Physical activity, Cardio-Respiratory Fitness, and Metabolic Traits in Rural Mexican Tarahumara

DEFF Research Database (Denmark)

Christensen, Dirk Lund; Alcala-Sanchez, Imelda; Leal-Berumen, Irene

2012-01-01

Objectives: To study the association between physical activity energy expenditure (PAEE) and cardio-respiratory fitness (CRF) with key metabolic traits and anthropometric measures in the Tarahumara of Mexico. Methods: A cross-sectional study was carried out in five rural communities in Chihuahua...... suggests high levels of overweight and hypertension in the Tarahumara, and points to fitness and physical activity as potential intervention targets although findings should be confirmed in larger samples.......) to estimate CRF. Random blood glucose level and resting blood pressure (BP) were measured with standard anthropometrics. Results: Mean (SD) PAEE was 71.2 (30.3) kJ kg21 day21 and CRF was 36.6 (6.5) mlO2 min21 kg21. Mean (SD) glucose was 127.9 (32.4) mg/dl, with 3.3% having diabetes. Mean (SD) systolic...

Astrocytes and energy metabolism.

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Prebil, Mateja; Jensen, Jørgen; Zorec, Robert; Kreft, Marko

2011-05-01

Astrocytes are glial cells, which play a significant role in a number of processes, including the brain energy metabolism. Their anatomical position between blood vessels and neurons make them an interface for effective glucose uptake from blood. After entering astrocytes, glucose can be involved in different metabolic pathways, e.g. in glycogen production. Glycogen in the brain is localized mainly in astrocytes and is an important energy source in hypoxic conditions and normal brain functioning. The portion of glucose metabolized into glycogen molecules in astrocytes is as high as 40%. It is thought that the release of gliotransmitters (such as glutamate, neuroactive peptides and ATP) into the extracellular space by regulated exocytosis supports a significant part of communication between astrocytes and neurons. On the other hand, neurotransmitter action on astrocytes has a significant role in brain energy metabolism. Therefore, understanding the astrocytes energy metabolism may help understanding neuron-astrocyte interactions.

Effect of genetic variants and traits related to glucose metabolism and their interaction with obesity on breast and colorectal cancer risk among postmenopausal women.

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Jung, Su Yon; Sobel, Eric M; Papp, Jeanette C; Zhang, Zuo-Feng

2017-04-26

Impaired glucose metabolism-related genetic variants and traits likely interact with obesity and related lifestyle factors, influencing postmenopausal breast and colorectal cancer (CRC), but their interconnected pathways are not fully understood. By stratifying via obesity and lifestyles, we partitioned the total effect of glucose metabolism genetic variants on cancer risk into two putative mechanisms: 1) indirect (risk-associated glucose metabolism genetic variants mediated by glucose metabolism traits) and 2) direct (risk-associated glucose metabolism genetic variants through pathways other than glucose metabolism traits) effects. Using 16 single-nucleotide polymorphisms (SNPs) associated with glucose metabolism and data from 5379 postmenopausal women in the Women's Health Initiative Harmonized and Imputed Genome-Wide Association Studies, we retrospectively assessed the indirect and direct effects of glucose metabolism-traits (fasting glucose, insulin, and homeostatic model assessment-insulin resistance [HOMA-IR]) using two quantitative tests. Several SNPs were associated with breast cancer and CRC risk, and these SNP-cancer associations differed between non-obese and obese women. In both strata, the direct effect of cancer risk associated with the SNP accounted for the majority of the total effect for most SNPs, with roughly 10% of cancer risk due to the SNP that was from an indirect effect mediated by glucose metabolism traits. No apparent differences in the indirect (glucose metabolism-mediated) effects were seen between non-obese and obese women. It is notable that among obese women, 50% of cancer risk was mediated via glucose metabolism trait, owing to two SNPs: in breast cancer, in relation to GCKR through glucose, and in CRC, in relation to DGKB/TMEM195 through HOMA-IR. Our findings suggest that glucose metabolism genetic variants interact with obesity, resulting in altered cancer risk through pathways other than those mediated by glucose metabolism traits.

Associations between APOE variants and metabolic traits and the impact of psychological stress.

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Sofia I Iqbal Kring

2011-01-01

Full Text Available In a previous study, we observed that associations between APOE rs439401 and metabolic traits were moderated by chronic stress. Thus, in a population of stressed and non-stressed Danish men, we examined whether associations between APOE rs439401 and a panel of metabolic quantitative traits, all metabolic traits which may lead to T2D and CVD were moderated by psychological stress.Obese young men (n = 475, BMI ≥ 31.0 kg/m(2 and a randomly selected control group (n = 709 identified from a population of 141,800 men were re-examined in two surveys (S-46: mean age 46, S-49: mean age 49 years where anthropometric and biochemical measures were available. Psychological stress factors were assessed by a self-administered 7-item questionnaire. Each item had the possible response categories "yes" and "no" and assessed familial problems and conflicts. Summing positive responses constituted a stress item score, which was then dichotomized into stressed and non-stressed. Logistic regression analysis, applying a recessive genetic model, was used to assess odds ratios (OR of the associations between APOE rs439401 genotypes and adverse levels of metabolic traits.The APOE rs439401 TT-genotype associated positively with BMI (OR = 1.09 [1.01; 1.17], waist circumference (OR = 1.09 [1.02; 1.17] in stressed men at S-46. Positive associations were observed for fasting plasma glucose (OR = 1.42 [1.07; 1.87], serum triglycerides (OR = 1.41 [1.05; 1.91] and with fasting plasma insulin (OR = 1.48 [1.05; 2.08] in stressed men at S-49. Rs439401 TT-genotype also associated positively with surrogate measures of insulin resistance (HOMA-IR; OR = 1.21 [1.03; 1.41] and inversely with insulin sensitivity (Stumvoll index; OR = 0.90 [0.82; 0.99], BIGTT-S(I; OR = 0.60 [0.43; 0.85] in stressed men. No significant associations were observed in non-stressed men, albeit the estimates showed similar but weaker trends as in stressed men.The present results suggest that the APOE rs439401

Personality traits and energy conservation

International Nuclear Information System (INIS)

Shen, Meng; Cui, Qingbin; Fu, Liping

2015-01-01

As a cost-effective solution to energy conservation, behavior based method focuses on changing people's behavior through normative feedback for energy efficiency. While the application of behavior-based method is promising, the challenge exists to achieve efficiently sustainable behavioral change. Based on multi-period observation of energy behavior at the Joint Base Andrews in Maryland, this paper presents a model-based approach aimed to improve the nationally popular and deep-seated benchmark setting strategy for normative feedback used in home energy reports. The improved approach has its merits of countering the undesirable boomerang effect and enhancing the effectiveness of normative feedback targeting different personalities. By introducing a modified opinion dynamics model, this paper simulates the process of energy behavior change and therefore identifies the driver and elementary rules of behavioral change. In particular, the paper defines various behavioral zones in accordance with people's personality and proposes a new customized energy reporting mechanism that maps normative benchmark to personality trait. The new energy reporting policy has strong industrial implication for promoting behavior-based method towards a sustained energy conservation movement. -- Highlights: •We explore the personality driving resident behavior change under peer pressure. •We map the distribution of behavior clusters driven by personality and benchmarks. •The model is tested using data from an experiment conducted in Maryland, U.S. •The population exposed to normative feedback can be divided into six categories. •A personality trait-based home energy reporting mechanism is proposed

Effect of lineage-specific metabolic traits of Lactobacillus reuteri on sourdough microbial ecology.

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Lin, Xiaoxi B; Gänzle, Michael G

2014-09-01

This study determined the effects of specific metabolic traits of Lactobacillus reuteri on its competitiveness in sourdoughs. The competitiveness of lactobacilli in sourdough generally depends on their growth rate; acid resistance additionally contributes to competitiveness in sourdoughs with long fermentation times. Glycerol metabolism via glycerol dehydratase (gupCDE) accelerates growth by the regeneration of reduced cofactors; glutamate metabolism via glutamate decarboxylase (gadB) increases acid resistance by generating a proton motive force. Glycerol and glutamate metabolisms are lineage-specific traits in L. reuteri; therefore, this study employed glycerol dehydratase-positive sourdough isolates of human-adapted L. reuteri lineage I, glutamate decarboxylase-positive strains of rodent-adapted L. reuteri lineage II, as well as mutants with deletions in gadB or gupCDE. The competitivenesses of the strains were quantified by inoculation of wheat and sorghum sourdoughs with defined strains, followed by propagation of doughs with a 10% inoculum and 12-h or 72-h fermentation cycles. Lineage I L. reuteri strains dominated sourdoughs propagated with 12-h fermentation cycles; lineage II L. reuteri strains dominated sourdoughs propagated with 72-h fermentation cycles. L. reuteri 100-23ΔgadB was outcompeted by its wild-type strain in sourdoughs fermented with 72-h fermentation cycles; L. reuteri FUA3400ΔgupCDE was outcompeted by its wild-type strain in sourdoughs fermented with both 12-h and 72-h fermentation cycles. Competition experiments with isogenic pairs of strains resulted in a constant rate of strain displacement of the less competitive mutant strain. In conclusion, lineage-specific traits of L. reuteri determine the competitiveness of this species in sourdough fermentations. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Relation of myeloperoxidase-463G/A polymorphism with metabolic syndrome and its component traits in Egyptian women.

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Mehanna, Eman T; Saleh, Samy M; Ghattas, Maivel H; Mesbah, Noha M; Abo-Elmatty, Dina M

2015-02-01

Myeloperoxidase is a heme protein secreted by activated macrophages and generates intermediates that oxidize lipoproteins. Myeloperoxidase-463G/A is a functional polymorphism involved in regulation of myeloperoxidase expression. The aim of this study is to assess the relation of myeloperoxidase-463G/A polymorphism with metabolic syndrome and its component traits in Egyptian women from the Suez Canal area. The study includes 100 healthy female subjects and 100 metabolic syndrome patients. The component traits of metabolic syndrome are determined and the genotypes of the polymorphisms assessed using the PCR-RFLP technique. There was no significant difference in the allele frequencies between the metabolic syndrome and control groups. However, the GA and AA genotypes were associated with lower total cholesterol, LDL-C, systolic and diastolic blood pressure in the patients. Myeloperoxidase-463G/A polymorphism is not associated with the incidence of metabolic syndrome.

Single feature polymorphism (SFP-based selective sweep identification and association mapping of growth-related metabolic traits in Arabidopsis thaliana

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Stitt Mark

2010-03-01

Full Text Available Abstract Background Natural accessions of Arabidopsis thaliana are characterized by a high level of phenotypic variation that can be used to investigate the extent and mode of selection on the primary metabolic traits. A collection of 54 A. thaliana natural accession-derived lines were subjected to deep genotyping through Single Feature Polymorphism (SFP detection via genomic DNA hybridization to Arabidopsis Tiling 1.0 Arrays for the detection of selective sweeps, and identification of associations between sweep regions and growth-related metabolic traits. Results A total of 1,072,557 high-quality SFPs were detected and indications for 3,943 deletions and 1,007 duplications were obtained. A significantly lower than expected SFP frequency was observed in protein-, rRNA-, and tRNA-coding regions and in non-repetitive intergenic regions, while pseudogenes, transposons, and non-coding RNA genes are enriched with SFPs. Gene families involved in plant defence or in signalling were identified as highly polymorphic, while several other families including transcription factors are depleted of SFPs. 198 significant associations between metabolic genes and 9 metabolic and growth-related phenotypic traits were detected with annotation hinting at the nature of the relationship. Five significant selective sweep regions were also detected of which one associated significantly with a metabolic trait. Conclusions We generated a high density polymorphism map for 54 A. thaliana accessions that highlights the variability of resistance genes across geographic ranges and used it to identify selective sweeps and associations between metabolic genes and metabolic phenotypes. Several associations show a clear biological relationship, while many remain requiring further investigation.

Epilepsy and astrocyte energy metabolism.

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Boison, Detlev; Steinhäuser, Christian

2018-06-01

Epilepsy is a complex neurological syndrome characterized by neuronal hyperexcitability and sudden, synchronized electrical discharges that can manifest as seizures. It is now increasingly recognized that impaired astrocyte function and energy homeostasis play key roles in the pathogenesis of epilepsy. Excessive neuronal discharges can only happen, if adequate energy sources are made available to neurons. Conversely, energy depletion during seizures is an endogenous mechanism of seizure termination. Astrocytes control neuronal energy homeostasis through neurometabolic coupling. In this review, we will discuss how astrocyte dysfunction in epilepsy leads to distortion of key metabolic and biochemical mechanisms. Dysfunctional glutamate metabolism in astrocytes can directly contribute to neuronal hyperexcitability. Closure of astrocyte intercellular gap junction coupling as observed early during epileptogenesis limits activity-dependent trafficking of energy metabolites, but also impairs clearance of the extracellular space from accumulation of K + and glutamate. Dysfunctional astrocytes also increase the metabolism of adenosine, a metabolic product of ATP degradation that broadly inhibits energy-consuming processes as an evolutionary adaptation to conserve energy. Due to the critical role of astroglial energy homeostasis in the control of neuronal excitability, metabolic therapeutic approaches that prevent the utilization of glucose might represent a potent antiepileptic strategy. In particular, high fat low carbohydrate "ketogenic diets" as well as inhibitors of glycolysis and lactate metabolism are of growing interest for the therapy of epilepsy. © 2017 Wiley Periodicals, Inc.

A trait based dynamic energy budget approach to explore emergent microalgal community structure

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Cheng, Y.; Bouskill, N.; Karaoz, U.; Geng, H.; Lane, T.; Pett-Ridge, J.; Mayali, X.; Brodie, E.

2015-12-01

Microalgae play important roles in the global carbon budget. Phytoplankton, including microalgae, are responsible for around 50% of global primary production, and also hold promise as a viable renewable biofuel source. Research has been underway for decades to realize the full potential of algal biofuels at the commercial scale, however, uni-algal ponds are typically threatened by collapse due to microalgal grazing and parasite invasions. Recently, it has been proposed that functionally diverse microalgal-bacterial communities can achieve high biomass and/or lipid yields, and are more stable (less susceptible to invasion) than a monoculture. Similar positive diversity-productivity relationships have been observed in a wide range of ecosystem studies, but the purposeful maintenance of a diverse microbiome is less common in managed systems. In our work, a trait based dynamic energy budget model was developed to explore emergent microalgal community structure under various environmental (e.g. light, temperature, nutrient availability) conditions. The complex algal community can be reduced into functional groups (guilds). Each guild (algae or bacteria) is characterized by distinct physiological traits (e.g. nutrient requirement, growth rate, substrate affinity, lipid production) constrained by biochemical trade-offs. These trait values are derived from literature and information encoded in genomic data. Metabolism of the algae and the bacterial species (symbiotic or non-symbiotic) are described within a dynamic energy budget framework. The model offers a mechanistic framework to predict the optimal microalgal community assemblage towards high productivity and resistance to invasion under prevailing environmental conditions.

Energy Metabolism Impairment in Migraine.

Science.gov (United States)

Cevoli, Sabina; Favoni, Valentina; Cortelli, Pietro

2018-06-22

Migraine is a common disabling neurological disorder which is characterised by recurring headache associated with a variety of sensory and autonomic symptoms. The pathophysiology of migraine remains not entirely understood, although many mechanisms involving the central and peripheral nervous system are now becoming clear. In particular, it is widely accepted that migraine is associated with energy metabolic impairment of the brain. The purpose of this review is to present an update overview of the energy metabolism involvement in the migraine pathophysiology. Several biochemical, morphological and magnetic resonance spectroscopy studies have confirmed the presence of energy production deficiency together with an increment of energy consumption in migraine patients. An increment of energy demand over a certain threshold create metabolic and biochemical preconditions for the onset of the migraine attack. The defect of oxidative energy metabolism in migraine is generalized. It remains to be determined if the mitochondrial deficit in migraine is primary or secondary. Riboflavin and Co-Enzyme Q10, both physiologically implicated in mitochondrial respiratory chain functioning, are effective in migraine prophylaxis, supporting the hypothesis that improving brain energy metabolism may reduce the susceptibility to migraine. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Exercise Effects for Children With Autism Spectrum Disorder: Metabolic Health, Autistic Traits, and Quality of Life.

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Toscano, Chrystiane V A; Carvalho, Humberto M; Ferreira, José P

2018-02-01

This study examined the effects of a 48-week exercise-based intervention on the metabolic profile, autism traits, and perceived quality of life in children with autism spectrum disorder (ASD). We randomly allocated 64 children with ASD (aged 6-12 years) to experimental ( n = 46) and control groups ( n = 18) and used multilevel regression modeling to examine responses to receiving or not receiving the intervention. The experimental group showed beneficial effects on metabolic indicators (high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total cholesterol), autism traits, and parent-perceived quality of life. Our results provide support for exercise and physical activity, including basic coordination and strength exercises, as important therapeutic interventions for children with ASD.

Microalgal bioengineering for sustainable energy development: Recent transgenesis and metabolic engineering strategies.

Science.gov (United States)

Banerjee, Chiranjib; Singh, Puneet Kumar; Shukla, Pratyoosh

2016-03-01

Exploring the efficiency of algae to produce remarkable products can be directly benefitted by studying its mechanism at systems level. Recent advents in biotechnology like flux balance analysis (FBA), genomics and in silico proteomics minimize the wet lab exertion. It is understood that FBA predicts the metabolic products, metabolic pathways and alternative pathway to maximize the desired product, and these are key components for microalgae bio-engineering. This review encompasses recent transgenesis techniques and metabolic engineering strategies applied to different microalgae for improving different traits. Further it also throws light on RNAi and riboswitch engineering based methods which may be advantageous for high throughput microalgal research. A valid and optimally designed microalga can be developed where every engineering strategies meet each other successfully and will definitely fulfill the market needs. It is also to be noted that Omics (viz. genetic and metabolic manipulation with bioinformatics) should be integrated to develop a strain which could prove to be a futuristic solution for sustainable development for energy. Copyright © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Adipose energy stores, physical work, and the metabolic syndrome: lessons from hummingbirds.

Science.gov (United States)

Hargrove, James L

2005-12-13

Hummingbirds and other nectar-feeding, migratory birds possess unusual adaptive traits that offer important lessons concerning obesity, diabetes and the metabolic syndrome. Hummingbirds consume a high sugar diet and have fasting glucose levels that would be severely hyperglycemic in humans, yet these nectar-fed birds recover most glucose that is filtered into the urine. Hummingbirds accumulate over 40% body fat shortly before migrations in the spring and autumn. Despite hyperglycemia and seasonally elevated body fat, the birds are not known to become diabetic in the sense of developing polyuria (glucosuria), polydipsia and polyphagia. The tiny (3-4 g) Ruby-throated hummingbird has among the highest mass-specific metabolic rates known, and loses most of its stored fat in 20 h by flying up to 600 miles across the Gulf of Mexico. During the breeding season, it becomes lean and maintains an extremely accurate energy balance. In addition, hummingbirds can quickly enter torpor and reduce resting metabolic rates by 10-fold. Thus, hummingbirds are wonderful examples of the adaptive nature of fat tissue, and may offer lessons concerning prevention of metabolic syndrome in humans.

The energy metabolism of megacities

International Nuclear Information System (INIS)

Facchini, Angelo; Kennedy, Chris; Stewart, Iain; Mele, Renata

2017-01-01

Highlights: • Energy metabolism leads to a better management of energy use in megacities. • Insights on strategies to improve energy efficiency and reduce resource consumption. • We find a regionalization of energy flows and sectoral energy use. • Scaling law for energy Vs density suggests strategies for compact cities planning. • Supports development of models to reduce GHG emissions and increase resilience. - Abstract: Due to their sheer size and complexity, megacities are extreme examples in which both negative and positive aspects of urbanization co-exist and are amplified. Especially in emerging countries they are becoming the dominant paradigm of the future urbanization, representing a sustainability challenge both from the point of view of energy and resource consumption, and from the point of view of climate change adaptation and mitigation. In this paper we compare the energy metabolism in 27 of the world’s megacities including details of mobile and stationary energy consumption patterns, fuels used, as well as end-use patterns and electricity generation mix. Our results show that per capita total energy consumption scales with urban population density according to a power law characterized by the universal −3/4 scaling, pointing out that compact cities are more energy efficient with respect to dispersed cities. By comparing energy sources and sectoral end use, also focusing on electricity use and generation source, we found a significant regionalization of energy metabolism, and we discuss the implication for resilience, infrastructure planning, GHG emissions, and policies for infrastructure decarbonization. The comparison of the energy metabolism can lead to a more appropriate management of energy use patterns and electricity generation mix in megacities, giving insights on strategies to improve urban energy efficiency and reducing environmental pressure of megacities.

A conserved role for syndecan family members in the regulation of whole-body energy metabolism.

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Maria De Luca

2010-06-01

Full Text Available Syndecans are a family of type-I transmembrane proteins that are involved in cell-matrix adhesion, migration, neuronal development, and inflammation. Previous quantitative genetic studies pinpointed Drosophila Syndecan (dSdc as a positional candidate gene affecting variation in fat storage between two Drosophila melanogaster strains. Here, we first used quantitative complementation tests with dSdc mutants to confirm that natural variation in this gene affects variability in Drosophila fat storage. Next, we examined the effects of a viable dSdc mutant on Drosophila whole-body energy metabolism and associated traits. We observed that young flies homozygous for the dSdc mutation had reduced fat storage and slept longer than homozygous wild-type flies. They also displayed significantly reduced metabolic rate, lower expression of spargel (the Drosophila homologue of PGC-1, and reduced mitochondrial respiration. Compared to control flies, dSdc mutants had lower expression of brain insulin-like peptides, were less fecund, more sensitive to starvation, and had reduced life span. Finally, we tested for association between single nucleotide polymorphisms (SNPs in the human SDC4 gene and variation in body composition, metabolism, glucose homeostasis, and sleep traits in a cohort of healthy early pubertal children. We found that SNP rs4599 was significantly associated with resting energy expenditure (P = 0.001 after Bonferroni correction and nominally associated with fasting glucose levels (P = 0.01 and sleep duration (P = 0.044. On average, children homozygous for the minor allele had lower levels of glucose, higher resting energy expenditure, and slept shorter than children homozygous for the common allele. We also observed that SNP rs1981429 was nominally associated with lean tissue mass (P = 0.035 and intra-abdominal fat (P = 0.049, and SNP rs2267871 with insulin sensitivity (P = 0.037. Collectively, our results in Drosophila and humans argue that

Association of adiponectin promoter variants with traits and clusters of metabolic syndrome in Arabs: family-based study.

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Zadjali, F; Al-Yahyaee, S; Hassan, M O; Albarwani, S; Bayoumi, R A

2013-09-25

Plasma levels of adiponectin are decreased in type 2 diabetes, obesity and hypertension. Our aim was to use a family-based analysis to identify the genetic variants of the adiponectin (ADIPOQ) gene that are associated with obesity, insulin resistance, dyslipidemia and hypertension, among Arabs. We screened 328 Arabs in one large extended family for single nucleotide polymorphisms (SNPs) in the promoter region of the ADIPOQ gene. Two common SNPs were detected: rs17300539 and rs266729. Evidences of association between traits related to the metabolic syndrome and the SNPs were studied by implementing quantitative genetic association analysis. Results showed that SNP rs266729 was significantly associated with body weight (p-value=0.001), waist circumference (p-value=0.037), BMI (p-value=0.015) and percentage of total body fat (p-value=0.003). Up to 4.1% of heritability of obesity traits was explained by the rs266729 locus. Further cross-sectional analysis showed that carriers of the G allele had significantly higher values of waist circumference, BMI and percentage of total body fat (p-values 0.014, 0.004 and 0.032, respectively). No association was detected between SNP rs266729 and other clusters of metabolic syndrome or their traits except for HOMA-IR and fasting plasma insulin levels, p-values 0.035 and 0.004, respectively. In contrast, both measured genotype and cross-sectional analysis failed to detect an association between the SNP rs17300539 with traits and clusters of metabolic syndrome. In conclusion, we showed family-based evidence of association of SNP rs266729 at ADIPOQ gene with traits defining obesity in Arab population. This is important for future prediction and prevention of obesity in population where obesity is in an increasing trend. © 2013 Elsevier B.V. All rights reserved.

Adipose energy stores, physical work, and the metabolic syndrome: lessons from hummingbirds

Directory of Open Access Journals (Sweden)

Hargrove James L

2005-12-01

Full Text Available Abstract Hummingbirds and other nectar-feeding, migratory birds possess unusual adaptive traits that offer important lessons concerning obesity, diabetes and the metabolic syndrome. Hummingbirds consume a high sugar diet and have fasting glucose levels that would be severely hyperglycemic in humans, yet these nectar-fed birds recover most glucose that is filtered into the urine. Hummingbirds accumulate over 40% body fat shortly before migrations in the spring and autumn. Despite hyperglycemia and seasonally elevated body fat, the birds are not known to become diabetic in the sense of developing polyuria (glucosuria, polydipsia and polyphagia. The tiny (3–4 g Ruby-throated hummingbird has among the highest mass-specific metabolic rates known, and loses most of its stored fat in 20 h by flying up to 600 miles across the Gulf of Mexico. During the breeding season, it becomes lean and maintains an extremely accurate energy balance. In addition, hummingbirds can quickly enter torpor and reduce resting metabolic rates by 10-fold. Thus, hummingbirds are wonderful examples of the adaptive nature of fat tissue, and may offer lessons concerning prevention of metabolic syndrome in humans.

Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits

DEFF Research Database (Denmark)

Dastani, Zari; Hivert, Marie-France; Timpson, Nicholas

2012-01-01

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European...

Energy metabolism in the liver.

Science.gov (United States)

Rui, Liangyou

2014-01-01

The liver is an essential metabolic organ, and its metabolic function is controlled by insulin and other metabolic hormones. Glucose is converted into pyruvate through glycolysis in the cytoplasm, and pyruvate is subsequently oxidized in the mitochondria to generate ATP through the TCA cycle and oxidative phosphorylation. In the fed state, glycolytic products are used to synthesize fatty acids through de novo lipogenesis. Long-chain fatty acids are incorporated into triacylglycerol, phospholipids, and/or cholesterol esters in hepatocytes. These complex lipids are stored in lipid droplets and membrane structures, or secreted into the circulation as very low-density lipoprotein particles. In the fasted state, the liver secretes glucose through both glycogenolysis and gluconeogenesis. During pronged fasting, hepatic gluconeogenesis is the primary source for endogenous glucose production. Fasting also promotes lipolysis in adipose tissue, resulting in release of nonesterified fatty acids which are converted into ketone bodies in hepatic mitochondria though β-oxidation and ketogenesis. Ketone bodies provide a metabolic fuel for extrahepatic tissues. Liver energy metabolism is tightly regulated by neuronal and hormonal signals. The sympathetic system stimulates, whereas the parasympathetic system suppresses, hepatic gluconeogenesis. Insulin stimulates glycolysis and lipogenesis but suppresses gluconeogenesis, and glucagon counteracts insulin action. Numerous transcription factors and coactivators, including CREB, FOXO1, ChREBP, SREBP, PGC-1α, and CRTC2, control the expression of the enzymes which catalyze key steps of metabolic pathways, thus controlling liver energy metabolism. Aberrant energy metabolism in the liver promotes insulin resistance, diabetes, and nonalcoholic fatty liver diseases. © 2014 American Physiological Society.

A Genome-Wide mQTL Analysis in Human Adipose Tissue Identifies Genetic Variants Associated with DNA Methylation, Gene Expression and Metabolic Traits

DEFF Research Database (Denmark)

Volkov, Petr; Olsson, Anders H; Gillberg, Linn

2016-01-01

Little is known about the extent to which interactions between genetics and epigenetics may affect the risk of complex metabolic diseases and/or their intermediary phenotypes. We performed a genome-wide DNA methylation quantitative trait locus (mQTL) analysis in human adipose tissue of 119 men, w...... and epigenetic variation in both cis and trans positions influencing gene expression in adipose tissue and in vivo (dys)metabolic traits associated with the development of obesity and diabetes.......Little is known about the extent to which interactions between genetics and epigenetics may affect the risk of complex metabolic diseases and/or their intermediary phenotypes. We performed a genome-wide DNA methylation quantitative trait locus (mQTL) analysis in human adipose tissue of 119 men......, where 592,794 single nucleotide polymorphisms (SNPs) were related to DNA methylation of 477,891 CpG sites, covering 99% of RefSeq genes. SNPs in significant mQTLs were further related to gene expression in adipose tissue and obesity related traits. We found 101,911 SNP-CpG pairs (mQTLs) in cis and 5...

Quantitative genetics parameters show partial independent evolutionary potential for body mass and metabolism in stonechats from different populations

NARCIS (Netherlands)

Tieleman, B. I.; Versteegh, M. A.; Helm, B.; Dingemanse, N. J.; Volff, Jean-Nicolas

2009-01-01

Phenotypic variation in physiological traits, such as energy metabolism, is commonly subjected to adaptive interpretations, but little is known about the heritable basis or genetic correlations among physiological traits in non-domesticated species. Basal metabolic rate (BMR) and body mass are

Root Transcriptomic Analysis Revealing the Importance of Energy Metabolism to the Development of Deep Roots in Rice (Oryza sativa L.

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Qiaojun Lou

2017-07-01

Full Text Available Drought is the most serious abiotic stress limiting rice production, and deep root is the key contributor to drought avoidance. However, the genetic mechanism regulating the development of deep roots is largely unknown. In this study, the transcriptomes of 74 root samples from 37 rice varieties, representing the extreme genotypes of shallow or deep rooting, were surveyed by RNA-seq. The 13,242 differentially expressed genes (DEGs between deep rooting and shallow rooting varieties (H vs. L were enriched in the pathway of genetic information processing and metabolism, while the 1,052 DEGs between the deep roots and shallow roots from each of the plants (D vs. S were significantly enriched in metabolic pathways especially energy metabolism. Ten quantitative trait transcripts (QTTs were identified and some were involved in energy metabolism. Forty-nine candidate DEGs were confirmed by qRT-PCR and microarray. Through weighted gene co-expression network analysis (WGCNA, we found 18 hub genes. Surprisingly, all these hub genes expressed higher in deep roots than in shallow roots, furthermore half of them functioned in energy metabolism. We also estimated that the ATP production in the deep roots was faster than shallow roots. Our results provided a lot of reliable candidate genes to improve deep rooting, and firstly highlight the importance of energy metabolism to the development of deep roots.

Root Transcriptomic Analysis Revealing the Importance of Energy Metabolism to the Development of Deep Roots in Rice (Oryza sativa L.).

Science.gov (United States)

Lou, Qiaojun; Chen, Liang; Mei, Hanwei; Xu, Kai; Wei, Haibin; Feng, Fangjun; Li, Tiemei; Pang, Xiaomeng; Shi, Caiping; Luo, Lijun; Zhong, Yang

2017-01-01

Drought is the most serious abiotic stress limiting rice production, and deep root is the key contributor to drought avoidance. However, the genetic mechanism regulating the development of deep roots is largely unknown. In this study, the transcriptomes of 74 root samples from 37 rice varieties, representing the extreme genotypes of shallow or deep rooting, were surveyed by RNA-seq. The 13,242 differentially expressed genes (DEGs) between deep rooting and shallow rooting varieties (H vs. L) were enriched in the pathway of genetic information processing and metabolism, while the 1,052 DEGs between the deep roots and shallow roots from each of the plants (D vs. S) were significantly enriched in metabolic pathways especially energy metabolism. Ten quantitative trait transcripts (QTTs) were identified and some were involved in energy metabolism. Forty-nine candidate DEGs were confirmed by qRT-PCR and microarray. Through weighted gene co-expression network analysis (WGCNA), we found 18 hub genes. Surprisingly, all these hub genes expressed higher in deep roots than in shallow roots, furthermore half of them functioned in energy metabolism. We also estimated that the ATP production in the deep roots was faster than shallow roots. Our results provided a lot of reliable candidate genes to improve deep rooting, and firstly highlight the importance of energy metabolism to the development of deep roots.

Basal metabolic rate can evolve independently of morphological and behavioural traits.

Science.gov (United States)

Mathot, K J; Martin, K; Kempenaers, B; Forstmeier, W

2013-09-01

Quantitative genetic analyses of basal metabolic rate (BMR) can inform us about the evolvability of the trait by providing estimates of heritability, and also of genetic correlations with other traits that may constrain the ability of BMR to respond to selection. Here, we studied a captive population of zebra finches (Taeniopygia guttata) in which selection lines for male courtship rate have been established. We measure BMR in these lines to see whether selection on male sexual activity would change BMR as a potentially correlated trait. We find that the genetic correlation between courtship rate and BMR is practically zero, indicating that the two traits can evolve independently of each other. Interestingly, we find that the heritability of BMR in our population (h(2)=0.45) is markedly higher than was previously reported for a captive zebra finch population from Norway. A comparison of the two studies shows that additive genetic variance in BMR has been largely depleted in the Norwegian population, especially the genetic variance in BMR that is independent of body mass. In our population, the slope of BMR increase with body mass differs not only between the sexes but also between the six selection lines, which we tentatively attribute to genetic drift and/or founder effects being strong in small populations. Our study therefore highlights two things. First, the evolvability of BMR may be less constrained by genetic correlations and lack of independent genetic variation than previously described. Second, genetic drift in small populations can rapidly lead to different evolvabilities across populations.

Long Non-Coding RNAs Associated with Metabolic Traits in Human White Adipose Tissue

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Hui Gao

2018-04-01

Full Text Available Long non-coding RNAs (lncRNAs belong to a recently discovered class of molecules proposed to regulate various cellular processes. Here, we systematically analyzed their expression in human subcutaneous white adipose tissue (WAT and found that a limited set was differentially expressed in obesity and/or the insulin resistant state. Two lncRNAs herein termed adipocyte-specific metabolic related lncRNAs, ASMER-1 and ASMER-2 were enriched in adipocytes and regulated by both obesity and insulin resistance. Knockdown of either ASMER-1 or ASMER-2 by antisense oligonucleotides in in vitro differentiated human adipocytes revealed that both genes regulated adipogenesis, lipid mobilization and adiponectin secretion. The observed effects could be attributed to crosstalk between ASMERs and genes within the master regulatory pathways for adipocyte function including PPARG and INSR. Altogether, our data demonstrate that lncRNAs are modulators of the metabolic and secretory functions in human fat cells and provide an emerging link between WAT and common metabolic conditions. Keywords: White adipose tissue, Adipocytes, Long non-coding RNAs, Metabolic traits, Lipolysis, Adiponectin

Exploration of Energy Metabolism in the Mouse Using Indirect Calorimetry: Measurement of Daily Energy Expenditure (DEE) and Basal Metabolic Rate (BMR).

Science.gov (United States)

Meyer, Carola W; Reitmeir, Peter; Tschöp, Matthias H

2015-09-01

Current comprehensive mouse metabolic phenotyping involves studying energy balance in cohorts of mice via indirect calorimetry, which determines heat release from changes in respiratory air composition. Here, we describe the measurement of daily energy expenditure (DEE) and basal metabolic rate (BMR) in mice. These well-defined metabolic descriptors serve as meaningful first-line read-outs for metabolic phenotyping and should be reported when exploring energy expenditure in mice. For further guidance, the issue of appropriate sample sizes and the frequency of sampling of metabolic measurements is also discussed. Copyright © 2015 John Wiley & Sons, Inc.

Energy Metabolism in the Liver

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Rui, Liangyou

2014-01-01

The liver is an essential metabolic organ, and its metabolic activity is tightly controlled by insulin and other metabolic hormones. Glucose is metabolized into pyruvate through glycolysis in the cytoplasm, and pyruvate is completely oxidized to generate ATP through the TCA cycle and oxidative phosphorylation in the mitochondria. In the fed state, glycolytic products are used to synthesize fatty acids through de novo lipogenesis. Long-chain fatty acids are incorporated into triacylglycerol, phospholipids, and cholesterol esters in hepatocytes, and these complex lipids are stored in lipid droplets and membrane structures, or secreted into the circulation as VLDL particles. In the fasted state, the liver secretes glucose through both breakdown of glycogen (glycogenolysis) and de novo glucose synthesis (gluconeogenesis). During pronged fasting, hepatic gluconeogenesis is the primary source of endogenous glucose production. Fasting also promotes lipolysis in adipose tissue to release nonesterified fatty acids which are converted into ketone bodies in the liver though mitochondrial β oxidation and ketogenesis. Ketone bodies provide a metabolic fuel for extrahepatic tissues. Liver metabolic processes are tightly regulated by neuronal and hormonal systems. The sympathetic system stimulates, whereas the parasympathetic system suppresses, hepatic gluconeogenesis. Insulin stimulates glycolysis and lipogenesis, but suppresses gluconeogenesis; glucagon counteracts insulin action. Numerous transcription factors and coactivators, including CREB, FOXO1, ChREBP, SREBP, PGC-1α, and CRTC2, control the expression of the enzymes which catalyze the rate-limiting steps of liver metabolic processes, thus controlling liver energy metabolism. Aberrant energy metabolism in the liver promotes insulin resistance, diabetes, and nonalcoholic fatty liver diseases (NAFLD). PMID:24692138

Genome-wide association mapping of leaf metabolic profiles for dissecting complex traits in maize.

Science.gov (United States)

Riedelsheimer, Christian; Lisec, Jan; Czedik-Eysenberg, Angelika; Sulpice, Ronan; Flis, Anna; Grieder, Christoph; Altmann, Thomas; Stitt, Mark; Willmitzer, Lothar; Melchinger, Albrecht E

2012-06-05

The diversity of metabolites found in plants is by far greater than in most other organisms. Metabolic profiling techniques, which measure many of these compounds simultaneously, enabled investigating the regulation of metabolic networks and proved to be useful for predicting important agronomic traits. However, little is known about the genetic basis of metabolites in crops such as maize. Here, a set of 289 diverse maize inbred lines was genotyped with 56,110 SNPs and assayed for 118 biochemical compounds in the leaves of young plants, as well as for agronomic traits of mature plants in field trials. Metabolite concentrations had on average a repeatability of 0.73 and showed a correlation pattern that largely reflected their functional grouping. Genome-wide association mapping with correction for population structure and cryptic relatedness identified for 26 distinct metabolites strong associations with SNPs, explaining up to 32.0% of the observed genetic variance. On nine chromosomes, we detected 15 distinct SNP-metabolite associations, each of which explained more then 15% of the genetic variance. For lignin precursors, including p-coumaric acid and caffeic acid, we found strong associations (P values to ) with a region on chromosome 9 harboring cinnamoyl-CoA reductase, a key enzyme in monolignol synthesis and a target for improving the quality of lignocellulosic biomass by genetic engineering approaches. Moreover, lignin precursors correlated significantly with lignin content, plant height, and dry matter yield, suggesting that metabolites represent promising connecting links for narrowing the genotype-phenotype gap of complex agronomic traits.

Traits to Ecosystems: The Ecological Sustainability Challenge When Developing Future Energy Crops

International Nuclear Information System (INIS)

Weih, Martin; Hoeber, Stefanie; Beyer, Friderike; Fransson, Petra

2014-01-01

Today, we are undertaking great efforts to improve biomass production and quality traits of energy crops. Major motivation for developing those crops is based on environmental and ecological sustainability considerations, which however often are de-coupled from the trait-based crop improvement programs. It is now time to develop appropriate methods to link crop traits to production system characteristics set by the plant and the biotic communities influencing it; and to the ecosystem processes affecting ecological sustainability. The relevant ecosystem processes involve the net productivity in terms of biomass and energy yields, the depletion of energy-demanding resources (e.g., nitrogen, N), the carbon dynamics in soil and atmosphere, and the resilience and temporal stability of the production system. In a case study, we compared aspects of N use efficiency in various varieties of an annual (spring wheat) and perennial (Salix) energy crop grown under two nutrient regimes in Sweden. For example, we found considerable variation among crops, varieties, and nutrient regimes in the energy yield per plant-internal N (megajoule per gram per year), which would result in different N resource depletion per unit energy produced.

Traits to Ecosystems: The Ecological Sustainability Challenge When Developing Future Energy Crops

Energy Technology Data Exchange (ETDEWEB)

Weih, Martin, E-mail: martin.weih@slu.se; Hoeber, Stefanie; Beyer, Friderike [Department of Crop Production Ecology, Swedish University of Agricultural Sciences, Uppsala (Sweden); Fransson, Petra [Department of Forest Mycology and Plant Pathology, Swedish University of Agricultural Sciences, Uppsala (Sweden)

2014-05-22

Today, we are undertaking great efforts to improve biomass production and quality traits of energy crops. Major motivation for developing those crops is based on environmental and ecological sustainability considerations, which however often are de-coupled from the trait-based crop improvement programs. It is now time to develop appropriate methods to link crop traits to production system characteristics set by the plant and the biotic communities influencing it; and to the ecosystem processes affecting ecological sustainability. The relevant ecosystem processes involve the net productivity in terms of biomass and energy yields, the depletion of energy-demanding resources (e.g., nitrogen, N), the carbon dynamics in soil and atmosphere, and the resilience and temporal stability of the production system. In a case study, we compared aspects of N use efficiency in various varieties of an annual (spring wheat) and perennial (Salix) energy crop grown under two nutrient regimes in Sweden. For example, we found considerable variation among crops, varieties, and nutrient regimes in the energy yield per plant-internal N (megajoule per gram per year), which would result in different N resource depletion per unit energy produced.

Influence of anaesthesia on energy metabolism in surgery

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Prigorodov М.V.

2013-03-01

Full Text Available The purpose of the article is to establish adequacy of protection of energy metabolism in a patient under anaes-thesiology in cholecystectomy from mini-access. Material et methods: 122 patients subjected to cholecystectomy from mini access have been surveyed. Among them 92 patients have got intravenous general anaesthesia with AVL, 30 patients have got prolonged epidural anaesthesia on spontaneous breath with insufflations of oxygen through an obverse mask with sedatations. Monitoring of energy-plastic metabolism has been carried out in all patients. Results: Groups of patients have been compared by anthropometrical data, traumatic interventions. In both groups of patients loss of energy to traumatic to an operation stage has insignificantly increased, but after the anaesthesia termination in the group of patients with intravenous anaesthesia loss of energy continued to rise, and in the group of patients with prolonged epidural blockade it has returned to the initial level. After the anaesthesia termination the energy metabolism became essential higher in the first group of patients in comparison with the second one (p <0,01. The energy-plastic metabolism increased in the first group of patients and decreased in the second. PEA during cholecystectomy from mini access provided a stable condition of energy and energy-plastic metabolism. The conclusion: The inspection of 122 patients subjected to cholecystectomy from mini access has established the following data: PEA on spontaneous breath with insufflations of oxygen through an obverse mask in comparison with intravenous general anaesthesia and AVL allows keeping on an optimum level of energy and energy-plastic metabolism.

Proteomic analysis indicates that mitochondrial energy metabolism in skeletal muscle tissue is negatively correlated with feed efficiency in pigs

Science.gov (United States)

Fu, Liangliang; Xu, Yueyuan; Hou, Ye; Qi, Xiaolong; Zhou, Lian; Liu, Huiying; Luan, Yu; Jing, Lu; Miao, Yuanxin; Zhao, Shuhong; Liu, Huazhen; Li, Xinyun

2017-03-01

Feed efficiency (FE) is a highly important economic trait in pig production. Investigating the molecular mechanisms of FE is essential for trait improvement. In this study, the skeletal muscle proteome of high-FE and low-FE pigs were investigated by the iTRAQ approach. A total of 1780 proteins were identified, among which 124 proteins were differentially expressed between the high- and low-FE pigs, with 74 up-regulated and 50 down-regulated in the high-FE pigs. Ten randomly selected differentially expressed proteins (DEPs) were validated by Western blotting and quantitative PCR (qPCR). Gene ontology (GO) analysis showed that all the 25 DEPs located in mitochondria were down-regulated in the high-FE pigs. Furthermore, the glucose-pyruvate-tricarboxylic acid (TCA)-oxidative phosphorylation energy metabolism signaling pathway was found to differ between high- and low-FE pigs. The key enzymes involved in the conversion of glucose to pyruvate were up-regulated in the high-FE pigs. Thus, our results suggested mitochondrial energy metabolism in the skeletal muscle tissue was negatively correlated with FE in pigs, and glucose utilization to generate ATP was more efficient in the skeletal muscle tissue of high-FE pigs. This study offered new targets and pathways for improvement of FE in pigs.

Phenotypic and genetic effects of contrasting ethanol environments on physiological and developmental traits in Drosophila melanogaster.

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Luis E Castañeda

Full Text Available A central problem in evolutionary physiology is to understand the relationship between energy metabolism and fitness-related traits. Most attempts to do so have been based on phenotypic correlations that are not informative for the evolutionary potential of natural populations. Here, we explored the effect of contrasting ethanol environments on physiological and developmental traits, their genetic (covariances and genetic architecture in Drosophila melanogaster. Phenotypic and genetic parameters were estimated in two populations (San Fernando and Valdivia, Chile, using a half-sib family design where broods were split into ethanol-free and ethanol-supplemented conditions. Our findings show that metabolic rate, body mass and development times were sensitive (i.e., phenotypic plasticity to ethanol conditions and dependent on population origin. Significant heritabilities were found for all traits, while significant genetic correlations were only found between larval and total development time and between development time and metabolic rate for flies of the San Fernando population developed in ethanol-free conditions. Posterior analyses indicated that the G matrices differed between ethanol conditions for the San Fernando population (mainly explained by differences in genetic (covariances of developmental traits, whereas the Valdivia population exhibited similar G matrices between ethanol conditions. Our findings suggest that ethanol-free environment increases the energy available to reduce development time. Therefore, our results indicate that environmental ethanol could modify the process of energy allocation, which could have consequences on the evolutionary response of natural populations of D. melanogaster.

Phenotypic and Genetic Effects of Contrasting Ethanol Environments on Physiological and Developmental Traits in Drosophila melanogaster

Science.gov (United States)

Castañeda, Luis E.; Nespolo, Roberto F.

2013-01-01

A central problem in evolutionary physiology is to understand the relationship between energy metabolism and fitness-related traits. Most attempts to do so have been based on phenotypic correlations that are not informative for the evolutionary potential of natural populations. Here, we explored the effect of contrasting ethanol environments on physiological and developmental traits, their genetic (co)variances and genetic architecture in Drosophila melanogaster. Phenotypic and genetic parameters were estimated in two populations (San Fernando and Valdivia, Chile), using a half-sib family design where broods were split into ethanol-free and ethanol-supplemented conditions. Our findings show that metabolic rate, body mass and development times were sensitive (i.e., phenotypic plasticity) to ethanol conditions and dependent on population origin. Significant heritabilities were found for all traits, while significant genetic correlations were only found between larval and total development time and between development time and metabolic rate for flies of the San Fernando population developed in ethanol-free conditions. Posterior analyses indicated that the G matrices differed between ethanol conditions for the San Fernando population (mainly explained by differences in genetic (co)variances of developmental traits), whereas the Valdivia population exhibited similar G matrices between ethanol conditions. Our findings suggest that ethanol-free environment increases the energy available to reduce development time. Therefore, our results indicate that environmental ethanol could modify the process of energy allocation, which could have consequences on the evolutionary response of natural populations of D. melanogaster. PMID:23505567

Sodium signaling and astrocyte energy metabolism

KAUST Repository

Chatton, Jean-Yves; Magistretti, Pierre J.; Barros, L. Felipe

2016-01-01

The Na+ gradient across the plasma membrane is constantly exploited by astrocytes as a secondary energy source to regulate the intracellular and extracellular milieu, and discard waste products. One of the most prominent roles of astrocytes in the brain is the Na+-dependent clearance of glutamate released by neurons during synaptic transmission. The intracellular Na+ load collectively generated by these processes converges at the Na,K-ATPase pump, responsible for Na+ extrusion from the cell, which is achieved at the expense of cellular ATP. These processes represent pivotal mechanisms enabling astrocytes to increase the local availability of metabolic substrates in response to neuronal activity. This review presents basic principles linking the intracellular handling of Na+ following activity-related transmembrane fluxes in astrocytes and the energy metabolic pathways involved. We propose a role of Na+ as an energy currency and as a mediator of metabolic signals in the context of neuron-glia interactions. We further discuss the possible impact of the astrocytic syncytium for the distribution and coordination of the metabolic response, and the compartmentation of these processes in cellular microdomains and subcellular organelles. Finally, we illustrate future avenues of investigation into signaling mechanisms aimed at bridging the gap between Na+ and the metabolic machinery. © 2016 Wiley Periodicals, Inc.

Sodium signaling and astrocyte energy metabolism

KAUST Repository

Chatton, Jean-Yves

2016-03-31

The Na+ gradient across the plasma membrane is constantly exploited by astrocytes as a secondary energy source to regulate the intracellular and extracellular milieu, and discard waste products. One of the most prominent roles of astrocytes in the brain is the Na+-dependent clearance of glutamate released by neurons during synaptic transmission. The intracellular Na+ load collectively generated by these processes converges at the Na,K-ATPase pump, responsible for Na+ extrusion from the cell, which is achieved at the expense of cellular ATP. These processes represent pivotal mechanisms enabling astrocytes to increase the local availability of metabolic substrates in response to neuronal activity. This review presents basic principles linking the intracellular handling of Na+ following activity-related transmembrane fluxes in astrocytes and the energy metabolic pathways involved. We propose a role of Na+ as an energy currency and as a mediator of metabolic signals in the context of neuron-glia interactions. We further discuss the possible impact of the astrocytic syncytium for the distribution and coordination of the metabolic response, and the compartmentation of these processes in cellular microdomains and subcellular organelles. Finally, we illustrate future avenues of investigation into signaling mechanisms aimed at bridging the gap between Na+ and the metabolic machinery. © 2016 Wiley Periodicals, Inc.

Invited review: overview of new traits and phenotyping strategies in dairy cattle with a focus on functional traits.

Science.gov (United States)

Egger-Danner, C; Cole, J B; Pryce, J E; Gengler, N; Heringstad, B; Bradley, A; Stock, K F

2015-02-01

For several decades, breeding goals in dairy cattle focussed on increased milk production. However, many functional traits have negative genetic correlations with milk yield, and reductions in genetic merit for health and fitness have been observed. Herd management has been challenged to compensate for these effects and to balance fertility, udder health and metabolic diseases against increased production to maximize profit without compromising welfare. Functional traits, such as direct information on cow health, have also become more important because of growing concern about animal well-being and consumer demands for healthy and natural products. There are major concerns about the impact of drugs used in veterinary medicine on the spread of antibiotic-resistant strains of bacteria that can negatively impact human health. Sustainability and efficiency are also increasingly important because of the growing competition for high-quality, plant-based sources of energy and protein. Disruptions to global environments because of climate change may encourage yet more emphasis on these traits. To be successful, it is vital that there be a balance between the effort required for data recording and subsequent benefits. The motivation of farmers and other stakeholders involved in documentation and recording is essential to ensure good data quality. To keep labour costs reasonable, existing data sources should be used as much as possible. Examples include the use of milk composition data to provide additional information about the metabolic status or energy balance of the animals. Recent advances in the use of mid-infrared spectroscopy to measure milk have shown considerable promise, and may provide cost-effective alternative phenotypes for difficult or expensive-to-measure traits, such as feed efficiency. There are other valuable data sources in countries that have compulsory documentation of veterinary treatments and drug use. Additional sources of data outside of the farm

Association of rs780094 in GCKR with metabolic traits and incident diabetes and cardiovascular disease: the ARIC Study.

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Mark Bi

2010-07-01

Full Text Available The minor T-allele of rs780094 in the glucokinase regulator gene (GCKR associates with a number of metabolic traits including higher triglyceride levels and improved glycemic regulation in study populations of mostly European ancestry. Using data from the Atherosclerosis Risk in Communities (ARIC Study, we sought to replicate these findings, examine them in a large population-based sample of African American study participants, and to investigate independent associations with other metabolic traits in order to determine if variation in GKCR contributes to their observed clustering. In addition, we examined the association of rs780094 with incident diabetes, coronary heart disease (CHD, and stroke over up mean follow-up times of 8, 15, and 15 years, respectively.Race-stratified analyses were conducted among 10,929 white and 3,960 black participants aged 45-64 at baseline assuming an additive genetic model and using linear and logistic regression and Cox proportional hazards models.Previous findings replicated among white participants in multivariable adjusted models: the T-allele of rs780094 was associated with lower fasting glucose (p = 10(-7 and insulin levels (p = 10(-6, lower insulin resistance (HOMA-IR, p = 10(-9, less prevalent diabetes (p = 10(-6, and higher CRP (p = 10(-8, 2-h postprandial glucose (OGTT, p = 10(-6, and triglyceride levels (p = 10(-31. Moreover, the T-allele was independently associated with higher HDL cholesterol levels (p = 0.022, metabolic syndrome prevalence (p = 0.043, and lower beta-cell function measured as HOMA-B (p = 0.011. Among black participants, the T-allele was associated only with higher triglyceride levels (p = 0.004 and lower insulin levels (p = 0.002 and HOMA-IR (p = 0.013. Prospectively, the T-allele was associated with reduced incidence of diabetes (p = 10(-4 among white participants, but not with incidence of CHD or stroke.Our findings indicate rs780094 has independent associations with multiple

Insulin Clearance Is Associated with Hepatic Lipase Activity and Lipid and Adiposity Traits in Mexican Americans.

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Artak Labadzhyan

Full Text Available Reduction in insulin clearance plays an important role in the compensatory response to insulin resistance. Given the importance of this trait to the pathogenesis of diabetes, a deeper understanding of its regulation is warranted. Our goal was to identify metabolic and cardiovascular traits that are independently associated with metabolic clearance rate of insulin (MCRI. We conducted a cross-sectional analysis of metabolic and cardiovascular traits in 765 participants from the Mexican-American Coronary Artery Disease (MACAD project who had undergone blood sampling, oral glucose tolerance test, euglycemic-hyperinsulinemic clamp, dual-energy X-ray absorptiometry, and carotid ultrasound. We assessed correlations of MCRI with traits from seven domains, including anthropometry, biomarkers, cardiovascular, glucose homeostasis, lipase activity, lipid profile, and liver function tests. We found inverse independent correlations between MCRI and hepatic lipase (P = 0.0004, insulin secretion (P = 0.0002, alanine aminotransferase (P = 0.0045, total fat mass (P = 0.014, and diabetes (P = 0.03. MCRI and apolipoprotein A-I exhibited a positive independent correlation (P = 0.035. These results generate a hypothesis that lipid and adiposity associated traits related to liver function may play a role in insulin clearance.

Heritability, parental transmission and environment correlation of pediatric-onset type 2 diabetes mellitus and metabolic syndrome-related traits.

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Miranda-Lora, América L; Vilchis-Gil, Jenny; Molina-Díaz, Mario; Flores-Huerta, Samuel; Klünder-Klünder, Miguel

2017-04-01

To estimate the heritability, parental transmission and environmental contributions to the phenotypic variation in type 2 diabetes mellitus and metabolic syndrome-related traits in families of Mexican children and adolescents. We performed a cross-sectional study of 184 tri-generational pedigrees with a total of 1160 individuals (99 families with a type 2 diabetes mellitus proband before age 19). The family history of type 2 diabetes mellitus in three generations was obtained by interview. Demographic, anthropometric, biochemical and lifestyle information was corroborated in parents and offspring. We obtained correlations for metabolic traits between relative pairs, and variance component methods were used to determine the heritability and environmental components. The heritability of early-onset of type 2 diabetes mellitus was 0.50 (p1.0e-7). The heritability was greater than 0.5 for hypertension, hypoalphalipoproteinemia, hypercholesterolemia, body mass index, waist circumference, blood pressure, 2-h insulin, and cholesterol (p1). In contrast, we observed a high environmental correlation (>0.50) for blood pressure, HbA1c and HDL-cholesterol after multivariate adjustment (ptype 2 diabetes mellitus and insulin resistance, were significantly correlated only through the mother and others, such as hypertriglyceridemia, were significantly correlated only through the father. This study demonstrates that type 2 diabetes mellitus and metabolic syndrome-related traits are highly heritable among Mexican children and adolescents. Furthermore, several cardiometabolic factors have strong heritability and/or high environmental contributions that highlight the complex architecture of these alterations. Copyright © 2017 Elsevier B.V. All rights reserved.

Systems biology and genome-wide approaches to unveil the molecular players involved in the pre-germinative metabolism: implications on seed technology traits.

Science.gov (United States)

Macovei, Anca; Pagano, Andrea; Leonetti, Paola; Carbonera, Daniela; Balestrazzi, Alma; Araújo, Susana S

2017-05-01

The pre-germinative metabolism is among the most fascinating aspects of seed biology. The early seed germination phase, or pre-germination, is characterized by rapid water uptake (imbibition), which directs a series of dynamic biochemical events. Among those are enzyme activation, DNA damage and repair, and use of reserve storage compounds, such as lipids, carbohydrates and proteins. Industrial seedling production and intensive agricultural production systems require seed stocks with high rate of synchronized germination and low dormancy. Consequently, seed dormancy, a quantitative trait related to the activation of the pre-germinative metabolism, is probably the most studied seed trait in model species and crops. Single omics, systems biology, QTLs and GWAS mapping approaches have unveiled a list of molecules and regulatory mechanisms acting at transcriptional, post-transcriptional and post-translational levels. Most of the identified candidate genes encode for regulatory proteins targeting ROS, phytohormone and primary metabolisms, corroborating the data obtained from simple molecular biology approaches. Emerging evidences show that epigenetic regulation plays a crucial role in the regulation of these mentioned processes, constituting a still unexploited strategy to modulate seed traits. The present review will provide an up-date of the current knowledge on seed pre-germinative metabolism, gathering the most relevant results from physiological, genetics, and omics studies conducted in model and crop plants. The effects exerted by the biotic and abiotic stresses and priming are also addressed. The possible implications derived from the modulation of pre-germinative metabolism will be discussed from the point of view of seed quality and technology.

Implications of central obesity-related variants in LYPLAL1, NRXN3, MSRA, and TFAP2B on quantitative metabolic traits in adult Danes.

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Dorthe S Bille

Full Text Available Two meta-analyses of genome-wide association studies (GWAS have suggested that four variants: rs2605100 in lysophospholipase-like 1 (LYPLAL1, rs10146997 in neuroxin 3 (NRXN3, rs545854 in methionine sulfoxide reductase A (MSRA, and rs987237 in transcription factor activating enhancer-binding protein 2 beta (TFAP2B associate with measures of central obesity. To elucidate potential underlying phenotypes we aimed to investigate whether these variants associated with: 1 quantitative metabolic traits, 2 anthropometric measures (waist circumference (WC, waist-hip ratio, and BMI, or 3 type 2 diabetes, and central and general overweight and obesity.The four variants were genotyped in Danish individuals using KASPar®. Quantitative metabolic traits were examined in a population-based sample (n = 6,038 and WC and BMI were furthermore analyzed in a combined study sample (n = 13,507. Case-control studies of diabetes and adiposity included 15,326 individuals. The major G-allele of LYPLAL1 rs2605100 associated with increased fasting serum triglyceride concentrations (per allele effect (β = 3%(1;5(95%CI, p(additive = 2.7×10(-3, an association driven by the male gender (p(interaction = 0.02. The same allele associated with increased fasting serum insulin concentrations (β = 3%(1;5, p(additive = 2.5×10(-3 and increased insulin resistance (HOMA-IR (β = 4%(1;6, p(additive = 1.5×10(-3. The minor G-allele of rs10146997 in NRXN3 associated with increased WC among women (β = 0.55cm (0.20;0.89, p(additive = 1.7×10(-3, p(interaction = 1.0×10(-3, but showed no associations with obesity related metabolic traits. The MSRA rs545854 and TFAP2B rs987237 showed nominal associations with central obesity; however, no underlying metabolic phenotypes became obvious, when investigating quantitative metabolic traits. None of the variants influenced the prevalence of type 2 diabetes.We demonstrate that several of the central

Associations of fatty acids in cerebrospinal fluid with peripheral glucose concentrations and energy metabolism.

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Reiner Jumpertz

Full Text Available Rodent experiments have emphasized a role of central fatty acid (FA species, such as oleic acid, in regulating peripheral glucose and energy metabolism. Thus, we hypothesized that central FAs are related to peripheral glucose regulation and energy expenditure in humans. To test this we measured FA species profiles in cerebrospinal fluid (CSF and plasma of 32 individuals who stayed in our clinical inpatient unit for 6 days. Body composition was measured by dual energy X-ray absorptiometry and glucose regulation by an oral glucose test (OGTT followed by measurements of 24 hour (24EE and sleep energy expenditure (SLEEP as well as respiratory quotient (RQ in a respiratory chamber. CSF was obtained via lumbar punctures; FA concentrations were measured by liquid chromatography/mass spectrometry. As expected, FA concentrations were higher in plasma compared to CSF. Individuals with high concentrations of CSF very-long-chain saturated FAs had lower rates of SLEEP. In the plasma moderate associations of these FAs with higher 24EE were observed. Moreover, CSF monounsaturated long-chain FA (palmitoleic and oleic acid concentrations were associated with lower RQs and lower glucose area under the curve during the OGTT. Thus, FAs in the CSF strongly correlated with peripheral metabolic traits. These physiological parameters were most specific to long-chain monounsaturated (C16:1, C18:1 and very-long-chain saturated (C24:0, C26:0 FAs.Together with previous animal experiments these initial cross-sectional human data indicate that central FA species are linked to peripheral glucose and energy homeostasis.

Cellular energy metabolism in T-lymphocytes.

Science.gov (United States)

Gaber, Timo; Strehl, Cindy; Sawitzki, Birgit; Hoff, Paula; Buttgereit, Frank

2015-01-01

Energy homeostasis is a hallmark of cell survival and maintenance of cell function. Here we focus on the impact of cellular energy metabolism on T-lymphocyte differentiation, activation, and function in health and disease. We describe the role of transcriptional and posttranscriptional regulation of lymphocyte metabolism on immune functions of T cells. We also summarize the current knowledge about T-lymphocyte adaptations to inflammation and hypoxia, and the impact on T-cell behavior of pathophysiological hypoxia (as found in tumor tissue, chronically inflamed joints in rheumatoid arthritis and during bone regeneration). A better understanding of the underlying mechanisms that control immune cell metabolism and immune response may provide therapeutic opportunities to alter the immune response under conditions of either immunosuppression or inflammation, potentially targeting infections, vaccine response, tumor surveillance, autoimmunity, and inflammatory disorders.

Microglia energy metabolism in metabolic disorder.

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Kalsbeek, Martin J T; Mulder, Laurie; Yi, Chun-Xia

2016-12-15

Microglia are the resident macrophages of the CNS, and are in charge of maintaining a healthy microenvironment to ensure neuronal survival. Microglia carry out a non-stop patrol of the CNS, make contact with neurons and look for abnormalities, all of which requires a vast amount of energy. This non-signaling energy demand increases after activation by pathogens, neuronal damage or other kinds of stimulation. Of the three major energy substrates - glucose, fatty acids and glutamine - glucose is crucial for microglia survival and several glucose transporters are expressed to supply sufficient glucose influx. Fatty acids are another source of energy for microglia and have also been shown to strongly influence microglial immune activity. Glutamine, although possibly suitable for use as an energy substrate by microglia, has been shown to have neurotoxic effects when overloaded. Microglial fuel metabolism might be associated with microglial reactivity under different pathophysiological conditions and a microglial fuel switch may thus be the underlying cause of hypothalamic dysregulation, which is associated with obesity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A Cellular Perspective on Brain Energy Metabolism and Functional Imaging

KAUST Repository

Magistretti, Pierre J.

2015-05-01

The energy demands of the brain are high: they account for at least 20% of the body\\'s energy consumption. Evolutionary studies indicate that the emergence of higher cognitive functions in humans is associated with an increased glucose utilization and expression of energy metabolism genes. Functional brain imaging techniques such as fMRI and PET, which are widely used in human neuroscience studies, detect signals that monitor energy delivery and use in register with neuronal activity. Recent technological advances in metabolic studies with cellular resolution have afforded decisive insights into the understanding of the cellular and molecular bases of the coupling between neuronal activity and energy metabolism and pointat a key role of neuron-astrocyte metabolic interactions. This article reviews some of the most salient features emerging from recent studies and aims at providing an integration of brain energy metabolism across resolution scales. © 2015 Elsevier Inc.

Cerebral energy metabolism during induced mitochondrial dysfunction

DEFF Research Database (Denmark)

Nielsen, T H; Bindslev, TT; Pedersen, S M

2013-01-01

In patients with traumatic brain injury as well as stroke, impaired cerebral oxidative energy metabolism may be an important factor contributing to the ultimate degree of tissue damage. We hypothesize that mitochondrial dysfunction can be diagnosed bedside by comparing the simultaneous changes...... in brain tissue oxygen tension (PbtO(2)) and cerebral cytoplasmatic redox state. The study describes cerebral energy metabolism during mitochondrial dysfunction induced by sevoflurane in piglets....

Hypothalamic control of energy and glucose metabolism.

Science.gov (United States)

Sisley, Stephanie; Sandoval, Darleen

2011-09-01

The central nervous system (CNS), generally accepted to regulate energy homeostasis, has been implicated in the metabolic perturbations that either cause or are associated with obesity. Normally, the CNS receives hormonal, metabolic, and neuronal input to assure adequate energy levels and maintain stable energy homeostasis. Recent evidence also supports that the CNS uses these same inputs to regulate glucose homeostasis and this aspect of CNS regulation also becomes impaired in the face of dietary-induced obesity. This review focuses on the literature surrounding hypothalamic regulation of energy and glucose homeostasis and discusses how dysregulation of this system may contribute to obesity and T2DM.

Pareto optimality in organelle energy metabolism analysis.

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Angione, Claudio; Carapezza, Giovanni; Costanza, Jole; Lió, Pietro; Nicosia, Giuseppe

2013-01-01

In low and high eukaryotes, energy is collected or transformed in compartments, the organelles. The rich variety of size, characteristics, and density of the organelles makes it difficult to build a general picture. In this paper, we make use of the Pareto-front analysis to investigate the optimization of energy metabolism in mitochondria and chloroplasts. Using the Pareto optimality principle, we compare models of organelle metabolism on the basis of single- and multiobjective optimization, approximation techniques (the Bayesian Automatic Relevance Determination), robustness, and pathway sensitivity analysis. Finally, we report the first analysis of the metabolic model for the hydrogenosome of Trichomonas vaginalis, which is found in several protozoan parasites. Our analysis has shown the importance of the Pareto optimality for such comparison and for insights into the evolution of the metabolism from cytoplasmic to organelle bound, involving a model order reduction. We report that Pareto fronts represent an asymptotic analysis useful to describe the metabolism of an organism aimed at maximizing concurrently two or more metabolite concentrations.

FTO gene associated fatness in relation to body fat distribution and metabolic traits throughout a broad range of fatness

DEFF Research Database (Denmark)

Kring, Sofia I I; Holst, Claus; Zimmermann, Esther

2008-01-01

A common single nucleotide polymorphism (SNP) of FTO (rs9939609, T/A) is associated with total body fatness. We investigated the association of this SNP with abdominal and peripheral fatness and obesity-related metabolic traits in middle-aged men through a broad range of fatness present already...

Spatial variation in the relationship between performance and metabolic rate in wild juvenile Atlantic salmon

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Grethe Robertsen; John D. Armstrong; Keith H. Nislow; Ivar Herfindal; Simon McKelvey; Sigurd Einum; Martin. Genner

2014-01-01

Maintenance of metabolic rate (MR, the energy cost of self-maintenance) is linked to behavioural traits and fitness and varies substantially within populations. Despite having received much attention, the causes and consequences of this variation remain obscure. Theoretically, such within-population variation in fitness-related traits can be maintained by environmental...

Common Variants of Homocysteine Metabolism Pathway Genes and Risk of Type 2 Diabetes and Related Traits in Indians

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Ganesh Chauhan

2012-01-01

Full Text Available Hyperhomocysteinemia, a risk factor for cardiovascular disorder, obesity, and type 2 diabetes, is prevalent among Indians who are at high risk of these metabolic disorders. We evaluated association of common variants of genes involved in homocysteine metabolism or its levels with type 2 diabetes, obesity, and related traits in North Indians. We genotyped 90 variants in initial phase (2.115 subjects and replicated top signals in an independent sample set (2.085 subjects. The variant MTHFR-rs1801133 was the top signal for association with type 2 diabetes (OR=0.78 (95%  CI=0.67–0.92, P=0.003 and was also associated with 2 h postload plasma glucose (P=0.04, high-density lipoprotein cholesterol (P=0.004, and total cholesterol (P=0.01 in control subjects. These associations were neither replicated nor significant after meta-analysis. Studies involving a larger study population and different ethnic groups are required before ruling out the role of these important candidate genes in type 2 diabetes, obesity, and related traits.

Aspects of astrocyte energy metabolism, amino acid neurotransmitter homoeostasis and metabolic compartmentation

DEFF Research Database (Denmark)

Kreft, Marko; Bak, Lasse Kristoffer; Waagepetersen, Helle S

2012-01-01

Astrocytes are key players in brain function; they are intimately involved in neuronal signalling processes and their metabolism is tightly coupled to that of neurons. In the present review, we will be concerned with a discussion of aspects of astrocyte metabolism, including energy......-generating pathways and amino acid homoeostasis. A discussion of the impact that uptake of neurotransmitter glutamate may have on these pathways is included along with a section on metabolic compartmentation....

Weight Management, Energy Metabolism, and Endocrine Hor¬mones- Review Article

OpenAIRE

Seyed-Ali MOSTAFAVI; Saeed HOSSEINI

2015-01-01

Energy expenditure is determined by basal metabolic rate, physical activity, and Thermic Effect of Foods (TEF). Some endocrine hormones have role in basal metabolism and hence in human energy expenditure. And some foods pose more thermic effects on the total body energy expenditure and therefore can influence body weight. This review was performed to discuss factors which may affect body metabolism and body weight. Latest medical databases and nutrition and metabolism books were reviewed. We ...

Construction and analysis of the model of energy metabolism in E. coli.

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Zixiang Xu

Full Text Available Genome-scale models of metabolism have only been analyzed with the constraint-based modelling philosophy and there have been several genome-scale gene-protein-reaction models. But research on the modelling for energy metabolism of organisms just began in recent years and research on metabolic weighted complex network are rare in literature. We have made three research based on the complete model of E. coli's energy metabolism. We first constructed a metabolic weighted network using the rates of free energy consumption within metabolic reactions as the weights. We then analyzed some structural characters of the metabolic weighted network that we constructed. We found that the distribution of the weight values was uneven, that most of the weight values were zero while reactions with abstract large weight values were rare and that the relationship between w (weight values and v (flux values was not of linear correlation. At last, we have done some research on the equilibrium of free energy for the energy metabolism system of E. coli. We found that E(out (free energy rate input from the environment can meet the demand of E(ch(in (free energy rate dissipated by chemical process and that chemical process plays a great role in the dissipation of free energy in cells. By these research and to a certain extend, we can understand more about the energy metabolism of E. coli.

Measuring maximum and standard metabolic rates using intermittent-flow respirometry: a student laboratory investigation of aerobic metabolic scope and environmental hypoxia in aquatic breathers.

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Rosewarne, P J; Wilson, J M; Svendsen, J C

2016-01-01

Metabolic rate is one of the most widely measured physiological traits in animals and may be influenced by both endogenous (e.g. body mass) and exogenous factors (e.g. oxygen availability and temperature). Standard metabolic rate (SMR) and maximum metabolic rate (MMR) are two fundamental physiological variables providing the floor and ceiling in aerobic energy metabolism. The total amount of energy available between these two variables constitutes the aerobic metabolic scope (AMS). A laboratory exercise aimed at an undergraduate level physiology class, which details the appropriate data acquisition methods and calculations to measure oxygen consumption rates in rainbow trout Oncorhynchus mykiss, is presented here. Specifically, the teaching exercise employs intermittent flow respirometry to measure SMR and MMR, derives AMS from the measurements and demonstrates how AMS is affected by environmental oxygen. Students' results typically reveal a decline in AMS in response to environmental hypoxia. The same techniques can be applied to investigate the influence of other key factors on metabolic rate (e.g. temperature and body mass). Discussion of the results develops students' understanding of the mechanisms underlying these fundamental physiological traits and the influence of exogenous factors. More generally, the teaching exercise outlines essential laboratory concepts in addition to metabolic rate calculations, data acquisition and unit conversions that enhance competency in quantitative analysis and reasoning. Finally, the described procedures are generally applicable to other fish species or aquatic breathers such as crustaceans (e.g. crayfish) and provide an alternative to using higher (or more derived) animals to investigate questions related to metabolic physiology. © 2016 The Fisheries Society of the British Isles.

Phenotypic flexibility of traits related to energy acquisition in mice divergently selected for basal metabolic rate (BMR).

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Ksiazek, Aneta; Czerniecki, Jan; Konarzewski, Marek

2009-03-01

Theoretical considerations suggest that one of the main factors determining phenotypic flexibility of the digestive system is the size (mass) of internal organs. To test this, we used mice from two lines selected for high and low levels of basal metabolic rate (BMR). Mice with higher BMRs also have larger internal organs and higher daily food consumption (C) under non-stressful conditions. We exposed animals from both lines to a sudden cold exposure by transferring them (without prior acclimation) from an ambient temperature of 23 degrees C to 5 degrees C. Cold exposure elicited a twofold increase in C and a 25% reduction of apparent digestive efficiency. For the same body mass-corrected C, small intestine, kidneys, heart and liver of cold-exposed low-BMR mice were smaller than those of the high-BMR line. Therefore, the internal organs of low-BMR animals were burdened with substantially higher metabolic loads (defined as C or digestible food intake per total mass of a particular organ). The mass-specific activity of citrate synthase (CS) in the liver and kidneys (but not heart) was also lower in the low-BMR mice. The magnitude of phenotypic flexibility of internal organ size and CS activity was strictly proportional to the organ mass (in the case of kidneys and liver, also mass-specific CS activity) prior to an increased energy demand. Thus, phenotypic flexibility had additive rather than multiplicative dynamics. Our results also suggest that variation in BMR positively correlates with the magnitude of an immediate spare capacity that fuels the initial response of internal organs to a sudden metabolic stress.

Adipose tissue remodeling: its role in energy metabolism and metabolic disorders

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Sung Sik eChoe

2016-04-01

Full Text Available The adipose tissue is a central metabolic organ in the regulation of whole-body energy homeostasis. The white adipose tissue (WAT functions as a key energy reservoir for other organs, whereas the brown adipose tissue (BAT accumulates lipids for cold-induced adaptive thermogenesis. Adipose tissues secret various hormones, cytokines, and metabolites (termed as adipokines that control systemic energy balance by regulating appetitive signals from the central nerve system as well as metabolic activity in peripheral tissues. In response to changes in the nutritional status, the adipose tissue undergoes dynamic remodeling, including quantitative and qualitative alterations in adipose tissue resident cells. A growing body of evidence indicates that adipose tissue remodeling in obesity is closely associated with adipose tissue function. Changes in the number and size of the adipocytes affect the microenvironment of expanded fat tissues, accompanied by alterations in adipokine secretion, adipocyte death, local hypoxia, and fatty acid fluxes. Concurrently, stromal vascular cells in the adipose tissue, including immune cells, are involved in numerous adaptive processes, such as dead adipocyte clearance, adipogenesis, and angiogenesis, all of which are dysregulated in obese adipose tissue remodeling. Chronic over-nutrition triggers uncontrolled inflammatory responses, leading to systemic low-grade inflammation and metabolic disorders, such as insulin resistance. This review will discuss current mechanistic understandings of adipose tissue remodeling processes in adaptive energy homeostasis and pathological remodeling of adipose tissue in connection with immune response.

Association of erythrocyte deformability with red blood cell distribution width in metabolic diseases and thalassemia trait.

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Vayá, Amparo; Alis, Rafael; Suescún, Marta; Rivera, Leonor; Murado, Julian; Romagnoli, Marco; Solá, Eva; Hernandez-Mijares, Antonio

2015-01-01

Increased red blood distribution width (RDW) in anemia is related to disturbances in the cellular surface/volume ratio, usually accompanied by morphological alterations, while it has been shown in inflammatory diseases that the activity of pro-inflammatory cytokines disturbing erythropoiesis increases RDW. Recently it has been reported that higher RDW is related with decreased erythrocyte deformability, and that it could be related with the association of RDW and increased risk of cardiovascular diseases. In order to analyze the influence of morphological alterations and proinflammatory status on the relationship between RDW and erythrocyte deformability, we analyzed erythrocyte deformability along with RDW and other hematological and biochemical parameters in 36 α-thalassemia, 20 β-thalassemia, 20 δβ-thalassemia trait carriers, 61 metabolic syndrome patients and 76 morbidly obese patients. RDW correlated inversely with erythrocyte deformability in minor β-thalassemia (r =-0.530, p thalassemia is often accompanied by more marked cell-shaped perturbations than other thalassemia traits. This could be the reason for this negative association only in this setting. Higher anisocytosis seems to be associated with greater morphologic alterations (shape/volume), which reduce erythrocyte deformability. The proinflammatory profile in metabolic patients can be related to the positive association of RDW with erythrocyte deformability found in these patients. However, further research is needed to explain the mechanisms underlying this association.

Metabolic regulation of neuronal plasticity by the energy sensor AMPK.

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Wyatt B Potter

Full Text Available Long Term Potentiation (LTP is a leading candidate mechanism for learning and memory and is also thought to play a role in the progression of seizures to intractable epilepsy. Maintenance of LTP requires RNA transcription, protein translation and signaling through the mammalian Target of Rapamycin (mTOR pathway. In peripheral tissue, the energy sensor AMP-activated Protein Kinase (AMPK negatively regulates the mTOR cascade upon glycolytic inhibition and cellular energy stress. We recently demonstrated that the glycolytic inhibitor 2-deoxy-D-glucose (2DG alters plasticity to retard epileptogenesis in the kindling model of epilepsy. Reduced kindling progression was associated with increased recruitment of the nuclear metabolic sensor CtBP to NRSF at the BDNF promoter. Given that energy metabolism controls mTOR through AMPK in peripheral tissue and the role of mTOR in LTP in neurons, we asked whether energy metabolism and AMPK control LTP. Using a combination of biochemical approaches and field-recordings in mouse hippocampal slices, we show that the master regulator of energy homeostasis, AMPK couples energy metabolism to LTP expression. Administration of the glycolytic inhibitor 2-deoxy-D-glucose (2DG or the mitochondrial toxin and anti-Type II Diabetes drug, metformin, or AMP mimetic AICAR results in activation of AMPK, repression of the mTOR pathway and prevents maintenance of Late-Phase LTP (L-LTP. Inhibition of AMPK by either compound-C or the ATP mimetic ara-A rescues the suppression of L-LTP by energy stress. We also show that enhanced LTP via AMPK inhibition requires mTOR signaling. These results directly link energy metabolism to plasticity in the mammalian brain and demonstrate that AMPK is a modulator of LTP. Our work opens up the possibility of using modulators of energy metabolism to control neuronal plasticity in diseases and conditions of aberrant plasticity such as epilepsy.

How low can you go? An adaptive energetic framework for interpreting basal metabolic rate variation in endotherms.

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Swanson, David L; McKechnie, Andrew E; Vézina, François

2017-12-01

Adaptive explanations for both high and low body mass-independent basal metabolic rate (BMR) in endotherms are pervasive in evolutionary physiology, but arguments implying a direct adaptive benefit of high BMR are troublesome from an energetic standpoint. Here, we argue that conclusions about the adaptive benefit of BMR need to be interpreted, first and foremost, in terms of energetics, with particular attention to physiological traits on which natural selection is directly acting. We further argue from an energetic perspective that selection should always act to reduce BMR (i.e., maintenance costs) to the lowest level possible under prevailing environmental or ecological demands, so that high BMR per se is not directly adaptive. We emphasize the argument that high BMR arises as a correlated response to direct selection on other physiological traits associated with high ecological or environmental costs, such as daily energy expenditure (DEE) or capacities for activity or thermogenesis. High BMR thus represents elevated maintenance costs required to support energetically demanding lifestyles, including living in harsh environments. BMR is generally low under conditions of relaxed selection on energy demands for high metabolic capacities (e.g., thermoregulation, activity) or conditions promoting energy conservation. Under these conditions, we argue that selection can act directly to reduce BMR. We contend that, as a general rule, BMR should always be as low as environmental or ecological conditions permit, allowing energy to be allocated for other functions. Studies addressing relative reaction norms and response times to fluctuating environmental or ecological demands for BMR, DEE, and metabolic capacities and the fitness consequences of variation in BMR and other metabolic traits are needed to better delineate organismal metabolic responses to environmental or ecological selective forces.

Timing of potential and metabolic brain energy

DEFF Research Database (Denmark)

Korf, Jakob; Gramsbergen, Jan Bert

2007-01-01

functions. We introduce the concepts of potential and metabolic brain energy to distinguish trans-membrane gradients of ions or neurotransmitters and the capacity to generate energy from intra- or extra-cerebral substrates, respectively. Higher brain functions, such as memory retrieval, speaking......The temporal relationship between cerebral electro-physiological activities, higher brain functions and brain energy metabolism is reviewed. The duration of action potentials and transmission through glutamate and GABA are most often less than 5 ms. Subjects may perform complex psycho......-physiological tasks within 50 to 200 ms, and perception of conscious experience requires 0.5 to 2 s. Activation of cerebral oxygen consumption starts after at least 100 ms and increases of local blood flow become maximal after about 1 s. Current imaging technologies are unable to detect rapid physiological brain...

The metabolic burden of sleep loss.

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Schmid, Sebastian M; Hallschmid, Manfred; Schultes, Bernd

2015-01-01

In parallel with the increasing prevalence of obesity and type 2 diabetes, sleep loss has become common in modern societies. An increasing number of epidemiological studies show an association between short sleep duration, sleep disturbances, and circadian desynchronisation of sleep with adverse metabolic traits, in particular obesity and type 2 diabetes. Furthermore, experimental studies point to distinct mechanisms by which insufficient sleep adversely affects metabolic health. Changes in the activity of neuroendocrine systems seem to be major mediators of the detrimental metabolic effects of insufficient sleep, through favouring neurobehavioural outcomes such as increased appetite, enhanced sensitivity to food stimuli, and, ultimately, a surplus in energy intake. The effect of curtailed sleep on physical activity and energy expenditure is less clear, but changes are unlikely to outweigh increases in food intake. Although long-term interventional studies proving a cause and effect association are still scarce, sleep loss seems to be an appealing target for the prevention, and probably treatment, of metabolic disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

Individually variable energy management during egg production is repeatable across breeding attempts.

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Williams, Tony D; Vézina, François; Speakman, John R

2009-04-01

It is axiomatic that whole-animal metabolism, measured for example as daily energy expenditure (DEE), plays a central role in determining reproductive success and survival (fitness) in all organisms. Nevertheless, strong evidence for consistent systematic relationships between DEE and either individual traits (age, sex, body size), environmental factors (e.g. food availability, temperature) or 'fitness' traits (e.g. number of offspring, survival) remains far from compelling in birds and mammals. Recently, we suggested that female birds might utilise complex, individually variable energy management strategies to meet the metabolic demands of reproduction, generating a wide spectrum of effects on reproductive DEE, from overcompensation (net decrease in DEE) to additive effects (net increase in DEE). Here we show that this individually variable adjustment or 'plasticity' in energy expenditure associated with egg production is repeatable among individuals between successive breeding attempts in female zebra finches (Taeniopygia guttata). Our study highlights the importance (a) of measuring 'plasticity' or change associated with transitions of physiological state (e.g. non-breeding to breeding) based on multiple measurements of the same individual, and (b) of extending consideration of how selection might drive the evolution of phenotypic plasticity per se to include physiological and metabolic traits.

Energy metabolism in astrocytes and neurons treated with manganese: relation among cell-specific energy failure, glucose metabolism, and intercellular trafficking using multinuclear NMR-spectroscopic analysis.

Science.gov (United States)

Zwingmann, Claudia; Leibfritz, Dieter; Hazell, Alan S

2003-06-01

A central question in manganese neurotoxicity concerns mitochondrial dysfunction leading to cerebral energy failure. To obtain insight into the underlying mechanism(s), the authors investigated cell-specific pathways of [1-13C]glucose metabolism by high-resolution multinuclear NMR-spectroscopy. Five-day treatment of neurons with 100-micro mol/L MnCl(2) led to 50% and 70% decreases of ATP/ADP and phosphocreatine-creatine ratios, respectively. An impaired flux of [1-13C]glucose through pyruvate dehydrogenase, which was associated with Krebs cycle inhibition and hence depletion of [4-13C]glutamate, [2-13C]GABA, and [13C]glutathione, hindered the ability of neurons to compensate for mitochondrial dysfunction by oxidative glucose metabolism and further aggravated neuronal energy failure. Stimulated glycolysis and oxidative glucose metabolism protected astrocytes against energy failure and oxidative stress, leading to twofold increased de novo synthesis of [3-13C]lactate and fourfold elevated [4-13C]glutamate and [13C]glutathione levels. Manganese, however, inhibited the synthesis and release of glutamine. Comparative NMR data obtained from cocultures showed disturbed astrocytic function and a failure of astrocytes to provide neurons with substrates for energy and neurotransmitter metabolism, leading to deterioration of neuronal antioxidant capacity (decreased glutathione levels) and energy metabolism. The results suggest that, concomitant to impaired neuronal glucose oxidation, changes in astrocytic metabolism may cause a loss of intercellular homeostatic equilibrium, contributing to neuronal dysfunction in manganese neurotoxicity.

Tributyltin disrupts feeding and energy metabolism in the goldfish (Carassius auratus).

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Zhang, Jiliang; Sun, Ping; Yang, Fan; Kong, Tao; Zhang, Ruichen

2016-06-01

Tributyltin (TBT) can induce obesogen response. However, little is known about the adverse effects of TBT on food intake and energy metabolism. The present study was designed to investigate the effects of TBT, at environmental concentrations of 2.44 and 24.4 ng/L (1 and 10 ng/L as Sn), on feeding and energy metabolism in goldfish (Carassius auratus). After exposure for 54 d, TBT increased the weight gain and food intake in fish. The patterns of brain neuropeptide genes expression were in line with potential orexigenic effects, with increased expression of neuropeptide Y and apelin, and decreased expression of pro-opiomelanocortin, ghrelin, cocaine and amphetamine-regulated transcript, and corticotropin-releasing factor. Interestingly, the energy metabolism indicators (oxygen consumption, ammonia exertion and swimming activity) and the serum thyroid hormones were all significantly increased at the 2.44 ng/L TBT group in fish. However, no changes of energy metabolism indicators or a decrease of thyroid hormones was found at the 24.4 ng/L TBT group, which indicated a complex disrupting effect on metabolism of TBT. In short, TBT can alter feeding and energy metabolism in fish, which might promote the obesogenic responses. Copyright © 2016 Elsevier Ltd. All rights reserved.

Energy metabolism and nutritional status in hospitalized patients with lung cancer.

Science.gov (United States)

Takemura, Yumi; Sasaki, Masaya; Goto, Kenichi; Takaoka, Azusa; Ohi, Akiko; Kurihara, Mika; Nakanishi, Naoko; Nakano, Yasutaka; Hanaoka, Jun

2016-09-01

This study aimed to investigate the energy metabolism of patients with lung cancer and the relationship between energy metabolism and proinflammatory cytokines. Twenty-eight patients with lung cancer and 18 healthy controls were enrolled in this study. The nutritional status upon admission was analyzed using nutritional screening tools and laboratory tests. The resting energy expenditure and respiratory quotient were measured using indirect calorimetry, and the predicted resting energy expenditure was calculated using the Harris-Benedict equation. Energy expenditure was increased in patients with advanced stage disease, and there were positive correlations between measured resting energy expenditure/body weight and interleukin-6 levels and between measured resting energy expenditure/predicted resting energy expenditure and interleukin-6 levels. There were significant relationships between body mass index and plasma leptin or acylated ghrelin levels. However, the level of appetite controlling hormones did not affect dietary intake. There was a negative correlation between plasma interleukin-6 levels and dietary intake, suggesting that interleukin-6 plays a role in reducing dietary intake. These results indicate that energy expenditure changes significantly with lung cancer stage and that plasma interleukin-6 levels affect energy metabolism and dietary intake. Thus, nutritional management that considers the changes in energy metabolism is important in patients with lung cancer.

Validated Predictions of Metabolic Energy Consumption for Submaximal Effort Movement

OpenAIRE

Tsianos, George A.; MacFadden, Lisa N.

2016-01-01

Author Summary Muscles consume metabolic energy to generate movement. Performing a movement over a long period of time or at a high intensity strains the respiratory and cardiovascular systems that need to replenish the energy reserves in muscle. Furthermore, consuming and replenishing metabolic energy involves biochemical reactions with byproducts that cause muscle fatigue. These biochemical reactions also produce heat that increases body temperature, potentially causing central fatigue. A m...

Adaptive evolution of mitochondrial energy metabolism genes associated with increased energy demand in flying insects.

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Yang, Yunxia; Xu, Shixia; Xu, Junxiao; Guo, Yan; Yang, Guang

2014-01-01

Insects are unique among invertebrates for their ability to fly, which raises intriguing questions about how energy metabolism in insects evolved and changed along with flight. Although physiological studies indicated that energy consumption differs between flying and non-flying insects, the evolution of molecular energy metabolism mechanisms in insects remains largely unexplored. Considering that about 95% of adenosine triphosphate (ATP) is supplied by mitochondria via oxidative phosphorylation, we examined 13 mitochondrial protein-encoding genes to test whether adaptive evolution of energy metabolism-related genes occurred in insects. The analyses demonstrated that mitochondrial DNA protein-encoding genes are subject to positive selection from the last common ancestor of Pterygota, which evolved primitive flight ability. Positive selection was also found in insects with flight ability, whereas no significant sign of selection was found in flightless insects where the wings had degenerated. In addition, significant positive selection was also identified in the last common ancestor of Neoptera, which changed its flight mode from direct to indirect. Interestingly, detection of more positively selected genes in indirect flight rather than direct flight insects suggested a stronger selective pressure in insects having higher energy consumption. In conclusion, mitochondrial protein-encoding genes involved in energy metabolism were targets of adaptive evolution in response to increased energy demands that arose during the evolution of flight ability in insects.

Environmental effects on energy metabolism and 86Rb elimination rates of fishes

International Nuclear Information System (INIS)

Peters, E.L.

1994-01-01

Relationships between energy metabolism and the turnover rates of number of important chemical and radiological elements (particularly the Group IA alkali metals: K, Rb, and Cs) have been observed in fishes. Using response surface statistics and fractional factorial ANOVA, the author examined the relative influences of temperature, salinity, food intake rate, mass, and their first order interactions on routine energy metabolism and 86 Rb elimination rates. Routine metabolic rates were increased primarily by increased temperature and salinity, with a strong body mass effect and a significant effect of food intake. 86 Rb elimination rates were increased primarily by increased temperature and salinity. There were no interactive effects between mass and either temperature or salinity for either routine energy metabolism or 86 Rb elimination rates. There was a significant interaction effect between temperature and salinity on routine energy metabolism rates, but not on 86 Rb elimination. The authors also observed a relationship between routine energy metabolism and 86 Rb elimination rates that may possibly be exploited as a means of estimating energy metabolic rates of fishes in the field. The statistical techniques used in this experiment have broad potential applications in assessing the contributions of combinations of environmental variables on contaminant kinetics, as well as in multiple toxicity testing, in that they greatly simplify experimental designs compared with traditional full-factorial methods

Islet transplantation in diabetic rats normalizes basal and exercise-induced energy metabolism

NARCIS (Netherlands)

Houwing, Harmina; Benthem, L.; Suylichem, P.T.R. van; Leest, J. van der; Strubbe, J.H.; Steffens, A.B.

Transplantation of islets of Langerhans in diabetic rats normalizes resting glucose and insulin levels, but it remains unclear whether islet transplantation restores resting and exercise-induced energy metabolism. Therefore, we compared energy metabolism in islet transplanted rats with energy

Associations Between Adiposity and Metabolic Syndrome Over Time: The Healthy Twin Study.

Science.gov (United States)

Song, Yun-Mi; Sung, Joohon; Lee, Kayoung

2017-04-01

We evaluated the association between changes in adiposity traits including anthropometric and fat mass indicators and changes in metabolic syndrome traits including metabolic syndrome clustering and individual components over time. We also assessed the shared genetic and environmental correlations between the two traits. Participants were 284 South Korean twin individuals and 279 nontwin family members had complete data for changes in adiposity traits and metabolic syndrome traits of the Healthy Twin study. Mixed linear model and bivariate variance-component analysis were applied. Over a period of 3.1 ± 0.6 years of study, changes in adiposity traits [body mass index (BMI), waist circumference, total fat mass, and fat mass to lean mass ratio] had significant associations with changes in metabolic syndrome clustering [high blood pressure, high serum glucose, high triglycerides (TG), and low high-density lipoprotein cholesterol] after adjusting for intra-familial and sibling correlations, age, sex, baseline metabolic syndrome clustering, and socioeconomic factors and health behaviors at follow-up. Change in BMI associated significantly with changes in individual metabolic syndrome components compared to other adiposity traits. Change in metabolic syndrome component TG was a better predictor of changes in adiposity traits compared to changes in other metabolic components. These associations were explained by significant environmental correlations but not by genetic correlations. Changes in anthropometric and fat mass indicators were positively associated with changes in metabolic syndrome clustering and those associations appeared to be regulated by environmental influences.

Immune-Challenged Fish Up-Regulate Their Metabolic Scope to Support Locomotion.

Directory of Open Access Journals (Sweden)

Camille Bonneaud

Full Text Available Energy-based trade-offs occur when investment in one fitness-related trait diverts energy away from other traits. The extent to which such trade-offs are shaped by limits on the rate of conversion of energy ingested in food (e.g. carbohydrates into chemical energy (ATP by oxidative metabolism rather than by the amount of food ingested in the first place is, however, unclear. Here we tested whether the ATP required for mounting an immune response will lead to a trade-off with ATP available for physical activity in mosquitofish (Gambusia holbrooki. To this end, we challenged fish either with lipopolysaccharide (LPS from E. coli or with Sheep Red Blood Cells (SRBC, and measured oxygen consumption at rest and during swimming at maximum speed 24h, 48h and 7 days post-challenge in order to estimate metabolic rates. Relative to saline-injected controls, only LPS-injected fish showed a significantly greater resting metabolic rate two days post-challenge and significantly higher maximal metabolic rates two and seven days post-challenge. This resulted in a significantly greater metabolic scope two days post-challenge, with LPS-fish transiently overcompensating by increasing maximal ATP production more than would be required for swimming in the absence of an immune challenge. LPS-challenged fish therefore increased their production of ATP to compensate physiologically for the energetic requirements of immune functioning. This response would avoid ATP shortages and allow fish to engage in an aerobically-challenging activity (swimming even when simultaneously mounting an immune response. Nevertheless, relative to controls, both LPS- and SRBC-fish displayed reduced body mass gain one week post-injection, and LPS-fish actually lost mass. The concomitant increase in metabolic scope and reduced body mass gain of LPS-challenged fish indicates that immune-associated trade-offs are not likely to be shaped by limited oxidative metabolic capacities, but may instead

Hypothalamic carnitine metabolism integrates nutrient and hormonal feedback to regulate energy homeostasis.

Science.gov (United States)

Stark, Romana; Reichenbach, Alex; Andrews, Zane B

2015-12-15

The maintenance of energy homeostasis requires the hypothalamic integration of nutrient feedback cues, such as glucose, fatty acids, amino acids, and metabolic hormones such as insulin, leptin and ghrelin. Although hypothalamic neurons are critical to maintain energy homeostasis research efforts have focused on feedback mechanisms in isolation, such as glucose alone, fatty acids alone or single hormones. However this seems rather too simplistic considering the range of nutrient and endocrine changes associated with different metabolic states, such as starvation (negative energy balance) or diet-induced obesity (positive energy balance). In order to understand how neurons integrate multiple nutrient or hormonal signals, we need to identify and examine potential intracellular convergence points or common molecular targets that have the ability to sense glucose, fatty acids, amino acids and hormones. In this review, we focus on the role of carnitine metabolism in neurons regulating energy homeostasis. Hypothalamic carnitine metabolism represents a novel means for neurons to facilitate and control both nutrient and hormonal feedback. In terms of nutrient regulation, carnitine metabolism regulates hypothalamic fatty acid sensing through the actions of CPT1 and has an underappreciated role in glucose sensing since carnitine metabolism also buffers mitochondrial matrix levels of acetyl-CoA, an allosteric inhibitor of pyruvate dehydrogenase and hence glucose metabolism. Studies also show that hypothalamic CPT1 activity also controls hormonal feedback. We hypothesis that hypothalamic carnitine metabolism represents a key molecular target that can concurrently integrate nutrient and hormonal information, which is critical to maintain energy homeostasis. We also suggest this is relevant to broader neuroendocrine research as it predicts that hormonal signaling in the brain varies depending on current nutrient status. Indeed, the metabolic action of ghrelin, leptin or insulin

Adipose energy stores, physical work, and the metabolic syndrome: lessons from hummingbirds

OpenAIRE

Hargrove, James L

2005-01-01

Abstract Hummingbirds and other nectar-feeding, migratory birds possess unusual adaptive traits that offer important lessons concerning obesity, diabetes and the metabolic syndrome. Hummingbirds consume a high sugar diet and have fasting glucose levels that would be severely hyperglycemic in humans, yet these nectar-fed birds recover most glucose that is filtered into the urine. Hummingbirds accumulate over 40% body fat shortly before migrations in the spring and autumn. Despite hyperglycemia...

Fatty acids in energy metabolism of the central nervous system.

Science.gov (United States)

Panov, Alexander; Orynbayeva, Zulfiya; Vavilin, Valentin; Lyakhovich, Vyacheslav

2014-01-01

In this review, we analyze the current hypotheses regarding energy metabolism in the neurons and astroglia. Recently, it was shown that up to 20% of the total brain's energy is provided by mitochondrial oxidation of fatty acids. However, the existing hypotheses consider glucose, or its derivative lactate, as the only main energy substrate for the brain. Astroglia metabolically supports the neurons by providing lactate as a substrate for neuronal mitochondria. In addition, a significant amount of neuromediators, glutamate and GABA, is transported into neurons and also serves as substrates for mitochondria. Thus, neuronal mitochondria may simultaneously oxidize several substrates. Astrocytes have to replenish the pool of neuromediators by synthesis de novo, which requires large amounts of energy. In this review, we made an attempt to reconcile β-oxidation of fatty acids by astrocytic mitochondria with the existing hypothesis on regulation of aerobic glycolysis. We suggest that, under condition of neuronal excitation, both metabolic pathways may exist simultaneously. We provide experimental evidence that isolated neuronal mitochondria may oxidize palmitoyl carnitine in the presence of other mitochondrial substrates. We also suggest that variations in the brain mitochondrial metabolic phenotype may be associated with different mtDNA haplogroups.

Lactate rescues neuronal sodium homeostasis during impaired energy metabolism

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Karus, Claudia; Ziemens, Daniel; Rose, Christine R

2015-01-01

Recently, we established that recurrent activity evokes network sodium oscillations in neurons and astrocytes in hippocampal tissue slices. Interestingly, metabolic integrity of astrocytes was essential for the neurons' capacity to maintain low sodium and to recover from sodium loads, indicating an intimate metabolic coupling between the 2 cell types. Here, we studied if lactate can support neuronal sodium homeostasis during impaired energy metabolism by analyzing whether glucose removal, pha...

Ontogeny of hepatic energy metabolism genes in mice as revealed by RNA-sequencing.

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Helen J Renaud

Full Text Available The liver plays a central role in metabolic homeostasis by coordinating synthesis, storage, breakdown, and redistribution of nutrients. Hepatic energy metabolism is dynamically regulated throughout different life stages due to different demands for energy during growth and development. However, changes in gene expression patterns throughout ontogeny for factors important in hepatic energy metabolism are not well understood. We performed detailed transcript analysis of energy metabolism genes during various stages of liver development in mice. Livers from male C57BL/6J mice were collected at twelve ages, including perinatal and postnatal time points (n = 3/age. The mRNA was quantified by RNA-Sequencing, with transcript abundance estimated by Cufflinks. One thousand sixty energy metabolism genes were examined; 794 were above detection, of which 627 were significantly changed during at least one developmental age compared to adult liver. Two-way hierarchical clustering revealed three major clusters dependent on age: GD17.5-Day 5 (perinatal-enriched, Day 10-Day 20 (pre-weaning-enriched, and Day 25-Day 60 (adolescence/adulthood-enriched. Clustering analysis of cumulative mRNA expression values for individual pathways of energy metabolism revealed three patterns of enrichment: glycolysis, ketogenesis, and glycogenesis were all perinatally-enriched; glycogenolysis was the only pathway enriched during pre-weaning ages; whereas lipid droplet metabolism, cholesterol and bile acid metabolism, gluconeogenesis, and lipid metabolism were all enriched in adolescence/adulthood. This study reveals novel findings such as the divergent expression of the fatty acid β-oxidation enzymes Acyl-CoA oxidase 1 and Carnitine palmitoyltransferase 1a, indicating a switch from mitochondrial to peroxisomal β-oxidation after weaning; as well as the dynamic ontogeny of genes implicated in obesity such as Stearoyl-CoA desaturase 1 and Elongation of very long chain fatty

Utilization of dietary glucose in the metabolic syndrome

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Alemany Marià

2011-10-01

Full Text Available Abstract This review is focused on the fate of dietary glucose under conditions of chronically high energy (largely fat intake, evolving into the metabolic syndrome. We are adapted to carbohydrate-rich diets similar to those of our ancestors. Glucose is the main energy staple, but fats are our main energy reserves. Starvation drastically reduces glucose availability, forcing the body to shift to fatty acids as main energy substrate, sparing glucose and amino acids. We are not prepared for excess dietary energy, our main defenses being decreased food intake and increased energy expenditure, largely enhanced metabolic activity and thermogenesis. High lipid availability is a powerful factor decreasing glucose and amino acid oxidation. Present-day diets are often hyperenergetic, high on lipids, with abundant protein and limited amounts of starchy carbohydrates. Dietary lipids favor their metabolic processing, saving glucose, which additionally spares amino acids. The glucose excess elicits hyperinsulinemia, which may derive, in the end, into insulin resistance. The available systems of energy disposal could not cope with the excess of substrates, since they are geared for saving not for spendthrift, which results in an unbearable overload of the storage mechanisms. Adipose tissue is the last energy sink, it has to store the energy that cannot be used otherwise. However, adipose tissue growth also has limits, and the excess of energy induces inflammation, helped by the ineffective intervention of the immune system. However, even under this acute situation, the excess of glucose remains, favoring its final conversion to fat. The sum of inflammatory signals and deranged substrate handling induce most of the metabolic syndrome traits: insulin resistance, obesity, diabetes, liver steatosis, hyperlipidemia and their compounded combined effects. Thus, a maintained excess of energy in the diet may result in difficulties in the disposal of glucose, eliciting

Thermodynamics of the living organisms. Allometric relationship between the total metabolic energy, chemical energy and body temperature in mammals

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Atanasov, Atanas Todorov

2017-11-01

The study present relationship between the total metabolic energy (ETME(c), J) derived as a function of body chemical energy (Gchem, J) and absolute temperature (Tb, K) in mammals: ETME(c) =Gchem (Tb/Tn). In formula the temperature Tn =2.73K appears normalization temperature. The calculated total metabolic energy ETME(c) differs negligible from the total metabolic energy ETME(J), received as a product between the basal metabolic rate (Pm, J/s) and the lifespan (Tls, s) of mammals: ETME = Pm×Tls. The physical nature and biological mean of the normalization temperature (Tn, K) is unclear. It is made the hypothesis that the kTn energy (where k= 1.3806×10-23 J/K -Boltzmann constant) presents energy of excitation states (modes) in biomolecules and body structures that could be in equilibrium with chemical energy accumulated in body. This means that the accumulated chemical energy allows trough all body molecules and structures to propagate excitations states with kTn energy with wavelength in the rage of width of biological membranes. The accumulated in biomolecules chemical energy maintains spread of the excited states through biomolecules without loss of energy.

Brain Ceramide Metabolism in the Control of Energy Balance

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Céline Cruciani-Guglielmacci

2017-10-01

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

Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: A multi-ethnic meta-analysis of 45,891 individuals

NARCIS (Netherlands)

Z. Dastani (Zari); M.-F. Hivert (Marie-France); N.J. Timpson (Nicholas); J.R.B. Perry (John); X. Yuan (Xin); R.A. Scott (Robert); P. Hennemann (Peter); I.M. Heid (Iris); J.R. Kizer (Jorge); L.-P. Lyytikäinen (Leo-Pekka); C. Fuchsberger (Christian); T. Tanaka (Toshiko); A.P. Morris (Andrew); K.S. Small (Kerrin); A.J. Isaacs (Aaron); M. Beekman (Marian); S. Coassin (Stefan); K. Lohman (Kurt); L. Qi (Lu); S. Kanoni (Stavroula); J.S. Pankow (James); H.-W. Uh (Hae-Won); Y. Wu (Ying); A. Bidulescu (Aurelian); L.J. Rasmussen-Torvik (Laura); C.M.T. Greenwood (Celia); M. Ladouceur (Martin); J.L. Grimsby (Jonna); A.K. Manning (Alisa); C.-T. Liu (Ching-Ti); J.S. Kooner (Jaspal); V. Mooser (Vincent); P. Vollenweider (Peter); K. Kapur (Karen); J. Chambers (John); N.J. Wareham (Nick); C. Langenberg (Claudia); R.R. Frants (Rune); J.A.P. Willems van Dijk (Ko); B.A. Oostra (Ben); S.M. Willems (Sara); C. Lamina (Claudia); T.W. Winkler (Thomas); B.M. Psaty (Bruce); R.P. Tracy (Russell); J. Brody (Jennifer); I. Chen (Ida); J. Viikari (Jorma); M. Kähönen (Mika); P.P. Pramstaller (Peter Paul); D.M. Evans (David); B. St Pourcain (Beate); N. Sattar (Naveed); A.R. Wood (Andrew); S. Bandinelli (Stefania); O.D. Carlson (Olga); J.M. Egan (Josephine); S. Böhringer (Stefan); D. van Heemst (Diana); L. Kedenko (Lyudmyla); K. Kristiansson (Kati); M.-L. Nuotio (Marja-Liisa); B.-M. Loo (Britt-Marie); T.B. Harris (Tamara); M. Garcia (Melissa); A. Kanaya (Alka); M. Haun (Margot); N. Klopp (Norman); H.E. Wichmann (Erich); P. Deloukas (Panagiotis); E. Katsareli (Efi); D.J. Couper (David); B.B. Duncan (Bruce); M. Kloppenburg (Margreet); L.S. Adair (Linda); J.B. Borja (Judith); J.G. Wilson (James); S. Musani (Solomon); X. Guo (Xiuqing); T. Johnson (Toby); R.K. Semple (Robert); T.M. Teslovich (Tanya); M.A. Allison (Matthew); S. Redline (Susan); S.G. Buxbaum (Sarah); K.L. Mohlke (Karen); I. Meulenbelt (Ingrid); C. Ballantyne (Christie); G.V. Dedoussis (George); F.B. Hu (Frank B.); Y. Liu (YongMei); B. Paulweber (Bernhard); T.D. Spector (Timothy); P.E. Slagboom (Eline); L. Ferrucci (Luigi); A. Jula (Antti); M. Perola (Markus); O.T. Raitakari (Olli T.); J.C. Florez (Jose); V. Salomaa (Veikko); J.G. Eriksson (Johan); T.M. Frayling (Timothy); A.A. Hicks (Andrew); T. Lehtimäki (Terho); G.D. Smith (George Davey); D.S. Siscovick (David); F. Kronenberg (Florian); C.M. van Duijn (Cornelia); R.J.F. Loos (Ruth); D.M. Waterworth (Dawn); J.B. Meigs (James); J. Dupuis (Josée); J.B. Richards (Brent)

2012-01-01

textabstractCirculating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of

Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals

NARCIS (Netherlands)

Dastani, Z.; Hivert, M.F.; Timpson, N.J.; Perry, J.R.; Yuan, X.; Scott, R.A.; Henneman, P.; Heid, I.M.; Kizer, J.R.; Lyytikäinen, L.P.; Fuchsberger, C.; Tanaka, T.; Morris, A.P.; Small, K.; Isaacs, A.; Beekman, M.; Coassin, S.; Lohman, K.; Qi, L.; Kanoni, S.; Pankow, J.S.; Uh, H.W.; Wu, Y.; Bidulescu, A.; Rasmussen-Torvik, L.J.; Greenwood, C.M.; Ladouceur, M.; Grimsby, J.; Manning, A.K.; Liu, C.T.; Kooner, J.; Mooser, V.E.; Vollenweider, P.; Kapur, K.A.; Chambers, J.; Wareham, N.J.; Langenberg, C.; Frants, R.; Willems van Dijk, K.; Oostra, B.A.; Willems, S.M.; Lamina, C.; Winkler, T.W.; Psaty, B.M.; Tracy, R.P.; Brody, J.; Chen, I.; Viikari, J.; Kähönen, M.; Pramstaller, P.P.; Evans, D.M.; St Pourcain, B.; Sattar, N.; Wood, A.R.; Bandinelli, S.; Carlson, O.D.; Egan, J.M.; Böhringer, S.; van Heemst, D.; Kedenko, L.; Kristiansson, K.; Nuotio, M.L.; Loo, B.M.; Harris, T.; Garcia, M.; Kanaya, A.; Haun, M.; Klopp, N.; Wichmann, H.E.; Deloukas, P.; Katsareli, E.; Couper, D.J.; Duncan, B.B.; Kloppenburg, M.; Adair, L.S.; Borja, J.B.; Hottenga, J.J.; de Geus, E.J.C.; Willemsen, G.; Boomsma, D.I.; Wilson, J.G.; Musani, G.; Guo, X.; Johnson, T.; Semple, R.; Teslovich, T.M.; Allison, M.A.; Redline, S.; Buxbaum, S.G.; Mohlke, K.L.; Meulenbelt, I.; Ballantyne, C.M.; Dedoussis, G.V.; Hu, F.B.; Liu, Y.; Paulweber, B.; Spector, T.D.; Slagboom, P.E.; Ferrucci, L.; Jula, A.; Perola, M.; Raitakari, O.; Florez, J.C.; Salomaa, V.; Eriksson, J.G.; Frayling, T.M.; Hicks, A.A.; Lehtimäki, T.; Smith, G.D.; Siscovick, D.S.; Kronenberg, F.; van Duijn, C.M.; Loos, R.J.; Waterworth, D.; Meigs, J.B.; Dupuis, J.; Richards, J.B.; Posthuma, D.; Penninx, B.W.J.H.; Vogelzangs, N.; Kathiresan, S.

2012-01-01

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European

Anaerobic energy metabolism in unicellular photosynthetic eukaryotes.

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Atteia, Ariane; van Lis, Robert; Tielens, Aloysius G M; Martin, William F

2013-02-01

Anaerobic metabolic pathways allow unicellular organisms to tolerate or colonize anoxic environments. Over the past ten years, genome sequencing projects have brought a new light on the extent of anaerobic metabolism in eukaryotes. A surprising development has been that free-living unicellular algae capable of photoautotrophic lifestyle are, in terms of their enzymatic repertoire, among the best equipped eukaryotes known when it comes to anaerobic energy metabolism. Some of these algae are marine organisms, common in the oceans, others are more typically soil inhabitants. All these species are important from the ecological (O(2)/CO(2) budget), biotechnological, and evolutionary perspectives. In the unicellular algae surveyed here, mixed-acid type fermentations are widespread while anaerobic respiration, which is more typical of eukaryotic heterotrophs, appears to be rare. The presence of a core anaerobic metabolism among the algae provides insights into its evolutionary origin, which traces to the eukaryote common ancestor. The predicted fermentative enzymes often exhibit an amino acid extension at the N-terminus, suggesting that these proteins might be compartmentalized in the cell, likely in the chloroplast or the mitochondrion. The green algae Chlamydomonas reinhardtii and Chlorella NC64 have the most extended set of fermentative enzymes reported so far. Among the eukaryotes with secondary plastids, the diatom Thalassiosira pseudonana has the most pronounced anaerobic capabilities as yet. From the standpoints of genomic, transcriptomic, and biochemical studies, anaerobic energy metabolism in C. reinhardtii remains the best characterized among photosynthetic protists. This article is part of a Special Issue entitled: The evolutionary aspects of bioenergetic systems. Copyright © 2012 Elsevier B.V. All rights reserved.

Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.

OpenAIRE

Dastani, Z.; Hivert, M. F.; Timpson, N.; Perry, J. R.; Yuan, X.; Scott, R. A.; Henneman, P.; Heid, I. M.; Kizer, J. R.; Lyytikäinen, L. P.; Fuchsberger, C.; Tanaka, T.; Morris, A. P.; Small, K.; Isaacs, A.

2012-01-01

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a...

Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.

OpenAIRE

Dastani, Zari; Hivert, Marie-France; Timpson, Nicholas; Perry, John Richard; Yuan, Xin; Scott, Robert; Henneman, Peter; Heid, Iris M; Kizer, Jorge R; Lyytikäinen, Leo-Pekka; Fuchsberger, Christian; Tanaka, Toshiko; Morris, Andrew P; Small, Kerrin; Isaacs, Aaron

2012-01-01

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = \\(4.5×10^{−8}–1.2×10^{−43}\\)). U...

A Genome-Wide mQTL Analysis in Human Adipose Tissue Identifies Genetic Variants Associated with DNA Methylation, Gene Expression and Metabolic Traits.

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Petr Volkov

Full Text Available Little is known about the extent to which interactions between genetics and epigenetics may affect the risk of complex metabolic diseases and/or their intermediary phenotypes. We performed a genome-wide DNA methylation quantitative trait locus (mQTL analysis in human adipose tissue of 119 men, where 592,794 single nucleotide polymorphisms (SNPs were related to DNA methylation of 477,891 CpG sites, covering 99% of RefSeq genes. SNPs in significant mQTLs were further related to gene expression in adipose tissue and obesity related traits. We found 101,911 SNP-CpG pairs (mQTLs in cis and 5,342 SNP-CpG pairs in trans showing significant associations between genotype and DNA methylation in adipose tissue after correction for multiple testing, where cis is defined as distance less than 500 kb between a SNP and CpG site. These mQTLs include reported obesity, lipid and type 2 diabetes loci, e.g. ADCY3/POMC, APOA5, CETP, FADS2, GCKR, SORT1 and LEPR. Significant mQTLs were overrepresented in intergenic regions meanwhile underrepresented in promoter regions and CpG islands. We further identified 635 SNPs in significant cis-mQTLs associated with expression of 86 genes in adipose tissue including CHRNA5, G6PC2, GPX7, RPL27A, THNSL2 and ZFP57. SNPs in significant mQTLs were also associated with body mass index (BMI, lipid traits and glucose and insulin levels in our study cohort and public available consortia data. Importantly, the Causal Inference Test (CIT demonstrates how genetic variants mediate their effects on metabolic traits (e.g. BMI, cholesterol, high-density lipoprotein (HDL, hemoglobin A1c (HbA1c and homeostatic model assessment of insulin resistance (HOMA-IR via altered DNA methylation in human adipose tissue. This study identifies genome-wide interactions between genetic and epigenetic variation in both cis and trans positions influencing gene expression in adipose tissue and in vivo (dysmetabolic traits associated with the development of

Emerging role of the brain in the homeostatic regulation of energy and glucose metabolism.

Science.gov (United States)

Roh, Eun; Song, Do Kyeong; Kim, Min-Seon

2016-03-11

Accumulated evidence from genetic animal models suggests that the brain, particularly the hypothalamus, has a key role in the homeostatic regulation of energy and glucose metabolism. The brain integrates multiple metabolic inputs from the periphery through nutrients, gut-derived satiety signals and adiposity-related hormones. The brain modulates various aspects of metabolism, such as food intake, energy expenditure, insulin secretion, hepatic glucose production and glucose/fatty acid metabolism in adipose tissue and skeletal muscle. Highly coordinated interactions between the brain and peripheral metabolic organs are critical for the maintenance of energy and glucose homeostasis. Defective crosstalk between the brain and peripheral organs contributes to the development of obesity and type 2 diabetes. Here we comprehensively review the above topics, discussing the main findings related to the role of the brain in the homeostatic regulation of energy and glucose metabolism.

Ammonia-induced energy disorders interfere with bilirubin metabolism in hepatocytes.

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Wang, Qiongye; Wang, Yanfang; Yu, Zujiang; Li, Duolu; Jia, Bin; Li, Jingjing; Guan, Kelei; Zhou, Yubing; Chen, Yanling; Kan, Quancheng

2014-08-01

Hyperammonemia and jaundice are the most common clinical symptoms of hepatic failure. Decreasing the level of ammonia in the blood is often accompanied by a reduction in bilirubin in patients with hepatic failure. Previous studies have shown that hyperammonemia can cause bilirubin metabolism disorders, however it is unclear exactly how hyperammonemia interferes with bilirubin metabolism in hepatocytes. The purpose of the current study was to determine the mechanism or mechanisms by which hyperammonemia interferes with bilirubin metabolism in hepatocytes. Cell viability and apoptosis were analyzed in primary hepatocytes that had been exposed to ammonium chloride. Mitochondrial morphology and permeability were observed and analyzed, intermediates of the tricarboxylic acid (TCA) cycle were determined and changes in the expression of enzymes related to bilirubin metabolism were analyzed after ammonia exposure. Hyperammonemia inhibited cell growth, induced apoptosis, damaged the mitochondria and hindered the TCA cycle in hepatocytes. This led to a reduction in energy synthesis, eventually affecting the expression of enzymes related to bilirubin metabolism, which then caused further problems with bilirubin metabolism. These effects were significant, but could be reversed with the addition of adenosine triphosphate (ATP). This study demonstrates that ammonia can cause problems with bilirubin metabolism by interfering with energy synthesis. Copyright © 2014 Elsevier Inc. All rights reserved.

Personality traits and childhood trauma as correlates of metabolic risk factors: the Netherlands Study of Depression and Anxiety (NESDA).

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van Reedt Dortland, Arianne K B; Giltay, Erik J; van Veen, Tineke; Zitman, Frans G; Penninx, Brenda W J H

2012-01-10

Personality and childhood trauma may affect cardiovascular disease (CVD) risk. However, evidence for an association with metabolic risk factors for CVD is limited and ambiguous. Moreover, despite their interrelatedness, personality and childhood trauma were not yet studied simultaneously. Therefore, we aimed to explore whether personality and childhood trauma are correlates of metabolic risk factors. Among 2755 participants of the Netherlands Study of Depression and Anxiety (NESDA), we investigated through linear regression models whether Big Five personality traits (i.e., extraversion, openness, agreeableness, neuroticism and conscientiousness) and childhood trauma type (i.e., emotional neglect, and psychological, physical and sexual abuse) were correlates of metabolic risk factors (i.e., lipids, waist circumference (WC), glucose and blood pressure). Basic covariates (i.e., age, sex and income level), lifestyle, severity of depressive symptoms and years of education were taken into account. Openness was the most robust favorable correlate, and sexual abuse was the most robust unfavorable correlate of lipids and WC, and of overall metabolic risk (β=-.070; pchildhood sexual abuse are at higher risk of dyslipidemia and abdominal obesity. Copyright © 2011 Elsevier Inc. All rights reserved.

Effect of hemoglobin and immunization status on energy metabolism of weanling pigs.

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Gentry, J L; Swinkels, J W; Lindemann, M D; Schrama, J W

1997-04-01

We investigated the effect of (Hb) and immunization status on energy metabolism of newly weaned pigs. An additional focus of the study was to determine the development of circadian rhythms as evidenced by heat production patterns. Twenty-four 4-wk-old crossbred weanling barrows were placed into groups of three based on weight and litter origin, and the groups were allotted to one of four treatments. Treatments were arranged as a 2 x 2 factorial. The factors included 1) Hb status (low vs high) and 2) immunization status (antigen vs placebo). Hemoglobin status was obtained by injecting 3-d-old barrows with 100 (low) or 200 mg (high) of Fe. At 4 wk, initial blood Hb concentrations were 6.0 mM for the low group and 7.8 mM for the high group. Energy metabolism was measured using two weekly total energy and nitrogen balance collections. Energy intake and retention were higher (P Energy metabolism was not affected (P > .10) by immunization status, and heat production was not affected (P > .10) by either Hb or immunization status. Total heat production (HTOT) increased (P light period compared with the dark period over the total experimental period but a decrease (P dark period was approximately half of that measured during the light period. In conclusion, Hb status affected energy metabolism; pigs having a high Hb status had a higher energy retention. Immunization status had minimal effects on energy metabolism and heat production. Additionally, the diurnal circadian rhythm seen in older pigs had not been established by 2 wk after weaning.

Mechanistic modeling of aberrant energy metabolism in human disease

Directory of Open Access Journals (Sweden)

Vineet eSangar

2012-10-01

Full Text Available Dysfunction in energy metabolism—including in pathways localized to the mitochondria—has been implicated in the pathogenesis of a wide array of disorders, ranging from cancer to neurodegenerative diseases to type II diabetes. The inherent complexities of energy and mitochondrial metabolism present a significant obstacle in the effort to understand the role that these molecular processes play in the development of disease. To help unravel these complexities, systems biology methods have been applied to develop an array of computational metabolic models, ranging from mitochondria-specific processes to genome-scale cellular networks. These constraint-based models can efficiently simulate aspects of normal and aberrant metabolism in various genetic and environmental conditions. Development of these models leverages—and also provides a powerful means to integrate and interpret—information from a wide range of sources including genomics, proteomics, metabolomics, and enzyme kinetics. Here, we review a variety of mechanistic modeling studies that explore metabolic functions, deficiency disorders, and aberrant biochemical pathways in mitochondria and related regions in the cell.

Energy requirements, protein-energy metabolism and balance, and carbohydrates in preterm infants.

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Hay, William W; Brown, Laura D; Denne, Scott C

2014-01-01

Energy is necessary for all vital functions of the body at molecular, cellular, organ, and systemic levels. Preterm infants have minimum energy requirements for basal metabolism and growth, but also have requirements for unique physiology and metabolism that influence energy expenditure. These include body size, postnatal age, physical activity, dietary intake, environmental temperatures, energy losses in the stool and urine, and clinical conditions and diseases, as well as changes in body composition. Both energy and protein are necessary to produce normal rates of growth. Carbohydrates (primarily glucose) are principle sources of energy for the brain and heart until lipid oxidation develops over several days to weeks after birth. A higher protein/energy ratio is necessary in most preterm infants to approximate normal intrauterine growth rates. Lean tissue is predominantly produced during early gestation, which continues through to term. During later gestation, fat accretion in adipose tissue adds increasingly large caloric requirements to the lean tissue growth. Once protein intake is sufficient to promote net lean body accretion, additional energy primarily produces more body fat, which increases almost linearly at energy intakes >80-90 kcal/kg/day in normal, healthy preterm infants. Rapid gains in adiposity have the potential to produce later life obesity, an increasingly recognized risk of excessive energy intake. In addition to fundamental requirements for glucose, protein, and fat, a variety of non-glucose carbohydrates found in human milk may have important roles in promoting growth and development, as well as production of a gut microbiome that could protect against necrotizing enterocolitis. © 2014 S. Karger AG, Basel.

Adaptations of energy metabolism during cerebellar neurogenesis are co-opted in medulloblastoma.

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Tech, Katherine; Deshmukh, Mohanish; Gershon, Timothy R

2015-01-28

Recent studies show that metabolic patterns typical of cancer cells, including aerobic glycolysis and increased lipogenesis, are not unique to malignancy, but rather originate in physiologic development. In the postnatal brain, where sufficient oxygen for energy metabolism is scrupulously maintained, neural progenitors nevertheless metabolize glucose to lactate and prioritize lipid synthesis over fatty acid oxidation. Medulloblastoma, a cancer of neural progenitors that is the most common malignant brain tumor in children, recapitulates the metabolic phenotype of brain progenitor cells. During the physiologic proliferation of neural progenitors, metabolic enzymes generally associated with malignancy, including Hexokinase 2 (Hk2) and Pyruvate kinase M2 (PkM2) configure energy metabolism to support growth. In these non-malignant cells, expression of Hk2 and PkM2 is driven by transcriptional regulators that are typically identified as oncogenes, including N-myc. Importantly, N-myc continues to drive Hk2 and PkM2 in medulloblastoma. Similarly E2F transcription factors and PPARγ function in both progenitors and medulloblastoma to optimize energy metabolism to support proliferation. These findings show that the "metabolic transformation" that is a hallmark of cancer is not specifically limited to cancer. Rather, metabolic transformation represents a co-opting of developmental programs integral to physiologic growth. Despite their physiologic origins, the molecular mechanisms that mediate metabolic transformation may nevertheless present ideal targets for novel anti-tumor therapy. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

[Modifications in myocardial energy metabolism in diabetic patients

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Grynberg, A

2001-11-01

The capacity of cardiac myocyte to regulate ATP production to face any change in energy demand is a major determinant of cardiac function. Because FA is the main heart fuel (although the most expensive one in oxygen, and prompt to induce deleterious effects), this process is based on a balanced fatty acid (FA) metabolism. Several pathological situations are associated with an accumulation of FA or derivatives, or with an excessive b-oxidation. The diabetic cardiomyocyte is characterised by an over consumption of FA. The control of the FA/glucose balance clearly appears as a new strategy for cytoprotection, particularly in diabetes and requires a reduced FA contribution to ATP production. Cardiac myocytes can control FA mitochondrial entry, but display weak ability to control FA uptake, thus the fate of non beta-oxidized FA appear as a new impairment for the cell. Both the trigger and the regulation of cardiac contraction result from membrane activity, and the other major FA function in the myocardium is their role in membrane homeostasis, through the phospholipid synthesis and remodeling pathways. Sudden death, hypercatecholaminemia, diabetes and heart failure have been associated with an altered PUFA content in cardiac membranes. Experimental data suggest that the 2 metabolic pathways involved in membrane homeostasis may represent therapeutic targets for cytoprotection. The drugs that increase cardiac phospholipid turnover (trimétazidine, ranolazine,...) display anti-ischemic non hemodynamic effect. This effect is based on a redirection of FA utilization towards phospholipid synthesis, which decrease their availability for energy production. A nutritional approach gave also promising results. Besides its anti-arrhythmic effect, the dietary docosahexaenoic acid is able to reduce FA energy consumption and hence oxygen demand. The cardiac metabolic pathways involving FA should be considered as a whole, precariously balanced. The diabetic heart being characterised by

Therapeutic Approaches Using Riboflavin in Mitochondrial Energy Metabolism Disorders.

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Henriques, Bárbara J; Lucas, Tânia G; Gomes, Cláudio M

2016-01-01

Riboflavin, or vitamin B2, plays an important role in the cell as biological precursor of FAD and FMN, two important flavin cofactors which are essential for the structure and function of flavoproteins. Riboflavin has been used in therapeutic approaches of various inborn errors of metabolism, notably in metabolic disorders resulting either from defects in proteins involved in riboflavin metabolism and transport or from defects in flavoenzymes. The scope of this review is to provide an updated perspective of clinical cases in which riboflavin was used as a potential therapeutic agent in disorders affecting mitochondrial energy metabolism. In particular, we discuss available mechanistic insights on the role of riboflavin as a pharmacological chaperone for the recovery of misfolded metabolic flavoenzymes.

Studies on growth, nitrogen and energy metabolism in rats

DEFF Research Database (Denmark)

Thorbek, G; Chwalibog, André; Eggum, B O

1982-01-01

Feed intake, growth, nitrogen retention and energy metabolism were measured in 12 male Wistar rats fed ad lib. for 14 weeks with non-purified diets. The feed intake increased rapidly in 4 weeks time from 16 g/d to 25 g/d, and then it was constant in the following 10 weeks. In relation to metabolic...

Sex differences of human cortical blood flow and energy metabolism.

Science.gov (United States)

Aanerud, Joel; Borghammer, Per; Rodell, Anders; Jónsdottir, Kristjana Y; Gjedde, Albert

2017-07-01

Brain energy metabolism is held to reflect energy demanding processes in neuropil related to the density and activity of synapses. There is recent evidence that men have higher density of synapses in temporal cortex than women. One consequence of these differences would be different rates of cortical energy turnover and blood flow in men and women. To test the hypotheses that rates of oxygen consumption (CMRO 2 ) and cerebral blood flow are higher in men than in women in regions of cerebral cortex, and that the differences persist with aging, we used positron emission tomography to determine cerebral blood flow and cerebral metabolic rate of oxygen as functions of age in healthy volunteers of both sexes. Cerebral metabolic rate of oxygen did not change with age for either sex and there were no differences of mean values of cerebral metabolic rate of oxygen between men and women in cerebral cortex. Women had significant decreases of cerebral blood flow as function of age in frontal and parietal lobes. Young women had significantly higher cerebral blood flow than men in frontal and temporal lobes, but these differences had disappeared at age 65. The absent sex difference of cerebral energy turnover suggests that the known differences of synaptic density between the sexes are counteracted by opposite differences of individual synaptic activity.

Genetic and environmental relationships of metabolic and weight phenotypes to metabolic syndrome and diabetes: the healthy twin study.

Science.gov (United States)

Song, Yun-Mi; Sung, Joohon; Lee, Kayoung

2015-02-01

We aimed to examine the relationships, including genetic and environmental correlations, between metabolic and weight phenotypes and factors related to diabetes and metabolic syndrome. Participants of the Healthy Twin Study without diabetes (n=2687; 895 monozygotic and 204 dizygotic twins, and 1588 nontwin family members; mean age, 42.5±13.1 years) were stratified according to body mass index (BMI) (metabolic syndrome categories at baseline. The metabolic traits, namely diabetes and metabolic syndrome, metabolic syndrome components, glycated hemoglobin (HbA1c) level, and homeostasis model assessment of insulin resistance (HOMA-IR), were assessed after 2.5±2.1 years. In a multivariate-adjusted model, those who had metabolic syndrome or overweight phenotypes at baseline were more likely to have higher HbA1C and HOMA-IR levels and abnormal metabolic syndrome components at follow-up as compared to the metabolically healthy normal weight subgroup. The incidence of diabetes was 4.4-fold higher in the metabolically unhealthy but normal weight individuals and 3.3-fold higher in the metabolically unhealthy and overweight individuals as compared with the metabolically healthy normal weight individuals. The heritability of the metabolic syndrome/weight phenotypes was 0.40±0.03. Significant genetic and environmental correlations were observed between the metabolic syndrome/weight phenotypes at baseline and the metabolic traits at follow-up, except for incident diabetes, which only had a significant common genetic sharing with the baseline phenotypes. The genetic and environmental relationships between the metabolic and weight phenotypes at baseline and the metabolic traits at follow-up suggest pleiotropic genetic mechanisms and the crucial role of lifestyle and behavioral factors.

Cellular energy metabolism maintains young status in old queen honey bees (Apis mellifera).

Science.gov (United States)

Lu, Cheng-Yen; Qiu, Jiantai Timothy; Hsu, Chin-Yuan

2018-05-02

Trophocytes and oenocytes of queen honey bees are used in studies of cellular longevity, but their cellular energy metabolism with age is poorly understood. In this study, the molecules involved in cellular energy metabolism were evaluated in the trophocytes and oenocytes of young and old queen bees. The findings indicated that there were no significant differences between young and old queen bees in β-oxidation, glycolysis, and protein synthesis. These results indicate that the cellular energy metabolism of trophocytes and oenocytes in old queen bees is similar to young queen bees and suggests that maintaining cellular energy metabolism in a young status may be associated with the longevity of queen bees. Fat and glycogen accumulation increased with age indicating that old queen bees are older than young queen bees. © 2018 Wiley Periodicals, Inc.

Circulating follistatin in relation to energy metabolism

DEFF Research Database (Denmark)

Hansen, Jakob Schiøler; Plomgaard, Peter

2016-01-01

a relation to energy metabolism. In this narrative review, we attempt to reconcile the existing findings on circulating follistatin with the novel concept that circulating follistatin is a liver-derived molecule regulated by the glucagon-to-insulin ratio. The picture emerging is that conditions associated...

Bedside Evaluation of Cerebral Energy Metabolism in Severe Community-Acquired Bacterial Meningitis

DEFF Research Database (Denmark)

Rom Poulsen, Frantz; Schulz, Mette; Jacobsen, Anne

2015-01-01

BACKGROUND: Mortality and morbidity have remained high in bacterial meningitis. Impairment of cerebral energy metabolism probably contributes to unfavorable outcome. Intracerebral microdialysis is routinely used to monitor cerebral energy metabolism, and recent experimental studies indicate...... that this technique may separate ischemia and non-ischemic mitochondrial dysfunction. The present study is a retrospective interpretation of biochemical data obtained in a series of patients with severe community-acquired meningitis. METHODS: Cerebral energy metabolism was monitored in 15 patients with severe...... community-acquired meningitis utilizing intracerebral microdialysis and bedside biochemical analysis. According to previous studies, cerebral ischemia was defined as lactate/pyruvate (LP) ratio >30 with intracerebral pyruvate level

Metabolic sensing neurons and the control of energy homeostasis.

Science.gov (United States)

Levin, Barry E

2006-11-30

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

Effects of the Mediterranean Diet before and after Weight Loss on Eating Behavioral Traits in Men with Metabolic Syndrome.

Science.gov (United States)

Carbonneau, Élise; Royer, Marie-Michelle; Richard, Caroline; Couture, Patrick; Desroches, Sophie; Lemieux, Simone; Lamarche, Benoît

2017-03-19

The objective of this study was to investigate the impact of the Mediterranean diet (MedDiet) consumed before and after weight loss on eating behavioral traits as measured by the Three-Factor Eating Questionnaire (TFEQ) in men with metabolic syndrome (MetS). In this fixed sequence study, 19 men with MetS (National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII) criteria), aged between 24 and 62 years, first consumed a five-week standardized North American control diet followed by a five-week MedDiet, both under weight-maintaining controlled-feeding conditions. This was followed by a 20-week caloric restriction weight loss period in free-living conditions, without specific recommendations towards adhering to the principles of the MedDiet. Participants were finally subjected to a final five-week MedDiet phase under isoenergetic controlled-feeding conditions. The MedDiet before weight loss had no impact on eating behavioral traits. Body weight reduction by caloric restriction (-10.2% of initial weight) was associated with increased cognitive restraint ( p < 0.0001) and with reduced disinhibition ( p = 0.02) and susceptibility to hunger ( p = 0.01). Feeding the MedDiet for five weeks under isoenergetic conditions after the weight loss phase had no further impact on eating behavioral traits. Results of this controlled-feeding study suggest that consumption of the MedDiet per se has no effect on eating behavioral traits as measured by TFEQ, unless it is combined with significant weight loss.

Effects of the Mediterranean Diet before and after Weight Loss on Eating Behavioral Traits in Men with Metabolic Syndrome

Directory of Open Access Journals (Sweden)

Élise Carbonneau

2017-03-01

Full Text Available The objective of this study was to investigate the impact of the Mediterranean diet (MedDiet consumed before and after weight loss on eating behavioral traits as measured by the Three-Factor Eating Questionnaire (TFEQ in men with metabolic syndrome (MetS. In this fixed sequence study, 19 men with MetS (National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII criteria, aged between 24 and 62 years, first consumed a five-week standardized North American control diet followed by a five-week MedDiet, both under weight-maintaining controlled-feeding conditions. This was followed by a 20-week caloric restriction weight loss period in free-living conditions, without specific recommendations towards adhering to the principles of the MedDiet. Participants were finally subjected to a final five-week MedDiet phase under isoenergetic controlled-feeding conditions. The MedDiet before weight loss had no impact on eating behavioral traits. Body weight reduction by caloric restriction (−10.2% of initial weight was associated with increased cognitive restraint (p < 0.0001 and with reduced disinhibition (p = 0.02 and susceptibility to hunger (p = 0.01. Feeding the MedDiet for five weeks under isoenergetic conditions after the weight loss phase had no further impact on eating behavioral traits. Results of this controlled-feeding study suggest that consumption of the MedDiet per se has no effect on eating behavioral traits as measured by TFEQ, unless it is combined with significant weight loss.

Therapeutic Implications of Targeting Energy Metabolism in Breast Cancer

Directory of Open Access Journals (Sweden)

Meena K. Sakharkar

2013-01-01

Full Text Available PPARs are ligand activated transcription factors. PPARγ agonists have been reported as a new and potentially efficacious treatment of inflammation, diabetes, obesity, cancer, AD, and schizophrenia. Since cancer cells show dysregulation of glycolysis they are potentially manageable through changes in metabolic environment. Interestingly, several of the genes involved in maintaining the metabolic environment and the central energy generation pathway are regulated or predicted to be regulated by PPARγ. The use of synthetic PPARγ ligands as drugs and their recent withdrawal/restricted usage highlight the lack of understanding of the molecular basis of these drugs, their off-target effects, and their network. These data further underscores the complexity of nuclear receptor signalling mechanisms. This paper will discuss the function and role of PPARγ in energy metabolism and cancer biology in general and its emergence as a promising therapeutic target in breast cancer.

Perspectives on the metabolic management of epilepsy through dietary reduction of glucose and elevation of ketone bodies.

Science.gov (United States)

Greene, Amanda E; Todorova, Mariana T; Seyfried, Thomas N

2003-08-01

Brain cells are metabolically flexible because they can derive energy from both glucose and ketone bodies (acetoacetate and beta-hydroxybutyrate). Metabolic control theory applies principles of bioenergetics and genome flexibility to the management of complex phenotypic traits. Epilepsy is a complex brain disorder involving excessive, synchronous, abnormal electrical firing patterns of neurons. We propose that many epilepsies with varied etiologies may ultimately involve disruptions of brain energy homeostasis and are potentially manageable through principles of metabolic control theory. This control involves moderate shifts in the availability of brain energy metabolites (glucose and ketone bodies) that alter energy metabolism through glycolysis and the tricarboxylic acid cycle, respectively. These shifts produce adjustments in gene-linked metabolic networks that manage or control the seizure disorder despite the continued presence of the inherited or acquired factors responsible for the epilepsy. This hypothesis is supported by information on the management of seizures with diets including fasting, the ketogenic diet and caloric restriction. A better understanding of the compensatory genetic and neurochemical networks of brain energy metabolism may produce novel antiepileptic therapies that are more effective and biologically friendly than those currently available.

STAT3 Activities and Energy Metabolism: Dangerous Liaisons

Energy Technology Data Exchange (ETDEWEB)

Camporeale, Annalisa, E-mail: annalisa.camporeale@unito.it [Molecular Biotechnology Center and Department of Molecular Biotechnology and Life Sciences, University of Turin, Via Nizza 52, Turin 10126 (Italy); Demaria, Marco [Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA 94945 (United States); Monteleone, Emanuele [Molecular Biotechnology Center and Department of Molecular Biotechnology and Life Sciences, University of Turin, Via Nizza 52, Turin 10126 (Italy); Giorgi, Carlotta [Department of Experimental and Diagnostic Medicine, Section of General Pathology, Laboratory for Technologies of Advances Therapies (LTTA), University of Ferrara, Via Fossato di Mortara 70, Ferrara 44121 (Italy); Wieckowski, Mariusz R. [Nencki Institute of Experimental Biology, Department of Biochemistry, Pasteur Str. 3, Warsaw 02-093 (Poland); Pinton, Paolo [Department of Experimental and Diagnostic Medicine, Section of General Pathology, Laboratory for Technologies of Advances Therapies (LTTA), University of Ferrara, Via Fossato di Mortara 70, Ferrara 44121 (Italy); Poli, Valeria, E-mail: annalisa.camporeale@unito.it [Molecular Biotechnology Center and Department of Molecular Biotechnology and Life Sciences, University of Turin, Via Nizza 52, Turin 10126 (Italy)

2014-07-31

STAT3 mediates cytokine and growth factor receptor signalling, becoming transcriptionally active upon tyrosine 705 phosphorylation (Y-P). Constitutively Y-P STAT3 is observed in many tumors that become addicted to its activity, and STAT3 transcriptional activation is required for tumor transformation downstream of several oncogenes. We have recently demonstrated that constitutively active STAT3 drives a metabolic switch towards aerobic glycolysis through the transcriptional induction of Hif-1α and the down-regulation of mitochondrial activity, in both MEF cells expressing constitutively active STAT3 (Stat3{sup C/C}) and STAT3-addicted tumor cells. This novel metabolic function is likely involved in mediating pre-oncogenic features in the primary Stat3{sup C/C} MEFs such as resistance to apoptosis and senescence and rapid proliferation. Moreover, it strongly contributes to the ability of primary Stat3{sup C/C} MEFs to undergo malignant transformation upon spontaneous immortalization, a feature that may explain the well known causative link between STAT3 constitutive activity and tumor transformation under chronic inflammatory conditions. Taken together with the recently uncovered role of STAT3 in regulating energy metabolism from within the mitochondrion when phosphorylated on Ser 727, these data place STAT3 at the center of a hub regulating energy metabolism under different conditions, in most cases promoting cell survival, proliferation and malignant transformation even though with distinct mechanisms.

STAT3 Activities and Energy Metabolism: Dangerous Liaisons

International Nuclear Information System (INIS)

Camporeale, Annalisa; Demaria, Marco; Monteleone, Emanuele; Giorgi, Carlotta; Wieckowski, Mariusz R.; Pinton, Paolo; Poli, Valeria

2014-01-01

STAT3 mediates cytokine and growth factor receptor signalling, becoming transcriptionally active upon tyrosine 705 phosphorylation (Y-P). Constitutively Y-P STAT3 is observed in many tumors that become addicted to its activity, and STAT3 transcriptional activation is required for tumor transformation downstream of several oncogenes. We have recently demonstrated that constitutively active STAT3 drives a metabolic switch towards aerobic glycolysis through the transcriptional induction of Hif-1α and the down-regulation of mitochondrial activity, in both MEF cells expressing constitutively active STAT3 (Stat3 C/C ) and STAT3-addicted tumor cells. This novel metabolic function is likely involved in mediating pre-oncogenic features in the primary Stat3 C/C MEFs such as resistance to apoptosis and senescence and rapid proliferation. Moreover, it strongly contributes to the ability of primary Stat3 C/C MEFs to undergo malignant transformation upon spontaneous immortalization, a feature that may explain the well known causative link between STAT3 constitutive activity and tumor transformation under chronic inflammatory conditions. Taken together with the recently uncovered role of STAT3 in regulating energy metabolism from within the mitochondrion when phosphorylated on Ser 727, these data place STAT3 at the center of a hub regulating energy metabolism under different conditions, in most cases promoting cell survival, proliferation and malignant transformation even though with distinct mechanisms

Mitochondrial uncoupling proteins and energy metabolism

Directory of Open Access Journals (Sweden)

Rosa Anna Busiello

2015-02-01

Full Text Available Understanding the metabolic factors that contribute to energy metabolism (EM is critical for the development of new treatments for obesity and related diseases. Mitochondrial oxidative phosphorylation is not perfectly coupled to ATP synthesis, and the process of proton-leak plays a crucial role. Proton-leak accounts for a significant part of the resting metabolic rate and therefore enhancement of this process represents a potential target for obesity treatment. Since their discovery, uncoupling proteins have stimulated great interest due to their involvement in mitochondrial-inducible proton-leak. Despite the widely accepted uncoupling/thermogenic effect of uncoupling protein one (UCP1, which was the first in this family to be discovered, the reactions catalyzed by its homologue UCP3 and the physiological role remain under debate.This review provides an overview of the role played by UCP1 and UCP3 in mitochondrial uncoupling/functionality as well as EM and suggests that they are a potential therapeutic target for treating obesity and its related diseases such as type II diabetes mellitus.

Effects of photoperiod on energy metabolism and thermogenesis in ...

African Journals Online (AJOL)

The plasticity in energy intake, basal metabolic rate (BMR) and nonshivering thermogenesis (NST) was very important for the regulations in energy balance and thermogenesis in Melano-bellied oriental vole exposed to different photoperiod. Change in brown adipose tissue (BAT) cytochrome c oxidase (COX) activity and ...

Performance and Energy Metabolism by Broiler Chickens Fed Maize ...

African Journals Online (AJOL)

Studies were conducted to evaluate the effect of replacing maize grain with different dietary levels of maize and millet offals on performance and energy metabolism in broiler chickens. Proximate composition and metabolizable energy (ME) values were determined. Feeding trial was also conducted to comparemaize and ...

Growth, meat and feed efficiency traits of lambs born to ewes submitted to energy restriction during mid-gestation.

Science.gov (United States)

Piaggio, L; Quintans, G; San Julián, R; Ferreira, G; Ithurralde, J; Fierro, S; Pereira, A S C; Baldi, F; Banchero, G E

2018-02-01

The objective of this study was to evaluate the effects of the energy restriction of gestation of adult ewes from day 45 to day 115 on lamb live performance parameters, carcass and meat traits. In experiment I, dietary energy was restricted at 70% of the metabolizable energy (ME) requirements, after which ewes were re-fed ad libitum until lambing. In experiment II, dietary energy was restricted at 60% of the ME requirements, and ewes were re-fed to ME requirements until lambing. All ewes grazed together from the end of the restriction periods to weaning. Lambs were weaned and lot fed until slaughter. Feed intake, weight gain and feed efficiency were recorded, and body fat thickness and ribeye area (REA) were measured in the longissimus thoracis muscle. After slaughter, carcass weight and yield, fat depth, carcass and leg length, and frenched rack and leg weights and yields were determined. Muscle fiber type composition, Warner-Bratzler shear force, pH and color were determined in the longissimus lumborum muscle. In experiment I, energy restriction followed by ad libitum feeding affected lamb birth weight (P0.05) were observed on later BW, REA, BF or carcass traits. Lambs born to non-restricted-fed ewes had higher (Penergy restriction followed by ME requirements feeding, affected (Pefficient (P=0.16) than lambs from unrestricted dams. Ribeye area and BF were not influenced by treatment. Treatment significantly affected slaughter weight, but had no effects on carcass yield and traits or on meat traits. The results obtained in both experiments indicate submitting ewes to energy restriction during gestation affects the performance of their progeny but the final outcome would depend on the ewe's re-feeding level during late gestation and the capacity of the offspring to compensate the in utero restriction after birth.

Basal Metabolic Rate and Energy Expenditure of Rural Farmers in ...

African Journals Online (AJOL)

Measurement of basal metabolic rate (BMR) provides an important baseline for the determination of an individual's total energy requirement. The study sought to establish human energy expenditure of rural farmers in Magubike village in Tanzania, through determination of BMR, physical activity level (PAL) and total energy ...

Energy metabolism in mobile, wild-sampled sharks inferred by plasma lipids.

Science.gov (United States)

Gallagher, Austin J; Skubel, Rachel A; Pethybridge, Heidi R; Hammerschlag, Neil

2017-01-01

Evaluating how predators metabolize energy is increasingly useful for conservation physiology, as it can provide information on their current nutritional condition. However, obtaining metabolic information from mobile marine predators is inherently challenging owing to their relative rarity, cryptic nature and often wide-ranging underwater movements. Here, we investigate aspects of energy metabolism in four free-ranging shark species ( n  = 281; blacktip, bull, nurse, and tiger) by measuring three metabolic parameters [plasma triglycerides (TAG), free fatty acids (FFA) and cholesterol (CHOL)] via non-lethal biopsy sampling. Plasma TAG, FFA and total CHOL concentrations (in millimoles per litre) varied inter-specifically and with season, year, and shark length varied within a species. The TAG were highest in the plasma of less active species (nurse and tiger sharks), whereas FFA were highest among species with relatively high energetic demands (blacktip and bull sharks), and CHOL concentrations were highest in bull sharks. Although temporal patterns in all metabolites were varied among species, there appeared to be peaks in the spring and summer, with ratios of TAG/CHOL (a proxy for condition) in all species displaying a notable peak in summer. These results provide baseline information of energy metabolism in large sharks and are an important step in understanding how the metabolic parameters can be assessed through non-lethal sampling in the future. In particular, this study emphasizes the importance of accounting for intra-specific and temporal variability in sampling designs seeking to monitor the nutritional condition and metabolic responses of shark populations.

Correlated Effects of Ocean Acidification and Warming on Behavioral and Metabolic Traits of a Large Pelagic Fish

Directory of Open Access Journals (Sweden)

Taryn D. Laubenstein

2018-05-01

Full Text Available Ocean acidification and warming are co-occurring stressors, yet their effects on early life stages of large pelagic fishes are not well known. Here, we determined the effects of elevated CO2 and temperature at levels projected for the end of the century on activity levels, boldness, and metabolic traits (i.e., oxygen uptake rates in larval kingfish (Seriola lalandi, a large pelagic fish with a circumglobal distribution. We also examined correlations between these behavioral and physiological traits measured under different treatments. Kingfish were reared from the egg stage to 25 days post-hatch in a full factorial design of ambient and elevated CO2 (~500 µatm and ~1000 µatm and temperature (21 °C and 25 °C. Activity levels were higher in fish from the elevated temperature treatment compared with fish reared under ambient temperature. However, elevated CO2 did not affect activity, and boldness was not affected by either elevated CO2 or temperature. Both elevated CO2 and temperature resulted in increased resting oxygen uptake rates compared to fish reared under ambient conditions, but neither affected maximum oxygen uptake rates nor aerobic scope. Resting oxygen uptake rates and boldness were negatively correlated under ambient temperature, but positively correlated under elevated temperature. Maximum oxygen uptake rates and boldness were also negatively correlated under ambient temperature. These findings suggest that elevated temperature has a greater impact on behavioral and physiological traits of larval kingfish than elevated CO2. However, elevated CO2 exposure did increase resting oxygen uptake rates and interact with temperature in complex ways. Our results provide novel behavioral and physiological data on the responses of the larval stage of a large pelagic fish to ocean acidification and warming conditions, demonstrate correlations between these traits, and suggest that these correlations could influence the direction and pace of

LKB1 promotes metabolic flexibility in response to energy stress.

Science.gov (United States)

Parker, Seth J; Svensson, Robert U; Divakaruni, Ajit S; Lefebvre, Austin E; Murphy, Anne N; Shaw, Reuben J; Metallo, Christian M

2017-09-01

The Liver Kinase B1 (LKB1) tumor suppressor acts as a metabolic energy sensor to regulate AMP-activated protein kinase (AMPK) signaling and is commonly mutated in various cancers, including non-small cell lung cancer (NSCLC). Tumor cells deficient in LKB1 may be uniquely sensitized to metabolic stresses, which may offer a therapeutic window in oncology. To address this question we have explored how functional LKB1 impacts the metabolism of NSCLC cells using 13 C metabolic flux analysis. Isogenic NSCLC cells expressing functional LKB1 exhibited higher flux through oxidative mitochondrial pathways compared to those deficient in LKB1. Re-expression of LKB1 also increased the capacity of cells to oxidize major mitochondrial substrates, including pyruvate, fatty acids, and glutamine. Furthermore, LKB1 expression promoted an adaptive response to energy stress induced by anchorage-independent growth. Finally, this diminished adaptability sensitized LKB1-deficient cells to combinatorial inhibition of mitochondrial complex I and glutaminase. Together, our data implicate LKB1 as a major regulator of adaptive metabolic reprogramming and suggest synergistic pharmacological strategies for mitigating LKB1-deficient NSCLC tumor growth. Copyright © 2016. Published by Elsevier Inc.

Invited review: Opportunities for genetic improvement of metabolic diseases.

Science.gov (United States)

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

2016-09-01

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

Impact of psychological stress on the associations between apolipoprotein E variants and metabolic traits: findings in an American sample of caregivers and controls.

Science.gov (United States)

Kring, Sofia I Iqbal; Brummett, Beverly H; Barefoot, John; Garrett, Melanie E; Ashley-Koch, Allison E; Boyle, Stephen H; Siegler, Ilene C; Sørensen, Thorkild I A; Williams, Redford B

2010-06-01

To examine the association between apolipoprotein E (APOE) gene variants and waist circumference, fasting plasma glucose, serum insulin, serum high-density lipoprotein cholesterol, and serum triglycerides, all metabolic traits known as cardiovascular disease (CVD) endophenotypes, in a population of stressed individuals and controls. Abdominal obesity, insulin resistance, elevated serum lipid concentration, and APOE polymorphisms have been associated with CVD risk. Current evidence supports the hypothesis that gene-environment interactions modulate serum lipid concentrations. The association between rs769450, rs405509, rs439401, and metabolic traits were analyzed in a U.S. sample of 126 white caregivers of a relative with Alzheimer';s disease or other major dementia and 122 white controls. The associations were analyzed, using multivariate analysis of variance adjusted for age, sex, and medications. Significant multivariate interactions were found, using both additive (p = .009) and dominant (p = .047) models between rs439401 (C/T) and caregiver stress in relation to a profile of metabolic variables. Univariate analyses found the TT genotype to be associated with more adverse levels of waist circumference (interaction, p = .026), triglycerides (interaction, p = .001) and high-density lipoprotein cholesterol (interaction, p = .001) among caregivers but with a more favorable profile of these endophenotypes among controls. There were no significant associations or interactions involving the other two single nucleotide polymorphisms. The APOE rs439401 TT genotype is associated with an adverse metabolic profile among chronically stressed individuals compared with individuals not similarly stressed in whom a more favorable profile is expressed. Confirmation of these results in further research would indicate that the TT genotype can be used to identify persons at high risk for CVD when subjected to chronic stress.

Effects of intraspecific variation in reproductive traits, pectoral fin use and burst swimming on metabolic rates and swimming performance in the Trinidadian guppy (Poecilia reticulata)

DEFF Research Database (Denmark)

Svendsen, Jon Christian; Banet, Amanda I.; Christensen, Rune Haubo Bojesen

2013-01-01

by the total body mass. Results showed that the metabolic rate increased curvilinearly with swimming speed. The slope of the relationship was used as an index of swimming cost. There was no evidence that reproductive traits correlated with swimming cost, MO2std or Ucrit. In contrast, data revealed strong...... swimming and pectoral fin movement over a wide speed range, presumably to support swimming stability and control, is an inefficient swimming behaviour. Finally, transition to burst-assisted swimming was associated with an increase in aerobic metabolic rate. Our study highlights factors other than swimming...

Mind your step: metabolic energy cost while walking an enforced gait pattern.

Science.gov (United States)

Wezenberg, D; de Haan, A; van Bennekom, C A M; Houdijk, H

2011-04-01

The energy cost of walking could be attributed to energy related to the walking movement and energy related to balance control. In order to differentiate between both components we investigated the energy cost of walking an enforced step pattern, thereby perturbing balance while the walking movement is preserved. Nine healthy subjects walked three times at comfortable walking speed on an instrumented treadmill. The first trial consisted of unconstrained walking. In the next two trials, subject walked while following a step pattern projected on the treadmill. The steps projected were either composed of the averaged step characteristics (periodic trial), or were an exact copy including the variability of the steps taken while walking unconstrained (variable trial). Metabolic energy cost was assessed and center of pressure profiles were analyzed to determine task performance, and to gain insight into the balance control strategies applied. Results showed that the metabolic energy cost was significantly higher in both the periodic and variable trial (8% and 13%, respectively) compared to unconstrained walking. The variation in center of pressure trajectories during single limb support was higher when a gait pattern was enforced, indicating a more active ankle strategy. The increased metabolic energy cost could originate from increased preparatory muscle activation to ensure proper foot placement and a more active ankle strategy to control for lateral balance. These results entail that metabolic energy cost of walking can be influenced significantly by control strategies that do not necessary alter global gait characteristics. Copyright © 2011 Elsevier B.V. All rights reserved.

Energy metabolism in Desulfovibrio vulgaris Hildenborough: insights from transcriptome analysis

Energy Technology Data Exchange (ETDEWEB)

Pereira, Patricia M.; He, Qiang; Valente, Filipa M.A.; Xavier, Antonio V.; Zhou, Jizhong; Pereira, Ines A.C.; Louro, Ricardo O.

2007-11-01

Sulphate-reducing bacteria are important players in the global sulphur and carbon cycles, with considerable economical and ecological impact. However, the process of sulphate respiration is still incompletely understood. Several mechanisms of energy conservation have been proposed, but it is unclear how the different strategies contribute to the overall process. In order to obtain a deeper insight into the energy metabolism of sulphate-reducers whole-genome microarrays were used to compare the transcriptional response of Desulfovibrio vulgaris Hildenborough grown with hydrogen/sulphate, pyruvate/sulphate, pyruvate with limiting sulphate, and lactate/thiosulphate, relative to growth in lactate/sulphate. Growth with hydrogen/sulphate showed the largest number of differentially expressed genes and the largest changes in transcript levels. In this condition the most up-regulated energy metabolism genes were those coding for the periplasmic [NiFeSe]hydrogenase, followed by the Ech hydrogenase. The results also provide evidence for the involvement of formate cycling and the recently proposed ethanol pathway during growth in hydrogen. The pathway involving CO cycling is relevant during growth on lactate and pyruvate, but not during growth in hydrogen as the most down-regulated genes were those coding for the CO-induced hydrogenase. Growth on lactate/thiosulphate reveals a down-regulation of several energymetabolism genes similar to what was observed in the presence of nitrite. This study identifies the role of several proteins involved in the energy metabolism of D. vulgaris and highlights several novel genes related to this process, revealing a more complex bioenergetic metabolism than previously considered.

Thermodynamic Aspects and Reprogramming Cellular Energy Metabolism during the Fibrosis Process

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Alexandre Vallée

2017-11-01

Full Text Available Fibrosis is characterized by fibroblast proliferation and fibroblast differentiation into myofibroblasts, which generate a relaxation-free contraction mechanism associated with excessive collagen synthesis in the extracellular matrix, which promotes irreversible tissue retraction evolving towards fibrosis. From a thermodynamic point of view, the mechanisms leading to fibrosis are irreversible processes that can occur through changing the entropy production rate. The thermodynamic behaviors of metabolic enzymes involved in fibrosis are modified by the dysregulation of both transforming growth factor β (TGF-β signaling and the canonical WNT/β-catenin pathway, leading to aerobic glycolysis, called the Warburg effect. Molecular signaling pathways leading to fibrosis are considered dissipative structures that exchange energy or matter with their environment far from the thermodynamic equilibrium. The myofibroblastic cells arise from exergonic processes by switching the core metabolism from oxidative phosphorylation to glycolysis, which generates energy and reprograms cellular energy metabolism to induce the process of myofibroblast differentiation. Circadian rhythms are far-from-equilibrium thermodynamic processes. They directly participate in regulating the TGF-β and WNT/β-catenin pathways involved in energetic dysregulation and enabling fibrosis. The present review focusses on the thermodynamic implications of the reprogramming of cellular energy metabolism, leading to fibroblast differentiation into myofibroblasts through the positive interplay between TGF-β and WNT/β-catenin pathways underlying in fibrosis.

An adult-based insulin resistance genetic risk score associates with insulin resistance, metabolic traits and altered fat distribution in Danish children and adolescents who are overweight or obese

DEFF Research Database (Denmark)

Graae, Anne-Sofie; Hollensted, Mette; Kloppenborg, Julie T

2018-01-01

and adolescents from a population-based study. Anthropometric data, dual-energy x-ray absorptiometry scans, BP, fasting plasma glucose, fasting serum insulin and fasting plasma lipid measurements were obtained, and HOMA-IR was calculated. The GRS53 was examined for association with metabolic traits in children...... by linear regressions using an additive genetic model. In overweight/obese children and adolescents, the GRS53 associated with higher HOMA-IR (β = 0.109 ± 0.050 (SE); p = 2.73 × 10-2), fasting plasma glucose (β = 0.010 ± 0.005 mmol/l; p = 2.51 × 10-2) and systolic BP SD score (β = 0.026 ± 0.012; p = 3...

Feeding-Related Traits Are Affected by Dosage of the foraging Gene in Drosophila melanogaster.

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Allen, Aaron M; Anreiter, Ina; Neville, Megan C; Sokolowski, Marla B

2017-02-01

Nutrient acquisition and energy storage are critical parts of achieving metabolic homeostasis. The foraging gene in Drosophila melanogaster has previously been implicated in multiple feeding-related and metabolic traits. Before foraging's functions can be further dissected, we need a precise genetic null mutant to definitively map its amorphic phenotypes. We used homologous recombination to precisely delete foraging, generating the for 0 null allele, and used recombineering to reintegrate a full copy of the gene, generating the {for BAC } rescue allele. We show that a total loss of foraging expression in larvae results in reduced larval path length and food intake behavior, while conversely showing an increase in triglyceride levels. Furthermore, varying foraging gene dosage demonstrates a linear dose-response on these phenotypes in relation to foraging gene expression levels. These experiments have unequivocally proven a causal, dose-dependent relationship between the foraging gene and its pleiotropic influence on these feeding-related traits. Our analysis of foraging's transcription start sites, termination sites, and splicing patterns using rapid amplification of cDNA ends (RACE) and full-length cDNA sequencing, revealed four independent promoters, pr1-4, that produce 21 transcripts with nine distinct open reading frames (ORFs). The use of alternative promoters and alternative splicing at the foraging locus creates diversity and flexibility in the regulation of gene expression, and ultimately function. Future studies will exploit these genetic tools to precisely dissect the isoform- and tissue-specific requirements of foraging's functions and shed light on the genetic control of feeding-related traits involved in energy homeostasis. Copyright © 2017 by the Genetics Society of America.

Sugar Metabolism in Hummingbirds and Nectar Bats.

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Suarez, Raul K; Welch, Kenneth C

2017-07-12

Hummingbirds and nectar bats coevolved with the plants they visit to feed on floral nectars rich in sugars. The extremely high metabolic costs imposed by small size and hovering flight in combination with reliance upon sugars as their main source of dietary calories resulted in convergent evolution of a suite of structural and functional traits. These allow high rates of aerobic energy metabolism in the flight muscles, fueled almost entirely by the oxidation of dietary sugars, during flight. High intestinal sucrase activities enable high rates of sucrose hydrolysis. Intestinal absorption of glucose and fructose occurs mainly through a paracellular pathway. In the fasted state, energy metabolism during flight relies on the oxidation of fat synthesized from previously-ingested sugar. During repeated bouts of hover-feeding, the enhanced digestive capacities, in combination with high capacities for sugar transport and oxidation in the flight muscles, allow the operation of the "sugar oxidation cascade", the pathway by which dietary sugars are directly oxidized by flight muscles during exercise. It is suggested that the potentially harmful effects of nectar diets are prevented by locomotory exercise, just as in human hunter-gatherers who consume large quantities of honey.

Sugar Metabolism in Hummingbirds and Nectar Bats

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Raul K. Suarez

2017-07-01

Full Text Available Hummingbirds and nectar bats coevolved with the plants they visit to feed on floral nectars rich in sugars. The extremely high metabolic costs imposed by small size and hovering flight in combination with reliance upon sugars as their main source of dietary calories resulted in convergent evolution of a suite of structural and functional traits. These allow high rates of aerobic energy metabolism in the flight muscles, fueled almost entirely by the oxidation of dietary sugars, during flight. High intestinal sucrase activities enable high rates of sucrose hydrolysis. Intestinal absorption of glucose and fructose occurs mainly through a paracellular pathway. In the fasted state, energy metabolism during flight relies on the oxidation of fat synthesized from previously-ingested sugar. During repeated bouts of hover-feeding, the enhanced digestive capacities, in combination with high capacities for sugar transport and oxidation in the flight muscles, allow the operation of the “sugar oxidation cascade”, the pathway by which dietary sugars are directly oxidized by flight muscles during exercise. It is suggested that the potentially harmful effects of nectar diets are prevented by locomotory exercise, just as in human hunter-gatherers who consume large quantities of honey.

Decoding how a soil bacterium extracts building blocks and metabolic energy from ligninolysis provides road map for lignin valorization

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Varman, Arul M.; He, Lian; Follenfant, Rhiannon; Wu, Weihua; Wemmer, Sarah; Wrobel, Steven A.; Tang, Yinjie J.; Singh, Seema

2016-01-01

Sphingobium sp. SYK-6 is a soil bacterium boasting a well-studied ligninolytic pathway and the potential for development into a microbial chassis for lignin valorization. An improved understanding of its metabolism will help researchers in the engineering of SYK-6 for the production of value-added chemicals through lignin valorization. We used 13C-fingerprinting, 13C metabolic flux analysis (13C-MFA), and RNA-sequencing differential expression analysis to uncover the following metabolic traits: (i) SYK-6 prefers alkaline conditions, making it an efficient host for the consolidated bioprocessing of lignin, and it also lacks the ability to metabolize sugars or organic acids; (ii) the CO2 release (i.e., carbon loss) from the ligninolysis-based metabolism of SYK-6 is significantly greater than the CO2 release from the sugar-based metabolism of Escherichia coli; (iii) the vanillin catabolic pathway (which is the converging point of majority of the lignin catabolic pathways) is coupled with the tetrahydrofolate-dependent C1 pathway that is essential for the biosynthesis of serine, histidine, and methionine; (iv) catabolic end products of lignin (pyruvate and oxaloacetate) must enter the tricarboxylic acid (TCA) cycle first and then use phosphoenolpyruvate carboxykinase to initiate gluconeogenesis; and (v) 13C-MFA together with RNA-sequencing differential expression analysis establishes the vanillin catabolic pathway as the major contributor of NAD(P)H synthesis. Therefore, the vanillin catabolic pathway is essential for SYK-6 to obtain sufficient reducing equivalents for its healthy growth; cosubstrate experiments support this finding. This unique energy feature of SYK-6 is particularly interesting because most heterotrophs rely on the transhydrogenase, the TCA cycle, and the oxidative pentose phosphate pathway to obtain NADPH. PMID:27634497

New targets to treat obesity and the metabolic syndrome.

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Martin, Kathleen A; Mani, Mitra V; Mani, Arya

2015-09-15

Metabolic syndrome (MetS) is a cluster ofassociated metabolic traits that collectively confer unsurpassed risk for development of cardiovascular disease (CVD) and type 2 diabetes compared to any single CVD risk factor. Truncal obesity plays an exceptionally critical role among all metabolic traits of the MetS. Consequently, the prevalence of the MetS has steadily increased with the growing epidemic of obesity. Pharmacotherapy has been available for obesity for more than one decade, but with little success in improving the metabolic profiles. The serotonergic drugs and inhibitors of pancreatic lipases were among the few drugs that were initially approved to treat obesity. At the present time, only the pancreatic lipase inhibitor orlistat is approved for long-term treatment of obesity. New classes of anti-diabetic drugs, including glucagon-like peptide 1 receptor (GLP-1R) agonists and Dipeptidyl-peptidase IV (DPP-IV) inhibitors, are currently being evaluated for their effects on obesity and metabolic traits. The genetic studies of obesity and metabolic syndrome have identified novel molecules acting on the hunger and satiety peptidergic signaling of the gut-hypothalamus axis or the melanocortin system of the brain and are promising targets for future drug development. The goal is to develop drugs that not only treat obesity, but also favorably impact its associated traits. Copyright © 2015 Elsevier B.V. All rights reserved.

Genome-Wide Association Study of Metabolic Traits Reveals Novel Gene-Metabolite-Disease Links

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Nicholls, Andrew W.; Salek, Reza M.; Marques-Vidal, Pedro; Morya, Edgard; Sameshima, Koichi; Montoliu, Ivan; Da Silva, Laeticia; Collino, Sebastiano; Martin, François-Pierre; Rezzi, Serge; Steinbeck, Christoph; Waterworth, Dawn M.; Waeber, Gérard; Vollenweider, Peter; Beckmann, Jacques S.; Le Coutre, Johannes; Mooser, Vincent; Bergmann, Sven; Genick, Ulrich K.; Kutalik, Zoltán

2014-01-01

Metabolic traits are molecular phenotypes that can drive clinical phenotypes and may predict disease progression. Here, we report results from a metabolome- and genome-wide association study on 1H-NMR urine metabolic profiles. The study was conducted within an untargeted approach, employing a novel method for compound identification. From our discovery cohort of 835 Caucasian individuals who participated in the CoLaus study, we identified 139 suggestively significant (P<5×10−8) and independent associations between single nucleotide polymorphisms (SNP) and metabolome features. Fifty-six of these associations replicated in the TasteSensomics cohort, comprising 601 individuals from São Paulo of vastly diverse ethnic background. They correspond to eleven gene-metabolite associations, six of which had been previously identified in the urine metabolome and three in the serum metabolome. Our key novel findings are the associations of two SNPs with NMR spectral signatures pointing to fucose (rs492602, P = 6.9×10−44) and lysine (rs8101881, P = 1.2×10−33), respectively. Fine-mapping of the first locus pinpointed the FUT2 gene, which encodes a fucosyltransferase enzyme and has previously been associated with Crohn's disease. This implicates fucose as a potential prognostic disease marker, for which there is already published evidence from a mouse model. The second SNP lies within the SLC7A9 gene, rare mutations of which have been linked to severe kidney damage. The replication of previous associations and our new discoveries demonstrate the potential of untargeted metabolomics GWAS to robustly identify molecular disease markers. PMID:24586186

Association Between Energy Balance and Metabolic Hormone Suppression During Ultraendurance Exercise.

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Geesmann, Bjoern; Gibbs, Jenna C; Mester, Joachim; Koehler, Karsten

2017-08-01

Ultraendurance athletes often accumulate an energy deficit when engaging in ultraendurance exercise, and on completion of the exercise, they exhibit endocrine changes that are reminiscent of starvation. However, it remains unclear whether these endocrine changes are a result of the exercise per se or secondary to the energy deficit and, more important, whether these changes can be attenuated by increased dietary intake. The goal of the study was to assess the relationship between changes in key metabolic hormones after ultraendurance exercise and measures of energy balance. Metabolic hormones, as well as energy intake and expenditure, were assessed in 14 well-trained male cyclists who completed a 1230-km ultraendurance cycling event. After completion of the event, serum testosterone (-67% ± 18%), insulin-like growth factor-1 (IGF-1) (-45% ± 8%), and leptin (-79% ± 9%) were significantly suppressed (P deficit to a 3593-kcal surplus. The marked suppression of testosterone, IGF-1, and leptin after ultraendurance exercise is comparable to changes occurring during acute starvation. The suppression of IGF-1, but not that of other metabolic hormones, was strongly associated with the magnitude of the energy deficit, indicating that athletes who attained a greater energy deficit exhibited a more pronounced drop in IGF-1. Future studies are needed to determine whether increased dietary intake can attenuate the endocrine response to ultraendurance exercise.

Adiponectin Levels and Longitudinal Changes in Metabolic Syndrome: The Healthy Twin Study.

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Song, Yun-Mi; Lee, Kayoung; Sung, Joohon

2015-09-01

We investigated the association of plasma adiponectin levels with longitudinal changes in metabolic syndrome and the metabolic syndrome-related traits [insulin and homeostasis model assessment of insulin resistance (HOMA-IR)], as well as their genetic and environmental correlations. A total of 1030 Koreans (380 men and 650 women; 44.0 ± 12.7 years old) without diabetes of the Healthy Twin Study visited at baseline (2005-2010) and returned for a follow-up examination 3.7 ± 1.2 years later. Baseline plasma adiponectin, metabolic syndrome components [waist circumference (WC), glucose, blood pressure, high-density lipoprotein cholesterol (HDL-C), and triglycerides (TGs)] and metabolic syndrome-related traits were measured at baseline and follow-up. After adjusting for age, sex, smoking, alcohol consumption, physical activity, caloric intake, education level, body mass index (BMI), family history of diabetes, and changes in BMI, 1 standard deviation increment in baseline adiponectin levels was associated with 38-63% lower odds of incident and persistent metabolic syndrome. After additionally adjusting for the baseline levels of each trait, baseline adiponectin levels were inversely associated with WC, blood pressure, insulin, HOMA-IR, and TGs values at follow-up. After adjusting for age, sex, and baseline values of each trait or sum of metabolic syndrome components, baseline adiponectin levels exhibited significantly inverse genetic and environmental correlations with insulin, HOMA-IR, and HDL-C values and the sum of metabolic syndrome components at follow-up. High adiponectin levels reduce the risk of developing metabolic syndrome and having persistent metabolic syndrome and increase of metabolic syndrome-related traits over time. These associations may be explained by pleiotropic genetic mechanisms.

Metabolic flexibility as an adaptation to energy resources and requirements in health and disease.

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Smith, Reuben L; Soeters, Maarten R; Wüst, Rob C I; Houtkooper, Riekelt H

2018-04-24

The ability to efficiently adapt metabolism by substrate sensing, trafficking, storage and utilization, dependent on availability and requirement is known as metabolic flexibility. In this review, we discuss the breadth and depth of metabolic flexibility and its impact on health and disease. Metabolic flexibility is essential to maintain energy homeostasis in times of either caloric excess or caloric restriction, and in times of either low or high energy demand, such as during exercise. The liver, adipose tissue and muscle govern systemic metabolic flexibility and manage nutrient sensing, uptake, transport, storage and expenditure by communication via endocrine cues. At a molecular level, metabolic flexibility relies on the configuration of metabolic pathways which is regulated by key metabolic enzymes and transcription factors, many of which interact closely with the mitochondria. Disrupted metabolic flexibility, or metabolic inflexibility, however, is associated with many pathological conditions including metabolic syndrome, type 2 diabetes mellitus, and cancer. Multiple factors like dietary composition and feeding frequency, exercise training, and use of pharmacological compounds influence metabolic flexibility and will be discussed here. Lastly, we outline important advances in metabolic flexibility research and discuss medical horizons and translational aspects.

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

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

2015-04-20

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

Connecting metabolism and reproduction: roles of central energy sensors and key molecular mediators.

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Roa, Juan; Tena-Sempere, Manuel

2014-11-01

It is well established that pubertal activation of the reproductive axis and maintenance of fertility are critically dependent on the magnitude of body energy reserves and the metabolic state of the organism. Hence, conditions of impaired energy homeostasis often result in deregulation of puberty and reproduction, whereas gonadal dysfunction can be associated with the worsening of the metabolic profile and, eventually, changes in body weight. While much progress has taken place in our knowledge about the neuroendocrine mechanisms linking metabolism and reproduction, our understanding of how such dynamic interplay happens is still incomplete. As paradigmatic example, much has been learned in the last two decades on the reproductive roles of key metabolic hormones (such as leptin, insulin and ghrelin), their brain targets and the major transmitters and neuropeptides involved. Yet, the molecular mechanisms whereby metabolic information is translated and engages into the reproductive circuits remain largely unsolved. In this work, we will summarize recent developments in the characterization of the putative central roles of key cellular energy sensors, such as mTOR, in this phenomenon, and will relate these with other molecular mechanisms likely contributing to the brain coupling of energy balance and fertility. In doing so, we aim to provide an updated view of an area that, despite still underdeveloped, may be critically important to fully understand how reproduction and metabolism are tightly connected in health and disease. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Regulation of longevity by FGF21: Interaction between energy metabolism and stress responses.

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Salminen, Antero; Kaarniranta, Kai; Kauppinen, Anu

2017-08-01

Fibroblast growth factor 21 (FGF21) is a hormone-like member of FGF family which controls metabolic multiorgan crosstalk enhancing energy expenditure through glucose and lipid metabolism. In addition, FGF21 acts as a stress hormone induced by endoplasmic reticulum stress and dysfunctions of mitochondria and autophagy in several tissues. FGF21 also controls stress responses and metabolism by modulating the functions of somatotropic axis and hypothalamic-pituitary-adrenal (HPA) pathway. FGF21 is a potent longevity factor coordinating interactions between energy metabolism and stress responses. Recent studies have revealed that FGF21 treatment can alleviate many age-related metabolic disorders, e.g. atherosclerosis, obesity, type 2 diabetes, and some cardiovascular diseases. In addition, transgenic mice overexpressing FGF21 have an extended lifespan. However, chronic metabolic and stress-related disorders involving inflammatory responses can provoke FGF21 resistance and thus disturb healthy aging process. First, we will describe the role of FGF21 in interorgan energy metabolism and explain how its functions as a stress hormone can improve healthspan. Next, we will examine both the induction of FGF21 expression via the integrated stress response and the molecular mechanism through which FGF21 enhances healthy aging. Finally, we postulate that FGF21 resistance, similarly to insulin resistance, jeopardizes human healthspan and accelerates the aging process. Copyright © 2017 Elsevier B.V. All rights reserved.

Causal relationship between adiponectin and metabolic traits: a Mendelian randomization study in a multiethnic population.

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Andrew Mente

Full Text Available Adiponectin, a secretagogue exclusively produced by adipocytes, has been associated with metabolic features, but its role in the development of the metabolic syndrome remains unclear.We investigated the association between serum adiponectin level and metabolic traits, using both observational and genetic epidemiologic approaches in a multiethnic population assembled in Canada.Clinical data and serum adiponectin level were collected in 1,157 participants of the SHARE/SHARE-AP studies. Participants were genotyped for the functional rs266729 and rs1260326 SNPs in ADIPOQ and GCKR genes.Adiponectin level was positively associated with HDL cholesterol and negatively associated with body mass index, waist-to-hip ratio, triglycerides, fasting glucose, fasting insulin, systolic and diastolic pressure (all P<0.002. The rs266729 minor G allele was associated with lower adiponectin and higher HOMA-IR (P = 0.004 and 0.003, respectively. The association between rs266729 SNP and HOMA-IR was no longer significant after adjustment for adiponectin concentration (P = 0.10. The rs266729 SNP was associated with HOMA-IR to an extent that exceeded its effect on adiponectin level (0.15 SD 95% C.I. [0.06, 0.24], P<0.001. There was no significant interaction between rs266729 SNP and ethnicity on adiponectin or HOMA-IR. In contrast, the SNP rs1260326 in GCKR was associated with HOMA-IR (P<0.001, but not with adiponectin level (P = 0.67.The association of the functional promoter polymorphism rs266729 with lower serum adiponectin and increased insulin resistance in diverse ethnic groups may suggest a causal relationship between adiponectin level and insulin resistance.

31P-magnetic resonance spectroscopy: Impaired energy metabolism in latent hyperthyroidism

International Nuclear Information System (INIS)

Theissen, P.; Kaldewey, S.; Moka, D.; Bunke, J.; Voth, E.; Schicha, H.

1993-01-01

31 Phosphorous magnetic resonance spectroscopy allows an in vivo examination of energy metabolism. The present study was designed to evaluate whether in patients with latent hyperthyroidism alterations of muscle energy metabolism could be found similar to those observed in patients with overt hyperthyroidism. In 10 patients with overt hyperthyroidism before therapy and 20 with latent hyperthyroidism (also without therapy) and in 24 healthy volunteers magnetic resonance spectroscopy of the calf muscle was performed within a 1.5-Tesla magnet. Muscle concentrations of phosphocreatine, inorganic phosphate, and ATP were quantified compared to an external standard solution of K 2 HPO 4 . In the patients with overt hyperthyroidism and with latent hyperthyroidism a significant decrease of phosphocreatine was found. Further, the ATP concentration in patients with latent and manifest hyperthyroidism tended towards lower values. There were no significant differences in the decrease of phosphocreatine and ATP between both patient groups. Therefore, this study for the first time shows that alterations of energy metabolism in latent hyperthyroidism can be measured and that they are similar to those observed in overt hyperthyroidism. (orig.) [de

Salinity modulates thermotolerance, energy metabolism and stress response in amphipods Gammarus lacustris

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Kseniya P. Vereshchagina

2016-11-01

Full Text Available Temperature and salinity are important abiotic factors for aquatic invertebrates. We investigated the influence of different salinity regimes on thermotolerance, energy metabolism and cellular stress defense mechanisms in amphipods Gammarus lacustris Sars from two populations. We exposed amphipods to different thermal scenarios and determined their survival as well as activity of major antioxidant enzymes (peroxidase, catalase, glutathione S-transferase and parameters of energy metabolism (content of glucose, glycogen, ATP, ADP, AMP and lactate. Amphipods from a freshwater population were more sensitive to the thermal challenge, showing higher mortality during acute and gradual temperature change compared to their counterparts from a saline lake. A more thermotolerant population from a saline lake had high activity of antioxidant enzymes. The energy limitations of the freshwater population (indicated by low baseline glucose levels, downward shift of the critical temperature of aerobic metabolism and inability to maintain steady-state ATP levels during warming was observed, possibly reflecting a trade-off between the energy demands for osmoregulation under the hypo-osmotic condition of a freshwater environment and protection against temperature stress.

High energy reactions in normal metabolism and ageing of animals

International Nuclear Information System (INIS)

Avdonina, E.N.; Nesmeyanov, N.

1983-01-01

Processes involving reactions on highly excited states are thought to be of great importance for normal metabolism and aging. Excess energy of the organism is transferred to result in the formation of highly excited states of macromolecules. UV, visible light or ionizing radiation created partially by the organism itself can change metabolic process rates. According to the authors, aging is associated with the defects of macromolecules owing to high energy processes. Gerontological changes in biological materials result from the elimination of low molecular weight molecules and from the formation of unsaturated compounds. Crosslinking of the compounds, accumulation of collagen and connective tissues, the energetic overload of the organism are listed as important features of aging. (V.N.)

Cytosolic Calcium Coordinates Mitochondrial Energy Metabolism with Presynaptic Activity

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Chouhan, Amit K.; Ivannikov, Maxim V.; Lu, Zhongmin; Sugimori, Mutsuyuki; Llinas, Rodolfo R.; Macleod, Gregory T.

2012-01-01

Most neurons fire in bursts, imposing episodic energy demands, but how these demands are coordinated with oxidative phosphorylation is still unknown. Here, using fluorescence imaging techniques on presynaptic termini of Drosophila motor neurons (MNs), we show that mitochondrial matrix pH (pHm), inner membrane potential (Δψm), and NAD(P)H levels ([NAD(P)H]m) increase within seconds of nerve stimulation. The elevations of pHm, Δψm, and [NAD(P)H]m indicate an increased capacity for ATP production. Elevations in pHm were blocked by manipulations which blocked mitochondrial Ca2+ uptake, including replacement of extracellular Ca2+ with Sr2+, and application of either tetraphenylphosphonium chloride or KB-R7943, indicating that it is Ca2+ that stimulates presynaptic mitochondrial energy metabolism. To place this phenomenon within the context of endogenous neuronal activity, the firing rates of a number of individually identified MNs were determined during fictive locomotion. Surprisingly, although endogenous firing rates are significantly different, there was little difference in presynaptic cytosolic Ca2+ levels ([Ca2+]c) between MNs when each fires at its endogenous rate. The average [Ca2+]c level (329±11nM) was slightly above the average Ca2+ affinity of the mitochondria (281±13nM). In summary, we show that when MNs fire at endogenous rates [Ca2+]c is driven into a range where mitochondria rapidly acquire Ca2+. As we also show that Ca2+ stimulates presynaptic mitochondrial energy metabolism, we conclude that [Ca2+]c levels play an integral role in coordinating mitochondrial energy metabolism with presynaptic activity in Drosophila MNs. PMID:22279208

In Vitro Effects of Sports and Energy Drinks on Streptococcus mutans Biofilm Formation and Metabolic Activity.

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Vinson, LaQuia A; Goodlett, Amy K; Huang, Ruijie; Eckert, George J; Gregory, Richard L

2017-09-15

Sports and energy drinks are being increasingly consumed and contain large amounts of sugars, which are known to increase Streptococcus mutans biofilm formation and metabolic activity. The purpose of this in vitro study was to investigate the effects of sports and energy drinks on S. mutans biofilm formation and metabolic activity. S. mutans UA159 was cultured with and without a dilution (1:3 ratio) of a variety of sports and energy drinks in bacterial media for 24 hours. The biofilm was washed, fixed, and stained. Biofilm growth was evaluated by reading absorbance of the crystal violet. Biofilm metabolic activity was measured by the biofilm-reducing XTT to a water-soluble orange compound. Gatorade Protein Recovery Shake and Starbucks Doubleshot Espresso Energy were found to significantly increase biofilm (30-fold and 22-fold, respectively) and metabolic activity (2-fold and 3-fold, respectively). However, most of the remaining drinks significantly inhibited biofilm growth and metabolic activity. Several sports and energy drinks, with sugars or sugar substitutes as their main ingredients inhibited S. mutans biofilm formation. Among the drinks evaluated, Gatorade Protein Recovery Chocolate Shake and Starbucks Doubleshot Energy appear to have cariogenic potential since they increased the biofilm formation and metabolic activity of S. mutans.

Within-day energy deficiency and metabolic perturbation in male endurance athletes

DEFF Research Database (Denmark)

Torstveit, Monica K; Fahrenholtz, Ida Lysdahl; Stenqvist, Thomas B

2018-01-01

) or normal RMR (RMRratio> 0.90, n=11). Despite no observed differences in 24-hour EB or EA between the groups, subjects with suppressed RMR spent more time in an energy deficit exceeding 400 kcal (20.9 [18.8 - 21.8] hours vs. 10.8 [2.5 - 16.4], P=0.023), and had larger single-hour energy deficits compared......Endurance athletes are at increased risk of relative energy deficiency associated with metabolic perturbation and impaired health. We aimed to estimate and compare within-day energy balance (WDEB) in male athletes with suppressed and normal resting metabolic rate (RMR) and explore if within...... to subjects with normal RMR (3265 ± 1963 kcal vs. -1340 ± 2439, P=0.023). Larger single-hour energy deficits were associated with higher cortisol levels (r = -0.499, P=0.004) and a lower testosterone:cortisol ratio (r = 0.431, P=0.015), but no associations with T3or fasting blood glucose were observed...

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

Science.gov (United States)

Goforth, Paulette B; Myers, Martin G

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

Impaired cardiac energy metabolism in embryos lacking adrenergic stimulation

Science.gov (United States)

Baker, Candice N.; Gidus, Sarah A.; Price, George F.; Peoples, Jessica N. R.

2014-01-01

As development proceeds from the embryonic to fetal stages, cardiac energy demands increase substantially, and oxidative phosphorylation of ADP to ATP in mitochondria becomes vital. Relatively little, however, is known about the signaling mechanisms regulating the transition from anaerobic to aerobic metabolism that occurs during the embryonic period. The main objective of this study was to test the hypothesis that adrenergic hormones provide critical stimulation of energy metabolism during embryonic/fetal development. We examined ATP and ADP concentrations in mouse embryos lacking adrenergic hormones due to targeted disruption of the essential dopamine β-hydroxylase (Dbh) gene. Embryonic ATP concentrations decreased dramatically, whereas ADP concentrations rose such that the ATP/ADP ratio in the adrenergic-deficient group was nearly 50-fold less than that found in littermate controls by embryonic day 11.5. We also found that cardiac extracellular acidification and oxygen consumption rates were significantly decreased, and mitochondria were significantly larger and more branched in adrenergic-deficient hearts. Notably, however, the mitochondria were intact with well-formed cristae, and there was no significant difference observed in mitochondrial membrane potential. Maternal administration of the adrenergic receptor agonists isoproterenol or l-phenylephrine significantly ameliorated the decreases in ATP observed in Dbh−/− embryos, suggesting that α- and β-adrenergic receptors were effective modulators of ATP concentrations in mouse embryos in vivo. These data demonstrate that adrenergic hormones stimulate cardiac energy metabolism during a critical period of embryonic development. PMID:25516547

Impaired cardiac energy metabolism in embryos lacking adrenergic stimulation.

Science.gov (United States)

Baker, Candice N; Gidus, Sarah A; Price, George F; Peoples, Jessica N R; Ebert, Steven N

2015-03-01

As development proceeds from the embryonic to fetal stages, cardiac energy demands increase substantially, and oxidative phosphorylation of ADP to ATP in mitochondria becomes vital. Relatively little, however, is known about the signaling mechanisms regulating the transition from anaerobic to aerobic metabolism that occurs during the embryonic period. The main objective of this study was to test the hypothesis that adrenergic hormones provide critical stimulation of energy metabolism during embryonic/fetal development. We examined ATP and ADP concentrations in mouse embryos lacking adrenergic hormones due to targeted disruption of the essential dopamine β-hydroxylase (Dbh) gene. Embryonic ATP concentrations decreased dramatically, whereas ADP concentrations rose such that the ATP/ADP ratio in the adrenergic-deficient group was nearly 50-fold less than that found in littermate controls by embryonic day 11.5. We also found that cardiac extracellular acidification and oxygen consumption rates were significantly decreased, and mitochondria were significantly larger and more branched in adrenergic-deficient hearts. Notably, however, the mitochondria were intact with well-formed cristae, and there was no significant difference observed in mitochondrial membrane potential. Maternal administration of the adrenergic receptor agonists isoproterenol or l-phenylephrine significantly ameliorated the decreases in ATP observed in Dbh-/- embryos, suggesting that α- and β-adrenergic receptors were effective modulators of ATP concentrations in mouse embryos in vivo. These data demonstrate that adrenergic hormones stimulate cardiac energy metabolism during a critical period of embryonic development. Copyright © 2015 the American Physiological Society.

Impact of psychological stress on the associations between apolipoprotein E variants and metabolic traits: findings in an American sample of caregivers and controls

DEFF Research Database (Denmark)

Kring, Sofia Iqbal; Brummett, Beverly H; Barefoot, John

2010-01-01

To examine the association between apolipoprotein E (APOE) gene variants and waist circumference, fasting plasma glucose, serum insulin, serum high-density lipoprotein cholesterol, and serum triglycerides, all metabolic traits known as cardiovascular disease (CVD) endophenotypes, in a population ...... of stressed individuals and controls. Abdominal obesity, insulin resistance, elevated serum lipid concentration, and APOE polymorphisms have been associated with CVD risk. Current evidence supports the hypothesis that gene-environment interactions modulate serum lipid concentrations....

Adenylate Kinase and AMP Signaling Networks: Metabolic Monitoring, Signal Communication and Body Energy Sensing

Directory of Open Access Journals (Sweden)

Andre Terzic

2009-04-01

Full Text Available Adenylate kinase and downstream AMP signaling is an integrated metabolic monitoring system which reads the cellular energy state in order to tune and report signals to metabolic sensors. A network of adenylate kinase isoforms (AK1-AK7 are distributed throughout intracellular compartments, interstitial space and body fluids to regulate energetic and metabolic signaling circuits, securing efficient cell energy economy, signal communication and stress response. The dynamics of adenylate kinase-catalyzed phosphotransfer regulates multiple intracellular and extracellular energy-dependent and nucleotide signaling processes, including excitation-contraction coupling, hormone secretion, cell and ciliary motility, nuclear transport, energetics of cell cycle, DNA synthesis and repair, and developmental programming. Metabolomic analyses indicate that cellular, interstitial and blood AMP levels are potential metabolic signals associated with vital functions including body energy sensing, sleep, hibernation and food intake. Either low or excess AMP signaling has been linked to human disease such as diabetes, obesity and hypertrophic cardiomyopathy. Recent studies indicate that derangements in adenylate kinase-mediated energetic signaling due to mutations in AK1, AK2 or AK7 isoforms are associated with hemolytic anemia, reticular dysgenesis and ciliary dyskinesia. Moreover, hormonal, food and antidiabetic drug actions are frequently coupled to alterations of cellular AMP levels and associated signaling. Thus, by monitoring energy state and generating and distributing AMP metabolic signals adenylate kinase represents a unique hub within the cellular homeostatic network.

Altitudinal patterns of diversity and functional traits of metabolically active microorganisms in stream biofilms

Science.gov (United States)

Wilhelm, Linda; Besemer, Katharina; Fragner, Lena; Peter, Hannes; Weckwerth, Wolfram; Battin, Tom J

2015-01-01

Resources structure ecological communities and potentially link biodiversity to energy flow. It is commonly believed that functional traits (generalists versus specialists) involved in the exploitation of resources depend on resource availability and environmental fluctuations. The longitudinal nature of stream ecosystems provides changing resources to stream biota with yet unknown effects on microbial functional traits and community structure. We investigated the impact of autochthonous (algal extract) and allochthonous (spruce extract) resources, as they change along alpine streams from above to below the treeline, on microbial diversity, community composition and functions of benthic biofilms. Combining bromodeoxyuridine labelling and 454 pyrosequencing, we showed that diversity was lower upstream than downstream of the treeline and that community composition changed along the altitudinal gradient. We also found that, especially for allochthonous resources, specialisation by biofilm bacteria increased along that same gradient. Our results suggest that in streams below the treeline biofilm diversity, specialisation and functioning are associated with increasing niche differentiation as potentially modulated by divers allochthonous and autochthonous constituents contributing to resources. These findings expand our current understanding on biofilm structure and function in alpine streams. PMID:25978543

Genetic regulation of bone metabolism in the chicken: similarities and differences to Mammalian systems.

Directory of Open Access Journals (Sweden)

Martin Johnsson

2015-05-01

Full Text Available Birds have a unique bone physiology, due to the demands placed on them through egg production. In particular their medullary bone serves as a source of calcium for eggshell production during lay and undergoes continuous and rapid remodelling. We take advantage of the fact that bone traits have diverged massively during chicken domestication to map the genetic basis of bone metabolism in the chicken. We performed a quantitative trait locus (QTL and expression QTL (eQTL mapping study in an advanced intercross based on Red Junglefowl (the wild progenitor of the modern domestic chicken and White Leghorn chickens. We measured femoral bone traits in 456 chickens by peripheral computerised tomography and femoral gene expression in a subset of 125 females from the cross with microarrays. This resulted in 25 loci for female bone traits, 26 loci for male bone traits and 6318 local eQTL loci. We then overlapped bone and gene expression loci, before checking for an association between gene expression and trait values to identify candidate quantitative trait genes for bone traits. A handful of our candidates have been previously associated with bone traits in mice, but our results also implicate unexpected and largely unknown genes in bone metabolism. In summary, by utilising the unique bone metabolism of an avian species, we have identified a number of candidate genes affecting bone allocation and metabolism. These findings can have ramifications not only for the understanding of bone metabolism genetics in general, but could also be used as a potential model for osteoporosis as well as revealing new aspects of vertebrate bone regulation or features that distinguish avian and mammalian bone.

Sex Differences in Energy Metabolism Need to Be Considered with Lifestyle Modifications in Humans

Directory of Open Access Journals (Sweden)

Betty N. Wu

2011-01-01

Full Text Available Women have a higher proportion of body fat compared to men. However, women consume fewer kilojoules per kilogram lean mass and burn fat more preferentially during exercise compared with men. During gestation, women store even greater amounts of fat that cannot be solely attributed to increased energy intake. These observations suggest that the relationship between kilojoules consumed and kilojoules utilised is different in men and women. The reason for these sex differences in energy metabolism is not known; however, it may relate to sex steroids, differences in insulin resistance, or metabolic effects of other hormones such as leptin. When considering lifestyle modifications, sex differences in energy metabolism should be considered. Moreover, elucidating the regulatory role of hormones in energy homeostasis is important for understanding the pathogenesis of obesity and perhaps in the future may lead to ways to reduce body fat with less energy restriction.

Energy Metabolism and Human Dosimetry of Tritium

International Nuclear Information System (INIS)

Galeriu, D.; Takeda, H.; Melintescu, A.; Trivedi, A.

2005-01-01

In the frame of current revision of human dosimetry of 14 C and tritium, undertaken by the International Commission of Radiological Protection, we propose a novel approach based on energy metabolism and a simple biokinetic model for the dynamics of dietary intake (organic 14 C, tritiated water and Organically Bound Tritium-OBT). The model predicts increased doses for HTO and OBT comparing to ICRP recommendations, supporting recent findings

The role of energy & fatty acid metabolism in obesity and insulin resistance

NARCIS (Netherlands)

Heemskerk, Mattijs Maria

2015-01-01

In today’s world, more people die from complications of overweight than from underweight. But not all individuals are equally prone to develop metabolic complications, such as obesity and insulin resistance. This thesis focuses on the differences in the energy and fatty acid metabolism that play a

How Energy Metabolism Supports Cerebral Function: Insights from 13C Magnetic Resonance Studies In vivo

Directory of Open Access Journals (Sweden)

Sarah Sonnay

2017-05-01

Full Text Available Cerebral function is associated with exceptionally high metabolic activity, and requires continuous supply of oxygen and nutrients from the blood stream. Since the mid-twentieth century the idea that brain energy metabolism is coupled to neuronal activity has emerged, and a number of studies supported this hypothesis. Moreover, brain energy metabolism was demonstrated to be compartmentalized in neurons and astrocytes, and astrocytic glycolysis was proposed to serve the energetic demands of glutamatergic activity. Shedding light on the role of astrocytes in brain metabolism, the earlier picture of astrocytes being restricted to a scaffold-associated function in the brain is now out of date. With the development and optimization of non-invasive techniques, such as nuclear magnetic resonance spectroscopy (MRS, several groups have worked on assessing cerebral metabolism in vivo. In this context, 1H MRS has allowed the measurements of energy metabolism-related compounds, whose concentrations can vary under different brain activation states. 1H-[13C] MRS, i.e., indirect detection of signals from 13C-coupled 1H, together with infusion of 13C-enriched glucose has provided insights into the coupling between neurotransmission and glucose oxidation. Although these techniques tackle the coupling between neuronal activity and metabolism, they lack chemical specificity and fail in providing information on neuronal and glial metabolic pathways underlying those processes. Currently, the improvement of detection modalities (i.e., direct detection of 13C isotopomers, the progress in building adequate mathematical models along with the increase in magnetic field strength now available render possible detailed compartmentalized metabolic flux characterization. In particular, direct 13C MRS offers more detailed dataset acquisitions and provides information on metabolic interactions between neurons and astrocytes, and their role in supporting neurotransmission. Here

Interrelationships between mitochondrial fusion, energy metabolism and oxidative stress during development in Caenorhabditis elegans

Energy Technology Data Exchange (ETDEWEB)

Yasuda, Kayo [Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1193 (Japan); Education and Research Support Center, Tokai University School of Medicine, Isehara, Kanagawa 259-1193 (Japan); Hartman, Philip S. [Biology Department, Texas Christian University, Fort Worth, TX 76129 (United States); Ishii, Takamasa [Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1193 (Japan); Suda, Hitoshi [School of High-Technology for Human Welfare, Tokai University, Nishino 317, Numazu, Shizuoka 410-0395 (Japan); Akatsuka, Akira [Education and Research Support Center, Tokai University School of Medicine, Isehara, Kanagawa 259-1193 (Japan); Shoyama, Tetsuji [School of High-Technology for Human Welfare, Tokai University, Nishino 317, Numazu, Shizuoka 410-0395 (Japan); Miyazawa, Masaki [Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1193 (Japan); Ishii, Naoaki, E-mail: nishii@is.icc.u-tokai.ac.jp [Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1193 (Japan)

2011-01-21

Research highlights: {yields} Growth and development of a fzo-1 mutant defective in the fusion process of mitochondria was delayed relative to the wild type of Caenorhabditis elegans. {yields} Oxygen sensitivity during larval development, superoxide production and carbonyl protein accumulation of the fzo-1 mutant were similar to wild type. {yields} fzo-1 animals had significantly lower metabolism than did N2 and mev-1 overproducing superoxide from mitochondrial electron transport complex II. {yields} Mitochondrial fusion can profoundly affect energy metabolism and development. -- Abstract: Mitochondria are known to be dynamic structures with the energetically and enzymatically mediated processes of fusion and fission responsible for maintaining a constant flux. Mitochondria also play a role of reactive oxygen species production as a byproduct of energy metabolism. In the current study, interrelationships between mitochondrial fusion, energy metabolism and oxidative stress on development were explored using a fzo-1 mutant defective in the fusion process and a mev-1 mutant overproducing superoxide from mitochondrial electron transport complex II of Caenorhabditis elegans. While growth and development of both single mutants was slightly delayed relative to the wild type, the fzo-1;mev-1 double mutant experienced considerable delay. Oxygen sensitivity during larval development, superoxide production and carbonyl protein accumulation of the fzo-1 mutant were similar to wild type. fzo-1 animals had significantly lower metabolism than did N2 and mev-1. These data indicate that mitochondrial fusion can profoundly affect energy metabolism and development.

Targeting energy metabolism in brain cancer through calorie restriction and the ketogenic diet

Directory of Open Access Journals (Sweden)

Seyfried B

2009-09-01

Full Text Available Malignant brain tumors are a significant health problem in children and adults and are largely unmanageable. As a metabolic disorder involving the dysregulation of glycolysis and respiration (the Warburg effect, malignant brain cancer can be managed through changes in metabolic environment. In contrast to malignant brain tumors that are mostly dependent on glycolysis for energy, normal neurons and glia readily transition to ketone bodies (β-hydroxybutyrate for energy in vivo when glucose levels are reduced. The transition from glucose to ketone bodies as a major energy source is an evolutionary conserved adaptation to food deprivation that permits the survival of normal cells during extreme shifts in nutritional environment. Only those cells with a flexible genome, honed through millions of years of environmental forcing and variability selection, can transition from one energy state to another. We propose a different approach to brain cancer management that exploits the metabolic flexibility of normal cells at the expense of the genetically defective and less metabolically flexible tumor cells. This approach to brain cancer management is supported from recent studies in orthotopic mouse brain tumor models and in human pediatric astrocytoma treated with calorie restriction and the ketogenic diet. Issues of implementation and use protocols are discussed.

Experimental ocean acidification alters the allocation of metabolic energy.

Science.gov (United States)

Pan, T-C Francis; Applebaum, Scott L; Manahan, Donal T

2015-04-14

Energy is required to maintain physiological homeostasis in response to environmental change. Although responses to environmental stressors frequently are assumed to involve high metabolic costs, the biochemical bases of actual energy demands are rarely quantified. We studied the impact of a near-future scenario of ocean acidification [800 µatm partial pressure of CO2 (pCO2)] during the development and growth of an important model organism in developmental and environmental biology, the sea urchin Strongylocentrotus purpuratus. Size, metabolic rate, biochemical content, and gene expression were not different in larvae growing under control and seawater acidification treatments. Measurements limited to those levels of biological analysis did not reveal the biochemical mechanisms of response to ocean acidification that occurred at the cellular level. In vivo rates of protein synthesis and ion transport increased ∼50% under acidification. Importantly, the in vivo physiological increases in ion transport were not predicted from total enzyme activity or gene expression. Under acidification, the increased rates of protein synthesis and ion transport that were sustained in growing larvae collectively accounted for the majority of available ATP (84%). In contrast, embryos and prefeeding and unfed larvae in control treatments allocated on average only 40% of ATP to these same two processes. Understanding the biochemical strategies for accommodating increases in metabolic energy demand and their biological limitations can serve as a quantitative basis for assessing sublethal effects of global change. Variation in the ability to allocate ATP differentially among essential functions may be a key basis of resilience to ocean acidification and other compounding environmental stressors.

Effects of photoperiod on energy metabolism and thermogenesis in ...

African Journals Online (AJOL)

Administrator

2010-12-27

Dec 27, 2010 ... levels, the responses of this species were studied in different photoperiods. Experiment data ... thermogenesis. Key words: Melano-bellied oriental vole, photoperiod, energy metabolism, brown adipose tissue, cytochrome c .... Folin phenol method with bovine serum albumin as standard (Lowry et al., 1951).

Genetic engineering of cytokinin metabolism: prospective way to improve agricultural traits of crop plants.

Science.gov (United States)

Zalabák, David; Pospíšilová, Hana; Šmehilová, Mária; Mrízová, Katarína; Frébort, Ivo; Galuszka, Petr

2013-01-01

Cytokinins (CKs) are ubiquitous phytohormones that participate in development, morphogenesis and many physiological processes throughout plant kingdom. In higher plants, mutants and transgenic cells and tissues with altered activity of CK metabolic enzymes or perception machinery, have highlighted their crucial involvement in different agriculturally important traits, such as productivity, increased tolerance to various stresses and overall plant morphology. Furthermore, recent precise metabolomic analyses have elucidated the specific occurrence and distinct functions of different CK types in various plant species. Thus, smooth manipulation of active CK levels in a spatial and temporal way could be a very potent tool for plant biotechnology in the future. This review summarises recent advances in cytokinin research ranging from transgenic alteration of CK biosynthetic, degradation and glucosylation activities and CK perception to detailed elucidation of molecular processes, in which CKs work as a trigger in model plants. The first attempts to improve the quality of crop plants, focused on cereals are discussed, together with proposed mechanism of action of the responses involved. Copyright © 2011 Elsevier Inc. All rights reserved.

The Role of Energy Metabolism in Cutaneous Sulfur Mustard Injury

National Research Council Canada - National Science Library

Martens, M. E

2006-01-01

.... Our research has shown that inhibition of energy metabolism and depletion of energy stores are a significant consequence of HD exposure and that this inhibition is severe enough to be a determining factor in both cell survival and repair of HD-induced damage. In this paper we present an overview of our results and conclusions to date and briefly discuss their implications.

Relationships between energy balance and health traits of dairy cattle in early lactation.

Science.gov (United States)

Collard, B L; Boettcher, P J; Dekkers, J C; Petitclerc, D; Schaeffer, L R

2000-11-01

The objective of the study was to calculate phenotypic relationships between energy balance in early lactation and health and reproduction in that lactation. Data were 26,701 daily records of dry matter intake and milk production, periodic measures of milk composition and body weight, and all health and reproductive information from 140 multiparous Holstein cows. Daily energy balance was calculated by multiplying feed intake by the concentration of energy of the ration and subtracting the amount of energy required for maintenance (based on parity and body weight) and for milk production (based on yield and concentrations of fat, protein, and lactose). Six measures of energy balance were defined: mean daily energy balance during the first 20, 50, and 100 d of lactation; minimum daily energy balance; days in negative energy balance; and total energy deficit. Measures of health were the numbers of occurrences of each of the following during lactation: all udder problems, mastitis, all locomotive problems, laminitis, digestive problems, and reproductive problems. Reproductive traits were the number of days to first observed estrus and number of inseminations. Several significant relationships between energy balance and health were observed. Increased digestive and locomotive problems were associated with longer and more extreme periods of negative energy balance.

Lymphocytes Mitochondrial Physiology as Biomarker of Energy Metabolism during Fasted and Fed Conditions

Directory of Open Access Journals (Sweden)

Erika Cortez

2012-01-01

Full Text Available Mitochondria are central coordinators of energy metabolism, and changes of their physiology have long been associated with metabolic disorders. Thus, observations of energy dynamics in different cell types are of utmost importance. Therefore, tools with quick and easy handling are needed for consistent evaluations of such interventions. In this paper, our main hypothesis is that during different nutritional situations lymphocytes mitochondrial physiology could be associated with the metabolism of other cell types, such as cardiomyocytes, and consequently be used as metabolic biomarker. Blood lymphocytes and heart muscle fibers were obtained from both fed and 24 h-fasted mice, and mitochondrial analysis was assessed by high-resolution respirometry and western blotting. Carbohydrate-linked oxidation and fatty acid oxidation were significantly higher after fasting. Carnitine palmitoil transferase 1 and uncouple protein 2 contents were increased in the fasted group, while the glucose transporters 1 and 4 and the ratio phosphorylated AMP-activated protein kinase/AMPK did not change between groups. In summary, under a nutritional status modification, mitochondria demonstrated earlier adaptive capacity than other metabolic sensors such as glucose transporters and AMPK, suggesting the accuracy of mitochondria physiology of lymphocytes as biomarker for metabolic changes.

Fluctuating selection on basal metabolic rate.

Science.gov (United States)

Nilsson, Johan F; Nilsson, Jan-Åke

2016-02-01

BMR (Basal metabolic rate) is an important trait in animal life history as it represents a significant part of animal energy budgets. BMR has also been shown to be positively related to sustainable work rate and maximal thermoregulatory capacity. To this date, most of the studies have focused on the causes of interspecific and intraspecific variation in BMR, and fairly little is known about the fitness consequences of different metabolic strategies. In this study, we show that winter BMR affects local survival in a population of wild blue tits (Cyanistes caeruleus), but that the selection direction differs between years. We argue that this fluctuating selection is probably a consequence of varying winter climate with a positive relation between survival and BMR during cold and harsh conditions, but a negative relation during mild winters. This fluctuating selection can not only explain the pronounced variation in BMR in wild populations, but will also give us new insights into how energy turnover rates can shape the life-history strategies of animals. Furthermore, the study shows that the process of global warming may cause directional selection for a general reduction in BMR, affecting the general life-history strategy on the population level.

Mitochondrial biogenesis and energy production in differentiating murine stem cells: a functional metabolic study.

Science.gov (United States)

Han, Sungwon; Auger, Christopher; Thomas, Sean C; Beites, Crestina L; Appanna, Vasu D

2014-02-01

The significance of metabolic networks in guiding the fate of the stem cell differentiation is only beginning to emerge. Oxidative metabolism has been suggested to play a major role during this process. Therefore, it is critical to understand the underlying mechanisms of metabolic alterations occurring in stem cells to manipulate the ultimate outcome of these pluripotent cells. Here, using P19 murine embryonal carcinoma cells as a model system, the role of mitochondrial biogenesis and the modulation of metabolic networks during dimethyl sulfoxide (DMSO)-induced differentiation are revealed. Blue native polyacrylamide gel electrophoresis (BN-PAGE) technology aided in profiling key enzymes, such as hexokinase (HK) [EC 2.7.1.1], glucose-6-phosphate isomerase (GPI) [EC 5.3.1.9], pyruvate kinase (PK) [EC 2.7.1.40], Complex I [EC 1.6.5.3], and Complex IV [EC 1.9.3.1], that are involved in the energy budget of the differentiated cells. Mitochondrial adenosine triphosphate (ATP) production was shown to be increased in DMSO-treated cells upon exposure to the tricarboxylic acid (TCA) cycle substrates, such as succinate and malate. The increased mitochondrial activity and biogenesis were further confirmed by immunofluorescence microscopy. Collectively, the results indicate that oxidative energy metabolism and mitochondrial biogenesis were sharply upregulated in DMSO-differentiated P19 cells. This functional metabolic and proteomic study provides further evidence that modulation of mitochondrial energy metabolism is a pivotal component of the cellular differentiation process and may dictate the final destiny of stem cells.

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....

Comparison of the metabolic energy cost of overground and treadmill walking in older adults.

Science.gov (United States)

Berryman, Nicolas; Gayda, Mathieu; Nigam, Anil; Juneau, Martin; Bherer, Louis; Bosquet, Laurent

2012-05-01

We assessed whether the metabolic energy cost of walking was higher when measured overground or on a treadmill in a population of healthy older adults. We also assessed the association between the two testing modes. Participants (n = 20, 14 men and 6 women aged between 65 and 83 years of age) were randomly divided into two groups. Half of them went through the overground-treadmill sequence while the other half did the opposite order. A familiarization visit was held for each participant prior to the actual testing. For both modes of testing, five walking speeds were experimented (0.67, 0.89, 1.11, 1.33 and 1.67 m s(-1)). Oxygen uptake was monitored for all walking speeds. We found a significant difference between treadmill and track metabolic energy cost of walking, whatever the walking speed. The results show that walking on the treadmill requires more metabolic energy than walking overground for all experimental speeds (P < 0.05). The association between both measures was low to moderate (0.17 < ICC < 0.65), and the standard error of measurement represented 6.9-15.7% of the average value. These data indicate that metabolic energy cost of walking results from a treadmill test does not necessarily apply in daily overground activities. Interventions aiming at reducing the metabolic energy cost of walking should be assessed with the same mode as it was proposed during the intervention. If the treadmill mode is necessary for any purposes, functional overground walking tests should be implemented to obtain a more complete and specific evaluation.

Dietary Energy Source in Dairy Cows in Early Lactation: Metabolites and Metabolic Hormones

NARCIS (Netherlands)

Knegsel, van A.T.M.; Brand, van den H.; Graat, E.A.M.; Dijkstra, J.; Jorritsma, R.; Decuypere, M.P.; Tamminga, S.; Kemp, B.

2007-01-01

Negative energy balance-related metabolic disorders suggest that the balance between available lipogenic and glucogenic nutrients is important. The objectives of this study were to compare the effects of a glucogenic or a lipogenic diet on liver triacylglycerides (TAG), metabolites, and metabolic

Resting and exercise energy metabolism in weight-reduced adults with severe obesity.

Science.gov (United States)

Hames, Kazanna C; Coen, Paul M; King, Wendy C; Anthony, Steven J; Stefanovic-Racic, Maja; Toledo, Frederico G S; Lowery, Jolene B; Helbling, Nicole L; Dubé, John J; DeLany, James P; Jakicic, John M; Goodpaster, Bret H

2016-06-01

To determine effects of physical activity (PA) with diet-induced weight loss on energy metabolism in adults with severe obesity. Adults with severe obesity (n = 11) were studied across 6 months of intervention, then compared with controls with less severe obesity (n = 7) or normal weight (n = 9). Indirect calorimetry measured energy metabolism during exercise and rest. Markers of muscle oxidation were determined by immunohistochemistry. Data were presented as medians. The intervention induced 7% weight loss (P = 0.001) and increased vigorous PA by 24 min/wk (P = 0.02). During exercise, energy expenditure decreased, efficiency increased (P ≤ 0.03), and fatty acid oxidation (FAO) did not change. Succinate dehydrogenase increased (P = 0.001), but fiber type remained the same. Post-intervention subjects' resting metabolism remained similar to controls. Efficiency was lower in post-intervention subjects compared with normal-weight controls exercising at 25 W (P ≤ 0.002) and compared with all controls exercising at 60% VO2peak (P ≤ 0.019). Resting and exercise FAO of post-intervention subjects remained similar to adults with less severe obesity. Succinate dehydrogenase and fiber type were similar across all body weight statuses. While metabolic adaptations to PA during weight loss occur in adults with severe obesity, FAO does not change. Resulting FAO during rest and exercise remains similar to adults with less severe obesity. © 2016 The Obesity Society.

In silico search of energy metabolism inhibitors for alternative leishmaniasis treatments.

Science.gov (United States)

Silva, Lourival A; Vinaud, Marina C; Castro, Ana Maria; Cravo, Pedro Vítor L; Bezerra, José Clecildo B

2015-01-01

Leishmaniasis is a complex disease that affects mammals and is caused by approximately 20 distinct protozoa from the genus Leishmania. Leishmaniasis is an endemic disease that exerts a large socioeconomic impact on poor and developing countries. The current treatment for leishmaniasis is complex, expensive, and poorly efficacious. Thus, there is an urgent need to develop more selective, less expensive new drugs. The energy metabolism pathways of Leishmania include several interesting targets for specific inhibitors. In the present study, we sought to establish which energy metabolism enzymes in Leishmania could be targets for inhibitors that have already been approved for the treatment of other diseases. We were able to identify 94 genes and 93 Leishmania energy metabolism targets. Using each gene's designation as a search criterion in the TriTrypDB database, we located the predicted peptide sequences, which in turn were used to interrogate the DrugBank, Therapeutic Target Database (TTD), and PubChem databases. We identified 44 putative targets of which 11 are predicted to be amenable to inhibition by drugs which have already been approved for use in humans for 11 of these targets. We propose that these drugs should be experimentally tested and potentially used in the treatment of leishmaniasis.

[Specific growth rate and the rate of energy metabolism in the ontogenesis of axolotl, Ambystoma mexicanum (Amphibia: Ambystomatidae)].

Science.gov (United States)

Vladimirova, I G; Kleĭmenov, S Iu; Alekseeva, T A; Radzinskaia, L I

2003-01-01

Concordant changes in the rate of energy metabolism and specific growth rate of axolotls have been revealed. Several periods of ontogeny are distinguished, which differ in the ratio of energy metabolism to body weight and, therefore, are described by different allometric equations. It is suggested that the specific growth rate of an animal determines the type of dependence of energy metabolism on body weight.

Differential response to ocean acidification in physiological traits of Concholepas concholepas populations

Science.gov (United States)

Lardies, Marco A.; Arias, María Belén; Poupin, María Josefina; Manríquez, Patricio H.; Torres, Rodrigo; Vargas, Cristian A.; Navarro, Jorge M.; Lagos, Nelson A.

2014-07-01

Phenotypic adaptation to environmental fluctuations frequently occurs by preexisting plasticity and its role as a major component of variation in physiological diversity is being widely recognized. Few studies have considered the change in phenotypic flexibility among geographic populations in marine calcifiers to ocean acidification projections, despite the fact that this type of study provides understanding about how the organism may respond to this chemical change in the ocean. We examined the geographic variation in CO2 seawater concentrations in the phenotype and in the reaction norm of physiological traits using a laboratory mesocosm approach with short-term acclimation in two contrasting populations (Antofagasta and Calfuco) of the intertidal snail Concholepas concholepas. Our results show that elevated pCO2 conditions increase standard metabolic rates in both populations of the snail juveniles, likely due to the higher energy cost of homeostasis. Juveniles of C. concholepas in the Calfuco (southern) population showed a lower increment of metabolic rate in high-pCO2 environments concordant with a lesser gene expression of a heat shock protein with respect to the Antofagasta (northern) population. Combined these results indicate a negative effect of ocean acidification on whole-organism functioning of C. concholepas. Finally, the significant Population × pCO2 level interaction in both studied traits indicates that there is variation between populations in response to high-pCO2 conditions.

Sex differences of human cortical blood flow and energy metabolism

DEFF Research Database (Denmark)

Aanerud, Joel; Borghammer, Per; Rodell, Anders

2017-01-01

cerebral blood flow and cerebral metabolic rate of oxygen as functions of age in healthy volunteers of both sexes. Cerebral metabolic rate of oxygen did not change with age for either sex and there were no differences of mean values of cerebral metabolic rate of oxygen between men and women in cerebral...... cortex. Women had significant decreases of cerebral blood flow as function of age in frontal and parietal lobes. Young women had significantly higher cerebral blood flow than men in frontal and temporal lobes, but these differences had disappeared at age 65. The absent sex difference of cerebral energy...... turnover suggests that the known differences of synaptic density between the sexes are counteracted by opposite differences of individual synaptic activity....

Citrate Defines a Regulatory Link Between Energy Metabolism and the Liver Hormone Hepcidin

OpenAIRE

Ladeira Courelas da Silva, Ana Rita

2017-01-01

Iron plays a critical role as an oxygen carrier in hemoglobin as well as a constituent of iron-sulfur clusters. Increasing evidence suggests that mechanisms maintaining iron homeostasis cross-talk to intermediary metabolism. The liver hormone hepcidin is the key regulator of systemic iron metabolism. Hepcidin transcriptional control is linked to the nutrient-sensing mTOR pathway, proliferative signals, gluconeogenic responses during starvation and hormones that modulate energy metabolism. The...

Computational Flux Balance Analysis Predicts that Stimulation of Energy Metabolism in Astrocytes and their Metabolic Interactions with Neurons Depend on Uptake of K+ Rather than Glutamate.

Science.gov (United States)

DiNuzzo, Mauro; Giove, Federico; Maraviglia, Bruno; Mangia, Silvia

2017-01-01

Brain activity involves essential functional and metabolic interactions between neurons and astrocytes. The importance of astrocytic functions to neuronal signaling is supported by many experiments reporting high rates of energy consumption and oxidative metabolism in these glial cells. In the brain, almost all energy is consumed by the Na + /K + ATPase, which hydrolyzes 1 ATP to move 3 Na + outside and 2 K + inside the cells. Astrocytes are commonly thought to be primarily involved in transmitter glutamate cycling, a mechanism that however only accounts for few % of brain energy utilization. In order to examine the participation of astrocytic energy metabolism in brain ion homeostasis, here we attempted to devise a simple stoichiometric relation linking glutamatergic neurotransmission to Na + and K + ionic currents. To this end, we took into account ion pumps and voltage/ligand-gated channels using the stoichiometry derived from available energy budget for neocortical signaling and incorporated this stoichiometric relation into a computational metabolic model of neuron-astrocyte interactions. We aimed at reproducing the experimental observations about rates of metabolic pathways obtained by 13 C-NMR spectroscopy in rodent brain. When simulated data matched experiments as well as biophysical calculations, the stoichiometry for voltage/ligand-gated Na + and K + fluxes generated by neuronal activity was close to a 1:1 relationship, and specifically 63/58 Na + /K + ions per glutamate released. We found that astrocytes are stimulated by the extracellular K + exiting neurons in excess of the 3/2 Na + /K + ratio underlying Na + /K + ATPase-catalyzed reaction. Analysis of correlations between neuronal and astrocytic processes indicated that astrocytic K + uptake, but not astrocytic Na + -coupled glutamate uptake, is instrumental for the establishment of neuron-astrocytic metabolic partnership. Our results emphasize the importance of K + in stimulating the activation of

Geochemical constraints on sources of metabolic energy for chemolithoautotrophy in ultramafic-hosted deep-sea hydrothermal systems.

Science.gov (United States)

McCollom, Thomas M

2007-12-01

Numerical models are employed to investigate sources of chemical energy for autotrophic microbial metabolism that develop during mixing of oxidized seawater with strongly reduced fluids discharged from ultramafic-hosted hydrothermal systems on the seafloor. Hydrothermal fluids in these systems are highly enriched in H(2) and CH(4) as a result of alteration of ultramafic rocks (serpentinization) in the subsurface. Based on the availability of chemical energy sources, inferences are made about the likely metabolic diversity, relative abundance, and spatial distribution of microorganisms within ultramafic-hosted systems. Metabolic reactions involving H(2) and CH(4), particularly hydrogen oxidation, methanotrophy, sulfate reduction, and methanogenesis, represent the predominant sources of chemical energy during fluid mixing. Owing to chemical gradients that develop from fluid mixing, aerobic metabolisms are likely to predominate in low-temperature environments (energy per kilogram of hydrothermal fluid, while anaerobic metabolic reactions can supply about 1 kJ, which is sufficient to support a maximum of approximately 120 mg (dry weight) of primary biomass production by aerobic organisms and approximately 20-30 mg biomass by anaerobes. The results indicate that ultramafic-hosted systems are capable of supplying about twice as much chemical energy as analogous deep-sea hydrothermal systems hosted in basaltic rocks.

Energy Metabolism during Anaerobic Methane Oxidation in ANME Archaea

Science.gov (United States)

McGlynn, Shawn E.

2017-01-01

Anaerobic methane oxidation in archaea is often presented to operate via a pathway of “reverse methanogenesis”. However, if the cumulative reactions of a methanogen are run in reverse there is no apparent way to conserve energy. Recent findings suggest that chemiosmotic coupling enzymes known from their use in methylotrophic and acetoclastic methanogens—in addition to unique terminal reductases—biochemically facilitate energy conservation during complete CH4 oxidation to CO2. The apparent enzyme modularity of these organisms highlights how microbes can arrange their energy metabolisms to accommodate diverse chemical potentials in various ecological niches, even in the extreme case of utilizing “reverse” thermodynamic potentials. PMID:28321009

The Gut Microbiota Modulates Energy Metabolism in the Hibernating Brown Bear Ursus arctos.

Science.gov (United States)

Sommer, Felix; Ståhlman, Marcus; Ilkayeva, Olga; Arnemo, Jon M; Kindberg, Jonas; Josefsson, Johan; Newgard, Christopher B; Fröbert, Ole; Bäckhed, Fredrik

2016-02-23

Hibernation is an adaptation that helps many animals to conserve energy during food shortage in winter. Brown bears double their fat depots during summer and use these stored lipids during hibernation. Although bears seasonally become obese, they remain metabolically healthy. We analyzed the microbiota of free-ranging brown bears during their active phase and hibernation. Compared to the active phase, hibernation microbiota had reduced diversity, reduced levels of Firmicutes and Actinobacteria, and increased levels of Bacteroidetes. Several metabolites involved in lipid metabolism, including triglycerides, cholesterol, and bile acids, were also affected by hibernation. Transplantation of the bear microbiota from summer and winter to germ-free mice transferred some of the seasonal metabolic features and demonstrated that the summer microbiota promoted adiposity without impairing glucose tolerance, suggesting that seasonal variation in the microbiota may contribute to host energy metabolism in the hibernating brown bear. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Intestinal Microbiota Contributes to Energy Balance, Metabolic Inflammation, and Insulin Resistance in Obesity

Directory of Open Access Journals (Sweden)

Joseph F. Cavallari

2017-09-01

Full Text Available Obesity is associated with increased risk of developing metabolic diseases such as type 2 diabetes. The origins of obesity are multi-factorial, but ultimately rooted in increased host energy accumulation or retention. The gut microbiota has been implicated in control of host energy balance and nutrient extraction from dietary sources. The microbiota also impacts host immune status and dysbiosis-related inflammation can augment insulin resistance, independently of obesity. Advances in microbial metagenomic analyses and directly manipulating bacterial-host models of obesity have contributed to our understanding of the relationship between gut bacteria and metabolic disease. Foodborne, or drug-mediated perturbations to the gut microbiota can increase metabolic inflammation, insulin resistance, and dysglycemia. There is now some evidence that specific bacterial species can influence obesity and related metabolic defects such as insulin sensitivity. Components of bacteria are sufficient to impact obesity-related changes in metabolism. In fact, different microbial components derived from the bacterial cell wall can increase or decrease insulin resistance. Improving our understanding of the how components of the microbiota alter host metabolism is positioned to aid in the development of dietary interventions, avoiding triggers of dysbiosis, and generating novel therapeutic strategies to combat increasing rates of obesity and diabetes.

Genetic modulation of energy metabolism in birds through mitochondrial function

NARCIS (Netherlands)

Tieleman, B. Irene; Versteegh, Maaike A.; Fries, Anthony; Helm, Barbara; Dingemanse, Niels J.; Gibbs, H. Lisle; Williams, Joseph B.

2009-01-01

Despite their central importance for the evolution of physiological variation, the genetic mechanisms that determine energy expenditure in animals have largely remained unstudied. We used quantitative genetics to confirm that both mass-specific and whole-organism basal metabolic rate (BMR) were

Astrocyte glycogen and brain energy metabolism.

Science.gov (United States)

Brown, Angus M; Ransom, Bruce R

2007-09-01

The brain contains glycogen but at low concentration compared with liver and muscle. In the adult brain, glycogen is found predominantly in astrocytes. Astrocyte glycogen content is modulated by a number of factors including some neurotransmitters and ambient glucose concentration. Compelling evidence indicates that astrocyte glycogen breaks down during hypoglycemia to lactate that is transferred to adjacent neurons or axons where it is used aerobically as fuel. In the case of CNS white matter, this source of energy can extend axon function for 20 min or longer. Likewise, during periods of intense neural activity when energy demand exceeds glucose supply, astrocyte glycogen is degraded to lactate, a portion of which is transferred to axons for fuel. Astrocyte glycogen, therefore, offers some protection against hypoglycemic neural injury and ensures that neurons and axons can maintain their function during very intense periods of activation. These emerging principles about the roles of astrocyte glycogen contradict the long held belief that this metabolic pool has little or no functional significance.

Energy Metabolism in the Liver

OpenAIRE

Rui, Liangyou

2014-01-01

The liver is an essential metabolic organ, and its metabolic activity is tightly controlled by insulin and other metabolic hormones. Glucose is metabolized into pyruvate through glycolysis in the cytoplasm, and pyruvate is completely oxidized to generate ATP through the TCA cycle and oxidative phosphorylation in the mitochondria. In the fed state, glycolytic products are used to synthesize fatty acids through de novo lipogenesis. Long-chain fatty acids are incorporated into triacylglycerol, p...

Trait-based approaches to zooplankton communities

DEFF Research Database (Denmark)

Lichtman, E.; Ohman, M.D.; Kiørboe, Thomas

2013-01-01

in ecosystem models. Characterizing zooplankton traits and trade-offs will also be helpful in understanding the selection pressures and diversity patterns that emerge in different ecosystems along major environmental gradients. Zooplankton traits can be characterized according to their function and type. Some......; develop novel predictive models that explicitly incorporate traits and associated trade-offs; and utilize these traits to explain and predict zooplankton community structure and dynamics under different environmental conditions, including global change scenarios......Zooplankton are major primary consumers and predators in most aquatic ecosystems. They exhibit tremendous diversity of traits, ecological strategies and, consequently, impacts on other trophic levels and the cycling of materials and energy. An adequate representation of this diversity in community...

Lactate rescues neuronal sodium homeostasis during impaired energy metabolism.

Science.gov (United States)

Karus, Claudia; Ziemens, Daniel; Rose, Christine R

2015-01-01

Recently, we established that recurrent activity evokes network sodium oscillations in neurons and astrocytes in hippocampal tissue slices. Interestingly, metabolic integrity of astrocytes was essential for the neurons' capacity to maintain low sodium and to recover from sodium loads, indicating an intimate metabolic coupling between the 2 cell types. Here, we studied if lactate can support neuronal sodium homeostasis during impaired energy metabolism by analyzing whether glucose removal, pharmacological inhibition of glycolysis and/or addition of lactate affect cellular sodium regulation. Furthermore, we studied the effect of lactate on sodium regulation during recurrent network activity and upon inhibition of the glial Krebs cycle by sodium-fluoroacetate. Our results indicate that lactate is preferentially used by neurons. They demonstrate that lactate supports neuronal sodium homeostasis and rescues the effects of glial poisoning by sodium-fluoroacetate. Altogether, they are in line with the proposed transfer of lactate from astrocytes to neurons, the so-called astrocyte-neuron-lactate shuttle.

Lactate rescues neuronal sodium homeostasis during impaired energy metabolism

Science.gov (United States)

Karus, Claudia; Ziemens, Daniel; Rose, Christine R

2015-01-01

Recently, we established that recurrent activity evokes network sodium oscillations in neurons and astrocytes in hippocampal tissue slices. Interestingly, metabolic integrity of astrocytes was essential for the neurons' capacity to maintain low sodium and to recover from sodium loads, indicating an intimate metabolic coupling between the 2 cell types. Here, we studied if lactate can support neuronal sodium homeostasis during impaired energy metabolism by analyzing whether glucose removal, pharmacological inhibition of glycolysis and/or addition of lactate affect cellular sodium regulation. Furthermore, we studied the effect of lactate on sodium regulation during recurrent network activity and upon inhibition of the glial Krebs cycle by sodium-fluoroacetate. Our results indicate that lactate is preferentially used by neurons. They demonstrate that lactate supports neuronal sodium homeostasis and rescues the effects of glial poisoning by sodium-fluoroacetate. Altogether, they are in line with the proposed transfer of lactate from astrocytes to neurons, the so-called astrocyte-neuron-lactate shuttle. PMID:26039160

Military training elicits marked increases in plasma metabolomic signatures of energy metabolism, lipolysis, fatty acid oxidation, and ketogenesis.

Science.gov (United States)

Karl, J Philip; Margolis, Lee M; Murphy, Nancy E; Carrigan, Christopher T; Castellani, John W; Madslien, Elisabeth H; Teien, Hilde-Kristin; Martini, Svein; Montain, Scott J; Pasiakos, Stefan M

2017-09-01

Military training studies provide unique insight into metabolic responses to extreme physiologic stress induced by multiple stressor environments, and the impacts of nutrition in mediating these responses. Advances in metabolomics have provided new approaches for extending current understanding of factors modulating dynamic metabolic responses in these environments. In this study, whole-body metabolic responses to strenuous military training were explored in relation to energy balance and macronutrient intake by performing nontargeted global metabolite profiling on plasma collected from 25 male soldiers before and after completing a 4-day, 51-km cross-country ski march that produced high total daily energy expenditures (25.4 MJ/day [SD 2.3]) and severe energy deficits (13.6 MJ/day [SD 2.5]). Of 737 identified metabolites, 478 changed during the training. Increases in 88% of the free fatty acids and 91% of the acylcarnitines, and decreases in 88% of the mono- and diacylglycerols detected within lipid metabolism pathways were observed. Smaller increases in 75% of the tricarboxylic acid cycle intermediates, and 50% of the branched-chain amino acid metabolites detected were also observed. Changes in multiple metabolites related to lipid metabolism were correlated with body mass loss and energy balance, but not with energy and macronutrient intakes or energy expenditure. These findings are consistent with an increase in energy metabolism, lipolysis, fatty acid oxidation, ketogenesis, and branched-chain amino acid catabolism during strenuous military training. The magnitude of the energy deficit induced by undereating relative to high energy expenditure, rather than macronutrient intake, appeared to drive these changes, particularly within lipid metabolism pathways. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Changes in energy metabolism accompanying pitting in blueberries stored at low temperature.

Science.gov (United States)

Zhou, Qian; Zhang, Chunlei; Cheng, Shunchang; Wei, Baodong; Liu, Xiuying; Ji, Shujuan

2014-12-01

Low-temperature storage and transport of blueberries is widely practiced in commercial blueberry production. In this research, the storage life of blueberries was extended at low temperature, but fruit stored for 30 d at 0°C pitted after 2d at room-temperature. Fruit cellular structure and physiological parameters accompanying pitting in blueberries were changed. The objective of this research was to characterise properties of energy metabolism accompanying pitting in blueberries during storage, including adenosine phosphates and mitochondrial enzymes involved in stress responses. Physiological and metabolic disorders, changes in cell ultrastructure, energy content and ATPase enzyme activity were observed in pitting blueberries. Energy shortages and increased activity of phenylalanine ammonia lyase (PAL) and lipoxygenase (LOX) were observed in fruit kept at shelf life. The results suggested that sufficient available energy status and a stable enzymatic system in blueberries collectively contribute to improve chilling tolerance, thereby alleviating pitting and maintaining quality of blueberry fruit in long-term cold storage. Copyright © 2014 Elsevier Ltd. All rights reserved.

Within-Day Energy Deficiency and Metabolic Perturbation in Male Endurance Athletes.

Science.gov (United States)

Torstveit, Monica Klungland; Fahrenholtz, Ida; Stenqvist, Thomas B; Sylta, Øystein; Melin, Anna

2018-06-26

Endurance athletes are at increased risk of relative energy deficiency associated with metabolic perturbation and impaired health. We aimed to estimate and compare within-day energy balance in male athletes with suppressed and normal resting metabolic rate (RMR) and explore whether within-day energy deficiency is associated with endocrine markers of energy deficiency. A total of 31 male cyclists, triathletes, and long-distance runners recruited from regional competitive sports clubs were included. The protocol comprised measurements of RMR by ventilated hood and energy intake and energy expenditure to predict RMR ratio (measured RMR/predicted RMR), energy availability, 24-hr energy balance and within-day energy balance in 1-hr intervals, assessment of body composition by dual-energy X-ray absorptiometry, and blood plasma analysis. Subjects were categorized as having suppressed (RMR ratio   0.90, n = 11) RMR. Despite there being no observed differences in 24-hr energy balance or energy availability between the groups, subjects with suppressed RMR spent more time in an energy deficit exceeding 400 kcal (20.9 [18.8-21.8] hr vs. 10.8 [2.5-16.4], p = .023) and had larger single-hour energy deficits compared with subjects with normal RMR (3,265 ± 1,963 kcal vs. -1,340 ± 2,439, p = .023). Larger single-hour energy deficits were associated with higher cortisol levels (r = -.499, p = .004) and a lower testosterone:cortisol ratio (r = .431, p = .015), but no associations with triiodothyronine or fasting blood glucose were observed. In conclusion, within-day energy deficiency was associated with suppressed RMR and catabolic markers in male endurance athletes.

Hypothalamic energy metabolism is impaired by doxorubicin independently of inflammation in non-tumour-bearing rats.

Science.gov (United States)

Antunes, Barbara M M; Lira, Fabio Santos; Pimentel, Gustavo Duarte; Rosa Neto, José Cesar; Esteves, Andrea Maculano; Oyama, Lila Missae; de Souza, Cláudio Teodoro; Gonçalves, Cinara Ludvig; Streck, Emilio Luiz; Rodrigues, Bruno; dos Santos, Ronaldo Vagner; de Mello, Marco Túlio

2015-08-01

We sought to explore the effects of doxorubicin on inflammatory profiles and energy metabolism in the hypothalamus of rats. To investigate these effects, we formed two groups: a control (C) group and a Doxorubicin (DOXO) group. Sixteen rats were randomly assigned to either the control (C) or DOXO groups. The hypothalamus was collected. The levels of interleukin (IL)-1β, IL-6, IL-10, TNF-α and energy metabolism (malate dehydrogenase, complex I and III activities) were analysed in the hypothalamus. The DOXO group exhibited a decreased body weight (p hypothalamus is a central organ that regulates a great number of functions, such as food intake, temperature and energy expenditure, among others. Doxorubicin can lead to deep anorexia and metabolic chaos; thus, we observed the effect of this chemotherapeutic drug on the inflammation and metabolism in rats after the administration of doxorubicin in order to understand the central effect in the hypothalamus. Drug treatment by doxorubicin is used as a cancer therapy; however the use of this drug may cause harmful alterations to the metabolism. Thus, further investigations are needed on the impact of drug therapy over the long term. Copyright © 2015 John Wiley & Sons, Ltd.

LGR4 and its role in intestinal protection and energy metabolism

Directory of Open Access Journals (Sweden)

Ziru eLi

2015-08-01

Full Text Available Leucine-rich repeat-containing G protein-coupled receptors (LGRs were identified by the unique nature of their long leucine-rich repeat extracellular domains. Distinct from classical G protein-coupled receptors which act via G proteins, LGR4 functions mainly through Wnt/β-catenin signaling to regulate cell proliferation, differentiation, and adult stem cell homeostasis. LGR4 is widely expressed in tissues ranging from the reproductive system, urinary system, sensory organs, digestive system, and the central nervous system, indicating LGR4 may have multiple functions in development. Here we focus on the digestive system by reviewing its effects on crypt cells differentiation and stem cells maintenance, which are important for cell regeneration after injury. Through effects on Wnt/β-catenin signaling and cell proliferation, LGR4 and its endogenous ligands, R-spondins, are involved in colon tumorigenesis. LGR4 also contributes to regulation of energy metabolism, including food intake, energy expenditure and lipid metabolism, as well as pancreatic β-cell proliferation and insulin secretion. This review summarizes the identification of LGR4, its endogenous ligand, ligand-receptor binding and intracellular signaling. Physiological functions include intestinal development and energy metabolism. The potential effects of LGR4 and its ligand in the treatment of inflammatory bowel disease, chemoradiotherapy induced gut damage, colorectal cancer and diabetes are also discussed.

Going beyond energy intensity to understand the energy metabolism of nations: The case of Argentina

International Nuclear Information System (INIS)

Recalde, Marina; Ramos-Martin, Jesús

2012-01-01

The link between energy consumption and economic growth has been widely studied in the economic literature. Understanding this relationship is important from both an environmental and a socio-economic point of view, as energy consumption is crucial to economic activity and human environmental impact. This relevance is even higher for developing countries, since energy consumption per unit of output varies through the phases of development, increasing from an agricultural stage to an industrial one and then decreasing for certain service based economies. In the Argentinean case, the relevance of energy consumption to economic development seems to be particularly important. While energy intensity seems to exhibit a U-Shaped curve from 1990 to 2003 decreasing slightly after that year, total energy consumption increases along the period of analysis. Why does this happen? How can we relate this result with the sustainability debate? All these questions are very important due to Argentinean hydrocarbons dependence and due to the recent reduction in oil and natural gas reserves, which can lead to a lack of security of supply. In this paper we study Argentinean energy consumption pattern for the period 1990–2007, to discuss current and future energy and economic sustainability. To this purpose, we developed a conventional analysis, studying energy intensity, and a non conventional analysis, using the Multi-Scale Integrated Analysis of Societal and Ecosystem Metabolism (MuSIASEM) accounting methodology. Both methodologies show that the development process followed by Argentina has not been good enough to assure sustainability in the long term. Instead of improving energy use, energy intensity has increased. The current composition of its energy mix, and the recent economic crisis in Argentina, as well as its development path, are some of the possible explanations. -- Highlights: ► We analyze Argentinean energy consumption and social metabolism using MuSIASEM. �

Hypothalamic control of energy metabolism via the autonomic nervous system

NARCIS (Netherlands)

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

2010-01-01

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

The SCFA receptor GPR43 and energy metabolism

Directory of Open Access Journals (Sweden)

Ikuo eKimura

2014-06-01

Full Text Available Free fatty acids (FFAs are essential nutrients and act as signaling molecules in various cellular processes via binding with FFA receptors. Of these receptors, GPR43 is activated by short chain fatty acids (SCFAs; e.g., acetate, propionate, and butyrate. During feeding, SCFAs are produced by microbial fermentation of dietary fiber in the gut, and these SCFAs become important energy sources for the host. The gut microbiota affects nutrient acquisition and energy regulation of the host and can influence the development of obesity, insulin resistance, and diabetes. Recently, GPR43 has been reported to regulate host energy homeostasis in the gastrointestinal tract and adipose tissues. Hence, GPR43 is also thought to be a potential drug target for metabolic disorders, such as obesity and diabetes. In this review, we summarize the identification, structure, and activities of GPR43, with a focus on host energy regulation, and present an essential overview of our current understanding of its physiological roles in host energy regulation that is mediated by gut microbiota. We also discuss the potential for GPR43 as a therapeutic target.

AHSG tag single nucleotide polymorphisms associate with type 2 diabetes and dyslipidemia: studies of metabolic traits in 7,683 white Danish subjects

DEFF Research Database (Denmark)

Andersen, Gitte; Burgdorf, Kristoffer Sølvsten; Sparsø, Thomas

2008-01-01

been largely successful. We related seven frequent AHSG tag single nucleotide polymorphisms to a range of metabolic traits, including type 2 diabetes, obesity, and dyslipidemia. RESEARCH DESIGN AND METHODS: The polymorphisms were genotyped in 7,683 white Danish subjects using Taqman allelic...... with dyslipidemia (P = 0.003 and P(corr) = 0.009). Thr248Met (rs4917) tended to associate with lower fasting and post-oral glucose tolerance test serum insulin release (P = 0.02, P(corr) = 0.1 for fasting and P = 0.04, P(corr) = 0.2 for area under the insulin curve) and improved insulin sensitivity estimated...

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

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Alexandre Fisette

2016-10-01

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

Interplay Between Diet, Gut Microbiota, Immune Cells and Energy Metabolism in Obesity Development

DEFF Research Database (Denmark)

Danneskiold-Samsøe, Niels Banhos

Obesity and associated metabolic disorders such as type 2 diabetes are major causes of morbidity and mortality globally. A major contributor to development of the obesity pandemic has been the increasing intake of energy dense diets, consisting of dietary fats combined with high-glycemic carbohyd......Obesity and associated metabolic disorders such as type 2 diabetes are major causes of morbidity and mortality globally. A major contributor to development of the obesity pandemic has been the increasing intake of energy dense diets, consisting of dietary fats combined with high......-glycemic carbohydrates such as refined grains and sugars. The lack of sufficient therapeutic options for obesity, and the inability of most individuals to reduce energy intake or increase expenditure highlight the importance of understanding its underlying biological mechanisms. Obesity is associated with low...... in glucose intolerance without inflammatory changes in visceral fat or the liver, but with changes to the gut microbiota. Finally we find that fat cell specific activity of cyclooxygenase-2, an enzyme important for metabolism of fat, decreases body fat mass and increases insulin sensitivity associated...

Genetic association study with metabolic syndrome and metabolic-related traits in a cross-sectional sample and a 10-year longitudinal sample of chinese elderly population.

Directory of Open Access Journals (Sweden)

Jinghui Yang

Full Text Available BACKGROUND: The metabolic syndrome (MetS has been known as partly heritable, while the number of genetic studies on MetS and metabolic-related traits among Chinese elderly was limited. METHODS: A cross-sectional analysis was performed among 2 014 aged participants from September 2009 to June 2010 in Beijing, China. An additional longitudinal study was carried out among the same study population from 2001 to 2010. Biochemical profile and anthropometric parameters of all the participants were measured. The associations of 23 SNPs located within 17 candidate genes (MTHFR, PPARγ, LPL, INSIG, TCF7L2, FTO, KCNJ11, JAZF1, CDKN2A/B, ADIPOQ, WFS1, CDKAL1, IGF2BP2, KCNQ1, MTNR1B, IRS1, ACE with overweight and obesity, diabetes, metabolic phenotypes, and MetS were examined in both studies. RESULTS: In this Chinese elderly population, prevalence of overweight, central obesity, diabetes, dyslipidemia, hypertension, and MetS were 48.3%, 71.0%, 32.4%, 75.7%, 68.3% and 54.5%, respectively. In the cross-sectional analyses, no SNP was found to be associated with MetS. Genotype TT of SNP rs4402960 within the gene IGF2BP2 was associated with overweight (odds ratio (OR  = 0.479, 95% confidence interval (CI: 0.316-0.724, p = 0.001 and genotype CA of SNP rs1801131 within the gene MTHFR was associated with hypertension (OR = 1.560, 95% CI: 1.194-2.240, p = 0.001. However, these associations were not observed in the longitudinal analyses. CONCLUSIONS: The associations of SNP rs4402960 with overweight as well as the association of SNP rs1801131 with hypertension were found to be statistically significant. No SNP was identified to be associated with MetS in our study with statistical significance.

Unique flexibility in energy metabolism allows mycobacteria to combat starvation and hypoxia.

Directory of Open Access Journals (Sweden)

Michael Berney

Full Text Available Mycobacteria are a group of obligate aerobes that require oxygen for growth, but paradoxically have the ability to survive and metabolize under hypoxia. The mechanisms responsible for this metabolic plasticity are unknown. Here, we report on the adaptation of Mycobacterium smegmatis to slow growth rate and hypoxia using carbon-limited continuous culture. When M. smegmatis is switched from a 4.6 h to a 69 h doubling time at a constant oxygen saturation of 50%, the cells respond through the down regulation of respiratory chain components and the F1Fo-ATP synthase, consistent with the cells lower demand for energy at a reduced growth rate. This was paralleled by an up regulation of molecular machinery that allowed more efficient energy generation (i.e. Complex I and the use of alternative electron donors (e.g. hydrogenases and primary dehydrogenases to maintain the flow of reducing equivalents to the electron transport chain during conditions of severe energy limitation. A hydrogenase mutant showed a 40% reduction in growth yield highlighting the importance of this enzyme in adaptation to low energy supply. Slow growing cells at 50% oxygen saturation subjected to hypoxia (0.6% oxygen saturation responded by switching on oxygen scavenging cytochrome bd, proton-translocating cytochrome bc1-aa3 supercomplex, another putative hydrogenase, and by substituting NAD+-dependent enzymes with ferredoxin-dependent enzymes thus highlighting a new pattern of mycobacterial adaptation to hypoxia. The expression of ferredoxins and a hydrogenase provides a potential conduit for disposing of and transferring electrons in the absence of exogenous electron acceptors. The use of ferredoxin-dependent enzymes would allow the cell to maintain a high carbon flux through its central carbon metabolism independent of the NAD+/NADH ratio. These data demonstrate the remarkable metabolic plasticity of the mycobacterial cell and provide a new framework for understanding their

Novel Metabolic Attributes of the Genus Cyanothece, Comprising a Group of Unicellular Nitrogen-Fixing Cyanobacteria

Science.gov (United States)

Bandyopadhyay, Anindita; Elvitigala, Thanura; Welsh, Eric; Stöckel, Jana; Liberton, Michelle; Min, Hongtao; Sherman, Louis A.; Pakrasi, Himadri B.

2011-01-01

ABSTRACT The genus Cyanothece comprises unicellular cyanobacteria that are morphologically diverse and ecologically versatile. Studies over the last decade have established members of this genus to be important components of the marine ecosystem, contributing significantly to the nitrogen and carbon cycle. System-level studies of Cyanothece sp. ATCC 51142, a prototypic member of this group, revealed many interesting metabolic attributes. To identify the metabolic traits that define this class of cyanobacteria, five additional Cyanothece strains were sequenced to completion. The presence of a large, contiguous nitrogenase gene cluster and the ability to carry out aerobic nitrogen fixation distinguish Cyanothece as a genus of unicellular, aerobic nitrogen-fixing cyanobacteria. Cyanothece cells can create an anoxic intracellular environment at night, allowing oxygen-sensitive processes to take place in these oxygenic organisms. Large carbohydrate reserves accumulate in the cells during the day, ensuring sufficient energy for the processes that require the anoxic phase of the cells. Our study indicates that this genus maintains a plastic genome, incorporating new metabolic capabilities while simultaneously retaining archaic metabolic traits, a unique combination which provides the flexibility to adapt to various ecological and environmental conditions. Rearrangement of the nitrogenase cluster in Cyanothece sp. strain 7425 and the concomitant loss of its aerobic nitrogen-fixing ability suggest that a similar mechanism might have been at play in cyanobacterial strains that eventually lost their nitrogen-fixing ability. PMID:21972240

The metabolic vascular syndrome - guide to an individualized treatment.

Science.gov (United States)

Hanefeld, Markolf; Pistrosch, Frank; Bornstein, Stefan R; Birkenfeld, Andreas L

2016-03-01

In ancient Greek medicine the concept of a distinct syndrome (going together) was used to label 'a group of signs and symptoms' that occur together and 'characterize a particular abnormality and condition'. The (dys)metabolic syndrome is a common cluster of five pre-morbid metabolic-vascular risk factors or diseases associated with increased cardiovascular morbidity, fatty liver disease and risk of cancer. The risk for major complications such as cardiovascular diseases, NASH and some cancers develops along a continuum of risk factors into clinical diseases. Therefore we still include hyperglycemia, visceral obesity, dyslipidemia and hypertension as diagnostic traits in the definition according to the term 'deadly quartet'. From the beginning elevated blood pressure and hyperglycemia were core traits of the metabolic syndrome associated with endothelial dysfunction and increased risk of cardiovascular disease. Thus metabolic and vascular abnormalities are in extricable linked. Therefore it seems reasonable to extend the term to metabolic-vascular syndrome (MVS) to signal the clinical relevance and related risk of multimorbidity. This has important implications for integrated diagnostics and therapeutic approach. According to the definition of a syndrome the rapid global rise in the prevalence of all traits and comorbidities of the MVS is mainly caused by rapid changes in life-style and sociocultural transition resp. with over- and malnutrition, low physical activity and social stress as a common soil.

Natural compounds regulate energy metabolism by the modulating the activity of lipid-sensing nuclear receptors.

Science.gov (United States)

Goto, Tsuyoshi; Kim, Young-Il; Takahashi, Nobuyuki; Kawada, Teruo

2013-01-01

Obesity causes excess fat accumulation in various tissues, most notoriously in the adipose tissue, along with other insulin-responsive organs such as skeletal muscle and the liver, which predisposes an individual to the development of metabolic abnormalities. The molecular mechanisms underlying obesity-induced metabolic abnormalities have not been completely elucidated; however, in recent years, the search for therapies to prevent the development of obesity and obesity-associated metabolic disorders has increased. It is known that several nuclear receptors, when activated by specific ligands, regulate carbohydrate and lipid metabolism at the transcriptional level. The expression of lipid metabolism-related enzymes is directly regulated by the activity of various nuclear receptors via their interaction with specific response elements in promoters of those genes. Many natural compounds act as ligands of nuclear receptors and regulate carbohydrate and lipid metabolism by regulating the activities of these nuclear receptors. In this review, we describe our current knowledge of obesity, the role of lipid-sensing nuclear receptors in energy metabolism, and several examples of food factors that act as agonists or antagonists of nuclear receptors, which may be useful for the management of obesity and the accompanying energy metabolism abnormalities. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Energy metabolism and glutamate-glutamine cycle in the brain: a stoichiometric modeling perspective.

Science.gov (United States)

Massucci, Francesco A; DiNuzzo, Mauro; Giove, Federico; Maraviglia, Bruno; Castillo, Isaac Perez; Marinari, Enzo; De Martino, Andrea

2013-10-10

The energetics of cerebral activity critically relies on the functional and metabolic interactions between neurons and astrocytes. Important open questions include the relation between neuronal versus astrocytic energy demand, glucose uptake and intercellular lactate transfer, as well as their dependence on the level of activity. We have developed a large-scale, constraint-based network model of the metabolic partnership between astrocytes and glutamatergic neurons that allows for a quantitative appraisal of the extent to which stoichiometry alone drives the energetics of the system. We find that the velocity of the glutamate-glutamine cycle (Vcyc) explains part of the uncoupling between glucose and oxygen utilization at increasing Vcyc levels. Thus, we are able to characterize different activation states in terms of the tissue oxygen-glucose index (OGI). Calculations show that glucose is taken up and metabolized according to cellular energy requirements, and that partitioning of the sugar between different cell types is not significantly affected by Vcyc. Furthermore, both the direction and magnitude of the lactate shuttle between neurons and astrocytes turn out to depend on the relative cell glucose uptake while being roughly independent of Vcyc. These findings suggest that, in absence of ad hoc activity-related constraints on neuronal and astrocytic metabolism, the glutamate-glutamine cycle does not control the relative energy demand of neurons and astrocytes, and hence their glucose uptake and lactate exchange.

Energy metabolism and glutamate-glutamine cycle in the brain: a stoichiometric modeling perspective

Science.gov (United States)

2013-01-01

Background The energetics of cerebral activity critically relies on the functional and metabolic interactions between neurons and astrocytes. Important open questions include the relation between neuronal versus astrocytic energy demand, glucose uptake and intercellular lactate transfer, as well as their dependence on the level of activity. Results We have developed a large-scale, constraint-based network model of the metabolic partnership between astrocytes and glutamatergic neurons that allows for a quantitative appraisal of the extent to which stoichiometry alone drives the energetics of the system. We find that the velocity of the glutamate-glutamine cycle (Vcyc) explains part of the uncoupling between glucose and oxygen utilization at increasing Vcyc levels. Thus, we are able to characterize different activation states in terms of the tissue oxygen-glucose index (OGI). Calculations show that glucose is taken up and metabolized according to cellular energy requirements, and that partitioning of the sugar between different cell types is not significantly affected by Vcyc. Furthermore, both the direction and magnitude of the lactate shuttle between neurons and astrocytes turn out to depend on the relative cell glucose uptake while being roughly independent of Vcyc. Conclusions These findings suggest that, in absence of ad hoc activity-related constraints on neuronal and astrocytic metabolism, the glutamate-glutamine cycle does not control the relative energy demand of neurons and astrocytes, and hence their glucose uptake and lactate exchange. PMID:24112710

Energy metabolism in BPH/2J genetically hypertensive mice.

Science.gov (United States)

Jackson, Kristy L; Nguyen-Huu, Thu-Phuc; Davern, Pamela J; Head, Geoffrey A

2014-05-01

Recent evidence indicates that genetic hypertension in BPH/2J mice is sympathetically mediated, but these mice also have lower body weight (BW) and elevated locomotor activity compared with BPN/3J normotensive mice, suggestive of metabolic abnormalities. The aim of the present study was to determine whether hypertension in BPH/2J mice is associated with metabolic differences. Whole-body metabolic and cardiovascular parameters were measured over 24 h by indirect calorimetry and radiotelemetry respectively, in conscious young (10-13 weeks) and older (22-23 weeks) BPH/2J, normotensive BPN/3J and C57Bl6 mice. Blood pressure (BP) was greater in BPH/2J compared with both normotensive strains at both ages (PBPH/2J compared with BPN/3J mice (PBPH/2J and normotensive mice when adjusted for activity (P>0.1) suggesting differences in this relationship are not responsible for hypertension. EchoMRI revealed that percentage body composition was comparable in BPN/3J and BPH/2J mice (P>0.1) and both strains gained weight similarly with age (P=0.3). Taken together, the present findings indicate that hypertension in BPH/2J mice does not appear to be related to altered energy metabolism.

Energy metabolism of rat cerebral cortex, hypothalamus and hypophysis during ageing.

Science.gov (United States)

Villa, R F; Ferrari, F; Gorini, A

2012-12-27

Ageing is one of the main risk factors for brain disorders. According to the neuroendocrine theory, ageing modifies the sensitivity of hypothalamus-pituitary-adrenal axis to homoeostatic signals coming from the cerebral cortex. The relationships between the energy metabolism of these areas have not been considered yet, in particular with respect to ageing. For these reasons, this study was undertaken to systematically investigate in female Sprague-Dawley rats aged 4, 6, 12, 18, 24, 28 months and in 4-month-old male ones, the catalytic properties of energy-linked enzymes of the Krebs' cycle, electron transport chain, glutamate and related amino acids on different mitochondrial subpopulations, i.e. non-synaptic perikaryal and intra-synaptic (two types) mitochondria. The biochemical enzymatic pattern of these mitochondria shows different expression of the above-mentioned enzymatic activities in the investigated brain areas, including frontal cerebral cortex, hippocampus, striatum, hypothalamus and hypophysis. The study shows that: (i) the energy metabolism of the frontal cerebral cortex is poorly affected by physiological ageing; (ii) the biochemical machinery of non-synaptic perikaryal mitochondria is differently expressed in the considered brain areas; (iii) at 4-6 months, hypothalamus and hypophysis possess lower oxidative metabolism with respect to the frontal cerebral cortex while (iv), during ageing, the opposite situation occurs. We hypothesised that these metabolic modifications likely try to grant HPA functionality in response to the incoming external stress stimuli increased during ageing. It is particularly notable that age-related changes in brain bioenergetics and in mitochondrial functionality may be considered as remarkable factors during physiological ageing and should play important roles in predisposing the brain to physiopathological events, tightly related to molecular mechanisms evoked for pharmacological treatments. Copyright © 2012 IBRO

Regional cerebral energy metabolism during intravenous anesthesia with etomidate, ketamine or thiopental

International Nuclear Information System (INIS)

Davis, D.W.

1987-01-01

Regional brain glucose utilization (rCMRglc) was measured in rats during steady-state levels of intravenous anesthesia to determine if alterations in brain function due to anesthesia could provide information on the mechanisms of anesthesia. Intravenous anesthetics from three different chemical classes were studied: etomidate, ketamine and thiopental. All rCMRglc experiments were conducted in freely moving rats in isolation chambers, with the use of [6- 14 C] glucose and guantitative autoradiography. Etomidate caused a rostral-to-caudal gradient of depression of rCMRglc. The four doses of etomidate did not differ in their effects on energy metabolism. Sub-anesthetic (5 mg kg -1 ) and anesthetic (30 mg kg -1 ) doses of ketamine produced markedly different patterns of behavior. Brain energy metabolism during the sub-anesthetic dose was stimulated in most regions, while the anesthetic dose selectively stimulated the hippocampus, leaving most brain regions unaffected. Thiopental produced a dose-dependent reduction of rCMRglc in all gray matter regions. No brain region was selectively affected. Comparison of the drug-specific alterations of cerebral energy metabolism suggests these anesthetics do not act through a common mechanism. The hypothesis that each acts by binding to specific cell membrane receptors is consistent with these observations

Changes in Microbial Energy Metabolism Measured by Nanocalorimetry during Growth Phase Transitions

Science.gov (United States)

Robador, Alberto; LaRowe, Douglas E.; Finkel, Steven E.; Amend, Jan P.; Nealson, Kenneth H.

2018-01-01

Calorimetric measurements of the change in heat due to microbial metabolic activity convey information about the kinetics, as well as the thermodynamics, of all chemical reactions taking place in a cell. Calorimetric measurements of heat production made on bacterial cultures have recorded the energy yields of all co-occurring microbial metabolic reactions, but this is a complex, composite signal that is difficult to interpret. Here we show that nanocalorimetry can be used in combination with enumeration of viable cell counts, oxygen consumption rates, cellular protein content, and thermodynamic calculations to assess catabolic rates of an isolate of Shewanella oneidensis MR-1 and infer what fraction of the chemical energy is assimilated by the culture into biomass and what fraction is dissipated in the form of heat under different limiting conditions. In particular, our results demonstrate that catabolic rates are not necessarily coupled to rates of cell division, but rather, to physiological rearrangements of S. oneidensis MR-1 upon growth phase transitions. In addition, we conclude that the heat released by growing microorganisms can be measured in order to understand the physiochemical nature of the energy transformation and dissipation associated with microbial metabolic activity in conditions approaching those found in natural systems. PMID:29449836

Targeting energy metabolism in brain cancer with calorically restricted ketogenic diets.

Science.gov (United States)

Seyfried, Thomas N; Kiebish, Michael; Mukherjee, Purna; Marsh, Jeremy

2008-11-01

Information is presented on the calorically restricted ketogenic diet (CRKD) as an alternative therapy for brain cancer. In contrast to normal neurons and glia, which evolved to metabolize ketone bodies as an alternative fuel to glucose under energy-restricted conditions, brain tumor cells are largely glycolytic due to mitochondrial defects and have a reduced ability to metabolize ketone bodies. The CRKD is effective in managing brain tumor growth in animal models and in patients, and appears to act through antiangiogenic, anti-inflammatory, and proapoptotic mechanisms.

Effect of Roundup® (glyphosate formulation) in the energy metabolism and reproductive traits of Hyalella castroi (Crustacea, Amphipoda, Dogielinotidae).

Science.gov (United States)

Dutra, Bibiana Kaiser; Fernandes, Felipe Amorim; Failace, Daniela Motta; Oliveira, Guendalina Turcato

2011-01-01

Roundup(®) (glyphosate formulation) is a nonselective and posts emergent herbicide used for controlling aquatic weeds and different concentrations are used in cultures around the world. The objective of this investigation was to examine the effects of Roundup(®) (glyphosate formulation) on the biochemical composition, levels of lipoperoxidation, Na(+)/K(+)ATPase activity and reproductive traits in the Hyalella castroi. Amphipods were collected in summer 2009, in the southern Brazilian highlands. In the laboratory, the animals were kept in aquariums under controlled conditions for 7 days, and after this period they were exposed to 0.36, 0.52, 1.08 and 2.16 mg/l of glyphosate for 7 days. After the period of exposure, the animals were immediately frozen for determination of glycogen, proteins, lipids, triglycerides, cholesterol, levels of lipoperoxidation, and Na(+)/K(+)ATPase activity. During each day of the cultivation reproductive traits (number of reproductive pairs, ovigerous females and eggs in the marsupium) were observed. All concentrations of Roundup(®) induced significant decreases in all biochemical parameters and Na(+)/K(+)ATPase activity, and significant increase in lipoperoxidation levels. Showing this form a potentially toxic effect at very low concentrations, this pattern of results can lead to significant changes in trophic structure of limnic environments because these amphipods are important links in food chain in these habitats.

In vivo imaging of cerebral energy metabolism with two-photon fluorescence lifetime microscopy of NADH.

Science.gov (United States)

Yaseen, Mohammad A; Sakadžić, Sava; Wu, Weicheng; Becker, Wolfgang; Kasischke, Karl A; Boas, David A

2013-02-01

Minimally invasive, specific measurement of cellular energy metabolism is crucial for understanding cerebral pathophysiology. Here, we present high-resolution, in vivo observations of autofluorescence lifetime as a biomarker of cerebral energy metabolism in exposed rat cortices. We describe a customized two-photon imaging system with time correlated single photon counting detection and specialized software for modeling multiple-component fits of fluorescence decay and monitoring their transient behaviors. In vivo cerebral NADH fluorescence suggests the presence of four distinct components, which respond differently to brief periods of anoxia and likely indicate different enzymatic formulations. Individual components show potential as indicators of specific molecular pathways involved in oxidative metabolism.

Regulation of lipid metabolism by energy availability: a role for the central nervous system.

Science.gov (United States)

Nogueiras, R; López, M; Diéguez, C

2010-03-01

The central nervous system (CNS) is crucial in the regulation of energy homeostasis. Many neuroanatomical studies have shown that the white adipose tissue (WAT) is innervated by the sympathetic nervous system, which plays a critical role in adipocyte lipid metabolism. Therefore, there are currently numerous reports indicating that signals from the CNS control the amount of fat by modulating the storage or oxidation of fatty acids. Importantly, some CNS pathways regulate adipocyte metabolism independently of food intake, suggesting that some signals possess alternative mechanisms to regulate energy homeostasis. In this review, we mainly focus on how neuronal circuits within the hypothalamus, such as leptin- ghrelin-and resistin-responsive neurons, as well as melanocortins, neuropeptide Y, and the cannabinoid system exert their actions on lipid metabolism in peripheral tissues such as WAT, liver or muscle. Dissecting the complicated interactions between peripheral signals and neuronal circuits regulating lipid metabolism might open new avenues for the development of new therapies preventing and treating obesity and its associated cardiometabolic sequelae.

GH and IGF1: roles in energy metabolism of long-living GH mutant mice.

Science.gov (United States)

Brown-Borg, Holly M; Bartke, Andrzej

2012-06-01

Of the multiple theories to explain exceptional longevity, the most robust of these has centered on the reduction of three anabolic protein hormones, growth hormone (GH), insulin-like growth factor, and insulin. GH mutant mice live 50% longer and exhibit significant differences in several aspects of energy metabolism as compared with wild-type mice. Mitochondrial metabolism is upregulated in the absence of GH, whereas in GH transgenic mice and dwarf mice treated with GH, multiple aspects of these pathways are suppressed. Core body temperature is markedly lower in dwarf mice, yet whole-body metabolism, as measured by indirect calorimetry, is surprisingly higher in Ames dwarf and Ghr-/- mice compared with normal controls. Elevated adiponectin, a key antiinflammatory cytokine, is also very likely to contribute to longevity in these mice. Thus, several important components related to energy metabolism are altered in GH mutant mice, and these differences are likely critical in aging processes and life-span extension.

Milk metabolome relates enteric methane emission to milk synthesis and energy metabolism pathways.

Science.gov (United States)

Antunes-Fernandes, E C; van Gastelen, S; Dijkstra, J; Hettinga, K A; Vervoort, J

2016-08-01

still related to CH4 intensity when FPCM was included as covariate. The UDP-hexose B is an intermediate of lactose metabolism, and citrate is an important intermediate of Krebs cycle-related energy processes. Therefore, the negative correlation of UDP-hexose B and citrate with CH4 intensity may reflect a decrease in metabolic activity in the mammary gland. Our results suggest that an integrative approach including milk yield and composition, and dietary and animal traits will help to explain the biological metabolism of dairy cows in relation to methane CH4 emission. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Weak Satiety Responsiveness Is a Reliable Trait Associated with Hedonic Risk Factors for Overeating among Women.

Science.gov (United States)

Dalton, Michelle; Hollingworth, Sophie; Blundell, John; Finlayson, Graham

2015-09-04

Some individuals exhibit a weak satiety response to food and may be susceptible to overconsumption. The current study identified women showing consistently low or high satiety responses to standardised servings of food across four separate days and compared them on behavioural, psychological and physiological risk factors for overeating and future weight gain. In a crossover design, 30 female participants (age: 28.0 ± 10.6; body mass index (BMI): 23.1 ± 3.0) recorded sensations of hunger in the post-prandial period following four graded energy level breakfasts. Satiety quotients were calculated to compare individuals on satiety responsiveness across conditions. Body composition, resting metabolic rate (RMR), energy intake, food reward and craving, and eating behaviour traits were assessed under controlled laboratory conditions. A distinct low satiety phenotype (LSP) was identified with good consistency across separate study days. These individuals had a higher RMR, greater levels of disinhibition and reported feeling lower control over food cravings. Further, they consumed more energy and exhibited greater wanting for high-fat food. The inverse pattern of characteristics was observed in those exhibiting a consistently high satiety phenotype (HSP). Weak satiety responsiveness is a reliable trait identifiable using the satiety quotient. The LSP was characterised by distinct behavioural and psychological characteristics indicating a risk for overeating, compared to HSP.

Metabolic and functional characterization of effects of developmental temperature in Drosophila melanogaster

DEFF Research Database (Denmark)

Schou, Mads Fristrup; Kristensen, Torsten Nygaard; Pedersen, Anders

2017-01-01

, and in particular, how physiological stress at extreme temperatures may counteract beneficial acclimation responses at benign temperatures. We exposed Drosophila melanogaster to ten developmental temperatures covering their entire permissible temperature range. We obtained metabolic profiles and reaction norms...... for several functional traits: egg-to-adult viability, developmental time, and heat and cold tolerance. Females were more heat tolerant than males, whereas no sexual dimorphism was found in cold tolerance. A group of metabolites, mainly free amino acids, had linear reaction norms. Several energy carrying...

Environmental physiology: effects of energy-related pollutants on daily cycles of energy metabolism, motor activity, and thermoregulation

International Nuclear Information System (INIS)

Sacher, G.A.; Rosenberg, R.S.; Duffy, P.H.; Obermeyer, W.; Russell, J.J.

1979-01-01

This section contains a summary of research on the effects of energy-related pollutants on daily cycles of energy metabolism, motor activity, and thermoregulation. So far, mice have been exposed to fast neutron-gamma radiation or to the chemical effluents of an atmospheric pressure experimental fluidized-bed combustor. The physiological parameters measured included: O 2 consumption; CO 2 production; motor activity; and deep body temperatures

Multiple correlation analyses of metabolic and endocrine profiles with fertility in primiparous and multiparous cows.

Science.gov (United States)

Wathes, D C; Bourne, N; Cheng, Z; Mann, G E; Taylor, V J; Coffey, M P

2007-03-01

Results from 4 studies were combined (representing a total of 500 lactations) to investigate the relationships between metabolic parameters and fertility in dairy cows. Information was collected on blood metabolic traits and body condition score at 1 to 2 wk prepartum and at 2, 4, and 7 wk postpartum. Fertility traits were days to commencement of luteal activity, days to first service, days to conception, and failure to conceive. Primiparous and multiparous cows were considered separately. Initial linear regression analyses were used to determine relationships among fertility, metabolic, and endocrine traits at each time point. All metabolic and endocrine traits significantly related to fertility were included in stepwise multiple regression analyses alone (model 1), including peak milk yield and interval to commencement of luteal activity (model 2), and with the further addition of dietary group (model 3). In multiparous cows, extended calving to conception intervals were associated prepartum with greater concentrations of leptin and lesser concentrations of nonesterified fatty acids and urea, and postpartum with reduced insulin-like growth factor-I at 2 wk, greater urea at 7 wk, and greater peak milk yield. In primiparous cows, extended calving to conception intervals were associated with more body condition and more urea prepartum, elevated urea postpartum, and more body condition loss by 7 wk. In conclusion, some metabolic measurements were associated with poorer fertility outcomes. Relationships between fertility and metabolic and endocrine traits varied both according to the lactation number of the cow and with the time relative to calving.

Effects of reducing dietary crude protein and metabolic energy in ...

African Journals Online (AJOL)

The objective of this experiment was to determine the effects of a pure reduction in the dietary crude protein (CP) and metabolic energy (ME) contents on growth performance, nutrient digestibility, blood profile, faecal microflora and odour gas emission in weaned pigs. A total of 80 weaned piglets ((Landrace × Yorkshire) ...

Sleep fragmentation alters brain energy metabolism without modifying hippocampal electrophysiological response to novelty exposure.

Science.gov (United States)

Baud, Maxime O; Parafita, Julia; Nguyen, Audrey; Magistretti, Pierre J; Petit, Jean-Marie

2016-10-01

Sleep is viewed as a fundamental restorative function of the brain, but its specific role in neural energy budget remains poorly understood. Sleep deprivation dampens brain energy metabolism and impairs cognitive functions. Intriguingly, sleep fragmentation, despite normal total sleep duration, has a similar cognitive impact, and in this paper we ask the question of whether it may also impair brain energy metabolism. To this end, we used a recently developed mouse model of 2 weeks of sleep fragmentation and measured 2-deoxy-glucose uptake and glycogen, glucose and lactate concentration in different brain regions. In order to homogenize mice behaviour during metabolic measurements, we exposed them to a novel environment for 1 h. Using an intra-hippocampal electrode, we first showed that hippocampal electroencephalograph (EEG) response to exploration was unaltered by 1 or 14 days of sleep fragmentation. However, after 14 days, sleep fragmented mice exhibited a lower uptake of 2-deoxy-glucose in cortex and hippocampus and lower cortical lactate levels than control mice. Our results suggest that long-term sleep fragmentation impaired brain metabolism to a similar extent as total sleep deprivation without affecting the neuronal responsiveness of hippocampus to a novel environment. © 2016 European Sleep Research Society.

Sleep fragmentation alters brain energy metabolism without modifying hippocampal electrophysiological response to novelty exposure

KAUST Repository

Baud, Maxime O.

2016-05-03

© 2016 European Sleep Research Society. Sleep is viewed as a fundamental restorative function of the brain, but its specific role in neural energy budget remains poorly understood. Sleep deprivation dampens brain energy metabolism and impairs cognitive functions. Intriguingly, sleep fragmentation, despite normal total sleep duration, has a similar cognitive impact, and in this paper we ask the question of whether it may also impair brain energy metabolism. To this end, we used a recently developed mouse model of 2 weeks of sleep fragmentation and measured 2-deoxy-glucose uptake and glycogen, glucose and lactate concentration in different brain regions. In order to homogenize mice behaviour during metabolic measurements, we exposed them to a novel environment for 1 h. Using an intra-hippocampal electrode, we first showed that hippocampal electroencephalograph (EEG) response to exploration was unaltered by 1 or 14 days of sleep fragmentation. However, after 14 days, sleep fragmented mice exhibited a lower uptake of 2-deoxy-glucose in cortex and hippocampus and lower cortical lactate levels than control mice. Our results suggest that long-term sleep fragmentation impaired brain metabolism to a similar extent as total sleep deprivation without affecting the neuronal responsiveness of hippocampus to a novel environment.

Thyroid hormones correlate with resting metabolic rate, not daily energy expenditure, in two charadriiform seabirds

Directory of Open Access Journals (Sweden)

Kyle H. Elliott

2013-04-01

Thyroid hormones affect in vitro metabolic intensity, increase basal metabolic rate (BMR in the lab, and are sometimes correlated with basal and/or resting metabolic rate (RMR in a field environment. Given the difficulty of measuring metabolic rate in the field—and the likelihood that capture and long-term restraint necessary to measure metabolic rate in the field jeopardizes other measurements—we examined the possibility that circulating thyroid hormone levels were correlated with RMR in two free-ranging bird species with high levels of energy expenditure (the black-legged kittiwake, Rissa tridactyla, and thick-billed murre, Uria lomvia. Because BMR and daily energy expenditure (DEE are purported to be linked, we also tested for a correlation between thyroid hormones and DEE. We examined the relationships between free and bound levels of the thyroid hormones thyroxine (T4 and triiodothyronine (T3 with DEE and with 4-hour long measurements of post-absorptive and thermoneutral resting metabolism (resting metabolic rate; RMR. RMR but not DEE increased with T3 in both species; both metabolic rates were independent of T4. T3 and T4 were not correlated with one another. DEE correlated with body mass in kittiwakes but not in murres, presumably owing to the larger coefficient of variation in body mass during chick rearing for the more sexually dimorphic kittiwakes. We suggest T3 provides a good proxy for resting metabolism but not DEE in these seabird species.

Sleep fragmentation alters brain energy metabolism without modifying hippocampal electrophysiological response to novelty exposure

KAUST Repository

Baud, Maxime O.; Parafita, Julia; Nguyen, Audrey; Magistretti, Pierre J.; Petit, Jean-Marie

2016-01-01

© 2016 European Sleep Research Society. Sleep is viewed as a fundamental restorative function of the brain, but its specific role in neural energy budget remains poorly understood. Sleep deprivation dampens brain energy metabolism and impairs

Variation on biomass yield and morphological traits of energy grasses from the genus Miscanthus during the first years of crop establishment

Energy Technology Data Exchange (ETDEWEB)

Jezowski, S.; Glowacka, K.; Kaczmarek, Z. [Institute of Plant Genetics, Polish Academy of Sciences, ul. Strzeszynska 34, 60-479 Poznan (Poland)

2011-02-15

This study presents the results of investigations of variation, genotype x year interactions and genotype x year x location interactions for the yield and morphological traits of several selected clones of energy grasses of the genus Miscanthus. The analyses were performed on the best clones of selected hybrid plants, which were obtained within the species M. sinensis or are the result of interspecific hybridization of M. sinensis and M. sacchariflorus. Analyses were conducted on the basis of three-year field trials at two locations. The young plants produced from in vitro cultures were planted at a density of one plant per m{sup 2}. The early stages of plant development, from planting until peak yield in the third year of cultivation, were analysed. Statistical analyses performed on the yield and morphological traits as well as changes in these characteristics over the successive years of the study showed considerable genotypic variation for traits under study. Moreover, significant genotype x year interactions as well as genotype x year x location interactions were observed in terms of yield and morphological traits. Based on the collective results of the study, we suggest that apart from M. x giganteus particularly hybrids of M. sinensis x M. sacchariflorus, should be taken into consideration in genetic and breeding studies on the improvement of yield from energy grasses of the genus Miscanthus. (author)

Catalonia's energy metabolism: Using the MuSIASEM approach at different scales

International Nuclear Information System (INIS)

Ramos-Martin, Jesus; Canellas-Bolta, Silvia; Giampietro, Mario; Gamboa, Gonzalo

2009-01-01

This paper applies the so-called Multi-Scale Integrated Analysis of Societal and Ecosystem Metabolism (MuSIASEM), based on Georgescu-Roegen's fund-flow model, to the Spanish region of Catalonia. It arrives to the conclusion that within the context of the end of cheap oil, the current development model of the Catalan economy, based on the growth of low-productivity sectors such as services and construction, must be changed. The change is needed not only because of the increasing scarcity of affordable energy and the increasing environmental impact of present development, but also because of the aging population. Moreover, the situation experienced by Catalonia is similar to that of other European countries and many other developed countries. This implies that we can expect a wave of major structural changes in the economy of developed countries worldwide. To make things more challenging, according to current trends, the energy intensity and exosomatic energy metabolism of Catalonia will keep increasing in the near future. To avoid a reduction in the standard of living of Catalans due to a reduction in the available energy it is important that the Government of Catalonia implement major adjustments and conservation efforts in both the household and paid-work sectors.

An Integrative Approach to Energy Carbon and Redox Metabolism In Cyanobacterium Synechocystis

Energy Technology Data Exchange (ETDEWEB)

Dr. Ross Overbeek

2003-06-30

The main objectives for the first year were to produce a detailed metabolic reconstruction of synechocystis sp.pcc6803 especially in interrelated arrears of photosynthesis respiration and central carbon metabolism to support a more complete understanding and modeling of this organism. Additionally, IG, Inc. provided detailed bioinformatic analysis of selected functional systems related to carbon and energy generation and utilization, and of the corresponding pathways functional roles and individual genes to support wet lab experiments by collaborators.

Energy metabolism of overweight women before, during and after weight reduction, assessed by indirect calorimetry

NARCIS (Netherlands)

Groot, de C.P.G.M.

1988-01-01

Previous studies had suggested that periods of low energy intake evoke compensatory adaptations in energy metabolism, which retard weight loss, and promote weight regain when energy intake returns to normal. The aim of this thesis was to investigate whether a slimming (low-energy) diet based on

Body size, body composition, and metabolic profile explain higher energy expenditure in overweight children

Science.gov (United States)

Lower relative rates of energy expenditure (EE), increased energetic efficiency, and altered fuel utilization purportedly associated with obesity have not been demonstrated indisputably in overweight children. We hypothesized that differences in energy metabolism between nonoverweight and overweight...

Rhabdomyosarcoma cells show an energy producing anabolic metabolic phenotype compared with primary myocytes

Directory of Open Access Journals (Sweden)

Higashi Richard M

2008-10-01

Full Text Available Abstract Background The functional status of a cell is expressed in its metabolic activity. We have applied stable isotope tracing methods to determine the differences in metabolic pathways in proliferating Rhabdomysarcoma cells (Rh30 and human primary myocytes in culture. Uniformly 13C-labeled glucose was used as a source molecule to follow the incorporation of 13C into more than 40 marker metabolites using NMR and GC-MS. These include metabolites that report on the activity of glycolysis, Krebs' cycle, pentose phosphate pathway and pyrimidine biosynthesis. Results The Rh30 cells proliferated faster than the myocytes. Major differences in flux through glycolysis were evident from incorporation of label into secreted lactate, which accounts for a substantial fraction of the glucose carbon utilized by the cells. Krebs' cycle activity as determined by 13C isotopomer distributions in glutamate, aspartate, malate and pyrimidine rings was considerably higher in the cancer cells than in the primary myocytes. Large differences were also evident in de novo biosynthesis of riboses in the free nucleotide pools, as well as entry of glucose carbon into the pyrimidine rings in the free nucleotide pool. Specific labeling patterns in these metabolites show the increased importance of anaplerotic reactions in the cancer cells to maintain the high demand for anabolic and energy metabolism compared with the slower growing primary myocytes. Serum-stimulated Rh30 cells showed higher degrees of labeling than serum starved cells, but they retained their characteristic anabolic metabolism profile. The myocytes showed evidence of de novo synthesis of glycogen, which was absent in the Rh30 cells. Conclusion The specific 13C isotopomer patterns showed that the major difference between the transformed and the primary cells is the shift from energy and maintenance metabolism in the myocytes toward increased energy and anabolic metabolism for proliferation in the Rh30 cells

Fluvoxamine alters the activity of energy metabolism enzymes in the brain

Directory of Open Access Journals (Sweden)

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.

Discovering the desirable alleles contributing to the lignocellulosic biomass traits in Saccharum germplasm collections for energy cane improvement

Energy Technology Data Exchange (ETDEWEB)

Wang, Jianping [Univ. of Florida, Gainesville, FL (United States); Sandhu, Hardev [Univ. of Florida, Gainesville, FL (United States)

2017-03-23

1) The success in crop improvement programs depends largely on the extent of genetic variability available. Germplasm collections assembles all the available genetic resources and are critical for long-term crop improvement. This world sugarcane germplasm collection contains enormous genetic variability for various morphological traits, biomass yield components, adaptation and many quality traits, prospectively imbeds a large number of valuable alleles for biofuel traits such as high biomass yield, quantity and quality of lignocelluloses, stress tolerance, and nutrient use efficiency. The germplasm collection is of little value unless it is characterized and utilized for crop improvement. In this project, we phenotypically and genotypically characterized the sugarcane world germplasm collection (The results were published in two papers already and another two papers are to be published). This data will be made available for public to refer to for germplasm unitization specifically in the sugarcane and energy cane breeding programs. In addition, we are identifying the alleles contributing to the biomass traits in sugarcane germplasm. This part of project is very challenging due to the large genome and highly polyploid level of this crop. We firstly established a high throughput sugarcane genotyping pipeline in the genome and bioinformatics era (a paper is published in 2016). We identified and modified a software for genome-wide association analysis of polyploid species. The results of the alleles associated to the biomass traits will be published soon, which will help the scientific community understand the genetic makeup of the biomass components of sugarcane. Molecular breeders can develop markers for marker assisted selection of biomass traits improvement. Further, the development and release of new energy cane cultivars through this project not only improved genetic diversity but also improved dry biomass yields and resistance to diseases. These new cultivars

A20 modulates lipid metabolism and energy production to promote liver regeneration.

Directory of Open Access Journals (Sweden)

Scott M Damrauer

2011-03-01

Full Text Available Liver regeneration is clinically of major importance in the setting of liver injury, resection or transplantation. We have demonstrated that the NF-κB inhibitory protein A20 significantly improves recovery of liver function and mass following extended liver resection (LR in mice. In this study, we explored the Systems Biology modulated by A20 following extended LR in mice.We performed transcriptional profiling using Affymetrix-Mouse 430.2 arrays on liver mRNA retrieved from recombinant adenovirus A20 (rAd.A20 and rAd.βgalactosidase treated livers, before and 24 hours after 78% LR. A20 overexpression impacted 1595 genes that were enriched for biological processes related to inflammatory and immune responses, cellular proliferation, energy production, oxidoreductase activity, and lipid and fatty acid metabolism. These pathways were modulated by A20 in a manner that favored decreased inflammation, heightened proliferation, and optimized metabolic control and energy production. Promoter analysis identified several transcriptional factors that implemented the effects of A20, including NF-κB, CEBPA, OCT-1, OCT-4 and EGR1. Interactive scale-free network analysis captured the key genes that delivered the specific functions of A20. Most of these genes were affected at basal level and after resection. We validated a number of A20's target genes by real-time PCR, including p21, the mitochondrial solute carriers SLC25a10 and SLC25a13, and the fatty acid metabolism regulator, peroxisome proliferator activated receptor alpha. This resulted in greater energy production in A20-expressing livers following LR, as demonstrated by increased enzymatic activity of cytochrome c oxidase, or mitochondrial complex IV.This Systems Biology-based analysis unravels novel mechanisms supporting the pro-regenerative function of A20 in the liver, by optimizing energy production through improved lipid/fatty acid metabolism, and down-regulated inflammation. These findings

Hypothalamic Energy Metabolism Is Impaired By Doxorubicin Independently Of Inflammation In Non-tumour-bearing Rats.

OpenAIRE

Antunes, Barbara M M; Lira, Fabio Santos; Pimentel, Gustavo Duarte; Rosa Neto, José Cesar; Esteves, Andrea Maculano; Oyama, Lila Missae; de Souza, Cláudio Teodoro; Gonçalves, Cinara Ludvig; Streck, Emilio Luiz; Rodrigues, Bruno; dos Santos, Ronaldo Vagner; de Mello, Marco Túlio

2016-01-01

We sought to explore the effects of doxorubicin on inflammatory profiles and energy metabolism in the hypothalamus of rats. To investigate these effects, we formed two groups: a control (C) group and a Doxorubicin (DOXO) group. Sixteen rats were randomly assigned to either the control (C) or DOXO groups. The hypothalamus was collected. The levels of interleukin (IL)-1β, IL-6, IL-10, TNF-α and energy metabolism (malate dehydrogenase, complex I and III activities) were analysed in the hypothala...

Association of bovine leptin polymorphisms with energy output and energy storage traits in progeny tested Holstein-Friesian dairy cattle sires

Science.gov (United States)

2010-01-01

Background Leptin modulates appetite, energy expenditure and the reproductive axis by signalling via its receptor the status of body energy stores to the brain. The present study aimed to quantify the associations between 10 novel and known single nucleotide polymorphisms in genes coding for leptin and leptin receptor with performance traits in 848 Holstein-Friesian sires, estimated from performance of up to 43,117 daughter-parity records per sire. Results All single nucleotide polymorphisms were segregating in this sample population and none deviated (P > 0.05) from Hardy-Weinberg equilibrium. Complete linkage disequilibrium existed between the novel polymorphism LEP-1609, and the previously identified polymorphisms LEP-1457 and LEP-580. LEP-2470 associated (P body condition score, reduced milk yield and shorter gestation (P fertility in the Holstein-Friesian dairy cow. PMID:20670403

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

Science.gov (United States)

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.

Sex-specific influences of mtDNA mitotype and diet on mitochondrial functions and physiological traits in Drosophila melanogaster.

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Wen C Aw

Full Text Available Here we determine the sex-specific influence of mtDNA type (mitotype and diet on mitochondrial functions and physiology in two Drosophila melanogaster lines. In many species, males and females differ in aspects of their energy production. These sex-specific influences may be caused by differences in evolutionary history and physiological functions. We predicted the influence of mtDNA mutations should be stronger in males than females as a result of the organelle's maternal mode of inheritance in the majority of metazoans. In contrast, we predicted the influence of diet would be greater in females due to higher metabolic flexibility. We included four diets that differed in their protein: carbohydrate (P:C ratios as they are the two-major energy-yielding macronutrients in the fly diet. We assayed four mitochondrial function traits (Complex I oxidative phosphorylation, reactive oxygen species production, superoxide dismutase activity, and mtDNA copy number and four physiological traits (fecundity, longevity, lipid content, and starvation resistance. Traits were assayed at 11 d and 25 d of age. Consistent with predictions we observe that the mitotype influenced males more than females supporting the hypothesis of a sex-specific selective sieve in the mitochondrial genome caused by the maternal inheritance of mitochondria. Also, consistent with predictions, we found that the diet influenced females more than males.

Basal metabolic rate in relation to body composition and daily energy expenditure in the field vole, Microtus agrestis

NARCIS (Netherlands)

Meerlo, P; Bolle, L; Visser, GH; Masman, D; Daan, S

1997-01-01

Basal metabolic rate in the field vole (Microtus agrestis) was studied in relation to body composition and daily energy expenditure in the field Daily energy expenditure was measured by means of doubly labelled water ((D2O)-O-18). In the same individuals, basal metabolic rate was subsequently

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

Directory of Open Access Journals (Sweden)

Anne eDrougard

2015-02-01

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

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

Science.gov (United States)

Drougard, Anne; Fournel, Audren; Valet, Philippe; Knauf, Claude

2015-01-01

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

Practicing Tai Chi had lower energy metabolism than walking but similar health benefits in terms of aerobic fitness, resting energy expenditure, body composition and self-perceived physical health.

Science.gov (United States)

Hui, Stanley Sai-Chuen; Xie, Yao Jie; Woo, Jean; Kwok, Timothy Chi-Yui

2016-08-01

To examine the effects of Tai Chi and walking training on aerobic fitness, resting energy expenditure (REE), body composition, and quality of life; as well as analyzing the energy metabolism during exercises, to determine which one had better advantage in improving health status. Three hundred seventy-four middle-aged Chinese subjects who were recruited from nine geographic areas in Sha Tin were randomized into Tai Chi, walking, or control groups at area level. The 12-week (45min per day, 5days per week) Tai Chi or brisk walking training were conducted in respective intervention groups. Measures were performed at baseline and end of trial. Another 30 subjects were recruited to compare the energy metabolism between practicing Tai Chi and walking. The between-group difference of VO2max was 3.3ml/min/kg for Tai Chi vs. control and 3.7ml/min/kg for walking vs. control (both Pwalking. Regarding to energy metabolism test, the self-paced walking produced approximately 46% higher metabolic costs than Tai Chi. Practicing Tai Chi consumes a smaller amount of energy metabolism but similar health benefits as self-paced brisk walking. Copyright © 2016. Published by Elsevier Ltd.

Energy Metabolism of the Brain, Including the Cooperation between Astrocytes and Neurons, Especially in the Context of Glycogen Metabolism.

Science.gov (United States)

Falkowska, Anna; Gutowska, Izabela; Goschorska, Marta; Nowacki, Przemysław; Chlubek, Dariusz; Baranowska-Bosiacka, Irena

2015-10-29

Glycogen metabolism has important implications for the functioning of the brain, especially the cooperation between astrocytes and neurons. According to various research data, in a glycogen deficiency (for example during hypoglycemia) glycogen supplies are used to generate lactate, which is then transported to neighboring neurons. Likewise, during periods of intense activity of the nervous system, when the energy demand exceeds supply, astrocyte glycogen is immediately converted to lactate, some of which is transported to the neurons. Thus, glycogen from astrocytes functions as a kind of protection against hypoglycemia, ensuring preservation of neuronal function. The neuroprotective effect of lactate during hypoglycemia or cerebral ischemia has been reported in literature. This review goes on to emphasize that while neurons and astrocytes differ in metabolic profile, they interact to form a common metabolic cooperation.

High Glucose-Induced Cardiomyocyte Death May Be Linked to Unbalanced Branched-Chain Amino Acids and Energy Metabolism

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Xi Zhang

2018-04-01

Full Text Available High glucose-induced cardiomyocyte death is a common symptom in advanced-stage diabetic patients, while its metabolic mechanism is still poorly understood. The aim of this study was to explore metabolic changes in high glucose-induced cardiomyocytes and the heart of streptozotocin-induced diabetic rats by 1H-NMR-based metabolomics. We found that high glucose can promote cardiomyocyte death both in vitro and in vivo studies. Metabolomic results show that several metabolites exhibited inconsistent variations in vitro and in vivo. However, we also identified a series of common metabolic changes, including increases in branched-chain amino acids (BCAAs: leucine, isoleucine and valine as well as decreases in aspartate and creatine under high glucose condition. Moreover, a reduced energy metabolism could also be a common metabolic characteristic, as indicated by decreases in ATP in vitro as well as AMP, fumarate and succinate in vivo. Therefore, this study reveals that a decrease in energy metabolism and an increase in BCAAs metabolism could be implicated in high glucose-induced cardiomyocyte death.

AMP-Activated Protein Kinase (AMPK) Regulates Energy Metabolism through Modulating Thermogenesis in Adipose Tissue

Science.gov (United States)

Wu, Lingyan; Zhang, Lina; Li, Bohan; Jiang, Haowen; Duan, Yanan; Xie, Zhifu; Shuai, Lin; Li, Jia; Li, Jingya

2018-01-01

Obesity occurs when excess energy accumulates in white adipose tissue (WAT), whereas brown adipose tissue (BAT), which is specialized in dissipating energy through thermogenesis, potently counteracts obesity. White adipocytes can be converted to thermogenic “brown-like” cells (beige cells; WAT browning) under various stimuli, such as cold exposure. AMP-activated protein kinase (AMPK) is a crucial energy sensor that regulates energy metabolism in multiple tissues. However, the role of AMPK in adipose tissue function, especially in the WAT browning process, is not fully understood. To illuminate the effect of adipocyte AMPK on energy metabolism, we generated Adiponectin-Cre-driven adipose tissue-specific AMPK α1/α2 KO mice (AKO). These AKO mice were cold intolerant and their inguinal WAT displayed impaired mitochondrial integrity and biogenesis, and reduced expression of thermogenic markers upon cold exposure. High-fat-diet (HFD)-fed AKO mice exhibited increased adiposity and exacerbated hepatic steatosis and fibrosis and impaired glucose tolerance and insulin sensitivity. Meanwhile, energy expenditure and oxygen consumption were markedly decreased in the AKO mice both in basal conditions and after stimulation with a β3-adrenergic receptor agonist, CL 316,243. In contrast, we found that in HFD-fed obese mouse model, chronic AMPK activation by A-769662 protected against obesity and related metabolic dysfunction. A-769662 alleviated HFD-induced glucose intolerance and reduced body weight gain and WAT expansion. Notably, A-769662 increased energy expenditure and cold tolerance in HFD-fed mice. A-769662 treatment also induced the browning process in the inguinal fat depot of HFD-fed mice. Likewise, A-769662 enhanced thermogenesis in differentiated inguinal stromal vascular fraction (SVF) cells via AMPK signaling pathway. In summary, a lack of adipocyte AMPKα induced thermogenic impairment and obesity in response to cold and nutrient-overload, respectively

Frequency of feeding, weight reduction and energy metabolism.

Science.gov (United States)

Verboeket-van de Venne, W P; Westerterp, K R

1993-01-01

A study was conducted to investigate the effect of feeding frequency on the rate and composition of weight loss and 24 h energy metabolism in moderately obese women on a 1000 kcal/day diet. During four consecutive weeks fourteen female adults (age 20-58 years, BMI 25.4-34.9 kg/m2) restricted their food intake to 1000 kcal/day. Seven subjects consumed the diet in two meals daily (gorging pattern), the others consumed the diet in three to five meals (nibbling pattern). Body mass and body composition, obtained by deuterium dilution, were measured at the start of the experiment and after two and four weeks of dieting. Sleeping metabolic rate (SMR) was measured at the same time intervals using a respiration chamber. At the end of the experiment 24 h energy expenditure (24 h EE) and diet-induced thermogenesis (DIT) were assessed by a 36 h stay in the respiration chamber. There was no significant effect of the feeding frequency on the rate of weight loss, fat mass loss or fat-free mass loss. Furthermore, fat mass and fat-free mass contributed equally to weight loss in subjects on both gorging and nibbling diet. Feeding frequency had no significant effect on SMR after two or four weeks of dieting. The decrease in SMR after four weeks was significantly greater in subjects on the nibbling diet. 24 h EE and DIT were not significantly different between the two feeding regimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysing leadership traits in establishing effective leadership at Eskom

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J. Lekganyane

2006-12-01

Full Text Available Purpose: Leadership is one of the crucial modern topics in the field of management. A leadership trait is one of the three components to be considered in establishing leadership success. The other two components not assessed in this research are ideal leadership behaviour and situational factors. Managers must act as leaders as they have a critical role to play to ensure effective change. This paper explores the leadership traits relevant to middle managers acting as leaders at Eskom. Design/Methodology/Approach: A theoretical analysis of literature in the field of leadership is conducted with a further focus on leadership traits. Quantitative research is done within Eskom by means of an e-mail survey to a random sample of employees on middle management level. Areas of possible improvement and leadership traits excellence are identified. Recommendations are made regarding leadership traits. Findings: The broad leadership trait categories tested include: intelligence; flexibility; sensitivity to others; stability; dominance; high energy; integrity (honesty and ethics; and finally locus of control. The most dominant traits based on the perception of the respondents are that they possess integrity, intelligence, high energy and the ability to act as leaders. Leadership traits that require great attention and are not as dominant are sensitivity to others, flexibility and to some extent stability. Implications: Managers must have the leadership ability and trait to influence employees in order to communicate, direct, negotiate and motivate with success. Teamwork and a relationship of trust are required in the modern and changing organisation in order to be successful in achieving organisational goals. Originality / Value: South Africa as well as Southern Africa could face an energy crisis in the near future. As Eskom is currently facing growing demand for services and is experiencing limitations to provide this continuous increase in demand, managers

Energy metabolism and inflammation in brain aging and Alzheimer's disease.

Science.gov (United States)

Yin, Fei; Sancheti, Harsh; Patil, Ishan; Cadenas, Enrique

2016-11-01

The high energy demand of the brain renders it sensitive to changes in energy fuel supply and mitochondrial function. Deficits in glucose availability and mitochondrial function are well-known hallmarks of brain aging and are particularly accentuated in neurodegenerative disorders such as Alzheimer's disease. As important cellular sources of H 2 O 2 , mitochondrial dysfunction is usually associated with altered redox status. Bioenergetic deficits and chronic oxidative stress are both major contributors to cognitive decline associated with brain aging and Alzheimer's disease. Neuroinflammatory changes, including microglial activation and production of inflammatory cytokines, are observed in neurodegenerative diseases and normal aging. The bioenergetic hypothesis advocates for sequential events from metabolic deficits to propagation of neuronal dysfunction, to aging, and to neurodegeneration, while the inflammatory hypothesis supports microglia activation as the driving force for neuroinflammation. Nevertheless, growing evidence suggests that these diverse mechanisms have redox dysregulation as a common denominator and connector. An independent view of the mechanisms underlying brain aging and neurodegeneration is being replaced by one that entails multiple mechanisms coordinating and interacting with each other. This review focuses on the alterations in energy metabolism and inflammatory responses and their connection via redox regulation in normal brain aging and Alzheimer's disease. Interaction of these systems is reviewed based on basic research and clinical studies. Copyright © 2016 Elsevier Inc. All rights reserved.

Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.

Directory of Open Access Journals (Sweden)

Zari Dastani

Full Text Available Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8-1.2×10(-43. Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans, we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10(-4. We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10(-3, n = 22,044, increased triglycerides (p = 2.6×10(-14, n = 93,440, increased waist-to-hip ratio (p = 1.8×10(-5, n = 77,167, increased glucose two hours post oral glucose tolerance testing (p = 4.4×10(-3, n = 15,234, increased fasting insulin (p = 0.015, n = 48,238, but with lower in HDL-cholesterol concentrations (p = 4.5×10(-13, n = 96,748 and decreased BMI (p = 1.4×10(-4, n = 121,335. These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.

Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.

Science.gov (United States)

Dastani, Zari; Hivert, Marie-France; Timpson, Nicholas; Perry, John R B; Yuan, Xin; Scott, Robert A; Henneman, Peter; Heid, Iris M; Kizer, Jorge R; Lyytikäinen, Leo-Pekka; Fuchsberger, Christian; Tanaka, Toshiko; Morris, Andrew P; Small, Kerrin; Isaacs, Aaron; Beekman, Marian; Coassin, Stefan; Lohman, Kurt; Qi, Lu; Kanoni, Stavroula; Pankow, James S; Uh, Hae-Won; Wu, Ying; Bidulescu, Aurelian; Rasmussen-Torvik, Laura J; Greenwood, Celia M T; Ladouceur, Martin; Grimsby, Jonna; Manning, Alisa K; Liu, Ching-Ti; Kooner, Jaspal; Mooser, Vincent E; Vollenweider, Peter; Kapur, Karen A; Chambers, John; Wareham, Nicholas J; Langenberg, Claudia; Frants, Rune; Willems-Vandijk, Ko; Oostra, Ben A; Willems, Sara M; Lamina, Claudia; Winkler, Thomas W; Psaty, Bruce M; Tracy, Russell P; Brody, Jennifer; Chen, Ida; Viikari, Jorma; Kähönen, Mika; Pramstaller, Peter P; Evans, David M; St Pourcain, Beate; Sattar, Naveed; Wood, Andrew R; Bandinelli, Stefania; Carlson, Olga D; Egan, Josephine M; Böhringer, Stefan; van Heemst, Diana; Kedenko, Lyudmyla; Kristiansson, Kati; Nuotio, Marja-Liisa; Loo, Britt-Marie; Harris, Tamara; Garcia, Melissa; Kanaya, Alka; Haun, Margot; Klopp, Norman; Wichmann, H-Erich; Deloukas, Panos; Katsareli, Efi; Couper, David J; Duncan, Bruce B; Kloppenburg, Margreet; Adair, Linda S; Borja, Judith B; Wilson, James G; Musani, Solomon; Guo, Xiuqing; Johnson, Toby; Semple, Robert; Teslovich, Tanya M; Allison, Matthew A; Redline, Susan; Buxbaum, Sarah G; Mohlke, Karen L; Meulenbelt, Ingrid; Ballantyne, Christie M; Dedoussis, George V; Hu, Frank B; Liu, Yongmei; Paulweber, Bernhard; Spector, Timothy D; Slagboom, P Eline; Ferrucci, Luigi; Jula, Antti; Perola, Markus; Raitakari, Olli; Florez, Jose C; Salomaa, Veikko; Eriksson, Johan G; Frayling, Timothy M; Hicks, Andrew A; Lehtimäki, Terho; Smith, George Davey; Siscovick, David S; Kronenberg, Florian; van Duijn, Cornelia; Loos, Ruth J F; Waterworth, Dawn M; Meigs, James B; Dupuis, Josee; Richards, J Brent; Voight, Benjamin F; Scott, Laura J; Steinthorsdottir, Valgerdur; Dina, Christian; Welch, Ryan P; Zeggini, Eleftheria; Huth, Cornelia; Aulchenko, Yurii S; Thorleifsson, Gudmar; McCulloch, Laura J; Ferreira, Teresa; Grallert, Harald; Amin, Najaf; Wu, Guanming; Willer, Cristen J; Raychaudhuri, Soumya; McCarroll, Steve A; Hofmann, Oliver M; Segrè, Ayellet V; van Hoek, Mandy; Navarro, Pau; Ardlie, Kristin; Balkau, Beverley; Benediktsson, Rafn; Bennett, Amanda J; Blagieva, Roza; Boerwinkle, Eric; Bonnycastle, Lori L; Boström, Kristina Bengtsson; Bravenboer, Bert; Bumpstead, Suzannah; Burtt, Noël P; Charpentier, Guillaume; Chines, Peter S; Cornelis, Marilyn; Crawford, Gabe; Doney, Alex S F; Elliott, Katherine S; Elliott, Amanda L; Erdos, Michael R; Fox, Caroline S; Franklin, Christopher S; Ganser, Martha; Gieger, Christian; Grarup, Niels; Green, Todd; Griffin, Simon; Groves, Christopher J; Guiducci, Candace; Hadjadj, Samy; Hassanali, Neelam; Herder, Christian; Isomaa, Bo; Jackson, Anne U; Johnson, Paul R V; Jørgensen, Torben; Kao, Wen H L; Kong, Augustine; Kraft, Peter; Kuusisto, Johanna; Lauritzen, Torsten; Li, Man; Lieverse, Aloysius; Lindgren, Cecilia M; Lyssenko, Valeriya; Marre, Michel; Meitinger, Thomas; Midthjell, Kristian; Morken, Mario A; Narisu, Narisu; Nilsson, Peter; Owen, Katharine R; Payne, Felicity; Petersen, Ann-Kristin; Platou, Carl; Proença, Christine; Prokopenko, Inga; Rathmann, Wolfgang; Rayner, N William; Robertson, Neil R; Rocheleau, Ghislain; Roden, Michael; Sampson, Michael J; Saxena, Richa; Shields, Beverley M; Shrader, Peter; Sigurdsson, Gunnar; Sparsø, Thomas; Strassburger, Klaus; Stringham, Heather M; Sun, Qi; Swift, Amy J; Thorand, Barbara; Tichet, Jean; Tuomi, Tiinamaija; van Dam, Rob M; van Haeften, Timon W; van Herpt, Thijs; van Vliet-Ostaptchouk, Jana V; Walters, G Bragi; Weedon, Michael N; Wijmenga, Cisca; Witteman, Jacqueline; Bergman, Richard N; Cauchi, Stephane; Collins, Francis S; Gloyn, Anna L; Gyllensten, Ulf; Hansen, Torben; Hide, Winston A; Hitman, Graham A; Hofman, Albert; Hunter, David J; Hveem, Kristian; Laakso, Markku; Morris, Andrew D; Palmer, Colin N A; Rudan, Igor; Sijbrands, Eric; Stein, Lincoln D; Tuomilehto, Jaakko; Uitterlinden, Andre; Walker, Mark; Watanabe, Richard M; Abecasis, Goncalo R; Boehm, Bernhard O; Campbell, Harry; Daly, Mark J; Hattersley, Andrew T; Pedersen, Oluf; Barroso, Inês; Groop, Leif; Sladek, Rob; Thorsteinsdottir, Unnur; Wilson, James F; Illig, Thomas; Froguel, Philippe; van Duijn, Cornelia M; Stefansson, Kari; Altshuler, David; Boehnke, Michael; McCarthy, Mark I; Soranzo, Nicole; Wheeler, Eleanor; Glazer, Nicole L; Bouatia-Naji, Nabila; Mägi, Reedik; Randall, Joshua; Elliott, Paul; Rybin, Denis; Dehghan, Abbas; Hottenga, Jouke Jan; Song, Kijoung; Goel, Anuj; Lajunen, Taina; Doney, Alex; Cavalcanti-Proença, Christine; Kumari, Meena; Timpson, Nicholas J; Zabena, Carina; Ingelsson, Erik; An, Ping; O'Connell, Jeffrey; Luan, Jian'an; Elliott, Amanda; McCarroll, Steven A; Roccasecca, Rosa Maria; Pattou, François; Sethupathy, Praveen; Ariyurek, Yavuz; Barter, Philip; Beilby, John P; Ben-Shlomo, Yoav; Bergmann, Sven; Bochud, Murielle; Bonnefond, Amélie; Borch-Johnsen, Knut; Böttcher, Yvonne; Brunner, Eric; Bumpstead, Suzannah J; Chen, Yii-Der Ida; Chines, Peter; Clarke, Robert; Coin, Lachlan J M; Cooper, Matthew N; Crisponi, Laura; Day, Ian N M; de Geus, Eco J C; Delplanque, Jerome; Fedson, Annette C; Fischer-Rosinsky, Antje; Forouhi, Nita G; Franzosi, Maria Grazia; Galan, Pilar; Goodarzi, Mark O; Graessler, Jürgen; Grundy, Scott; Gwilliam, Rhian; Hallmans, Göran; Hammond, Naomi; Han, Xijing; Hartikainen, Anna-Liisa; Hayward, Caroline; Heath, Simon C; Hercberg, Serge; Hillman, David R; Hingorani, Aroon D; Hui, Jennie; Hung, Joe; Kaakinen, Marika; Kaprio, Jaakko; Kesaniemi, Y Antero; Kivimaki, Mika; Knight, Beatrice; Koskinen, Seppo; Kovacs, Peter; Kyvik, Kirsten Ohm; Lathrop, G Mark; Lawlor, Debbie A; Le Bacquer, Olivier; Lecoeur, Cécile; Li, Yun; Mahley, Robert; Mangino, Massimo; Martínez-Larrad, María Teresa; McAteer, Jarred B; McPherson, Ruth; Meisinger, Christa; Melzer, David; Meyre, David; Mitchell, Braxton D; Mukherjee, Sutapa; Naitza, Silvia; Neville, Matthew J; Orrù, Marco; Pakyz, Ruth; Paolisso, Giuseppe; Pattaro, Cristian; Pearson, Daniel; Peden, John F; Pedersen, Nancy L; Pfeiffer, Andreas F H; Pichler, Irene; Polasek, Ozren; Posthuma, Danielle; Potter, Simon C; Pouta, Anneli; Province, Michael A; Rayner, Nigel W; Rice, Kenneth; Ripatti, Samuli; Rivadeneira, Fernando; Rolandsson, Olov; Sandbaek, Annelli; Sandhu, Manjinder; Sanna, Serena; Sayer, Avan Aihie; Scheet, Paul; Seedorf, Udo; Sharp, Stephen J; Shields, Beverley; Sigurðsson, Gunnar; Sijbrands, Eric J G; Silveira, Angela; Simpson, Laila; Singleton, Andrew; Smith, Nicholas L; Sovio, Ulla; Swift, Amy; Syddall, Holly; Syvänen, Ann-Christine; Tönjes, Anke; Uitterlinden, André G; van Dijk, Ko Willems; Varma, Dhiraj; Visvikis-Siest, Sophie; Vitart, Veronique; Vogelzangs, Nicole; Waeber, Gérard; Wagner, Peter J; Walley, Andrew; Ward, Kim L; Watkins, Hugh; Wild, Sarah H; Willemsen, Gonneke; Witteman, Jaqueline C M; Yarnell, John W G; Zelenika, Diana; Zethelius, Björn; Zhai, Guangju; Zhao, Jing Hua; Zillikens, M Carola; Borecki, Ingrid B; Meneton, Pierre; Magnusson, Patrik K E; Nathan, David M; Williams, Gordon H; Silander, Kaisa; Bornstein, Stefan R; Schwarz, Peter; Spranger, Joachim; Karpe, Fredrik; Shuldiner, Alan R; Cooper, Cyrus; Serrano-Ríos, Manuel; Lind, Lars; Palmer, Lyle J; Hu, Frank B; Franks, Paul W; Ebrahim, Shah; Marmot, Michael; Kao, W H Linda; Pramstaller, Peter Paul; Wright, Alan F; Stumvoll, Michael; Hamsten, Anders; Buchanan, Thomas A; Valle, Timo T; Rotter, Jerome I; Penninx, Brenda W J H; Boomsma, Dorret I; Cao, Antonio; Scuteri, Angelo; Schlessinger, David; Uda, Manuela; Ruokonen, Aimo; Jarvelin, Marjo-Riitta; Peltonen, Leena; Mooser, Vincent; Sladek, Robert; Musunuru, Kiran; Smith, Albert V; Edmondson, Andrew C; Stylianou, Ioannis M; Koseki, Masahiro; Pirruccello, James P; Chasman, Daniel I; Johansen, Christopher T; Fouchier, Sigrid W; Peloso, Gina M; Barbalic, Maja; Ricketts, Sally L; Bis, Joshua C; Feitosa, Mary F; Orho-Melander, Marju; Melander, Olle; Li, Xiaohui; Li, Mingyao; Cho, Yoon Shin; Go, Min Jin; Kim, Young Jin; Lee, Jong-Young; Park, Taesung; Kim, Kyunga; Sim, Xueling; Ong, Rick Twee-Hee; Croteau-Chonka, Damien C; Lange, Leslie A; Smith, Joshua D; Ziegler, Andreas; Zhang, Weihua; Zee, Robert Y L; Whitfield, John B; Thompson, John R; Surakka, Ida; Spector, Tim D; Smit, Johannes H; Sinisalo, Juha; Scott, James; Saharinen, Juha; Sabatti, Chiara; Rose, Lynda M; Roberts, Robert; Rieder, Mark; Parker, Alex N; Pare, Guillaume; O'Donnell, Christopher J; Nieminen, Markku S; Nickerson, Deborah A; Montgomery, Grant W; McArdle, Wendy; Masson, David; Martin, Nicholas G; Marroni, Fabio; Lucas, Gavin; Luben, Robert; Lokki, Marja-Liisa; Lettre, Guillaume; Launer, Lenore J; Lakatta, Edward G; Laaksonen, Reijo; Kyvik, Kirsten O; König, Inke R; Khaw, Kay-Tee; Kaplan, Lee M; Johansson, Åsa; Janssens, A Cecile J W; Igl, Wilmar; Hovingh, G Kees; Hengstenberg, Christian; Havulinna, Aki S; Hastie, Nicholas D; Harris, Tamara B; Haritunians, Talin; Hall, Alistair S; Groop, Leif C; Gonzalez, Elena; Freimer, Nelson B; Erdmann, Jeanette; Ejebe, Kenechi G; Döring, Angela; Dominiczak, Anna F; Demissie, Serkalem; Deloukas, Panagiotis; de Faire, Ulf; Crawford, Gabriel; Chen, Yii-der I; Caulfield, Mark J; Boekholdt, S Matthijs; Assimes, Themistocles L; Quertermous, Thomas; Seielstad, Mark; Wong, Tien Y; Tai, E-Shyong; Feranil, Alan B; Kuzawa, Christopher W; Taylor, Herman A; Gabriel, Stacey B; Holm, Hilma; Gudnason, Vilmundur; Krauss, Ronald M; Ordovas, Jose M; Munroe, Patricia B; Kooner, Jaspal S; Tall, Alan R; Hegele, Robert A; Kastelein, John J P; Schadt, Eric E; Strachan, David P; Reilly, Muredach P; Samani, Nilesh J; Schunkert, Heribert; Cupples, L Adrienne; Sandhu, Manjinder S; Ridker, Paul M; Rader, Daniel J; Kathiresan, Sekar

2012-01-01

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10(-3), n = 22,044), increased triglycerides (p = 2.6×10(-14), n = 93,440), increased waist-to-hip ratio (p = 1.8×10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10(-13), n = 96,748) and decreased BMI (p = 1.4×10(-4), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.

The metabochip, a custom genotyping array for genetic studies of metabolic, cardiovascular, and anthropometric traits

DEFF Research Database (Denmark)

Voight, Benjamin F; Kang, Hyun Min; Ding, Jun

2012-01-01

Genome-wide association studies have identified hundreds of loci for type 2 diabetes, coronary artery disease and myocardial infarction, as well as for related traits such as body mass index, glucose and insulin levels, lipid levels, and blood pressure. These studies also have pointed to thousands...... dramatic cost efficiencies compared to designing single-trait follow-up reagents, and provides the opportunity to compare results across a range of related traits. The metabochip and similar custom genotyping arrays offer a powerful and cost-effective approach to follow-up large-scale genotyping...

A review of some metabolic changes in protein-energy malnutrition.

Science.gov (United States)

Akuyam, S A

2007-06-01

Protein-energy malnutrition (PEM) is a major public health problem in the tropical and subtropical regions of the world and often arises during protein and / or energy deficit due to nutritional inadequacy, infections and poor socio-economic and environmental conditions. It is the most common nutritional disorder affecting children in developing countries and the third most common disease of childhood in such countries. PEM has a lasting effect on immune functions, growth and development of children, learning ability, social adjustment, work efficiency and productivity of labour. It seems that many deaths from PEM occur as a result of outdated clinical practices and that improving these practices reduces the rate of morbidity and mortality. This paper reviews various metabolic changes in protein-energy malnutrition (PEM). It gives an overview of the theoretical basis for the understanding of the biochemical derangements in PEM. It aims at stimulating the paediatricians and clinical chemists to read more on the recent advances in this broad subject with the view to improving the understanding of the current laboratory investigation of PEM. This review demonstrates that the metabolic changes in PEM include water and electrolytes imbalance, amino acids and proteins deficiencies, carbohydrates and energy deficiencies, hypolipidaemias, hypolipoproteinaemias, hormonal imbalance, deficiency of anti-oxidant vitamins and enzymes, depression of cell-mediated immune complexes and decrease in amino acids and trace elements in skin and hair. The review therefore suggests that assessment of these conditions in PEM patients could improve the management of this group of patients and hence reduce the rate of morbidity and mortality from PEM.

Differential regulation of metabolic parameters by energy deficit and hunger.

Science.gov (United States)

Kitka, Tamás; Tuza, Sebestyén; Varga, Balázs; Horváth, Csilla; Kovács, Péter

2015-10-01

Hypocaloric diet decreases both energy expenditure (EE) and respiratory exchange rate (RER), affecting the efficacy of dieting inversely. Energy deficit and hunger may be modulated separately both in human and animal studies by drug treatment or food restriction. Thus it is important to separate the effects of energy deficit and hunger on EE and RER. Three parallel and analogous experiments were performed using three pharmacologically distinct anorectic drugs: rimonabant, sibutramine and tramadol. Metabolic parameters of vehicle- and drug-treated and pair-fed diet-induced obese mice from the three experiments underwent common statistical analysis to identify effects independent of the mechanisms of action. Diet-induced obesity (DIO) test of tramadol was also performed to examine its anti-obesity efficacy. RER was decreased similarly by drug treatments and paired feeding throughout the experiment irrespective of the cause of reduced food intake. Contrarily, during the passive phase, EE was decreased more by paired feeding than by both vehicle and drug treatment irrespective of the drug used. In the active phase, EE was influenced by the pharmacological mechanisms of action. Tramadol decreased body weight in the DIO test. Our results suggest that RER is mainly affected by the actual state of energy balance; conversely, EE is rather influenced by hunger. Therefore, pharmacological medications that decrease hunger may enhance the efficacy of a hypocaloric diet by maintaining metabolic rate. Furthermore, our results yield the proposal that effects of anorectic drugs on EE and RER should be determined compared to vehicle and pair-fed groups, respectively, in animal models. Copyright © 2015 Elsevier Inc. All rights reserved.

Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans

NARCIS (Netherlands)

Timmers, Silvie; Konings, Ellen; Bilet, Lena; Houtkooper, Riekelt H.; Weijer, van de Tineke; Hoeks, Joris; Krieken, van der Sophie; Ryu, Dongryeol; Kersten, Sander; Moonen-Kornips, Esther; Goossens, Gijs H.; Hesselink, Matthijs K.; Kunz, Iris; Schrauwen-Hinderling, Vera B.; Blaak, Ellen E.; Auwerx, Johan; Schrauwen, Patrick

2011-01-01

Resveratrol is a naturally occurring compound that profoundly affects energy metabolism and mitochondrial function and serves as a calorie restriction mimetic, at least in animal models of obesity. Here we treated 10 healthy, obese men with placebo and 150 mg/day resveratrol in a randomized

Disruption of quercetin metabolism by fungicide affects energy production in honey bees (Apis mellifera).

Science.gov (United States)

Mao, Wenfu; Schuler, Mary A; Berenbaum, May R

2017-03-07

Cytochrome P450 monooxygenases (P450) in the honey bee, Apis mellifera , detoxify phytochemicals in honey and pollen. The flavonol quercetin is found ubiquitously and abundantly in pollen and frequently at lower concentrations in honey. Worker jelly consumed during the first 3 d of larval development typically contains flavonols at very low levels, however. RNA-Seq analysis of gene expression in neonates reared for three days on diets with and without quercetin revealed that, in addition to up-regulating multiple detoxifying P450 genes, quercetin is a negative transcriptional regulator of mitochondrion-related nuclear genes and genes encoding subunits of complexes I, III, IV, and V in the oxidative phosphorylation pathway. Thus, a consequence of inefficient metabolism of this phytochemical may be compromised energy production. Several P450s metabolize quercetin in adult workers. Docking in silico of 121 pesticide contaminants of American hives into the active pocket of CYP9Q1, a broadly substrate-specific P450 with high quercetin-metabolizing activity, identified six triazole fungicides, all fungal P450 inhibitors, that dock in the catalytic site. In adults fed combinations of quercetin and the triazole myclobutanil, the expression of five of six mitochondrion-related nuclear genes was down-regulated. Midgut metabolism assays verified that adult bees consuming quercetin with myclobutanil metabolized less quercetin and produced less thoracic ATP, the energy source for flight muscles. Although fungicides lack acute toxicity, they may influence bee health by interfering with quercetin detoxification, thereby compromising mitochondrial regeneration and ATP production. Thus, agricultural use of triazole fungicides may put bees at risk of being unable to extract sufficient energy from their natural food.

Change in energy metabolism of in vitro produced embryos: an alternative to make them more cryoresistant?

Directory of Open Access Journals (Sweden)

Luzia Renata Oliveira Dias

2017-08-01

Full Text Available For the development of in vitro produced (IVP as well as in vivo produced bovine embryos, it is extremely important that their energy metabolism works properly because the embryo must be able to metabolize energy substrates that are necessary for producing energy. Lipids play an important role in early embryonic development, acting as source of energy for oocytes and embryos. However, it is known that oocytes and embryos, mainly IVP, accumulate large amounts of lipids in the cytoplasm. Although they are extremely important in embryonic development, lipids have been associated with the reduced survival of bovine embryos following cryopreservation. There is evidence that at least four different categories of lipids affect embryo survival after cryopreservation, including triglycerides (TAG, free fatty acids, cholesterol and phospholipids. Thus, many studies are being conducted to improve the resistance of IVP embryos to the cryopreservation process by reducing the concentration or removing the source of serum from the medium or by reducing oocyte/embryo lipids using mechanical or chemical means. Regarding the use of delipidating agents that reduce the uptake and synthesis of fatty acids (FA by cells, substances such as phenazine ethosulfate (PES, forskolin, L-carnitine and isomers of conjugated linoleic acid (CLA have been utilized. This review aims to address important issues related to embryonic energy metabolism, the importance of lipid metabolism and its relation to the cryopreservation of IVP bovine embryos by summarizing the latest research in this field.

Free fatty acid receptors and their role in regulation of energy metabolism.

Science.gov (United States)

Hara, Takafumi; Kimura, Ikuo; Inoue, Daisuke; Ichimura, Atsuhiko; Hirasawa, Akira

2013-01-01

The free fatty acid receptor (FFAR) is a G protein-coupled receptor (GPCR) activated by free fatty acids (FFAs), which play important roles not only as essential nutritional components but also as signaling molecules in numerous physiological processes. In the last decade, FFARs have been identified by the GPCR deorphanization strategy derived from the human genome database. To date, several FFARs have been identified and characterized as critical components in various physiological processes. FFARs are categorized according to the chain length of FFA ligands that activate each FFAR; FFA2 and FFA3 are activated by short chain FFAs, GPR84 is activated by medium-chain FFAs, whereas FFA1 and GPR120 are activated by medium- or long-chain FFAs. FFARs appear to act as physiological sensors for food-derived FFAs and digestion products in the gastrointestinal tract. Moreover, they are considered to be involved in the regulation of energy metabolism mediated by the secretion of insulin and incretin hormones and by the regulation of the sympathetic nerve systems, taste preferences, and inflammatory responses related to insulin resistance. Therefore, because FFARs can be considered to play important roles in physiological processes and various pathophysiological processes, FFARs have been targeted in therapeutic strategies for the treatment of metabolic disorders including type 2 diabetes and metabolic syndrome. In this review, we present a summary of recent progress regarding the understanding of their physiological roles in the regulation of energy metabolism and their potential as therapeutic targets.

Characterization of gene expression associated with drought avoidance and tolerance traits in a perennial grass species.

Directory of Open Access Journals (Sweden)

Peng Zhou

Full Text Available To understand molecular mechanisms of perennial grass adaptation to drought stress, genes associated with drought avoidance or tolerance traits were identified and their expression patterns were characterized in C4 hybrid bermudagrass [Cynodon dactylon (L. Pers.×C. transvaalensis Burtt Davy, cv. Tifway] and common bermudagrass (C. dactylon, cv. C299. Plants of drought-tolerant 'Tifway' and drought-sensitive 'C299' were exposed to drought for 5 d (mild stress and 10 d (severe stress by withholding irrigation in a growth chamber. 'Tifway' maintained significantly lower electrolyte leakage and higher relative water content than 'C299' at both 5 and 10 d of drought stress. Four cDNA libraries via suppression subtractive hybridization analysis were constructed and identified 277 drought-responsive genes in the two genotypes at 5 and 10 d of drought stress, which were mainly classified into the functional categories of stress defense, metabolism, osmoregulation, membrane system, signal and regulator, structural protein, protein synthesis and degradation, and energy metabolism. Quantitative-PCR analysis confirmed the expression of 36 drought up-regulated genes that were more highly expressed in drought-tolerant 'Tifway' than drought-sensitive 'C299', including those for drought avoidance traits, such as cuticle wax formation (CER1 and sterol desaturase, for drought tolerance traits, such as dehydration-protective proteins (dehydrins, HVA-22-like protein and oxidative stress defense (superoxide dismutase, dehydroascorbate reductase, 2-Cys peroxiredoxins, and for stress signaling (EREBP-4 like protein and WRKY transcription factor. The results suggest that the expression of genes for stress signaling, cuticle wax accumulation, antioxidant defense, and dehydration-protective protein accumulation could be critically important for warm-season perennial grass adaptation to long-term drought stress.

Mitochondrial energy metabolism of rat hippocampus after treatment with the antidepressants desipramine and fluoxetine.

Science.gov (United States)

Villa, Roberto Federico; Ferrari, Federica; Bagini, Laura; Gorini, Antonella; Brunello, Nicoletta; Tascedda, Fabio

2017-07-15

Alterations in mitochondrial functions have been hypothesized to participate in the pathogenesis of depression, because brain bioenergetic abnormalities have been detected in depressed patients by neuroimaging in vivo studies. However, this hypothesis is not clearly demonstrated in experimental studies: some suggest that antidepressants are inhibitors of mitochondrial metabolism, while others observe the opposite. In this study, the effects of 21-day treatment with desipramine (15 mg/kg) and fluoxetine (10 mg/kg) were examined on the energy metabolism of rat hippocampus, evaluating the catalytic activity of regulatory enzymes of mitochondrial energy-yielding metabolic pathways. Because of the micro-heterogeneity of brain mitochondria, we have distinguished between (a) non-synaptic mitochondria (FM) of neuronal perikaryon (post-synaptic compartment) and (b) intra-synaptic light (LM) and heavy (HM) mitochondria (pre-synaptic compartment). Desipramine and fluoxetine changed the catalytic activity of specific enzymes in the different types of mitochondria: (a) in FM, both drugs enhanced cytochrome oxidase and glutamate dehydrogenase, (b) in LM, the overall bioenergetics was unaffected and (c) in HM only desipramine increased malate dehydrogenase and decreased the activities of Electron Transport Chain Complexes. These results integrate the pharmacodynamic features of desipramine and fluoxetine at subcellular level, overcoming the previous conflicting data about the effects of antidepressants on brain energy metabolism, mainly referred to whole brain homogenates or to bulk of cerebral mitochondria. With the differentiation in non-synaptic and intra-synaptic mitochondria, this study demonstrates that desipramine and fluoxetine lead to adjustments in the mitochondrial bioenergetics respect to the energy requirements of pre- and post-synaptic compartments. Copyright © 2017 Elsevier Ltd. All rights reserved.

Teaching Energy Metabolism Using Scientific Articles: Implementation of a Virtual Learning Environment for Medical Students

Science.gov (United States)

de Espindola, Marina Bazzo; El-Bacha, Tatiana; Giannella, Tais Rabetti; Struchiner, Miriam; da Silva, Wagner S.; Da Poian, Andrea T.

2010-01-01

This work describes the use of a virtual learning environment (VLE) applied to the biochemistry class for undergraduate, first-year medical students at the Federal University of Rio de Janeiro. The course focused on the integration of energy metabolism, exploring metabolic adaptations in different physiological or pathological states such as…

Enzymes of energy metabolism in hatchlings of amazonian freshwater turtles (Testudines, Podocnemididae

Directory of Open Access Journals (Sweden)

WP. Duncan

Full Text Available The metabolic profiles of selected tissues were analyzed in hatchlings of the Amazonian freshwater turtles Podocnemis expansa, P. unifilis and P. sextuberculata. Metabolic design in these species was judged based on the key enzymes of energy metabolism, with special emphasis on carbohydrate, lipid, amino acid and ketone body metabolism. All species showed a high glycolytic potential in all sampled tissues. Based on low levels of hexokinase, glycogen may be an important fuel for these species. The high lactate dehydrogenase activity in the liver may play a significant role in carbohydrate catabolism, possibly during diving. Oxidative metabolism in P. sextuberculata appears to be designed for the use of lipids, amino acids and ketone bodies. The maximal activities of 3-hydroxyacyl-CoA dehydrogenase, malate dehydrogenase, glutamine dehydrogenase, alanine aminotransferase and succinyl-CoA keto transferase display high aerobic potential, especially in muscle and liver tissues of this species. Although amino acids and ketone bodies may be important fuels for oxidative metabolism, carbohydrates and lipids are the major fuels used by P. expansa and P. unifilis. Our results are consistent with the food habits and lifestyle of Amazonian freshwater turtles. The metabolic design, based on enzyme activities, suggests that hatchlings of P. unifilis and P. expansa are predominately herbivorous, whereas P. sextuberculata rely on a mixed diet of animal matter and vegetation.

Weak Satiety Responsiveness Is a Reliable Trait Associated with Hedonic Risk Factors for Overeating among Women

Directory of Open Access Journals (Sweden)

Michelle Dalton

2015-09-01

Full Text Available Some individuals exhibit a weak satiety response to food and may be susceptible to overconsumption. The current study identified women showing consistently low or high satiety responses to standardised servings of food across four separate days and compared them on behavioural, psychological and physiological risk factors for overeating and future weight gain. In a crossover design, 30 female participants (age: 28.0 ± 10.6; body mass index (BMI: 23.1 ± 3.0 recorded sensations of hunger in the post-prandial period following four graded energy level breakfasts. Satiety quotients were calculated to compare individuals on satiety responsiveness across conditions. Body composition, resting metabolic rate (RMR, energy intake, food reward and craving, and eating behaviour traits were assessed under controlled laboratory conditions. A distinct low satiety phenotype (LSP was identified with good consistency across separate study days. These individuals had a higher RMR, greater levels of disinhibition and reported feeling lower control over food cravings. Further, they consumed more energy and exhibited greater wanting for high-fat food. The inverse pattern of characteristics was observed in those exhibiting a consistently high satiety phenotype (HSP. Weak satiety responsiveness is a reliable trait identifiable using the satiety quotient. The LSP was characterised by distinct behavioural and psychological characteristics indicating a risk for overeating, compared to HSP.

Bone morphogenetic proteins in inflammation, glucose homeostasis and adipose tissue energy metabolism

DEFF Research Database (Denmark)

Grgurevic, Lovorka; Christensen, Gitte Lund; Schulz, Tim J

2016-01-01

implicated in pancreas development as well as control of adult glucose homeostasis. Lastly, we review the recently recognized role of BMPs in brown adipose tissue formation and their consequences for energy expenditure and adiposity. In summary, BMPs play a pivotal role in metabolism beyond their role...... homeostasis (anaemia, hemochromatosis) and oxidative damage. The second and third parts of this review focus on BMPs in the development of metabolic pathologies such as type-2 diabetes mellitus and obesity. The pancreatic beta cells are the sole source of the hormone insulin and BMPs have recently been...

Calorie Restriction-like Effects of 30 Days of Resveratrol Supplementation on Energy Metabolism and Metabolic Profile in Obese Humans

NARCIS (Netherlands)

Timmers, S.; Konings, E.; Bilet, L.; Houtkooper, R.H.; Weijer, van de T.; Goossens, G.H.; Hoeks, J.; Krieken, van der S.; Ryu, D.; Kersten, A.H.; Moonen-Kornips, E.; Hesselink, M.K.C.; Kunz, I.; Schrauwen-Hinderling, V.B.; Blaak, E.E.; Auwerx, J.; Schrauwen, P.

2011-01-01

Resveratrol is a natural compound that affects energy metabolism and mitochondrial function and serves as a calorie restriction mimetic, at least in animal models of obesity. Here, we treated 11 healthy, obese men with placebo and 150 mg/day resveratrol (resVida) in a randomized double-blind

Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans

NARCIS (Netherlands)

Timmers, Silvie; Konings, Ellen; Bilet, Lena; Houtkooper, Riekelt H.; van de Weijer, Tineke; Goossens, Gijs H.; Hoeks, Joris; van der Krieken, Sophie; Ryu, Dongryeol; Kersten, Sander; Moonen-Kornips, Esther; Hesselink, Matthijs K. C.; Kunz, Iris; Schrauwen-Hinderling, Vera B.; Blaak, Ellen E.; Auwerx, Johan; Schrauwen, Patrick

2011-01-01

Resveratrol is a natural compound that affects energy metabolism and mitochondrial function and serves as a calorie restriction mimetic, at least in animal models of obesity. Here, we treated 11 healthy, obese men with placebo and 150 mg/day resveratrol (resVida) in a randomized double-blind

Sex matters: The effects of biological sex on adipose tissue biology and energy metabolism

Directory of Open Access Journals (Sweden)

Teresa G. Valencak

2017-08-01

Full Text Available Adipose tissue is a complex and multi-faceted organ. It responds dynamically to internal and external stimuli, depending on the developmental stage and activity of the organism. The most common functional subunits of adipose tissue, white and brown adipocytes, regulate and respond to endocrine processes, which then determine metabolic rate as well as adipose tissue functions. While the molecular aspects of white and brown adipose biology have become clearer in the recent past, much less is known about sex-specific differences in regulation and deposition of adipose tissue, and the specific role of the so-called pink adipocytes during lactation in females. This review summarises the current understanding of adipose tissue dynamics with a focus on sex-specific differences in adipose tissue energy metabolism and endocrine functions, focussing on mammalian model organisms as well as human-derived data. In females, pink adipocytes trans-differentiate during pregnancy from subcutaneous white adipocytes and are responsible for milk-secretion in mammary glands. Overlooking biological sex variation may ultimately hamper clinical treatments of many aspects of metabolic disorders. Keywords: Body fatness, Adipose tissue, Sex-specific differences, Adipokines, Adipocytes, Obesity, Energy metabolism

Comparison of Various Indices of Energy Metabolism in Recumbent and Healthy Dairy Cows

OpenAIRE

Guyot, Hugues; Detilleux, Johann; Lebreton, Pascal; Garnier, Catherine; Bonvoisin, Marie; Rollin, Frederic; Sandersen, Charlotte

2017-01-01

Background Downer cow syndrome (DCS) is often diagnosed in dairy cattle during the early post-partum period. The etiology of this condition is not completely understood, as it can be related to the energetic or electrolyte metabolism, as well as to infectious diseases or to trauma. Hypothesis/Objectives The aim of this study is to compare energy metabolism and insulin sensitivity indices and various biochemical parameters between recumbent and healthy dairy cows. Animals A prospective study h...

Personality, tobacco consumption, physical inactivity, obesity markers, and metabolic components as risk factors for cardiovascular disease in the general population.

Science.gov (United States)

Pocnet, Cornelia; Antonietti, Jean-Philippe; Strippoli, Marie-Pierre F; Glaus, Jennifer; Rossier, Jérôme; Preisig, Martin

2017-09-01

The aim of this study was to investigate the relationship between personality traits, tobacco consumption, physical inactivity, obesity markers and metabolic components as cardiovascular risk factors (CVRFs). A total of 2543 participants from the general population (CoLaus|PsyCoLaus) had provided complete information on physical health and unhealthy behaviors and completed the Revised NEO Five-Factor Inventory. Our results show a strong cross-correlation between obesity markers and metabolic components suggesting that their combination could represent an important CVRF. Moreover, socio-demographic characteristics, tobacco consumption, and physical inactivity were associated with both obesity markers and metabolic components latent traits. The conscientiousness personality trait was significantly associated with obesity markers, but played a modest role. Indeed, higher conscientiousness was associated with lower level of obesity indicators. However, no link between personality and metabolic components were found. In sum, our data suggest that health related behaviours have more effect on the development of cardiovascular diseases than personality traits.

VAPB/ALS8 MSP ligands regulate striated muscle energy metabolism critical for adult survival in caenorhabditis elegans.

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Sung Min Han

Full Text Available Mutations in VAPB/ALS8 are associated with amyotrophic lateral sclerosis (ALS and spinal muscular atrophy (SMA, two motor neuron diseases that often include alterations in energy metabolism. We have shown that C. elegans and Drosophila neurons secrete a cleavage product of VAPB, the N-terminal major sperm protein domain (vMSP. Secreted vMSPs signal through Roundabout and Lar-like receptors expressed on striated muscle. The muscle signaling pathway localizes mitochondria to myofilaments, alters their fission/fusion balance, and promotes energy production. Here, we show that neuronal loss of the C. elegans VAPB homolog triggers metabolic alterations that appear to compensate for muscle mitochondrial dysfunction. When vMSP levels drop, cytoskeletal or mitochondrial abnormalities in muscle induce elevated DAF-16, the Forkhead Box O (FoxO homolog, transcription factor activity. DAF-16 promotes muscle triacylglycerol accumulation, increases ATP levels in adults, and extends lifespan, despite reduced muscle mitochondria electron transport chain activity. Finally, Vapb knock-out mice exhibit abnormal muscular triacylglycerol levels and FoxO target gene transcriptional responses to fasting and refeeding. Our data indicate that impaired vMSP signaling to striated muscle alters FoxO activity, which affects energy metabolism. Abnormalities in energy metabolism of ALS patients may thus constitute a compensatory mechanism counterbalancing skeletal muscle mitochondrial dysfunction.

Homozygous carriers of the G allele of rs4664447 of the glucagon gene (GCG) are characterised by decreased fasting and stimulated levels of insulin, glucagon and glucagon-like peptide (GLP)-1

DEFF Research Database (Denmark)

Torekov, S S; Ma, L; Grarup, N

2011-01-01

The glucagon gene (GCG) encodes several hormones important for energy metabolism: glucagon, oxyntomodulin and glucagon-like peptide (GLP)-1 and -2. Variants in GCG may associate with type 2 diabetes, obesity and/or related metabolic traits.......The glucagon gene (GCG) encodes several hormones important for energy metabolism: glucagon, oxyntomodulin and glucagon-like peptide (GLP)-1 and -2. Variants in GCG may associate with type 2 diabetes, obesity and/or related metabolic traits....

Genetic analysis of efficiency traits in Austrian dairy cattle and their relationships with body condition score and lameness.

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Köck, A; Ledinek, M; Gruber, L; Steininger, F; Fuerst-Waltl, B; Egger-Danner, C

2018-01-01

This study is part of a larger project whose overall objective was to evaluate the possibilities for genetic improvement of efficiency in Austrian dairy cattle. In 2014, a 1-yr data collection was carried out. Data from 6,519 cows kept on 161 farms were recorded. In addition to routinely recorded data (e.g., milk yield, fertility, disease data), data of novel traits [e.g., body weight (BW), body condition score (BCS), lameness score, body measurements] and individual feeding information and feed quality were recorded on each test-day. The specific objective of this study was to estimate genetic parameters for efficiency (related) traits and to investigate their relationships with BCS and lameness in Austrian Fleckvieh, Brown Swiss, and Holstein cows. The following efficiency (related) traits were considered: energy-corrected milk (ECM), BW, dry matter intake (DMI), energy intake (INEL), ratio of milk output to metabolic BW (ECM/BW 0.75 ), ratio of milk output to DMI (ECM/DMI), and ratio of milk energy output to total energy intake (LE/INEL, LE = energy in milk). For Fleckvieh, the heritability estimates of the efficiency (related) traits ranged from 0.11 for LE/INEL to 0.44 for BW. Heritabilities for BCS and lameness were 0.19 and 0.07, respectively. Repeatabilities were high and ranged from 0.30 for LE/INEL to 0.83 for BW. Heritability estimates were generally lower for Brown Swiss and Holstein, but repeatabilities were in the same range as for Fleckvieh. In all 3 breeds, more-efficient cows were found to have a higher milk yield, lower BW, slightly higher DMI, and lower BCS. Higher efficiency was associated with slightly fewer lameness problems, most likely due to the lower BW (especially in Fleckvieh) and higher DMI of the more-efficient cows. Body weight and BCS were positively correlated. Therefore, when selecting for a lower BW, BCS is required as additional information because, otherwise, no distinction between large animals with low BCS and smaller animals

Visceral metabolism and efficiency of energy use by ruminants

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Kozloski Gilberto Vilmar

2001-01-01

Full Text Available The visceral system (liver and portal-drained viscera represents an interface between diet and the animal, and it acts as the main site of regulation of nutrients that are used for maintenance, growth, lactation, reproduction, and physical activities of animals. However the functions carried out by visceral organs have, however, a significant energetic cost and are influenced by a variety of factors, such as the level of feed intake and diet composition, among others. As a result, variable quantities of substances are metabolized by them and, thus, the pattern and the quantity of nutrients available to the peripheral tissues can be quite different from those absorbed at the intestinal lumen. Probably, the major source of variation in the efficiency of utilization of metabolizable energy among feeds is associated mainly with visceral metabolism and it is unlikely that the ratio ketogenic/glucogenic of absorbed substances has determinant effect under physiological conditions.

Genetic networks of liver metabolism revealed by integration of metabolic and transcriptional profiling.

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Christine T Ferrara

2008-03-01

Full Text Available Although numerous quantitative trait loci (QTL influencing disease-related phenotypes have been detected through gene mapping and positional cloning, identification of the individual gene(s and molecular pathways leading to those phenotypes is often elusive. One way to improve understanding of genetic architecture is to classify phenotypes in greater depth by including transcriptional and metabolic profiling. In the current study, we have generated and analyzed mRNA expression and metabolic profiles in liver samples obtained in an F2 intercross between the diabetes-resistant C57BL/6 leptin(ob/ob and the diabetes-susceptible BTBR leptin(ob/ob mouse strains. This cross, which segregates for genotype and physiological traits, was previously used to identify several diabetes-related QTL. Our current investigation includes microarray analysis of over 40,000 probe sets, plus quantitative mass spectrometry-based measurements of sixty-seven intermediary metabolites in three different classes (amino acids, organic acids, and acyl-carnitines. We show that liver metabolites map to distinct genetic regions, thereby indicating that tissue metabolites are heritable. We also demonstrate that genomic analysis can be integrated with liver mRNA expression and metabolite profiling data to construct causal networks for control of specific metabolic processes in liver. As a proof of principle of the practical significance of this integrative approach, we illustrate the construction of a specific causal network that links gene expression and metabolic changes in the context of glutamate metabolism, and demonstrate its validity by showing that genes in the network respond to changes in glutamine and glutamate availability. Thus, the methods described here have the potential to reveal regulatory networks that contribute to chronic, complex, and highly prevalent diseases and conditions such as obesity and diabetes.

Comparison of cell wall metabolism in the pulp of three cultivars of 'Nanfeng' tangerine differing in mastication trait.

Science.gov (United States)

Lei, Ying; Liu, Yong-Zhong; Gu, Qing-Qing; Yang, Xiao-Yan; Deng, Xiu-Xin; Chen, Jin-Yin

2012-02-01

Like sweet orange (Citrus sinensis), tangerine (Citrus reticulata) is another citrus crop grown widely throughout the world. However, whether it shares a common mechanism with sweet orange in forming a given mastication trait is still unclear. In this study, three 'Nanfeng' tangerine cultivars, 'Yangxiao-26' ('YX-26') with inferior mastication trait, elite 'YX-26' with moderate mastication trait and 'Miguang' ('MG') with superior mastication trait, were selected to investigate the formation mechanism of mastication trait. 'MG' had the lowest contents of total pectin, protopectin and lignin and the highest gene expression levels of citrus polygalacturonase (PG) and pectin methylesterase (PME) at the end of fruit ripening, whereas 'YX-26' had the lowest water-soluble pectin (WSP) content, the highest lignin content and the lowest PG and PME expression levels. The contents of cellulose and hemicellulose were similar among the three tangerines. The fruit mastication trait of C. reticulata was determined by the proportions of WSP and protopectin as well as lignin content, not by cellulose and hemicellulose contents. Pectin content could be a major contribution to the feeling of mastication trait, while PG and PME exhibited an important role in forming a given mastication trait according to the present results as well as previous results for C. sinensis. Copyright © 2011 Society of Chemical Industry.

Metabolic substrate use and the turnover of endogenous energy reserves in broad-tailed hummingbirds (Selasphorus platycercus).

Science.gov (United States)

Carleton, Scott A; Bakken, Bradley Hartman; Del Rio, Carlos Martínez

2006-07-01

We fed broad-tailed hummingbirds (Selasphorus platycercus) diets of contrasting carbon isotope composition and measured changes in the delta(13)C of expired breath through time. By measuring the delta(13)C in the breath of fed and fasted birds we were able to quantify the fraction of metabolism fueled by assimilated sugars and endogenous energy reserves. These measurements also allowed us to estimate the fractional turnover of carbon in the hummingbirds' energy reserves. When hummingbirds were feeding, they fueled their metabolism largely ( approximately 90%) with assimilated sugars. The rate of carbon isotope incorporation into the energy reserves of hummingbirds was higher when birds were gaining as opposed to losing body mass. The average residence time of a carbon atom in the hummingbirds' energy reserves ranged from 1 to 2 days.

Aspects of Energy Metabolism in Mangalitsa Pigs Exposed at Thermic Neutral Temperature

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Monica Pârvu

2011-10-01

Full Text Available The studies aimed the energy metabolism determination in Mangalitsa pigs exposed at thermic neutral temperature, compared to Large White pigs. The experimental period was between 80 and 100 kg liveweight. The animals had free access to standard, isoprotein and isocalory diets, with 13.5% crude protein (CP and 3100 kcal/kg metabolizable energy. Feed intake was measured on a daily basis. The energy-protein balance was calculated on the basis of comparative slaughter made at the beginning and end of the experiment. The metabolizable energy (MEc was estimated by chemical analysis (feed and excreta using mathematical modelling and the Whittemore’s formula. The metabolizable energy utilization efficiency was 0.61 at Large White and 0.53 at Mangalitsa.

Glutamate dehydrogenase is essential to sustain neuronal oxidative energy metabolism during stimulation

DEFF Research Database (Denmark)

Hohnholt, Michaela C; Andersen, Vibe H; Andersen, Jens V

2017-01-01

by glutamate was significantly lower in brain mitochondria from GDH KO mice and synaptosomes were not able to increase their respiration upon an elevated energy demand. The role of GDH for metabolism of glutamine and the respiratory capacity underscore the importance of GDH for neurons particularly during...

A potential mechanism of energy-metabolism oscillation in an aerobic chemostat culture of the yeast Saccharomyces cerevisiae.

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Xu, Zhaojun; Tsurugi, Kunio

2006-04-01

The energy-metabolism oscillation in aerobic chemostat cultures of yeast is a periodic change of the respiro-fermentative and respiratory phase. In the respiro-fermentative phase, the NADH level was kept high and respiration was suppressed, and glucose was anabolized into trehalose and glycogen at a rate comparable to that of catabolism. On the transition to the respiratory phase, cAMP levels increased triggering the breakdown of storage carbohydrates and the increased influx of glucose into the glycolytic pathway activated production of glycerol and ethanol consuming NADH. The resulting increase in the NAD(+)/NADH ratio stimulated respiration in combination with a decrease in the level of ATP, which was consumed mainly in the formation of biomass accompanying budding, and the accumulated ethanol and glycerol were gradually degraded by respiration via NAD(+)-dependent oxidation to acetate and the respiratory phase ceased after the recovery of NADH and ATP levels. However, the mRNA levels of both synthetic and degradative enzymes of storage carbohydrates were increased around the early respiro-fermentative phase, when storage carbohydrates are being synthesized, suggesting that the synthetic enzymes were expressed directly as active forms while the degradative enzymes were activated late by cAMP. In summary, the energy-metabolism oscillation is basically regulated by a feedback loop of oxido-reductive reactions of energy metabolism mediated by metabolites like NADH and ATP, and is modulated by metabolism of storage carbohydrates in combination of post-translational and transcriptional regulation of the related enzymes. A potential mechanism of energy-metabolism oscillation is proposed.

Exercising for Life? Energy Metabolism, Body Composition, and Longevity in Mice Exercising at Different Intensities

NARCIS (Netherlands)

Vaanholt, Lobke M.; Daan, Serge; Garland, Theodore; Visser, G. Henk; Garland Jr., Theodore

2010-01-01

Studies that have found a positive influence of moderate, non-exhaustive exercise on life expectancy contradict the rate-of-living theory, which predicts that high energy expenditure in exercising animals should shorten life. We investigated effects of exercise on energy metabolism and life span in

Formate as an energy source for microbial metabolism in chemosynthetic zones of hydrothermal ecosystems.

Science.gov (United States)

Windman, Todd; Zolotova, Natalya; Schwandner, Florian; Shock, Everett L

2007-12-01

Formate, a simple organic acid known to support chemotrophic hyperthermophiles, is found in hot springs of varying temperature and pH. However, it is not yet known how metabolic strategies that use formate could contribute to primary productivity in hydrothermal ecosystems. In an effort to provide a quantitative framework for assessing the role of formate metabolism, concentration data for dissolved formate and many other solutes in samples from Yellowstone hot springs were used, together with data for coexisting gas compositions, to evaluate the overall Gibbs energy for many reactions involving formate oxidation or reduction. The result is the first rigorous thermodynamic assessment of reactions involving formate oxidation to bicarbonate and reduction to methane coupled with various forms of iron, nitrogen, sulfur, hydrogen, and oxygen for hydrothermal ecosystems. We conclude that there are a limited number of reactions that can yield energy through formate reduction, in contrast to numerous formate oxidation reactions that can yield abundant energy for chemosynthetic microorganisms. Because the energy yields are so high, these results challenge the notion that hydrogen is the primary energy source of chemosynthetic microbes in hydrothermal ecosystems.

Molecular Interaction of Bone Marrow Adipose Tissue with Energy Metabolism.

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Suchacki, Karla J; Cawthorn, William P

2018-01-01

The last decade has seen a resurgence in the study of bone marrow adipose tissue (BMAT) across diverse fields such as metabolism, haematopoiesis, skeletal biology and cancer. Herein, we review the most recent developments of BMAT research in both humans and rodents, including the distinct nature of BMAT; the autocrine, paracrine and endocrine interactions between BMAT and various tissues, both in physiological and pathological scenarios; how these interactions might impact energy metabolism; and the most recent technological advances to quantify BMAT. Though still dwarfed by research into white and brown adipose tissues, BMAT is now recognised as endocrine organ and is attracting increasing attention from biomedical researchers around the globe. We are beginning to learn the importance of BMAT both within and beyond the bone, allowing us to better appreciate the role of BMAT in normal physiology and disease.

Energy Metabolism and Inflammation in Brain Aging and Alzheimer’s Disease

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Yin, Fei; Sancheti, Harsh; Patil, Ishan; Cadenas, Enrique

2016-01-01

The high energy demand of the brain renders it sensitive to changes in energy fuel supply and mitochondrial function. Deficits in glucose availability and mitochondrial function are well-known hallmarks of brain aging and are particularly accentuated in neurodegenerative disorders such as Alzheimer’s disease. As important cellular sources of H2O2, mitochondrial dysfunction is usually associated with altered redox status. Bioenergetic deficits and chronic oxidative stress are both major contributors to cognitive decline associated with brain aging and Alzheimer’s disease. Neuroinflammatory changes, including microglial activation and production of inflammatory cytokines, are observed in neurodegenerative diseases and normal aging. The bioenergetic hypothesis advocates for sequential events from metabolic deficits to propagation of neuronal dysfunction, to aging, and to neurodegeneration, while the inflammatory hypothesis supports microglia activation as the driving force for neuroinflammation. Nevertheless, growing evidence suggests that these diverse mechanisms have redox dysregulation as a common denominator and connector. An independent view of the mechanisms underlying brain aging and neurodegeneration is being replaced by one that entails multiple mechanisms coordinating and interacting with each other. This review focuses on the alterations in energy metabolism and inflammatory responses and their connection via redox regulation in normal brain aging and Alzheimer’s disease. Interactions of these systems is reviewed based on basic research and clinical studies. PMID:27154981

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

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Cantó, Carles; Menzies, Keir; Auwerx, Johan

2015-01-01

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

Metabolic risk factors in mice divergently selected for BMR fed high fat and high carb diets.

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Sadowska, Julita; Gębczyński, Andrzej K; Konarzewski, Marek

2017-01-01

Factors affecting contribution of spontaneous physical activity (SPA; activity associated with everyday tasks) to energy balance of humans are not well understood, as it is not clear whether low activity is related to dietary habits, precedes obesity or is a result of thereof. In particular, human studies on SPA and basal metabolic rates (BMR, accounting for >50% of human energy budget) and their associations with diet composition, metabolic thrift and obesity are equivocal. To clarify these ambiguities we used a unique animal model-mice selected for divergent BMR rates (the H-BMR and L-BMR line type) presenting a 50% between-line type difference in the primary selected trait. Males of each line type were divided into three groups and fed either a high fat, high carb or a control diet. They then spent 4 months in individual cages under conditions emulating human "sedentary lifestyle", with SPA followed every month and measurements of metabolic risk indicators (body fat mass %, blood lipid profile, fasting blood glucose levels and oxidative damage in the livers, kidneys and hearts) taken at the end of study. Mice with genetically determined high BMR assimilated more energy and had higher SPA irrespective of type of diet. H-BMR individuals were characterized by lower dry body fat mass %, better lipid profile and lower fasting blood glucose levels, but higher oxidative damage in the livers and hearts. Genetically determined high BMR may be a protective factor against diet-induced obesity and most of the metabolic syndrome indicators. Elevated spontaneous activity is correlated with high BMR, and constitutes an important factor affecting individual capability to sustain energy balance even under energy dense diets.

Effects of Dietary Protein Source and Quantity during Weight Loss on Appetite, Energy Expenditure, and Cardio-Metabolic Responses

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Jia Li

2016-01-01

Full Text Available Higher protein meals increase satiety and the thermic effect of feeding (TEF in acute settings, but it is unclear whether these effects remain after a person becomes acclimated to energy restriction or a given protein intake. This study assessed the effects of predominant protein source (omnivorous, beef/pork vs. lacto-ovo vegetarian, soy/legume and quantity (10%, 20%, or 30% of energy from protein on appetite, energy expenditure, and cardio-metabolic indices during energy restriction (ER in overweight and obese adults. Subjects were randomly assigned to one protein source and then consumed diets with different quantities of protein (4 weeks each in a randomized crossover manner. Perceived appetite ratings (free-living and in-lab, TEF, and fasting cardio-metabolic indices were assessed at the end of each 4-week period. Protein source and quantity did not affect TEF, hunger, or desire to eat, other than a modestly higher daily composite fullness rating with 30% vs. 10% protein diet (p = 0.03. While the 20% and 30% protein diets reduced cholesterol, triacylglycerol, and APO-B vs. 10% protein (p < 0.05, protein source did not affect cardio-metabolic indices. In conclusion, diets varying in protein quantity with either beef/pork or soy/legume as the predominant source have minimal effects on appetite control, energy expenditure and cardio-metabolic risk factors during ER-induced weight loss.

Simulating the physiology of athletes during endurance sports events: modelling human energy conversion and metabolism

NARCIS (Netherlands)

van Beek, J.H.G.M.; Supandi, F.B.; Gavai, Anand; de Graaf, A.A.; Binsl, T.W.; Hettling, H.

2011-01-01

The human physiological system is stressed to its limits during endurance sports competition events.We describe a whole body computational model for energy conversion during bicycle racing. About 23 per cent of the metabolic energy is used for muscle work, the rest is converted to heat. We

Simulating the physiology of athletes during endurance sports events: Modelling human energy conversion and metabolism

NARCIS (Netherlands)

Beek, J.H.G.M. van; Supandi, F.; Gavai, A.K.; Graaf, A.A. de; Binsl, T.W.; Hettling, H.

2011-01-01

The human physiological system is stressed to its limits during endurance sports competition events.We describe a whole body computational model for energy conversion during bicycle racing. About 23 per cent of the metabolic energy is used for muscle work, the rest is converted to heat. We

A Transcript-Specific eIF3 Complex Mediates Global Translational Control of Energy Metabolism

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Meera Shah

2016-08-01

Full Text Available The multi-subunit eukaryotic translation initiation factor eIF3 is thought to assist in the recruitment of ribosomes to mRNA. The expression of eIF3 subunits is frequently disrupted in human cancers, but the specific roles of individual subunits in mRNA translation and cancer remain elusive. Using global transcriptomic, proteomic, and metabolomic profiling, we found a striking failure of Schizosaccharomyces pombe cells lacking eIF3e and eIF3d to synthesize components of the mitochondrial electron transport chain, leading to a defect in respiration, endogenous oxidative stress, and premature aging. Energy balance was maintained, however, by a switch to glycolysis with increased glucose uptake, upregulation of glycolytic enzymes, and strict dependence on a fermentable carbon source. This metabolic regulatory function appears to be conserved in human cells where eIF3e binds metabolic mRNAs and promotes their translation. Thus, via its eIF3d-eIF3e module, eIF3 orchestrates an mRNA-specific translational mechanism controlling energy metabolism that may be disrupted in cancer.

The metabochip, a custom genotyping array for genetic studies of metabolic, cardiovascular, and anthropometric traits.

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Benjamin F Voight

Full Text Available Genome-wide association studies have identified hundreds of loci for type 2 diabetes, coronary artery disease and myocardial infarction, as well as for related traits such as body mass index, glucose and insulin levels, lipid levels, and blood pressure. These studies also have pointed to thousands of loci with promising but not yet compelling association evidence. To establish association at additional loci and to characterize the genome-wide significant loci by fine-mapping, we designed the "Metabochip," a custom genotyping array that assays nearly 200,000 SNP markers. Here, we describe the Metabochip and its component SNP sets, evaluate its performance in capturing variation across the allele-frequency spectrum, describe solutions to methodological challenges commonly encountered in its analysis, and evaluate its performance as a platform for genotype imputation. The metabochip achieves dramatic cost efficiencies compared to designing single-trait follow-up reagents, and provides the opportunity to compare results across a range of related traits. The metabochip and similar custom genotyping arrays offer a powerful and cost-effective approach to follow-up large-scale genotyping and sequencing studies and advance our understanding of the genetic basis of complex human diseases and traits.

PET studies of brain energy metabolism in a model of subcortical dementia: progressive supranuclear Palsy

International Nuclear Information System (INIS)

Blin, J.; Baron, J.C.; Cambon, H.

1988-01-01

In 41 patients with clinically determined Progressive Supranuclear Palsy, a model of degenerative subcortical dementia, alterations in regional brain energy metabolism with respect to control subjects have been investigated using positron computed tomography and correlated to clinical and neuropsychological scores. A generalized significant reduction in brain metabolism was found, which predominated in the prefrontal cortex in accordance with, and statistically correlated to, the frontal neuropsychological score

[Coactivators in energy metabolism: peroxisome proliferator-activated receptor-gamma coactivator 1 family].

Science.gov (United States)

Wang, Rui; Chang, Yong-sheng; Fang, Fu-de

2009-12-01

Peroxisome proliferator-activated receptor gamma coactivator 1 (PGC1) family is highly expressed in tissues with high energy metabolism. They coactivate transcription factors in regulating genes engaged in processes such as gluconeogenesis, adipose beta-oxydation, lipoprotein synthesis and secretion, mitochondrial biogenesis, and oxidative metabolism. Protein conformation studies demonstrated that they lack DNA binding domains and act as coactivators through physical interaction with transcription factors. PGC1 activity is regulated at transcription level or by multiple covalent chemical modifications such as phosphorylation, methylation and acetylation/deacetylation. Abnormal expression of PGC1 coactivators usually is closely correlated with diseases such as diabetes, obesity, hyperglycemia, hyperlipemia, and arterial and brain neuron necrosis diseases.

GH and IGF1: Roles in Energy Metabolism of Long-Living GH Mutant Mice

OpenAIRE

Brown-Borg, Holly M.; Bartke, Andrzej

2012-01-01

Of the multiple theories to explain exceptional longevity, the most robust of these has centered on the reduction of three anabolic protein hormones, growth hormone (GH), insulin-like growth factor, and insulin. GH mutant mice live 50% longer and exhibit significant differences in several aspects of energy metabolism as compared with wild-type mice. Mitochondrial metabolism is upregulated in the absence of GH, whereas in GH transgenic mice and dwarf mice treated with GH, multiple aspects of t...

Simulating antler growth and energy, nitrogen, calcium and phosphorus metabolism in caribou

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Ron Moen

1998-03-01

Full Text Available We added antler growth and mineral metabolism modules to a previously developed energetics model for ruminants to simulate energy and mineral balance of male and female caribou throughout an annual cycle. Body watet, fat, protein, and ash are monitored on a daily time step, and energy costs associated with reproduction and body mass changes are simulated. In order to simulate antler growth, we had to predict calcium and phosphorus metabolism as it is affected by antler growth, gestation, and lactation. We used data on dietary digestibility, protein, calcium and phosphorus content, and seasonal patterns in body mass to predict the energy, nitrogen, calcium, and phosphorus balances of a "generic" male and female caribou. Antler growth in males increased energy requirements during antler growth by 8 to 16%, depending on the efficiency with which energy was used for antler growth. Female energy requirements for antler growth were proportionately much smaller because of the smaller size of female antlers. Protein requirements for antler growth in both males and females were met by forage intake. Calcium and phosphorus must be resorbed from bone during peak antler growth in males, when > 25 g/day of calcium and > 12 g/day of phosphorus are being deposited in antlers. Females are capable of meeting calcium needs during antler growth without bone resorption, but phosphorus was resorbed from bone during the final stages of antler mineralization. After energy, phosphorus was most likely to limit growth of antlers for both males and females in our simulations. Input parameters can be easily changed to represent caribou from specific geographic regions in which dietary nutrient content or body mass patterns differ from those in our "generic" caribou. The model can be used to quantitatively analyze the evolutionary basis for development of antlers in female caribou, and the relationship between body mass and antler size in the Cervidae.

The effects of home oxygen therapy on energy metabolism in patients with COPD

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Kırıcı Berber, Nurcan; Yetkin, Özkan; Kılıç, Talat; Berber, Ilhami; Özgel, Mehmet

2018-01-01

Background COPD is preventable and treatable and is characterized by completely nonreversible airflow obstruction. In this study, we aimed to investigate the effect of long-term oxygen therapy on patients with stage 4 COPD who were followed up and treated at the polyclinic or clinic service. We evaluated the effects of oxygen therapy on energy metabolism and physical activity in patients with COPD. Methods Nineteen patients with COPD (16 male/3 female), treated with oxygen therapy for the first time, were included in this study. Analysis of arterial blood gases and pulmonary function test was performed. Metabolic Holter device (SenseWear® Armband) was placed pre- and post-oxygen therapy on the patients’ arm for at least 3 days. This device captures Holter data in a digitized electronic system, and the daily average value was calculated from the data. Results Post-oxygen treatment showed a significant increase in energy expenditure by patients with COPD (pretreatment, 1,497±596 joule; posttreatment, 2,977±5,985 joule; P=0.044). Moreover, number of steps during walking (pretreatment, 2,056±256; posttreatment, 2,120±195; P=0.03), resting (pretreatment, 6.36±3.31 hours; posttreatment, 3.47±2.19 hours; P<0.03), and sleeping (pretreatment, 4.23±2.13 hours; posttreatment, 2.33±1.42 hours; P<0.00) showed significant differences. Increased daily energy expenditure in patients with respiratory failure was detected with long-term oxygen therapy. In addition, the immobility of patients decreased and duration of physical activity increased in patients with COPD. Conclusion In this study, positive effects of long-term oxygen therapy have been demonstrated with respect to energy metabolism and physical activity of patients with COPD. Thus, we recommend that medication adherence and long-term oxygen therapy should begin early in patients with COPD.

The metabolic ER stress sensor IRE1α suppresses alternative activation of macrophages and impairs energy expenditure in obesity.

Science.gov (United States)

Shan, Bo; Wang, Xiaoxia; Wu, Ying; Xu, Chi; Xia, Zhixiong; Dai, Jianli; Shao, Mengle; Zhao, Feng; He, Shengqi; Yang, Liu; Zhang, Mingliang; Nan, Fajun; Li, Jia; Liu, Jianmiao; Liu, Jianfeng; Jia, Weiping; Qiu, Yifu; Song, Baoliang; Han, Jing-Dong J; Rui, Liangyou; Duan, Sheng-Zhong; Liu, Yong

2017-05-01

Obesity is associated with metabolic inflammation and endoplasmic reticulum (ER) stress, both of which promote metabolic disease progression. Adipose tissue macrophages (ATMs) are key players orchestrating metabolic inflammation, and ER stress enhances macrophage activation. However, whether ER stress pathways underlie ATM regulation of energy homeostasis remains unclear. Here, we identified inositol-requiring enzyme 1α (IRE1α) as a critical switch governing M1-M2 macrophage polarization and energy balance. Myeloid-specific IRE1α abrogation in Ern1 f/f ; Lyz2-Cre mice largely reversed high-fat diet (HFD)-induced M1-M2 imbalance in white adipose tissue (WAT) and blocked HFD-induced obesity, insulin resistance, hyperlipidemia and hepatic steatosis. Brown adipose tissue (BAT) activity, WAT browning and energy expenditure were significantly higher in Ern1 f/f ; Lyz2-Cre mice. Furthermore, IRE1α ablation augmented M2 polarization of macrophages in a cell-autonomous manner. Thus, IRE1α senses protein unfolding and metabolic and immunological states, and consequently guides ATM polarization. The macrophage IRE1α pathway drives obesity and metabolic syndrome through impairing BAT activity and WAT browning.

Effect of melatonin and lighting schedule on energy metabolism in broiler chickens

NARCIS (Netherlands)

Apeldoorn, E.J.; Schrama, J.W.; Mashaly, M.M.; Parmentier, H.K.

1999-01-01

The effect of melatonin and lighting schedule on energy metabolism in broiler chickens was studied. Eight groups of six female broiler chickens each were assigned to a continuous lighting schedule [23 h light (L):1 h darkness (D)] or an intermittent lighting schedule (1L:3D), and were fed a diet

Experience in the modular teaching of the integrated course of metabolism and energy

Institute of Scientific and Technical Information of China (English)

Jian HUANG; Qian LI; Xue-mei TONG; Rong YANG; Ping ZHANG

2015-01-01

The teaching of eight-year clinical medicine program of Shanghai Jiao Tong University School of Medicine was reformed since 2009 to replace the traditional teaching model with modular teaching. As one of reformed courses,the metabolism and energy course combines biochemistry and physiology related knowledge points and endeavors to overcome shortcomings of traditional basic medical knowledge education,such as simple learning contents,isolation between basic medicine and clinical medicine,simple teaching methods of teachers,and passive learning methods of students. After 6 years of teaching practice,the new teaching model has been recognized by both teachers and students and the teaching quality improves comprehensively,but there are still some shortcomings that need to be overcome. This paper summarizes the gain and loss of the modular teaching of integrated course of metabolism and energy,so as to provide reference for extending the reform of modular teaching and further improving the teaching quality.

Role of resting metabolic rate and energy expenditure in hunger and appetite control: a new formulation.

Science.gov (United States)

Blundell, John E; Caudwell, Phillipa; Gibbons, Catherine; Hopkins, Mark; Naslund, Erik; King, Neil; Finlayson, Graham

2012-09-01

A long-running issue in appetite research concerns the influence of energy expenditure on energy intake. More than 50 years ago, Otto G. Edholm proposed that "the differences between the intakes of food [of individuals] must originate in differences in the expenditure of energy". However, a relationship between energy expenditure and energy intake within any one day could not be found, although there was a correlation over 2 weeks. This issue was never resolved before interest in integrative biology was replaced by molecular biochemistry. Using a psychobiological approach, we have studied appetite control in an energy balance framework using a multi-level experimental system on a single cohort of overweight and obese human subjects. This has disclosed relationships between variables in the domains of body composition [fat-free mass (FFM), fat mass (FM)], metabolism, gastrointestinal hormones, hunger and energy intake. In this Commentary, we review our own and other data, and discuss a new formulation whereby appetite control and energy intake are regulated by energy expenditure. Specifically, we propose that FFM (the largest contributor to resting metabolic rate), but not body mass index or FM, is closely associated with self-determined meal size and daily energy intake. This formulation has implications for understanding weight regulation and the management of obesity.

Insight into Energy Conservation via Alternative Carbon Monoxide Metabolism in Carboxydothermus pertinax Revealed by Comparative Genome Analysis.

Science.gov (United States)

Fukuyama, Yuto; Omae, Kimiho; Yoneda, Yasuko; Yoshida, Takashi; Sako, Yoshihiko

2018-05-04

Carboxydothermus species are some of the most studied thermophilic carboxydotrophs. Their varied carboxydotrophic growth properties suggest distinct strategies for energy conservation via CO metabolism. In this study, we used comparative genome analysis of the genus Carboxydothermus to show variations in the CO dehydrogenase/energy-converting hydrogenase gene cluster, which is responsible for CO metabolism with H 2 production (hydrogenogenic CO metabolism). Indeed, ability or inability to produce H 2 with CO oxidation is explained by the presence or absence of this gene cluster in C. hydrogenoformans , C. islandicus , and C. ferrireducens Interestingly, despite its hydrogenogenic CO metabolism, C. pertinax lacks the Ni-CO dehydrogenase catalytic subunit (CooS-I) and its transcriptional regulator encoding genes in this gene cluster probably due to inversion. Transcriptional analysis in C. pertinax showed that the Ni-CO dehydrogenase gene ( cooS-II ) and distantly encoded energy-converting hydrogenase related genes were remarkably upregulated under 100% CO. In addition, when thiosulfate was available as a terminal electron acceptor under 100% CO, C. pertinax maximum cell density and maximum specific growth rate were 3.1-fold and 1.5-fold higher, respectively, than when thiosulfate was absent. The amount of H 2 produced was only 63% of the consumed CO, less than expected according to hydrogenogenic CO oxidation: CO + H 2 O → CO 2 + H 2 Accordingly, C. pertinax would couple CO oxidation by Ni-CO dehydrogenase-II with simultaneous reduction of not only H 2 O but thiosulfate when grown under 100% CO. IMPORTANCE Anaerobic hydrogenogenic carboxydotrophs are thought to fill a vital niche with scavenging potentially toxic CO and producing H 2 as available energy source for thermophilic microbes. This hydrogenogenic carboxydotrophy relies on a Ni-CO dehydrogenase/energy-converting hydrogenase gene cluster. This feature is thought to be as common to these organisms. However

Metabolic functions of Pseudomonas fluorescens strains from Populus deltoides depend on rhizosphere or endosphere isolation compartment

Directory of Open Access Journals (Sweden)

Collin M Timm

2015-10-01

Full Text Available The bacterial microbiota of plants is diverse, with 1,000s of operational taxonomic units (OTUs associated with any individual plant. In this work we investigate the differences between 19 sequenced Pseudomonas fluorescens strains, isolated from Populus deltoides rhizosphere and endosphere and which represent a single OTU, using phenotypic analysis, comparative genomics, and metabolic models. While no traits were exclusive to either endosphere or rhizosphere P. fluorescens isolates, multiple pathways relevant for plant-bacterial interactions are enriched in endosphere isolate genomes. Further, growth phenotypes such as phosphate solubilization, protease activity, denitrification and root growth promotion are biased towards endosphere isolates. Endosphere isolates have significantly more metabolic pathways for plant signaling compounds and an increased metabolic range that includes utilization of energy rich nucleotides and sugars, consistent with endosphere colonization. Rhizosphere P. fluorescens have fewer pathways representative of plant-bacterial interactions but show metabolic bias towards chemical substrates often found in root exudates. This work reveals the diverse functions that may contribute to colonization of the endosphere by bacteria and are enriched among closely related isolates.

Effects of season, temperature, and body mass on the standard metabolic rate of tegu lizards (Tupinambis merianae).

Science.gov (United States)

Toledo, Luís F; Brito, Simone P; Milsom, William K; Abe, Augusto S; Andrade, Denis V

2008-01-01

Abstract This study examined how the standard metabolic rate of tegu lizards, a species that undergoes large ontogenetic changes in body weight with associated changes in life-history traits, is affected by changes in body mass, body temperature, season, and life-history traits. We measured rates of oxygen consumption (Vo(2)) in 90 individuals ranging in body mass from 10.4 g to 3.75 kg at three experimental temperatures (17 degrees , 25 degrees , and 30 degrees C) over the four seasons. We found that standard metabolic rate scaled to the power of 0.84 of body mass at all experimental temperatures in all seasons and that thermal sensitivity of metabolism was relatively low (Q(10) approximately 2.0-2.5) over the range from 17 degrees to 30 degrees C regardless of body size or season. Metabolic rates did vary seasonally, being higher in spring and summer than in autumn and winter at the same temperatures, and this was true regardless of animal size. Finally, in this study, the changes in life-history traits that occurred ontogenetically were not accompanied by significant changes in metabolic rate.

Functional traits, convergent evolution, and periodic tables of niches.

Science.gov (United States)

Winemiller, Kirk O; Fitzgerald, Daniel B; Bower, Luke M; Pianka, Eric R

2015-08-01

Ecology is often said to lack general theories sufficiently predictive for applications. Here, we examine the concept of a periodic table of niches and feasibility of niche classification schemes from functional trait and performance data. Niche differences and their influence on ecological patterns and processes could be revealed effectively by first performing data reduction/ordination analyses separately on matrices of trait and performance data compiled according to logical associations with five basic niche 'dimensions', or aspects: habitat, life history, trophic, defence and metabolic. Resultant patterns then are integrated to produce interpretable niche gradients, ordinations and classifications. Degree of scheme periodicity would depend on degrees of niche conservatism and convergence causing species clustering across multiple niche dimensions. We analysed a sample data set containing trait and performance data to contrast two approaches for producing niche schemes: species ordination within niche gradient space, and niche categorisation according to trait-value thresholds. Creation of niche schemes useful for advancing ecological knowledge and its applications will depend on research that produces functional trait and performance datasets directly related to niche dimensions along with criteria for data standardisation and quality. As larger databases are compiled, opportunities will emerge to explore new methods for data reduction, ordination and classification. © 2015 The Authors. Ecology Letters published by CNRS and John Wiley & Sons Ltd.

Effects of Dietary Protein Source and Quantity during Weight Loss on Appetite, Energy Expenditure, and Cardio-Metabolic Responses.

Science.gov (United States)

Li, Jia; Armstrong, Cheryl L H; Campbell, Wayne W

2016-01-26

Higher protein meals increase satiety and the thermic effect of feeding (TEF) in acute settings, but it is unclear whether these effects remain after a person becomes acclimated to energy restriction or a given protein intake. This study assessed the effects of predominant protein source (omnivorous, beef/pork vs. lacto-ovo vegetarian, soy/legume) and quantity (10%, 20%, or 30% of energy from protein) on appetite, energy expenditure, and cardio-metabolic indices during energy restriction (ER) in overweight and obese adults. Subjects were randomly assigned to one protein source and then consumed diets with different quantities of protein (4 weeks each) in a randomized crossover manner. Perceived appetite ratings (free-living and in-lab), TEF, and fasting cardio-metabolic indices were assessed at the end of each 4-week period. Protein source and quantity did not affect TEF, hunger, or desire to eat, other than a modestly higher daily composite fullness rating with 30% vs. 10% protein diet (p = 0.03). While the 20% and 30% protein diets reduced cholesterol, triacylglycerol, and APO-B vs. 10% protein (p appetite control, energy expenditure and cardio-metabolic risk factors during ER-induced weight loss.

Role of interleukin 1 and tumor necrosis factor on energy metabolism in rabbits

International Nuclear Information System (INIS)

Tredget, E.E.; Yu, Y.M.; Zhong, S.; Burini, R.; Okusawa, S.; Gelfand, J.A.; Dinarello, C.A.; Young, V.R.; Burke, J.F.

1988-01-01

A study of the combined effects of intravenous infusion of the recombinant cytokines beta-interleukin 1 (IL-1) and alpha-tumor necrosis factor (TNF) on energy substrate metabolism in awake, conditioned, adult rabbits was performed. After a 2-h basal or control period, 48-h fasted rabbits were administered TNF and IL-1 as a bolus (5 micrograms/kg) followed by a continuous intravenous infusion (25 ng.kg-1.min-1) for 3 h. Significant increases in plasma lactate (P less than 0.01), glucose (P less than 0.01), and triglycerides (P less than 0.05) occurred during the combined infusion of IL-1 and TNF, whereas neither cytokine alone had no effect. There was a 33% increase in the rate of glucose appearance (P less than 0.05), but glucose clearance was not altered compared with the control period. Glucose oxidation increased during the combined cytokine infusion period and glucose recycling increased by 600% (P less than 0.002). Lactic acidosis and decreased oxygen consumption, as a result of the cytokine infusions, indicated development of anaerobic glycolytic metabolism. A reduction in the activity state of hepatic mitochondrial pyruvate dehydrogenase (65 vs. 82% in control animals, P less than 0.05) was consistent with the observed increase in anaerobic glycolysis. Thus the combined infusion of IL-1 and TNF in rabbits produces metabolic manifestations seen in severe injury and sepsis in human patients and, as such, may account for the profound alterations of energy metabolism seen in these conditions

Role of interleukin 1 and tumor necrosis factor on energy metabolism in rabbits

Energy Technology Data Exchange (ETDEWEB)

Tredget, E.E.; Yu, Y.M.; Zhong, S.; Burini, R.; Okusawa, S.; Gelfand, J.A.; Dinarello, C.A.; Young, V.R.; Burke, J.F.

1988-12-01

A study of the combined effects of intravenous infusion of the recombinant cytokines beta-interleukin 1 (IL-1) and alpha-tumor necrosis factor (TNF) on energy substrate metabolism in awake, conditioned, adult rabbits was performed. After a 2-h basal or control period, 48-h fasted rabbits were administered TNF and IL-1 as a bolus (5 micrograms/kg) followed by a continuous intravenous infusion (25 ng.kg-1.min-1) for 3 h. Significant increases in plasma lactate (P less than 0.01), glucose (P less than 0.01), and triglycerides (P less than 0.05) occurred during the combined infusion of IL-1 and TNF, whereas neither cytokine alone had no effect. There was a 33% increase in the rate of glucose appearance (P less than 0.05), but glucose clearance was not altered compared with the control period. Glucose oxidation increased during the combined cytokine infusion period and glucose recycling increased by 600% (P less than 0.002). Lactic acidosis and decreased oxygen consumption, as a result of the cytokine infusions, indicated development of anaerobic glycolytic metabolism. A reduction in the activity state of hepatic mitochondrial pyruvate dehydrogenase (65 vs. 82% in control animals, P less than 0.05) was consistent with the observed increase in anaerobic glycolysis. Thus the combined infusion of IL-1 and TNF in rabbits produces metabolic manifestations seen in severe injury and sepsis in human patients and, as such, may account for the profound alterations of energy metabolism seen in these conditions.

Insulin resistance and protein energy metabolism in patients with advanced chronic kidney disease.

Science.gov (United States)

Siew, Edward D; Ikizler, Talat Alp

2010-01-01

Insulin resistance (IR), the reciprocal of insulin sensitivity is a known complication of advanced chronic kidney disease (CKD) and is associated with a number of metabolic derangements. The complex metabolic abnormalities observed in CKD such as vitamin D deficiency, obesity, metabolic acidosis, inflammation, and accumulation of "uremic toxins" are believed to contribute to the etiology of IR and acquired defects in the insulin-receptor signaling pathway in this patient population. Only a few investigations have explored the validity of commonly used assessment methods in comparison to gold standard hyperinsulinemic hyperglycemic clamp technique in CKD patients. An important consequence of insulin resistance is its role in the pathogenesis of protein energy wasting, a state of metabolic derangement characterized by loss of somatic and visceral protein stores not entirely accounted for by inadequate nutrient intake. In the general population, insulin resistance has been associated with accelerated protein catabolism. Among end-stage renal disease (ESRD) patients, enhanced muscle protein breakdown has been observed in patients with Type II diabetes compared to ESRD patients without diabetes. In the absence of diabetes mellitus (DM) or severe obesity, insulin resistance is detectable in dialysis patients and strongly associated with increased muscle protein breakdown, primarily mediated by the ubiquitin-proteasome pathway. Recent epidemiological data indicate a survival advantage and better nutritional status in insulin-free Type II DM patients treated with insulin sensitizer thiazolidinediones. Given the high prevalence of protein energy wasting in ESRD and its unequivocal association with adverse clinical outcomes, insulin resistance may represent an important modifiable target for intervention in the ESRD population.

Altered energy metabolism in an irradiated population of lizards at the Nevada Test Site

International Nuclear Information System (INIS)

Nagy, K.A.; Medica, P.A.

1985-01-01

Field metabolic rates (via doubly labeled water), body compartmentalization of energy stores, and energy assimilation efficiencies were measured to assess all avenues of energy utilization in Uta stansburiana living in a low-level γ-irradiated plot in Rock Valley, Nevada. Comparison of energy budgets for radiation-sterilized females with those of nonirradiated control lizards revealed several substantial differences. Sterile females were heavier, mainly because they had extraordinarily large energy (fat) storage depots. Sterile females had much lower rates of energy expenditure via respiration and lower rates of energy intake by feeding. These differences are interpreted as indirect responses to radiation-induced sterility. There is little evidence of direct radiation effects on physiological functions other than reproduction

High energy diets-induced metabolic and prediabetic painful polyneuropathy in rats.

Directory of Open Access Journals (Sweden)

Fang Xie

Full Text Available To establish the role of the metabolic state in the pathogenesis of polyneuropathy, an age- and sex-matched, longitudinal study in rats fed high-fat and high-sucrose diets (HFSD or high-fat, high-sucrose and high-salt diets (HFSSD relative to controls was performed. Time courses of body weight, systolic blood pressure, fasting plasma glucose (FPG, insulin, free fatty acids (FFA, homeostasis model assessment-insulin resistance index (HOMA-IR, thermal and mechanical sensitivity and motor coordination were measured in parallel. Finally, large and small myelinated fibers (LMF, SMF as well as unmyelinated fibers (UMF in the sciatic nerves and ascending fibers in the spinal dorsal column were quantitatively assessed under electron microscopy. The results showed that early metabolic syndrome (hyperinsulinemia, dyslipidemia, and hypertension and prediabetic conditions (impaired fasting glucose could be induced by high energy diet, and these animals later developed painful polyneuropathy characterized by myelin breakdown and LMF loss in both peripheral and central nervous system. In contrast SMF and UMF in the sciatic nerves were changed little, in the same animals. Therefore the phenomenon that high energy diets induce bilateral mechanical, but not thermal, pain hypersensitivity is reflected by severe damage to LMF, but mild damage to SMF and UMF. Moreover, dietary sodium (high-salt deteriorates the neuropathic pathological process induced by high energy diets, but paradoxically high salt consumption, may reduce, at least temporarily, chronic pain perception in these animals.

High Energy Diets-Induced Metabolic and Prediabetic Painful Polyneuropathy in Rats

Science.gov (United States)

Hou, Jun-Feng; Jiao, Kai; Costigan, Michael; Chen, Jun

2013-01-01

To establish the role of the metabolic state in the pathogenesis of polyneuropathy, an age- and sex-matched, longitudinal study in rats fed high-fat and high-sucrose diets (HFSD) or high-fat, high-sucrose and high-salt diets (HFSSD) relative to controls was performed. Time courses of body weight, systolic blood pressure, fasting plasma glucose (FPG), insulin, free fatty acids (FFA), homeostasis model assessment-insulin resistance index (HOMA-IR), thermal and mechanical sensitivity and motor coordination were measured in parallel. Finally, large and small myelinated fibers (LMF, SMF) as well as unmyelinated fibers (UMF) in the sciatic nerves and ascending fibers in the spinal dorsal column were quantitatively assessed under electron microscopy. The results showed that early metabolic syndrome (hyperinsulinemia, dyslipidemia, and hypertension) and prediabetic conditions (impaired fasting glucose) could be induced by high energy diet, and these animals later developed painful polyneuropathy characterized by myelin breakdown and LMF loss in both peripheral and central nervous system. In contrast SMF and UMF in the sciatic nerves were changed little, in the same animals. Therefore the phenomenon that high energy diets induce bilateral mechanical, but not thermal, pain hypersensitivity is reflected by severe damage to LMF, but mild damage to SMF and UMF. Moreover, dietary sodium (high-salt) deteriorates the neuropathic pathological process induced by high energy diets, but paradoxically high salt consumption, may reduce, at least temporarily, chronic pain perception in these animals. PMID:23451227

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

Science.gov (United States)

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

2012-09-18

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

Global Metabolic Reconstruction and Metabolic Gene Evolution in the Cattle Genome

Science.gov (United States)

Kim, Woonsu; Park, Hyesun; Seo, Seongwon

2016-01-01

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

Adipose tissue lipolysis and energy metabolism in early cancer cachexia in mice

Science.gov (United States)

Kliewer, Kara L; Ke, Jia-Yu; Tian, Min; Cole, Rachel M; Andridge, Rebecca R; Belury, Martha A

2015-01-01

Cancer cachexia is a progressive metabolic disorder that results in depletion of adipose tissue and skeletal muscle. A growing body of literature suggests that maintaining adipose tissue mass in cachexia may improve quality-of-life and survival outcomes. Studies of lipid metabolism in cachexia, however, have generally focused on later stages of the disorder when severe loss of adipose tissue has already occurred. Here, we investigated lipid metabolism in adipose, liver and muscle tissues during early stage cachexia – before severe fat loss – in the colon-26 murine model of cachexia. White adipose tissue mass in cachectic mice was moderately reduced (34–42%) and weight loss was less than 10% of initial body weight in this study of early cachexia. In white adipose depots of cachectic mice, we found evidence of enhanced protein kinase A - activated lipolysis which coincided with elevated total energy expenditure and increased expression of markers of brown (but not white) adipose tissue thermogenesis and the acute phase response. Total lipids in liver and muscle were unchanged in early cachexia while markers of fatty oxidation were increased. Many of these initial metabolic responses contrast with reports of lipid metabolism in later stages of cachexia. Our observations suggest intervention studies to preserve fat mass in cachexia should be tailored to the stage of cachexia. Our observations also highlight a need for studies that delineate the contribution of cachexia stage and animal model to altered lipid metabolism in cancer cachexia and identify those that most closely mimic the human condition. PMID:25457061

Role of resting metabolic rate and energy expenditure in hunger and appetite control: a new formulation

Directory of Open Access Journals (Sweden)

John E. Blundell

2012-09-01

Full Text Available A long-running issue in appetite research concerns the influence of energy expenditure on energy intake. More than 50 years ago, Otto G. Edholm proposed that “the differences between the intakes of food [of individuals] must originate in differences in the expenditure of energy”. However, a relationship between energy expenditure and energy intake within any one day could not be found, although there was a correlation over 2 weeks. This issue was never resolved before interest in integrative biology was replaced by molecular biochemistry. Using a psychobiological approach, we have studied appetite control in an energy balance framework using a multi-level experimental system on a single cohort of overweight and obese human subjects. This has disclosed relationships between variables in the domains of body composition [fat-free mass (FFM, fat mass (FM], metabolism, gastrointestinal hormones, hunger and energy intake. In this Commentary, we review our own and other data, and discuss a new formulation whereby appetite control and energy intake are regulated by energy expenditure. Specifically, we propose that FFM (the largest contributor to resting metabolic rate, but not body mass index or FM, is closely associated with self-determined meal size and daily energy intake. This formulation has implications for understanding weight regulation and the management of obesity.

Food Components Modulate Obesity and Energy Metabolism via the Transcriptional Regulation of Lipid-Sensing Nuclear Receptors.

Science.gov (United States)

Goto, Tsuyoshi; Takahashi, Nobuyuki; Kawada, Teruo

2015-01-01

Obesity is a major risk factor for chronic diseases such as diabetes, cardiovascular diseases, and hypertension. Many modern people have a tendency to overeat owing to stress and loosening of self-control. Moreover, energy expenditure varies greatly among individuals. Scientific reduction of obesity is important under these circumstances. Furthermore, recent research on molecular levels has clarified the differentiation of adipocytes, the level of subsequent fat accumulation, and the secretion of the biologically active adipokines by adipocytes. Adipose tissues and obesity have become the most important target for the prevention and treatment of many chronic diseases. We have identified various food-derived compounds modulating nuclear receptors, especially peroxisome proliferators-activated receptor(PPAR), in the regulation of energy metabolism and obesity. In this review, we discuss the PPARs that are most important in obesity and energy metabolism.

Analysis of the porcine APOA2 gene expression in liver, polymorphism identification and association with fatty acid composition traits

NARCIS (Netherlands)

Ballester, M.; Revilla, M.; Puig-Oliveras, A.; Marchesi, J.A.; Castello, A.; Corominas, J.; Fernandez, A.I.; Folch, J.M.

2016-01-01

APOA2 is a protein implicated in triglyceride, fatty acid and glucose metabolism. In pigs, the APOA2 gene is located on pig chromosome 4 (SSC4) in a QTL region affecting fatty acid composition, fatness and growth traits. In this study, we evaluated APOA2 as a candidate gene for meat quality traits

Parametric recursive system identification and self-adaptive modeling of the human energy metabolism for adaptive control of fat weight.

Science.gov (United States)

Őri, Zsolt P

2017-05-01

A mathematical model has been developed to facilitate indirect measurements of difficult to measure variables of the human energy metabolism on a daily basis. The model performs recursive system identification of the parameters of the metabolic model of the human energy metabolism using the law of conservation of energy and principle of indirect calorimetry. Self-adaptive models of the utilized energy intake prediction, macronutrient oxidation rates, and daily body composition changes were created utilizing Kalman filter and the nominal trajectory methods. The accuracy of the models was tested in a simulation study utilizing data from the Minnesota starvation and overfeeding study. With biweekly macronutrient intake measurements, the average prediction error of the utilized carbohydrate intake was -23.2 ± 53.8 kcal/day, fat intake was 11.0 ± 72.3 kcal/day, and protein was 3.7 ± 16.3 kcal/day. The fat and fat-free mass changes were estimated with an error of 0.44 ± 1.16 g/day for fat and -2.6 ± 64.98 g/day for fat-free mass. The daily metabolized macronutrient energy intake and/or daily macronutrient oxidation rate and the daily body composition change from directly measured serial data are optimally predicted with a self-adaptive model with Kalman filter that uses recursive system identification.

Phenotypic and Genetic Correlations of Feed Efficiency Traits with Growth and Carcass Traits in Nellore Cattle Selected for Postweaning Weight

Science.gov (United States)

Ceacero, Thais Matos; Mercadante, Maria Eugênia Zerlotti; Cyrillo, Joslaine Noely dos Santos Gonçalves; Canesin, Roberta Carrilho; Bonilha, Sarah Figueiredo Martins; de Albuquerque, Lucia Galvão

2016-01-01

This study evaluated phenotypic (rph) and genetic correlations (rg) between 8 feed efficiency traits and other traits of economic interest including weight at selection (WS), loin-eye area (LEA), backfat thickness (BF), and rump fat thickness (RF) in Nellore cattle. Feed efficiency traits were gain:feed, residual feed intake (RFI), residual feed intake adjusted for backfat thickness (RFIb) and for backfat and rump fat thickness (RFIsf), residual body weight gain (RG), residual intake and body weight gain (RIG), and residual intake and body weight gain using RFIb (RIGb) and RFIsf (RIGsf). The variance components were estimated by the restricted maximum likelihood method using a two-trait animal model. The heritability estimates (h2) were 0.14, 0.24, 0.20, 0.22, 0.19, 0.15, 0.11 and 0.11 for gain:feed, RFI, RFIb, RFIsf, RG, RIG, RIGb and RIGsf, respectively. All rph values between traits were close to zero, except for the correlation of feed efficiency traits with dry matter intake and average daily gain. High rg values were observed for the correlation of dry matter intake, average daily gain and metabolic weight with WS and hip height (>0.61) and low to medium values (0.15 to 0.48) with the carcass traits (LEA, BF, RF). Among the feed efficiency traits, RG showed the highest rg with WS and hip height (0.34 and 0.25) and the lowest rg with subcutaneous fat thickness (-0.17 to 0.18). The rg values of RFI, RFIb and RFIsf with WS (0.17, 0.23 and 0.22), BF (0.37, 0.33 and 0.33) and RF (0.30, 0.31 and 0.32) were unfavorable. The rg values of gain:feed, RIG, RIGb and RIGsf with WS were low and favorable (0.07 to 0.22), while medium and unfavorable (-0.22 to -0.45) correlations were observed with fat thickness. The inclusion of subcutaneous fat thickness in the models used to calculate RFI did not reduce the rg between these traits. Selecting animals for higher feed efficiency will result in little or no genetic change in growth and will decrease subcutaneous fat thickness

A Transcript-Specific eIF3 Complex Mediates Global Translational Control of Energy Metabolism.

Science.gov (United States)

Shah, Meera; Su, Dan; Scheliga, Judith S; Pluskal, Tomáš; Boronat, Susanna; Motamedchaboki, Khatereh; Campos, Alexandre Rosa; Qi, Feng; Hidalgo, Elena; Yanagida, Mitsuhiro; Wolf, Dieter A

2016-08-16

The multi-subunit eukaryotic translation initiation factor eIF3 is thought to assist in the recruitment of ribosomes to mRNA. The expression of eIF3 subunits is frequently disrupted in human cancers, but the specific roles of individual subunits in mRNA translation and cancer remain elusive. Using global transcriptomic, proteomic, and metabolomic profiling, we found a striking failure of Schizosaccharomyces pombe cells lacking eIF3e and eIF3d to synthesize components of the mitochondrial electron transport chain, leading to a defect in respiration, endogenous oxidative stress, and premature aging. Energy balance was maintained, however, by a switch to glycolysis with increased glucose uptake, upregulation of glycolytic enzymes, and strict dependence on a fermentable carbon source. This metabolic regulatory function appears to be conserved in human cells where eIF3e binds metabolic mRNAs and promotes their translation. Thus, via its eIF3d-eIF3e module, eIF3 orchestrates an mRNA-specific translational mechanism controlling energy metabolism that may be disrupted in cancer. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Adaptive remodeling of skeletal muscle energy metabolism in high-altitude hypoxia: Lessons from AltitudeOmics.

Science.gov (United States)

Chicco, Adam J; Le, Catherine H; Gnaiger, Erich; Dreyer, Hans C; Muyskens, Jonathan B; D'Alessandro, Angelo; Nemkov, Travis; Hocker, Austin D; Prenni, Jessica E; Wolfe, Lisa M; Sindt, Nathan M; Lovering, Andrew T; Subudhi, Andrew W; Roach, Robert C

2018-05-04

Metabolic responses to hypoxia play important roles in cell survival strategies and disease pathogenesis in humans. However, the homeostatic adjustments that balance changes in energy supply and demand to maintain organismal function under chronic low oxygen conditions remain incompletely understood, making it difficult to distinguish adaptive from maladaptive responses in hypoxia-related pathologies. We integrated metabolomic and proteomic profiling with mitochondrial respirometry and blood gas analyses to comprehensively define the physiological responses of skeletal muscle energy metabolism to 16 days of high-altitude hypoxia (5260 m) in healthy volunteers from the AltitudeOmics project. In contrast to the view that hypoxia down-regulates aerobic metabolism, results show that mitochondria play a central role in muscle hypoxia adaptation by supporting higher resting phosphorylation potential and enhancing the efficiency of long-chain acylcarnitine oxidation. This directs increases in muscle glucose toward pentose phosphate and one-carbon metabolism pathways that support cytosolic redox balance and help mitigate the effects of increased protein and purine nucleotide catabolism in hypoxia. Muscle accumulation of free amino acids favor these adjustments by coordinating cytosolic and mitochondrial pathways to rid the cell of excess nitrogen, but might ultimately limit muscle oxidative capacity in vivo Collectively, these studies illustrate how an integration of aerobic and anaerobic metabolism is required for physiological hypoxia adaptation in skeletal muscle, and highlight protein catabolism and allosteric regulation as unexpected orchestrators of metabolic remodeling in this context. These findings have important implications for the management of hypoxia-related diseases and other conditions associated with chronic catabolic stress. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Metabolic syndrome-related composite factors over 5 years in the STANISLAS family study: genetic heritability and common environmental influences.

Science.gov (United States)

Herbeth, Bernard; Samara, Anastasia; Ndiaye, Coumba; Marteau, Jean-Brice; Berrahmoune, Hind; Siest, Gérard; Visvikis-Siest, Sophie

2010-06-03

We estimated genetic heritability and common environmental influences for various traits related to metabolic syndrome in young families from France. At entrance and after 5 years, nineteen traits related to metabolic syndrome were measured in a sample of families drawn from the STANISLAS study. In addition, 5 aggregates of these traits were identified using factor analysis. At entrance, genetic heritability was high (20 to 44%) for plasma lipids and lipoproteins, uric acid, fasting glucose, and the related clusters "risk lipids" and "protective lipids". Intermediate or low genetic heritability (less than 20%) was shown for triglycerides, adiposity indices, blood pressure, hepatic enzyme activity, inflammatory makers and the related clusters: "liver enzymes", "adiposity/blood pressure" and "inflammation". Moreover, common environmental influences were significant for all the parameters. With regard to 5-year changes, polygenic variance was low and not statistically significant for any of the individual variables or clusters whereas shared environment influence was significant. In these young families, genetic heritability of metabolic syndrome-related traits was generally lower than previously reported while the common environmental influences were greater. In addition, only shared environment contributed to short-term changes of these traits. Copyright 2010 Elsevier B.V. All rights reserved.

Novel metabolic attributes of the genus cyanothece, comprising a group of unicellular nitrogen-fixing Cyanothece.

Science.gov (United States)

Bandyopadhyay, Anindita; Elvitigala, Thanura; Welsh, Eric; Stöckel, Jana; Liberton, Michelle; Min, Hongtao; Sherman, Louis A; Pakrasi, Himadri B

2011-01-01

The genus Cyanothece comprises unicellular cyanobacteria that are morphologically diverse and ecologically versatile. Studies over the last decade have established members of this genus to be important components of the marine ecosystem, contributing significantly to the nitrogen and carbon cycle. System-level studies of Cyanothece sp. ATCC 51142, a prototypic member of this group, revealed many interesting metabolic attributes. To identify the metabolic traits that define this class of cyanobacteria, five additional Cyanothece strains were sequenced to completion. The presence of a large, contiguous nitrogenase gene cluster and the ability to carry out aerobic nitrogen fixation distinguish Cyanothece as a genus of unicellular, aerobic nitrogen-fixing cyanobacteria. Cyanothece cells can create an anoxic intracellular environment at night, allowing oxygen-sensitive processes to take place in these oxygenic organisms. Large carbohydrate reserves accumulate in the cells during the day, ensuring sufficient energy for the processes that require the anoxic phase of the cells. Our study indicates that this genus maintains a plastic genome, incorporating new metabolic capabilities while simultaneously retaining archaic metabolic traits, a unique combination which provides the flexibility to adapt to various ecological and environmental conditions. Rearrangement of the nitrogenase cluster in Cyanothece sp. strain 7425 and the concomitant loss of its aerobic nitrogen-fixing ability suggest that a similar mechanism might have been at play in cyanobacterial strains that eventually lost their nitrogen-fixing ability. The unicellular cyanobacterial genus Cyanothece has significant roles in the nitrogen cycle in aquatic and terrestrial environments. Cyanothece sp. ATCC 51142 was extensively studied over the last decade and has emerged as an important model photosynthetic microbe for bioenergy production. To expand our understanding of the distinctive metabolic capabilities of

Metabolic profiling of a mapping population exposes new insights in the regulation of seed metabolism and seed, fruit, and plant relations.

Directory of Open Access Journals (Sweden)

David Toubiana

Full Text Available To investigate the regulation of seed metabolism and to estimate the degree of metabolic natural variability, metabolite profiling and network analysis were applied to a collection of 76 different homozygous tomato introgression lines (ILs grown in the field in two consecutive harvest seasons. Factorial ANOVA confirmed the presence of 30 metabolite quantitative trait loci (mQTL. Amino acid contents displayed a high degree of variability across the population, with similar patterns across the two seasons, while sugars exhibited significant seasonal fluctuations. Upon integration of data for tomato pericarp metabolite profiling, factorial ANOVA identified the main factor for metabolic polymorphism to be the genotypic background rather than the environment or the tissue. Analysis of the coefficient of variance indicated greater phenotypic plasticity in the ILs than in the M82 tomato cultivar. Broad-sense estimate of heritability suggested that the mode of inheritance of metabolite traits in the seed differed from that in the fruit. Correlation-based metabolic network analysis comparing metabolite data for the seed with that for the pericarp showed that the seed network displayed tighter interdependence of metabolic processes than the fruit. Amino acids in the seed metabolic network were shown to play a central hub-like role in the topology of the network, maintaining high interactions with other metabolite categories, i.e., sugars and organic acids. Network analysis identified six exceptionally highly co-regulated amino acids, Gly, Ser, Thr, Ile, Val, and Pro. The strong interdependence of this group was confirmed by the mQTL mapping. Taken together these results (i reflect the extensive redundancy of the regulation underlying seed metabolism, (ii demonstrate the tight co-ordination of seed metabolism with respect to fruit metabolism, and (iii emphasize the centrality of the amino acid module in the seed metabolic network. Finally, the study

The energy metabolism of Fasciola hepatica during its development in the final host

NARCIS (Netherlands)

Tielens, A.G.M.; Heuvel, J.M. van den; Bergh, S.G. van den

1984-01-01

Mature liver flukes, Fasciola hepatica, of different ages were isolated from the bile ducts of experimentally infected rats. Their energy metabolism was studied during aerobic incubation with [6-14C]glucose. The results showed that the aerobic potentials of the parenchymal liver flukes are not lost

Increasing serotonin concentrations alter calcium and energy metabolism in dairy cows.

Science.gov (United States)

Laporta, Jimena; Moore, Spencer A E; Weaver, Samantha R; Cronick, Callyssa M; Olsen, Megan; Prichard, Austin P; Schnell, Brian P; Crenshaw, Thomas D; Peñagaricano, Francisco; Bruckmaier, Rupert M; Hernandez, Laura L

2015-07-01

A 4×4 Latin square design in which varied doses (0, 0.5, 1.0, and 1.5 mg/kg) of 5-hydroxy-l-tryptophan (5-HTP, a serotonin precursor) were intravenously infused into late-lactation, non-pregnant Holstein dairy cows was used to determine the effects of serotonin on calcium and energy metabolism. Infusion periods lasted 4 days, with a 5-day washout between periods. Cows were infused at a constant rate for 1 h each day. Blood was collected pre- and 5, 10, 30, 60, 90, and 120 min post-infusion, urine was collected pre- and post-infusion, and milk was collected daily. All of the 5-HTP doses increased systemic serotonin as compared to the 0 mg/kg dose, and the 1.0 and 1.5 mg/kg doses increased circulating glucose and non-esterified fatty acids (NEFA) and decreased beta-hydroxybutyrate (βHBA) concentrations. Treatment of cows with either 1.0 or 1.5 mg/kg 5-HTP doses decreased urine calcium elimination, and the 1.5 mg/kg dose increased milk calcium concentrations. No differences were detected in the heart rates, respiration rates, or body temperatures of the cows; however, manure scores and defecation frequency were affected. Indeed, cows that received 5-HTP defecated more, and the consistency of their manure was softer. Treatment of late-lactation dairy cows with 5-HTP improved energy metabolism, decreased loss of calcium into urine, and increased calcium secretion into milk. Further research should target the effects of increasing serotonin during the transition period to determine any benefits for post-parturient calcium and glucose metabolism. © 2015 Society for Endocrinology.

Flexibility in metabolic rate confers a growth advantage under changing food availability.

Science.gov (United States)

Auer, Sonya K; Salin, Karine; Rudolf, Agata M; Anderson, Graeme J; Metcalfe, Neil B

2015-09-01

1. Phenotypic flexibility in physiological, morphological and behavioural traits can allow organisms to cope with environmental challenges. Given recent climate change and the degree of habitat modification currently experienced by many organisms, it is therefore critical to quantify the degree of phenotypic variation present within populations, individual capacities to change and what their consequences are for fitness. 2. Flexibility in standard metabolic rate (SMR) may be particularly important since SMR reflects the minimal energetic cost of living and is one of the primary traits underlying organismal performance. SMR can increase or decrease in response to food availability, but the consequences of these changes for growth rates and other fitness components are not well known. 3. We examined individual variation in metabolic flexibility in response to changing food levels and its consequences for somatic growth in juvenile brown trout (Salmo trutta). 4. SMR increased when individuals were switched to a high food ration and decreased when they were switched to a low food regime. These shifts in SMR, in turn, were linked with individual differences in somatic growth; those individuals that increased their SMR more in response to elevated food levels grew fastest, while growth at the low food level was fastest in those individuals that depressed their SMR most. 5. Flexibility in energy metabolism is therefore a key mechanism to maximize growth rates under the challenges imposed by variability in food availability and is likely to be an important determinant of species' resilience in the face of global change. © 2015 The Authors. Journal of Animal Ecology published by John Wiley & Sons Ltd on behalf of British Ecological Society.

Anemone bleaching increases the metabolic demands of symbiont anemonefish.

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Norin, Tommy; Mills, Suzanne C; Crespel, Amélie; Cortese, Daphne; Killen, Shaun S; Beldade, Ricardo

2018-04-11

Increased ocean temperatures are causing mass bleaching of anemones and corals in the tropics worldwide. While such heat-induced loss of algal symbionts (zooxanthellae) directly affects anemones and corals physiologically, this damage may also cascade on to other animal symbionts. Metabolic rate is an integrative physiological trait shown to relate to various aspects of organismal performance, behaviour and locomotor capacity, and also shows plasticity during exposure to acute and chronic stressors. As climate warming is expected to affect the physiology, behaviour and life history of animals, including ectotherms such as fish, we measured if residing in bleached versus unbleached sea anemones ( Heteractis magnifica ) affected the standard (i.e. baseline) metabolic rate and behaviour (activity) of juvenile orange-fin anemonefish ( Amphiprion chrysopterus ) . Metabolic rate was estimated from rates of oxygen uptake [Formula: see text], and the standard metabolic rate [Formula: see text] of anemonefish from bleached anemones was significantly higher by 8.2% compared with that of fish residing in unbleached anemones, possibly due to increased stress levels. Activity levels did not differ between fish from bleached and unbleached anemones. As [Formula: see text] reflects the minimum cost of living, the increased metabolic demands may contribute to the negative impacts of bleaching on important anemonefish life history and fitness traits observed previously (e.g. reduced spawning frequency and lower fecundity). © 2018 The Author(s).

Altered metabolism in cancer

Directory of Open Access Journals (Sweden)

Locasale Jason W

2010-06-01

Full Text Available Abstract Cancer cells have different metabolic requirements from their normal counterparts. Understanding the consequences of this differential metabolism requires a detailed understanding of glucose metabolism and its relation to energy production in cancer cells. A recent study in BMC Systems Biology by Vasquez et al. developed a mathematical model to assess some features of this altered metabolism. Here, we take a broader look at the regulation of energy metabolism in cancer cells, considering their anabolic as well as catabolic needs. See research article: http://www.biomedcentral.com/1752-0509/4/58/

Improving the reliability of female fertility breeding values using type and milk yield traits that predict energy status in Australian Holstein cattle.

Science.gov (United States)

González-Recio, O; Haile-Mariam, M; Pryce, J E

2016-01-01

The objectives of this study were (1) to propose changing the selection criteria trait for evaluating fertility in Australia from calving interval to conception rate at d 42 after the beginning of the mating season and (2) to use type traits as early fertility predictors, to increase the reliability of estimated breeding values for fertility. The breeding goal in Australia is conception within 6 wk of the start of the mating season. Currently, the Australian model to predict fertility breeding values (expressed as a linear transformation of calving interval) is a multitrait model that includes calving interval (CVI), lactation length (LL), calving to first service (CFS), first nonreturn rate (FNRR), and conception rate. However, CVI has a lower genetic correlation with the breeding goal (conception within 6 wk of the start of the mating season) than conception rate. Milk yield, type, and fertility data from 164,318 cow sired by 4,766 bulls were used. Principal component analysis and genetic correlation estimates between type and fertility traits were used to select type traits that could subsequently be used in a multitrait analysis. Angularity, foot angle, and pin set were chosen as type traits to include in an index with the traits that are included in the multitrait fertility model: CVI, LL, CFS, FNRR, and conception rate at d 42 (CR42). An index with these 8 traits is expected to achieve an average bull first proof reliability of 0.60 on the breeding objective (conception within 6 wk of the start of the mating season) compared with reliabilities of 0.39 and 0.45 for CR42 only or the current 5-trait Australian model. Subsequently, we used the first eigenvector of a principal component analysis with udder texture, bone quality, angularity, and body condition score to calculate an energy status indicator trait. The inclusion of the energy status indicator trait composite in a multitrait index with CVI, LL, CFS, FNRR, and CR42 achieved a 12-point increase in

Regulation of neurotrophic factors and energy metabolism by antidepressants in astrocytes

KAUST Repository

Martin, Jean Luc; Magistretti, Pierre J.; Allaman, Igor

2013-01-01

There is growing evidence that astrocytes are involved in the neuropathology of major depression. In particular, decreases in glial cell density observed in the cerebral cortex of individuals with major depressive disorder are accompanied by a reduction of several astrocytic markers suggesting that astrocyte dysfunction may contribute to the pathophysiology of major depression. In rodents, glial loss in the prefrontal cortex is sufficient to induce depressive-like behaviors and antidepressant treatment prevents the stress-induced reduction of astrocyte number in the hippocampus. Collectively, these data support the existence of a link between astrocyte loss or dysfunction, depressive-like behavior and antidepressant treatment. Astrocytes are increasingly recognized to play important roles in neuronal development, neurotransmission, synaptic plasticity and maintenance of brain homeostasis. It is also well established that astrocytes provide trophic, structural, and metabolic support to neurons. In this article, we review evidence that antidepressants regulate energy metabolism and neurotrophic factor expression with particular emphasis on studies in astrocytes. These observations support a role for astrocytes as new targets for antidepressants. The contribution of changes in astrocyte glucose metabolism and neurotrophic factor expression to the therapeutic effects of antidepressants remains to be established. © 2013 Bentham Science Publishers.

Regulation of neurotrophic factors and energy metabolism by antidepressants in astrocytes

KAUST Repository

Martin, Jean Luc

2013-09-01

There is growing evidence that astrocytes are involved in the neuropathology of major depression. In particular, decreases in glial cell density observed in the cerebral cortex of individuals with major depressive disorder are accompanied by a reduction of several astrocytic markers suggesting that astrocyte dysfunction may contribute to the pathophysiology of major depression. In rodents, glial loss in the prefrontal cortex is sufficient to induce depressive-like behaviors and antidepressant treatment prevents the stress-induced reduction of astrocyte number in the hippocampus. Collectively, these data support the existence of a link between astrocyte loss or dysfunction, depressive-like behavior and antidepressant treatment. Astrocytes are increasingly recognized to play important roles in neuronal development, neurotransmission, synaptic plasticity and maintenance of brain homeostasis. It is also well established that astrocytes provide trophic, structural, and metabolic support to neurons. In this article, we review evidence that antidepressants regulate energy metabolism and neurotrophic factor expression with particular emphasis on studies in astrocytes. These observations support a role for astrocytes as new targets for antidepressants. The contribution of changes in astrocyte glucose metabolism and neurotrophic factor expression to the therapeutic effects of antidepressants remains to be established. © 2013 Bentham Science Publishers.

Association of bovine leptin polymorphisms with energy output and energy storage traits in progeny tested Holstein-Friesian dairy cattle sires

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Waters Sinead M

2010-07-01

Full Text Available Abstract Background Leptin modulates appetite, energy expenditure and the reproductive axis by signalling via its receptor the status of body energy stores to the brain. The present study aimed to quantify the associations between 10 novel and known single nucleotide polymorphisms in genes coding for leptin and leptin receptor with performance traits in 848 Holstein-Friesian sires, estimated from performance of up to 43,117 daughter-parity records per sire. Results All single nucleotide polymorphisms were segregating in this sample population and none deviated (P > 0.05 from Hardy-Weinberg equilibrium. Complete linkage disequilibrium existed between the novel polymorphism LEP-1609, and the previously identified polymorphisms LEP-1457 and LEP-580. LEP-2470 associated (P Conclusions Several leptin polymorphisms (LEP-2470, LEP-1238, LEP-963, Y7F and R25C associated with the energetically expensive process of lactogenesis. Only SNP Y7F associated with energy storage. Associations were also observed between leptin polymorphisms and calving difficulty, gestation length and calf perinatal mortality. The lack of an association between the leptin variants investigated with calving interval in this large data set would question the potential importance of these leptin variants, or indeed leptin, in selection for improved fertility in the Holstein-Friesian dairy cow.

Rethinking Energy in Parkinsonian Motor Symptoms: A Potential Role for Neural Metabolic Deficits

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Shinichi eAmano

2015-01-01

Full Text Available Parkinson’s disease (PD is characterized as a chronic and progressive neurodegenerative disorder that results in a variety of debilitating symptoms, including bradykinesia, resting tremor, rigidity, and postural instability. Research spanning several decades has emphasized basal ganglia dysfunction, predominantly resulting from dopaminergic cell loss, as the primarily cause of the aforementioned parkinsonian features. But, why those particular features manifest themselves remains an enigma. The goal of this paper is to develop a theoretical framework that parkinsonian motor features are behavioral consequence of a long-term adaptation to their inability (inflexibility or lack of capacity to meet energetic demands, due to neural metabolic deficits arising from mitochondrial dysfunction associated with PD. Here, we discuss neurophysiological changes that are generally associated with PD, such as selective degeneration of dopaminergic neurons in the substantia nigra pars compacta, in conjunction with metabolic and mitochondrial dysfunction. We then characterize the cardinal motor symptoms of PD, bradykinesia, resting tremor, rigidity and gait disturbance, reviewing literature to demonstrate how these motor patterns are actually energy efficient from a metabolic perspective. We will also develop three testable hypotheses: (1 neural metabolic deficits precede the increased rate of neurodegeneration and onset of behavioral symptoms in PD, (2 motor behavior of persons with PD are more sensitive to changes in metabolic/bioenergetic state, and (3 improvement of metabolic function could lead to better motor performance in persons with PD. These hypotheses are designed to introduce a novel viewpoint that can elucidate the connections between metabolic, neural and motor function in PD.

NAD(H) and NADP(H) Redox Couples and Cellular Energy Metabolism.

Science.gov (United States)

Xiao, Wusheng; Wang, Rui-Sheng; Handy, Diane E; Loscalzo, Joseph

2018-01-20

The nicotinamide adenine dinucleotide (NAD + )/reduced NAD + (NADH) and NADP + /reduced NADP + (NADPH) redox couples are essential for maintaining cellular redox homeostasis and for modulating numerous biological events, including cellular metabolism. Deficiency or imbalance of these two redox couples has been associated with many pathological disorders. Recent Advances: Newly identified biosynthetic enzymes and newly developed genetically encoded biosensors enable us to understand better how cells maintain compartmentalized NAD(H) and NADP(H) pools. The concept of redox stress (oxidative and reductive stress) reflected by changes in NAD(H)/NADP(H) has increasingly gained attention. The emerging roles of NAD + -consuming proteins in regulating cellular redox and metabolic homeostasis are active research topics. The biosynthesis and distribution of cellular NAD(H) and NADP(H) are highly compartmentalized. It is critical to understand how cells maintain the steady levels of these redox couple pools to ensure their normal functions and simultaneously avoid inducing redox stress. In addition, it is essential to understand how NAD(H)- and NADP(H)-utilizing enzymes interact with other signaling pathways, such as those regulated by hypoxia-inducible factor, to maintain cellular redox homeostasis and energy metabolism. Additional studies are needed to investigate the inter-relationships among compartmentalized NAD(H)/NADP(H) pools and how these two dinucleotide redox couples collaboratively regulate cellular redox states and cellular metabolism under normal and pathological conditions. Furthermore, recent studies suggest the utility of using pharmacological interventions or nutrient-based bioactive NAD + precursors as therapeutic interventions for metabolic diseases. Thus, a better understanding of the cellular functions of NAD(H) and NADP(H) may facilitate efforts to address a host of pathological disorders effectively. Antioxid. Redox Signal. 28, 251-272.

Freshwater Biological Traits Database (Traits)

Science.gov (United States)

The traits database was compiled for a project on climate change effects on river and stream ecosystems. The traits data, gathered from multiple sources, focused on information published or otherwise well-documented by trustworthy sources.

Energy metabolism of synaptosomes from different neuronal systems of rat cerebellum during aging: a functional proteomic characterization.

Science.gov (United States)

Ferrari, Federica; Gorini, Antonella; Villa, Roberto Federico

2015-01-01

Functional proteomics was used to characterize age-related changes in energy metabolism of different neuronal pathways within the cerebellar cortex of Wistar rats aged 2, 6, 12, 18, and 24 months. The "large" synaptosomes, derived from the glutamatergic mossy fibre endings which make synaptic contact with the granule cells of the granular layer, and the "small" synaptosomes, derived from the pre-synaptic terminals of granule cells making synaptic contact with the dendrites of Purkinje cells, were isolated by a combined differential/gradient centrifugation technique. Because most brain disorders are associated with bioenergetic changes, the maximum rate (Vmax) of selected enzymes of glycolysis, Krebs' cycle, glutamate and amino acids metabolism, and acetylcholine catabolism were evaluated. The results show that "large" and "small" synaptosomes possess specific and independent metabolic features. This study represents a reliable model to study in vivo (1) the physiopathological molecular mechanisms of some brain diseases dependent on energy metabolism, (2) the responsiveness to noxious stimuli, and (3) the effects of drugs, discriminating their action sites at subcellular level on specific neuronal pathways.

Genome scale metabolic modeling of cancer

DEFF Research Database (Denmark)

Nilsson, Avlant; Nielsen, Jens

2017-01-01

of metabolism which allows simulation and hypotheses testing of metabolic strategies. It has successfully been applied to many microorganisms and is now used to study cancer metabolism. Generic models of human metabolism have been reconstructed based on the existence of metabolic genes in the human genome......Cancer cells reprogram metabolism to support rapid proliferation and survival. Energy metabolism is particularly important for growth and genes encoding enzymes involved in energy metabolism are frequently altered in cancer cells. A genome scale metabolic model (GEM) is a mathematical formalization...

Modulation of Energy Intake and Expenditure Due to Habitual Physical Exercise.

Science.gov (United States)

Martin, Matoulek; Krystof, Slaby; Jiri, Radvansky; Martina, Dankova; Renata, Vetrovska; Ondrej, Mikes; Stepan, Svacina; Vladimir, Tuka

2016-01-01

The 20th and 21st centuries are marked by an increase in life expectancy on one hand and on the other hand by the increase of so called civilization diseases. Their share one common trait: the energy metabolism imbalance, with low energy expenditure and high energy uptake. Our age can be viewed as the age of inactivity and wealth. The aim of the present review is to highlight the influence of habitual physical activity on energy metabolism and balance. Energy balance is the difference between energy intake and energy expenditure, where energy expenditure further divides into resting metabolic rate, thermic effect of feeding and energy used by physical activity. In general population, resting metabolic rate remains constant and proportional to muscle body mass. Muscle mass increases with exercise, especially resistance exercise, concomitantly with increasing energy expenditure. The effect of exercise on appetite is very strong, proportional to exercise intensity. An acute bout of aerobic exercise suppresses appetite by decreasing ghrelin plasma levels, and increasing gut hormones. Different subgroups of patients respond differently to the same exercise or habitual activity and have thus distinct effects on energy balance. Different myokines plasma levels after exercise could explain these different reactions although most of their effect is still unclear. Physical activity plays an important role in the prevention and treatment of many disorders, like obesity, type 1 and type 2 diabetes, dyslipidaemia, hypertension, coronary heart disease, osteoporosis, psychiatric and neurologic disorders. It is evident, that physical activity has an effect not only on energy balance but also has a direct effect on other body organ via its own molecules - myokines. The pharmacological effect of myokines gives hope that one day we could have a "myokine drug" that could be used in patients who are unable to exercise. Until then we should use our "muscle-pharmacy" and try to convince

Metabolic Vascular Syndrome: New Insights into a Multidimensional Network of Risk Factors and Diseases.

Science.gov (United States)

Scholz, Gerhard H; Hanefeld, Markolf

2016-10-01

Since 1981, we have used the term metabolic syndrome to describe an association of a dysregulation in lipid metabolism (high triglycerides, low high-density lipoprotein cholesterol, disturbed glucose homeostasis (enhanced fasting and/or prandial glucose), gout, and hypertension), with android obesity being based on a common soil (overnutrition, reduced physical activity, sociocultural factors, and genetic predisposition). We hypothesized that main traits of the syndrome occur early and are tightly connected with hyperinsulinemia/insulin resistance, procoagulation, and cardiovascular diseases. To establish a close link between the traits of the metabolic vascular syndrome, we focused our literature search on recent original work and comprehensive reviews dealing with the topics metabolic syndrome, visceral obesity, fatty liver, fat tissue inflammation, insulin resistance, atherogenic dyslipidemia, arterial hypertension, and type 2 diabetes mellitus. Recent research supports the concept that the metabolic vascular syndrome is a multidimensional and interactive network of risk factors and diseases based on individual genetic susceptibility and epigenetic changes where metabolic dysregulation/metabolic inflexibility in different organs and vascular dysfunction are early interconnected. The metabolic vascular syndrome is not only a risk factor constellation but rather a life-long abnormality of a closely connected interactive cluster of developing diseases which escalate each other and should continuously attract the attention of every clinician.

Changes in the carbohydrate-energy metabolism with radiation-induced intestine syndrome

International Nuclear Information System (INIS)

Kendysh, I.N.; Grozdov, S.P.

1981-01-01

A local exposure of the rat abdomen in a dose of 3.6 cC/kg decreases the oxygen uptake, oxidation of glucose and fatty acids, glucose tolerance and insulin resistance, and also causes a trend toward lactic acidosis. These changes in the carbohydrate-energy metabolism are normalized with the administration of insulin and dichloracetate, and they may be interpreted as consequences of a shock provoked by a massive predominant injury to the intestine [ru

Metabolic clues to salubrious longevity in the brain of the longest-lived rodent: the naked mole-rat.

Science.gov (United States)

Triplett, Judy C; Swomley, Aaron; Kirk, Jessime; Lewis, Katilyn; Orr, Miranda; Rodriguez, Karl; Cai, Jian; Klein, Jon B; Buffenstein, Rochelle; Butterfield, D Allan

2015-08-01

Naked mole-rats (NMRs) are the oldest-living rodent species. Living underground in a thermally stable ecological niche, NMRs have evolved certain exceptional traits, resulting in sustained health spans, negligible cognitive decline, and a pronounced resistance to age-related disease. Uncovering insights into mechanisms underlying these extraordinary traits involved in successful aging may conceivably provide crucial clues to extend the human life span and health span. One of the most fundamental processes inside the cell is the production of ATP, which is an essential fuel in driving all other energy-requiring cellular activities. Not surprisingly, a prominent hallmark in age-related diseases, such as neurodegeneration and cancer, is the impairment and dysregulation of metabolic pathways. Using a two-dimensional polyacrylamide gel electrophoresis proteomics approach, alterations in expression and phosphorylation levels of metabolic proteins in the brains of NMRs, aged 2-24 years, were evaluated in an age-dependent manner. We identified 13 proteins with altered levels and/or phosphorylation states that play key roles in various metabolic pathways including glycolysis, β-oxidation, the malate-aspartate shuttle, the Tricarboxylic Acid Cycle (TCA) cycle, the electron transport chain, NADPH production, as well as the production of glutamate. New insights into potential pathways involved in metabolic aspects of successful aging have been obtained by the identification of key proteins through which the NMR brain responds and adapts to the aging process and how the NMR brain adapted to resist age-related degeneration. This study examines the changes in the proteome and phosphoproteome in the brain of the naked mole-rat aged 2-24 years. We identified 13 proteins (labeled in red) with altered expression and/or phosphorylation levels that are conceivably associated with sustained metabolic functions in the oldest NMRs that may promote a sustained health span and life span. �

Physiological aspects of energy metabolism and gastrointestinal effects of carbohydrates.

Science.gov (United States)

Elia, M; Cummings, J H

2007-12-01

The energy values of carbohydrates continue to be debated. This is because of the use of different energy systems, for example, combustible, digestible, metabolizable, and so on. Furthermore, ingested macronutrients may not be fully available to tissues, and the tissues themselves may not be able fully to oxidize substrates made available to them. Therefore, for certain carbohydrates, the discrepancies between combustible energy (cEI), digestible energy (DE), metabolizable energy (ME) and net metabolizable energy (NME) may be considerable. Three food energy systems are in use in food tables and for food labelling in different world regions based on selective interpretation of the digestive physiology and metabolism of food carbohydrates. This is clearly unsatisfactory and confusing to the consumer. While it has been suggested that an enormous amount of work would have to be undertaken to change the current ME system into an NME system, the additional changes may not be as great as anticipated. In experimental work, carbohydrate is high in the macronutrient hierarchy of satiation. However, studies of eating behaviour indicate that it does not unconditionally depend on the oxidation of one nutrient, and argue against the operation of a simple carbohydrate oxidation or storage model of feeding behaviour to the exclusion of other macronutrients. The site, rate and extent of carbohydrate digestion in, and absorption from the gut are key to understanding the many roles of carbohydrate, although the concept of digestibility has different meanings. Within the nutrition community, the characteristic patterns of digestion that occur in the small (upper) vs large (lower) bowel are known to impact in contrasting ways on metabolism, while in the discussion of the energy value of foods, digestibility is defined as the proportion of combustible energy that is absorbed over the entire length of the gastrointestinal tract. Carbohydrates that reach the large bowel are fermented to

Comparison Between Cerebral Tissue Oxygen Tension and Energy Metabolism in Experimental Subdural Hematoma

DEFF Research Database (Denmark)

Nielsen, Troels Halfeld; Engell, Susanne I; Johnsen, Rikke Aagaard

2011-01-01

BACKGROUND: An experimental swine model (n = 7) simulating an acute subdural hematoma (ASDH) was employed (1) to explore the relation between the brain tissue oxygenation (PbtO(2)) and the regional cerebral energy metabolism as obtained by microdialysis, and (2) to define the lowest level of PbtO(2...

Energy Metabolism of the Brain, Including the Cooperation between Astrocytes and Neurons, Especially in the Context of Glycogen Metabolism

OpenAIRE

Falkowska, Anna; Gutowska, Izabela; Goschorska, Marta; Nowacki, Przemys?aw; Chlubek, Dariusz; Baranowska-Bosiacka, Irena

2015-01-01

Glycogen metabolism has important implications for the functioning of the brain, especially the cooperation between astrocytes and neurons. According to various research data, in a glycogen deficiency (for example during hypoglycemia) glycogen supplies are used to generate lactate, which is then transported to neighboring neurons. Likewise, during periods of intense activity of the nervous system, when the energy demand exceeds supply, astrocyte glycogen is immediately converted to lactate, s...

The Essential Role of Cholesterol Metabolism in the Intracellular Survival of Mycobacterium leprae Is Not Coupled to Central Carbon Metabolism and Energy Production.

Science.gov (United States)

Marques, Maria Angela M; Berrêdo-Pinho, Marcia; Rosa, Thabatta L S A; Pujari, Venugopal; Lemes, Robertha M R; Lery, Leticia M S; Silva, Carlos Adriano M; Guimarães, Ana Carolina R; Atella, Georgia C; Wheat, William H; Brennan, Patrick J; Crick, Dean C; Belisle, John T; Pessolani, Maria Cristina V

2015-12-01

Mycobacterium leprae induces the formation of lipid droplets, which are recruited to pathogen-containing phagosomes in infected macrophages and Schwann cells. Cholesterol is among the lipids with increased abundance in M. leprae-infected cells, and intracellular survival relies on cholesterol accumulation. The present study investigated the capacity of M. leprae to acquire and metabolize cholesterol. In silico analyses showed that oxidation of cholesterol to cholest-4-en-3-one (cholestenone), the first step of cholesterol degradation catalyzed by the enzyme 3β-hydroxysteroid dehydrogenase (3β-HSD), is apparently the only portion of the cholesterol catabolic pathway seen in Mycobacterium tuberculosis preserved by M. leprae. Incubation of bacteria with radiolabeled cholesterol confirmed the in silico predictions. Radiorespirometry and lipid analyses performed after incubating M. leprae with [4-(14)C]cholesterol or [26-(14)C]cholesterol showed the inability of this pathogen to metabolize the sterol rings or the side chain of cholesterol as a source of energy and carbon. However, the bacteria avidly incorporated cholesterol and, as expected, converted it to cholestenone both in vitro and in vivo. Our data indicate that M. leprae has lost the capacity to degrade and utilize cholesterol as a nutritional source but retains the enzyme responsible for its oxidation to cholestenone. Thus, the essential role of cholesterol metabolism in the intracellular survival of M. leprae is uncoupled from central carbon metabolism and energy production. Further elucidation of cholesterol metabolism in the host cell during M. leprae infection will establish the mechanism by which this lipid supports M. leprae intracellular survival and will open new avenues for novel leprosy therapies. Our study focused on the obligate intracellular pathogen Mycobacterium leprae and its capacity to metabolize cholesterol. The data make an important contribution for those interested in understanding the

Generality of leaf trait relationships: A test across six biomes

Energy Technology Data Exchange (ETDEWEB)

Reich, P.B. [Univ. of Minnesota, Saint Paul, MN (United States). Dept. of Forest Resources; Ellsworth, D.S. [Brookhaven National Lab., Upton, NY (United States). Dept. of Applied Science; Walters, M.B. [Michigan State Univ., East Lansing, MI (United States). Dept. of Forestry; Vose, J.M. [Forest Service, Otto, NC (United States). Coweeta Hydrological Lab.; Gresham, C. [Clemson Univ., Georgetown, SC (United States). Baruch Forest Inst.; Volin, J.C. [Florida Atlantic Univ., Davie, FL (United States). Div. of Science; Bowman, W.D. [Inst. of Arctic and Alpine Research, Boulder, CO (United States). Mountain Research Station]|[Univ. of Colorado, Boulder, CO (United States). Dept. of Evolutionary, Population, and Organismic Biology

1999-09-01

Convergence in interspecific leaf trait relationships across diverse taxonomic groups and biomes would have important evolutionary and ecological implications. Such convergence has been hypothesized to result from trade-offs that limit the combination of plant traits for any species. Here the authors address this issue by testing for biome differences in the slope and intercept of interspecific relationships among leaf traits: longevity, net photosynthetic capacity (A{sub max}), leaf diffusive conductance (G{sub S}), specific leaf area (SLA), and nitrogen (N) status, for more than 100 species in six distinct biomes of the Americas. The six biomes were: alpine tundra-subalpine forest ecotone, cold temperate forest-prairie ecotone, montane cool temperate forest, desert shrubland, subtropical forest, and tropical rain forest. Despite large differences in climate and evolutionary history, in all biomes mass-based leaf N (N{sub mass}), SLA, G{sub S}, and A{sub max} were positively related to one another and decreased with increasing leaf life span. The relationships between pairs of leaf traits exhibited similar slopes among biomes, suggesting a predictable set of scaling relationships among key leaf morphological, chemical, and metabolic traits that are replicated globally among terrestrial ecosystems regardless of biome or vegetation type. However, the intercept (i.e., the overall elevation of regression lines) of relationships between pairs of leaf traits usually differed among biomes. With increasing aridity across sites, species had greater A{sub max} for a given level of G{sub S} and lower SLA for any given leaf life span. Using principal components analysis, most variation among species was explained by an axis related to mass-based leaf traits (A{sub max}, N, and SLA) while a second axis reflected climate, G{sub S}, and other area-based leaf traits.

The genetic basis of natural variation in oenological traits in Saccharomyces cerevisiae.

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Francisco Salinas

Full Text Available Saccharomyces cerevisiae is the main microorganism responsible for wine alcoholic fermentation. The oenological phenotypes resulting from fermentation, such as the production of acetic acid, glycerol, and residual sugar concentration are regulated by multiple genes and vary quantitatively between different strain backgrounds. With the aim of identifying the quantitative trait loci (QTLs that regulate oenological phenotypes, we performed linkage analysis using three crosses between highly diverged S. cerevisiae strains. Segregants from each cross were used as starter cultures for 20-day fermentations, in synthetic wine must, to simulate actual winemaking conditions. Linkage analysis on phenotypes of primary industrial importance resulted in the mapping of 18 QTLs. We tested 18 candidate genes, by reciprocal hemizygosity, for their contribution to the observed phenotypic variation, and validated five genes and the chromosome II right subtelomeric region. We observed that genes involved in mitochondrial metabolism, sugar transport, nitrogen metabolism, and the uncharacterized ORF YJR030W explained most of the phenotypic variation in oenological traits. Furthermore, we experimentally validated an exceptionally strong epistatic interaction resulting in high level of succinic acid between the Sake FLX1 allele and the Wine/European MDH2 allele. Overall, our work demonstrates the complex genetic basis underlying wine traits, including natural allelic variation, antagonistic linked QTLs and complex epistatic interactions between alleles from strains with different evolutionary histories.

Acetate formation in the energy metabolism of parasitic helminths and protists.

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Tielens, Aloysius G M; van Grinsven, Koen W A; Henze, Katrin; van Hellemond, Jaap J; Martin, William

2010-03-15

Formation and excretion of acetate as a metabolic end product of energy metabolism occurs in many protist and helminth parasites, such as the parasitic helminths Fasciola hepatica, Haemonchus contortus and Ascaris suum, and the protist parasites, Giardia lamblia, Entamoeba histolytica, Trichomonas vaginalis as well as Trypanosoma and Leishmania spp. In all of these parasites acetate is a main end product of their energy metabolism, whereas acetate formation does not occur in their mammalian hosts. Acetate production might therefore harbour novel targets for the development of new anti-parasitic drugs. In parasites, acetate is produced from acetyl-CoA by two different reactions, both involving substrate level phosphorylation, that are catalysed by either a cytosolic acetyl-CoA synthetase (ACS) or an organellar acetate:succinate CoA-transferase (ASCT). The ACS reaction is directly coupled to ATP synthesis, whereas the ASCT reaction yields succinyl-CoA for ATP formation via succinyl-CoA synthetase (SCS). Based on recent work on the ASCTs of F. hepatica, T. vaginalis and Trypanosoma brucei we suggest the existence of three subfamilies of enzymes within the CoA-transferase family I. Enzymes of these three subfamilies catalyse the ASCT reaction in eukaryotes via the same mechanism, but the subfamilies share little sequence homology. The CoA-transferases of the three subfamilies are all present inside ATP-producing organelles of parasites, those of subfamily IA in the mitochondria of trypanosomatids, subfamily IB in the mitochondria of parasitic worms and subfamily IC in hydrogenosome-bearing parasites. Together with the recent characterisation among non-parasitic protists of yet a third route of acetate formation involving acetate kinase (ACK) and phosphotransacetylase (PTA) that was previously unknown among eukaryotes, these recent developments provide a good opportunity to have a closer look at eukaryotic acetate formation. (c) 2010 Australian Society for Parasitology

Brain energy metabolism and blood flow differences in healthy aging

DEFF Research Database (Denmark)

Aanerud, Joel; Borghammer, Per; Chakravarty, M Mallar

2012-01-01

Cerebral metabolic rate of oxygen consumption (CMRO(2)), cerebral blood flow (CBF), and oxygen extraction fraction (OEF) are important indices of healthy aging of the brain. Although a frequent topic of study, changes of CBF and CMRO(2) during normal aging are still controversial, as some authors......, and in the temporal cortex. Because of the inverse relation between OEF and capillary oxygen tension, increased OEF can compromise oxygen delivery to neurons, with possible perturbation of energy turnover. The results establish a possible mechanism of progression from healthy to unhealthy brain aging, as the regions...

Effects of an energy-dense diet and nicotinic acid supplementation on production and metabolic variables of primiparous or multiparous cows in periparturient period.

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Tienken, Reka; Kersten, Susanne; Frahm, Jana; Meyer, Ulrich; Locher, Lena; Rehage, Jürgen; Huber, Korinna; Kenéz, Ákos; Sauerwein, Helga; Mielenz, Manfred; Dänicke, Sven

2015-01-01

It is well observed that feeding energy-dense diets in dairy cows during the dry period can cause metabolic imbalances after parturition. Especially dairy cows with high body condition score (BCS) and fed an energy-dense diet were prone to develop production diseases due to metabolic disturbances postpartum. An experiment was conducted to determine the effects of an energy-dense diet and nicotinic acid (NA) on production and metabolic variables of primiparous and multiparous cows in late pregnancy and early lactation which were not pre-selected for high BCS. Thirty-six multiparous and 20 primiparous German Holstein cows with equal body conditions were fed with energy-dense (60% concentrate/40% roughage mixture; HC group) or adequate (30% concentrate/70% roughage mixture; LC group) diets prepartum. After parturition, concentrate proportion was dropped to 30% for all HC and LC groups and was increased to 50% within 16 days for LC and within 24 days for HC cows. In addition, half of the cows per group received 24 g NA supplement per day and cow aimed to attenuate the lipid mobilisation postpartum. Feeding energy-dense diets to late-pregnant dairy cows elevated the dry matter (p metabolic deviation postpartum as the effects of prepartum concentrate feeding were not carried over into postpartum period. Multiparous cows responded more profoundly to energy-dense feeding prepartum compared with primiparous cows, and parity-related differences in the transition from late pregnancy to lactation were obvious pre- and postpartum. The supplementation with 24 g NA did not reveal any effect on energy metabolism. This study clearly showed that energy-dense feeding prepartum did not result in metabolic imbalances postpartum in multiparous and primiparous cows not selected for high BCS. A genetic predisposition for an anabolic metabolic status as indicated by high BCS may be crucial for developing production diseases at the onset of lactation.

Fatty acid metabolism: target for metabolic syndrome

OpenAIRE

Wakil, Salih J.; Abu-Elheiga, Lutfi A.

2009-01-01

Fatty acids are a major energy source and important constituents of membrane lipids, and they serve as cellular signaling molecules that play an important role in the etiology of the metabolic syndrome. Acetyl-CoA carboxylases 1 and 2 (ACC1 and ACC2) catalyze the synthesis of malonyl-CoA, the substrate for fatty acid synthesis and the regulator of fatty acid oxidation. They are highly regulated and play important roles in the energy metabolism of fatty acids in animals, including humans. They...

Relationship between regional brain glucose metabolism and temperament factor of personality

Energy Technology Data Exchange (ETDEWEB)

Cho, Sang Soo; Lee, Eun Ju; Yoon, Eun Jin; Kim, Yu Kyeong; Lee, Won Woo; Kim, Sang Eun [Seoul National University College of Medicine, Seoul (Korea, Republic of)

2005-07-01

Temperament factor of personality has been considered to have correlation with activity in a specific central monoaminergic system. In an attempt to explore neuronal substrate of biogenetic personality traits, we examined the relationship between regional brain glucose metabolism and temperament factor of personality. Twenty right-handed healthy subjects (age, 24{+-}4 yr: 10 females and 10 males) were studied with FDG PET. Their temperaments were assessed using the Temperament and Character Inventory (TCI), which consisted of four temperament factors (harm avoidance (HA), novelty seeking (NS), reward dependence (RD), persistency) and three personality factors. The relationship between regional glucose metabolism and each temperament score was tested using SPM99 (P < 0.005, uncorrected). NS score was negatively correlated with glucose metabolism in the frontal areas, insula, and superior temporal gyrus mainly in the right hemisphere. Positive correlation between NS score and glucose metabolism was observed in the left superior temporal gyrus. HA score showed negative correlation with glucose metabolism in the middle and orbitofrontal gyri as well as in the parahippocampal gyrus. RD score was positively correlated with glucose metabolism in the left middle frontal gyrus and negative correlated in the posterior cingulate gyrus and caudate nucleus. We identified the relationship between regional brain glucose metabolism and temperamental personality trait. Each temperament factor had a relation with functions of specific brain areas. These results help understand biological background of personality and specific feedback circuits associated with each temperament factor.

Relationship between regional brain glucose metabolism and temperament factor of personality

International Nuclear Information System (INIS)

Cho, Sang Soo; Lee, Eun Ju; Yoon, Eun Jin; Kim, Yu Kyeong; Lee, Won Woo; Kim, Sang Eun

2005-01-01

Temperament factor of personality has been considered to have correlation with activity in a specific central monoaminergic system. In an attempt to explore neuronal substrate of biogenetic personality traits, we examined the relationship between regional brain glucose metabolism and temperament factor of personality. Twenty right-handed healthy subjects (age, 24±4 yr: 10 females and 10 males) were studied with FDG PET. Their temperaments were assessed using the Temperament and Character Inventory (TCI), which consisted of four temperament factors (harm avoidance (HA), novelty seeking (NS), reward dependence (RD), persistency) and three personality factors. The relationship between regional glucose metabolism and each temperament score was tested using SPM99 (P < 0.005, uncorrected). NS score was negatively correlated with glucose metabolism in the frontal areas, insula, and superior temporal gyrus mainly in the right hemisphere. Positive correlation between NS score and glucose metabolism was observed in the left superior temporal gyrus. HA score showed negative correlation with glucose metabolism in the middle and orbitofrontal gyri as well as in the parahippocampal gyrus. RD score was positively correlated with glucose metabolism in the left middle frontal gyrus and negative correlated in the posterior cingulate gyrus and caudate nucleus. We identified the relationship between regional brain glucose metabolism and temperamental personality trait. Each temperament factor had a relation with functions of specific brain areas. These results help understand biological background of personality and specific feedback circuits associated with each temperament factor

Effect of carbon/nitrogen ratio on carbohydrate metabolism and light energy dissipation mechanisms in Arabidopsis thaliana.

Science.gov (United States)

Huarancca Reyes, Thais; Scartazza, Andrea; Lu, Yu; Yamaguchi, Junji; Guglielminetti, Lorenzo

2016-08-01

Carbon (C) and nitrogen (N) nutrient sources are essential elements for metabolism, and their availability must be tightly coordinated for the optimal growth and development in plants. Plants are able to sense and respond to different C/N conditions via specific partitioning of C and N sources and the regulation of a complex cellular metabolic activity. We studied how the interaction between C and N signaling could affect carbohydrate metabolism, soluble sugar levels, photochemical efficiency of photosystem II (PSII) and the ability to drive the excess energy in Arabidopsis seedlings under moderated and disrupted C/N-nutrient conditions. Invertase and sucrose synthase activities were markedly affected by C/N-nutrient status depending on the phosphorylation status, suggesting that these enzymes may necessarily be modulated by their direct phosphorylation or phosphorylation of proteins that form complex with them in response to C/N stress. In addition, the enzymatic activity of these enzymes was also correlated with the amount of sugars, which not only act as substrate but also as signaling compounds. Analysis of chlorophyll fluorescence in plants under disrupted C/N condition suggested a reduction of electron transport rate at PSII level associated with a higher capacity for non-radiative energy dissipation in comparison with plants under moderated C/N condition. In conclusion, the tight coordination between C and N not only affects the carbohydrates metabolism and their concentration within plant tissues, but also the partitioning of the excitation energy at PSII level between radiative (electron transport) and non-radiative (heat) dissipation pathways. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Genetic associations of ketosis and displaced abomasum with milk production traits in early first lactation of Canadian Holsteins.

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Koeck, A; Miglior, F; Jamrozik, J; Kelton, D F; Schenkel, F S

2013-07-01

The aim of this study was to investigate the genetic associations of ketosis and displaced abomasum with milk production traits in early first lactation of Canadian Holsteins. Health data recorded by producers were available from the national dairy cattle health system in Canada. Test-day records of milk, fat, and protein yields were obtained from the routine milk recoding scheme. Ketosis and displaced abomasum were defined as binary traits (0 = healthy; 1 = sick) based on whether or not the cow had at least 1 case of the respective disease in the period from calving to 100 d after calving. Mean frequencies of ketosis and displaced abomasum were 4.1 and 2.7%, respectively. The following milk production traits were considered: milk yield, fat percentage (Fat%), protein percentage (Prot%), fat-to-protein (F:P) ratio, and F:P ratio >1.5. The trait F:P ratio >1.5 was scored as 1 or 0, based on whether or not the cow had an F:P ratio >1.5. For milk production traits, the first (5-30 d in milk) and the second (31-60 d in milk) test days were considered. Data were analyzed using bivariate linear animal models. Average heritabilities of 0.02 and 0.04 were obtained for ketosis and displaced abomasum, respectively. For milk production traits, the lowest heritabilities were obtained for F:P >1.5 (0.04 to 0.08), whereas the highest estimates were found for Prot% (0.27 to 0.38). Ketosis and displaced abomasum were genetically uncorrelated with milk yield in early lactation. Moderate favorable correlations were found between metabolic diseases and milk composition traits. Ketosis was significantly correlated with Fat% (0.33), F:P ratio (0.30), and F:P ratio >1.5 (0.35) at the first test day, whereas all genetic correlations with milk composition traits at the second test day were not significant and close to zero. Significant favorable genetic correlations were also found between displaced abomasum and F:P ratio (0.26), F:P ratio >1.5 (0.25) and Prot% (-0.19) at the first test

CO2 and temperature effects on morphological and physiological traits affecting risk of drought-induced mortality.

Science.gov (United States)

Duan, Honglang; Chaszar, Brian; Lewis, James D; Smith, Renee A; Huxman, Travis E; Tissue, David T

2018-04-26

Despite a wealth of eco-physiological assessments of plant response to extreme drought, few studies have addressed the interactive effects of global change factors on traits driving mortality. To understand the interaction between hydraulic and carbon metabolic traits influencing tree mortality, which may be independently influenced by atmospheric [CO2] and temperature, we grew Eucalyptus sideroxylon A. Cunn. ex Woolls from seed in a full-factorial [CO2] (280, 400 and 640 μmol mol-1, Cp, Ca and Ce, respectively) and temperature (ambient and ambient +4 °C, Ta and Te, respectively) experiment. Prior to drought, growth across treatment combinations resulted in significant variation in physiological and morphological traits, including photosynthesis (Asat), respiration (Rd), stomatal conductance, carbohydrate storage, biomass and leaf area (LA). Ce increased Asat, LA and leaf carbohydrate concentration compared with Ca, while Cp generated the opposite response; Te reduced Rd. However, upon imposition of drought, Te hastened mortality (9 days sooner compared with Ta), while Ce significantly exacerbated drought stress when combined with Te. Across treatments, earlier time-to-mortality was mainly associated with lower (more negative) leaf water potential (Ψl) during the initial drought phase, along with higher water loss across the first 3 weeks of water limitation. Among many variables, Ψl was more important than carbon status in predicting time-to-mortality across treatments, yet leaf starch was associated with residual variation within treatments. These results highlight the need to carefully consider the integration, interaction and hierarchy of traits contributing to mortality, along with their responses to environmental drivers. Both morphological traits, which influence soil resource extraction, and physiological traits, which affect water-for-carbon exchange to the atmosphere, must be considered to adequately predict plant response to drought. Researchers have

Energy metabolism in rat mast cells in relation to histamine secretion

DEFF Research Database (Denmark)

Johansen, T

1987-01-01

1. The relation between the energy metabolism and the secretory activity of rat peritoneal mast cells has been studied by determination of the cellular content of ATP and the rate of lactate production reflecting the rate of ATP synthesis under various experimental conditions. Secretion...... and the cellular ATP content at the time of cell activation was demonstrated. This may indicate a direct link between ATP and the secretory mechanism. 3. The possibility of an increased utilization of ATP during histamine secretion was explored in mast cells exposed to metabolic inhibitors. Incubation of mast...... cells with 2-deoxyglucose (2-DG) decreased the ATP content of the cells, and a long-lasting and stable level of mast cell ATP was observed. This is explained by a small decrease in the rate of ATP-synthesis by 2-DG. In 2-DG-treated cells secretion of histamine in response to compound 48...

Restriction on an energy-dense diet improves markers of metabolic health and cellular aging in mice through decreasing hepatic mTOR activity.

Science.gov (United States)

Schloesser, Anke; Campbell, Graeme; Glüer, Claus-Christian; Rimbach, Gerald; Huebbe, Patricia

2015-02-01

Dietary restriction (DR) on a normal low-fat diet improves metabolic health and may prolong life span. However, it is still uncertain whether restriction of an energy-dense, high-fat diet would also be beneficial and mitigate age-related processes. In the present study, we determined biomarkers of metabolic health, energy metabolism, and cellular aging in obesity-prone mice subjected to 30% DR on a high-fat diet for 6 months. Dietary-restricted mice had significantly lower body weights, less adipose tissue, lower energy expenditure, and altered substrate oxidation compared to their ad libitum-fed counterparts. Hepatic major urinary proteins (Mup) expression, which is linked to glucose and energy metabolism, and biomarkers of metabolic health, including insulin, glucose, cholesterol, and leptin/adiponectin ratio, were likewise reduced in high-fat, dietary-restricted mice. Hallmarks of cellular senescence such as Lamp2a and Hsc70 that mediate chaperone-mediated autophagy were induced and mechanistic target of rapamycin (mTOR) signaling mitigated upon high-fat DR. In contrast to DR applied in low-fat diets, anti-oxidant gene expression, proteasome activity, as well as 5'-adenosine monophosphate-activated protein kinase (AMPK) activation were not changed, suggesting that high-fat DR may attenuate some processes associated with cellular aging without the induction of cellular stress response or energy deprivation.

Mechanistic drivers of flexibility in summit metabolic rates of small birds.

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David Swanson

Full Text Available Flexible metabolic phenotypes allow animals to adjust physiology to better fit ecological or environmental demands, thereby influencing fitness. Summit metabolic rate (Msum = maximal thermogenic capacity is one such flexible trait. Skeletal muscle and heart masses and myocyte metabolic intensity are potential drivers of Msum flexibility in birds. We examined correlations of skeletal muscle and heart masses and pectoralis muscle citrate synthase (CS activity (an indicator of cellular metabolic intensity with Msum in house sparrows (Passer domesticus and dark-eyed juncos (Junco hyemalis to determine whether these traits are associated with Msum variation. Pectoralis mass was positively correlated with Msum for both species, but no significant correlation remained for either species after accounting for body mass (Mb variation. Combined flight and leg muscle masses were also not significantly correlated with Msum for either species. In contrast, heart mass was significantly positively correlated with Msum for juncos and nearly so (P = 0.054 for sparrows. Mass-specific and total pectoralis CS activities were significantly positively correlated with Msum for sparrows, but not for juncos. Thus, myocyte metabolic intensity influences Msum variation in house sparrows, although the stronger correlation of total (r = 0.495 than mass-specific (r = 0.378 CS activity with Msum suggests that both pectoralis mass and metabolic intensity impact Msum. In contrast, neither skeletal muscle masses nor pectoralis metabolic intensity varied with Msum in juncos. However, heart mass was associated with Msum variation in both species. These data suggest that drivers of metabolic flexibility are not uniform among bird species.

Prenatal programming in an obese swine model: sex-related effects of maternal energy restriction on morphology, metabolism and hypothalamic gene expression.

Science.gov (United States)

Óvilo, Cristina; González-Bulnes, Antonio; Benítez, Rita; Ayuso, Miriam; Barbero, Alicia; Pérez-Solana, Maria L; Barragán, Carmen; Astiz, Susana; Fernández, Almudena; López-Bote, Clemente

2014-02-01

Maternal energy restriction during pregnancy predisposes to metabolic alterations in the offspring. The present study was designed to evaluate phenotypic and metabolic consequences following maternal undernutrition in an obese pig model and to define the potential role of hypothalamic gene expression in programming effects. Iberian sows were fed a control or a 50 % restricted diet for the last two-thirds of gestation. Newborns were assessed for body and organ weights, hormonal and metabolic status, and hypothalamic expression of genes implicated in energy homeostasis, glucocorticoid function and methylation. Weight and adiposity were measured in adult littermates. Newborns of the restricted sows were lighter (P control newborns of both the sexes (P metabolic stress by nutrient insufficiency. A lower hypothalamic expression of anorexigenic peptides (LEPR and POMC, P controls (Pmetabolic alterations in the offspring. Differences in gene expression at birth and higher growth and adiposity in adulthood suggest a female-specific programming effect for a positive energy balance, possibly due to overexposure to endogenous stress-induced glucocorticoids.

Redistribution of whole-body energy metabolism by exercise. A positron emission tomography study

International Nuclear Information System (INIS)

Masud, M.M.; Miyake, Masayasu; Watanuki, Shoichi; Itoh, Masatoshi; Tashiro, Manabu; Fujimoto, Toshihiko

2009-01-01

Our aim was to evaluate changes in glucose metabolism of skeletal muscles and viscera induced by different workloads using 18 F-2-fluoro-2-deoxyglucose ([ 18 F]FDG) and three-dimensional positron emission tomography (3-D PET). Five male volunteers performed ergometer bicycle exercise for 40 min at 40% and 70% of the maximal O 2 consumption (VO 2max ). [ 18 ]FDG was injected 10 min later following the exercise task. Whole-body 3-D PET was performed. Five other male volunteers were studied as a control to compare with the exercise group. The PET image data were analyzed using manually defined regions of interest to quantify the regional metabolic rate of glucose (rMRGlc). Group comparisons were made using analysis of variance, and significant differences (P 18 F]FDG-PET can be used as an index of organ energy metabolism for moderate exercise workloads (70% VO 2max ). The results of this investigation may contribute to sports medicine and rehabilitation science. (author)

SirT1 regulates energy metabolism and response to caloric restriction in mice.

Directory of Open Access Journals (Sweden)

Gino Boily

Full Text Available The yeast sir2 gene and its orthologues in Drosophila and C. elegans have well-established roles in lifespan determination and response to caloric restriction. We have studied mice carrying two null alleles for SirT1, the mammalian orthologue of sir2, and found that these animals inefficiently utilize ingested food. These mice are hypermetabolic, contain inefficient liver mitochondria, and have elevated rates of lipid oxidation. When challenged with a 40% reduction in caloric intake, normal mice maintained their metabolic rate and increased their physical activity while the metabolic rate of SirT1-null mice dropped and their activity did not increase. Moreover, CR did not extend lifespan of SirT1-null mice. Thus, SirT1 is an important regulator of energy metabolism and, like its orthologues from simpler eukaryotes, the SirT1 protein appears to be required for a normal response to caloric restriction.

Constraints on energy intake in fish: the link between diet composition, energy metabolism, and energy intake in rainbow trout.

Directory of Open Access Journals (Sweden)

Subramanian Saravanan

Full Text Available The hypothesis was tested that fish fed to satiation with iso-energetic diets differing in macronutrient composition will have different digestible energy intakes (DEI but similar total heat production. Four iso-energetic diets (2 × 2 factorial design were formulated having a contrast in i the ratio of protein to energy (P/E: high (H(P/E vs. low (L(P/E and ii the type of non-protein energy (NPE source: fat vs. carbohydrate which were iso-energetically exchanged. Triplicate groups (35 fish/tank of rainbow trout were hand-fed each diet twice daily to satiation for 6 weeks under non-limiting water oxygen conditions. Feed intake (FI, DEI (kJ kg(-0.8 d(-1 and growth (g kg(-0.8 d(-1 of trout were affected by the interaction between P/E ratio and NPE source of the diet (P0.05. Our data suggest that the control of DEI in trout might be a function of heat production, which in turn might reflect a physiological limit related with oxidative metabolism.

Metabolite analysis of Mycobacterium species under aerobic and hypoxic conditions reveals common metabolic traits.

Science.gov (United States)

Drapal, Margit; Wheeler, Paul R; Fraser, Paul D

2016-08-01

A metabolite profiling approach has been implemented to elucidate metabolic adaptation at set culture conditions in five Mycobacterium species (two fast- and three slow-growing) with the potential to act as model organisms for Mycobacterium tuberculosis (Mtb). Analysis has been performed over designated growth phases and under representative environments (nutrient and oxygen depletion) experienced by Mtb during infection. The procedure was useful in determining a range of metabolites (60-120 compounds) covering nucleotides, amino acids, organic acids, saccharides, fatty acids, glycerols, -esters, -phosphates and isoprenoids. Among these classes of compounds, key biomarker metabolites, which can act as indicators of pathway/process activity, were identified. In numerous cases, common metabolite traits were observed for all five species across the experimental conditions (e.g. uracil indicating DNA repair). Amino acid content, especially glutamic acid, highlighted the different properties between the fast- and slow-growing mycobacteria studied (e.g. nitrogen assimilation). The greatest similarities in metabolite composition between fast- and slow-growing mycobacteria were apparent under hypoxic conditions. A comparison to previously reported transcriptomic data revealed a strong correlation between changes in transcription and metabolite content. Collectively, these data validate the changes in the transcription at the metabolite level, suggesting transcription exists as one of the predominant modes of cellular regulation in Mycobacterium. Sectors with restricted correlation between metabolites and transcription (e.g. hypoxic cultivation) warrant further study to elucidate and exploit post-transcriptional modes of regulation. The strong correlation between the laboratory conditions used and data derived from in vivo conditions, indicate that the approach applied is a valuable addition to our understanding of cell regulation in these Mycobacterium species.

Nitrogen and phosphorus availabilities interact to modulate leaf trait scaling relationships across six plant functional types in a controlled-environment study.

Science.gov (United States)

Crous, Kristine Y; O'Sullivan, Odhran S; Zaragoza-Castells, Joana; Bloomfield, Keith J; Negrini, A Clarissa A; Meir, Patrick; Turnbull, Matthew H; Griffin, Kevin L; Atkin, Owen K

2017-08-01

Nitrogen (N) and phosphorus (P) have key roles in leaf metabolism, resulting in a strong coupling of chemical composition traits to metabolic rates in field-based studies. However, in such studies, it is difficult to disentangle the effects of nutrient supply per se on trait-trait relationships. Our study assessed how high and low N (5 mM and 0.4 mM, respectively) and P (1 mM and 2 μM, respectively) supply in 37 species from six plant functional types (PTFs) affected photosynthesis (A) and respiration (R) (in darkness and light) in a controlled environment. Low P supply increased scaling exponents (slopes) of area-based log-log A-N or R-N relationships when N supply was not limiting, whereas there was no P effect under low N supply. By contrast, scaling exponents of A-P and R-P relationships were altered by P and N supply. Neither R : A nor light inhibition of leaf R was affected by nutrient supply. Light inhibition was 26% across nutrient treatments; herbaceous species exhibited a lower degree of light inhibition than woody species. Because N and P supply modulates leaf trait-trait relationships, the next generation of terrestrial biosphere models may need to consider how limitations in N and P availability affect trait-trait relationships when predicting carbon exchange. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

Physical activity energy expenditure vs cardiorespiratory fitness level in impaired glucose metabolism

DEFF Research Database (Denmark)

Lidegaard, Lærke P; Hansen, Anne-Louise Smidt; Johansen, Nanna B

2015-01-01

Aim/hypothesis: Little is known about the relative roles of physical activity energy expenditure (PAEE) and cardiorespiratory fitness (CRF) as determinants of glucose regulation. The aim of this study was to examine the associations of PAEE and CRF with markers of glucose metabolism, and to test...... the hypothesis that CRF modifies the association between PAEE and glucose metabolism. Methods: We analysed cross-sectional data from 755 adults from the Danish ADDITION-PRO study. On the basis of OGTT results, participants without known diabetes were classified as having normal glucose tolerance, isolated...... impaired fasting glycaemia (i-IFG), isolated impaired glucose tolerance (i-IGT), combined IFG + IGT or screen-detected diabetes mellitus. Markers of insulin sensitivity and beta cell function were determined. PAEE was measured using a combined heart rate and movement sensor. CRF (maximal oxygen uptake...

I, IGF-II and IGFBP-II with production traits in breeder hens

African Journals Online (AJOL)

USER

2010-02-08

Feb 8, 2010 ... have shown that circulating IGF-I affects growth rate, body composition and lipid metabolism in ... about 2500 birds of two sexes were kept to produce hatching eggs and chicks produced from these eggs ... Economic indexes are calculated for these traits and birds of two sexes are selected based on their ...

Adaptive trade-offs in juvenile salmonid metabolism associated with habitat partitioning between coho salmon and steelhead trout in coastal streams.

Science.gov (United States)

Van Leeuwen, Travis E; Rosenfeld, Jordan S; Richards, Jeffrey G

2011-09-01

1. Adaptive trade-offs are fundamental to the evolution of diversity and the coexistence of similar taxa and occur when complimentary combinations of traits maximize efficiency of resource exploitation or survival at different points on environmental gradients. 2. Standard metabolic rate (SMR) is a key physiological trait that reflects adaptations to baseline metabolic performance, whereas active metabolism reflects adaptations to variable metabolic output associated with performance related to foraging, predator avoidance, aggressive interactions or migratory movements. Benefits of high SMR and active metabolism may change along a resource (productivity) gradient, indicating that a trade-off exists among active metabolism, resting metabolism and energy intake. 3. We measured and compared SMR, maximal metabolic rate (MMR), aerobic scope (AS), swim performance (UCrit) and growth of juvenile hatchery and wild steelhead and coho salmon held on high- and low-food rations in order to better understand the potential significance of variation in SMR to growth, differentiation between species, and patterns of habitat use along a productivity gradient. 4. We found that differences in SMR, MMR, AS, swim performance and growth rate between steelhead trout and coho salmon were reduced in hatchery-reared fish compared with wild fish. Wild steelhead had a higher MMR, AS, swim performance and growth rate than wild coho, but adaptations between species do not appear to involve differences in SMR or to trade-off increased growth rate against lower swim performance, as commonly observed for high-growth strains. Instead, we hypothesize that wild steelhead may be trading off higher growth rate for lower food consumption efficiency, similar to strategies adopted by anadromous vs. resident brook trout and Atlantic salmon vs. brook trout. This highlights potential differences in food consumption and digestion strategies as cryptic adaptations ecologically differentiating salmonid species

Impact of the Polymorphism Near MC4R (rs17782313 on Obesity- and Metabolic-Related Traits in Women Participating in an Aerobic Training Program

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Leońska-Duniec Agata

2017-08-01

Full Text Available The C/T polymorphism (rs17782313 mapped 188 kb downstream of the melanocortin-4 receptor gene (MC4R shows a strong relationship with an increased body mass index (BMI and the risk of type 2 diabetes. However, the information on polymorphism’s potential modifying effect on obesity- and metabolic-related traits achieved through training is still unknown. Therefore, we decided to check if selected body measurements observed in physically active participants would be modulated by the genotype. The genotype distribution was examined in a group of 201 Polish women measured for chosen traits before and after the completion of a 12 week moderate-intensive aerobic training program. A statistically significant relationship between the glucose level and the genotype was identified (p = 0.046. Participants with CC and CT genotypes had a higher glucose level during the entire study period compared with the TT genotype. However, our results did not confirm the relationship between the C allele and an increased BMI or other obesity-related traits. Additionally, we did not observe a near MC4R C/T polymorphism x physical activity interaction. However, our results revealed that majority of obesity-related variables changed significantly during the 12 week training program. The effect sizes (d of these changes ranged from small to medium (d = 0.11-0.80, whereas the largest effect (d = 0.80; i.e. medium was reported for the fat mass content (FM. We found a relationship between the near MC4R C/T polymorphism and an increased glucose level, and it is thus a candidate to influence type 2 diabetes. Interestingly, after the 12 week training program, participants with the C (risk allele with fasting hyperglycemia had a normal glucose level. Although, this change was not statistically significant, it shows an important trend which needs further investigation.

Effect of the pattern of food intake on human energy metabolism.

Science.gov (United States)

Verboeket-van de Venne, W P; Westerterp, K R; Kester, A D

1993-07-01

The pattern of food intake can affect the regulation of body weight and lipogenesis. We studied the effect of meal frequency on human energy expenditure (EE) and its components. During 1 week ten male adults (age 25-61 years, body mass index 20.7-30.4 kg/m2) were fed to energy balance at two meals/d (gorging pattern) and during another week at seven meals/d (nibbling pattern). For the first 6 d of each week the food was provided at home, followed by a 36 h stay in a respiration chamber. O2 consumption and CO2 production (and hence EE) were calculated over 24 h. EE in free-living conditions was measured over the 2 weeks with doubly-labelled water (average daily metabolic rate, ADMR). The three major components of ADMR are basal metabolic rate (BMR), diet-induced thermogenesis (DIT) and EE for physical activity (ACT). There was no significant effect of meal frequency on 24 h EE or ADMR. Furthermore, BMR and ACT did not differ between the two patterns. DIT was significantly elevated in the gorging pattern, but this effect was neutralized by correction for the relevant time interval. With the method used for determination of DIT no significant effect of meal frequency on the contribution of DIT to ADMR could be demonstrated.

Energy metabolism after U.V.-irradiation in a sensitive yeast strain

International Nuclear Information System (INIS)

Kiefer, J.

1976-01-01

Stationary-phase cells of an excision-repair deficient diploid yeast (strain 2094) were UV-irradiated at exposures of up to 440 erg mm -2 and then resuspended in fresh medium. Measurements of energy metabolism per cell at periods of up to 6 hours after irradiation showed that cellular respiration was increased for all doses tested from about 3 hours after exposure, whereas fermentation did not start before about 2 hours after irradiation, never significantly exceeded control values and was markedly inhibited by the higher doses. The results suggest that respiration is under nuclear control, since a mutation in one gene is thought to be the only difference between this strain and the wild-type. The D 0 value of about 360 erg mm -2 found for the relative cellular fermentation at 2 hours after irradiation was used to give an estimate of the size of the structural gene involved, of about 3000 nucleotides, or a protein with 1000 amino-acid residues, compatible with the molecular weight of alcohol dehydrogenase. Fermentation can therefore be inhibited in this sensitive strain by lesions in the structural gene of a key enzyme. Since respiration was increased even more in repair-deficient than in repair-proficient strains, it must be assumed that higher energy metabolism is not linked to the repair process, but rather reflects a general disturbance in cellular regulation. (U.K.)

Cellular metabolic rate is influenced by life-history traits in tropical and temperate birds.

Science.gov (United States)

Jimenez, Ana Gabriela; Van Brocklyn, James; Wortman, Matthew; Williams, Joseph B

2014-01-01

In general, tropical birds have a "slow pace of life," lower rates of whole-animal metabolism and higher survival rates, than temperate species. A fundamental challenge facing physiological ecologists is the understanding of how variation in life-history at the whole-organism level might be linked to cellular function. Because tropical birds have lower rates of whole-animal metabolism, we hypothesized that cells from tropical species would also have lower rates of cellular metabolism than cells from temperate species of similar body size and common phylogenetic history. We cultured primary dermal fibroblasts from 17 tropical and 17 temperate phylogenetically-paired species of birds in a common nutritive and thermal environment and then examined basal, uncoupled, and non-mitochondrial cellular O2 consumption (OCR), proton leak, and anaerobic glycolysis (extracellular acidification rates [ECAR]), using an XF24 Seahorse Analyzer. We found that multiple measures of metabolism in cells from tropical birds were significantly lower than their temperate counterparts. Basal and uncoupled cellular metabolism were 29% and 35% lower in cells from tropical birds, respectively, a decrease closely aligned with differences in whole-animal metabolism between tropical and temperate birds. Proton leak was significantly lower in cells from tropical birds compared with cells from temperate birds. Our results offer compelling evidence that whole-animal metabolism is linked to cellular respiration as a function of an animal's life-history evolution. These findings are consistent with the idea that natural selection has uniquely fashioned cells of long-lived tropical bird species to have lower rates of metabolism than cells from shorter-lived temperate species.

Cellular metabolic rate is influenced by life-history traits in tropical and temperate birds.

Directory of Open Access Journals (Sweden)

Ana Gabriela Jimenez

Full Text Available In general, tropical birds have a "slow pace of life," lower rates of whole-animal metabolism and higher survival rates, than temperate species. A fundamental challenge facing physiological ecologists is the understanding of how variation in life-history at the whole-organism level might be linked to cellular function. Because tropical birds have lower rates of whole-animal metabolism, we hypothesized that cells from tropical species would also have lower rates of cellular metabolism than cells from temperate species of similar body size and common phylogenetic history. We cultured primary dermal fibroblasts from 17 tropical and 17 temperate phylogenetically-paired species of birds in a common nutritive and thermal environment and then examined basal, uncoupled, and non-mitochondrial cellular O2 consumption (OCR, proton leak, and anaerobic glycolysis (extracellular acidification rates [ECAR], using an XF24 Seahorse Analyzer. We found that multiple measures of metabolism in cells from tropical birds were significantly lower than their temperate counterparts. Basal and uncoupled cellular metabolism were 29% and 35% lower in cells from tropical birds, respectively, a decrease closely aligned with differences in whole-animal metabolism between tropical and temperate birds. Proton leak was significantly lower in cells from tropical birds compared with cells from temperate birds. Our results offer compelling evidence that whole-animal metabolism is linked to cellular respiration as a function of an animal's life-history evolution. These findings are consistent with the idea that natural selection has uniquely fashioned cells of long-lived tropical bird species to have lower rates of metabolism than cells from shorter-lived temperate species.

Comparison of Various Indices of Energy Metabolism in Recumbent and Healthy Dairy Cows.

Science.gov (United States)

Guyot, Hugues; Detilleux, Johann; Lebreton, Pascal; Garnier, Catherine; Bonvoisin, Marie; Rollin, Frederic; Sandersen, Charlotte

2017-01-01

Downer cow syndrome (DCS) is often diagnosed in dairy cattle during the early post-partum period. The etiology of this condition is not completely understood, as it can be related to the energetic or electrolyte metabolism, as well as to infectious diseases or to trauma. The aim of this study is to compare energy metabolism and insulin sensitivity indices and various biochemical parameters between recumbent and healthy dairy cows. A prospective study has been undertaken on 361 recumbent and 80 healthy Holstein cows. Plasmatic glucose, insulin, non-esterified fatty acid (NEFA) and β-hydroxybutyrate (BHB) were assayed in all cows in order to calculate the insulin sensitivity indices but also minerals (Calcium, Phosphorous and Magnesium), thyroxin and creatine kinase. Body Condition Scores (BCS) was assessed. Significant differences in NEFA, and the glucose and insulin sensitivity indices ("Homeostasis Model Assessment" HOMA, "Revised Quantitative Insulin Sensitivity Check Index" RQUICKI, RQUICKI-BHB) were observed between healthy and recumbent cows in the early post-parturient period indicating disturbances of glucose and insulin homeostasis in the recumbent cows. In the same manner, mineral concentrations were significantly different between healthy and recumbent cows. Glucose, insulin NEFA, and HOMA, were different between early post-partum downer cows and the DCS-affected cows later in lactation. Results indicate disturbances in energy homeostasis in DCS-affected dairy cows. Further research should determine a prognostic value of the indices in cows suffering from recumbency of metabolic origin.

Comparison of Various Indices of Energy Metabolism in Recumbent and Healthy Dairy Cows.

Directory of Open Access Journals (Sweden)

Hugues Guyot

Full Text Available Downer cow syndrome (DCS is often diagnosed in dairy cattle during the early post-partum period. The etiology of this condition is not completely understood, as it can be related to the energetic or electrolyte metabolism, as well as to infectious diseases or to trauma.The aim of this study is to compare energy metabolism and insulin sensitivity indices and various biochemical parameters between recumbent and healthy dairy cows.A prospective study has been undertaken on 361 recumbent and 80 healthy Holstein cows.Plasmatic glucose, insulin, non-esterified fatty acid (NEFA and β-hydroxybutyrate (BHB were assayed in all cows in order to calculate the insulin sensitivity indices but also minerals (Calcium, Phosphorous and Magnesium, thyroxin and creatine kinase. Body Condition Scores (BCS was assessed.Significant differences in NEFA, and the glucose and insulin sensitivity indices ("Homeostasis Model Assessment" HOMA, "Revised Quantitative Insulin Sensitivity Check Index" RQUICKI, RQUICKI-BHB were observed between healthy and recumbent cows in the early post-parturient period indicating disturbances of glucose and insulin homeostasis in the recumbent cows. In the same manner, mineral concentrations were significantly different between healthy and recumbent cows. Glucose, insulin NEFA, and HOMA, were different between early post-partum downer cows and the DCS-affected cows later in lactation.Results indicate disturbances in energy homeostasis in DCS-affected dairy cows. Further research should determine a prognostic value of the indices in cows suffering from recumbency of metabolic origin.

The relationship between basal metabolic rate and daily energy expenditure in birds and mammals

NARCIS (Netherlands)

Ricklefs, RE; Konarzewski, M; Daan, S

We examined the relationship between daily energy expenditure (DEE) and basal metabolic rate (BMR) in birds and mammals. Two models of the relationship between DEE and BMR were distinguished: a ''shared pathways'' model in which DEE replaces BMR in the active organism and a ''partitioned pathways''

Dynamic changes in energy metabolism upon embryonic stem cell differentiation support developmental toxicant identification

NARCIS (Netherlands)

Dartel, van D.A.M.; Schulpen, S.H.; Theunissen, P.T.; Bunschoten, A.; Piersma, A.H.; Keijer, J.

2014-01-01

Embryonic stem cells (ESC) are widely used to study embryonic development and to identify developmental toxicants. Particularly, the embryonic stem cell test (EST) is well known as in vitro model to identify developmental toxicants. Although it is clear that energy metabolism plays a crucial role in

Glucose stimulates intestinal epithelial crypt proliferation by modulating cellular energy metabolism.

Science.gov (United States)

Zhou, Weinan; Ramachandran, Deepti; Mansouri, Abdelhak; Dailey, Megan J

2018-04-01

The intestinal epithelium plays an essential role in nutrient absorption, hormone release, and barrier function. Maintenance of the epithelium is driven by continuous cell renewal by stem cells located in the intestinal crypts. The amount and type of diet influence this process and result in changes in the size and cellular make-up of the tissue. The mechanism underlying the nutrient-driven changes in proliferation is not known, but may involve a shift in intracellular metabolism that allows for more nutrients to be used to manufacture new cells. We hypothesized that nutrient availability drives changes in cellular energy metabolism of small intestinal epithelial crypts that could contribute to increases in crypt proliferation. We utilized primary small intestinal epithelial crypts from C57BL/6J mice to study (1) the effect of glucose on crypt proliferation and (2) the effect of glucose on crypt metabolism using an extracellular flux analyzer for real-time metabolic measurements. We found that glucose increased both crypt proliferation and glycolysis, and the glycolytic pathway inhibitor 2-deoxy-d-glucose (2-DG) attenuated glucose-induced crypt proliferation. Glucose did not enhance glucose oxidation, but did increase the maximum mitochondrial respiratory capacity, which may contribute to glucose-induced increases in proliferation. Glucose activated Akt/HIF-1α signaling pathway, which might be at least in part responsible for glucose-induced glycolysis and cell proliferation. These results suggest that high glucose availability induces an increase in crypt proliferation by inducing an increase in glycolysis with no change in glucose oxidation. © 2017 Wiley Periodicals, Inc.

The Contribution of Different Components in QiShenYiQi Pills® to Its Potential to Modulate Energy Metabolism in Protection of Ischemic Myocardial Injury

Directory of Open Access Journals (Sweden)

Yuan-Chen Cui

2018-04-01

Full Text Available Ischemic heart diseases remain a challenge for clinicians. QiShenYiQi pills® (QSYQ has been reported to be curative during coronary heart diseases with modulation of energy metabolism as one of the underlying mechanisms. In this study, we detected the effect of QSYQ and its components on rat myocardial structure, mitochondrial respiratory chain complexes activity and energy metabolism, and heart function after 30 min of cardiac ischemia, with focusing on the contribution of each component to its potential to regulate energy metabolism. Results showed that treatment with QSYQ and all its five components protected myocardial structure from damage by ischemia. QSYQ also attenuated release of myocardial cTnI, and restored the production of ATP after cardiac ischemia. AS-IV and Rb1, but not Rg1, R1, and DLA, had similar effect as QSYQ in regulation of energy metabolism. These results indicate that QSYQ may prevent ischemia-induced cardiac injury via regulation of energy metabolism, to which each of its components contributes differently.

Potential hepatic toxicity of buprofezin at sublethal concentrations: ROS-mediated conversion of energy metabolism.

Science.gov (United States)

Ji, Xiaotong; Ku, Tingting; Zhu, Na; Ning, Xia; Wei, Wei; Li, Guangke; Sang, Nan

2016-12-15

Buprofezin is known for its broad-spectrum action and environmental safety. The popularity of buprofezin has raised concerns about its potentially adverse effects on human health and risk to the environment. In this study, we first identified the liver as one of the major organs in which buprofezin accumulated, and we detected a severe oxidative stress response. Next, we demonstrated that sublethal concentrations of buprofezin promoted the conversion of energy metabolism from the aerobic tricarboxylic acid (TCA) cycle and oxidative phosphorylation to anaerobic glycolysis. Importantly, reactive oxygen species (ROS) generation partially accounted for the shunting of the energy metabolism through the buprofezin-mediated inhibition of cytochrome c oxidase activity. ROS directly perturbed the activities of several key TCA cycle enzymes, stimulated glycolysis, and indirectly disturbed the activity of the respiratory chain complex by altering mitochondrial DNA (mtDNA). These findings clarify the potential mechanisms of buprofezin toxicity and provide biomarkers for buprofezin-mediated hepatotoxicity at sublethal concentrations. Copyright © 2016 Elsevier B.V. All rights reserved.

Energy Metabolism and Transfer of {sup 3}H and {sup 14}C in Mammals and Birds - Energy metabolism and transfer of {sup 3}H and {sup 14}C in mammals, birds, and fish

Energy Technology Data Exchange (ETDEWEB)

Melintescu, Anca; Galeriu, Dan [' Horia Hulubei' National Institute for Physics and Nuclear Engineering, Department of Environmental Physics and Life, 30 Reactorului St., POB MG-6, Bucharest-Magurele, RO-077125 (Romania); Beresford, Nicholas A. [NERC Centre for Ecology and Hydrology, Lancaster Environment Centre, Library Av. Bailrigg, Lancaster LA1 4AP (United Kingdom)

2014-07-01

The transfer of {sup 3}H and {sup 14}C in environment needs to be modelled differently than that of other radionuclides released from nuclear facilities because hydrogen and carbon are key components of biological tissues and the carbon and hydrogen life cycles. A detailed understanding of the behaviour of {sup 3}H and {sup 14}C in the food chain is essential because {sup 3}H may be released in large quantities from CANDU (Canadian Deuterium Uranium) reactors and future thermonuclear reactors, and {sup 14}C accumulates in the environment because of its long half-life. In recent years, the authors published both a simple and a complex dynamic metabolic model for {sup 3}H and {sup 14}C transfer to farm and wild animals. The models applications for wild animals were restricted to few examples. There is an increased interest to extend the models for a larger selection of wild animals, birds and fish to support developments such as the International Commission for Radiological Protection (ICRP) environmental protection framework. In this paper we describe activities to expand {sup 3}H and {sup 14}C models to cover a wider range of wildlife. The updated model of the dynamics of tritium transfer in aquatic food chains (AQUATRIT model) developed by the authors was successfully tested for small and large (trout) fish. Wild mammals and birds generally have a lower fat content than domestic species and must adapt to variable environmental conditions. The body mass is an important parameter involved in radionuclide transfer. The environmental temperature, type of animal, and diet must also be considered. The model input parameters for wild mammals are poorly defined because the experimental data are too few and the intraspecific variability is higher than that for farm and laboratory mammals. In the present study, our previously published approach considering the use of energy metabolism and the link between energy and organic matter turnover rate at the whole body and organ

Standard metabolic rate is associated with gestation duration, but not clutch size, in speckled cockroaches Nauphoeta cinerea

Directory of Open Access Journals (Sweden)

Natalie G. Schimpf

2012-09-01

Metabolic rate varies significantly between individuals, and these differences persist even when the wide range of biotic and abiotic factors that influence metabolism are accounted for. It is important to understand the life history implications of variation in metabolic rate, but they remain poorly characterised despite a growing body of work examining relationships between metabolism and a range of traits. In the present study we used laboratory-bred families (one sire to three dams of Nauphoeta cinerea (Olivier (speckled cockroaches to examine the relationship between standard metabolic rate (SMR and reproductive performance (number of offspring and gestation duration. We show that SMR is negatively associated with female gestation duration. Age at mating is negatively associated with gestation duration for females, and mass is negatively associated with the average gestation duration of the females a male was mated with. In addition to the results in the current literature, the results from the present study suggest that the association between metabolism and life history is more complex than simple relationships between metabolism and various fitness traits. Future work should consider longitudinal, ontogenetic as well as selective and quantitative genetic breeding approaches to fully examine the associations between metabolism and fitness.

Changes in energy metabolism in relation to physical activity due to fermentable carbohydrates in group housed, growing pigs

NARCIS (Netherlands)

Schrama, J.W.; Bakker, G.C.M.

1999-01-01

Fermentable nonstarch polysaccharides (dietary fiber) affect energy retention in group-housed growing pigs by reducing physical activity. This study assessed the effects of fermentation and bulkiness of dietary carbohydrates on physical activity in relation to energy metabolism. Eight clusters of 14

Changes in energy metabolism in relation to physical activity due to fermentable carbohydrates in group-housed growing pigs

NARCIS (Netherlands)

Schrama, J.W.; Bakker, G.C.M.

1999-01-01

Fermentable nonstarch polysaccharides (dietary fiber) affect energy retention in group-housed growing pigs by reducing physical activity. This study assessed the effects of fermentation and bulkiness of dietary carbohydrates on physical activity in relation to energy metabolism. Eight clusters of 14