people between the ages of 12 and 25 years (5.3%) misused over-the-counter cough and cold medications in 2006. In this study, we developed a serum metabolomic method by gas chromatography-mass spectrometry (GC-MS) to evaluate the effect of abuse of dextromethorphan on rats. The dextromethorphan-treated rats were given 12, 24 and 48 mg/kg (low, medium, high) of dextromethorphan by intragastric administration each day for 3 days. Partial least squares-discriminate analysis revealed that intragastric administration of dextromethorphan induced metabolic perturbations. Compared with the control (healthy) group, the levels of propanoic acid, urea, heptafluorobutanoic acid, 2-hexyldecanoic acid and butanedioic acid of the low group decreased; levels of propanoic acid and heptafluorobutanoic acid of the medium group decreased, while that of benzoic acid increased; and levels of 2-hexyldecanoic acid, glycerol and butanedioic acid of the high group increased. These biomarkers are involved in the citric acid cycle, urea cycle, glycerolipid metabolism and tricarboxylic acid cycle. The results indicate that the metabolomic method by GC-MS may be useful to elucidate abuse of dextromethorphan. According to the pathological changes in the liver at different dosages, dextromethorphan is not hepatotoxic after intragastric administration of 12, 24 and 48 mg/kg for 3 days. Copyright © 2016 John Wiley & Sons, Ltd.

Metabolic Rather Than Body Composition Measurements Are Associated With Lower Serum Natriuretic Peptide Concentrations in Normal Weight and Obese Men

DEFF Research Database (Denmark)

Asferg, Camilla L; Nielsen, Søren J; Andersen, Ulrik B

2014-01-01

BACKGROUND: Several studies have shown that obese persons have lower circulating natriuretic peptide (NP) concentrations. The cause of the relative NP deficiency seen in obese persons is poorly understood, although variation in body composition and metabolic abnormalities has been suggested to play...... a role. Thus, the aim of this study was to assess whether variation in circulating NP concentrations would be associated with differences in metabolic disturbances rather than with differences in body composition. METHODS: In 27 normal weight men (body mass index (BMI) = 20.0-24.9kg/m(2)) and 103 obese...... weight ± SD was 74.9±6.7kg in the normal weight men and 106.1±10.8kg in obese men. Applying multiple regressions, adjusting for age and weight status (normal weight vs. obese), serum MR-proANP concentrations were significantly inversely associated with serum insulin concentrations (β = -0.39; P

Alterations of the Lipid Metabolome in Dairy Cows Experiencing Excessive Lipolysis Early Postpartum.

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Humer, Elke; Khol-Parisini, Annabella; Metzler-Zebeli, Barbara U; Gruber, Leonhard; Zebeli, Qendrim

2016-01-01

A decrease in insulin sensitivity enhances adipose tissue lipolysis helping early lactation cows counteracting their energy deficit. However, excessive lipolysis poses serious health risks for cows, and its underlying mechanisms are not clearly understood. The present study used targeted ESI-LC-MS/MS-based metabolomics and indirect insulin sensitivity measurements to evaluate metabolic alterations in the serum of dairy cows of various parities experiencing variable lipolysis early postpartum. Thirty (12 primiparous and 18 multiparous) cows of Holstein Friesian and Simmental breeds, fed the same diet and kept under the same management conditions, were sampled at d 21 postpartum and classified as low (n = 10), medium (n = 8), and high (n = 12) lipolysis groups, based on serum concentration of nonesterified fatty acids. Overall, excessive lipolysis in the high group came along with impaired estimated insulin sensitivity and characteristic shifts in acylcarnitine, sphingomyelin, phosphatidylcholine and lysophospholipid metabolome profiles compared to the low group. From the detected phosphatidylcholines mainly those with diacyl-residues showed differences among lipolysis groups. Furthermore, more than half of the detected sphingomyelins were increased in cows experiencing high lipomobilization. Additionally, strong differences in serum acylcarnitines were noticed among lipolysis groups. The study suggests an altered serum phospholipidome in dairy cows associated with an increase in certain long-chain sphingomyelins and the progression of disturbed insulin function. In conclusion, the present study revealed 37 key metabolites as part of alterations in the synthesis or breakdown of sphingolipids and phospholipids associated with lowered estimated insulin sensitivity and excessive lipolysis in early-lactating cows.

Alterations of the Lipid Metabolome in Dairy Cows Experiencing Excessive Lipolysis Early Postpartum

Science.gov (United States)

Humer, Elke; Khol-Parisini, Annabella; Metzler-Zebeli, Barbara U.; Gruber, Leonhard; Zebeli, Qendrim

2016-01-01

A decrease in insulin sensitivity enhances adipose tissue lipolysis helping early lactation cows counteracting their energy deficit. However, excessive lipolysis poses serious health risks for cows, and its underlying mechanisms are not clearly understood. The present study used targeted ESI-LC-MS/MS-based metabolomics and indirect insulin sensitivity measurements to evaluate metabolic alterations in the serum of dairy cows of various parities experiencing variable lipolysis early postpartum. Thirty (12 primiparous and 18 multiparous) cows of Holstein Friesian and Simmental breeds, fed the same diet and kept under the same management conditions, were sampled at d 21 postpartum and classified as low (n = 10), medium (n = 8), and high (n = 12) lipolysis groups, based on serum concentration of nonesterified fatty acids. Overall, excessive lipolysis in the high group came along with impaired estimated insulin sensitivity and characteristic shifts in acylcarnitine, sphingomyelin, phosphatidylcholine and lysophospholipid metabolome profiles compared to the low group. From the detected phosphatidylcholines mainly those with diacyl-residues showed differences among lipolysis groups. Furthermore, more than half of the detected sphingomyelins were increased in cows experiencing high lipomobilization. Additionally, strong differences in serum acylcarnitines were noticed among lipolysis groups. The study suggests an altered serum phospholipidome in dairy cows associated with an increase in certain long-chain sphingomyelins and the progression of disturbed insulin function. In conclusion, the present study revealed 37 key metabolites as part of alterations in the synthesis or breakdown of sphingolipids and phospholipids associated with lowered estimated insulin sensitivity and excessive lipolysis in early-lactating cows. PMID:27383746

Alterations of the Lipid Metabolome in Dairy Cows Experiencing Excessive Lipolysis Early Postpartum.

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Elke Humer

Full Text Available A decrease in insulin sensitivity enhances adipose tissue lipolysis helping early lactation cows counteracting their energy deficit. However, excessive lipolysis poses serious health risks for cows, and its underlying mechanisms are not clearly understood. The present study used targeted ESI-LC-MS/MS-based metabolomics and indirect insulin sensitivity measurements to evaluate metabolic alterations in the serum of dairy cows of various parities experiencing variable lipolysis early postpartum. Thirty (12 primiparous and 18 multiparous cows of Holstein Friesian and Simmental breeds, fed the same diet and kept under the same management conditions, were sampled at d 21 postpartum and classified as low (n = 10, medium (n = 8, and high (n = 12 lipolysis groups, based on serum concentration of nonesterified fatty acids. Overall, excessive lipolysis in the high group came along with impaired estimated insulin sensitivity and characteristic shifts in acylcarnitine, sphingomyelin, phosphatidylcholine and lysophospholipid metabolome profiles compared to the low group. From the detected phosphatidylcholines mainly those with diacyl-residues showed differences among lipolysis groups. Furthermore, more than half of the detected sphingomyelins were increased in cows experiencing high lipomobilization. Additionally, strong differences in serum acylcarnitines were noticed among lipolysis groups. The study suggests an altered serum phospholipidome in dairy cows associated with an increase in certain long-chain sphingomyelins and the progression of disturbed insulin function. In conclusion, the present study revealed 37 key metabolites as part of alterations in the synthesis or breakdown of sphingolipids and phospholipids associated with lowered estimated insulin sensitivity and excessive lipolysis in early-lactating cows.

Whole-body pre-cooling does not alter human muscle metabolism during sub-maximal exercise in the heat.

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Booth, J; Wilsmore, B R; Macdonald, A D; Zeyl, A; Mcghee, S; Calvert, D; Marino, F E; Storlien, L H; Taylor, N A

2001-06-01

Muscle metabolism was investigated in seven men during two 35 min cycling trials at 60% peak oxygen uptake, at 35 degrees C and 50% relative humidity. On one occasion, exercise was preceded by whole-body cooling achieved by immersion in water during a reduction in temperature from 29 to 24 degrees C, and, for the other trial, by immersion in water at a thermoneutral temperature (control, 34.8 degrees C). Pre-cooling did not alter oxygen uptake during exercise (P > 0.05), whilst the change in cardiac frequency and body mass both tended to be lower following pre-cooling (0.05 whole-body pre-cooling does not alter muscle metabolism during submaximal exercise in the heat. It is more likely that thermoregulatory and cardiovascular strain are reduced, through lower muscle and core temperatures.

Chromium supplementation alters the glucose and lipid metabolism of feedlot cattle during the receiving period

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Crossbreed steers (n = 20; 235 ± 4 kg) were fed 53 d during a receiving period to determine if supplementing chromium (Cr; KemTRACE®brand Chromium Propionate 0.04%, Kemin Industries) would alter the glucose or lipid metabolism of newly received cattle. Chromium premixes were supplemented to add 0 (C...

Opium can differently alter blood glucose, sodium and potassium in male and female rats.

Science.gov (United States)

Karam, Gholamreza Asadi; Rashidinejad, Hamid Reza; Aghaee, Mohammad Mehdi; Ahmadi, Jafar; Rahmani, Mohammad Reza; Mahmoodi, Mehdi; Azin, Hosein; Mirzaee, Mohammad Reza; Khaksari, Mohammad

2008-04-01

To determine the effects of opium on serum glucose, potassium and sodium in male and female Wistar rat, opium solution (60 mg/kg) injected intraperitoneally and the same volume of distilled water was used as control (7 rats in each group). Blood samples were collected at 0, 30, 60, 120, 240 and 360 minutes after injection from orbit cavity and the values of serum glucose, sodium (Na(+)) and potassium (K(+)) were measured. The data were then analyzed by the repeated measure ANOVA based on sex and case-control group. P opium solution injection, in female rats compared to a control group. However, the male rats had this rise at 30, 60 and 120 minutes after opium solution injection compared to control group. While serum glucose in male rats was significantly higher than females at 30, 60 and 120 minutes, this value was higher in the female rats at 360 minutes. Therefore, serum glucose alterations following opium injection was significantly different in groups and in the sexes at different times. Sodium (Na(+)) rose at 60, 240 and 360 minutes significantly in all rats compared to control group. However, sodium alteration following opium injection was significantly different only between treated and control groups but sex-independent at all times. Potassium (K(+)) increased significantly at 60, 120, 240 and 360 minutes in male rats, compared to a control group. In female rats K(+) significantly raised at 30, 120, 240 and 360 minutes. Therefore, the alteration of K(+) in male and female rats was found time dependent and sex independent. According to our results, opium increased serum glucose in male and female rats differently, and it interferes with metabolic pathways differently on a gender dependent basis. Opium raised serum Na(+) and K(+), thus it interfere with water regulation and blood pressure via different mechanism.

The influence of altered gravity on carbohydrate metabolism in excised wheat leaves

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Obenland, D. M.; Brown, C. S.

1994-01-01

We developed a system to study the influence of altered gravity on carbohydrate metabolism in excised wheat leaves by means of clinorotation. The use of excised leaves in our clinostat studies offered a number of advantages over the use of whole plants, most important of which were minimization of exogenous mechanical stress and a greater amount of carbohydrate accumulation during the time of treatment. We found that horizontal clinorotation of excised wheat leaves resulted in significant reductions in the accumulation of fructose, sucrose, starch and fructan relative to control, vertically clinorotated leaves. Photosynthesis, dark respiration and the extractable activities of ADP glucose pyrophosphorylase (EC 2.7.7.27), sucrose phosphate synthase (EC 2.4.4.14), sucrose sucrose fructosyltransferase (EC 2.4.1.99), and fructan hydrolase (EC 3.2.1.80) were unchanged due to altered gravity treatment.

Altered serum microRNAs as biomarkers for the early diagnosis of pulmonary tuberculosis infection.

Science.gov (United States)

Qi, Yuhua; Cui, Lunbiao; Ge, Yiyue; Shi, Zhiyang; Zhao, Kangchen; Guo, Xiling; Yang, Dandan; Yu, Hao; Cui, Lan; Shan, Yunfeng; Zhou, Minghao; Wang, Hua; Lu, Zuhong

2012-12-28

Pulmonary tuberculosis (TB) is a highly lethal infectious disease and early diagnosis of TB is critical for the control of disease progression. The objective of this study was to profile a panel of serum microRNAs (miRNAs) as potential biomarkers for the early diagnosis of pulmonary TB infection. Using TaqMan Low-Density Array (TLDA) analysis followed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) validation, expression levels of miRNAs in serum samples from 30 patients with active tuberculosis and 60 patients with Bordetella pertussis (BP), varicella-zoster virus (VZV) and enterovirus (EV) were analyzed. The Low-Density Array data showed that 97 miRNAs were differentially expressed in pulmonary TB patient sera compared with healthy controls (90 up-regulated and 7 down-regulated). Following qRT-PCR confirmation and receiver operational curve (ROC) analysis, three miRNAs (miR-361-5p, miR-889 and miR-576-3p) were shown to distinguish TB infected patients from healthy controls and other microbial infections with moderate sensitivity and specificity (area under curve (AUC) value range, 0.711-0.848). Multiple logistic regression analysis of a combination of these three miRNAs showed an enhanced ability to discriminate between these two groups with an AUC value of 0.863. Our study suggests that altered levels of serum miRNAs have great potential to serve as non-invasive biomarkers for early detection of pulmonary TB infection.

A hypothalamic–pituitary–adrenal axis-associated neuroendocrine metabolic programmed alteration in offspring rats of IUGR induced by prenatal caffeine ingestion

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Xu, D. [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China); Wu, Y.; Liu, F.; Liu, Y.S.; Shen, L.; Lei, Y.Y.; Liu, J. [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Ping, J. [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China); Qin, J. [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Zhang, C. [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Chen, L.B. [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Magdalou, J. [UMR 7561 CNRS-Nancy Université, Faculté de Médicine, Vandoeuvre-lès-Nancy (France); Wang, H., E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China)

2012-11-01

Caffeine is a definite factor of intrauterine growth retardation (IUGR). Previously, we have confirmed that prenatal caffeine ingestion inhibits the development of hypothalamic–pituitary–adrenal (HPA) axis, and alters the glucose and lipid metabolism in IUGR fetal rats. In this study, we aimed to verify a programmed alteration of neuroendocrine metabolism in prenatal caffeine ingested-offspring rats. The results showed that prenatal caffeine (120 mg/kg.day) ingestion caused low body weight and high IUGR rate of pups; the concentrations of blood adrenocorticotropic hormone (ACTH) and corticosterone in caffeine group were significantly increased in the early postnatal period followed by falling in late stage; the level of blood glucose was unchanged, while blood total cholesterol (TCH) and triglyceride (TG) were markedly enhanced in adult. After chronic stress, the concentrations and the gain rates of blood ACTH and corticosterone were obviously increased, meanwhile, the blood glucose increased while the TCH and TG decreased in caffeine group. Further, the hippocampal mineralocorticoid receptor (MR) expression in caffeine group was initially decreased and subsequently increased after birth. After chronic stress, the 11β-hydroxysteroid dehydrogenase-1, glucocorticoid receptor (GR), MR as well as the MR/GR ratio were all significantly decreased. These results suggested that prenatal caffeine ingestion induced the dysfunction of HPA axis and associated neuroendocrine metabolic programmed alteration in IUGR offspring rats, which might be related with the functional injury of hippocampus. These observations provide a valuable experimental basis for explaining the susceptibility of IUGR offspring to metabolic syndrome and associated diseases. -- Highlights: ► Prenatal caffeine ingestion induced HPA axis dysfunction in IUGR offspring rats. ► Caffeine induced a neuroendocrine metabolic programmed alteration in offspring rats. ► Caffeine induced a functional injury

A hypothalamic–pituitary–adrenal axis-associated neuroendocrine metabolic programmed alteration in offspring rats of IUGR induced by prenatal caffeine ingestion

International Nuclear Information System (INIS)

Xu, D.; Wu, Y.; Liu, F.; Liu, Y.S.; Shen, L.; Lei, Y.Y.; Liu, J.; Ping, J.; Qin, J.; Zhang, C.; Chen, L.B.; Magdalou, J.; Wang, H.

2012-01-01

Caffeine is a definite factor of intrauterine growth retardation (IUGR). Previously, we have confirmed that prenatal caffeine ingestion inhibits the development of hypothalamic–pituitary–adrenal (HPA) axis, and alters the glucose and lipid metabolism in IUGR fetal rats. In this study, we aimed to verify a programmed alteration of neuroendocrine metabolism in prenatal caffeine ingested-offspring rats. The results showed that prenatal caffeine (120 mg/kg.day) ingestion caused low body weight and high IUGR rate of pups; the concentrations of blood adrenocorticotropic hormone (ACTH) and corticosterone in caffeine group were significantly increased in the early postnatal period followed by falling in late stage; the level of blood glucose was unchanged, while blood total cholesterol (TCH) and triglyceride (TG) were markedly enhanced in adult. After chronic stress, the concentrations and the gain rates of blood ACTH and corticosterone were obviously increased, meanwhile, the blood glucose increased while the TCH and TG decreased in caffeine group. Further, the hippocampal mineralocorticoid receptor (MR) expression in caffeine group was initially decreased and subsequently increased after birth. After chronic stress, the 11β-hydroxysteroid dehydrogenase-1, glucocorticoid receptor (GR), MR as well as the MR/GR ratio were all significantly decreased. These results suggested that prenatal caffeine ingestion induced the dysfunction of HPA axis and associated neuroendocrine metabolic programmed alteration in IUGR offspring rats, which might be related with the functional injury of hippocampus. These observations provide a valuable experimental basis for explaining the susceptibility of IUGR offspring to metabolic syndrome and associated diseases. -- Highlights: ► Prenatal caffeine ingestion induced HPA axis dysfunction in IUGR offspring rats. ► Caffeine induced a neuroendocrine metabolic programmed alteration in offspring rats. ► Caffeine induced a functional injury

Metabolic dysfunction and altered mitochondrial dynamics in the utrophin-dystrophin deficient mouse model of duchenne muscular dystrophy.

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Meghna Pant

Full Text Available The utrophin-dystrophin deficient (DKO mouse model has been widely used to understand the progression of Duchenne muscular dystrophy (DMD. However, it is unclear as to what extent muscle pathology affects metabolism. Therefore, the present study was focused on understanding energy expenditure in the whole animal and in isolated extensor digitorum longus (EDL muscle and to determine changes in metabolic enzymes. Our results show that the 8 week-old DKO mice consume higher oxygen relative to activity levels. Interestingly the EDL muscle from DKO mouse consumes higher oxygen per unit integral force, generates less force and performs better in the presence of pyruvate thus mimicking a slow twitch muscle. We also found that the expression of hexokinase 1 and pyruvate kinase M2 was upregulated several fold suggesting increased glycolytic flux. Additionally, there is a dramatic increase in dynamin-related protein 1 (Drp 1 and mitofusin 2 protein levels suggesting increased mitochondrial fission and fusion, a feature associated with increased energy demand and altered mitochondrial dynamics. Collectively our studies point out that the dystrophic disease has caused significant changes in muscle metabolism. To meet the increased energetic demand, upregulation of metabolic enzymes and regulators of mitochondrial fusion and fission is observed in the dystrophic muscle. A better understanding of the metabolic demands and the accompanied alterations in the dystrophic muscle can help us design improved intervention therapies along with existing drug treatments for the DMD patients.

Polymorphisms for ghrelin with consequences on satiety and metabolic alterations.

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Perret, Jason; De Vriese, Carine; Delporte, Christine

2014-07-01

To understand the current trend of ghrelin genetic variations on the control of satiety, eating behaviours, obesity, and metabolic alterations, and its development over the last 18 months. Several polymorphisms of the ghrelin gene, its receptor gene and ghrelin's acylating enzyme, ghrelin O-acyl transferase, have been identified and studied over the last decade in relation to control of satiety, obesity, eating behaviours, metabolic syndrome, glucose homeostasis, and type 2 diabetes. However, the effects described are either small or nonsignificant and often subjected to contradictory conclusions between studies. In the last 18 months, several of these areas of investigations have been revisited under more controlled conditions or have been subjected to meta-analysis. The effects of ghrelin gene polymorphism, is a complex area of investigation, due to ghrelin's interplay with a host of various factors part of an integrative network. However, taken together, results suggest that there are no or nonsignificant effects of the common genetic variants. A better understanding of the network, probably by a systems biology type approach, will be necessary to assign the exact role played by gene polymorphism of the component of the ghrelin axis.

Effect of changes of serum IGF-II and CT contents on bone metabolism in healthy subjects

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Xie Rongxing; Chen Wenhan; Chen Shaozhu

2005-01-01

Objective: To explore the effect of changes of serum insulin like growth factor II (IGF-II) and calcitonin (CT) on bone metabolism in both male and female healthy subjects of different age groups. Methods: Serum IGF-II and CT contents were determined with RIA in 180 healthy subjects of both sexes in 5 age groups (27-39, 40-49, 50-59, 60-69 and over 70). Results: The serum contents of IGF-II and CT decreased gradually as the age increased. The IGF-II contents in subjects above 70 were significantly lower than those in all other subjects (P<0.01); the values in subjects of the age group 27-39 were also significantly higher than those in the 60-69 group (P<0.05). Again, the serum CT contents in subjects over 50 were significantly lower than those in subjects below 50 (P<0.05, P<0.01). There were little differences among the levels in both sexes, with the exception of a slight but not significant lower value in the females above 50. Conclusion: In older subjects, the decreased contents of serum IGF-II would exert less modulation on osteoblastic activity while the decreased contents of CT would exert less inhibition on osteolytic activity. The contents in older females were even lower due to the decreased estrogen level. Combination of these two factors would lead to the initiation and development of osteoporosis. (authors)

Using direct infusion mass spectrometry for serum metabolomics in Alzheimer's disease.

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González-Domínguez, R; García-Barrera, T; Gómez-Ariza, J L

2014-11-01

Currently, there is no cure for Alzheimer's disease and early diagnosis is very difficult, since no biomarkers have been established with the necessary reliability and specificity. For the discovery of new biomarkers, the application of omics is emerging, especially metabolomics based on the use of mass spectrometry. In this work, an analytical approach based on direct infusion electrospray mass spectrometry was applied for the first time to blood serum samples in order to elucidate discriminant metabolites. Complementary methodologies of extraction and mass spectrometry analysis were employed for comprehensive metabolic fingerprinting. Finally, the application of multivariate statistical tools allowed us to discriminate Alzheimer patients and healthy controls, and identify some compounds as potential markers of disease. This approach provided a global vision of disease, given that some important metabolic pathways could be studied, such as membrane destabilization processes, oxidative stress, hypometabolism, or neurotransmission alterations. Most remarkable results are the high levels of phospholipids containing saturated fatty acids, respectively, polyunsaturated ones and the high concentration of whole free fatty acids in Alzheimer's serum samples. Thus, these results represent an interesting approximation to understand the pathogenesis of disease and the identification of potential biomarkers.

Change in Serum Bilirubin Level as a Predictor of Incident Metabolic Syndrome.

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Lee, You-Bin; Lee, Seung-Eun; Jun, Ji Eun; Jee, Jae Hwan; Bae, Ji Cheol; Jin, Sang-Man; Kim, Jae Hyeon

2016-01-01

Serum bilirubin level was negatively associated with the prevalence of metabolic syndrome (MetS) in previous cross-sectional studies. However, bilirubin variance preceding the development of MetS has yet to be investigated. We aimed to determine the effect of change in bilirubin concentration on the risk of incident MetS in healthy Korean adults. We conducted a retrospective longitudinal study of subjects who had undergone at least four yearly health check-ups between 2006 and 2012. Of 24,185 total individuals who received annual check-ups, 11,613 non-MetS participants with a baseline bilirubin level not exceeding 34.2 μmol/l were enrolled. We evaluated the association between percent change in bilirubin and risk of incident MetS. During 55,407 person-years of follow-up, 2,439 cases of incident MetS developed (21.0%). Baseline serum bilirubin level clearly showed no association with the development of MetS in men but an independent significant inverse association in women which attenuated (hence may be mediated) by elevated homeostatic model assessment index 2 for insulin resistance (HOMA2-IR). However, increased risk for incident MetS was observed in higher percent change in bilirubin quartiles, with hazard ratios of 2.415 (95% CI 2.094-2.785) in men and 2.156 (95% CI 1.738-2.675) in women in the fourth quartile, compared to the lowest quartile, after adjusting for age, smoking status, medication history, alanine aminotransferase, uric acid, estimated glomerular filtration rate, fasting glucose, baseline diabetes mellitus prevalence, systolic blood pressure, waist circumference, and body mass index. The hazard ratios per one standard deviation increase in percent change in bilirubin as a continuous variable were 1.277 (95% CI 1.229-1.326) in men and 1.366 (95% CI 1.288-1.447) in women. Increases in serum bilirubin concentration were positively associated with a higher risk of incident MetS. Serum bilirubin increment might be a sensitive marker for the development

Assessment of serum lipid metabolism index and cytokine levels in patients with type 2 diabetes mellitus complicated by coronary heart disease after telmisartan combined with lipid-lowering drug treatment

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Xin Wang

2017-07-01

Full Text Available Objective: To study the effect of telmisartan combined with lipid-lowering drug therapy on serum lipid metabolism index and cytokine levels in patients with type 2 diabetes mellitus complicated by coronary heart disease. Methods: A total of 106 patients with type 2 diabetes mellitus complicated by coronary heart disease who were treated in our hospital between September 2013 and October 2016 were collected and then divided into the control group (n=55 who received conventional treatment + lipid-lowering drug treatment and the observation group (n=51 who received conventional treatment + lipid-lowering drug + telmisartan treatment after the therapies were reviewed. Before and after treatment, serum levels of lipid metabolism indexes, inflammatory mediators and oxidative stress indexes were compared between two groups of patients. Results: Before treatment, the differences in serum levels of lipid metabolism indexes, inflammatory mediators and oxidative stress indexes were not statistically significant between two groups of patients. After treatment, serum TG and LDL-C levels in observation group were lower than those in control group while HDL-C level was higher than that in control group; serum inflammatory mediators IL-6, IL-8, HMGB1 and TNF-α levels were lower than those in control group; serum oxidative stress indexes MDA and ROS levels were lower than those in control group while GSH-Px level was higher than that in control group. Conclusion: Telmisartan combined with lipid-lowering drug therapy can effectively optimize the lipid metabolism and reduce the systemic inflammatory response and oxidative stress response in patients with type 2 diabetes mellitus complicated by coronary heart disease.

Opium and heroin alter biochemical parameters of human's serum.

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Kouros, Divsalar; Tahereh, Haghpanah; Mohammadreza, Afarinesh; Minoo, Mahmoudi Zarandi

2010-05-01

Iran is a significant consumer of opium, and, generally, of opioids, in the world. Addiction is one of the important issues of the 21st century and is an imperative issue in Iran. Long-term consumption of opioids affects homeostasis. To determine the effects of opium and heroin consumption on serum biochemical parameters. In a cross-sectional study, subjects who had consumed heroin (n = 35) or opium (n = 42) for more than two years and 35 nonaddict volunteers as the control group were compared in regard to various biochemical parameters such as fasting blood sugar (FBS), Na(+), K(+), Ca(2+), blood urea nitrogen (BUN), uric acid (UA), triglyceride (TG), cholesterol, creatinine, and total protein. Chromatography was used to confirm opioid consumption, and the concentration of biochemical parameters was determined by laboratory diagnostic tests on serum. No significant differences were found in Na(+), Ca(2+), BUN, UA, TG, creatinine, and total protein concentrations among the three groups. FBS, K(+), and UA levels were significantly lower in opium addicts compared to the control group. Serum Ca(2+) concentration of heroin addicts showed a significant decrease compared to that of the control group. Both addict groups showed a significant decrease in serum cholesterol levels. Chronic use of opium and heroin can change serum FBS, K(+), Ca(2+), UA, and cholesterol. This study, one of few on the effects of opium on serum biochemical parameters in human subjects, has the potential to contribute to the investigation of new approaches for further basic studies.

The Effects of Curcumin and Curcumin-Phospholipid Complex on the Serum Pro-oxidant-Antioxidant Balance in Subjects with Metabolic Syndrome.

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Ghazimoradi, Maryam; Saberi-Karimian, Maryam; Mohammadi, Farzane; Sahebkar, Amirhossein; Tavallaie, Shima; Safarian, Hamideh; Ferns, Gordon A; Ghayour-Mobarhan, Majid; Moohebati, Mohsen; Esmaeili, Habibollah; Ahmadinejad, Malihe

2017-11-01

Metabolic syndrome (MetS) is defined by a clustering of metabolic and anthropometric abnormalities and is associated by an increased risk of cardiovascular disease. We have investigated the effect of curcumin supplementation on the serum pro-oxidant-antioxidant balance (PAB) in patients with MetS. This double-blind, randomized, placebo-controlled trial was conducted over 6 weeks. Subjects (n = 120) were randomly allocated to one of three groups (curcumin, phospholipidated curcumin, and placebo). The curcumin group received 1 g/day of simple curcumin, the phospholipidated curcumin group received 1 g/day of phospholipidated curcumin (containing 200 mg of pure curcumin), and the control group received 1 g/day of placebo. Serum PAB was measured before and after the intervention (at baseline and at 6 weeks). Data analyses were performed using spss software (version 16.0). Serum PAB increased significantly in the curcumin group (p curcumin group, elevation of PAB level was not significant (p = 0.053). The results of our study did not suggest any improvement of PAB following supplementation with curcumin in MetS subjects. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

C75, a fatty acid synthase inhibitor, modulates AMP-activated protein kinase to alter neuronal energy metabolism.

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Landree, Leslie E; Hanlon, Andrea L; Strong, David W; Rumbaugh, Gavin; Miller, Ian M; Thupari, Jagan N; Connolly, Erin C; Huganir, Richard L; Richardson, Christine; Witters, Lee A; Kuhajda, Francis P; Ronnett, Gabriele V

2004-01-30

C75, a synthetic inhibitor of fatty acid synthase (FAS), is hypothesized to alter the metabolism of neurons in the hypothalamus that regulate feeding behavior to contribute to the decreased food intake and profound weight loss seen with C75 treatment. In the present study, we characterize the suitability of primary cultures of cortical neurons for studies designed to investigate the consequences of C75 treatment and the alteration of fatty acid metabolism in neurons. We demonstrate that in primary cortical neurons, C75 inhibits FAS activity and stimulates carnitine palmitoyltransferase-1 (CPT-1), consistent with its effects in peripheral tissues. C75 alters neuronal ATP levels and AMP-activated protein kinase (AMPK) activity. Neuronal ATP levels are affected in a biphasic manner with C75 treatment, decreasing initially, followed by a prolonged increase above control levels. Cerulenin, a FAS inhibitor, causes a similar biphasic change in ATP levels, although levels do not exceed control. C75 and cerulenin modulate AMPK phosphorylation and activity. TOFA, an inhibitor of acetyl-CoA carboxylase, increases ATP levels, but does not affect AMPK activity. Several downstream pathways are affected by C75 treatment, including glucose metabolism and acetyl-CoA carboxylase (ACC) phosphorylation. These data demonstrate that C75 modulates the levels of energy intermediates, thus, affecting the energy sensor AMPK. Similar effects in hypothalamic neurons could form the basis for the effects of C75 on feeding behavior.

Quantitative HRMAS proton total correlation spectroscopy applied to cultured melanoma cells treated by chloroethyl nitrosourea: demonstration of phospholipid metabolism alterations.

Science.gov (United States)

Morvan, Daniel; Demidem, Aicha; Papon, Janine; Madelmont, Jean Claude

2003-02-01

Recent NMR spectroscopy developments, such as high-resolution magic angle spinning (HRMAS) probes and correlation-enhanced 2D sequences, now allow improved investigations of phospholipid (Plp) metabolism. Using these modalities we previously demonstrated that a mouse-bearing melanoma tumor responded to chloroethyl nitrosourea (CENU) treatment in vivo by altering its Plp metabolism. The aims of the present study were to investigate whether HRMAS proton total correlation spectroscopy (TOCSY) could be used as a quantitative technique to probe Plp metabolism, and to determine the Plp metabolism response of cultured B16 melanoma cells to CENU treatment in vitro. The exploited TOCSY signals of Plp derivatives arose from scalar coupling among the protons of neighbor methylene groups within base headgroups (choline and ethanolamine). For strongly expressed Plp derivatives, TOCSY signals were compared to saturation recovery signals and demonstrated a linear relationship. HRMAS proton TOCSY was thus used to provide concentrations of Plp derivatives during long-term follow-up of CENU-treated cell cultures. Strong Plp metabolism alteration was observed in treated cultured cells in vitro involving a down-regulation of phosphocholine, and a dramatic and irreversible increase of phosphoethanolamine. These findings are discussed in relation to previous in vivo data, and to Plp metabolism enzymatic involvement. Copyright 2003 Wiley-Liss, Inc.

Altered dopamine and serotonin metabolism in motorically asymptomatic R6/2 mice.

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Fanny Mochel

Full Text Available The pattern of cerebral dopamine (DA abnormalities in Huntington disease (HD is complex, as reflected by the variable clinical benefit of both DA antagonists and agonists in treating HD symptoms. In addition, little is known about serotonin metabolism despite the early occurrence of anxiety and depression in HD. Post-mortem enzymatic changes are likely to interfere with the in vivo profile of biogenic amines. Hence, in order to reliably characterize the regional and chronological profile of brain neurotransmitters in a HD mouse model, we used a microwave fixation system that preserves in vivo concentrations of dopaminergic and serotoninergic amines. DA was decreased in the striatum of R6/2 mice at 8 and 12 weeks of age while DA metabolites, 3-methoxytyramine and homovanillic acid, were already significantly reduced in 4-week-old motorically asymptomatic R6/2 mice. In the striatum, hippocampus and frontal cortex of 4, 8 and 12-week-old R6/2 mice, serotonin and its metabolite 5-hydroxyindoleacetic acid were significantly decreased in association with a decreased turnover of serotonin. In addition, automated high-resolution behavioural analyses displayed stress-like behaviours such as jumping and grooming and altered spatial learning in R6/2 mice at age 4 and 6 weeks respectively. Therefore, we describe the earliest alterations of DA and serotonin metabolism in a HD murine model. Our findings likely underpin the neuropsychological symptoms at time of disease onset in HD.

Metabolic alterations, HFE gene mutations and atherogenic lipoprotein modifications in patients with primary iron overload.

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Meroño, Tomás; Brites, Fernando; Dauteuille, Carolane; Lhomme, Marie; Menafra, Martín; Arteaga, Alejandra; Castro, Marcelo; Saez, María Soledad; Ballerga, Esteban González; Sorroche, Patricia; Rey, Jorge; Lesnik, Philippe; Sordá, Juan Andrés; Chapman, M John; Kontush, Anatol; Daruich, Jorge

2015-05-01

Iron overload (IO) has been associated with glucose metabolism alterations and increased risk of cardiovascular disease (CVD). Primary IO is associated with mutations in the HFE gene. To which extent HFE gene mutations and metabolic alterations contribute to the presence of atherogenic lipoprotein modifications in primary IO remains undetermined. The present study aimed to assess small, dense low-density lipoprotein (LDL) levels, chemical composition of LDL and high-density lipoprotein (HDL) particles, and HDL functionality in IO patients. Eighteen male patients with primary IO and 16 sex- and age-matched controls were recruited. HFE mutations (C282Y, H63D and S65C), measures of insulin sensitivity and secretion (calculated from the oral glucose tolerance test), chemical composition and distribution profile of LDL and HDL subfractions (isolated by gradient density ultracentrifugation) and HDL functionality (as cholesterol efflux and antioxidative activity) were studied. IO patients compared with controls exhibited insulin resistance (HOMA-IR (homoeostasis model assessment-estimated insulin resistance): +93%, PHFE genotypes. C282Y homozygotes (n=7) presented a reduced β-cell function and insulin secretion compared with non-C282Y patients (n=11) (-58% and -73%, respectively, PHFE gene mutations are involved in the presence of atherogenic lipoprotein modifications in primary IO. To what extent such alterations could account for an increase in CVD risk remains to be determined.

Clerodendron glandulosum Coleb., Verbenaceae, ameliorates high fat diet-induced alteration in lipid and cholesterol metabolism in rats

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RN Jadeja

Full Text Available The present study was undertaken to evaluate the efficacy of freeze dried extract of Clerodendron glandulosum Coleb., Verbenaceae, leaves (FECG on alteration in lipid and cholesterol metabolism in high fat diet fed hyperlipidemic rats. Plasma and hepatic lipid profiles, lipid and cholesterol metabolizing enzymes in target tissues and fecal total lipids and bile acid contents were evaluated in FECG treated normolipidemic and hyperlipidemic rats. These results were compared with synthetic hypolipidemic drug Lovastatin (LVS. Results indicate that FECG was able to positively regulate induced experimental hyperlipidemia by significant alteration in plasma and tissue lipid profiles. These results can be attributed to reduced absorption, effective elimination and augmented catabolism of lipids and cholesterol possibly due to high content of saponin and phytosterols in C. glandulosum. Use of C. glandulosum extract as a potential therapeutic agent against hypercholesterolemia and hypertriglyceridemia is indicated.

The Role of Serum Leptin and IL-6 Levels in Post Viral Hepatitis Cirrhotic patients

International Nuclear Information System (INIS)

Mohamed, S.K.

2010-01-01

Chronic liver disease is characterized by numerous metabolic alterations resulting in the clinical picture of malnutrition or even cachexia and contributing to complications such as hepatic encephalopathy and ascites. Leptin is a hormone that plays an important role in regulating energy intake and expenditure including appetite and metabolism. Interleukin-6 (IL-6), on the other hand, is generally considered to be one of the important cytokines that regulate immunologic and metabolic actions. The aim of the present study was to investigate serum leptin and IL-6 levels in liver cirrhosis, as well as to determine their levels in relation to liver functions and lipid profile. This study was conducted on 25 patients with post- viral hepatic cirrhosis compared to 20 healthy matched individuals served as controls with the same age and sex. The severity of the disease assessed with Child-Pugh criteria yielded 8 patients (3 women, 5 men) with stage A, 10 patients (4 women, 6 men) with stage B and 7 patients (2 women, 5 men) with stage C. Compared to controls, body mass index (BMI) was decreased and reached statistical significance in group C liver cirrhosis (P< 0.05). Also, serum leptin level was highly significantly decreased in the three groups, while IL-6 level showed highly significant increase. Leptin level negatively correlated with aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total bilirubin and positively correlated with serum albumin, triglycerides (TG), cholesterol and low density lipoprotein (LDL). In contrast, serum IL-6 level positively correlated with parameters of liver functions and negatively correlated with parameters of lipid profile. Additionally, there was highly significant negative correlation between serum leptin and IL-6 levels (P < 0.001) in post-hepatic cirrhotic patients. We concluded that leptin and IL-6 have important role in diagnosis and prognosis of patients with post-hepatic liver cirrhosis

The Role of Serum Leptin and IL-6 Levels in Post Viral Hepatitis Cirrhotic patients

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Mohamed, S.K., E-mail: Safaa-K-mohamed@hotmail.co [Health Radiation Research Department, National Center for Radiation Research and Technology, P. O. Box:29 Nasr City, Cairo (Egypt)

2010-07-01

Chronic liver disease is characterized by numerous metabolic alterations resulting in the clinical picture of malnutrition or even cachexia and contributing to complications such as hepatic encephalopathy and ascites. Leptin is a hormone that plays an important role in regulating energy intake and expenditure including appetite and metabolism. Interleukin-6 (IL-6), on the other hand, is generally considered to be one of the important cytokines that regulate immunologic and metabolic actions. The aim of the present study was to investigate serum leptin and IL-6 levels in liver cirrhosis, as well as to determine their levels in relation to liver functions and lipid profile. This study was conducted on 25 patients with post- viral hepatic cirrhosis compared to 20 healthy matched individuals served as controls with the same age and sex. The severity of the disease assessed with Child-Pugh criteria yielded 8 patients (3 women, 5 men) with stage A, 10 patients (4 women, 6 men) with stage B and 7 patients (2 women, 5 men) with stage C. Compared to controls, body mass index (BMI) was decreased and reached statistical significance in group C liver cirrhosis (P< 0.05). Also, serum leptin level was highly significantly decreased in the three groups, while IL-6 level showed highly significant increase. Leptin level negatively correlated with aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total bilirubin and positively correlated with serum albumin, triglycerides (TG), cholesterol and low density lipoprotein (LDL). In contrast, serum IL-6 level positively correlated with parameters of liver functions and negatively correlated with parameters of lipid profile. Additionally, there was highly significant negative correlation between serum leptin and IL-6 levels (P < 0.001) in post-hepatic cirrhotic patients. We concluded that leptin and IL-6 have important role in diagnosis and prognosis of patients with post-hepatic liver cirrhosis

Quantifying Diet-Induced Metabolic Changes of the Human Gut Microbiome

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Shoaie, Saeed; Ghaffari, Pouyan; Kovatcheva-Datchary, Petia

2015-01-01

The human gut microbiome is known to be associated with various human disorders, but a major challenge is to go beyond association studies and elucidate causalities. Mathematical modeling of the human gut microbiome at a genome scale is a useful tool to decipher microbe-microbe, diet...... of single bacteria and whole communities in vitro. Focusing on metabolic interactions between the diet, gut microbiota, and host metabolism, we demonstrated the predictive power of the toolbox in a diet-intervention study of 45 obese and overweight individuals and validated our predictions by fecal...... and blood metabolomics data. Thus, modeling could quantitatively describe altered fecal and serum amino acid levels in response to diet intervention....

Influence of physical and emotional activity on the metabolic profile of blood serum of race horses

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T. I. Bayeva

2016-09-01

Full Text Available In the article data are presented on dynamics of the level of indicators of metabolic profile of blood serum of race horses of the Ukrainian riding breed in the conditions of physical and emotional loading. Clinically healthy race horses were the object of  research. Blood was taken from the jugular vein to obtain serum and for further biochemical research. For the research 12 race horses from a training group were chosen. From time to time the animals took part in competitions; they were not specially used in races and were mostly used for the training of junior riders and sportsmen of different levels. Blood was taken in conditions of relative rest after ordinary training and after emotional stress during the entertainment performances when a large number of people were present and loud music was played. In the blood serum the following biochemical indicators were defined: whole protein, urea, creatinine, uric acid, total bilirubin and its fractions, glucose, cholestererol, triacylglycerol, calcium, ferrum, lactate, pyruvate, activity of the AlAT, SGOT, GGTP, LDH, an alkaline phosphatase – which makes it possible to determine reasonably accurately the adaptation potential of a horse under various types of loading. We established that during training and psychoemotional loading of racing horses of the training group of the Ukrainian riding breed, multidirectional changes in the level of biochemical indicators of blood serum occurred, which is evidence of stress in the metabolic processes in the animals’ organisms. Concentration of a biomarker of an oxidative stress, uric acid, increased after physical loading by 8.6%, and after emotional loading by 55.1%, which demonstrates that emotional stress had the more negative effect, indicating insufficient adaptation by the horses before demonstration performances. After physical loading, reaction of transamination in the horses’ liver cells intensified, and after emotional loading its intensity

Systemic distribution of single-walled carbon nanotubes in a novel model: alteration of biochemical parameters, metabolic functions, liver accumulation, and inflammation in vivo

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Principi E

2016-09-01

Full Text Available Elisa Principi,1,* Rossana Girardello,2,* Antonino Bruno,1,* Isabella Manni,3 Elisabetta Gini,2 Arianna Pagani,1 Annalisa Grimaldi,2 Federico Ivaldi,4 Terenzio Congiu,5 Daniela De Stefano,1 Giulia Piaggio,3 Magda de Eguileor,2 Douglas M Noonan,1,2 Adriana Albini1 1Vascular Biology and Angiogenesis, Scientific and Technology Pole, IRCCS MultiMedica, Milano, 2Department of Biotechnology and Life Sciences, University of Insubria, Varese, 3Department of Research, Advanced Diagnosis and Innovation, Regina Elena National Cancer Institute, Rome, 4Department of Neuroscience, Ophthalmology and Genetics, University of Genoa, Genoa, 5Department of Surgical and Morphological Sciences, University of Insubria, Varese, Italy *These authors contributed equally to this work Abstract: The increasing use of carbon nanotubes (CNTs in several industrial applications raises concerns on their potential toxicity due to factors such as tissue penetrance, small dimensions, and biopersistence. Using an in vivo model for CNT environmental exposure, mimicking CNT exposition at the workplace, we previously found that CNTs rapidly enter and disseminate in the organism, initially accumulating in the lungs and brain and later reaching the liver and kidneys via the bloodstream in CD1 mice. Here, we monitored and traced the accumulation of single-walled CNTs (SWCNTs, administered systemically in mice, in different organs and the subsequent biological responses. Using the novel in vivo model, MITO-Luc bioluminescence reporter mice, we found that SWCNTs induce systemic cell proliferation, indicating a dynamic response of cells of both bone marrow and the immune system. We then examined metabolic (water/food consumption and dejections, functional (serum enzymes, and morphological (organs and tissues alterations in CD1 mice treated with SWCNTs, using metabolic cages, performing serum analyses, and applying histological, immunohistochemical, and ultrastructural (transmission electron

3'-Azido-3'-deoxythymidine (AZT) induces apoptosis and alters metabolic enzyme activity in human placenta

International Nuclear Information System (INIS)

Collier, Abby C.; Helliwell, Rachel J.A.; Keelan, Jeffrey A.; Paxton, James W.; Mitchell, Murray D.; Tingle, Malcolm D.

2003-01-01

The anti-HIV drug 3'-azido-3'-deoxythymidine (AZT) is the drug of choice for preventing maternal-fetal HIV transmission during pregnancy. Our aim was to assess the cytotoxic effects of AZT on human placenta in vitro. The mechanisms of AZT-induced effects were investigated using JEG-3 choriocarcinoma cells and primary explant cultures from term and first-trimester human placentas. Cytotoxicity measures included trypan blue exclusion, MTT, and reactive oxygen species (ROS) assays. Apoptosis was measured with an antibody specific to cleaved caspase-3 and by rescue of cells by the general caspase inhibitor Boc-D-FMK. The effect of AZT on the activities of glutathione-S-transferase, β-glucuronidase, UDP-glucuronosyl transferase, cytochrome P450 (CYP) 1A, and CYP reductase (CYPR) in the placenta was assessed using biochemical assays and immunoblotting. AZT increased ROS levels, decreased cellular proliferation rates, was toxic to mitochondria, and initiated cell death by a caspase-dependent mechanism in the human placenta in vitro. In the absence of serum, the effects of AZT were amplified in all the models used. AZT also increased the amounts of activity of GST, β-glucuronidase, and CYP1A, whereas UGT and CYPR were decreased. We conclude that AZT causes apoptosis in the placenta and alters metabolizing enzymes in human placental cells. These findings have implications for the safe administration of AZT in pregnancy with respect to the maintenance of integrity of the maternal-fetal barrier

Blood metabolomics analysis identifies abnormalities in the citric acid cycle, urea cycle, and amino acid metabolism in bipolar disorder.

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Yoshimi, Noriko; Futamura, Takashi; Kakumoto, Keiji; Salehi, Alireza M; Sellgren, Carl M; Holmén-Larsson, Jessica; Jakobsson, Joel; Pålsson, Erik; Landén, Mikael; Hashimoto, Kenji

2016-06-01

Bipolar disorder (BD) is a severe and debilitating psychiatric disorder. However, the precise biological basis remains unknown, hampering the search for novel biomarkers. We performed a metabolomics analysis to discover novel peripheral biomarkers for BD. We quantified serum levels of 116 metabolites in mood-stabilized male BD patients (n = 54) and age-matched male healthy controls (n = 39). After multivariate logistic regression, serum levels of pyruvate, N-acetylglutamic acid, α-ketoglutarate, and arginine were significantly higher in BD patients than in healthy controls. Conversely, serum levels of β-alanine, and serine were significantly lower in BD patients than in healthy controls. Chronic (4-weeks) administration of lithium or valproic acid to adult male rats did not alter serum levels of pyruvate, N-acetylglutamic acid, β-alanine, serine, or arginine, but lithium administration significantly increased serum levels of α-ketoglutarate. The metabolomics analysis demonstrated altered serum levels of pyruvate, N-acetylglutamic acid, β-alanine, serine, and arginine in BD patients. The present findings suggest that abnormalities in the citric acid cycle, urea cycle, and amino acid metabolism play a role in the pathogenesis of BD.

Autism as a disorder of deficiency of brain-derived neurotrophic factor and altered metabolism of polyunsaturated fatty acids.

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Das, Undurti N

2013-10-01

Autism has a strong genetic and environmental basis in which inflammatory markers and factors concerned with synapse formation, nerve transmission, and information processing such as brain-derived neurotrophic factor (BDNF), polyunsaturated fatty acids (PUFAs): arachidonic (AA), eicosapentaenoic (EPA), and docosahexaenoic acids (DHA) and their products and neurotransmitters: dopamine, serotonin, acetylcholine, γ-aminobutyric acid, and catecholamines and cytokines are altered. Antioxidants, vitamins, minerals, and trace elements are needed for the normal metabolism of neurotrophic factors, eicosanoids, and neurotransmitters, supporting reports of their alterations in autism. But, the exact relationship among these factors and their interaction with genes and proteins concerned with brain development and growth is not clear. It is suggested that maternal infections and inflammation and adverse events during intrauterine growth of the fetus could lead to alterations in the gene expression profile and proteomics that results in dysfunction of the neuronal function and neurotransmitters, alteration(s) in the metabolism of PUFAs and their metabolites resulting in excess production of proinflammatory eicosanoids and cytokines and a deficiency of anti-inflammatory cytokines and bioactive lipids that ultimately results in the development of autism. Based on these evidences, it is proposed that selective delivery of BDNF and methods designed to augment the production of anti-inflammatory cytokines and eicosanoids and PUFAs may prevent, arrest, or reverse the autism disease process. Copyright © 2013 Elsevier Inc. All rights reserved.

Metabolic profile of santa inês ewes whith low body condition score during peripartum

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Nayara Resende Nasciutti

2012-02-01

Full Text Available The objective of this study was to analyse the variations in the metabolic profile of protein, energy enzyme and mineral of Santa Inês ewes with low body condition score (BCS during peripartum. Blood samples were collected from 12 animals by jugular venipuncture to determine the serum biochemical profiles of protein, energy, mineral and enzyme metabolisms. Samples were collected on the following days: days 28, 21, 14, and 7 before lambing, at birth and, at days 2, 4, 7, 14, 21, and 28 postpartum (dpp. The samples were centrifuged and the serum analysed by Automated-Analyser. There was no alteration of the BCS during the 28 dpp, between 0.6 and 2.1 ± 2.4 ± 0.5, and was considered, as lean. The values of the total serum protein, globulin, albumin, and albumin/globulin ratio were reduced effective from the period before birth until 28dpp. The values of beta-hydroxybutyrate, calcium, phosphorus and magnesium remained below those of reference values. The concentrations of alanin aminotransferase (ALT were decreased particularly during the weeks before delivery. It was concluded that Santa Inês sheep with low body condition score demonstrated a reduction in the metabolism of proteins, energy, mineral and enzyme during peripartum.

Low normal thyroid function attenuates serum alanine aminotransferase elevations in the context of metabolic syndrome and insulin resistance in white people

NARCIS (Netherlands)

Dullaart, Robin P. F.; van den Berg, Eline H.; van der Klauw, Melanie; Blokzijl, Hans

Objectives: Thyroid hormones play a key role in hepatic lipid metabolism. Although hypothyroidismis associated with increased prevalence of non-alcoholic fatty liver disease (NAFLD), the relationship of NAFLD with low normal thyroid function is unclear. We tested the association of serum alanine

Gender-specific increase in susceptibility to metabolic syndrome of offspring rats after prenatal caffeine exposure with post-weaning high-fat diet

Energy Technology Data Exchange (ETDEWEB)

Li, Jing [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Luo, Hanwen [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Wu, Yimeng; He, Zheng; Zhang, Li; Guo, Yu [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Ma, Lu [Department of Epidemiology & Health Statistics, Public Health School of Wuhan University, Wuhan 430071 (China); Magdalou, Jacques [UMR 7561 CNRS-NancyUniversité, Faculté de Médicine, Vandoeuvre-lès-Nancy (France); Chen, Liaobin [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071 (China); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071 (China)

2015-05-01

Prenatal caffeine exposure (PCE) alters the hypothalamic–pituitary–adrenocortical (HPA) axis-associated neuroendocrine metabolic programming and induces an increased susceptibility to metabolic syndrome (MS) in intrauterine growth retardation (IUGR) offspring rats. High-fat diet (HFD) is one of the main environmental factors accounting for the incidence of MS. In this study, we aimed to clarify the gender-specific increase in susceptibility to MS in offspring rats after PCE with post-weaning HFD. Maternal Wistar rats were administered with caffeine (120 mg/kg·d) from gestational day 11 until delivery. The offspring rats with normal diet or HFD were euthanized at postnatal week 24, and blood samples were collected. Results showed that PCE not only reduced serum adrenocorticotropic hormone (ACTH) and corticosterone levels, but also enhanced serum glucose, triglyceride and total cholesterol (TCH) concentrations in the offspring rats. Moreover, several interactions among PCE, HFD and gender were observed by a three-way ANOVA analysis. In PCE offspring, HFD could aggravate the degree of increased serum triglyceride level. Meanwhile, serum corticosterone levels of females were decreased more obviously than those of males in PCE offspring. The results also revealed interactions between HFD and gender in the levels of serum ACTH, triglyceride and TCH, which were changed more evidently in female HFD offspring. These results indicate that HFD could exacerbate the dysfunction of lipid metabolism and the susceptibility to MS induced by PCE, and the female offspring are more sensitive to HFD-induced neuroendocrine metabolic dysfunction than their male counterparts. - Highlights: • Caffeine induced HPA axis dysfunction in offspring rats fed by high-fat diet (HFD). • Caffeine induced an increased susceptibility to metabolic syndrome. • HFD aggravated susceptibility to metabolic syndrome induced by caffeine. • Female was more sensitive to HFD-induced neuroendocrine

Gender-specific increase in susceptibility to metabolic syndrome of offspring rats after prenatal caffeine exposure with post-weaning high-fat diet

International Nuclear Information System (INIS)

Li, Jing; Luo, Hanwen; Wu, Yimeng; He, Zheng; Zhang, Li; Guo, Yu; Ma, Lu; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

2015-01-01

Prenatal caffeine exposure (PCE) alters the hypothalamic–pituitary–adrenocortical (HPA) axis-associated neuroendocrine metabolic programming and induces an increased susceptibility to metabolic syndrome (MS) in intrauterine growth retardation (IUGR) offspring rats. High-fat diet (HFD) is one of the main environmental factors accounting for the incidence of MS. In this study, we aimed to clarify the gender-specific increase in susceptibility to MS in offspring rats after PCE with post-weaning HFD. Maternal Wistar rats were administered with caffeine (120 mg/kg·d) from gestational day 11 until delivery. The offspring rats with normal diet or HFD were euthanized at postnatal week 24, and blood samples were collected. Results showed that PCE not only reduced serum adrenocorticotropic hormone (ACTH) and corticosterone levels, but also enhanced serum glucose, triglyceride and total cholesterol (TCH) concentrations in the offspring rats. Moreover, several interactions among PCE, HFD and gender were observed by a three-way ANOVA analysis. In PCE offspring, HFD could aggravate the degree of increased serum triglyceride level. Meanwhile, serum corticosterone levels of females were decreased more obviously than those of males in PCE offspring. The results also revealed interactions between HFD and gender in the levels of serum ACTH, triglyceride and TCH, which were changed more evidently in female HFD offspring. These results indicate that HFD could exacerbate the dysfunction of lipid metabolism and the susceptibility to MS induced by PCE, and the female offspring are more sensitive to HFD-induced neuroendocrine metabolic dysfunction than their male counterparts. - Highlights: • Caffeine induced HPA axis dysfunction in offspring rats fed by high-fat diet (HFD). • Caffeine induced an increased susceptibility to metabolic syndrome. • HFD aggravated susceptibility to metabolic syndrome induced by caffeine. • Female was more sensitive to HFD-induced neuroendocrine

Serum Trace Element Presentation in Female Wistar Rats ...

African Journals Online (AJOL)

Serum Trace Element Presentation in Female Wistar Rats administered with Paracetamol & Paracetamol/Methionine. AA Iyanda, FAA Adeniyi. Abstract. A number of therapeutic agents are known to alter serum trace element levels with dangerous consequences. An earlier study had demonstrated significant alteration in the ...

Serum irisin levels in patients with psoriasis.

Science.gov (United States)

Baran, Anna; Myśliwiec, Hanna; Kiluk, Paulina; Świderska, Magdalena; Flisiak, Iwona

2017-06-01

Irisin has been proposed to regulate metabolic diseases such as obesity, diabetes or metabolic syndrome which are common comorbidities in psoriasis. The aim of this study was to evaluate the serum irisin level in psoriasis and elucidate possible associations with disease activity, inflammatory or metabolic parameters and topical treatment. Thirty-seven individuals with active plaque-type psoriasis and 15 healthy controls were enrolled. Blood samples were collected before and after two weeks of therapy. Serum irisin concentrations were examined by enzyme-linked immunosorbent assay (ELISA). The results were correlated with psoriasis area and severity index (PASI), body mass index (BMI), inflammatory and biochemical markers, lipid profile and effectiveness of topical treatment. Irisin serum levels were insignificantly increased in psoriatic patients in comparison to the controls (p = 0.38). No significant correlations between investigated adipokine and several indicators of metabolic disorders, nor BMI (p = 0.37) or PASI (p = 0.5) were found. Significant positive correlations with C-reactive protein (CRP) (0.009), lipocalin-2 (p = 0.02), age (p = 0.02) and disease duration (p = 0.008) were noted. After topical treatment, serum irisin level did not significantly change (p = 0.31), despite clinical improvement. Irisin might be a marker of inflammation in psoriatic patients, but may not be a reliable indicator of metabolic conditions, severity of psoriasis nor efficacy of antipsoriatic treatment.

Altered serum microRNAs as biomarkers for the early diagnosis of pulmonary tuberculosis infection

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Qi Yuhua

2012-12-01

Full Text Available Abstract Background Pulmonary tuberculosis (TB is a highly lethal infectious disease and early diagnosis of TB is critical for the control of disease progression. The objective of this study was to profile a panel of serum microRNAs (miRNAs as potential biomarkers for the early diagnosis of pulmonary TB infection. Methods Using TaqMan Low-Density Array (TLDA analysis followed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR validation, expression levels of miRNAs in serum samples from 30 patients with active tuberculosis and 60 patients with Bordetella pertussis (BP, varicella-zoster virus (VZV and enterovirus (EV were analyzed. Results The Low-Density Array data showed that 97 miRNAs were differentially expressed in pulmonary TB patient sera compared with healthy controls (90 up-regulated and 7 down-regulated. Following qRT-PCR confirmation and receiver operational curve (ROC analysis, three miRNAs (miR-361-5p, miR-889 and miR-576-3p were shown to distinguish TB infected patients from healthy controls and other microbial infections with moderate sensitivity and specificity (area under curve (AUC value range, 0.711-0.848. Multiple logistic regression analysis of a combination of these three miRNAs showed an enhanced ability to discriminate between these two groups with an AUC value of 0.863. Conclusions Our study suggests that altered levels of serum miRNAs have great potential to serve as non-invasive biomarkers for early detection of pulmonary TB infection.

Early social deprivation impairs pair bonding and alters serum corticosterone and the NAcc dopamine system in mandarin voles.

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Yu, Peng; An, Shucheng; Tai, Fadao; Wang, Jianli; Wu, Ruiyong; Wang, Bo

2013-12-01

Early life stress has a long-term negative impact on emotion, learning, memory and adult sexual behavior, and these deficits most likely impair pair bonding. Here, we investigated whether early social deprivation (ED) affects the formation of pair bonds in socially monogamous mandarin voles (Microtus mandarinus). In a partner preference test (PPT), ED-reared adult females and males did not show a preference for their partner, spent more time exploring the cage of an unfamiliar animal and directed high levels of aggression toward unfamiliar animals. In social interaction test, ED increased exploring behavior only in females, but increased movement around the partner and reduced inactivity in both males and females. Three days of cohabitation did not alter serum corticosterone levels in ED-reared males, but increased corticosterone levels in males that received bi-parental care (PC). Interestingly, serum corticosterone levels in ED- and PC-reared females declined after cohabitation. ED significantly increased basal serum corticosterone levels in males, but had no effect on females. ED significantly up-regulated the levels of dopamine and the mRNA expression of dopamine 1-type receptor (D1R) in the nucleus accumbens (NAcc) in females and males. ED suppressed dopamine 2-type receptor mRNA (D2R) expression in females, but increased this in males. After three days of cohabitation, levels of D1R mRNA and D2R mRNA expression changed in opposite directions in PC-reared voles, but in the same direction in ED-reared males, and only the expression of D2R mRNA increased in ED-reared females. Our results indicate that early social deprivation inhibits pair bonding at adulthood. This inhibition is possibly associated with sex-specific alterations in serum corticosterone, levels of dopamine and mRNA expression of two types of dopamine receptors in the NAcc. Copyright © 2013 Elsevier Ltd. All rights reserved.

Acute Sleep Loss Induces Tissue-Specific Epigenetic and Transcriptional Alterations to Circadian Clock Genes in Men.

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Cedernaes, Jonathan; Osler, Megan E; Voisin, Sarah; Broman, Jan-Erik; Vogel, Heike; Dickson, Suzanne L; Zierath, Juleen R; Schiöth, Helgi B; Benedict, Christian

2015-09-01

Shift workers are at increased risk of metabolic morbidities. Clock genes are known to regulate metabolic processes in peripheral tissues, eg, glucose oxidation. This study aimed to investigate how clock genes are affected at the epigenetic and transcriptional level in peripheral human tissues following acute total sleep deprivation (TSD), mimicking shift work with extended wakefulness. In a randomized, two-period, two-condition, crossover clinical study, 15 healthy men underwent two experimental sessions: x sleep (2230-0700 h) and overnight wakefulness. On the subsequent morning, serum cortisol was measured, followed by skeletal muscle and subcutaneous adipose tissue biopsies for DNA methylation and gene expression analyses of core clock genes (BMAL1, CLOCK, CRY1, PER1). Finally, baseline and 2-h post-oral glucose load plasma glucose concentrations were determined. In adipose tissue, acute sleep deprivation vs sleep increased methylation in the promoter of CRY1 (+4%; P = .026) and in two promoter-interacting enhancer regions of PER1 (+15%; P = .036; +9%; P = .026). In skeletal muscle, TSD vs sleep decreased gene expression of BMAL1 (-18%; P = .033) and CRY1 (-22%; P = .047). Concentrations of serum cortisol, which can reset peripheral tissue clocks, were decreased (2449 ± 932 vs 3178 ± 723 nmol/L; P = .039), whereas postprandial plasma glucose concentrations were elevated after TSD (7.77 ± 1.63 vs 6.59 ± 1.32 mmol/L; P = .011). Our findings demonstrate that a single night of wakefulness can alter the epigenetic and transcriptional profile of core circadian clock genes in key metabolic tissues. Tissue-specific clock alterations could explain why shift work may disrupt metabolic integrity as observed herein.

Low serum cholesterol, serotonin metabolism, and violent death

NARCIS (Netherlands)

P.H.A. Steegmans

1995-01-01

textabstractA high serum cholesterol level is a well documented risk factor for atherosclerotic cardiovascular disease. Consequently, a low serum cholesterol has in general been viewed as beneficial. However, since the early 70s, results from several cohort studies and randomized trials have

Increase in serum albumin concentration is associated with prediabetes development and progression to overt diabetes independently of metabolic syndrome.

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Jun, Ji Eun; Lee, Seung-Eun; Lee, You-Bin; Jee, Jae Hwan; Bae, Ji Cheol; Jin, Sang-Man; Hur, Kyu Yeon; Lee, Moon-Kyu; Kim, Jae Hyeon

2017-01-01

Serum albumin concentration is associated with both type 2 diabetes and metabolic syndrome (MetS). We sought to investigate whether baseline serum albumin and change in serum albumin could be independent risk factors for prediabetes in subjects without MetS. We further examined the effect of serum albumin on progression to overt diabetes in subjects who developed prediabetes. Among 10,792 participants without diabetes and MetS who consecutively underwent yearly health check-ups over six years, 9,807 subjects without incident MetS were enrolled in this longitudinal retrospective study. The risk of developing prediabetes (impared fasting glucose or hemoglobin A1c) was analyzed according to baseline and percent change in serum albumin concentration using Cox regression analysis. Serial changes in serum albumin concentration were measured from baseline to one year before prediabetes diagnosis, and then from the time of prediabetes diagnosis to progression to overt diabetes or final follow-up. A total of 4,398 incident cases of prediabetes developed during 35,807 person-years (median 3.8 years). The hazard ratio for incident prediabetes decreased as percent change in serum albumin concentration (quartiles and per 1%) increased in a crude and fully adjusted model. However, baseline serum albumin concentration itself was not associated with prediabetic risk. Serum albumin levels kept increasing until the end of follow-up in prediabetic subjects who returned to normal glycemic status, whereas these measures did not change in prediabetic subjects who developed type 2 diabetes. Serum albumin concentration measured at the end of follow-up was the highest in the regression group, compared to the stationary (p = 0.014) or progression groups (p = 0.009). Increase in serum albumin concentration might protect against early glycemic deterioration and progression to type 2 diabetes even in subjects without MetS.

Physical exercise in overweight to obese individuals induces metabolic- and neurotrophic-related structural brain plasticity

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Karsten eMueller

2015-07-01

Full Text Available Previous cross-sectional studies on body-weight-related alterations in brain structure revealed profound changes in the gray matter (GM and white matter (WM that resemble findings obtained from individuals with advancing age. This suggests that obesity may lead to structural brain changes that are comparable with brain aging. Here, we asked whether weight-loss-dependent improved metabolic and neurotrophic functioning parallels the reversal of obesity-related alterations in brain structure. To this end we applied magnetic resonance imaging together with voxel-based morphometry and diffusion-tensor imaging in overweight to obese individuals who participated in a fitness course with intensive physical training three days per week over a period of three months. After the fitness course, participants presented, with inter-individual heterogeneity, a reduced body mass index (BMI, reduced serum leptin concentrations, elevated high-density lipoprotein-cholesterol (HDL-C, and alterations of serum brain-derived neurotrophic factor (BDNF concentrations suggesting changes of metabolic and neurotrophic function. Exercise-dependent changes in BMI and serum concentration of BDNF, leptin, and HDL-C were related to an increase in GM density in the left hippocampus, the insular cortex, and the left cerebellar lobule. We also observed exercise-dependent changes of diffusivity parameters in surrounding WM structures as well as in the corpus callosum. These findings suggest that weight-loss due to physical exercise in overweight to obese participants induces profound structural brain plasticity, not primarily of sensorimotor brain regions involved in physical exercise, but of regions previously reported to be structurally affected by an increased body weight and functionally implemented in gustation and cognitive processing.

The alterations of serum FGF-21 levels, metabolic and body composition in early breast cancer patients receiving adjuvant endocrine therapy.

Science.gov (United States)

Akyol, Murat; Alacacioglu, Ahmet; Demir, Leyla; Kucukzeybek, Yuksel; Yildiz, Yasar; Gumus, Zehra; Kara, Mete; Salman, Tarik; Varol, Umut; Taskaynatan, Halil; Oflazoglu, Utku; Bayoglu, Vedat; Tarhan, Mustafa Oktay

2017-01-01

In early breast cancer patients, the effects of hormonal therapy (tamoxifen and aromatase inhibitors) on plasma fibroblast growth factor 21 (FGF-21), lipid levels and body composition have not yet been investigated. Therefore, we aimed to analyze the relationship between FGF-21 and body composition as well as the effects of tamoxifen and aromatase inhibitors on plasma lipid levels, FGF-21, and body composition. A total of 72 patients were treated with either tamoxifen or aromatase inhibitors due to their menopausal status after adjuvant radiotherapy. Each patient was followed-up over a period of 1 year. Changes in body composition and serum lipid profile, glucose and FGF-21 levels were evaluated. We recorded the type of hormonal therapy, body mass index, waist-to-hip ratio, lipid profile, and FGF-21 levels both at the beginning and after 12 months. There was a statistically significant decrease in serum FGF-21 levels after 12 months of adjuvant endocrine therapy (46 ± 19.21 pg/ml vs. 30.99 ± 13.81 pg/ml, pbody water (pbody composition, glucose, lipid profile and FGF-21 were similar in tamoxifen and aromatase inhibitor groups. A positive correlation was found between basal weight, fat mass, fat-free mass and serum FGF-21 levels; however, the correlation was maintained only for the fat-free mass at the 12th month. As part of the present study, we suggest that both tamoxifen and aromatase inhibitors can reduce FGF-21 levels independently of body compositions, and these drugs can provide antihyperlipidemic, antidiabetic and cardio-protective effects. We also recommend that serum FGF-21 level can be utilized as a tumor biomarker in early-stage breast cancer and for monitoring purposes. FGF-21 levels may help physicians estimate prognosis, too. Further studies with larger populations may shed light on the role of FGF-21 in breast cancer.

Amyloid-beta aggregates cause alterations of astrocytic metabolic phenotype: impact on neuronal viability.

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Allaman, Igor; Gavillet, Mathilde; Bélanger, Mireille; Laroche, Thierry; Viertl, David; Lashuel, Hilal A; Magistretti, Pierre J

2010-03-03

Amyloid-beta (Abeta) peptides play a key role in the pathogenesis of Alzheimer's disease and exert various toxic effects on neurons; however, relatively little is known about their influence on glial cells. Astrocytes play a pivotal role in brain homeostasis, contributing to the regulation of local energy metabolism and oxidative stress defense, two aspects of importance for neuronal viability and function. In the present study, we explored the effects of Abeta peptides on glucose metabolism in cultured astrocytes. Following Abeta(25-35) exposure, we observed an increase in glucose uptake and its various metabolic fates, i.e., glycolysis (coupled to lactate release), tricarboxylic acid cycle, pentose phosphate pathway, and incorporation into glycogen. Abeta increased hydrogen peroxide production as well as glutathione release into the extracellular space without affecting intracellular glutathione content. A causal link between the effects of Abeta on glucose metabolism and its aggregation and internalization into astrocytes through binding to members of the class A scavenger receptor family could be demonstrated. Using astrocyte-neuron cocultures, we observed that the overall modifications of astrocyte metabolism induced by Abeta impair neuronal viability. The effects of the Abeta(25-35) fragment were reproduced by Abeta(1-42) but not by Abeta(1-40). Finally, the phosphoinositide 3-kinase (PI3-kinase) pathway appears to be crucial in these events since both the changes in glucose utilization and the decrease in neuronal viability are prevented by LY294002, a PI3-kinase inhibitor. This set of observations indicates that Abeta aggregation and internalization into astrocytes profoundly alter their metabolic phenotype with deleterious consequences for neuronal viability.

Effects Of Walker 256 Carcinoma On Metabolic Alterations During The Evolution Of Pregnancy.

OpenAIRE

Cintra-Gomes M.C.; Cury L.; Parreira M.R.; Elias C.F.; Areas M.A.

1990-01-01

The control of pregnant cancer patients is difficult because it involves both mother and fetus, and the metabolic alterations in the cancer host induce a massive mobilization of nutrients diverted to the neoplastic cells. The purpose of the present study was to determine the evolution of the Walker 256 carcinoma in pregnant rats and its consequences on fetal development. The results showed that the tumors displayed a very rapid rate of growth and induced a reduction in fetal weights in the pr...

Effect of metabolic syndrome on mitsugumin 53 expression and function.

Directory of Open Access Journals (Sweden)

Hanley Ma

Full Text Available Metabolic syndrome is a cluster of risk factors, such as obesity, insulin resistance, and hyperlipidemia that increases the individual's likelihood of developing cardiovascular diseases. Patients inflicted with metabolic disorders also suffer from tissue repair defect. Mitsugumin 53 (MG53 is a protein essential to cellular membrane repair. It facilitates the nucleation of intracellular vesicles to sites of membrane disruption to create repair patches, contributing to the regenerative capacity of skeletal and cardiac muscle tissues upon injury. Since individuals suffering from metabolic syndrome possess tissue regeneration deficiency and MG53 plays a crucial role in restoring membrane integrity, we studied MG53 activity in mice models exhibiting metabolic disorders induced by a 6 month high-fat diet (HFD feeding. Western blotting showed that MG53 expression is not altered within the skeletal and cardiac muscles of mice with metabolic syndrome. Rather, we found that MG53 levels in blood circulation were actually reduced. This data directly contradicts findings presented by Song et. al that indict MG53 as a causative factor for metabolic syndrome (Nature 494, 375-379. The diminished MG53 serum level observed may contribute to the inadequate tissue repair aptitude exhibited by diabetic patients. Furthermore, immunohistochemical analyses reveal that skeletal muscle fibers of mice with metabolic disorders experience localization of subcellular MG53 around mitochondria. This clustering may represent an adaptive response to oxidative stress resulting from HFD feeding and may implicate MG53 as a guardian to protect damaged mitochondria. Therapeutic approaches that elevate MG53 expression in serum circulation may be a novel method to treat the degenerative tissue repair function of diabetic patients.

A comparison of the metabolism of the abortifacient compounds from Ponderosa pine needles in conditioned versus naive cattle.

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Welch, K D; Gardner, D R; Pfister, J A; Panter, K E; Zieglar, J; Hall, J O

2012-12-01

Isocupressic acid (ICA) is the abortifacient compound in ponderosa pine (Pinus ponderosa L.) needles, which can cause late-term abortions in cattle (Bos taurus). However, cattle rapidly metabolize ICA to agathic acid (AGA) and subsequent metabolites. When pine needles are dosed orally to cattle, no ICA is detected in their serum, whereas AGA is readily detected. Recent research has demonstrated that AGA is also an abortifacient compound in cattle. The observation has been made that when cattle are dosed with labdane acids for an extended time, the concentration of AGA in serum increases for 1 to 2 d but then decreases to baseline after 5 to 6 d even though they are still being dosed twice daily. Therefore, in this study we investigated whether cattle conditioned to pine needles metabolize ICA, and its metabolites, faster than naïve cattle. Agathic acid was readily detected in the serum of naïve cattle fed ponderosa pine needles, whereas very little AGA was detected in the serum of cattle conditioned to pine needles. We also compared the metabolism of ICA in vitro using rumen cultures from pine-needle-conditioned and naïve cattle. In the rumen cultures from conditioned cattle, AGA concentrations were dramatically less than rumen cultures from naïve cattle. Thus, an adaptation occurs to cattle conditioned to pine needles such that the metabolism AGA by the rumen microflora is altered.

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

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

2017-12-01

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

Radiation-induced Changes in the Electrophoretic Profile of Serum Albumin

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Celso Vieira Lima

2018-01-01

Full Text Available ABSTRACT Albumin protein profiles were investigated in electrophoresis system in relation to the whole body exposition to the radiation. Two groups of rats Wistar were set up as the control (CG and the irradiated one (IG. The IG was exposed to Co-60 at a dose of 5 Gy. After a 72-hour exposition, 300 μL of blood was collected in the inferior vena cava, renal, jugular, hepatic, and pulmonary veins and the serum separated. The albumin protein was identified by vertical electrophoresis in acrylamide Commassi blue or silver stained. The calibration procedure was applied to albumin samples with well-known concentrations. The mathematical correlation was developed involving electrophoretic parameters of band intensities and sizes from gel representation, providing values of protein concentrations in comparison with standard bands with known concentrations. There were significant differences in the physiological concentrations in the jugular and pulmonary sites in relation to renal and cava regional sites. Significant differences induced by radiation in serum albumin concentration were also found in hepatic and jugular sites. Alteration of albumin concentration was found as a nearly effect from whole body irradiation. This phenomenon points out to alterations in cell metabolism in the liver justified by a possible indication of proteomics damage from radiation.

Inhaled ozone (O3)-induces changes in serum metabolomic and liver transcriptomic profiles in rats☆

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Miller, Desinia B.; Karoly, Edward D.; Jones, Jan C.; Ward, William O.; Vallanat, Beena D.; Andrews, Debora L.; Schladweiler, Mette C.; Snow, Samantha J.; Bass, Virginia L.; Richards, Judy E.; Ghio, Andrew J.; Cascio, Wayne E.; Ledbetter, Allen D.; Kodavanti, Urmila P.

2016-01-01

Air pollution has been linked to increased incidence of diabetes. Recently, we showed that ozone (O3) induces glucose intolerance, and increases serum leptin and epinephrine in Brown Norway rats. In this study, we hypothesized that O3 exposure will cause systemic changes in metabolic homeostasis and that serum metabolomic and liver transcriptomic profiling will provide mechanistic insights. In the first experiment, male Wistar Kyoto (WKY) rats were exposed to filtered air (FA) or O3 at 0.25, 0.50, or 1.0 ppm, 6 h/day for two days to establish concentration-related effects on glucose tolerance and lung injury. In a second experiment, rats were exposed to FA or 1.0 ppm O3, 6 h/day for either one or two consecutive days, and systemic metabolic responses were determined immediately after or 18 h post-exposure. O3 increased serum glucose and leptin on day 1. Glucose intolerance persisted through two days of exposure but reversed 18 h-post second exposure. O3 increased circulating metabolites of glycolysis, long-chain free fatty acids, branched-chain amino acids and cholesterol, while 1,5-anhydroglucitol, bile acids and metabolites of TCA cycle were decreased, indicating impaired glycemic control, proteolysis and lipolysis. Liver gene expression increased for markers of glycolysis, TCA cycle and gluconeogenesis, and decreased for markers of steroid and fat biosynthesis. Genes involved in apoptosis and mitochondrial function were also impacted by O3. In conclusion, short-term O3 exposure induces global metabolic derangement involving glucose, lipid, and amino acid metabolism, typical of a stress–response. It remains to be examined if these alterations contribute to insulin resistance upon chronic exposure. PMID:25838073

LIPID METABOLISM INDICES AND FATTY ACIDS PROFILE IN THE BLOOD SERUM OF BROILER CHICKENS FED A DIET WITH LIGNOCELLULOSE

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M Bogusławska-Tryk

Full Text Available ABSTRACT The aim of the research was to determine lipid metabolism indices and fatty acid profile in the blood serum of Ross 308 chickens (n = 48, fed a finisher mixture supplemented with 0, 0.25, 0.5 and 1.0% of lignocellulose. The feeding trial lasted from 21 to 42 d of the birds' age. Blood samples were collected from each chicken at 42d of age from the pterygoid canal vein. In the blood serum the content of triglycerides (TG, total cholesterol (TCHOL and high density lipoprotein (HDL fraction was determined by the spectrophotometric method. The fatty acids concentration was estimated with the use of the gas chromatography method. Lignocellulose in doses of 0.5 and 1.0% significantly reduced the concentration of triglycerides and low density lipoprotein (LDL fraction. Saturated fatty acids (SFA and monounsaturated fatty acids (MUFA content was not affected by dietary treatments whereas lignocellulose significantly influenced the profile of polyunsaturated fatty acids (PUFA from n-3 and n-6 families. Insoluble fiber decreased (p< 0.05 serum concentration of a-linolenic acid (C18:3n-3 and increased share of docosahexaenoic acid (C22:6n-3, dihomogammalinolenic acid (C20:3n-6 and arachidonic acid (C20:4n-6 in total PUFA, compared to the control birds. The results of the present study have shown that the incorporation of limited amounts of lignocellulose into the broiler diet can influence the lipid metabolism in the chickens.

Uric acid, an important screening tool to detect inborn errors of metabolism: a case series.

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Jasinge, Eresha; Kularatnam, Grace Angeline Malarnangai; Dilanthi, Hewa Warawitage; Vidanapathirana, Dinesha Maduri; Jayasena, Kandana Liyanage Subhashinie Priyadarshika Kapilani Menike; Chandrasiri, Nambage Dona Priyani Dhammika; Indika, Neluwa Liyanage Ruwan; Ratnayake, Pyara Dilani; Gunasekara, Vindya Nandani; Fairbanks, Lynette Dianne; Stiburkova, Blanka

2017-09-06

Uric acid is the metabolic end product of purine metabolism in humans. Altered serum and urine uric acid level (both above and below the reference ranges) is an indispensable marker in detecting rare inborn errors of metabolism. We describe different case scenarios of 4 Sri Lankan patients related to abnormal uric acid levels in blood and urine. CASE 1: A one-and-half-year-old boy was investigated for haematuria and a calculus in the bladder. Xanthine crystals were seen in microscopic examination of urine sediment. Low uric acid concentrations in serum and low urinary fractional excretion of uric acid associated with high urinary excretion of xanthine and hypoxanthine were compatible with xanthine oxidase deficiency. CASE 2: An 8-month-old boy presented with intractable seizures, feeding difficulties, screaming episodes, microcephaly, facial dysmorphism and severe neuro developmental delay. Low uric acid level in serum, low fractional excretion of uric acid and radiological findings were consistent with possible molybdenum cofactor deficiency. Diagnosis was confirmed by elevated levels of xanthine, hypoxanthine and sulfocysteine levels in urine. CASE 3: A 3-year-10-month-old boy presented with global developmental delay, failure to thrive, dystonia and self-destructive behaviour. High uric acid levels in serum, increased fractional excretion of uric acid and absent hypoxanthine-guanine phosphoribosyltransferase enzyme level confirmed the diagnosis of Lesch-Nyhan syndrome. CASE 4: A 9-year-old boy was investigated for lower abdominal pain, gross haematuria and right renal calculus. Low uric acid level in serum and increased fractional excretion of uric acid pointed towards hereditary renal hypouricaemia which was confirmed by genetic studies. Abnormal uric acid level in blood and urine is a valuable tool in screening for clinical conditions related to derangement of the nucleic acid metabolic pathway.

Multifunctional roles of enolase in Alzheimer's disease brain: beyond altered glucose metabolism.

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Butterfield, D Allan; Lange, Miranda L Bader

2009-11-01

Enolase enzymes are abundantly expressed, cytosolic carbon-oxygen lyases known for their role in glucose metabolism. Recently, enolase has been shown to possess a variety of different regulatory functions, beyond glycolysis and gluconeogenesis, associated with hypoxia, ischemia, and Alzheimer's disease (AD). AD is an age-associated neurodegenerative disorder characterized pathologically by elevated oxidative stress and subsequent damage to proteins, lipids, and nucleic acids, appearance of neurofibrillary tangles and senile plaques, and loss of synapse and neuronal cells. It is unclear if development of a hypometabolic environment is a consequence of or contributes to AD pathology, as there is not only a significant decline in brain glucose levels in AD, but also there is an increase in proteomics identified oxidatively modified glycolytic enzymes that are rendered inactive, including enolase. Previously, our laboratory identified alpha-enolase as one the most frequently up-regulated and oxidatively modified proteins in amnestic mild cognitive impairment (MCI), early-onset AD, and AD. However, the glycolytic conversion of 2-phosphoglycerate to phosphoenolpyruvate catalyzed by enolase does not directly produce ATP or NADH; therefore it is surprising that, among all glycolytic enzymes, alpha-enolase was one of only two glycolytic enzymes consistently up-regulated from MCI to AD. These findings suggest enolase is involved with more than glucose metabolism in AD brain, but may possess other functions, normally necessary to preserve brain function. This review examines potential altered function(s) of brain enolase in MCI, early-onset AD, and AD, alterations that may contribute to the biochemical, pathological, clinical characteristics, and progression of this dementing disorder.

Induction of autophagy by ARHI (DIRAS3) alters fundamental metabolic pathways in ovarian cancer models

International Nuclear Information System (INIS)

Ornelas, Argentina; McCullough, Christopher R.; Lu, Zhen; Zacharias, Niki M.; Kelderhouse, Lindsay E.; Gray, Joshua; Yang, Hailing; Engel, Brian J.; Wang, Yan; Mao, Weiqun; Sutton, Margie N.; Bhattacharya, Pratip K.; Bast, Robert C. Jr.; Millward, Steven W.

2016-01-01

Autophagy is a bulk catabolic process that modulates tumorigenesis, therapeutic resistance, and dormancy. The tumor suppressor ARHI (DIRAS3) is a potent inducer of autophagy and its expression results in necroptotic cell death in vitro and tumor dormancy in vivo. ARHI is down-regulated or lost in over 60 % of primary ovarian tumors yet is dramatically up-regulated in metastatic disease. The metabolic changes that occur during ARHI induction and their role in modulating death and dormancy are unknown. We employed Nuclear Magnetic Resonance (NMR)-based metabolomic strategies to characterize changes in key metabolic pathways in both cell culture and xenograft models of ARHI expression and autophagy. These pathways were further interrogated by cell-based immunofluorescence imaging, tracer uptake studies, targeted metabolic inhibition, and in vivo PET/CT imaging. Induction of ARHI in cell culture models resulted in an autophagy-dependent increase in lactate production along with increased glucose uptake and enhanced sensitivity to glycolytic inhibitors. Increased uptake of glutamine was also dependent on autophagy and dramatically sensitized cultured ARHI-expressing ovarian cancer cell lines to glutaminase inhibition. Induction of ARHI resulted in a reduction in mitochondrial respiration, decreased mitochondrial membrane potential, and decreased Tom20 staining suggesting an ARHI-dependent loss of mitochondrial function. ARHI induction in mouse xenograft models resulted in an increase in free amino acids, a transient increase in [ 18 F]-FDG uptake, and significantly altered choline metabolism. ARHI expression has previously been shown to trigger autophagy-associated necroptosis in cell culture. In this study, we have demonstrated that ARHI expression results in decreased cellular ATP/ADP, increased oxidative stress, and decreased mitochondrial function. While this bioenergetic shock is consistent with programmed necrosis, our data indicates that the accompanying up

The metabolic impact of methamphetamine on the systemic metabolism of rats and potential markers of methamphetamine abuse.

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Zheng, Tian; Liu, Linsheng; Shi, Jian; Yu, Xiaoyi; Xiao, Wenjing; Sun, Runbing; Zhou, Yahong; Aa, Jiye; Wang, Guangji

2014-07-01

Although the stimulating and psychotropic effects of methamphetamine (METH) on the nervous system are well documented, the impact of METH abuse on biological metabolism and the turnover of peripheral transmitters are poorly understood. Metabolomics has the potential to reveal the effect of METH abuse on systemic metabolism and potential markers suggesting the underlying mechanism of toxicity. In this study, male Sprague Dawley rats were intraperitoneally injected with METH at escalating doses of mg kg(-1) for 5 consecutive days and then were withdrawn for 2 days. The metabolites in the serum and urine were profiled and the systemic effects of METH on metabolic pathways were evaluated. Multivariate statistical analysis showed that METH caused distinct deviations, whereas the withdrawal of METH restored the metabolic patterns towards baseline. METH administration elevated energy metabolism, which was manifested by the distinct depletion of branched-chain amino acids, accelerated tricarboxylic-acid cycle and lipid metabolism, reduced serum glycerol-3-phosphate, and elevated serum and urinary 3-hydroxybutyrate and urinary glycerol. In addition to the increased serum levels of the excitatory amino acids glutamate and aspartate (the inhibitory neurotransmitters in the brain), a marked decline in serum alanine and glycine after METH treatment suggested the activation and decreased inhibition of the nervous system and hence elevated nervous activity. Withdrawal of METH for 2 days efficiently restored all but a few metabolites to baseline, including serum creatinine, citrate, 2-ketoglutarate, and urinary lactate. Therefore, these metabolites are potential markers of METH use, and they may be used to facilitate the diagnosis of METH abuse.

Genetic alterations in fatty acid transport and metabolism genes are associated with metastatic progression and poor prognosis of human cancers.

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Nath, Aritro; Chan, Christina

2016-01-04

Reprogramming of cellular metabolism is a hallmark feature of cancer cells. While a distinct set of processes drive metastasis when compared to tumorigenesis, it is yet unclear if genetic alterations in metabolic pathways are associated with metastatic progression of human cancers. Here, we analyzed the mutation, copy number variation and gene expression patterns of a literature-derived model of metabolic genes associated with glycolysis (Warburg effect), fatty acid metabolism (lipogenesis, oxidation, lipolysis, esterification) and fatty acid uptake in >9000 primary or metastatic tumor samples from the multi-cancer TCGA datasets. Our association analysis revealed a uniform pattern of Warburg effect mutations influencing prognosis across all tumor types, while copy number alterations in the electron transport chain gene SCO2, fatty acid uptake (CAV1, CD36) and lipogenesis (PPARA, PPARD, MLXIPL) genes were enriched in metastatic tumors. Using gene expression profiles, we established a gene-signature (CAV1, CD36, MLXIPL, CPT1C, CYP2E1) that strongly associated with epithelial-mesenchymal program across multiple cancers. Moreover, stratification of samples based on the copy number or expression profiles of the genes identified in our analysis revealed a significant effect on patient survival rates, thus confirming prominent roles of fatty acid uptake and metabolism in metastatic progression and poor prognosis of human cancers.

Association of Serum Ceruloplasmin Level with Obesity: Some Components of Metabolic Syndrome and High-Sensitive C-Reactive Protein in Iran

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Seyyed Morteza Safavi

2012-01-01

Full Text Available Background. One of the mechanisms that has been suggested for obesity related metabolic disturbances is obesity-induced inflammation. Pro-inflammatory cytokines generated in adipose tissue can increase hepatic synthesis of inflammation-sensitive plasma proteins (ISPs including ceruloplasmin (Cp. In this study we aimed to investigate the relation between serum Cp level and obesity. Methods. 61 persons with body mass index (BMI ≥ 25 kg/m2 (case group and 61 persons with BMI < 25 kg/m2 (control group were included in this study with a case-control design. Serum Cp levels, triglyceride level, fating blood glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol and hsCRP were measured in both groups. Results. We did not observe any significant association between serum Cp level and BMI in all subjects [OR: 1.02 (CI, 0.967 to 1.07] and in case (β=0.012, P=0.86 and control groups (β=0.49, P=0.07 separately. However, in control group, this positive association was marginally significant. We found a positive correlation between serum Cp level and serum triglyceride level. Conclusion. Serum Cp level was not related to obesity in this group of subjects. None of the baseline variables could predict obesity in this group of subjects, including serum Cp level, FBS, total cholesterol, LDL and HDL- cholesterols and hsCRP.

Protective effect of Psidium guajava leaf extract on altered carbohydrate metabolism in streptozotocin-induced diabetic rats.

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Khan, Haseena Banu Hedayathullah; Shanmugavalli, R; Rajendran, Deepa; Bai, Mookambikai Ramya; Sorimuthu, Subramanian

2013-12-01

Psidium guajava is an important plant of high medicinal value and has been used in traditional systems of medicine against various ailments. The antidiabetic effect of the ethanolic extract of Psidium guajava leaves and also its protective effect on altered glucose metabolism was evaluated in streptozotocin (stz)-induced diabetic rat model. Diabetes was induced in rats by means of intraperitoneal injection of 50-mg/kg body weight (b.wt.) of stz. Diabetes-induced rats were randomly divided into two groups. One group of rats was treated with Psidium guajava leaf extract at a dosage of 300-mg/kg b.wt. and the other group of rats was treated with the standard drug glyclazide at a dosage of 5-mg/kg b.wt. for 30 days. The blood glucose levels, plasma insulin, Hb, HbA1c were measured. The effect on the drug on altered glucose metabolizing enzymes were also studied. Treatment with Psidium guajava extract showed a significant reduction in blood glucose and HbA1c levels and a significant increase in plasma insulin levels. The drug also significantly restored the activities of carbohydrate metabolizing enzymes. This suggests that the potential antidiabetic effect of the ethanolic extract of the Psidium guajava leaves may be due to the presence of flavonoids and other phenolic components present in the drug.

Serum levels of parathyroid hormone and markers of bone metabolism in patients with rheumatoid arthritis. Relationship to disease activity and glucocorticoid treatment

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Jensen, Tonny Joran; Hansen, M; Madsen, J C

2001-01-01

OBJECTIVE: To evaluate the influence of inflammatory activity and glucocorticoid (GC) treatment on serum parathyroid hormone (s-PTH) and bone metabolism in patients with rheumatoid arthritis (RA). Furthermore, in patients with active RA, to examine the PTH secretion and Ca2+ set point before and ....... The increased levels of markers of type I collagen metabolism (s-ICTP, Pyr) and s-AlbCorrCa2+ in patients with active disease and patients treated with GC may be a result of increased degradation in synovium, cartilage and bone due to the inflammatory process.......OBJECTIVE: To evaluate the influence of inflammatory activity and glucocorticoid (GC) treatment on serum parathyroid hormone (s-PTH) and bone metabolism in patients with rheumatoid arthritis (RA). Furthermore, in patients with active RA, to examine the PTH secretion and Ca2+ set point before...... groups. The levels of urine pyridinoline (Pyr) and s-albumin-corrected calcium (s-AlbCorrCa2+) were elevated in patients with active disease and patients treated with GC. S-PTH and s-phosphate were within normal ranges. S-TAP, s-ICTP, Pyr and s-AlbCorrCa2+ correlated positively with indices of disease...

Proteomic analysis revealed alterations of the Plasmodium falciparum metabolism following salicylhydroxamic acid exposure

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Torrentino-Madamet M

2011-09-01

Full Text Available Marylin Torrentino-Madamet1, Lionel Almeras2, Christelle Travaillé1, Véronique Sinou1, Matthieu Pophillat3, Maya Belghazi4, Patrick Fourquet3, Yves Jammes5, Daniel Parzy11UMR-MD3, Université de la Méditerranée, Antenne IRBA de Marseille (IMTSSA, Le Pharo, 2Unité de Recherche en Biologie et Epidémiologie Parasitaires, Antenne IRBA de Marseille (IMTSSA, Le Pharo, 3Centre d'Immunologie de Marseille Luminy, Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique, Université de la Méditerranée, 4Centre d'Analyse Protéomique de Marseille, Institut Fédératif de Recherche Jean Roche, Faculté de Médecine Nord, 5UMR-MD2, Physiologie et Physiopathologie en Conditions d'Oxygénations Extrêmes, Institut Fédératif de Recherche Jean Roche, Faculté de Médecine Nord, Marseille, FranceObjectives: Although human respiratory metabolism is characterized by the mitochondrial electron transport chain, some organisms present a “branched respiratory chain.” This branched pathway includes both a classical and an alternative respiratory chain. The latter involves an alternative oxidase. Though the Plasmodium falciparum alternative oxidase is not yet identified, a specific inhibitor of this enzyme, salicylhydroxamic acid (SHAM, showed a drug effect on P. falciparum respiratory function using oxygen consumption measurements. The present study aimed to highlight the metabolic pathways that are affected in P. falciparum following SHAM exposure.Design: A proteomic approach was used to analyze the P. falciparum proteome and determine the metabolic pathways altered following SHAM treatment. To evaluate the SHAM effect on parasite growth, the phenotypic alterations of P. falciparum after SHAM or/and hyperoxia exposure were observed.Results: After SHAM exposure, 26 proteins were significantly deregulated using a fluorescent two dimensional-differential gel electrophoresis. Among these deregulated proteins

Metabolic Signatures of Kidney Yang Deficiency Syndrome and Protective Effects of Two Herbal Extracts in Rats Using GC/TOF MS

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Linjing Zhao

2013-01-01

Full Text Available Kidney Yang Deficiency Syndrome (KDS-Yang, a typical condition in Chinese medicine, shares similar clinical signs of the glucocorticoid withdrawal syndrome. To date, the underlying mechanism of KDS-Yang has been remained unclear, especially at the metabolic level. In this study, we report a metabolomic profiling study on a classical model of KDS-Yang in rats induced by hydrocortisone injection to characterize the metabolic transformation using gas chromatography/time-of-flight mass spectrometry. WKY1, a polysaccharide extract from Astragalus membranaceus and Lycium barbarum, and WKY2, an aqueous extract from a similar formula containing Astragalus membranaceus, Lycium barbarum, Morinda officinalis, Taraxacum mongolicum, and Cinnamomum cassia presl, were used separately for protective treatments of KDS-Yang. The changes of serum metabolic profiles indicated that significant alterations of key metabolic pathways in response to abrupt hydrocortisone perturbation, including decreased energy metabolism (lactic acid, acetylcarnitine, lipid metabolism (free fatty acids, 1-monolinoleoylglycerol, and cholesterol, gut microbiota metabolism (indole-3-propionic acid, biosynthesis of catecholamine (norepinephrine, and elevated alanine metabolism, were attenuated or normalized with different degrees by the pretreatment of WKY1 or WKY2, which is consistent with the observations in which the two herbal agents could ameliorate biochemical markers of serum cortisone, adrenocorticotropic (ACTH, and urine 17-hydroxycorticosteroids (17-OHCS.

Does canine inflammatory bowel disease influence gut microbial profile and host metabolism?

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Xu, Jia; Verbrugghe, Adronie; Lourenço, Marta; Janssens, Geert P J; Liu, Daisy J X; Van de Wiele, Tom; Eeckhaut, Venessa; Van Immerseel, Filip; Van de Maele, Isabel; Niu, Yufeng; Bosch, Guido; Junius, Greet; Wuyts, Brigitte; Hesta, Myriam

2016-06-16

Inflammatory bowel disease (IBD) refers to a diverse group of chronic gastrointestinal diseases, and gut microbial dysbiosis has been proposed as a modulating factor in its pathogenesis. Several studies have investigated the gut microbial ecology of dogs with IBD but it is yet unclear if this microbial profile can alter the nutrient metabolism of the host. The aim of the present study was to characterize the faecal bacterial profile and functionality as well as to determine host metabolic changes in IBD dogs. Twenty-three dogs diagnosed with IBD and ten healthy control dogs were included. Dogs with IBD were given a clinical score using the canine chronic enteropathy clinical activity index (CCECAI). Faecal short-chain fatty acids (SCFA) and ammonia concentrations were measured and quantitative PCR was performed. The concentration of plasma amino acids, acylcarnitines, serum folate, cobalamin, and indoxyl sulfate was determined. No significant differences in the abundance of a selection of bacterial groups and fermentation metabolites were observed between the IBD and control groups. However, significant negative correlations were found between CCECAI and the faecal proportion of Lactobacillus as well as between CCECAI and total SCFA concentration. Serum folate and plasma citrulline were decreased and plasma valine was increased in IBD compared to control dogs. Increased plasma free carnitine and total acylcarnitines were observed in IBD compared with control dogs, whereas short-chain acylcarnitines (butyrylcarnitine + isobutyrylcarnitine and, methylmalonylcarnitine) to free carnitine ratios decreased. Dogs with IBD had a higher 3-hydroxyisovalerylcarnitine + isovalerylcarnitine to leucine ratio compared to control dogs. Canine IBD induced a wide range of changes in metabolic profile, especially for the plasma concentrations of short-chain acylcarnitines and amino acids, which could have evolved from tissue damage and alteration in host metabolism. In

High-fat diet feeding alters metabolic response to fasting/non fasting conditions. Effect on caveolin expression and insulin signalling.

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Gómez-Ruiz, Ana; Milagro, Fermín I; Campión, Javier; Martínez, J Alfredo; de Miguel, Carlos

2011-04-13

The effect of food intake on caveolin expression in relation to insulin signalling was studied in skeletal muscle and adipocytes from retroperitoneal (RP) and subcutaneous (SC) adipose tissue, comparing fasted (F) to not fasted (NF) rats that had been fed a control or high-fat (HF) diet for 72 days. Serum glucose was analysed enzymatically and insulin and leptin by ELISA. Caveolins and insulin signalling intermediaries (IR, IRS-1 and 2 and GLUT4) were determined by RT-PCR and western blotting. Caveolin and IR phosphorylation was measured by immunoprecipitation. Data were analysed with Mann-Whitney U test. High-fat fed animals showed metabolic alterations and developed obesity and insulin resistance. In skeletal muscle, food intake (NF) induced activation of IR and increased expression of IRS-2 in control animals with normal metabolic response. HF animals became overweight, hyperglycaemic, hyperinsulinemic, hyperleptinemic and showed insulin resistance. In skeletal muscle of these animals, food intake (NF) also induced IRS-2 expression together with IR, although this was not active. Caveolin 3 expression in this tissue was increased by food intake (NF) in animals fed either diet. In RP adipocytes of control animals, food intake (NF) decreased IR and IRS-2 expression but increased that of GLUT4. A similar but less intense response was found in SC adipocytes. Food intake (NF) did not change caveolin expression in RP adipocytes with either diet, but in SC adipocytes of HF animals a reduction was observed. Food intake (NF) decreased caveolin-1 phosphorylation in RP but increased it in SC adipocytes of control animals, whereas it increased caveolin-2 phosphorylation in both types of adipocytes independently of the diet. Animals fed a control-diet show a normal response to food intake (NF), with activation of the insulin signalling pathway but without appreciable changes in caveolin expression, except a small increase of caveolin-3 in muscle. Animals fed a high-fat diet

Adipose tissue and metabolic and inflammatory responses to stroke are altered in obese mice

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Michael J. Haley

2017-10-01

Full Text Available Obesity is an independent risk factor for stroke, although several clinical studies have reported that obesity improves stroke outcome. Obesity is hypothesised to aid recovery by protecting against post-stroke catabolism. We therefore assessed whether obese mice had an altered metabolic and inflammatory response to stroke. Obese ob/ob mice underwent a 20-min middle cerebral artery occlusion and 24-h reperfusion. Lipid metabolism and expression of inflammatory cytokines were assessed in the plasma, liver and adipose tissue. The obese-specific metabolic response to stroke was assessed in plasma using non-targeted ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS metabolomics coupled with univariate and multivariate analysis. Obesity had no effect on the extent of weight loss 24 h after stroke but affected the metabolic and inflammatory responses to stroke, predominantly affecting lipid metabolism. Specifically, obese mice had increases in plasma free fatty acids and expression of adipose lipolytic enzymes. Metabolomics identified several classes of metabolites affected by stroke in obese mice, including fatty acids and membrane lipids (glycerophospholipids, lysophospholipids and sphingolipids. Obesity also featured increases in inflammatory cytokines in the plasma and adipose tissue. Overall, these results demonstrate that obesity affected the acute metabolic and inflammatory response to stroke and suggest a potential role for adipose tissue in this effect. These findings could have implications for longer-term recovery and also further highlight the importance of considering comorbidities in preclinical stroke research, especially when identifying biomarkers for stroke. However, further work is required to assess whether these changes translate into long-term effects on recovery.

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.

Purification of PON1 from human serum and assessment of enzyme kinetics against metal toxicity.

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Ekinci, Deniz; Beydemir, Sükrü

2010-06-01

Paraoxonase-1 (PON1) is an organophosphate hydrolyser enzyme which has also antioxidant properties in metabolism. Due to its crucial functions, inhibition of the enzyme is undesirable and very dangerous. PON1 enzyme activity should not be altered in any case. Inhibitory investigations of this enzyme are therefore important and useful. Metal toxicology of enzymes has become popular in the recent years. Here, we report the in vitro inhibitory effects of some metal ions, including Pb(+2), Cr(+2), Fe(+2), and Zn(+2), on the activity of human serum PON1 (hPON1; EC 3.1.8.1.). For this purpose, we purified the enzyme from human serum and analyzed the alterations in the enzyme activity in the presence of metal ions. The results show that metal ions exhibit inhibitory effects on hPON1 at low concentrations with IC (50) values ranging from 0.838 to 7.410 mM. Metal ions showed different inhibition mechanisms: lead and iron were competitive, chrome was noncompetitive, and zinc was uncompetitive. Lead was determined to be the most effective inhibitor.

Patients with Treatment-Requiring Chronic Graft versus Host Disease after Allogeneic Stem Cell Transplantation Have Altered Metabolic Profiles due to the Disease and Immunosuppressive Therapy: Potential Implication for Biomarkers

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Håkon Reikvam

2018-01-01

Full Text Available Chronic graft versus host disease (cGVHD is a common long-term complication after allogeneic hematopoietic stem cell transplantation. The objective of our study was to compare the metabolic profiles for allotransplant recipients and thereby identify metabolic characteristics of patients with treatment-requiring cGVHD. The study included 51 consecutive patients (29 men and 22 women; median age: 44 years, range: 15–66 years transplanted with peripheral blood stem cells derived from human leukocyte antigen-matched family donors. All serum samples investigated by global metabolomic profiling were collected approximately 1 year posttransplant (median 358 days. Thirty-one of the 51 patients (61% had cGVHD 1 year posttransplant. The affected organs were (number of patients liver/bile duct (23, eyes (15, gastrointestinal tract (14, skin (13, mouth (10, lungs (3, and urogenital tract (1. We compared the metabolic profile for patients with and without cGVHD, and a Random Forrest Classification Analysis then resulted in 75% accuracy in differentiating the two groups. The 30 top-ranked metabolites from this comparison included increased levels of bile acids, several metabolites from the cytokine-responsive kynurenine pathway for tryptophan degradation, pro-inflammatory lipid metabolites, phenylalanine and tyrosine metabolites derived from the gut microbial flora, and metabolites reflecting increased oxidative stress. However, nine of these 30 top-ranked metabolites were probably altered due to cyclosporine or steroid treatment, and we therefore did a hierarchical clustering analysis including all 51 patients but only based on the other 21 cGVHD-specific metabolites. This analysis identified three patient subsets: one cluster included mainly patients without cGVHD and had generally low metabolite levels; another cluster included mainly patients with cGVHD (most patients with at least three affected organs and high metabolite levels, and the last

Serum Leptin Levels in Polycystic Ovary Syndrome and Its Relationship with Metabolic and Hormonal Profile in Pakistani Females

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Mukhtiar Baig

2014-01-01

Full Text Available The study aimed to investigate the levels of serum leptin in PCOS females and to correlate it with metabolic and hormonal parameters. Sixty-two PCOS and ninety normal cycling (NC females with matched age and body mass index (BMI were recruited for this cross-sectional study. Serum leptin, FSH, LH, E2, free testosterone, progesterone, thyroid profile, and FBG levels were measured. The mean leptin levels in PCOS and NC were not significantly different (45.56 ng/mL ± 1.49 vs 41.78 ± 1.31 ng/mL, P>0.05; however, leptin levels showed a strong correlation with BMI in PCOS and NC group (r=0.77, P<0.0001; r=0.82, P<0.0001, resp.. High E2 levels in NC had a significant correlation with leptin whereas FBG correlated with leptin in PCOS (r=0.51, P=0.005. TSH had a substantial correlation (r=0.49, P<0.005; r=0.69, P<0.005 in PCOS and NC, respectively. There was no significant difference found in circulating leptin concentration between PCOS and NC subjects. Leptin levels in PCOS were related with metabolic impairments manifested by disturbance in FBG levels and impairment of reproductive functions in terms of reduced E2 secretion.

Metabolic alterations in broiler chickens experimentally infected with sporulated oocysts of Eimeria maxima.

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Freitas, Fagner Luiz da Costa

2014-01-01

Metabolic and morphometric alterations of the duodenal villi caused by parasitism of chickens by Eimeria maxima were evaluated, using 100 male Cobb birds, randomly distributed into two groups (control and infected). The infected group was inoculated with 0.5 ml of a solution containing 5 × 10³ sporulated oocysts of Eimeria maxima. Ten birds per sample were sacrificed on the 6th, 11th, 22nd and 41st days post-infection (dpi). In order to evaluate the alterations, samples of duodenum, jejunum and ileum fragments were collected after necropsy for histological analysis. Villus biometry was determined by means of a slide graduated in microns that was attached to a binocular microscope. To evaluate the biochemical data, 5 ml of blood were sampled from the birds before sacrifice. The statistical analyses were performed using the GraphPad 5 statistical software for Windows. Tukey's multiple comparison test (p maxima causes both qualitative and quantitative alterations to the structure of the intestinal villi, thereby interfering with the absorption of nutrients such as calcium, phosphorus, magnesium, protein and lipids, with consequent reductions in the birds' weights.

Study on the relationship between serum IL-6, Sgp80, Sgp130 levels and bone metabolism in patients with Graves' disease

International Nuclear Information System (INIS)

Liu Chunyu; Mu Junqing; Zou Jianwen; Liu Songtao

2007-01-01

Objective: To investigate the relationship between serum IL-6, Sgp80, Sgpl30 levels and bone metabolism in patients with Graves' disease. Methods: Serum levels of IL-6 (with RIA), Sgp80, Sgpl30 (with ELISA) as well as BMD of proximal femur region were determined in 78 patients with Graves' disease (26 not treated yet, 26 partially remitted and 26 in remission) and 30 controls. Results: The serum IL-6 and Sgpl30 levels in all the patients with Graves' disease were significantly higher than those in controls (P 3 , FT 4 , phosphorous, BGP and urinary hydroxy proline levels. BMD of the proximal femur region in patients partially remitted were much lower than that in controls (P<0.05). Conclusion: Serum Sgp80 level might be taken as an important parameter in studying of Graves' disease. Bone loss, both cortical and trabecular, occurred in patients with Graves' disease. Increase of bone formation as well as bone resorption were primary, not secondary to each other. (authors)

A High-Fat Diet Causes Impairment in Hippocampal Memory and Sex-Dependent Alterations in Peripheral Metabolism

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Erica L. Underwood

2016-01-01

Full Text Available While high-fat diets are associated with rising incidence of obesity/type-2 diabetes and can induce metabolic and cognitive deficits, sex-dependent comparisons are rarely systematically made. Effects of exclusive consumption of a high-fat diet (HFD on systemic metabolism and on behavioral measures of hippocampal-dependent memory were compared in young male and female LE rats. Littermates were fed from weaning either a HFD or a control diet (CD for 12 wk prior to testing. Sex-different effects of the HFD were observed in classic metabolic signs associated with type-2 diabetes. Males fed the HFD became obese, and had elevated fasted blood glucose levels, elevated corticosterone, and impaired glucose-tolerance, while females on the HFD exhibited only elevated corticosterone. Regardless of peripheral metabolism alteration, rats of both sexes fed the HFD were equally impaired in a spatial object recognition memory task associated with impaired hippocampal function. While the metabolic changes reported here have been characterized previously in males, the set of diet-induced effects observed here in females are novel. Impaired memory can have significant cognitive consequences, over the short-term and over the lifespan. A significant need exists for comparative research into sex-dependent differences underlying obesity and metabolic syndromes relating systemic, cognitive, and neural plasticity mechanisms.

Serum progranulin levels in relation to insulin resistance in childhood obesity.

Science.gov (United States)

Alissa, Eman M; Sutaih, Rima H; Kamfar, Hayat Z; Alagha, Abdulmoeen E; Marzouki, Zuhair M

2017-11-27

Progranulin is an adipokine that is involved in the inflammatory response, glucose metabolism, insulin resistance, and may therefore be involved in chronic subclinical inflammation associated with the pathogenesis of childhood obesity. We aimed to investigate the association of circulating progranulin levels with metabolic parameters in children and to assess the importance of progranulin as a biomarker for metabolic diseases. A total of 150 children were consecutively recruited from the Pediatric Nutrition Clinics at King Abdulaziz University Hospital in Jeddah, Saudi Arabia. Children were classified into four groups based on quartile for serum progranulin. Anthropometric variables were measured in all study subjects. Fasting blood samples were collected for measurement of blood glucose, insulin and lipid profile. Children within the upper quartile for serum progranulin concentration were heavier, more insulin resistant and had higher concentrations of serum total cholesterol, triglycerides, insulin and high sensitivity C reactive protein compared to those in the lower quartile. On correlation analysis, serum progranulin concentrations were significantly related to general and central adiposity, metabolic parameters, markers of inflammation and insulin resistance. Stepwise multiple regression showed that 26.6% of the variability in serum progranulin could be explained by measures of adiposity. The increased serum progranulin concentrations were closely related to measures of adiposity, metabolic parameters, inflammatory marker and insulin resistance indices, suggesting that progranulin may be an excellent biomarker for obesity in childhood.

Metabolic Profiling Analysis of the Alleviation Effect of Treatment with Baicalin on Cinnabar Induced Toxicity in Rats Urine and Serum

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Guangyue Su

2017-05-01

Full Text Available Objectives: Baicalin is the main bioactive flavonoid constituent isolated from Scutellaria baicalensis Georgi. The mechanisms of protection of liver remain unclear. In this study, 1H NMR-based metabonomics approach has been used to investigate the alleviation effect of Baicalin.Method:1H NMR metabolomics analyses of urine and serum from rats, was performed to illuminate the alleviation effect of Baicalin on mineral medicine (cinnabar-induced liver and kidney toxicity.Results: The metabolic profiles of groups receiving Baicalin at a dose of 80 mg/kg were remarkably different from cinnabar, and meanwhile, the level of endogenous metabolites returned to normal compared to group cinnabar. PLS-DA scores plots demonstrated that the variation tendency of control and Baicalein are apart from Cinnabar. The metabolic profiles of group Baicalein were similar to those of group control. Statistics results were confirmed by the histopathological examination and biochemical assay.Conclusion: Baicalin have the alleviation effect to the liver and kidney damage induced by cinnabar. The Baicalin could regulate endogenous metabolites associated with the energy metabolism, choline metabolism, amino acid metabolism, and gut flora.

Effects of independently altering body weight and body mass on the metabolic cost of running.

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Teunissen, Lennart P J; Grabowski, Alena; Kram, Rodger

2007-12-01

The metabolic cost of running is substantial, despite the savings from elastic energy storage and return. Previous studies suggest that generating vertical force to support body weight and horizontal forces to brake and propel body mass are the major determinants of the metabolic cost of running. In the present study, we investigated how independently altering body weight and body mass affects the metabolic cost of running. Based on previous studies, we hypothesized that reducing body weight would decrease metabolic rate proportionally, and adding mass and weight would increase metabolic rate proportionally. Further, because previous studies show that adding mass alone does not affect the forces generated on the ground, we hypothesized that adding mass alone would have no substantial effect on metabolic rate. We manipulated the body weight and body mass of 10 recreational human runners and measured their metabolic rates while they ran at 3 m s(-1). We reduced weight using a harness system, increased mass and weight using lead worn about the waist, and increased mass alone using a combination of weight support and added load. We found that net metabolic rate decreased in less than direct proportion to reduced body weight, increased in slightly more than direct proportion to added load (added mass and weight), and was not substantially different from normal running with added mass alone. Adding mass alone was not an effective method for determining the metabolic cost attributable to braking/propelling body mass. Runners loaded with mass alone did not generate greater vertical or horizontal impulses and their metabolic costs did not substantially differ from those of normal running. Our results show that generating force to support body weight is the primary determinant of the metabolic cost of running. Extrapolating our reduced weight data to zero weight suggests that supporting body weight comprises at most 74% of the net cost of running. However, 74% is probably an

Clinico-haematological and serum biochemical alterations in ...

African Journals Online (AJOL)

An increase in serum CRE and BUN values were recorded in all cases of pyometra which reduced to lower levels during both treatments in follow-ups. All the haemato-biochemical parameters were comparable to their respective reference values after either medicinal treatment or ovariohysterectomy of dogs. Thus the dogs ...

Cause of impaired carbohydrate metabolism in hyperthyroidism

International Nuclear Information System (INIS)

Foeldes, J.; Megyesi, K.; Koranyi, L.

1984-01-01

Hyperthyroidism (HT) affects glucose metabolism in various ways. The role of insulin, glucagon and growth-hormone (GH) was determined. After glucose loading the insulin response is weaker in HT than in euthyroid subjects. Enhanced degradation of insulin has been reported. It is suggested that in HT the serum insulin concentration declines at a slightly accelerated rate. In HT the deranged carbohydrate metabolism might be a consequence of altered tissue sensitivity to insulin. To elucidate this problem insulin receptors on erythrocytes obtained from hyperthyroid women were investigated. The maximal specific binding of 125 I-insulin to RBC of hyperthyroid patients was decreased and the analysis refers to a decreased receptor concentration in RBC. The nature of glucagon secretion and its influence on glucose metabolism in HT was investigated. The basal plasma glucagon is elevated in hyperthyroid patients. The suppression of glucagon secretion induced by an oral glucose loading was of significantly lesser degree in hyperthyroid patients than in controls. Applying the erythrocyte receptor assay a decreased specific binding of 125 I-glucagon to RBC of hyperthyroid patients has been found and data indicate a significantly less glucagon receptor concentration in thyrotoxicosis. Physiological elevations of serum GH levels led to a significant impairment of glucose metabolism. Beside the GH-RH and somatostatin, the dopaminergic neurotransmitter system participates in the regulation of GH secretion too. It has been demonstrated that after administration of the dopamine agonist l-dopa the GH response was weaker in HT than in controls. This indicates that in thyrotoxicosis the GH secretion can not be stimulated in such a degree as in euthyroidism. (author)

Cause of impaired carbohydrate metabolism in hyperthyroidism

Energy Technology Data Exchange (ETDEWEB)

Foeldes, J.; Megyesi, K.; Koranyi, L. (Semmelweis Orvostudomanyi Egyetem, Budapest (Hungary))

1984-01-01

Hyperthyroidism (HT) affects glucose metabolism in various ways. The role of insulin, glucagon and growth-hormone (GH) was determined. After glucose loading the insulin response is weaker in HT than in euthyroid subjects. Enhanced degradation of insulin has been reported. It is suggested that in HT the serum insulin concentration declines at a slightly accelerated rate. In HT the deranged carbohydrate metabolism might be a consequence of altered tissue sensitivity to insulin. To elucidate this problem insulin receptors on erythrocytes obtained from hyperthyroid women were investigated. The maximal specific binding of /sup 125/I-insulin to RBC of hyperthyroid patients was decreased and the analysis refers to a decreased receptor concentration in RBC. The nature of glucagon secretion and its influence on glucose metabolism in HT was investigated. The basal plasma glucagon is elevated in hyperthyroid patients. The suppression of glucagon secretion induced by an oral glucose loading was of significantly lesser degree in hyperthyroid patients than in controls. Applying the erythrocyte receptor assay a decreased specific binding of /sup 125/I-glucagon to RBC of hyperthyroid patients has been found and data indicate a significantly less glucagon receptor concentration in thyrotoxicosis. Physiological elevations of serum GH levels led to a significant impairment of glucose metabolism. Beside the GH-RH and somatostatin, the dopaminergic neurotransmitter system participates in the regulation of GH secretion too. It has been demonstrated that after administration of the dopamine agonist l-dopa the GH response was weaker in HT than in controls. This indicates that in thyrotoxicosis the GH secretion can not be stimulated in such a degree as in euthyroidism.

Nucleic acid metabolism in sea urchin embryos and its alteration after x-irradiation

International Nuclear Information System (INIS)

Kimura, I.

1974-01-01

Nucleic acid metabolism observed during embryogenesis of the sea urchin (Hemicentrotus pulcherrimus) and its alteration after x irradiation were studied on both qualitative and quantitative bases. MAK chromatographic analysis has revealed that the stage-dependent synthesis of RNA occurred during embryogenesis: some RNA families were observed specifically for early cleavage stage, not being observed at stages later than gastrulation. Further, they were modified by irradiation pari passu with delay and inhibition of cleavage. These results were discussed in comparison with our previous results on normal and regenerating rat liver

Altered Transport and Metabolism of Phenolic Compounds in Obesity and Diabetes: Implications for Functional Food Development and Assessment12

Science.gov (United States)

Redan, Benjamin W; Buhman, Kimberly K; Novotny, Janet A; Ferruzzi, Mario G

2016-01-01

Interest in the application of phenolic compounds from the diet or supplements for the prevention of chronic diseases has grown substantially, but the efficacy of such approaches in humans is largely dependent on the bioavailability and metabolism of these compounds. Although food and dietary factors have been the focus of intense investigation, the impact of disease states such as obesity or diabetes on their absorption, metabolism, and eventual efficacy is important to consider. These factors must be understood in order to develop effective strategies that leverage bioactive phenolic compounds for the prevention of chronic disease. The goal of this review is to discuss the inducible metabolic systems that may be influenced by disease states and how these effects impact the bioavailability and metabolism of dietary phenolic compounds. Because current studies generally report that obesity and/or diabetes alter the absorption and excretion of these compounds, this review includes a description of the absorption, conjugation, and excretion pathways for phenolic compounds and how they are potentially altered in disease states. A possible mechanism that will be discussed related to the modulation of phenolic bioavailability and metabolism may be linked to increased inflammatory status from increased amounts of adipose tissue or elevated plasma glucose concentrations. Although more studies are needed, the translation of benefits derived from dietary phenolic compounds to individuals with obesity or diabetes may require the consideration of dosing strategies or be accompanied by adjunct therapies to improve the bioavailability of these compounds. PMID:28140326

Studies on the possible role of thyroid hormone in altered muscle protein turnover during sepsis

International Nuclear Information System (INIS)

Hasselgren, P.O.; Chen, I.W.; James, J.H.; Sperling, M.; Warner, B.W.; Fischer, J.E.

1987-01-01

Five days after thyroidectomy (Tx) or sham-Tx in young male Sprague-Dawley rats, sepsis was induced by cecal ligation and puncture (CLP). Control animals underwent laparotomy and manipulation of the cecum without ligation or puncture. Sixteen hours after CLP or laparotomy, protein synthesis and degradation were measured in incubated extensor digitorum longus (EDL) and soleus (SOL) muscles by determining rate of 14 C-phenylalanine incorporation into protein and tyrosine release into incubation medium, respectively. Triiodothyronine (T3) was measured in serum and muscle tissue. Protein synthesis was reduced by 39% and 22% in EDL and SOL, respectively, 16 hours after CLP in sham-Tx rats. The response to sepsis of protein synthesis was abolished in Tx rats. Protein breakdown was increased by 113% and 68% in EDL and SOL, respectively, 16 hours after CLP in sham-Tx animals. The increase in muscle proteolysis during sepsis was blunted in hypothyroid animals and was 42% and 49% in EDL and SOL, respectively. T3 in serum was reduced by sepsis, both in Tx and sham-Tx rats. T3 in muscle, however, was maintained or increased during sepsis. Abolished or blunted response of muscle protein turnover after CLP in hypothyroid animals may reflect a role of thyroid hormones in altered muscle protein metabolism during sepsis. Reduced serum levels of T3, but maintained or increased muscle concentrations of the hormone, suggests that increased T3 uptake by muscle may be one mechanism of low T3 syndrome in sepsis, further supporting the concept of a role for thyroid hormone in metabolic alterations in muscle during sepsis

Association between serum uric acid, metabolic syndrome and microalbuminuria in previously untreated essential hypertensive patients.

Science.gov (United States)

Rodilla, Enrique; Pérez-Lahiguera, Francisco; Costa, José A; González, Carmen; Miralles, Amparo; Moral, Desamparados; Pascual, José María

2009-01-17

The aim of the study was to assess the association of serum uric acid levels with microalbuminuria -urinary albumin excretion (UAE)> or = 30mg/24h-. Cross-sectional study in 429 (220 women) hypertensive, non diabetic, never treated patients (mean age: 47 years) with glomerular filtration rate > or =60ml/min/1.73m(2). The prevalence of microalbuminuria was 20.5%; 18% had hyperuricemia and 47% fulfilled the criteria for metabolic syndrome (MS). Baseline UAE correlated in the unvaried analysis to diastolic blood pressure, waist circumference, high-density lipoprotein cholesterol and uric acid. In multiple linear regression models, only MS (beta=0.113; p=0.03), and serum uric acid values (beta=0.04; p=0.05) were independently associated with logUAE, after adjustment for age and sex. Hyperuricemia (serum uric acid level > or =7.0mg/dl for men and > or =6.5mg/dl for women; odds ratio=2.18; 95% confidence interval, 1.21-3.92; p=0.010), and MS (odds ratio=2.16; 95% confidence interval, 1.32-3.53; p=0.002) were independently associated with a higher risk of microalbuminuria in multiple logistic regression analyses. The prevalence of microalbuminuria was 45.8% in patients with coexistent MS and hyperuricemia, as compared to 13.6% in hypertensive patients without it (p<0.001). In patients with concomitant MS and hyperuricemia the probability of being microalbuminuric was 3.7 times higher than in patients without those factors. Serum uric acid level is associated with microalbuminuria. Coexistence of MS and hyperuricemia in hypertensive patients increases almost 4 times the odds of being microalbuminuric.

A hypothalamic-pituitary-adrenal axis-associated neuroendocrine metabolic programmed alteration in offspring rats of IUGR induced by prenatal caffeine ingestion.

Science.gov (United States)

Xu, D; Wu, Y; Liu, F; Liu, Y S; Shen, L; Lei, Y Y; Liu, J; Ping, J; Qin, J; Zhang, C; Chen, L B; Magdalou, J; Wang, H

2012-11-01

Caffeine is a definite factor of intrauterine growth retardation (IUGR). Previously, we have confirmed that prenatal caffeine ingestion inhibits the development of hypothalamic-pituitary-adrenal (HPA) axis, and alters the glucose and lipid metabolism in IUGR fetal rats. In this study, we aimed to verify a programmed alteration of neuroendocrine metabolism in prenatal caffeine ingested-offspring rats. The results showed that prenatal caffeine (120 mg/kg.day) ingestion caused low body weight and high IUGR rate of pups; the concentrations of blood adrenocorticotropic hormone (ACTH) and corticosterone in caffeine group were significantly increased in the early postnatal period followed by falling in late stage; the level of blood glucose was unchanged, while blood total cholesterol (TCH) and triglyceride (TG) were markedly enhanced in adult. After chronic stress, the concentrations and the gain rates of blood ACTH and corticosterone were obviously increased, meanwhile, the blood glucose increased while the TCH and TG decreased in caffeine group. Further, the hippocampal mineralocorticoid receptor (MR) expression in caffeine group was initially decreased and subsequently increased after birth. After chronic stress, the 11β-hydroxysteroid dehydrogenase-1, glucocorticoid receptor (GR), MR as well as the MR/GR ratio were all significantly decreased. These results suggested that prenatal caffeine ingestion induced the dysfunction of HPA axis and associated neuroendocrine metabolic programmed alteration in IUGR offspring rats, which might be related with the functional injury of hippocampus. These observations provide a valuable experimental basis for explaining the susceptibility of IUGR offspring to metabolic syndrome and associated diseases. Copyright © 2012 Elsevier Inc. All rights reserved.

CSF and Serum Biomarkers Focusing on Cerebral Vasospasm and Ischemia after Subarachnoid Hemorrhage

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Carla S. Jung

2013-01-01

Full Text Available Delayed cerebral vasospasm (CVS and delayed cerebral ischemia (DCI remain severe complications after subarachnoid hemorrhage (SAH. Although focal changes in cerebral metabolism indicating ischemia are detectable by microdialysis, routinely used biomarkers are missing. We therefore sought to evaluate a panel of possible global markers in serum and cerebrospinal fluid (CSF of patients after SAH. CSF and serum of SAH patients were analyzed retrospectively. In CSF, levels of inhibitory, excitatory, and structural amino acids were detected by high-performance liquid chromatography (HPLC. In serum, neuron-specific enolase (NSE and S100B level were measured and examined in conjunction with CVS and DCI. CVS was detected by arteriography, and ischemic lesions were assessed by computed tomography (CT scans. All CSF amino acids were altered after SAH. CSF glutamate, glutamine, glycine, and histidine were significantly correlated with arteriographic CVS. CSF glutamate and serum S100B were significantly correlated with ischemic events after SAH; however, NSE did not correlate neither with ischemia nor with vasospasm. Glutamate, glutamine, glycine, and histidine might be used in CSF as markers for CVS. Glutamate also indicates ischemia. Serum S100B, but not NSE, is a suitable marker for ischemia. These results need to be validated in larger prospective cohorts.

Adipose Tissue Dysfunction and Altered Systemic Amino Acid Metabolism Are Associated with Non-Alcoholic Fatty Liver Disease

NARCIS (Netherlands)

Cheng, Sulin; Wiklund, Petri; Autio, Reija; Borra, Ronald; Ojanen, Xiaowei; Xu, Leiting; Törmäkangas, Timo; Alen, Markku

2015-01-01

BACKGROUND: Fatty liver is a major cause of obesity-related morbidity and mortality. The aim of this study was to identify early metabolic alterations associated with liver fat accumulation in 50- to 55-year-old men (n = 49) and women (n = 52) with and without NAFLD. METHODS: Hepatic fat content was

Use of serum gamma glutamyl transferase as a biomarker of stress and metabolic dysfunctions in Rathi cattle of arid tract in India

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Kataria N.

2012-08-01

Full Text Available The investigation was carried out to determine serum gamma glutamyl transferase enzyme as a biomarker of stress and metabolic dysfunctions in Rathi cattle of arid tract in India. Blood samples were collected to harvest serum from healthy male and female, drought affected, ketotic cows, recently aborted cows, cows with diarrhoea, cows with traumatic pericarditis, calves with urinary calculi, cows affected with urea poisoning and cows affected with acidosis. The mean values of γ glutamyl transferase showed significant variations (p≤0.05 according to sex and age in the healthy group of animals. The normal range in healthy animals was from 12 to 34 UL-1. In affected group an average 23.69 times rise in the value was observed from that of healthy group. Cows affected with urea poisoning and acidosis were having highest mean values whereas drought affected animals were having least value. It was concluded that present study attempted to provide a new insight about an old enzyme. As the number of animals in the present study was statistically sufficient therefore the mean value of healthy group can be used as reference value for γ GT in Rathi cattle and other cattle breeds which can help to interpret the variations of serum γ GT in various metabolic diseases of cattle.

Assessment of serum biomarkers in rats after exposure to pesticides of different chemical classes

International Nuclear Information System (INIS)

Moser, Virginia C.; Stewart, Nicholas; Freeborn, Danielle L.; Crooks, James; MacMillan, Denise K.; Hedge, Joan M.; Wood, Charles E.; McMahen, Rebecca L.; Strynar, Mark J.; Herr, David W.

2015-01-01

There is increasing emphasis on the use of biomarkers of adverse outcomes in safety assessment and translational research. We evaluated serum biomarkers and targeted metabolite profiles after exposure to pesticides (permethrin, deltamethrin, imidacloprid, carbaryl, triadimefon, fipronil) with different neurotoxic actions. Adult male Long–Evans rats were evaluated after single exposure to vehicle or one of two doses of each pesticide at the time of peak effect. The doses were selected to produce similar magnitude of behavioral effects across chemicals. Serum or plasma was analyzed using commercial cytokine/protein panels and targeted metabolomics. Additional studies of fipronil used lower doses (lacking behavioral effects), singly or for 14 days, and included additional markers of exposure and biological activity. Biomarker profiles varied in the number of altered analytes and patterns of change across pesticide classes, and discriminant analysis could separate treatment groups from control. Low doses of fipronil produced greater effects when given for 14 days compared to a single dose. Changes in thyroid hormones and relative amounts of fipronil and its sulfone metabolite also differed between the dosing regimens. Most cytokine changes reflected alterations in inflammatory responses, hormone levels, and products of phospholipid, fatty acid, and amino acid metabolism. These findings demonstrate distinct blood-based analyte profiles across pesticide classes, dose levels, and exposure duration. These results show promise for detailed analyses of these biomarkers and their linkages to biological pathways. - Highlights: • Pesticides typical of different classes produced distinct patterns of change in biomarker panels. • Based on the panels used, alterations suggest impacts on immune, metabolism, and homeostasis functions. • Some changes may reflect actions on neurotransmitter systems involved in immune modulation. • Fipronil effects on thyroid and kinetics

Assessment of serum biomarkers in rats after exposure to pesticides of different chemical classes

Energy Technology Data Exchange (ETDEWEB)

Moser, Virginia C., E-mail: Moser.ginger@epa.gov [Neurotoxicology Branch/Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Stewart, Nicholas; Freeborn, Danielle L. [Neurotoxicology Branch/Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Crooks, James; MacMillan, Denise K. [Analytical Chemistry Research Core/Research Cores Unit, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Hedge, Joan M.; Wood, Charles E. [Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); McMahen, Rebecca L. [ORISE fellow, Human Exposure and Atmospheric Sciences Division, National Exposure Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Strynar, Mark J. [Human Exposure and Atmospheric Sciences Division, National Exposure Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Herr, David W. [Neurotoxicology Branch/Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711 (United States)

2015-01-15

There is increasing emphasis on the use of biomarkers of adverse outcomes in safety assessment and translational research. We evaluated serum biomarkers and targeted metabolite profiles after exposure to pesticides (permethrin, deltamethrin, imidacloprid, carbaryl, triadimefon, fipronil) with different neurotoxic actions. Adult male Long–Evans rats were evaluated after single exposure to vehicle or one of two doses of each pesticide at the time of peak effect. The doses were selected to produce similar magnitude of behavioral effects across chemicals. Serum or plasma was analyzed using commercial cytokine/protein panels and targeted metabolomics. Additional studies of fipronil used lower doses (lacking behavioral effects), singly or for 14 days, and included additional markers of exposure and biological activity. Biomarker profiles varied in the number of altered analytes and patterns of change across pesticide classes, and discriminant analysis could separate treatment groups from control. Low doses of fipronil produced greater effects when given for 14 days compared to a single dose. Changes in thyroid hormones and relative amounts of fipronil and its sulfone metabolite also differed between the dosing regimens. Most cytokine changes reflected alterations in inflammatory responses, hormone levels, and products of phospholipid, fatty acid, and amino acid metabolism. These findings demonstrate distinct blood-based analyte profiles across pesticide classes, dose levels, and exposure duration. These results show promise for detailed analyses of these biomarkers and their linkages to biological pathways. - Highlights: • Pesticides typical of different classes produced distinct patterns of change in biomarker panels. • Based on the panels used, alterations suggest impacts on immune, metabolism, and homeostasis functions. • Some changes may reflect actions on neurotransmitter systems involved in immune modulation. • Fipronil effects on thyroid and kinetics

Photochemical alteration of organic carbon draining permafrost soils shifts microbial metabolic pathways and stimulates respiration.

Science.gov (United States)

Ward, Collin P; Nalven, Sarah G; Crump, Byron C; Kling, George W; Cory, Rose M

2017-10-03

In sunlit waters, photochemical alteration of dissolved organic carbon (DOC) impacts the microbial respiration of DOC to CO 2 . This coupled photochemical and biological degradation of DOC is especially critical for carbon budgets in the Arctic, where thawing permafrost soils increase opportunities for DOC oxidation to CO 2 in surface waters, thereby reinforcing global warming. Here we show how and why sunlight exposure impacts microbial respiration of DOC draining permafrost soils. Sunlight significantly increases or decreases microbial respiration of DOC depending on whether photo-alteration produces or removes molecules that native microbial communities used prior to light exposure. Using high-resolution chemical and microbial approaches, we show that rates of DOC processing by microbes are likely governed by a combination of the abundance and lability of DOC exported from land to water and produced by photochemical processes, and the capacity and timescale that microbial communities have to adapt to metabolize photo-altered DOC.The role of dissolved organic carbon (DOC) photo-alteration in the microbial respiration of DOC to CO 2 is unclear. Here, the authors show that the impact of this mechanism depends on whether photo-alteration of DOC produces or removes molecules used by native microbial communities prior to light exposure.

Type V Collagen is Persistently Altered after Inguinal Hernia Repair

DEFF Research Database (Denmark)

Lorentzen, L; Henriksen, N A; Juhl, P

2018-01-01

BACKGROUND AND AIMS: Hernia formation is associated with alterations of collagen metabolism. Collagen synthesis and degradation cause a systemic release of products, which are measurable in serum. Recently, we reported changes in type V and IV collagen metabolisms in patients with inguinal...... elective cholecystectomy served as controls (n = 10). Whole venous blood was collected 35-55 months after operation. Biomarkers for type V collagen synthesis (Pro-C5) and degradation (C5M) and those for type IV collagen synthesis (P4NP) and degradation (C4M2) were measured by a solid-phase competitive...... assay. RESULTS: The turnover of type V collagen (Pro-C5/C5M) was slightly higher postoperatively when compared to preoperatively in the inguinal hernia group (P = 0.034). In addition, the results revealed a postoperatively lower type V collagen turnover level in the inguinal hernia group compared...

Effect of Thyroglobulin Autoantibodies on the Metabolic Clearance of Serum Thyroglobulin.

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Latrofa, Francesco; Ricci, Debora; Bottai, Sara; Brozzi, Federica; Chiovato, Luca; Piaggi, Paolo; Marinò, Michele; Vitti, Paolo

2018-03-01

In order to establish whether thyroglobulin autoantibodies (TgAb) influence the metabolic clearance of thyroglobulin (Tg) in humans, serum Tg and TgAb were correlated shortly after radioiodine ( 131 I) treatment. Samples were collected from 30 consecutive patients undergoing 131 I activity for Graves' hyperthyroidism at the time of treatment and every 15 days thereafter, up to 90 days. Tg and TgAb were measured by immunometric assays (functional sensitivities: 0.1 ng/mL and 8 IU/mL). Tg was detectable in all patients at day 0. Tg concentrations rose from a mean of 33.2 ng/mL [confidence interval (CI) 17.8-61.0 ng/mL] at day 0 to a mean of 214.6 ng/mL [CI 116.9-393.4 ng/mL] at day 30 and then steadily decreased, reaching the lowest concentration at day 90 (M = 10.9 ng/mL [CI 5.5-20.9 ng/mL]). Compared to their levels at day 0 (M = 23.6 IU/mL [CI 10.5-52.9 IU/mL]), TgAb remained stable through day 15 and then gradually increased up to a mean of 116.6 IU/mL [CI 51.9-262.2 IU/mL] at day 90. Patients were then split into two groups according to their TgAb status at day 0: undetectable (metabolic clearance of Tg, supporting the concept that their interference in the measurement of Tg is mainly due to an in vivo effect.

Pakistanis living in Oslo have lower serum 1,25-dihydroxyvitamin D levels but higher serum ionized calcium levels compared with ethnic Norwegians. The Oslo Health Study

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Holvik, Kristin; Meyer, Haakon E; Søgaard, Anne Johanne; Haug, Egil; Falch, Jan A

2007-01-01

Background Persons of Pakistani origin living in Oslo have a much higher prevalence of vitamin D deficiency and secondary hyperparathyroidism but similar bone mineral density compared with ethnic Norwegians. Our objective was to investigate whether Pakistani immigrants living in Oslo have an altered vitamin D metabolism by means of compensatory higher serum levels of 1,25-dihydroxyvitamin D (s-1,25(OH)2D) compared with ethnic Norwegians; and whether serum levels of ionized calcium (s-Ca2+) differ between Pakistanis and Norwegians. Methods In a cross-sectional, population-based study venous serum samples were drawn from 94 Pakistani men and 67 Pakistani women aged 30–60 years, and 290 Norwegian men and 270 Norwegian women aged 45–60 years; in total 721 subjects. Results Pakistanis had lower s-1,25(OH)2D compared with Norwegians (p Oslo with low vitamin D status and secondary hyperparathyroidism have lower s-1,25(OH)2D compared with ethnic Norwegians. However, the Pakistanis have higher s-Ca2+. The cause of the higher s-Ca2+ in Pakistanis in spite of their higher iPTH remains unclear. PMID:17945003

Metabonomic Analysis Reveals Efficient Ameliorating Effects of Acupoint Stimulations on the Menopause-caused Alterations in Mammalian Metabolism

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Zhang, Limin; Wang, Yulan; Xu, Yunxiang; Lei, Hehua; Zhao, Ying; Li, Huihui; Lin, Xiaosheng; Chen, Guizhen; Tang, Huiru

2014-01-01

Acupoint stimulations are effective in ameliorating symptoms of menopause which is an unavoidable ageing consequence for women. To understand the mechanistic aspects of such treatments, we systematically analyzed the effects of acupoint laser-irradiation and catgut-embedding on the ovariectomy-induced rat metabolic changes using NMR and GC-FID/MS methods. Results showed that ovariectomization (OVX) caused comprehensive metabolic changes in lipid peroxidation, glycolysis, TCA cycle, choline and amino acid metabolisms. Both acupoint laser-irradiation and catgut-embedding ameliorated the OVX-caused metabonomic changes more effectively than hormone replacement therapy (HRT) with nilestriol. Such effects of acupoint stimulations were highlighted in alleviating lipid peroxidation, restoring glucose homeostasis and partial reversion of the OVX-altered amino acid metabolism. These findings provided new insights into the menopause effects on mammalian biochemistry and beneficial effects of acupoint stimulations in comparison with HRT, demonstrating metabonomics as a powerful approach for potential applications in disease prognosis and developments of effective therapies.

Diabetes induces metabolic alterations in dental pulp.

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Leite, Mariana Ferreira; Ganzerla, Emily; Marques, Márcia Martins; Nicolau, José

2008-10-01

Diabetes can interfere in tissue nutrition and can impair dental pulp metabolism. This disease causes oxidative stress in cells and tissues. However, little is known about the antioxidant system in the dental pulp of diabetics. Thus, it would be of importance to study this system in this tissue in order to verify possible alterations indicative of oxidative stress. The aim of this study was to evaluate some parameters of antioxidant system of the dental pulp of healthy (n = 8) and diabetic rats (n = 8). Diabetes was induced by streptozotocin in rats. Six weeks after diabetes induction, a pool of the dental pulp of the 4 incisors of each rat (healthy and diabetic) was used for the determination of total protein and sialic acid concentrations and catalase and peroxidase activities. Data were compared by a Student t test (p pulps from both groups presented similar total protein concentrations and peroxidase activity. Dental pulps of diabetic rats exhibited significantly lower free, conjugated, and total sialic acid concentrations than those of control tissues. Catalase activity in diabetic dental pulps was significantly enhanced in comparison with that of control pulps. The result of the present study is indicative of oxidative stress in the dental pulp caused by diabetes. The increase of catalase activity and the reduction of sialic acid could be resultant of reactive oxygen species production.

Ocean acidification alters early successional coral reef communities and their rates of community metabolism.

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Sam H C Noonan

Full Text Available Ocean acidification is expected to alter community composition on coral reefs, but its effects on reef community metabolism are poorly understood. Here we document how early successional benthic coral reef communities change in situ along gradients of carbon dioxide (CO2, and the consequences of these changes on rates of community photosynthesis, respiration, and light and dark calcification. Ninety standardised benthic communities were grown on PVC tiles deployed at two shallow-water volcanic CO2 seeps and two adjacent control sites in Papua New Guinea. Along the CO2 gradient, both the upward facing phototrophic and the downward facing cryptic communities changed in their composition. Under ambient CO2, both communities were dominated by calcifying algae, but with increasing CO2 they were gradually replaced by non-calcifying algae (predominantly green filamentous algae, cyanobacteria and macroalgae, which increased from ~30% to ~80% cover. Responses were weaker in the invertebrate communities, however ascidians and tube-forming polychaetes declined with increasing CO2. Differences in the carbonate chemistry explained a far greater amount of change in communities than differences between the two reefs and successional changes from five to 13 months, suggesting community successions are established early and are under strong chemical control. As pH declined from 8.0 to 7.8, rates of gross photosynthesis and dark respiration of the 13-month old reef communities (upper and cryptic surfaces combined significantly increased by 10% and 20%, respectively, in response to altered community composition. As a consequence, net production remained constant. Light and dark calcification rates both gradually declined by 20%, and low or negative daily net calcification rates were observed at an aragonite saturation state of <2.3. The study demonstrates that ocean acidification as predicted for the end of this century will strongly alter reef communities, and

Serum Amyloid A Production Is Triggered by Sleep Deprivation in Mice and Humans: Is That the Link between Sleep Loss and Associated Comorbidities?

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de Oliveira, Edson M.; Visniauskas, Bruna; Tufik, Sergio; Andersen, Monica L.; Chagas, Jair R.; Campa, Ana

2017-01-01

Serum amyloid A (SAA) was recently associated with metabolic endotoxemia, obesity and insulin resistance. Concurrently, insufficient sleep adversely affects metabolic health and is an independent predisposing factor for obesity and insulin resistance. In this study we investigated whether sleep loss modulates SAA production. The serum SAA concentration increased in C57BL/6 mice subjected to sleep restriction (SR) for 15 days or to paradoxical sleep deprivation (PSD) for 72 h. Sleep restriction also induced the upregulation of Saa1.1/Saa2.1 mRNA levels in the liver and Saa3 mRNA levels in adipose tissue. SAA levels returned to the basal range after 24 h in paradoxical sleep rebound (PSR). Metabolic endotoxemia was also a finding in SR. Increased plasma levels of SAA were also observed in healthy human volunteers subjected to two nights of total sleep deprivation (Total SD), returning to basal levels after one night of recovery. The observed increase in SAA levels may be part of the initial biochemical alterations caused by sleep deprivation, with potential to drive deleterious conditions such as metabolic endotoxemia and weight gain. PMID:28335560

Serum heart type fatty acid binding protein levels are not changed in hyperthyroidism.

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Ozbek, Mustafa; Gungunes, Askin; Sahin, Mustafa; Ginis, Zeynep; Ucan, Bekir; Sayki, Muyesser; Tutal, Esra; Cakal, Erman; Kuşkonmaz, Serife M; Öztürk, Mehmet A; Delibasi, Tuncay

2016-09-01

Heart type fatty acid binding protein (H-FABP) is a small protein and released into the circulation when myocardial damage has occurred. Previous studies have demonstrated that H-FABP is closely associated with cardiac and some endocrinologic disorders including prediabetes, metabolic syndrome, and acromegaly. Hyperthyroism is a well-known disorder associated with cardiovascular diseases. We aimed to investigate the effect of hyperthyrodism on H-FABP levels. Forty six patients with hyperthyroidism with no known history of coronary artery disease and 40 healthy controls are involved in the study. Serum H-FABP levels are measured using sandwich enzyme-linked immunosorbent assay. There was no significant difference between serum H-FABP levels of patients with hyperthyroidism and controls (871±66 pg/mL, and 816±66 pg/mL, respectively P=0.56). There was no significant correlation between H-FABP, free triiodothyronine (fT3), free thyroxine (fT4), and thyroid stimulating hormone (TSH) levels in patients and controls. Serum H-FABP levels are not altered in patients with hyperthyroidism.

Abnormalities in biomarkers of mineral and bone metabolism in kidney donors.

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Kasiske, Bertram L; Kumar, Rajiv; Kimmel, Paul L; Pesavento, Todd E; Kalil, Roberto S; Kraus, Edward S; Rabb, Hamid; Posselt, Andrew M; Anderson-Haag, Teresa L; Steffes, Michael W; Israni, Ajay K; Snyder, Jon J; Singh, Ravinder J; Weir, Matthew R

2016-10-01

Previous studies have suggested that kidney donors may have abnormalities of mineral and bone metabolism typically seen in chronic kidney disease. This may have important implications for the skeletal health of living kidney donors and for our understanding of the pathogenesis of long-term mineral and bone disorders in chronic kidney disease. In this prospective study, 182 of 203 kidney donors and 173 of 201 paired normal controls had markers of mineral and bone metabolism measured before and at 6 and 36 months after donation (ALTOLD Study). Donors had significantly higher serum concentrations of intact parathyroid hormone (24.6% and 19.5%) and fibroblast growth factor-23 (9.5% and 8.4%) at 6 and 36 months, respectively, as compared to healthy controls, and significantly reduced tubular phosphate reabsorption (-7.0% and -5.0%) and serum phosphate concentrations (-6.4% and -2.3%). Serum 1,25-dihydroxyvitamin D3 concentrations were significantly lower (-17.1% and -12.6%), while 25-hydroxyvitamin D (21.4% and 19.4%) concentrations were significantly higher in donors compared to controls. Moreover, significantly higher concentrations of the bone resorption markers, carboxyterminal cross-linking telopeptide of bone collagen (30.1% and 13.8%) and aminoterminal cross-linking telopeptide of bone collagen (14.2% and 13.0%), and the bone formation markers, osteocalcin (26.3% and 2.7%) and procollagen type I N-terminal propeptide (24.3% and 8.9%), were observed in donors. Thus, kidney donation alters serum markers of bone metabolism that could reflect impaired bone health. Additional long-term studies that include assessment of skeletal architecture and integrity are warranted in kidney donors. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Identification of Ganglioside GM3 Molecular Species in Human Serum Associated with Risk Factors of Metabolic Syndrome.

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Lucas Veillon

Full Text Available Serum GM3 molecular species were quantified in 125 Japanese residents using tandem mass spectrometry multiple reaction monitoring. Individuals were categorized by the presence or absence of metabolic disease risk factors including visceral fat accumulation, hyperglycemia and dyslipidemia. A total of 23 GM3 molecular species were measured, of these, eight were found to be significantly elevated in individuals with visceral fat accumulation and metabolic disease, defined as the presence of hyperglycemia and dyslipidemia. All of the GM3 molecular species were composed of the sphingoid base sphingosine (d18:1 (Δ4 and, interestingly, six of the eight elevated GM3 molecular species contained a hydroxylated ceramide moiety. The hydroxylated GM3 species were, in order of decreasing abundance, d18:1-h24:0 ≈ d18:1-h24:1 > d18:1-h22:0 » d18:1-h20:0 > d18:1-h21:0 > d18:1-h18:1. Univariate and multiple linear regression analyses were conducted using a number of clinical health variables associated with obesity, type 2 diabetes, metabolic disease, atherosclerosis and hypertension. GM3(d18:1-h24:1 was identified as the best candidate for metabolic screening, proving to be significantly correlated with intima-media thickness, used for the detection of atherosclerotic disease in humans, and a number of metabolic disease risk factors including autotaxin, LDL-c and homeostatic model assessment insulin resistance (HOMA-IR.

Chronic chlorpyrifos exposure elicits diet-specific effects on metabolism and the gut microbiome in rats.

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Fang, Bing; Li, Jin Wang; Zhang, Ming; Ren, Fa Zheng; Pang, Guo Fang

2018-01-01

Chlorpyrifos is a commonly-used pesticide which was reported to interfere with hormone signaling and metabolism, however, little is known about its effect on gut microbiota. In this study, adult male rats fed a normal (NF) or high fat (HF) diet were exposed to 0.3 or 3.0 mg chlorpyrifos/kg bodyweight/day or vehicle alone for 9 weeks. Effects on bodyweight, serum levels of glucose, lipid, cytokines, and gut microbiome community structure were measured. The effects of chlorpyrifos on metabolism were dose- and diet-dependent, with NF-fed rats administered the low dose showing the largest metabolic changes. NF-fed rats exposed to chlorpyrifos exhibited a pro-obesity phenotype compared with their controls, whereas there was no difference in pro-obesity phenotype between HF-fed groups. Chlorpyrifos exposure significantly reduced serum insulin, C-peptide, and amylin concentrations in NF- and HF-fed rats, leaving serum glucose and lipid profiles unaffected. Chlorpyrifos exposure also significantly altered gut microbiota composition, including the abundance of opportunistic pathogens, short chain fatty acid-producing bacteria and other bacteria previously associated with obese and diabetic phenotypes. The abundance of bacteria associated with neurotoxicity and islet injury was also significantly increased by chlorpyrifos. Our results suggest risk assessments for chlorpyrifos exposure should consider other effects in addition to neurotoxicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Serum aminotransferases in nonalcoholic fatty liver disease are a signature of liver metabolic perturbations at the amino acid and Krebs cycle level.

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Sookoian, Silvia; Castaño, Gustavo O; Scian, Romina; Fernández Gianotti, Tomas; Dopazo, Hernán; Rohr, Cristian; Gaj, Graciela; San Martino, Julio; Sevic, Ina; Flichman, Diego; Pirola, Carlos J

2016-02-01

Extensive epidemiologic studies have shown that cardiovascular disease and the metabolic syndrome (MetS) are associated with serum concentrations of liver enzymes; however, fundamental characteristics of this relation are currently unknown. We aimed to explore the role of liver aminotransferases in nonalcoholic fatty liver disease (NAFLD) and MetS. Liver gene- and protein-expression changes of aminotransferases, including their corresponding isoforms, were evaluated in a case-control study of patients with NAFLD (n = 42), which was proven through a biopsy (control subjects: n = 10). We also carried out a serum targeted metabolite profiling to the glycolysis, gluconeogenesis, and Krebs cycle (n = 48) and an exploration by the next-generation sequencing of aminotransferase genes (n = 96). An in vitro study to provide a biological explanation of changes in the transcriptional level and enzymatic activity of aminotransferases was included. Fatty liver was associated with a deregulated liver expression of aminotransferases, which was unrelated to the disease severity. Metabolite profiling showed that serum aminotransferase concentrations are a signature of liver metabolic perturbations, particularly at the amino acid metabolism and Krebs cycle level. A significant and positive association between systolic hypertension and liver expression levels of glutamic-oxaloacetic transaminase 2 (GOT2) messenger RNA (Spearman R = 0.42, P = 0.03) was observed. The rs6993 located in the 3' untranslated region of the GOT2 locus was significantly associated with features of the MetS, including arterial hypertension [P = 0.028; OR: 2.285 (95% CI: 1.024, 5.09); adjusted by NAFLD severity] and plasma lipid concentrations. In the context of an abnormal hepatic triglyceride accumulation, circulating aminotransferases rise as a consequence of the need for increased reactions of transamination to cope with the liver metabolic derangement that is associated with greater gluconeogenesis and

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

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

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

Rat brain CYP2D enzymatic metabolism alters acute and chronic haloperidol side-effects by different mechanisms.

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Miksys, Sharon; Wadji, Fariba Baghai; Tolledo, Edgor Cole; Remington, Gary; Nobrega, Jose N; Tyndale, Rachel F

2017-08-01

Risk for side-effects after acute (e.g. parkinsonism) or chronic (e.g. tardive dyskinesia) treatment with antipsychotics, including haloperidol, varies substantially among people. CYP2D can metabolize many antipsychotics and variable brain CYP2D metabolism can influence local drug and metabolite levels sufficiently to alter behavioral responses. Here we investigated a role for brain CYP2D in acutely and chronically administered haloperidol levels and side-effects in a rat model. Rat brain, but not liver, CYP2D activity was irreversibly inhibited with intracerebral propranolol and/or induced by seven days of subcutaneous nicotine pre-treatment. The role of variable brain CYP2D was investigated in rat models of acute (catalepsy) and chronic (vacuous chewing movements, VCMs) haloperidol side-effects. Selective inhibition and induction of brain, but not liver, CYP2D decreased and increased catalepsy after acute haloperidol, respectively. Catalepsy correlated with brain, but not hepatic, CYP2D enzyme activity. Inhibition of brain CYP2D increased VCMs after chronic haloperidol; VCMs correlated with brain, but not hepatic, CYP2D activity, haloperidol levels and lipid peroxidation. Baseline measures, hepatic CYP2D activity and plasma haloperidol levels were unchanged by brain CYP2D manipulations. Variable rat brain CYP2D alters side-effects from acute and chronic haloperidol in opposite directions; catalepsy appears to be enhanced by a brain CYP2D-derived metabolite while the parent haloperidol likely causes VCMs. These data provide novel mechanistic evidence for brain CYP2D altering side-effects of haloperidol and other antipsychotics metabolized by CYP2D, suggesting that variation in human brain CYP2D may be a risk factor for antipsychotic side-effects. Copyright © 2017 Elsevier Inc. All rights reserved.

The effect of alterations in total coenzyme A on metabolic pathways in the liver and heart

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Schlosser, C.A.S.

1989-01-01

The first set of experiments involved in vitro experiments using primary cultures of rat hepatocytes. A range of conditions were developed which resulted in cell cultures with variations in total CoA over a range of 1.3 to 2.9 nmol/mg protein with identical hormonal activation which simulated metabolic stress. Elevations of total CoA levels above that of controls due to preincubation with cyanamide plus pantothenate were correlated with diminished rates of total ketone body production, 3-hydroxybutyrate production and ratios of 3 hydroxybutyrate/acetoactetate with palmitate as substrate. In contrast, cells with elevated total CoA levels had higher rates of [ 14 C] CO 2 production from radioactive palmitate which implied greater flux of acetyl CoA units into the TCA cycle and less to the pathway of ketogenesis. The second set of experiments were designed to alter total CoA levels in vivo by maintaining rats on a chronic ethanol diet with or without pantothenate-supplementation. The effect of alterations of CoA on mitochondrial metabolism was evaluated by measuring substrate oxidation rates in liver and heat mitochondria as well as ketone body production with palmitoyl-1-carnitine as substrate

CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands.

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Lamas, Bruno; Richard, Mathias L; Leducq, Valentin; Pham, Hang-Phuong; Michel, Marie-Laure; Da Costa, Gregory; Bridonneau, Chantal; Jegou, Sarah; Hoffmann, Thomas W; Natividad, Jane M; Brot, Loic; Taleb, Soraya; Couturier-Maillard, Aurélie; Nion-Larmurier, Isabelle; Merabtene, Fatiha; Seksik, Philippe; Bourrier, Anne; Cosnes, Jacques; Ryffel, Bernhard; Beaugerie, Laurent; Launay, Jean-Marie; Langella, Philippe; Xavier, Ramnik J; Sokol, Harry

2016-06-01

Complex interactions between the host and the gut microbiota govern intestinal homeostasis but remain poorly understood. Here we reveal a relationship between gut microbiota and caspase recruitment domain family member 9 (CARD9), a susceptibility gene for inflammatory bowel disease (IBD) that functions in the immune response against microorganisms. CARD9 promotes recovery from colitis by promoting interleukin (IL)-22 production, and Card9(-/-) mice are more susceptible to colitis. The microbiota is altered in Card9(-/-) mice, and transfer of the microbiota from Card9(-/-) to wild-type, germ-free recipients increases their susceptibility to colitis. The microbiota from Card9(-/-) mice fails to metabolize tryptophan into metabolites that act as aryl hydrocarbon receptor (AHR) ligands. Intestinal inflammation is attenuated after inoculation of mice with three Lactobacillus strains capable of metabolizing tryptophan or by treatment with an AHR agonist. Reduced production of AHR ligands is also observed in the microbiota from individuals with IBD, particularly in those with CARD9 risk alleles associated with IBD. Our findings reveal that host genes affect the composition and function of the gut microbiota, altering the production of microbial metabolites and intestinal inflammation.

Relationship of serum magnesium levels and other metabolic indices in renal transplant recipients receiving cyclosporine

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Ahmadi F

2008-10-01

Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Cyclosporine is one of the main immunosuppressors used for renal transplant recipients, and is given to prevent transplant rejection. Although the drug increases the survival of patients and grafted organs, it has some side effects independent of its effect on the immune system that are usually ignored. In this study, we evaluate the effect of cyclosporine on serum Mg levels and metabolic side effects in renal graft patients."n"n Methods: In this study, we followed 157 renal transplant recipients (62 females and 95 males who were being treated with cyclosporine at a private clinic to prevent transplant rejection. The patients were first physically examined and then blood samples were obtained in order to measure levels of cyclosporine, Mg, creatinine, fasting blood sugar, lipids, calcium, phosphorus, and uric acid levels. We then analyzed the data for correlations between serum Mg levels, cyclosporine and other metabolic complications."n"n Results: The mean levels of Mg and cyclosporine were 196±0.31mg/dl and 371±192 μg/dl, respectively. Hypomagnesemia was detected in 16 patients (10.2%.There was a significant negative correlation (p<0.05 between levels of Mg and cyclosporine levels (r=-0.53, serum