scholarly journals Metabolic Flexibility and Mitochondrial Bioenergetics in the Failing Heart. Therapeutic Approaches

2021 ◽  
Vol 31 (2) ◽  
pp. 269-282
Author(s):  
Mariana G. ROSCA
Keyword(s):  
Energy Demand ◽  
Ketone Bodies ◽  
Critical Role ◽  
Redox Status ◽  
High Energy ◽  
Energy Deficit ◽  
Metabolic Flexibility ◽  
Therapeutic Approaches ◽  
Atp Production ◽  
Reduced Ejection Fraction

Objectives. We will review current concepts regarding bioenergetic decline in heart failure (HF). In the heart, the high energy demand must be met by continuous ATP generation. Cardiac energetic machinery orchestrates the ATP production by using oxidation of multiple energetic substrates including fatty acids (FA), glucose, amino acids and ketone bodies. The normal heart is metabolically flexible and able to use different energetic fuels during physiologic or pathologic circumstances to better match the energy demand. Mitochondria have critical role in maintaining cardiac metabolic flexibility. Methods. We analyzed the scientific literature pertinent to HF and mitochondrial dysfunction. Results. The general consent is that metabolic fl exibility is lost in HF with either preserved or reduced ejection fraction (HFpEF and HFrEF, respectively). The prototype of HFpEF is the metabolic heart disease that is characterized by increased reliance on FA oxidation for ATP production and decreased glucose oxidation, while HFrEF presents a decreased FA oxidation. Both types of HF are associated with a decline in mitochondrial function leading to increased oxidative stress, abnormalities in the redox status and energy deficit. Conclusion. Current research is committed to find novel metabolically targeted therapeutic approaches to improve energetic metabolism and alleviate HF progression.

scholarly journals Neuroprotection in Glaucoma: NAD+/NADH Redox State as a Potential Biomarker and Therapeutic Target

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1402
Author(s):  
Bledi Petriti ◽  
Pete A. Williams ◽  
Gerassimos Lascaratos ◽  
Kai-Yin Chau ◽  
David F. Garway-Heath
Keyword(s):  
Mitochondrial Function ◽  
Energy Demand ◽  
Redox State ◽  
High Energy ◽  
Therapeutic Modality ◽  
Retinal Ganglion ◽  
Atp Production ◽  
Potential Biomarker ◽  
Reduced Nicotinamide Adenine Dinucleotide ◽  
Susceptibility And Resistance

Glaucoma is the leading cause of irreversible blindness worldwide. Its prevalence and incidence increase exponentially with age and the level of intraocular pressure (IOP). IOP reduction is currently the only therapeutic modality shown to slow glaucoma progression. However, patients still lose vision despite best treatment, suggesting that other factors confer susceptibility. Several studies indicate that mitochondrial function may underlie both susceptibility and resistance to developing glaucoma. Mitochondria meet high energy demand, in the form of ATP, that is required for the maintenance of optimum retinal ganglion cell (RGC) function. Reduced nicotinamide adenine dinucleotide (NAD+) levels have been closely correlated to mitochondrial dysfunction and have been implicated in several neurodegenerative diseases including glaucoma. NAD+ is at the centre of various metabolic reactions culminating in ATP production—essential for RGC function. In this review we present various pathways that influence the NAD+(H) redox state, affecting mitochondrial function and making RGCs susceptible to degeneration. Such disruptions of the NAD+(H) redox state are generalised and not solely induced in RGCs because of high IOP. This places the NAD+(H) redox state as a potential systemic biomarker for glaucoma susceptibility and progression; a hypothesis which may be tested in clinical trials and then translated to clinical practice.

CPT1A-mediated Fat Oxidation, Mechanisms, and Therapeutic Potential

Endocrinology ◽  
2020 ◽  
Vol 161 (2) ◽  
Author(s):  
Isabel R Schlaepfer ◽  
Molishree Joshi
Keyword(s):  
Fatty Acids ◽  
Energy Demand ◽  
Therapeutic Potential ◽  
Critical Role ◽  
High Energy ◽  
The Body ◽  
Acid Oxidation ◽  
Mitochondrial Fatty Acid Oxidation ◽  
Mitochondrial Fatty Acid ◽  
Rate Limiting

Abstract Energy homeostasis during fasting or prolonged exercise depends on mitochondrial fatty acid oxidation (FAO). This pathway is crucial in many tissues with high energy demand and its disruption results in inborn FAO deficiencies. More than 15 FAO genetic defects have been currently described, and pathological variants described in circumpolar populations provide insights into its critical role in metabolism. The use of fatty acids as energy requires more than 2 dozen enzymes and transport proteins, which are involved in the activation and transport of fatty acids into the mitochondria. As the key rate-limiting enzyme of FAO, carnitine palmitoyltransferase I (CPT1) regulates FAO and facilitates adaptation to the environment, both in health and in disease, including cancer. The CPT1 family of proteins contains 3 isoforms: CPT1A, CPT1B, and CPT1C. This review focuses on CPT1A, the liver isoform that catalyzes the rate-limiting step of converting acyl-coenzyme As into acyl-carnitines, which can then cross membranes to get into the mitochondria. The regulation of CPT1A is complex and has several layers that involve genetic, epigenetic, physiological, and nutritional modulators. It is ubiquitously expressed in the body and associated with dire consequences linked with genetic mutations, metabolic disorders, and cancers. This makes CPT1A an attractive target for therapeutic interventions. This review discusses our current understanding of CPT1A expression, its role in heath and disease, and the potential for therapeutic opportunities targeting this enzyme.

scholarly journals Role of Oxidative Stress in Metabolic and Subcellular Abnormalities in Diabetic Cardiomyopathy

2020 ◽  
Vol 21 (7) ◽  
pp. 2413 ◽  
Author(s):  
Naranjan S. Dhalla ◽  
Anureet K. Shah ◽  
Paramjit S. Tappia
Keyword(s):  
Oxidative Stress ◽  
Diabetic Cardiomyopathy ◽  
Cardiac Dysfunction ◽  
Critical Role ◽  
Renin Angiotensin System ◽  
High Energy ◽  
Diabetic Heart ◽  
Therapeutic Approaches ◽  
Angiotensin System

Although the presence of cardiac dysfunction and cardiomyopathy in chronic diabetes has been recognized, the pathophysiology of diabetes-induced metabolic and subcellular changes as well as the therapeutic approaches for the prevention of diabetic cardiomyopathy are not fully understood. Cardiac dysfunction in chronic diabetes has been shown to be associated with Ca2+-handling abnormalities, increase in the availability of intracellular free Ca2+ and impaired sensitivity of myofibrils to Ca2+. Metabolic derangements, including depressed high-energy phosphate stores due to insulin deficiency or insulin resistance, as well as hormone imbalance and ultrastructural alterations, are also known to occur in the diabetic heart. It is pointed out that the activation of the sympathetic nervous system and renin–angiotensin system generates oxidative stress, which produces defects in subcellular organelles including sarcolemma, sarcoplasmic reticulum and myofibrils. Such subcellular remodeling plays a critical role in the pathogenesis of diabetic cardiomyopathy. In fact, blockade of the effects of neurohormonal systems has been observed to attenuate oxidative stress and occurrence of subcellular remodeling as well as metabolic abnormalities in the diabetic heart. This review is intended to describe some of the subcellular and metabolic changes that result in cardiac dysfunction in chronic diabetes. In addition, the therapeutic values of some pharmacological, metabolic and antioxidant interventions will be discussed. It is proposed that a combination therapy employing some metabolic agents or antioxidants with insulin may constitute an efficacious approach for the prevention of diabetic cardiomyopathy.

scholarly journals Critical role for free radicals on sprint exercise-induced CaMKII and AMPKα phosphorylation in human skeletal muscle

2013 ◽  
Vol 114 (5) ◽  
pp. 566-577 ◽  
Author(s):  
David Morales-Alamo ◽  
Jesús Gustavo Ponce-González ◽  
Amelia Guadalupe-Grau ◽  
Lorena Rodríguez-García ◽  
Alfredo Santana ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Energy Demand ◽  
Human Skeletal Muscle ◽  
Critical Role ◽  
Recovery Period ◽  
Muscle Metabolism ◽  
High Energy ◽  
Vastus Lateralis Muscle ◽  
Sprint Exercise

The extremely high energy demand elicited by sprint exercise is satisfied by an increase in O2 consumption combined with a high glycolytic rate, leading to a marked lactate accumulation, increased AMP-to-ATP ratio, and reduced NAD+/NADH.H+ and muscle pH, which are accompanied by marked Thr172 AMP-activated protein kinase (AMPK)-α phosphorylation during the recovery period by a mechanism not fully understood. To determine the role played by reactive nitrogen and oxygen species (RNOS) on Thr172-AMPKα phosphorylation in response to cycling sprint exercise, nine voluntary participants performed a single 30-s sprint (Wingate test) on two occasions: one 2 h after the ingestion of placebo and another after the intake of antioxidants (α-lipoic acid, vitamin C, and vitamin E) in a double-blind design. Vastus lateralis muscle biopsies were obtained before, immediately postsprint, and 30 and 120 min postsprint. Performance and muscle metabolism were similar during both sprints. The NAD+-to-NADH.H+ ratio was similarly reduced (84%) and the AMP-to-ATP ratio was similarly increased (×21-fold) immediately after the sprints. Thr286 Ca2+/calmodulin-dependent protein kinase II (CaMKII) and Thr172-AMPKα phosphorylations were increased after the control sprint (with placebo) but not when the sprints were preceded by the ingestion of antioxidants. Ser485-AMPKα1/Ser491-AMPKα2 phosphorylation, a known inhibitory mechanism of Thr172-AMPKα phosphorylation, was increased only with antioxidant ingestion. In conclusion, RNOS play a crucial role in AMPK-mediated signaling after sprint exercise in human skeletal muscle. Antioxidant ingestion 2 h before sprint exercise abrogates the Thr172-AMPKα phosphorylation response observed after the ingestion of placebo by reducing CaMKII and increasing Ser485-AMPKα1/Ser491-AMPKα2 phosphorylation. Sprint performance, muscle metabolism, and AMP-to-ATP and NAD+-to-NADH.H+ ratios are not affected by the acute ingestion of antioxidants.

scholarly journals Active Buildings Based on Passivhaus Standard to Reduce the Energy Deficit of Regional Electric Network: Proposal Analysis

Electronics ◽  
2021 ◽  
Vol 10 (19) ◽  
pp. 2361
Author(s):  
Josué Aarón López-Leyva ◽  
Carolina Barrera-Silva ◽  
Luisa Fernanda Sarmiento-Leyva ◽  
María Fernanda González-Romero
Keyword(s):  
Distributed Generation ◽  
Energy Demand ◽  
Renewable Energy Sources ◽  
Energy Generation ◽  
High Energy ◽  
Energy Deficit ◽  
Electrical Network ◽  
Net Generation ◽  
Base Case ◽  
Heating And Cooling

This manuscript presents the analysis of a real distributed generation network considering the integration of Active Buildings that meet the Passivhaus standard criteria at the Premium level, as a base case model. The novelty aspect presented in this paper is the interconnection of Active Buildings based on the Passivhaus standard at the Premium level with the National Electricity System (particularly, in Mexico’s North Baja California region) to mitigate the energy deficit. The objective of the proposal grid is to reduce the energy deficit (≈600 MW) due to the high energy demand in the region and the reduced energy generation through conventional and renewable energy sources. In a particular way, the energy rehabilitation of some buildings was analyzed with the aim of reducing the energy demand of each one and then adding energy generation through renewable sources. As a result, all Passivhaus standard criteria (i.e., heating and cooling demands, heating and cooling loads, among others) were met. Regarding the Active Buildings performance in each distributed generation circuit, an overall installed power capacity of ≈2.3 MW was obtained, which corresponds to ≈19.1% of the maximum capacity, and ≈34.30% of the recommended integration capacity. In addition, adequate results were obtained related to the import and export of energy between distributed generation circuits, i.e., the energy exchange is up to ≈106.8 kW, intending to reduce the energy contribution of the utility electrical network. Finally, the analysis of the Active Buildings showed an increase in the net generation forecast, up to ≈2.25 MW.

Energy metabolism in patients with diabetes and heart failure

2019 ◽  
pp. 32-36
Keyword(s):  
Heart Failure ◽  
Energy Metabolism ◽  
Oxidative Phosphorylation ◽  
Energy Demand ◽  
Glucose Oxidation ◽  
High Energy ◽  
Energy Deficit ◽  
Diabetic Patients ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Myocardial Energy Metabolism

The heart has a very high energy demand, which is mostly met by mitochondrial oxidative phosphorylation and, to a lesser extent, by glycolysis. In heart failure, there are substantial alterations in myocardial energy metabolism that lead to an “energy-deficient” state. This includes a marked reduction in overall mitochondrial oxidative phosphorylation and an uncoupling between high glycolysis rates and low glucose oxidation, which together contributes to the energy deficit and deteriorates contractile dysfunction. Cardiac ketone oxidation is also increased in heart failure, although it has yet to be determined whether this is an adaptive or maladaptive alteration. Diabetes is a major risk factor for heart failure development. It induces alterations in myocardial energy metabolism and is often associated with ventricular dysfunction. Similar to heart failure, a major change in myocardial energy metabolism in diabetic patients is a reduction in glucose oxidation, which negatively influences cardiac function. In both heart failure and diabetes, a growing body of evidence suggests that targeting myocardial energy metabolism by optimizing cardiac energy substrate preference could be a potential therapeutic approach to improve patient outcomes.

scholarly journals Cardiac mitochondrial function depends on BUD23 mediated ribosome programming

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Matthew Baxter ◽  
Maria Voronkov ◽  
Toryn Poolman ◽  
Gina Galli ◽  
Christian Pinali ◽  
...  
Keyword(s):  
Mitochondrial Function ◽  
Energy Demand ◽  
Critical Role ◽  
A549 Cells ◽  
Gc Content ◽  
High Energy ◽  
Mouse Development ◽  
Mitochondrial Content ◽  
And Function ◽  
External Stimuli

Efficient mitochondrial function is required in tissues with high energy demand such as the heart, and mitochondrial dysfunction is associated with cardiovascular disease. Expression of mitochondrial proteins is tightly regulated in response to internal and external stimuli. Here we identify a novel mechanism regulating mitochondrial content and function, through BUD23-dependent ribosome generation. BUD23 was required for ribosome maturation, normal 18S/28S stoichiometry and modulated the translation of mitochondrial transcripts in human A549 cells. Deletion of Bud23 in murine cardiomyocytes reduced mitochondrial content and function, leading to severe cardiomyopathy and death. We discovered that BUD23 selectively promotes ribosomal interaction with low GC-content 5’UTRs. Taken together we identify a critical role for BUD23 in bioenergetics gene expression, by promoting efficient translation of mRNA transcripts with low 5’UTR GC content. BUD23 emerges as essential to mouse development, and to postnatal cardiac function.

Changes in lipid peroxidation during pregnancy and after delivery in rats: effect of pinealectomy

Reproduction ◽  
2000 ◽  
pp. 143-149 ◽  
Author(s):  
RM Sainz ◽  
RJ Reiter ◽  
JC Mayo ◽  
J Cabrera ◽  
DX Tan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Oxidative Damage ◽  
Energy Demand ◽  
Physiological State ◽  
High Energy ◽  
Free Radical Scavengers ◽  
Radical Scavengers ◽  
Oxygen Requirement ◽  
Pregnant Rats

Pregnancy is a physiological state accompanied by a high energy demand of many bodily functions and an increased oxygen requirement. Because of the increased intake and utilization of oxygen, increased levels of oxidative stress would be expected. In the present study, the degree of lipid peroxidation was examined in different tissues from non-pregnant and pregnant rats after the delivery of their young. Melatonin and other indole metabolites are known to be direct free radical scavengers and indirect antioxidants. Thus the effect of pinealectomy at 1 month before pregnancy on the accumulation of lipid damage was investigated in non-pregnant and pregnant rats after the delivery of their young. Malonaldehyde and 4-hydroxyalkenal concentrations were measured in the lung, uterus, liver, brain, kidney, thymus and spleen from intact and pinealectomized pregnant rats soon after birth of their young and at 14 and 21 days after delivery. The same parameters were also evaluated in intact and pinealectomized non-pregnant rats. Shortly after delivery, lipid oxidative damage was increased in lung, uterus, brain, kidney and thymus of the mothers. No differences were detected in liver and spleen. Pinealectomy enhanced this effect in the uterus and lung. It is concluded that during pregnancy high levels of oxidative stress induce an increase in oxidative damage to lipids, which in some cases is inhibited by the antioxidative actions of pineal indoles.

scholarly journals The Quorum Sensing Auto-Inducer 2 (AI-2) Stimulates Nitrogen Fixation and Favors Ethanol Production over Biomass Accumulation in Zymomonas mobilis

2021 ◽  
Vol 22 (11) ◽  
pp. 5628
Author(s):  
Valquíria Campos Alencar ◽  
Juliana de Fátima dos Santos Silva ◽  
Renata Ozelami Vilas Boas ◽  
Vinícius Manganaro Farnézio ◽  
Yara N. L. F. de Maria ◽  
...  
Keyword(s):  
Nitrogen Fixation ◽  
Quorum Sensing ◽  
Ethanol Production ◽  
N2 Fixation ◽  
Energy Demand ◽  
Zymomonas Mobilis ◽  
Biomass Accumulation ◽  
High Energy ◽  
Gram Negative ◽  
Expression Of Genes

Autoinducer 2 (or AI-2) is one of the molecules used by bacteria to trigger the Quorum Sensing (QS) response, which activates expression of genes involved in a series of alternative mechanisms, when cells reach high population densities (including bioluminescence, motility, biofilm formation, stress resistance, and production of public goods, or pathogenicity factors, among others). Contrary to most autoinducers, AI-2 can induce QS responses in both Gram-negative and Gram-positive bacteria, and has been suggested to constitute a trans-specific system of bacterial communication, capable of affecting even bacteria that cannot produce this autoinducer. In this work, we demonstrate that the ethanologenic Gram-negative bacterium Zymomonas mobilis (a non-AI-2 producer) responds to exogenous AI-2 by modulating expression of genes involved in mechanisms typically associated with QS in other bacteria, such as motility, DNA repair, and nitrogen fixation. Interestingly, the metabolism of AI-2-induced Z. mobilis cells seems to favor ethanol production over biomass accumulation, probably as an adaptation to the high-energy demand of N2 fixation. This opens the possibility of employing AI-2 during the industrial production of second-generation ethanol, as a way to boost N2 fixation by these bacteria, which could reduce costs associated with the use of nitrogen-based fertilizers, without compromising ethanol production in industrial plants.

scholarly journals IoT Platform for Energy Sustainability in University Campuses

Sensors ◽  
2021 ◽  
Vol 21 (2) ◽  
pp. 357
Author(s):  
Pedro Moura ◽  
José Ignacio Moreno ◽  
Gregorio López López ◽  
Manuel Alvarez-Campana
Keyword(s):  
Energy Demand ◽  
New Technologies ◽  
Low Cost ◽  
Sustainable Use ◽  
High Energy ◽  
Appropriate Technology ◽  
Monitoring And Control ◽  
Energy Sustainability ◽  
University Campuses ◽  
Iot Platform

University campuses are normally constituted of large buildings responsible for high energy demand, and are also important as demonstration sites for new technologies and systems. This paper presents the results of achieving energy sustainability in a testbed composed of a set of four buildings that constitute the Telecommunications Engineering School of the Universidad Politécnica de Madrid. In the paper, after characterizing the consumption of university buildings for a complete year, different options to achieve more sustainable use of energy are presented, considering the integration of renewable generation sources, namely photovoltaic generation, and monitoring and controlling electricity demand. To ensure the implementation of the desired monitoring and control, an internet of things (IoT) platform based on wireless sensor network (WSN) infrastructure was designed and installed. Such a platform supports a smart system to control the heating, ventilation, and air conditioning (HVAC) and lighting systems in buildings. Furthermore, the paper presents the developed IoT-based platform, as well as the implemented services. As a result, the paper illustrates how providing old existing buildings with the appropriate technology can contribute to the objective of transforming such buildings into nearly zero-energy buildings (nZEB) at a low cost.

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