Fasting enhances mitochondrial efficiency in duckling skeletal muscle by acting on the substrate oxidation system

AbstractPrimary human myotubes represent an alternative system to intact skeletal muscle for the study of human diseases related to changes in muscle energy metabolism. This work aimed to study if fatty acid and glucose metabolism in human myotubes in vitro were related to muscle of origin, donor gender, age, or body mass index (BMI). Myotubes from a total of 82 donors were established from three different skeletal muscles, i.e., musculus vastus lateralis, musculus obliquus internus abdominis, and musculi interspinales, and cellular energy metabolism was evaluated. Multiple linear regression analyses showed that donor age had a significant effect on glucose and oleic acid oxidation after correcting for gender, BMI, and muscle of origin. Donor BMI was the only significant contributor to cellular oleic acid uptake, whereas cellular glucose uptake did not rely on any of the variables examined. Despite the effect of age on substrate oxidation, cellular mRNA expression of pyruvate dehydrogenase kinase 4 (PDK4) and peroxisome proliferator–activated receptor gamma coactivator 1 alpha (PPARGC1A) did not correlate with donor age. In conclusion, donor age significantly impacts substrate oxidation in cultured human myotubes, whereas donor BMI affects cellular oleic acid uptake.

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Effect of β1- and β2-adrenergic stimulation on energy expenditure, substrate oxidation, and UCP3 expression in humans

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00175.2003 ◽

2003 ◽

Vol 285 (4) ◽

pp. E775-E782 ◽

Cited By ~ 50

Author(s):

Joris Hoeks ◽

Marleen A. van Baak ◽

Matthijs K. C. Hesselink ◽

Gabby B. Hul ◽

Hubert Vidal ◽

...

Keyword(s):

Skeletal Muscle ◽

Energy Expenditure ◽

Mrna Expression ◽

Uncoupling Protein ◽

Plasma Free Fatty Acid ◽

Substrate Oxidation ◽

Mrna Levels ◽

Adrenergic Stimulation ◽

Before And After ◽

Plasma Ffa

In humans, β-adrenergic stimulation increases energy and fat metabolism. In the case of β1-adrenergic stimulation, it is fueled by an increased lipolysis. We examined the effect of β2-adrenergic stimulation, with and without a blocker of lipolysis, on thermogenesis and substrate oxidation. Furthermore, the effect of β1-and β2-adrenergic stimulation on uncoupling protein 3 (UCP3) mRNA expression was studied. Nine lean males received a 3-h infusion of dobutamine (DOB, β1) or salbutamol (SAL, β2). Also, we combined SAL with acipimox to block lipolysis (SAL+ACI). Energy and substrate metabolism were measured continuously, blood was sampled every 30 min, and muscle biopsies were taken before and after infusion. Energy expenditure significantly increased ∼13% in all conditions. Fat oxidation increased 47 ± 7% in the DOB group and 19 ± 7% in the SAL group but remained unchanged in the SAL+ACI condition. Glucose oxidation decreased 40 ± 9% upon DOB, remained unchanged during SAL, and increased 27 ± 11% upon SAL+ACI. Plasma free fatty acid (FFA) levels were increased by SAL (57 ± 11%) and DOB (47 ± 16%), whereas SAL+ACI caused about fourfold lower FFA levels compared with basal levels. No change in UCP3 was found after DOB or SAL, whereas SAL+ACI downregulated skeletal muscle UCP3 mRNA levels 38 ± 13%. In conclusion, β2-adrenergic stimulation directly increased energy expenditure independently of plasma FFA levels. Furthermore, this is the first study to demonstrate a downregulation of skeletal muscle UCP3 mRNA expression after the lowering of plasma FFA concentrations in humans, despite an increase in energy expenditure upon β2-adrenergic stimulation.

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Effect of functional overload on substrate oxidation capacity of skeletal muscle

Journal of Applied Physiology ◽

10.1152/jappl.1981.50.6.1272 ◽

1981 ◽

Vol 50 (6) ◽

pp. 1272-1276 ◽

Cited By ~ 17

Author(s):

K. M. Baldwin ◽

V. Valdez ◽

L. F. Schrader ◽

R. E. Herrick

Keyword(s):

Skeletal Muscle ◽

Substrate Oxidation ◽

Oxidation Capacity

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A Primary Reduced TCA Flux Governs Substrate Oxidation in T2D Skeletal Muscle

Current Diabetes Reviews ◽

10.2174/157339912803529841 ◽

2012 ◽

Vol 8 (6) ◽

pp. 458-479 ◽

Cited By ~ 1

Author(s):

Michael Gaster

Keyword(s):

Skeletal Muscle ◽

Substrate Oxidation

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Top-down control analysis of the effect of temperature on ectotherm oxidative phosphorylation

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00240.2004 ◽

2004 ◽

Vol 287 (4) ◽

pp. R794-R800 ◽

Cited By ~ 23

Author(s):

M. E. Chamberlin

Keyword(s):

Oxygen Consumption ◽

Membrane Potential ◽

Oxidative Phosphorylation ◽

Substrate Oxidation ◽

The State ◽

Proton Leak ◽

Control Analysis ◽

Top Down ◽

Temperature Ranges ◽

Oxidation System

Top-down control and elasticity analysis was conducted on mitochondria isolated from the midgut of the tobacco hornworm ( Manduca sexta) to assess how temperature affects oxidative phosphorylation in a eurythermic ectotherm. Oxygen consumption and protonmotive force (measured as membrane potential in the presence of nigericin) were monitored at 15, 25, and 35°C. State 4 respiration displayed a Q10 of 2.4–2.7 when measured over two temperature ranges (15–25°C and 25–35°C). In state 3, the Q10s for respiration were 2.0 and 1.7 for the lower and higher temperature ranges, respectively. The kinetic responses (oxygen consumption) of the substrate oxidation system, proton leak, and phosphorylation system increased as temperature rose, although the proton leak and substrate oxidation system showed the greatest thermal sensitivity. Whereas there were temperature-induced changes in the activities of the oxidative phosphorylation subsystems, there was no change in the state 4 membrane potential and little change in the state 3 membrane potential. Top-down control analysis revealed that control over respiration did not change with temperature. In state 4, control of respiration was shared nearly equally by the proton leak and the substrate oxidation system, whereas in state 3 the substrate oxidation system exerted over 90% of the control over respiration. The proton leak and phosphorylation system account for <10% of the temperature-induced change in the state 3 respiration rate. Therefore, when the temperature is changed, the state 3 respiration rate is altered primarily because of temperature's effect on the substrate oxidation system.

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Control of oxidative phosphorylation during insect metamorphosis

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00144.2004 ◽

2004 ◽

Vol 287 (2) ◽

pp. R314-R321 ◽

Cited By ~ 15

Author(s):

M. E. Chamberlin

Keyword(s):

Membrane Potential ◽

Oxidative Phosphorylation ◽

Adenine Nucleotide ◽

Substrate Oxidation ◽

Proton Leak ◽

Protonmotive Force ◽

Control Analysis ◽

Membrane Area ◽

Early Stages ◽

Oxidation System

The midgut of the tobacco hornworm ( Manduca sexta) is a highly aerobic tissue that is destroyed and replaced by a pupal epithelium at metamorphosis. To determine how oxidative phosphorylation is altered during the programmed death of the larval cells, top-down control analysis was performed on mitochondria isolated from the midguts of larvae before and after the commitment to pupation. Oxygen consumption and protonmotive force (measured as membrane potential in the presence of nigericin) were monitored to determine the kinetic responses of the substrate oxidation system, proton leak, and phosphorylation system to changes in the membrane potential. Mitochondria from precommitment larvae have higher respiration rates than those from postcommitment larvae. State 4 respiration is controlled by the proton leak and the substrate oxidation system. In state 3, the substrate oxidation system exerted 90% of the control over respiration, and this high level of control did not change with development. Elasticity analysis, however, revealed that, after commitment, the activity of the substrate oxidation system falls. This decline may be due, in part, to a loss of cytochrome c from the mitochondria. There are no differences in the kinetics of the phosphorylation system, indicating that neither the F1F0 ATP synthase nor the adenine nucleotide translocase is affected in the early stages of metamorphosis. An increase in proton conductance was observed in mitochondria isolated from postcommitment larvae, indicating that membrane area, lipid composition, or proton-conducting proteins may be altered during the early stages of the programmed cell death of the larval epithelium.

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