scholarly journals β-Hydroxybutyrate Increases Exercise Capacity Associated with Changes in Mitochondrial Function in Skeletal Muscle

Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1930
Author(s):  
Matías Monsalves-Alvarez ◽  
Pablo Esteban Morales ◽  
Mauricio Castro-Sepulveda ◽  
Carlos Sepulveda ◽  
Juan Manuel Rodriguez ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Capacity ◽  
Tibialis Anterior ◽  
Performance Test ◽  
Term Treatment ◽  
Mitochondrial Morphology ◽  
Time To Exhaustion ◽  
Short Term Treatment ◽  
Mitofusin 2 ◽  
And Function

β-hydroxybutyrate is the main ketone body generated by the liver under starvation. Under these conditions, it can sustain ATP levels by its oxidation in mitochondria. As mitochondria can modify its shape and function under different nutritional challenges, we study the chronic effects of β-hydroxybutyrate supplementation on mitochondrial morphology and function, and its relation to exercise capacity. Male C57BL/6 mice were supplemented with β-hydroxybutyrate mineral salt (3.2%) or control (CT, NaCl/KCl) for six weeks and submitted to a weekly exercise performance test. We found an increase in distance, maximal speed, and time to exhaustion at two weeks of supplementation. Fatty acid metabolism and OXPHOS subunit proteins declined at two weeks in soleus but not in tibialis anterior muscles. Oxygen consumption rate on permeabilized fibers indicated a decrease in the presence of pyruvate in the short-term treatment. Both the tibialis anterior and soleus showed decreased levels of Mitofusin 2, while electron microscopy assessment revealed a significant reduction in mitochondrial cristae shape in the tibialis anterior, while a reduction in the mitochondrial number was observed only in soleus. These results suggest that short, but not long-term, β-hydroxybutyrate supplementation increases exercise capacity, associated with modifications in mitochondrial morphology and function in mouse skeletal muscle.

scholarly journals Transient neonatal exposure to hyperoxia, an experimental model of preterm birth, leads to skeletal muscle atrophy and fiber type switching

2021 ◽  
Author(s):  
Alyson Deprez ◽  
Zakaria Orfi ◽  
Alexandra Radu ◽  
Ying He ◽  
Daniela Ravizzoni Dartora ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Preterm Birth ◽  
Exercise Capacity ◽  
Skeletal Muscles ◽  
Fiber Type ◽  
Female Rats ◽  
Male Rats ◽  
Antioxidant Defenses ◽  
Increased Risk ◽  
And Function

Individuals born preterm show reduced exercise capacity and increased risk for pulmonary and cardiovascular diseases, but the impact of preterm birth on skeletal muscle, an inherently critical part of cardiorespiratory fitness, remains unknown. We evaluated the impacts of preterm birth-related conditions on the development, growth, and function of skeletal muscle using a recognized preclinical rodent model in which newborn rats are exposed to 80% oxygen from day 3 to 10 of life. We analyzed different hindlimb muscles of male and female rats at 10 days (neonatal), 4 weeks (juvenile) and 16 weeks (young adults). Neonatal high oxygen exposure increased the generation of reactive oxygen species and the signs of inflammation in skeletal muscles, which was associated with muscle fiber atrophy, fiber type shifting (reduced proportion of type I slow fibers and increased proportion of type IIb fast-fatigable fibers), and impairment in muscle function. These effects were maintained until adulthood. Fast-twitch muscles were more vulnerable to the effects of hyperoxia than slow-twitch muscles. Male rats, which expressed lower antioxidant defenses, were more susceptible than females to oxygen-induced myopathy. Overall, preterm birth-related conditions have long-lasting effects on the composition, morphology, and function of skeletal muscles; and these effects are sex-specific. Oxygen-induced changes in skeletal muscles could contribute to the reduced exercise capacity and to increased risk of diseases of preterm born individuals.

Autoradiographic analysis of RNA synthesis in the oocyte—nurse cell complex of the polychaete Ophryotrocha labronica

Development ◽  
1985 ◽  
Vol 88 (1) ◽  
pp. 249-263
Author(s):  
Hadar Emanuelsson
Keyword(s):  
Nurse Cell ◽  
Term Treatment ◽  
Cell Complex ◽  
Short Term Treatment ◽  
Electron Microscope Autoradiography ◽  
Yolk Granules ◽  
Precursor Material ◽  
Autoradiographic Analysis ◽  
And Function ◽  
In Situ Hybridizations

Females of the polychaete Ophryotrocha labronica have been pulse labelled with [5-3H] undine, and the incorporation of label into the RNA of the oocyte-nurse cell complex was followed by light and electron microscope autoradiography. Up to its regression the polyploid nurse cell displays an intense synthesis of rRNA and mRNA, which sustains an extensive production of electron-dense protein granules in it. Concomitantly rRNA and mRNA are synthesized also in the oocyte. Short-term treatment (7h) of polychaete females with α-amanitin provokes serious disturbances of oogenesis and subsequent embryonic development, irrespective of when it is applied during oogenesis. In contrast actinomycin gives such effects only when it is applied at the onset of oogenesis. A previous investigation has demonstrated that nurse cell granules are gradually exported through an intercellular canal to the oocyte, where a fraction of them is incorporated into the typical yolk granules. The present labelling experiments indicate that nurse cell RNA is associated with the exported yolk precursor material. From inhibition experiments with α-amanitin and from in situ hybridizations with a poly(U)probe it appears that mRNA is particularly involved. At the final collapse of the nurse cell practically all its contents are transferred to the oocyte. From that time the ooplasm is found to contain nuage-like RNA aggregates, which in contrast to other [5-3H]uridine-labelled ooplasmic structures (yolk granules, and minor granules and aggregates) have a non-uniform distribution. The possible origin and function of these aggregates is discussed. The investigation indicates that the nurse cell has a significant export of RNA essentially similar to that from insect nurse cells.

scholarly journals Plectin isoform P1b and P1d deficiencies differentially affect mitochondrial morphology and function in skeletal muscle

2015 ◽  
Vol 24 (16) ◽  
pp. 4530-4544 ◽  
Author(s):  
Lilli Winter ◽  
Andrey V. Kuznetsov ◽  
Michael Grimm ◽  
Anikó Zeöld ◽  
Irmgard Fischer ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mitochondrial Morphology ◽  
And Function

scholarly journals Cerebrovascular function and mitochondrial bioenergetics after ischemia-reperfusion in male rats

2017 ◽  
Vol 39 (6) ◽  
pp. 1056-1068 ◽  
Author(s):  
Ibolya Rutkai ◽  
Ivan Merdzo ◽  
Sanjay V Wunnava ◽  
Genevieve T Curtin ◽  
Prasad VG Katakam ◽  
...  
Keyword(s):  
Ischemia Reperfusion ◽  
Cerebral Arteries ◽  
Male Rats ◽  
Mitochondrial Morphology ◽  
Sprague Dawley ◽  
Mitofusin 2 ◽  
Cerebrovascular Function ◽  
Sprague Dawley Rats ◽  
Activity Measurements ◽  
And Function

The underlying factors promoting increased mitochondrial proteins, mtDNA, and dilation to mitochondrial-specific agents in male rats following tMCAO are not fully elucidated. Our goal was to determine the morphological and functional effects of ischemia/reperfusion (I/R) on mitochondria using electron microscopy, Western blot, mitochondrial oxygen consumption rate (OCR), and Ca2+ sparks activity measurements in middle cerebral arteries (MCAs) from male Sprague Dawley rats (Naïve, tMCAO, Sham). We found a greatly increased OCR in ipsilateral MCAs (IPSI) compared with contralateral (CONTRA), Sham, and Naïve MCAs. Consistent with our earlier findings, the expression of Mitofusin-2 and OPA-1 was significantly decreased in IPSI arteries compared with Sham and Naïve. Mitochondrial morphology was disrupted in vascular smooth muscle, but morphology with normal and perhaps greater numbers of mitochondria were observed in IPSI compared with CONTRA MCAs. Consistently, there were significantly fewer baseline Ca2+ events in IPSI MCAs compared with CONTRA, Sham, and Naïve. Mitochondrial depolarization significantly increased Ca2+ sparks activity in the IPSI, Sham, Naïve, but not in the CONTRA group. Our data indicate that altered mitochondrial structure and function occur in MCAs exposed to I/R and that these changes impact not only OCR but Ca2+ sparks activity in both IPSI and CONTRA MCAs.

Exercise capacity and skeletal muscle structure and function before and after balloon mitral valvuloplasty

1995 ◽  
Vol 76 (10) ◽  
pp. 684-688 ◽  
Author(s):  
Clifford W. Barlow ◽  
Jeremy E.H. Long ◽  
Garry Brown ◽  
Pravin Manga ◽  
Theo E. Meyer ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Capacity ◽  
Structure And Function ◽  
Mitral Valvuloplasty ◽  
Muscle Structure ◽  
Before And After ◽  
And Function

A form of mitofusin 2 (Mfn2) lacking the transmembrane domains and the COOH-terminal end stimulates metabolism in muscle and liver cells

2013 ◽  
Vol 305 (10) ◽  
pp. E1208-E1221 ◽  
Author(s):  
Jessica Segalés ◽  
José C. Paz ◽  
María Isabel Hernández-Alvarez ◽  
David Sala ◽  
Juan Pablo Muñoz ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mitochondrial Dynamics ◽  
Coiled Coil ◽  
Respiratory Control ◽  
Liver Cells ◽  
Transmembrane Domains ◽  
Mitochondrial Fusion ◽  
Metabolic Effects ◽  
Mitochondrial Morphology ◽  
Mitofusin 2

Mitofusin 2 (Mfn2), a protein that participates in mitochondrial fusion, is required to maintain normal mitochondrial metabolism in skeletal muscle and liver. Given that muscle Mfn2 is repressed in obese or type 2 diabetic subjects, this protein may have a potential pathophysiological role in these conditions. To evaluate whether the metabolic effects of Mfn2 can be dissociated from its function in mitochondrial dynamics, we studied a form of human Mfn2, lacking the two transmembrane domains and the COOH-terminal coiled coil (ΔMfn2). This form localized in mitochondria but did not alter mitochondrial morphology in cells or in skeletal muscle fibers. The expression of ΔMfn2 in mouse skeletal muscle stimulated glucose oxidation and enhanced respiratory control ratio, which occurred in the absence of changes in mitochondrial mass. ΔMfn2 did not stimulate mitochondrial respiration in Mfn2-deficient muscle cells. The expression of ΔMfn2 in mouse liver or in hepatoma cells stimulated gluconeogenesis. In addition, ΔMfn2 activated basal and maximal respiration both in muscle and liver cells. In all, we show that a form of Mfn2 lacking mitochondrial fusion activity stimulates mitochondrial function and enhances glucose metabolism in muscle and liver tissues. This study suggests that Mfn2 regulates metabolism independently of changes in mitochondrial morphology.

scholarly journals Curcumin Ameliorates Heat-Induced Injury through NADPH Oxidase–Dependent Redox Signaling and Mitochondrial Preservation in C2C12 Myoblasts and Mouse Skeletal Muscle

2020 ◽  
Vol 150 (9) ◽  
pp. 2257-2267 ◽  
Author(s):  
Tianzheng Yu ◽  
Jacob Dohl ◽  
Li Wang ◽  
Yifan Chen ◽  
Heath G Gasier ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Nadph Oxidase ◽  
Tissue Injury ◽  
Heat Exposure ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Mitochondrial Morphology ◽  
Ros Production ◽  
C2c12 Myoblasts ◽  
Mitochondrial Ros ◽  
And Function

ABSTRACT Background Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and the mitochondrial electron transport chain are the primary sources of reactive oxygen species (ROS). Previous studies have shown that severe heat exposure damages mitochondria and causes excessive mitochondrial ROS production that contributes to the pathogenesis of heat-related illnesses. Objectives We tested whether the antioxidant curcumin could protect against heat-induced mitochondrial dysfunction and skeletal muscle injury, and characterized the possible mechanism. Methods Mouse C2C12 myoblasts and rat flexor digitorum brevis (FDB) myofibers were treated with 5 μM curcumin; adult male C57BL/6J mice received daily curcumin (15, 50, or 100 mg/kg body weight) by gavage for 10 consecutive days. We compared ROS levels and mitochondrial morphology and function between treatment and nontreatment groups under unheated or heat conditions, and investigated the upstream mechanism and the downstream effect of curcumin-regulated ROS production. Results In C2C12 myoblasts, curcumin prevented heat-induced mitochondrial fragmentation, ROS overproduction, and apoptosis (all P < 0.05). Curcumin treatment for 2 and 4 h at 37°C induced increases in ROS levels by 42% and 59% (dihydroethidium-derived fluorescence), accompanied by increases in NADPH oxidase protein expression by 24% and 32%, respectively (all P < 0.01). In curcumin-treated cells, chemical inhibition and genetic knockdown of NADPH oxidase restored ROS to levels similar to those of controls, indicating NADPH oxidase mediates curcumin-stimulated ROS production. Moreover, curcumin induced ROS-dependent shifting of the mitochondrial fission–fusion balance toward fusion, and increases in mitochondrial mass by 143% and membrane potential by 30% (both P < 0.01). In rat FDB myofibers and mouse gastrocnemius muscles, curcumin preserved mitochondrial morphology and function during heat stress, and prevented heat-induced mitochondrial ROS overproduction and tissue injury (all P < 0.05). Conclusions Curcumin regulates ROS hormesis favoring mitochondrial fusion/elongation, biogenesis, and improved function in rodent skeletal muscle. Curcumin may be an effective therapeutic target for heat-related illness and other mitochondrial diseases.

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