Effect of acute exercise on citrate synthase activity in untrained and trained human skeletal muscle

Oxidative function during exercise was evaluated in 11 young athletes with marked skeletal muscle hypertrophy induced by long-term resistance training (RTA; body mass 102.6 Ϯ 7.3 kg, mean Ϯ SD) and 11 controls (CTRL; body mass 77.8 Ϯ 6.0 kg). Pulmonary O2 uptake (V O2) and vastus lateralis muscle fractional O2 extraction (by near-infrared spectroscopy) were determined during an incremental cycle ergometer (CE) and one-leg knee-extension (KE) exercise. Mitochondrial respiration was evaluated ex vivo by high-resolution respirometry in permeabilized vastus lateralis fibers obtained by biopsy. Quadriceps femoris muscle cross-sectional area, volume (determined by magnetic resonance imaging), and strength were greater in RTA vs. CTRL (by ϳ40%, ϳ33%, and ϳ20%, respectively). V O2peak during CE was higher in RTA vs. CTRL (4.05 Ϯ 0.64 vs. 3.56 Ϯ 0.30 l/min); no difference between groups was observed during KE. The O2 cost of CE exercise was not different between groups. When divided per muscle mass (for CE) or quadriceps muscle mass (for KE), V O2 peak was lower (by 15-20%) in RTA vs. CTRL. Vastus lateralis fractional O2 extraction was lower in RTA vs. CTRL at all work rates, during both CE and KE. RTA had higher ADP-stimulated mitochondrial respiration (56.7 Ϯ 23.7 pmol O2·s Ϫ1 ·mg Ϫ1 ww) vs. CTRL (35.7 Ϯ 10.2 pmol O2·s Ϫ1 ·mg Ϫ1 ww) and a tighter coupling of oxidative phosphorylation. In RTA, the greater muscle mass and maximal force and the enhanced mitochondrial respiration seem to compensate for the hypertrophy-induced impaired peripheral O2 diffusion. The net results are an enhanced whole body oxidative function at peak exercise and unchanged efficiency and O 2 cost at submaximal exercise, despite a much greater body mass. skeletal muscle hypertrophy; mitochondrial respiration; oxidative metabolism during exercise RESISTANCE TRAINING PROGRAMS have been developed with the aim of improving variables of muscle function such as strength, power, speed, local muscular endurance, coordination, and flexibility (21). Resistance training is now considered an important part of training and rehabilitation programs for healthy subjects and for various types of patients, such as cardiac patients (45), patients with pulmonary diseases (10), patients undergoing prolonged bed-rest periods (2), or elderly subjects (28). In these populations, the combination of resistance training with the more conventional endurance exercise improves the patients' outcomes and quality of life (45).An increase in the cross-sectional area of skeletal muscle fibers and a shift of fiber-type distribution toward type 2 fibers are typical adaptations induced by resistance training; these adaptations enhance the muscle force-generating potential (12) but could represent an impairment to skeletal muscle oxidative metabolism. On the other hand, muscles with higher maximal force would need to recruit a lower number of motor units, and therefore more oxidative (and more efficient) muscle fibers (20,26). According to other authors, strength training may increas...

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“…5A). CS activity, taken as an estimate of mitochondrial content (24), was similar in the two groups (Fig. 5B).…”

Section: Resultsmentioning

confidence: 61%

Skeletal muscle oxidative function in vivo and ex vivo in athletes with marked hypertrophy from resistance training

Salvadego

Domenis

Lazzer

et al. 2013

Journal of Applied Physiology

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“…3D and data not shown). Further, the activity of citrate synthase, a marker of mitochondrial density (20), was identical in PASK Ϫ/Ϫ and WT soleus muscle extracts (Fig. 3E).…”

Section: Pask ؊/؊ Mice Exhibit Increased Whole-body Energy Expenditurmentioning

confidence: 76%

PAS kinase is required for normal cellular energy balance

Hao¹,

Cardon²,

Swiatek³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

156

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The metabolic syndrome, a complex set of phenotypes typically associated with obesity and diabetes, is an increasing threat to global public health. Fundamentally, the metabolic syndrome is caused by a failure to properly sense and respond to cellular metabolic cues. We studied the role of the cellular metabolic sensor PAS kinase (PASK) in the pathogenesis of metabolic disease by using PASK ؊/؊ mice. We identified tissue-specific metabolic phenotypes caused by PASK deletion consistent with its role as a metabolic sensor. Specifically, PASK ؊/؊ mice exhibited impaired glucose-stimulated insulin secretion in pancreatic ␤-cells, altered triglyceride storage in liver, and increased metabolic rate in skeletal muscle. Further, PASK deletion caused nearly complete protection from the deleterious effects of a high-fat diet including obesity and insulin resistance. We also demonstrate that these cellular effects, increased rate of oxidative metabolism and ATP production, occur in cultured cells. We therefore hypothesize that PASK acts in a cell-autonomous manner to maintain cellular energy homeostasis and is a potential therapeutic target for metabolic disease.metabolism ͉ PAS domain ͉ nutrient sensing ͉ obesity B ecause of changes in diet and lifestyle, the incidence of obesity and type 2 diabetes is increasing dramatically worldwide. Type 2 diabetes arises when pancreatic ␤-cells fail to secrete sufficient insulin to compensate for peripheral insulin resistance, a condition severely aggravated by obesity (1, 2). Type 2 diabetes is now widely viewed as a manifestation of a broader underlying metabolic disorder called the metabolic syndrome, which is characterized by hyperglycemia, hyperinsulinemia, dyslipidemia, hypertension, visceral obesity, and cardiovascular disease (3). The World Health Organization estimates that the current decade will witness a 46% increase in diabetes incidence worldwide (from 151 million to 221 million), with the vast majority of this increase being due to metabolic syndrome-related type 2 diabetes (4).Cellular energy and nutrient sensors determine how cells respond to excessive nutrients, and aberrant nutrient and energy sensing is a contributing factor to metabolic syndrome development (5, 6). AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) are two well studied and evolutionarily conserved cellular energy and nutrient sensors. AMPK is activated in response to intracellular ATP depletion and acts to switch the cellular metabolic program from ATP consumption to ATP production (7). In contrast to AMPK, mTOR is activated by sufficient cellular energy or nutrients, particularly amino acids (8). Activation of mTOR stimulates cell growth by increasing protein synthesis through phosphorylation of ribosomal S6 kinase (S6K) and eIF4E-binding protein (9). Decreased AMPK activity and elevated mTOR activity have been linked with obesity, diabetes, and cancer (10-12).Like AMPK and mTOR, PAS kinase (PASK) is a nutrientresponsive protein kinase conserved from yeast to humans. Th...

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“…Modulators of COX have been identified and are thought to be an important regulatory mechanism of this enzyme complex (41,42). In addition, evidence that acute exercise increases skeletal muscle citrate synthase activity well before mRNA transcription and protein synthesis increases has been reported (43,44). Skeletal muscle citrate synthase activity did not increase after 5 h of insulin infusion in one study (45), which is consistent with the current results showing no significant insulin effect on enzyme activity after 4 h. Nevertheless, changes in allosteric activators or inhibitors of these oxidative enzymes must be considered.…”

Section: Discussionmentioning

confidence: 99%

Effect of insulin on human skeletal muscle mitochondrial ATP production, protein synthesis, and mRNA transcripts

Stump

Short

Bigelow

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

418

369

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Mitochondria are the primary site of skeletal muscle fuel metabolism and ATP production. Although insulin is a major regulator of fuel metabolism, its effect on mitochondrial ATP production is not known. Here we report increases in vastus lateralis muscle mitochondrial ATP production capacity (32-42%) in healthy humans (P < 0.01) i.v. infused with insulin (1.5 milliunits͞kg of fat-free mass per min) while clamping glucose, amino acids, glucagon, and growth hormone. Increased ATP production occurred in association with increased mRNA levels from both mitochondrial (NADH dehydrogenase subunit IV) and nuclear [cytochrome c oxidase (COX) subunit IV] genes (164 -180%) encoding mitochondrial proteins (P < 0.05). In addition, muscle mitochondrial protein synthesis, and COX and citrate synthase enzyme activities were increased by insulin (P < 0.05). Further studies demonstrated no effect of low to high insulin levels on muscle mitochondrial ATP production for people with type 2 diabetes mellitus, whereas matched nondiabetic controls increased 16 -26% (P < 0.02) when four different substrate combinations were used. In conclusion, insulin stimulates mitochondrial oxidative phosphorylation in skeletal muscle along with synthesis of gene transcripts and mitochondrial protein in human subjects. Skeletal muscle of type 2 diabetic patients has a reduced capacity to increase ATP production with high insulin levels.cytochrome c oxidase ͉ NADH dehydrogenase subunit IV ͉ amino acids ͉ citrate synthase

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Effect of acute exercise on citrate synthase activity in untrained and trained human skeletal muscle

Cited by 146 publications

References 31 publications

Skeletal muscle oxidative function in vivo and ex vivo in athletes with marked hypertrophy from resistance training

Skeletal muscle oxidative function in vivo and ex vivo in athletes with marked hypertrophy from resistance training

PAS kinase is required for normal cellular energy balance

Effect of insulin on human skeletal muscle mitochondrial ATP production, protein synthesis, and mRNA transcripts

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