The role of energy/substrate in microbial hormesis

Background Isoflurane enhances mechanical function in hearts subject to normothermic global or regional ischemia. The authors examined the effectiveness of isoflurane in preserving mechanical function in hearts subjected to cardioplegic arrest and prolonged hypothermic no-flow storage. The role of isoflurane in altering myocardial glucose metabolism during storage and reperfusion during these conditions and the contribution of adenosine triphosphate-sensitive potassium (K(atp)) channel activation in mediating the functional and metabolic effects of isoflurane preconditioning was determined. Methods Isolated working rat hearts were subjected to cardioplegic arrest with St. Thomas' II solution, hypothermic no-flow storage for 8 h, and subsequent aerobic reperfusion. The consequences of isoflurane treatment were assessed during the following conditions: (1) isoflurane exposure before and during storage; (2) brief isoflurane exposure during early nonworking poststorage reperfusion; and (3) isoflurane preconditioning before storage. The selective mitochondrial and sarcolemmal K(atp) channel antagonists, 5-hydroxydecanoate and HMR 1098, respectively, were used to assess the role of K(atp) channel activation on glycogen consumption during storage in isoflurane-preconditioned hearts. Results Isoflurane enhanced recovery of mechanical function if present before and during storage. Isoflurane preconditioning was also protective. Isoflurane reduced glycogen consumption during storage under the aforementioned circumstances. Storage of isoflurane-preconditioned hearts in the presence of 5-hydroxydecanoate prevented the reduction in glycogen consumption during storage and abolished the beneficial effect of isoflurane preconditioning on recovery of mechanical function. Conclusions Isoflurane provides additive protection of hearts subject to cardioplegic arrest and prolonged hypothermic no-flow storage and favorably alters energy substrate metabolism by modulating glycolysis during ischemia. The effects of isoflurane preconditioning on glycolysis during hypothermic no-flow storage appears to be associated with activation of mitochondrial K(atp) channels.

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Effects of adenosine, exercise, and moderate acute hypoxia on energy substrate utilization of human skeletal muscle

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00245.2011 ◽

2012 ◽

Vol 302 (3) ◽

pp. R385-R390 ◽

Cited By ~ 19

Author(s):

Ilkka Heinonen ◽

Jukka Kemppainen ◽

Kimmo Kaskinoro ◽

Juha E. Peltonen ◽

Hannu T. Sipilä ◽

...

Keyword(s):

Skeletal Muscle ◽

Glucose Uptake ◽

Human Skeletal Muscle ◽

Acute Hypoxia ◽

Knee Extension ◽

Substrate Utilization ◽

Energy Substrate ◽

Skeletal Muscle Glucose Uptake ◽

Knee Extension Exercise

Glucose metabolism increases in hypoxia and can be influenced by endogenous adenosine, but the role of adenosine for regulating glucose metabolism at rest or during exercise in hypoxia has not been elucidated in humans. We studied the effects of exogenous adenosine on human skeletal muscle glucose uptake and other blood energy substrates [free fatty acid (FFA) and lactate] by infusing adenosine into the femoral artery in nine healthy young men. The role of endogenous adenosine was studied by intra-arterial adenosine receptor inhibition (aminophylline) during dynamic one-leg knee extension exercise in normoxia and acute hypoxia corresponding to ∼3,400 m of altitude. Extraction and release of energy substrates were studied by arterial-to-venous (A-V) blood samples, and total uptake or release was determined by the product of A-V differences and muscle nutritive perfusion measured by positron emission tomography. The results showed that glucose uptake increased from a baseline value of 0.2 ± 0.2 to 2.0 ± 2.2 μmol·100 g−1·min−1 during adenosine infusion ( P < 0.05) at rest. Although acute hypoxia enhanced arterial FFA levels, it did not affect muscle substrate utilization at rest. During exercise, glucose uptake was higher (195%) during acute hypoxia compared with normoxia ( P = 0.058), and aminophylline had no effect on energy substrate utilization during exercise, despite that arterial FFA levels were increased. In conclusion, exogenous adenosine at rest and acute moderate hypoxia during low-intensity knee-extension exercise increases skeletal muscle glucose uptake, but the increase in hypoxia appears not to be mediated by adenosine.

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Expression of monocarboxylate transporter mRNAs in mouse brain: Support for a distinct role of lactate as an energy substrate for the neonatal vs. adult brain

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.95.7.3990 ◽

1998 ◽

Vol 95 (7) ◽

pp. 3990-3995 ◽

Cited By ~ 201

Author(s):

L. Pellerin ◽

G. Pellegri ◽

J.-L. Martin ◽

P. J. Magistretti

Keyword(s):

Mouse Brain ◽

Adult Brain ◽

Monocarboxylate Transporter ◽

Energy Substrate ◽

Distinct Role

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Carbohydrate Availability and Physical Performance: Physiological Overview and Practical Recommendations

Nutrients ◽

10.3390/nu11051084 ◽

2019 ◽

Vol 11 (5) ◽

pp. 1084 ◽

Cited By ~ 15

Author(s):

Fernando Mata ◽

Pedro L. Valenzuela ◽

Jaume Gimenez ◽

Carles Tur ◽

Diogo Ferreria ◽

...

Keyword(s):

Resistance Training ◽

Physical Performance ◽

Sport Performance ◽

Limiting Factor ◽

Energy Substrate ◽

Negative Results ◽

Exercise Induced ◽

The One ◽

Practical Recommendations

Strong evidence during the last few decades has highlighted the importance of nutrition for sport performance, the role of carbohydrates (CHO) being of special interest. Glycogen is currently not only considered an energy substrate but also a regulator of the signaling pathways that regulate exercise-induced adaptations. Thus, low or high CHO availabilities can result in both beneficial or negative results depending on the purpose. On the one hand, the depletion of glycogen levels is a limiting factor of performance during sessions in which high exercise intensities are required; therefore ensuring a high CHO availability before and during exercise is of major importance. A high CHO availability has also been positively related to the exercise-induced adaptations to resistance training. By contrast, a low CHO availability seems to promote endurance-exercise-induced adaptations such as mitochondrial biogenesis and enhanced lipolysis. In the present narrative review, we aim to provide a holistic overview of how CHO availability impacts physical performance as well as to provide practical recommendations on how training and nutrition might be combined to maximize performance. Attending to the existing evidence, no universal recommendations regarding CHO intake can be given to athletes as nutrition should be periodized according to training loads and objectives.

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Role of developmental factors in the switch from pyruvate to glucose as the major exogenous energy substrate in the preimplantation mouse embryo

Reproduction Fertility and Development ◽

10.1071/rd97071 ◽

1999 ◽

Vol 11 (8) ◽

pp. 425 ◽

Cited By ~ 24

Author(s):

Karen L. Martin ◽

Henry J. Leese

Keyword(s):

Developmental Stage ◽

Preimplantation Embryo ◽

Cell Number ◽

Substrate Preference ◽

Energy Substrate ◽

Developmental Factors ◽

Embryonic Genome ◽

Preimplantation Mouse

Preimplantation mouse embryos, cultured in vitro and those freshly flushed from the reproductive tract, exhibit a switch in energy substrate preference, from pyruvate during the early preimplantation stages, to glucose at the blastocyst stage. Although the biochemical basis of this phenomenon is quite well characterized, its timing and possible association with developmental factors have not been considered. We have therefore examined the role of five developmental factors in determining the timing of the switch, namely: (1) embryo age (in hours post hCG); (2) developmental stage; (3) cytokinesis; (4) cell number; and (5) activation of the embryonic genome. One-cell embryos, which develop more slowly than 2-cell embryos in vitro, were used to investigate the role of embryo age and developmental stage. Cytochalasin D, which inhibits cytokinesis and delays the timing of compaction and cavitation, was used to investigate the role of cell division and developmental stage. Finally, transcription of the embryonic genome was examined with the inhibitor, α-amanitin. Pyruvate and glucose consumption by single embryos were measured using a non-invasive ultramicrofluorometric technique. The results showed that the timing of the switch in energy substrate preference is precisely regulated in the mouse preimplantation embryo. Activation of the embryonic genome is a prerequisite for the switch and its timing is closely associated with developmental stage, specifically compaction and/or cavitation. Cell number, cytokinesis and embryo age appeared to be unrelated to the timing of the switch. These conclusions may well be extrapolated to other species, since an increase in net glucose uptake, if not always at the expense of pyruvate, is a feature of preimplantation embryo metabolism in all mammals studied.

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Myocardial mechanical dysfunction following endotoxemia: role of changes in energy substrate metabolism

Basic Research in Cardiology ◽

10.1007/s00395-016-0544-7 ◽

2016 ◽

Vol 111 (2) ◽

Cited By ~ 2

Author(s):

Hamid Soraya ◽

Waleed G. T. Masoud ◽

Manoj Gandhi ◽

Alireza Garjani ◽

Alexander S. Clanachan

Keyword(s):

Energy Substrate ◽

Substrate Metabolism

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The role of exogenous energy substrates in blastocoele fluid accumulation in the rat

Zygote ◽

10.1017/s0967199400001787 ◽

1994 ◽

Vol 2 (1) ◽

pp. 69-77 ◽

Cited By ~ 17

Author(s):

Daniel R. Brison ◽

Henry J. Leese

Keyword(s):

Direct Relationship ◽

Lactate Production ◽

Single Layer ◽

Mammalian Development ◽

Fluid Accumulation ◽

Energy Substrates ◽

Energy Substrate ◽

Non Invasive ◽

The Relationship

SummaryPreimplantation mammalian development culminates in the formation of a fluid-filled cavity, the blastocoele, which is a prerequisite for successful implantation and further development. The blastocoele is enclosed by a single layer of polarised cells, the trophectoderm, which is the first epithelium formed in development. In embryos of the mouse and the rabbit, a basolaterally located Na+/K+-ATPase hydrolyses ATP to drive the vectorial transport of ions, which is responsible for the accumulation of blastocoele fluid. Using non-invasive assays of energy substrate consumption and blastocoele fluid accumulation, experiments were carried out on single preimplantation rat embryos, to establish: (1) the roles of the Na+/K+-ATPase and exogenous energy substrates, and (2) the relationship between the consumption and metabolism of energy substrates and fluid accumulation, during blastocoele cavity formation in this species. Ouabain 0.5 mM and energy-substrate-free medium both caused an inhibition in the number of embryos forming a blastocoele in culture, and also reduced the rate of fluid accumulation by day 5 blastocysts collapsed in cytochalasin-D and allowed to re-expand. Ouabain also reduced the consumption of glucose (but not pyruvate) and the production of lactate by re-expanding blastocysts. In the absence of the inhibitor, a direct relationship was seen between fluid accumulation and both glucose (but not pyruvate) consumption and lactate production. However, ouabain had no effect on intact, expanded blastocysts. These results suggest that (1) a basolaterally located, ouabain-inhibitable Na+/K+-ATPase is involved in rat blastocoele formation, (2) this process is dependent on exogenous energy substrates, and (3) there may be a direct relationship between the metabolism of glucose via glycolysis, and blastocoele fluid accumulation.

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Role of adult hippocampal neurogenesis in the antidepressant actions of lactate

Molecular Psychiatry ◽

10.1038/s41380-021-01122-0 ◽

2021 ◽

Author(s):

Anthony Carrard ◽

Frédéric Cassé ◽

Charline Carron ◽

Sophie Burlet-Godinot ◽

Nicolas Toni ◽

...

Keyword(s):

Synaptic Plasticity ◽

Animal Models ◽

Memory Consolidation ◽

Hippocampal Neurogenesis ◽

Adult Hippocampal Neurogenesis ◽

Signaling Molecule ◽

Energy Substrate ◽

Antidepressant Effects ◽

Adult Hippocampus

AbstractIn addition to its role as a neuronal energy substrate and signaling molecule involved in synaptic plasticity and memory consolidation, recent evidence shows that lactate produces antidepressant effects in animal models. However, the mechanisms underpinning lactate’s antidepressant actions remain largely unknown. In this study, we report that lactate reverses the effects of corticosterone on depressive-like behavior, as well as on the inhibition of both the survival and proliferation of new neurons in the adult hippocampus. Furthermore, the inhibition of adult hippocampal neurogenesis prevents the antidepressant-like effects of lactate. Pyruvate, the oxidized form of lactate, did not mimic the effects of lactate on adult hippocampal neurogenesis and depression-like behavior. Finally, our data suggest that conversion of lactate to pyruvate with the concomitant production of NADH is necessary for the neurogenic and antidepressant effects of lactate.

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