Human skeletal muscle PDH kinase activity and isoform expression during a 3-day high-fat/low-carbohydrate diet

2001 ◽  
Vol 281 (6) ◽  
pp. E1151-E1158 ◽  
Author(s):  
Sandra J. Peters ◽  
Robert A. Harris ◽  
Pengfei Wu ◽  
Tanya L. Pehleman ◽  
George J. F. Heigenhauser ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Dietary Intervention ◽  
Specific Activity ◽  
Vastus Lateralis ◽  
Protein A ◽  
Pyruvate Dehydrogenase Kinase ◽  
Vastus Lateralis Muscle ◽  
High Fat ◽  
Low Carbohydrate Diet ◽  
Low Carbohydrate

The increase in skeletal muscle pyruvate dehydrogenase kinase (PDK) activity was measured in skeletal muscle of six healthy males after a eucaloric high-fat/low-carbohydrate (HF/LC; 5% carbohydrate, 73% fat, and 22% protein of total energy intake) diet compared with a standardized prediet (50% carbohdyrate, 30% fat, and 21% protein). Biopsies were obtained from the vastus lateralis muscle after 3 days on the prediet ( day 0) and after 1, 2, and 3 days of the HF/LC diet. Intact mitchondria were extracted from fresh muscle and analyzed for PDK activity and Western blotting of PDK2 and PDK4 protein. A second biopsy was taken at each time point and frozen for Northern blot analysis of PDK2 and PDK4 mRNAs. PDK activity increased in a linear fashion over the 3-day HF/LC diet and was significantly higher than control by 1 day. PDK activity was 0.09 ± 0.03, 0.18 ± 0.05, 0.30 ± 0.07, and 0.37 ± 0.09 min−1 at 0, 1, 2, and 3 days, respectively. PDK4 protein and mRNA increased maximally by day 1, and PDK2 protein and mRNA were unaffected by the HF/LC diet. Resting respiratory exchange ratios decreased after 1 day of the HF/LC diet (from 0.79 ± 0.02 to 0.72 ± 0.02) and remained depressed throughout the 3-day dietary intervention (0.68 ± 0.01). The immediate shift to fat utilization was accompanied by increased blood glycerol, β-hydroxybutyrate, and plasma free fatty acid concentrations. These results suggest that the continuing increase in PDK activity over the 3-day HF/LC diet is not due to increasing PDK protein beyond 1 day. This could be due to the contribution of another isoform to the total PDK activity or to a continual increase in PDK4 or PDK2 specific activity.

Enzymatic regulation of glucose disposal in human skeletal muscle after a high-fat, low-carbohydrate diet

2005 ◽  
Vol 98 (1) ◽  
pp. 100-107 ◽  
Author(s):  
Tanya L. Pehleman ◽  
Sandra J. Peters ◽  
George J. F. Heigenhauser ◽  
Lawrence L. Spriet
Keyword(s):  
Skeletal Muscle ◽  
Active Form ◽  
Whole Body ◽  
Glucose Disposal ◽  
Oral Glucose ◽  
Vastus Lateralis Muscle ◽  
High Fat ◽  
Carbohydrate Diet ◽  
Low Carbohydrate Diet ◽  
Low Carbohydrate

Whole body glucose disposal and skeletal muscle hexokinase, glycogen synthase (GS), pyruvate dehydrogenase (PDH), and PDH kinase (PDK) activities were measured in aerobically trained men after a standardized control diet (Con; 51% carbohydrate, 29% fat, and 20% protein of total energy intake) and a 56-h eucaloric, high-fat, low-carbohydrate diet (HF/LC; 5% carbohydrate, 73% fat, and 22% protein). An oral glucose tolerance test (OGTT; 1 g/kg) was administered after the Con and HF/LC diets with vastus lateralis muscle biopsies sampled pre-OGTT and 75 min after ingestion of the oral glucose load. The 90-min area under the blood glucose and plasma insulin concentration vs. time curves increased by 2-fold and 1.25-fold, respectively, after the HF/LC diet. The pre-OGTT fraction of GS in its active form and the maximal activity of hexokinase were not affected by the HF/LC diet. However, the HF/LC diet increased PDK activity (0.19 ± 0.05 vs. 0.08 ± 0.02 min−1) and decreased PDH activation (0.38 ± 0.08 vs. 0.79 ± 0.10 mmol acetyl-CoA·kg wet muscle−1·min−1) before the OGTT vs. Con. During the OGTT, GS and PDH activation increased by the same magnitude in both diets, such that PDH activation remained lower during the HF/LC OGTT (0.60 ± 0.11 vs. 1.04 ± 0.09 mmol acetyl-CoA·kg−1·min−1). These data demonstrate that the decreased glucose disposal during the OGTT after the 56-h HF/LC diet was in part related to decreased oxidative carbohydrate disposal in skeletal muscle and not to decreased glycogen storage. The rapid increase in PDK activity during the HF/LC diet appeared to account for the reduced potential for oxidative carbohydrate disposal.

Human skeletal muscle pyruvate dehydrogenase kinase activity increases after a low-carbohydrate diet

1998 ◽  
Vol 275 (6) ◽  
pp. E980-E986 ◽  
Author(s):  
Sandra J. Peters ◽  
Timothy A. St. Amand ◽  
Richard A. Howlett ◽  
George J. F. Heigenhauser ◽  
Lawrence L. Spriet
Keyword(s):  
Skeletal Muscle ◽  
Pyruvate Dehydrogenase ◽  
Human Skeletal Muscle ◽  
Citrate Synthase ◽  
Vastus Lateralis ◽  
Active Form ◽  
Pyruvate Dehydrogenase Kinase ◽  
Acid Oxidation ◽  
Low Carbohydrate Diet ◽  
Low Carbohydrate

To characterize human skeletal muscle enzymatic adaptation to a low-carbohydrate, high-fat, and high-protein diet (LCD), subjects consumed a eucaloric diet consisting of 5% of the total energy intake from carbohydrate, 63% from fat, and 33% from protein for 6 days compared with their normal diet (52% carbohydrate, 33% fat, and 14% protein). Biopsies were taken from the vastus lateralis before and after 3 and 6 days on a LCD. Intact mitochondria were extracted from fresh muscle and analyzed for pyruvate dehydrogenase (PDH) kinase, total PDH, and carnitine palmitoyltransferase I activities and mitochondrial ATP production rate (using carbohydrate and fat substrates). β-Hydroxyacyl CoA dehydrogenase, active PDH (PDHa), and citrate synthase activities were also measured on whole muscle homogenates. PDH kinase (PDHK) was calculated as the absolute value of the apparent first-order rate constant of the inactivation of PDH in the presence of 0.3 mM Mg2+-ATP. PDHK increased dramatically from 0.10 ± 0.02 min−1 to 0.35 ± 0.09 min−1 at 3 days and 0.49 ± 0.06 min−1 after 6 days. Resting PDHa activity decreased from 0.63 ± 0.17 to 0.17 ± 0.04 mmol ⋅ min−1 ⋅ kg−1after 6 days on the diet, whereas total PDH activity did not change. Activities for all other enzymes were unaltered by the LCD. In summary, severe deficiency of dietary carbohydrate combined with a twofold increase in dietary fat and protein caused a rapid three- to fivefold increase in PDHK activity in human skeletal muscle. The increased PDHK activity downregulated the amount of PDH in its active form at rest and decreased carbohydrate metabolism. However, an increase in the activities of enzymes involved in fatty acid oxidation did not occur.

Effects of prior exercise and a low-carbohydrate diet on muscle sarcoplasmic reticulum function during cycling in women

2006 ◽  
Vol 101 (3) ◽  
pp. 695-706 ◽  
Author(s):  
T. A. Duhamel ◽  
H. J. Green ◽  
J. G. Perco ◽  
J. Ouyang
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Atpase Activity ◽  
Vastus Lateralis ◽  
Phase 1 ◽  
Vastus Lateralis Muscle ◽  
Low Carbohydrate Diet ◽  
Hill Slope ◽  
Low Carbohydrate ◽  
Exercise Induced

The effects of exercise and diet on sarcoplasmic reticulum Ca2+-cycling properties in female vastus lateralis muscle were investigated in two groups of women following four different conditions. The conditions were 4 days of a low-carbohydrate (Lo CHO) and glycogen-depleting exercise plus a Lo CHO diet (Ex + Lo CHO) ( experiment 2) and 4 days of normal CHO (Norm CHO) and glycogen-depleting exercise plus Norm CHO (Ex + Norm CHO) ( experiment 1). Peak aerobic power (V̇o2peak) was 38.1 ± 1.4 (SE); n = 9 and 35.6 ± 1.4 ml·kg−1·min−1; n = 9, respectively. Sarcoplasmic reticulum properties measured in vitro in homogenates (μmol·g protein−1·min−1) indicated exercise-induced reductions ( P < 0.05) in maximal Ca2+-ATPase activity (0 > 30, 60 min > fatigue), Ca2+ uptake (0 > 30 > 60 min, fatigue), and Ca2+ release, both phase 1 (0, 30 > 60 min, fatigue) and phase 2 (0 > 30, 60 min, fatigue; 30 min > fatigue) in Norm CHO. Exercise was without effect in altering the Hill slope ( nH), defined as the slope of relationship between Ca2+-ATPase activity and Ca2+ concentration. No differences were observed between Norm CHO and Ex+Norm CHO. Compared with Norm CHO, Lo CHO resulted in a lower ( P < 0.05) Ca2+ uptake, phase 1 Ca2+ release (30 min), and nH. Ex + Lo CHO resulted in a greater ( P < 0.05) Ca2+ uptake and nH compared with Lo CHO. The results demonstrate that Lo CHO alone can disrupt SR Ca2+ cycling and that, with the exception of Ca2+ release, a glycogen-depleting session of exercise before Lo CHO can reverse the effects.

Glycogen synthase activation in human skeletal muscle: effects of diet and exercise.

1979 ◽  
Vol 236 (6) ◽  
pp. E660 ◽  
Author(s):  
R G Kochan ◽  
D R Lamb ◽  
S A Lutz ◽  
C V Perrill ◽  
E M Reimann ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glycogen Synthase ◽  
Vastus Lateralis ◽  
Exercise Bout ◽  
Carbohydrate Diet ◽  
Low Carbohydrate Diet ◽  
Low Carbohydrate ◽  
Increased Sensitivity ◽  
Glycogen Stores

We investigated the role of glycogen synthase in supranormal resynthesis (supercompensation) of skeletal muscle glycogen after exhaustive exercise. Six healthy men exercised 60 min by cycling with one leg at 75% VO2max, recovered 3 days on a low-carbohydrate diet, exercised again, and recovered 4 days on high-carbohydrate diet. Glycogen and glycogen synthase activities at several glucose-6-phosphate (G6P) concentrations were measured in biopsy samples of m. vastus lateralis. Dietary alterations alone did not affect glycogen, whereas exercise depleted glycogen stores. After the second exercise bout, glycogen returned to normal within 24 h and reached supercompensated levels by 48 h of recovery. Glycogen synthase activation state strikingly increased after exercise in exercised muscle and remained somewhat elevated for the first 48 h of recovery in both muscles. We suggest that 1) forms of glycogen synthase intermediate to I (G6P-independent) and D (G6P-dependent) forms are present in vivo, and 2) glycogen supercompensation can in part be explained by the formation of intermediate forms of glycogen synthase that exhibit relatively low activity ratios, but an increased sensitivity to activation by G6P.

scholarly journals Consumo e dietas “low carb high fat high protein” suas implicações metabólicas, clínicas e nutricionais: uma revisão integrativa

2021 ◽  
Vol 10 (16) ◽  
pp. e282101623575
Author(s):  
Saulo Leite de Paula ◽  
Maria Rosimar Teixeira Matos ◽  
Yanna Cavalcante Martins ◽  
Noênia Alves de Araújo ◽  
Francisco Sydney Henrique da Silva ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Protein A ◽  
High Protein ◽  
Dietary Carbohydrates ◽  
High Fat ◽  
Carbohydrate Diet ◽  
Pubmed Central ◽  
Low Carbohydrate Diet ◽  
Low Carbohydrate ◽  
Disease Protein

O consumo da dieta da “moda”ow Carb High fat High Protein’ (LCHFHP) está cada vez mais frequente na atualidade por ocasionar erda de peso mais rápida e consequente melhoria na qualidade de vida. A presente revisão integrativa visa identificar as implicações metabólicas, clínicas e nutricionais relacionadas ao consumo de dietas Low Carb High fat High Protein. A pesquisa bibliográfica foi realizada através de buscas nas bases de dados eletrônicas Pubmed Central e Elsevier, no período de 2006 a 2018, com a utilização dos seguintes descritores: “carbohydrate; dietary carbohydrates; diet, low carbohydrate; diet, carbohydrate-restricted; ketosis; diabetes; motor active; obesity; cardiovascular disease; protein; physical activite.” Inicialmente foram encontrados 68.219 artigos. Desses, 40 foram pré-selecionados cumprindo critérios de inclusão. Porém, dentre estes 40, 28 estavam dentro do perfil do estudo. A maioria dos estudos embora demonstrando efeitos positivos com o consumo de dieta LCHFHP, ao curto prazo, quanto à perda de peso, redução no percentual de gordura corporal, melhora da sensibilidade à insulina e no controle glicêmico e redução na utilização de medicações, mostraram que nem sempre esses efeitos foram atribuídos à redução de carboidratos na dieta. Além desses benefícios não terem sido evidenciados ao longo prazo, observou-se aumento nos níveis séricos dos biomarcadores inflamatórios, da extensão da aterosclerose e na morbidade e mortalidade cardiovascular. Realizou-se de mais estudos, principalmente ao longo prazo e com amostragem maior, no sentido de melhor averiguar os benefícios ou riscos decorrentes do consumo dessas dietas, bem como mecanismo de ação, principalmente diante das doenças crônicas não transmissíveis.

Greater effect of diet than exercise training on the fatty acid profile of rat skeletal muscle

2004 ◽  
Vol 96 (3) ◽  
pp. 974-980 ◽  
Author(s):  
Nigel Turner ◽  
Jong Sam Lee ◽  
Clinton R. Bruce ◽  
Todd W. Mitchell ◽  
Paul L. Else ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Exercise Training ◽  
High Intensity ◽  
Vastus Lateralis ◽  
Membrane Phospholipid ◽  
Muscle Membrane ◽  
Vastus Lateralis Muscle ◽  
High Fat ◽  
Fa Composition

We determined the interaction of diet and exercise-training intensity on membrane phospholipid fatty acid (FA) composition in skeletal muscle from 36 female Sprague-Dawley rats. Animals were randomly divided into one of two dietary conditions: high-carbohydrate (64.0% carbohydrate by energy, n = 18) or high fat (78.1% fat by energy, n = 18). Rats in each diet condition were then allocated to one of three subgroups: control, which performed no exercise training; low-intensity (8 m/min) treadmill run training; or high-intensity (28 m/min) run training. All exercise-trained rats ran 1,000 m/session, 4 days/wk for 8 wk and were killed 48 h after the last training bout. Membrane phospholipids were extracted, and FA composition was determined in the red and white vastus lateralis muscles. Diet exerted a major influence on phospholipid FA composition, with the high-fat diet being associated with a significantly ( P < 0.01) elevated ratio of n-6/n-3 FA for both red (2.7–3.2 vs. 1.0–1.1) and white vastus lateralis muscle (2.5–2.9 vs. 1.2). In contrast, alterations in FA composition as a result of either exercise-training protocol were only minor in comparison. We conclude that, under the present experimental conditions, a change in the macronutrient content of the diet was a more potent modulator of skeletal muscle membrane phospholipid FA composition compared with either low- or high-intensity treadmill exercise training.

Transcriptional regulation of gene expression in human skeletal muscle during recovery from exercise

2000 ◽  
Vol 279 (4) ◽  
pp. E806-E814 ◽  
Author(s):  
Henriette Pilegaard ◽  
George A. Ordway ◽  
Bengt Saltin ◽  
P. Darrell Neufer
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Human Skeletal Muscle ◽  
Molecular Mechanisms ◽  
Uncoupling Protein ◽  
Pyruvate Dehydrogenase Kinase ◽  
Heme Oxygenase 1 ◽  
Metabolic Efficiency ◽  
Vastus Lateralis Muscle ◽  
Mrna Levels

Exercise training elicits a number of adaptive changes in skeletal muscle that result in an improved metabolic efficiency. The molecular mechanisms mediating the cellular adaptations to exercise training in human skeletal muscle are unknown. To test the hypothesis that recovery from exercise is associated with transcriptional activation of specific genes, six untrained male subjects completed 60–90 min of exhaustive one-legged knee extensor exercise for five consecutive days. On day 5, nuclei were isolated from biopsies of the vastus lateralis muscle of the untrained and the trained leg before exercise and from the trained leg immediately after exercise and after 15 min, 1 h, 2 h, and 4 h of recovery. Transcriptional activity of the uncoupling protein 3 (UCP3), pyruvate dehydrogenase kinase 4 (PDK4), and heme oxygenase-1 (HO-1) genes (relative to β-actin) increased by three- to sevenfold in response to exercise, peaking after 1–2 h of recovery. Increases in mRNA levels followed changes in transcription, peaking between 2 and 4 h after exercise. Lipoprotein lipase and carnitine pamitoyltransferase I gene transcription and mRNA levels showed similar but less dramatic induction patterns, with increases ranging from two- to threefold. In a separate study, a single 4-h bout of cycling exercise ( n = 4) elicited from 5 to >20-fold increases in UCP3, PDK4, and HO-1 transcription, suggesting that activation of these genes may be related to the duration or intensity of exercise. These data demonstrate that exercise induces transient increases in transcription of metabolic genes in human skeletal muscle. Moreover, the findings suggest that the cumulative effects of transient increases in transcription during recovery from consecutive bouts of exercise may represent the underlying kinetic basis for the cellular adaptations associated with exercise training.

Muscle glycogen availability and temperature regulation in humans

1989 ◽  
Vol 66 (1) ◽  
pp. 72-78 ◽  
Author(s):  
L. Martineau ◽  
I. Jacobs
Keyword(s):  
Skeletal Muscle ◽  
Muscle Glycogen ◽  
Temperature Regulation ◽  
Vastus Lateralis ◽  
Water Immersion ◽  
Vastus Lateralis Muscle ◽  
Glycogen Concentration ◽  
Exercise Regimen ◽  
Before And After ◽  
Muscle Groups

The effects of intramuscular glycogen availability on human temperature regulation were studied in eight seminude subjects immersed in 18 degrees C water for 90 min or until rectal temperature (Tre) decreased to 35.5 degrees C. Each subject was immersed three times over a 3-wk period. Each immersion followed 2.5 days of a specific dietary and/or exercise regimen designed to elicit low (L), normal (N), or high (H) glycogen levels in large skeletal muscle groups. Muscle glycogen concentration was determined in biopsies taken from the vastus lateralis muscle before and after each immersion. Intramuscular glycogen concentration before the immersion was significantly different among the L, N, and H trials (P less than 0.01), averaging 247 +/- 15, 406 +/- 23, and 548 +/- 42 (SE) mmol glucose units.kg dry muscle-1, respectively. The calculated metabolic heat production during the first 30 min of immersion was significantly lower during L compared with N or H (P less than 0.05). The rate at which Tre decreased was more rapid during the L immersion than either N or H (P less than 0.05), and the time during the immersion at which Tre first began to decrease also appeared sooner during L than N or H. The results suggest that low skeletal muscle glycogen levels are associated with more rapid body cooling during water immersion in humans. Higher than normal muscle glycogen levels, however, do not increase cold tolerance.

Muscle blood flow during exercise in sedentary and trained hypothyroid rats

1995 ◽  
Vol 269 (6) ◽  
pp. H1949-H1954 ◽  
Author(s):  
R. M. McAllister ◽  
M. D. Delp ◽  
K. A. Thayer ◽  
M. H. Laughlin
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Citrate Synthase ◽  
Vastus Lateralis ◽  
Muscle Blood Flow ◽  
Treadmill Running ◽  
Exercise Intolerance ◽  
Vastus Lateralis Muscle ◽  
Blood Flows ◽  
Vastus Intermedius

Hypothyroidism is characterized by exercise intolerance. We hypothesized that active muscle blood flow during in vivo exercise is inadequate in the hypothyroid state. Additionally, we hypothesized that endurance exercise training would restore normal blood flow during acute exercise. To test these hypotheses, rats were made hypothyroid (Hypo) over 3-4 mo with propylthiouracil. A subset of Hypo rats was trained (THypo) on a treadmill at 30 m/min (15% grade) for 60 min/day 5 days/wk over 10-15 wk. Hypothyroidism was evidenced by approximately 80% reductions in plasma triiodothyronine levels in Hypo and THypo and by 40-50% reductions in citrate synthase activities in high oxidative muscles in Hypo compared with euthyroid (Eut) rats. Training efficacy was indicated by increased (25-100%) citrate synthase activities in muscles of THypo vs. Hypo. Regional blood flows were determined by the radiolabeled microsphere method before exercise and at 1-2 min of treadmill running at 15 m/min (0% grade). Preexercise muscle blood flows were generally similar among groups. During exercise, however, flows were lower in Hypo than in Eut for high oxidative muscles such as the red section of vastus lateralis [277 +/- 24 and 153 +/- 13 (SE) ml.min-1.100 g-1 for Eut and Hypo, respectively; P < 0.01] and vastus intermedius (317 +/- 32 and 187 +/- 20 ml.min-1.100 g-1 for Eut and Hypo, respectively; P < 0.01) muscles. Training (THypo) did not normalize these flows (168 +/- 24 and 181 +/- 24 ml.min-1.100 g-1 for red section of vastus lateralis and vastus intermedius muscles, respectively). Blood flows to low oxidative muscle, such as the white section of vastus lateralis muscle, were similar among groups (21 +/- 5, 25 +/- 4, and 34 +/- 7 ml.min-1.100 g-1 for Eut, Hypo, and THypo, respectively; P = NS). These findings indicate that hypothyroidism is associated with reduced blood flow to skeletal muscle during exercise, suggesting that impaired delivery of nutrients to and/or removal of metabolites from skeletal muscle contributes to the poor exercise tolerance characteristic of hypothyroidism.

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