scholarly journals Randomized Trial: D-Glyceric Acid Activates Mitochondrial Metabolism in 50–60-Year-Old Healthy Humans

2021 ◽  
Vol 2 ◽  
Author(s):  
O. Petteri Hirvonen ◽  
Heikki Kyröläinen ◽  
Maarit Lehti ◽  
Heikki Kainulainen
Keyword(s):  
Energy Metabolism ◽  
Systemic Inflammation ◽  
Plasma Concentrations ◽  
Human Study ◽  
Membrane Integrity ◽  
Mitochondrial Metabolism ◽  
Whole Body ◽  
Placebo Control ◽  
Glyceric Acid ◽  
Mitochondrial Energy Metabolism

Background: Based on earlier studies, natural metabolite D-glyceric acid (DGA) does not seem to play any role in whole-body metabolism. Nevertheless, one ethanol oxidation-related rat study with controversial results raised our interest. According to preparatory studies for the regulatory approval of DGA, some highly conserved mechanism seems to subtly activate the cellular energy metabolism. Therefore, the present 25-days double-blind human study with placebo control was initiated.Purpose: The main target in the present study with 27 healthy 50–60-year-old human volunteers was to find out whether an “acute” 4-days and a longer 21-days exogenous DGA regimen caused moderate activation of the mitochondrial energy metabolism. The simultaneous target was to find out whether a halved dose of DGA continued to be an effective regimen.Main Findings: The results revealed the following statistically significant findings: 1) plasma concentrations of metabolites related to aerobic energy production, especially lactate, were strongly reduced, 2) systemic inflammation was lowered both in 4- and 21-days, 3) mitochondria-related mRNA expressions in circulating immune cells were noticeably modulated at Day4, 4) cellular membrane integrity seemed to be sharply enhanced, and 5) cellular NADH/NAD+ -ratio was upregulated.Conclusion: Mitochondrial metabolism was clearly upregulated at the whole-body level in both 4- and 21 days. At the same time, the effect of DGA was very well tolerated. Based on received solid results, the DGA regimen may alleviate acute and chronic energy metabolic challenges in main organs like the liver, CNS, and skeletal muscles. Enhanced membrane integrity combined with lower systemic inflammation and activated metabolic flows by the DGA regimen may be beneficial especially for the aging population.

scholarly journals Double Blinded Clinical Study on D-Glyceric Acid, a Potential Novel Energy Metabolic Signaling Metabolite

2021 ◽  
Author(s):  
Olli Petteri Hirvonen ◽  
Heikki Kyröläinen ◽  
Heikki Kainulainen
Keyword(s):  
Energy Metabolism ◽  
Human Study ◽  
Whole Body ◽  
Plasma Metabolites ◽  
Placebo Control ◽  
Glyceric Acid ◽  
Subclinical Inflammation ◽  
Gene Expressions ◽  
Physical Exercises ◽  
Double Blinded

Abstract Based on earlier few studies natural metabolite D-glyceric acid does not seem to play any major role in cellular metabolism. Nevertheless, one study that concentrated on ethanol oxidation in the liver increased our curiosity. Therefore, research leading to the present 25 days lasting double blinded human study with placebo control was initiated. Main targets in the present study were: 1) to find out whether acute and long-term exogenous D-glyceric acid (DGA) regimen will cause activation related to energy metabolism in healthy 50-60-year old humans, and 2) to find out whether elevated levels of endogenous DGA can be found in the plasma after 30 min of a strenuous cycling exercise. Additional target was to find out whether certain effects of exogenous DGA regimen resemble the effects of physical exercises, and whether lowered halved dose of DGA regimen during a 14-day follow-up period continues to be effective. The main results revealed that: I) there was an acute effect on plasma glucose maintenance from DGA regimen, II) plasma metabolites and gene expressions related to aerobic energy production were strongly modulated, and subclinical inflammation was lowered already after the 4-day DGA regimen, and III) cycling with increasing load towards exhaustion increased endogenous levels of DGA in human plasma (p=0.013). Because the amounts of administered DGA were exceedingly small and cannot directly have caused observed substantial changes, we hypothesise that an increase in tissue DGA concentration causes an endogenous signal or a cascade of intracellular signals: “ more ATP is needed immediately ”. At the whole body level, the signal causes metabolic activation cascade that resembles initiation of physical exercises but without literally no signs of exhaustion. Tested exogenous DGA regimen possessed an effect even on circulating immune cells. Based on obtained results, the DGA regimen may facilitate in resolving energy metabolic challenges in main organs, like fatty liver, and simultaneously it seemed to lower systemic inflammation. The DGA regimen can possibly alleviate chronic diseases and disorders related to energy metabolism and/or elevated subclinical inflammation.Trial registration number (18th of Jan 2021), ClinicalTrials.gov Identifier: NCT04713319

Pyruvate metabolism of perfused rat lungs after exposure to 100% oxygen

1986 ◽  
Vol 60 (5) ◽  
pp. 1605-1609 ◽  
Author(s):  
D. J. Bassett ◽  
E. Bowen-Kelly
Keyword(s):  
Energy Metabolism ◽  
Oxidative Phosphorylation ◽  
Mitochondrial Metabolism ◽  
Early Event ◽  
Pyruvate Metabolism ◽  
Mitochondrial Energy Metabolism ◽  
Linear Rate ◽  
Rat Lungs ◽  
14Co2 Production

Previous studies with lung homogenates have suggested that pulmonary O2 toxicity is in part a result of inhibited mitochondrial energy metabolism. In this study, mitochondrial metabolism was determined by measurements of 14CO2 production from [1–14C]-pyruvate in perfused lungs, isolated after 0, 3, 6, 12, and 24 h of exposure to 100% O2. Measurements were made under normal and stimulated conditions brought about by uncoupling oxidative phosphorylation with 2,4-dinitrophenol (DNP). Lungs were ventilated with 5% CO2 in O2 and perfused for 100 min with 12.5 mM 14C labeled pyruvate. Unexposed lungs gave a linear rate of 14CO2 production of 121 +/- 16 mumol/h/g dry wt (n = 5), which was maximally stimulated 84% by perfusion with 0.8 mMDNP. Twenty-four hours of exposure to 100% O2 did not significantly affect 14CO2 production. In contrast, DNP failed to significantly stimulate pyruvate metabolism to CO2 in lungs exposed for greater than 3 h to 100% O2. These latter data suggested that O2 exposure makes lung mitochondria unable to respond to increased ATP demands associated with DNP uncoupling. Compromised energy metabolism is therefore an important early event in O2 toxicity.

Therapeutic Approaches Using Riboflavin in Mitochondrial Energy Metabolism Disorders

2016 ◽  
Vol 17 (13) ◽  
pp. 1527-1534 ◽  
Author(s):  
Bárbara J. Henriques ◽  
Tânia G. Lucas ◽  
Cláudio M. Gomes
Keyword(s):  
Energy Metabolism ◽  
Therapeutic Approaches ◽  
Mitochondrial Energy Metabolism

Mitochondrial energy metabolism is negatively regulated by cannabinoid receptor 1 in intact human epidermis

2020 ◽  
Vol 29 (7) ◽  
pp. 616-622 ◽  
Author(s):  
Attila Oláh ◽  
Majid Alam ◽  
Jérémy Chéret ◽  
Nikolett Gréta Kis ◽  
Zoltán Hegyi ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Cannabinoid Receptor ◽  
Human Epidermis ◽  
Cannabinoid Receptor 1 ◽  
Mitochondrial Energy Metabolism

scholarly journals Effect of dietary protein on energy metabolism including protein synthesis in the spiny lobster Sagmariasus verreauxi

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shuangyao Wang ◽  
Chris G. Carter ◽  
Quinn P. Fitzgibbon ◽  
Basseer M. Codabaccus ◽  
Gregory G. Smith
Keyword(s):  
Protein Synthesis ◽  
Energy Metabolism ◽  
Dietary Protein ◽  
Spiny Lobster ◽  
Ammonia Excretion ◽  
Metabolic Energy ◽  
Whole Body ◽  
Body Protein ◽  
Energy Substrate ◽  
Sagmariasus Verreauxi

AbstractThis is the first study in an aquatic ectotherm to combine a stoichiometric bioenergetic approach with an endpoint stochastic model to explore dietary macronutrient content. The combination of measuring respiratory gas (O2 and CO2) exchange, nitrogenous (ammonia and urea) excretion, specific dynamic action (SDA), metabolic energy substrate use, and whole-body protein synthesis in spiny lobster, Sagmariasus verreauxi, was examined in relation to dietary protein. Three isoenergetic feeds were formulated with varying crude protein: 40%, 50% and 60%, corresponding to CP40, CP50 and CP60 treatments, respectively. Total CO2 and ammonia excretion, SDA magnitude and coefficient, and protein synthesis in the CP60 treatment were higher compared to the CP40 treatment. These differences demonstrate dietary protein influences post-prandial energy metabolism. Metabolic use of each major energy substrate varied at different post-prandial times, indicating suitable amounts of high-quality protein with major non-protein energy-yielding nutrients, lipid and carbohydrate, are critical for lobsters. The average contribution of protein oxidation was lowest in the CP50 treatment, suggesting mechanisms underlying the most efficient retention of dietary protein and suitable dietary inclusion. This study advances understanding of how deficient and surplus dietary protein affects energy metabolism and provides approaches for fine-scale feed evaluation to support sustainable aquaculture.

scholarly journals Mitochondrial P2X7 receptor localization modulates energy metabolism enhancing physical performance

Function ◽  
2021 ◽  
Author(s):  
Alba Clara Sarti ◽  
Valentina Vultaggio-Poma ◽  
Simonetta Falzoni ◽  
Sonia Missiroli ◽  
Anna Lisa Giuliani ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Physical Fitness ◽  
P2x7 Receptor ◽  
Human Fibroblasts ◽  
Atp Synthesis ◽  
Heart Tissue ◽  
Mitochondrial Potential ◽  
Mitochondrial Energy Metabolism ◽  
Microglia Cell ◽  
Basal Expression

Abstract Basal expression of the P2X7 receptor (P2X7R) improves mitochondrial metabolism, ATP synthesis and overall fitness of immune and non-immune cells. We investigated P2X7R contribution to energy metabolism and subcellular localization in fibroblasts (mouse embryo fibroblasts and HEK293 human fibroblasts), mouse microglia (primary brain microglia and the N13 microglia cell line), and heart tissue. The P2X7R localizes to mitochondria, and its lack a) decreases basal respiratory rate, ATP-coupled respiration, maximal uncoupled respiration, resting mitochondrial potential, mitochondrial matrix Ca2+ level, b) modifies expression pattern of oxidative phosphorylation (OxPhos) enzymes, and c) severely affects cardiac performance. Hearts from P2rx7-deleted versus WT mice are larger, heart mitochondria smaller, and stroke volume (SV), ejection fraction (EF), fractional shortening (FS) and cardiac output (CO), are significantly decreased. Accordingly, physical fitness of P2X7R-null mice is severely reduced. Thus, the P2X7R is a key modulator of mitochondrial energy metabolism and a determinant of physical fitness.

scholarly journals Systemic oxidative stress is associated with lower aerobic capacity and impaired skeletal muscle energy metabolism in heart failure patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Takashi Yokota ◽  
Shintaro Kinugawa ◽  
Kagami Hirabayashi ◽  
Mayumi Yamato ◽  
Shingo Takada ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Skeletal Muscle ◽  
Energy Metabolism ◽  
Aerobic Capacity ◽  
Plantar Flexion ◽  
Exercise Intolerance ◽  
Whole Body ◽  
Resonance Spectroscopy ◽  
Systemic Oxidative Stress

AbstractOxidative stress plays a role in the progression of chronic heart failure (CHF). We investigated whether systemic oxidative stress is linked to exercise intolerance and skeletal muscle abnormalities in patients with CHF. We recruited 30 males: 17 CHF patients, 13 healthy controls. All participants underwent blood testing, cardiopulmonary exercise testing, and magnetic resonance spectroscopy (MRS). The serum thiobarbituric acid reactive substances (TBARS; lipid peroxides) were significantly higher (5.1 ± 1.1 vs. 3.4 ± 0.7 μmol/L, p < 0.01) and the serum activities of superoxide dismutase (SOD), an antioxidant, were significantly lower (9.2 ± 7.1 vs. 29.4 ± 9.7 units/L, p < 0.01) in the CHF cohort versus the controls. The oxygen uptake (VO2) at both peak exercise and anaerobic threshold was significantly depressed in the CHF patients; the parameters of aerobic capacity were inversely correlated with serum TBARS and positively correlated with serum SOD activity. The phosphocreatine loss during plantar-flexion exercise and intramyocellular lipid content in the participants' leg muscle measured by 31phosphorus- and 1proton-MRS, respectively, were significantly elevated in the CHF patients, indicating abnormal intramuscular energy metabolism. Notably, the skeletal muscle abnormalities were related to the enhanced systemic oxidative stress. Our analyses revealed that systemic oxidative stress is related to lowered whole-body aerobic capacity and skeletal muscle dysfunction in CHF patients.

scholarly journals Physiologically Based Pharmacokinetic Models of Probenecid and Furosemide to Predict Transporter Mediated Drug-Drug Interactions

2020 ◽  
Vol 37 (12) ◽  
Author(s):  
Hannah Britz ◽  
Nina Hanke ◽  
Mitchell E. Taub ◽  
Ting Wang ◽  
Bhagwat Prasad ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Organic Anion ◽  
Plasma Concentrations ◽  
Whole Body ◽  
Time Profiles ◽  
Pbpk Models ◽  
Physiologically Based Pharmacokinetic ◽  
Concentration Time ◽  
Anion Transporter ◽  
Physiologically Based

Abstract Purpose To provide whole-body physiologically based pharmacokinetic (PBPK) models of the potent clinical organic anion transporter (OAT) inhibitor probenecid and the clinical OAT victim drug furosemide for their application in transporter-based drug-drug interaction (DDI) modeling. Methods PBPK models of probenecid and furosemide were developed in PK-Sim®. Drug-dependent parameters and plasma concentration-time profiles following intravenous and oral probenecid and furosemide administration were gathered from literature and used for model development. For model evaluation, plasma concentration-time profiles, areas under the plasma concentration–time curve (AUC) and peak plasma concentrations (Cmax) were predicted and compared to observed data. In addition, the models were applied to predict the outcome of clinical DDI studies. Results The developed models accurately describe the reported plasma concentrations of 27 clinical probenecid studies and of 42 studies using furosemide. Furthermore, application of these models to predict the probenecid-furosemide and probenecid-rifampicin DDIs demonstrates their good performance, with 6/7 of the predicted DDI AUC ratios and 4/5 of the predicted DDI Cmax ratios within 1.25-fold of the observed values, and all predicted DDI AUC and Cmax ratios within 2.0-fold. Conclusions Whole-body PBPK models of probenecid and furosemide were built and evaluated, providing useful tools to support the investigation of transporter mediated DDIs.

scholarly journals Plasma membrane integrity: implications for health and disease

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Dustin A. Ammendolia ◽  
William M. Bement ◽  
John H. Brumell
Keyword(s):  
Plasma Membrane ◽  
Membrane Damage ◽  
Membrane Integrity ◽  
Whole Body ◽  
Plasma Membrane Integrity ◽  
Plasma Membrane Damage ◽  
Cellular Environment ◽  
Health And Disease ◽  
Repair Pathways ◽  
The Impact

AbstractPlasma membrane integrity is essential for cellular homeostasis. In vivo, cells experience plasma membrane damage from a multitude of stressors in the extra- and intra-cellular environment. To avoid lethal consequences, cells are equipped with repair pathways to restore membrane integrity. Here, we assess plasma membrane damage and repair from a whole-body perspective. We highlight the role of tissue-specific stressors in health and disease and examine membrane repair pathways across diverse cell types. Furthermore, we outline the impact of genetic and environmental factors on plasma membrane integrity and how these contribute to disease pathogenesis in different tissues.

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