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.

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.

scholarly journals Low-carbohydrate diet induces metabolic depression: a possible mechanism to conserve glycogen

2017 ◽  
Vol 313 (4) ◽  
pp. R347-R356 ◽  
Author(s):  
Hugh S. Winwood-Smith ◽  
Craig E. Franklin ◽  
Craig R. White
Keyword(s):  
Physical Activity ◽  
Weight Loss ◽  
Metabolic Rate ◽  
Metabolic Depression ◽  
Carbohydrate Diet ◽  
Low Carbohydrate Diet ◽  
Low Carbohydrate ◽  
Glycogen Stores ◽  
Over Time

Long-term studies have found that low-carbohydrate diets are more effective for weight loss than calorie-restricted diets in the short term but equally or only marginally more effective in the long term. Low-carbohydrate diets have been linked to reduced glycogen stores and increased feelings of fatigue. We propose that reduced physical activity in response to lowered glycogen explains the diminishing weight loss advantage of low-carbohydrate compared with low-calorie diets over longer time periods. We explored this possibility by feeding adult Drosophila melanogaster a standard or a low-carbohydrate diet for 9 days and measured changes in metabolic rate, glycogen stores, activity, and body mass. We hypothesized that a low-carbohydrate diet would cause a reduction in glycogen stores, which recover over time, a reduction in physical activity, and an increase in resting metabolic rate. The low-carbohydrate diet reduced glycogen stores, which recovered over time. Activity was unaffected by diet, but metabolic rate was reduced, in the low-carbohydrate group. We conclude that metabolic depression could explain the decreased effectiveness of low-carbohydrate diets over time and recommend further investigation of long-term metabolic effects of dietary interventions and a greater focus on physiological plasticity within the study of human nutrition.

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.

Skeletal Muscle PDH Activity And Pulmonary VO2 Kinetics are Attenuated After A Low Carbohydrate Diet

2014 ◽  
Vol 46 ◽  
pp. 94-95
Author(s):  
John R. Leckie ◽  
Joshua P. Nederveen ◽  
Jamie Whitfield ◽  
Tim J. Doherty ◽  
Donald H. Paterson ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Carbohydrate Diet ◽  
Low Carbohydrate Diet ◽  
Low Carbohydrate ◽  
Vo2 Kinetics

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.

scholarly journals Flight activity and glycogen depletion on a low-carbohydrate diet

2020 ◽  
Vol 223 (14) ◽  
pp. jeb228379
Author(s):  
Hugh S. Winwood-Smith ◽  
Craig R. White ◽  
Craig E. Franklin
Keyword(s):  
Physical Activity ◽  
Flight Activity ◽  
Metabolic Depression ◽  
Glycogen Depletion ◽  
Carbohydrate Diet ◽  
Low Carbohydrate Diet ◽  
Low Carbohydrate ◽  
Time Periods ◽  
Glycogen Stores ◽  
Increased Activity

ABSTRACTGlycogen is a critical store for locomotion. Depleted glycogen stores are associated with increased fatigue during exercise. The reduced effectiveness of low-carbohydrate diets for weight loss over longer time periods may arise because such diets reduce glycogen stores and thereby energy expenditure via physical activity. To explore the effect of a low-carbohydrate diet on activity and glycogen utilisation, we fed adult Drosophila melanogaster a standard or low-carbohydrate diet for 9 days and measured patterns of flight activity and rates of glycogen depletion. We hypothesised that flight activity and rates of glycogen depletion would be reduced on a low-carbohydrate diet. Flight activity was elevated in the low-carbohydrate group but glycogen depletion rates were unchanged. We conclude that increased activity is probably a foraging response to carbohydrate deficiency and speculate that the previously demonstrated metabolic depression that occurs on a low-carbohydrate diet in this species may allow for increased flight activity without increased glycogen depletion.

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