Markers Of Energy Metabolism Research Articles

Predictive value of selected biomarkers related to metabolism and oxidative stress in children with autism spectrum disorder.

Autism spectrum disorder (ASD) as a neurodevelopmental disorder is characterized by impairments in social interaction, communication, and restricted, repetitive behavior. Several and reproducible studies have suggested that oxidative stress may represent one of the primary etiological mechanism of ASD that can be targeted for therapeutic intervention. In the present study, multiple regression and combined receiver operating characteristic (ROC) analysis were used to search for a relationship between impaired energy and oxidative metabolic pathways in the etiology of ASD and to find the linear combination that maximizes the partial area under a ROC curve for a pre-identified set of markers related to energy metabolism and oxidative stress. Thirty children with ASD and 30 age and gender matched controls were enrolled in the study. Using either spectrophotometric or ELISA-colorimetric assay, levels of lipid peroxides, vitamin E, vitamin C, glutathione (GSH)/glutathione disulfide (GSSG) together with the enzymatic activity of catalase, plasma glutathione peroxidase (GPx), and blood superoxide dismutase (SOD), were measured in peripheral blood samples, as biomarkers related to oxidative stress. Creatine kinase, ectonucleotidases (ADPase and ATPase) Na+/K+ (ATPase), lactate, inorganic phosphate, and levels of adenosine monophosphate (AMP), adenosine diphosphate (ADP), and adenosine triphosphate (ATP) together with adenylate energy charge, were also measured as markers of impaired energy metabolism. Statistical analysis using ROC curves, multiple and logistic regression were performed. A remarkable increase in the area under the curve for most of the combined markers, representing both energy impaired metabolism or oxidative stress, was observed by using combined ROC analyses. Moreover, higher specificity and sensitivity of the combined markers were also reported. The present study indicated that the measurement of the predictive value of selected biomarkers related to energy metabolism and oxidative stress in children with ASD using ROC analysis should lead to the better identification of the etiological mechanism of ASD associated with metabolism and diet. Agents with activity against the impaired metabolic pathway associated with ASD including the metabolic defects and involved enzymes hold a promise as a novel therapy for ASD.

Anti-fatigue activity of sea cucumber peptides prepared from Stichopus japonicus in an endurance swimming rat model.

Sea cucumber (Stichopus japonicus) is a well-known nutritious and luxurious seafood in Asia which has attracted increasing attention because of its nutrition and bioactivities in recent years. In this study, the anti-fatigue activity of sea cucumber peptides (SCP) prepared from S. japonicus was evaluated in a load-induced endurance swimming model. The SCP prepared in this study was mainly made up of low-molecular-weight peptides (<2 kDa). The analysis result of amino acid composition revealed that SCP was rich in glycine, glutamic acid and proline. The endurance capability of rats to fatigue was significantly improved by SCP treatment. Meanwhile, the remarkable alterations of energy metabolic markers, antioxidant enzymes, antioxidant capacity and oxidative stress biomarkers were normalized. Moreover, administration of SCP could modulate alterations of inflammatory cytokines and downregulate the overexpression of TRL4 and NF-κB. SCP has anti-fatigue activity and it exerted its anti-fatigue effect probably through normalizing energy metabolism as well as alleviating oxidative damage and inflammatory responses. © 2017 Society of Chemical Industry.

Effects of coconut oil consumption on energy metabolism, cardiometabolic risk markers, and appetitive responses in women with excess body fat.

Virgin coconut oil (VCO) is a medium-chain fatty acid source with popularly attributed benefits on obesity management. However, its role on obesity requires elucidation due to its saturated nature. In the study herein, we investigated acute effects of VCO consumption on energy metabolism, cardiometabolic risk markers, and appetitive responses in women with excess body fat. Fifteen adult women with excess body fat (37.43±0.83%) participated in this randomized, crossover, controlled study. Two isocaloric mixed breakfasts containing 25mL of VCO or control (extra-virgin olive oil-C) were evaluated. Resting energy expenditure (REE), fat oxidation rate (FOR), diet induced thermogenesis (DIT) and appetitive subjective responses were assessed at fasting and postprandial periods (up to 240min). Cardiometabolic risk markers were assessed at fasting and up to 180min postprandially. VCO did not affect REE, FOR, and DIT compared to C. In addition, VCO did not cause deleterious change in triglycerides, total cholesterol, HDL-c, LDL-c, triglycerides/HDL-c ratio, uric acid, glucose and Homeostasis Model Assessment of Insulin Resistance Index (HOMA-IR) (P time×treatment>0.05). However, VCO suppressed less hunger (P time×treatment=0.003), total satiety (P iAUC=0.021) and total fullness (P iAUC=0.035) responses than C. VCO consumption did not acutely change energy metabolism and cardiometabolic risk markers when added to a mixed breakfast but promoted less appetitive responses.

Docosahexaenoic Acid (DHA), not Leucine, May Protect HepG2 Cells from Palmitate‐Induced Non‐Alcoholic Fatty Liver Disease

Non‐alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in the United States, affecting 70 million adults and ~3% of young children. NAFLD is characterized by an accumulation of fat in the liver cells that is not caused by alcohol. NAFLD is closely associated with obesity and insulin resistance, which are precursors for development of type 2 diabetes. Recent data suggests that the PPARs (PPARα and PPARγ may be connected to the development and progression of NAFLD, which make them potential biomarkers for treating and diagnosing NAFLD. Currently, there are several approaches to treating NAFLD, including nutrition therapy and specific food recommendations. Diets high in protein, high in the branched‐chain amino acid leucine, and diets high in polyunsaturated fatty acids, such as DHA, have been linked with weight reduction and improved insulin resistance. However, neither has been evaluated as a treatment for NAFLD. Therefore, the objective of this study was to analyze the ability of leucine and DHA to act either synergistically or alone to reduce markers of NAFLD using HepG2 cells treated with palmitate as an in vitro model. HepG2 cells (80% confluent) received one of 6 treatments for 48 hours: control, vector control, 0.75 mM palmitate, 5 mM leucine + palmitate, 0.1 mM DHA + palmitate, or leucine + DHA + palmitate. Lipid deposition and markers of energy metabolism were measured. Data was analyzed using one‐way ANOVA with P &lt; 0.05 indicating significance. There was no effect of leucine on cellular lipid deposition. However, cells treated with DHA had significantly less lipid deposition compared to cells treated with palmitate or palmitate + leucine. Palmitate increased Tfam expression compared to controls, however, there was no further effect of leucine. Palmitate + DHA and palmitate + leucine + DHA significantly increased Tfam expression compared to control, palmitate and palmitate + leucine. Palmitate significantly lowered PGC1a and PPARg expression, however treatment with DHA further decreased PGC1α and PPARγ compared to controls and palmitate, alone. Preliminary data shows no treatment effect on SIRT1 or mTOR phosphorylation. Taken together, these data suggest that DHA, not leucine, has the potential to reduce markers of NAFLD in HepG2 cells.Support or Funding InformationArkansas Biosciences Institute. University of Arkansas State Undergraduate Research Fellowship.

7,8-Dihydroxyflavone facilitates the action exercise to restore plasticity and functionality: Implications for early brain trauma recovery

Metabolic dysfunction accompanying traumatic brain injury (TBI) severely impairs the ability of injured neurons to comply with functional demands. This limits the success of rehabilitative strategies by compromising brain plasticity and function, and highlights the need for early interventions to promote energy homeostasis. We sought to examine whether the TrkB agonist, 7,8-dihydroxyflavone (7,8-DHF) normalizes brain energy deficits and reestablishes more normal patterns of functional connectivity, while enhancing the effects of exercise during post-TBI period. Moderate fluid percussion injury (FPI) was performed and 7,8-DHF (5mg/kg, i.p.) was administered in animals subjected to FPI that either had access to voluntary wheel running for 7days after injury or were sedentary. Compared to sham-injured controls, TBI resulted in reduced hippocampal activation of the BDNF receptor TrkB and associated CREB, reduced levels of plasticity markers GAP-43 and Syn I, as well as impaired memory as indicated by the Barnes maze task. While 7,8-DHF treatment and exercise individually mitigated TBI-induced effects, administration of 7,8-DHF concurrently with exercise facilitated memory performance and augmented levels of markers of cell energy metabolism viz., PGC-1α, COII and AMPK. In parallel to these findings, resting-state functional MRI (fMRI) acquired at 2weeks after injury showed that 7,8-DHF with exercise enhanced hippocampal functional connectivity, and suggests 7,8-DHF and exercise to promote increases in functional connectivity. Together, these findings indicate that post-injury 7,8-DHF treatment promotes enhanced levels of cell metabolism, synaptic plasticity in combination with exercise increases in brain circuit function that facilitates greater physical rehabilitation after TBI.

Abstract P285: Small Dose of Medium Chain Fatty Acids From Coconut Oil Does Not Enhance Thermogenesis in Overweight Adolescents

Background: Previous research has shown that consumption of medium chain triglycerides (MCT) in overweight adults can increase energy expenditure and improve weight management, but no research has been done in children. Our study tests the effects of a test oil enriched in MCT from coconut oil, on energy expenditure, satiety, and metabolic markers in overweight and obese adolescents. Methods: We conducted a randomized, double blind, crossover study in which 15 children, age 13-18 y, with a body mass index &gt;85 th percentile for age and sex, were enrolled. Two test meals were administered which contained 20 g of fat from either corn oil or an MCT-enriched baking fat (providing approximately 4.7 g of fatty acids with chain lengths ≤12C). A fasting blood sample was taken before breakfast and the thermic effect of food (TEF) was assessed using indirect calorimetry for 6 h. During the test, satiety was measured using visual analog scales (VAS) and additional blood samples were obtained from an intravenous catheter at times 30, 45, 60, 120, and 180 min post-meal for measurement of hormones and metabolites. Results: There was no significant effect of fat type, time, or fat type x time interaction on TEF, appetite and satiety, glucose, and insulin area under the curve (AUC). However, there was a significant effect of fat type on leptin (P = 0.027), triglycerides (P = 0.020), and peptide YY (P = 0.0085) whereby leptin and triglyceride concentrations were lower with corn oil consumption and peptide YY concentrations were higher. Conclusions: Our results do not suggest that this MCT-rich test oil enhances thermogenesis and satiety in children. Given that this is the only current study of its kind, more research is needed into the use of MCT as a tool in weight management in overweight and obese children.

Restricting the time of access to fresh forage reduces intake and energy balance but does not affect the digestive utilization of nutrients in beef heifers

The effect of restricting the time of access to a high-quality fresh forage on the intake and digestion of nutrients was studied in heifers. Twenty-four Hereford heifers (body weight (BW) 153±18kg) housed in metabolic cages were randomized according to a BW-based block design and were randomly assigned to receive one of the four following treatments: 24, 8, 6 or 4h of daily access to freshly cut pasture (Lolium multiflorum and Trifolium repens) (T24, T8, T6 and T4, respectively). Their feeding behavior (classified according to the categories of ‘eating’, ‘ruminating’ or ‘other’), intake rate, intake and digestibility of nutrients, ruminal environment, microbial protein synthesis and blood markers of energy and protein metabolism were assessed. The intake for all of the feed fractions decreased at an increasing rate (from 6h of access) as the time of access to forage decreased (linear: P<0.001; quadratic: P<0.035). During the first 4h of feeding, animals linearly increased the eating time and the intake rate (P<0.001 and P=0.006, respectively), and decreased the ruminating time (P=0.014) as the time of access to forage decreased. Neither forage digestibility, nor ruminal microbial protein synthesis efficiency, were affected by the restrictions. The metabolizable energy balance linearly decreased (P<0.001) and N retention decreased at an increasing rate (from 8h of access; linear: P<0.003, quadratic P<0.030), with decreasing time of access to forage. The ruminal pH and NH3-N concentration were affected by treatment and time (P<0.001). Ruminal pH increased at an increasing rate (from 8h of access) as the time of access to forage decreased. Meanwhile, NH3-N concentration linearly decreased as the time of access to forage decreased. There was a significant interaction between treatment and time for pH and NH3-N (P<0.001), being both variables less stable during the day in restricted animals than in unrestricted ones. The concentrations of blood glucose, urea and insulin were not affected by the restrictions. In general, the effects of the restriction seem to have been less evident on digestion than on ingestion. Fasting beef heifers led to behavioral changes in order to maintain the dry matter intake, but these changes resulted insufficient when the time of access to forage drops below 6h per day.

Relationship between pre-partum body condition score changes, acute phase proteins and energy metabolism markers during the peripartum period in dairy cows

This study evaluated the relationship of pre-partum BCS variations on the acute phase response around parturition and milk production of dairy cows. The animals were divided into two groups: cows that gained BCS from the third to the first week pre-partum (GBC = n 11) and those that lost BCS (LBC = n 9) in the same period. Blood samples were collected pre and post-partum to determine serum concentrations of glucose (GLU), non-esterified fatty acids (NEFA), insulin (INS), albumin (ALB), paraoxonase (PON), haptoglobin (HP) and blood cell counts. The GBC group showed higher PON concentration in the postpartum (p < .05) and higher ALB concentration both pre and postpartum periods (p < .05), whereas the LBC animals showed a higher HP concentration in both periods (p < .05). Milk yield increased 3 kg/cow/day in the group that increased their BCS (p < .03). The LBC cows showed increased monocyte counts (p < .03), in addition to having a greater number of animals with the neutrophil:lymphocyte ratio higher than 1 (p < .03). The remaining parameters did not differ between groups. In conclusion, animals that lost BCS during the pre-partum period demonstrated to have a higher inflammatory status around parturition and lower milk production.

MiRNA-133a-UCP2 pathway regulates inflammatory bowel disease progress by influencing inflammation, oxidative stress and energy metabolism.

To investigate the role of the miR-133a-UCP2 pathway in the pathogenesis of inflammatory bowel disease (IBD) and to explore the potential downstream mechanisms with respect to inflammation, oxidative stress and energy metabolism. C57BL/6 mice were fed dextran sulfate sodium (DSS) liquid for 7 consecutive days, followed by the administration of saline to the DSS group, UCP2 siRNA to the UCP2 group and a miR-133a mimic to the miR-133a group on days 8 and 11. Body weight, stool consistency and rectal bleeding were recorded daily, and these composed the disease activity index (DAI) score for the assessment of disease severity. After cervical dislocation was performed on day 14, the length of the colon in each mouse was measured, and colonic tissue was collected for further study, which included the following: haematoxylin and eosin staining, UCP2 and miR-133a detection by immunohistochemical staining, western blot and quantitative real-time PCR, measurement of apoptosis by TUNEL assay, and the assessment of inflammation (TNF-α, IL-1β, IL-6 and MCP1), oxidative stress (H2O2 and MDA) and metabolic parameters (ATP) by ELISA and colorimetric methods. An animal model of IBD was successfully established, as shown by an increased DAI score, shortened colon length and specific pathologic changes, along with significantly increased UCP2 and decreased miR-133a levels. Compared with the DSS group, the severity of IBD was alleviated in the UCP2 and the miR-133a groups after successful UCP2 knockdown and miR-133a overexpression. The extent of apoptosis, as well as the levels of TNF-α, IL-1β, MDA and ATP, were significantly increased in both the UCP2 and miR-133a groups compared with the DSS group. The miR-133a-UCP2 pathway participates in IBD by altering downstream inflammation, oxidative stress and markers of energy metabolism, which provides novel clues and potential therapeutic targets for IBD.

Antifatigue Effect of Luteolin-6-C-Neohesperidoside on Oxidative Stress Injury Induced by Forced Swimming of Rats through Modulation of Nrf2/ARE Signaling Pathways.

Luteolin-6-C-neohesperidoside (LN) is a flavonoid isolated from moso bamboo leaf. This study was performed to evaluate the antifatigue effect of LN on a rat model undergoing the weight-loaded forced swimming test (FST). Briefly, male Sprague-Dawley rats (20–22 weeks old) were forced to undertake exhaustive swimming every other day for 3 weeks. Each swimming session was followed by the administration of distilled water, LN (25–75 mg/kg), or ascorbic acid (100 mg/kg) 1 h later. Oral administration of LN significantly improved exercise endurance; normalized alterations in energy metabolic markers; and decreased serum lactic acid, lactate dehydrogenase, and blood urea nitrogen levels of rats that underwent FST. Moreover, LN enhanced the activities of antioxidant enzymes and antioxidant capacity, as measured by enzyme activity assays, RT-PCR, and Western blotting, as well as decreasing the levels of proinflammatory cytokines such as tumor necrosis factor-α, interleukin-1β (IL-1β), and IL-6 and increasing the level of anti-inflammatory (IL-10) in the liver and skeletal muscle. These results suggested that LN reduces both physical and mental effects of chronic fatigue, probably by attenuating oxidative stress injury and inflammatory responses in the liver and skeletal muscle. This study thus supports the use of LN in functional foods for antifatigue and antioxidant effects.

ВЛИЯНИЕ ИСКУССТВЕННОЙ ВЕНТИЛЯЦИИ ЛЕГКИХ НА РЕАЛЬНУЮ ЭНЕРГОПОТРЕБНОСТЬ У ПАЦИЕНТОВ ХИРУРГИЧЕСКОГО ОТДЕЛЕНИЯ РЕАНИМАЦИИ И ИНТЕНСИВНОЙ ТЕРАПИИ

Elective or emergence surgery often is closely connected with development of hypercatabolism-hypermetabolism syndrome. Non-effective and late nutritional support in surgical critically ill patients lead to several consequences and complications such as: wound and nosocomial infectons, gastric stress ulcers, pressure ulcers, prolonged artificial lung ventilation, increased length of stay in ICU and hospital. Energy deficit is one of the important components of critical illness and it corresponds with multiple organ dysfunction progression. Prospective study was provided in 18 beds surgical intensive care unit (SICU). 106 patient medical cards were divided into 4 groupstwo control and two basic with espiratory support (subgroup with artificial lung ventilation and subgroup without artificial lung ventilation). We compared the effectiviness of two methods for the estimation of patients energy needsspecial equations and indirect calorimetry. As a result we found out that main markers of energy and protein metabolism and nutritive status were significantly higher in indirect calorimetry groupswith and without artificial lung ventilation. Conclusion: Indirect calorimetry method usage for the estimation of energy needs in surgical ICU patients is more effective than special equations method during first 7 days of critical illness and may be recommended for clinical practice implication.

Adaptation of exercise-induced stress in well-trained healthy young men.

What is the central question of this study? Exercise is known to induce stress-related physiological responses, such as changes in intestinal barrier function. Our aim was to determine the test-retest repeatability of these responses in well-trained individuals. What is the main finding and its importance? Responses to strenuous exercise, as indicated by stress-related markers such as intestinal integrity markers and myokines, showed high test-retest variation. Even in well-trained young men an adapted response is seen after a single repetition after 1 week. This finding has implications for the design of studies aimed at evaluating physiological responses to exercise. Strenuous exercise induces different stress-related physiological changes, potentially including changes in intestinal barrier function. In the Protégé Study (ISRCTN14236739; www.isrctn.com), we determined the test-retest repeatability in responses to exercise in well-trained individuals. Eleven well-trained men (27±4 years old) completed an exercise protocol that consisted of intensive cycling intervals, followed by an overnight fast and an additional 90min cycling phase at 50% of maximal workload the next morning. The day before (rest), and immediately after the exercise protocol (exercise) a lactulose and rhamnose solution was ingested. Markers of energy metabolism, lactulose-to-rhamnose ratio, several cytokines and potential stress-related markers were measured at rest and during exercise. In addition, untargeted urine metabolite profiles were obtained. The complete procedure (Test) was repeated 1week later (Retest) to assess repeatability. Metabolic effect parameters with regard to energy metabolism and urine metabolomics were similar for both the Test and Retest period, underlining comparable exercise load. Following exercise, intestinal permeability (1h plasma lactulose-to-rhamnose ratio) and the serum interleukin-6, interleukin-10, fibroblast growth factor-21 and muscle creatine kinase concentrations were significantly increased compared with rest only during the first test and not when the test was repeated. Responses to strenuous exercise in well-trained young men, as indicated by intestinal markers and myokines, show adaptation in Test-Retest outcome. This might be attributable to a carry-over effect of the defense mechanisms triggered during the Test. This finding has implications for the design of studies aimed at evaluating physiological responses to exercise.

Muscle catabolic capacities and global hepatic epigenome are modified in juvenile rainbow trout fed different vitamin levels at first feeding

Based on the concept of nutritional programming in mammals, we tested whether a short term hyper or hypo vitamin stimulus during first-feeding could induce long-lasting changes in nutrient metabolism in rainbow trout. Trout alevins received during the 4 first weeks of exogenous feeding a diet either without supplemental vitamins (NOSUP), a diet supplemented with a vitamin premix to satisfy the minimal requirement in all the vitamins (NRC) or a diet with a vitamin premix corresponding to an optimal vitamin nutrition (OVN). Following a common rearing period on the control diet, all three groups were then evaluated in terms of metabolic marker gene expressions at the end of the feeding period (day 119). Whereas no gene modifications for proteins involved in energy and lipid metabolism were observed in whole alevins (short-term effect), some of these genes showed a long-term molecular adaptation in the muscle of juveniles (long-term effect). Indeed, muscle of juveniles subjected at an early feeding of the OVN diet displayed up-regulated expression of markers of lipid catabolism (3-hydroxyacyl-CoA dehydrogenase – HOAD - enzyme) and mitochondrial energy metabolism (Citrate synthase - cs, Ubiquitinol cytochrome c reductase core protein 2 - QCR2, cytochrome oxidase 4 - COX4, ATP synthase form 5 - ATP5A) compared to fish fed the NOSUP diet. Moreover, some key enzymes involved in glucose catabolism (Muscle Pyruvate kinase - PKM) and amino acid catabolism (Glutamate dehydrogenase - GDH3) were also up regulated in muscle of juvenile fish fed with the OVN diet at first-feeding compared to fish fed the NOSUP diet. We researched if these permanently modified gene expressions could be related to global modifications of epigenetic marks (global DNA methylation and global histone acetylation and methylation). There was no variation of the epigenetic marks in muscle. However, we found changes in hepatic DNA methylation, global H3 acetylation and H3K4 methylation, dependent on the vitamin intake at early life. In summary, our data show, for the first time in fish, that a short-term vitamin-stimulus during early life may durably influence muscle energy and lipid metabolism as well as some hepatic epigenetic marks in rainbow trout. Statement of relevanceProgramming at first feeding with different levels of vitamins was successfully tested in fish for the first time. These data proove one more time the importance of the early life on the fish metabolism in adults.

Classification for Longevity Potential: The Use of Novel Biomarkers.

In older people, chronological age may not be the best predictor of residual lifespan and mortality, because with age the heterogeneity in health is increasing. Biomarkers for biological age and residual lifespan are being developed to predict disease and mortality better at an individual level than chronological age. In the current paper, we aim to classify a group of older people into those with longevity potential or controls. In the Leiden Longevity Study participated 1671 offspring of nonagenarian siblings, as the group with longevity potential, and 744 similarly aged controls. Using known risk factors for cardiovascular disease, previously reported markers for human longevity and other physiological measures as predictors, classification models for longevity potential were constructed with multiple logistic regression of the offspring-control status. The Framingham Risk Score (FRS) is predictive for longevity potential [area under the receiver operating characteristic curve (AUC) = 64.7]. Physiological parameters involved in immune responses and glucose, lipid and energy metabolism further improve the prediction performance for longevity potential (AUCmale = 71.4, AUCfemale = 68.7). Using the FRS, the classification of older people in groups with longevity potential and controls is moderate, but can be improved to a reasonably good classification in combination with markers of immune response, glucose, lipid, and energy metabolism. We show that individual classification of older people for longevity potential may be feasible using biomarkers from a wide variety of different biological processes.

Trait-related alterations of N-acetylaspartate in euthymic bipolar patients: A longitudinal proton magnetic resonance spectroscopy study

BackgroundNeurochemical changes are responsible for bipolar disorder (BD) pathophysiology. Despite current progress in BD research, mood- and trait-related alterations in BD continue to elicit further investigation. MethodsIn this study, we report a longitudinal proton magnetic resonance spectroscopy study evaluating dorsomedial prefrontal cortex (DMPFC) metabolites N-acetylaspartate (NAA), creatine plus phosphocreatine (total creatine [tCr]), phosphorylcholine plus glycerophosphocholine, myo-inositol, and glutamate plus glutamine levels of manic and euthymic adult BD type I patients (n=48) treated with standard antimanic medicines, compared to matching healthy controls (n=44). ResultsDMPFC NAA values and NAA/tCr ratio were significantly lower in euthymic BD patients when compared with healthy controls with similar levels of other metabolites in all groups, indicating a trait-related NAA abnormality in euthymic BD patients. Limitationsof our study include a relatively low (1.5T) magnetic resonance field strength and variable drugs administered to achieve euthymia despite the best efforts to standardize the open fashion treatment. ConclusionsOur study contributes to the integrating models of trait-related metabolite alterations observed in euthymia since NAA is considered as a marker of neuronal viability and mitochondrial energy metabolism. In light of supporting and conflicting results reported previously, future studies with longitudinal designs and larger patient groups are warranted to better define both state- and trait-related cerebral metabolic alterations associated with BD pathophysiology.

Leucine supplementation at the onset of high-fat feeding does not prevent weight gain or improve glycemic regulation in male Sprague-Dawley rats.

Obesity is a major public health concern and it is essential to identify effective treatments and preventative strategies to stop continued increases in obesity rates. The potential functional roles of the branched chain amino acid leucine make this amino acid an attractive candidate for the treatment and/or prevention of obesity. The objective of this study was to determine if long-term leucine supplementation could prevent the development of obesity and reduce the risk factors for chronic disease in rats fed a high-fat (60% fat) diet. Male Sprague-Dawley rats (n=30 per dietary treatment) were meal-fed (3 meals/day) either a control, low-fat diet (LF), control+leucine (LFL), high-fat (HF), or high-fat+leucine (HFL) for 42days. On day 42, rats were sacrificed at 0, 30, or 90min postprandial. Animals fed the HF and HFL diets had higher (P<0.05) final body weights and weight gain compared to animals fed the LF and LFL diets. Leucine supplementation increased epididymal fat mass (P<0.05) and decreased muscle mass (P<0.05). There was no effect of leucine supplementation on postprandial glucose or insulin response. However, there was a significant effect (P<0.05) of diet and time on free fatty acid concentrations. There was no effect of leucine on muscle markers of protein synthesis (4E-BP1, p70S6K) or energy metabolism (Akt, AMPK). Leucine supplementation decreased (P<0.05) PGC1α expression and increased (P<0.05) PPARγ expression in skeletal muscle. In conclusion, long-term leucine supplementation does not prevent weight gain, improve body composition, or improve glycemic control in rats fed a high-fat diet.

Lean-seafood intake decreases urinary markers of mitochondrial lipid and energy metabolism in healthy subjects: Metabolomics results from a randomized crossover intervention study.

Proteins constitute an important part of the human diet, but understanding of the effects of different dietary protein sources on human metabolism is sparse. We aimed to elucidate diet-induced metabolic changes through untargeted urinary metabolomics after four weeks of intervention with lean-seafood or nonseafood diets. It is shown that lean-seafood intake reduces urinary excretion of metabolites involved in mitochondrial lipid and energy metabolism possibly facilitating a higher lipid catabolism in healthy subjects. In a randomized controlled trial with crossover design, 20 healthy subjects consumed two balanced diets that varied in main protein sources for 4 weeks. Morning spot urine samples were collected before and after each intervention period. Untargeted metabolomics based on (1) H NMR spectroscopy and LC-MS analyses were applied to characterize the urinary metabolic response to the interventions. The lean-seafood diet period reduced the urinary level of l-carnitine, 2,6-dimethylheptanoylcarnitine, and N-methyl-2-pyridone-5-carboxamide, relative to the nonseafood period. The dietary analysis revealed that the higher urinary level of trimethylamine-N-oxide after the lean-seafood diet period and guanidinoacetate and 3-methylhistidine after the nonseafood diet period was related to the endogenous content of these compounds in the diets. Our data reveal that 4 weeks of lean-seafood intake reduces urinary excretion of metabolites involved in mitochondrial lipid and energy metabolism possibly facilitating a higher lipid catabolism in healthy subjects after the lean-seafood intake.

Daily Administration of Short-Acting Liothyronine Is Associated with Significant Triiodothyronine Excursions and Fails to Alter Thyroid-Responsive Parameters.

Although most studies of levothyroxine-liothyronine combination therapy employ once-daily hormone administration, the kinetics of once-daily liothyronine have been studied infrequently. The aim of this study was to document both the peak and trough serum triiodothyronine (T3) levels that occur with once-daily liothyronine administration, along with changes in thyroid-responsive parameters. Participants with hypothyroidism were studied prospectively at an academic institution. Patients were switched from levothyroxine monotherapy to liothyronine monotherapy with 15 μg liothyronine for two weeks, and then continued liothyronine at doses of 30-45 μg for a further four weeks in an open-label, single-arm study. Weekly trough levels of T3 were documented. In addition, hourly T3 concentrations immediately following liothyronine tablet administration were documented for eight hours during the sixth week of therapy. Serum thyrotropin (TSH) and free thyroxine (fT4) concentrations were documented. Biochemical markers, markers of energy metabolism, anthropometric parameters, well-being, and hyperthyroid symptoms were also assessed. Mean serum TSH levels increased from 1.56 ± 0.81 mIU/L at baseline to 5.90 ± 5.74 mIU/L at two weeks and 3.84 ± 3.66 mIU/L at six weeks. Trough T3 levels decreased from 99.5 ± 22.9 to 91.9 ± 40.2 at two weeks and recovered to 96.1 ± 32.2 at six weeks. The peak T3 concentration after dosing of liothyronine during week 6 was 292.8 ± 152.3 ng/dL. fT4 levels fell once levothyroxine was discontinued and plateaued at 0.44 ng/dL at week 4. The sex hormone binding globulin (SHBG) concentration decreased at week 2 (p = 0.002). Hyperthyroid symptoms and SF36-PCS scores increased significantly at weeks 4-5 of liothyronine therapy (p = 0.04-0.005). Preference for liothyronine therapy increased from 6% to 39% over the study period. Once-daily dosing of liothyronine at doses of 30-45 μg did not return serum TSH to the values seen during levothyroxine therapy. There were significant excursions in serum total and free T3 concentrations with once-daily therapy. Trials of combination therapy are likely to be associated with similar excursions, albeit of a lesser magnitude. Only the physical component score of the SF36 questionnaire and hyperthyroid symptoms changed significantly with conversion to liothyronine monotherapy. Sustained release preparations with stable serum T3 profiles may have entirely different outcomes.

Seasonal variability of metabolic markers and oxidative balance in freshwater amphipod Hyalella kaingang (Crustacea, Amphipoda)

Amphipods are widely used as bioindicator organisms, in view of their ease of collection and cultivation, sexual dimorphism and abundance, in aquatic environments. In the present study male (n=30) and female (n=30) amphipod Hyalella kaingang were collected during the middle of each season from a nature preserve (Research Center PRÓ-MATA) in São Francisco de Paula, Southern Brazil. Proteins, glycogen, lipids, triglycerides, glycerol, and lipid peroxidation (superoxide dismutase, catalase, and glutathione S-transferase activity) were measured. The results obtained for the markers of energy metabolism, antioxidant enzymes, and lipid peroxidation revealed a clear seasonal variation. The patterns of proteins, glycerol, and glutathione S-transferase activity did not differ between sexes; conversely, differential responses in males and females over the year were observed for all other parameters (glycogen, lipids, triglycerides, lipid peroxidation, and superoxide dismutase and catalase activity). These responses appear to be strongly influenced by a prolonged reproductive period (autumn through spring, peaking in autumn); by the degree of exploratory activity, particularly in the summer and autumn; and by abiotic factors, such as temperature and photoperiod. The responses observed in the summer and autumn (decrease in levels of proteins, glycogen and fats, and increase in lipid peroxidation levels and glutathione S-transferase activity), suggest that this season represents a critical time point for these animals. The parameters studied herein may be used as biomarkers to assess the environmental conditions in the aquatic habitat.

The impact of nutritional and environmental stressors on the immune response, oxidative stress and energy use of rainbow trout (Oncorhynchus mykiss).

The impact of nutritional and environmental stressors on the immune response, oxidative stress and energy use of rainbow trout (Oncorhynchus mykiss).