scholarly journals Muscle interleukin-6 and fasting-induced PDH regulation in mouse skeletal muscle

2017 ◽  
Vol 312 (3) ◽  
pp. E204-E214 ◽  
Author(s):  
Anders Gudiksen ◽  
Laerke Bertholdt ◽  
Mikkel Birkkjaer Vingborg ◽  
Henriette Watson Hansen ◽  
Stine Ringholm ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Respiratory Exchange Ratio ◽  
Active Form ◽  
Substrate Utilization ◽  
Whole Body ◽  
Metabolic Flexibility ◽  
Prolonged Fasting ◽  
Fat Utilization ◽  
Fasted State ◽  
Regulatory Impact

Fasting prompts a metabolic shift in substrate utilization from carbohydrate to predominant fat oxidation in skeletal muscle, and pyruvate dehydrogenase (PDH) is seen as a controlling link between the competitive oxidation of carbohydrate and fat during metabolic challenges like fasting. Interleukin (IL)-6 has been proposed to be released from muscle with concomitant effects on both glucose and fat utilization. The aim was to test the hypothesis that muscle IL-6 has a regulatory impact on fasting-induced suppression of skeletal muscle PDH. Skeletal muscle-specific IL-6 knockout (IL-6 MKO) mice and floxed littermate controls (control) were either fed or fasted for 6 or 18 h. Lack of muscle IL-6 elevated the respiratory exchange ratio in the fed and early fasting state, but not with prolonged fasting. Activity of PDH in the active form (PDHa) was higher in fed and fasted IL-6 MKO than in control mice at 18 h, but not at 6 h, whereas lack of muscle IL-6 did not prevent downregulation of PDHa activity in skeletal muscle or changes in plasma and muscle substrate levels in response to 18 h of fasting. Phosphorylation of three of four sites on PDH-E1α increased with 18 h of fasting, but was lower in IL-6 MKO mice than in control. In addition, both PDK4 mRNA and protein increased with 6 and 18 h of fasting in both genotypes, but PDK4 protein was lower in IL-6 MKO than in control. In conclusion, skeletal muscle IL-6 seems to regulate whole body substrate utilization in the fed, but not fasted, state and influence skeletal muscle PDHa activity in a circadian manner. However, skeletal muscle IL-6 is not required for maintaining metabolic flexibility in response to fasting.

Effects of prolonged fasting on AMPK signaling, gene expression, and mitochondrial respiratory chain content in skeletal muscle from lean and obese individuals

2013 ◽  
Vol 304 (9) ◽  
pp. E1012-E1021 ◽  
Author(s):  
Marjolein A. Wijngaarden ◽  
Gerard C. van der Zon ◽  
Ko Willems van Dijk ◽  
Hanno Pijl ◽  
Bruno Guigas
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Respiratory Chain ◽  
Mitochondrial Respiratory Chain ◽  
Whole Body ◽  
Prolonged Fasting ◽  
Metabolic Gene Expression ◽  
Obese Subjects ◽  
Metabolic Inflexibility ◽  
Mitochondrial Respiratory

Obesity in humans is often associated with metabolic inflexibility, but the underlying molecular mechanisms remain incompletely understood. The aim of the present study was to investigate how adaptation to prolonged fasting affects energy/nutrient-sensing pathways and metabolic gene expression in skeletal muscle from lean and obese individuals. Twelve lean and 14 nondiabetic obese subjects were fasted for 48 h. Whole body glucose/lipid oxidation rates were determined by indirect calorimetry, and blood and skeletal muscle biopsies were collected and analyzed. In response to fasting, body weight loss was similar in both groups, but the decrease in plasma insulin and leptin and the concomitant increase in growth hormone were significantly attenuated in obese subjects. The fasting-induced shift from glucose toward lipid oxidation was also severely blunted. At the molecular level, the expression of insulin receptor-β (IRβ) was lower in skeletal muscle from obese subjects at baseline, whereas the fasting-induced reductions in insulin signaling were similar in both groups. The protein expression of mitochondrial respiratory chain components, although not modified by fasting, was significantly reduced in obese subjects. Some minor differences in metabolic gene expression were observed at baseline and in response to fasting. Surprisingly, fasting reduced AMPK activity in lean but not in obese subjects, whereas the expression of AMPK subunits was not affected. We conclude that whole body metabolic inflexibility in response to prolonged fasting in obese humans is associated with lower skeletal muscle IRβ and mitochondrial respiratory chain content as well as a blunted decline of AMPK 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.

PGC-1α increases PDH content but does not change acute PDH regulation in mouse skeletal muscle

2010 ◽  
Vol 299 (5) ◽  
pp. R1350-R1359 ◽  
Author(s):  
Kristian Kiilerich ◽  
Helle Adser ◽  
Anne H. Jakobsen ◽  
Per A. Pedersen ◽  
D. Grahame Hardie ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Content ◽  
Pyruvate Dehydrogenase ◽  
Active Form ◽  
Pyruvate Dehydrogenase Kinase ◽  
Whole Body ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mouse Skeletal Muscle ◽  
Ppar Γ

The aim of this study was to test whether the transcriptional coactivator peroxisome proliferator-activated receptor (PPAR)-γ coactivator (PGC)1α regulates the content of pyruvate dehydrogenase (PDH)-E1α and influences PDH activity through regulation of pyruvate dehydrogenase kinase-4 (PDK4) expression and subsequently PDH phosphorylation. PGC-1α whole body knockout (KO), muscle-specific PGC-1α overexpressing mice (MCK PGC-1α), and littermate wild-type (WT) mice underwent two interventions known to affect PDH. Quadriceps muscles were removed from fed and 24-h fasted mice as well as at 6 h of recovery after 1-h running and from mice that did not run acutely. PDH-E1α protein content and PDH-E1α phosphorylation were lower in PGC-1α KO and higher in MCK PGC-1α mice at rest, but, while MCK PGC-1α had higher PDK4 protein content, KO of PGC-1α had no effect on PDK4 protein content. The differences in phosphorylation partly vanished when expressing phosphorylation relative to the PDH-E1α content with only a maintained elevated phosphorylation in MCK PGC-1α mice. Fasting upregulated PDK4 protein in PGC-1α KO, MCK PGC-1α and WT mice, but this was not consistently associated with increased PDH-E1α phosphorylation. Downregulation of the activity of PDH in the active form (PDHa) at 6-h recovery from exercise in both the PGC-1α KO and MCK PGC-1α mice and the association between PDH-E1α phosphorylation and PDHa activity in PGC-1α KO mice indicate that PGC-1α is not required for these responses. In conclusion, PGC-1α regulates PDH-E1α protein content in parallel with mitochondrial oxidative proteins, but does not seem to influence PDH regulation in mouse skeletal muscle in response to fasting and in recovery from exercise.

Exercise-induced pyruvate dehydrogenase activation is not affected by 7 days of bed rest

2011 ◽  
Vol 111 (3) ◽  
pp. 751-757 ◽  
Author(s):  
Kristian Kiilerich ◽  
Stine Ringholm ◽  
Rasmus S. Biensø ◽  
James P. Fisher ◽  
Ninna Iversen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Intolerance ◽  
Muscle Glycogen ◽  
Pyruvate Dehydrogenase ◽  
Active Form ◽  
Bed Rest ◽  
Whole Body ◽  
Oral Glucose ◽  
Before And After ◽  
Exercise Induced

To test the hypothesis that physical inactivity impairs the exercise-induced modulation of pyruvate dehydrogenase (PDH), six healthy normally physically active male subjects completed 7 days of bed rest. Before and immediately after the bed rest, the subjects completed an oral glucose tolerance test (OGTT) and a one-legged knee extensor exercise bout [45 min at 60% maximal load (Wmax)] with muscle biopsies obtained from vastus lateralis before, immediately after exercise, and at 3 h of recovery. Blood samples were taken from the femoral vein and artery before and after 40 min of exercise. Glucose intake elicited a larger ( P ≤ 0.05) insulin response after bed rest than before, indicating glucose intolerance. There were no differences in lactate release/uptake across the exercising muscle before and after bed rest, but glucose uptake after 40 min of exercise was larger ( P ≤ 0.05) before bed rest than after. Muscle glycogen content tended to be higher (0.05< P ≤ 0.10) after bed rest than before, but muscle glycogen breakdown in response to exercise was similar before and after bed rest. PDH-E1α protein content did not change in response to bed rest or in response to the exercise intervention. Exercise increased ( P ≤ 0.05) the activity of PDH in the active form (PDHa) and induced ( P ≤ 0.05) dephosphorylation of PDH-E1α on Ser293, Ser295 and Ser300, with no difference before and after bed rest. In conclusion, although 7 days of bed rest induced whole body glucose intolerance, exercise-induced PDH regulation in skeletal muscle was not changed. This suggests that exercise-induced PDH regulation in skeletal muscle is maintained in glucose-intolerant (e.g., insulin resistant) individuals.

scholarly journals Substrate utilization during exercise in formerly morbidly obese women

2001 ◽  
Vol 90 (3) ◽  
pp. 1007-1012 ◽  
Author(s):  
Nicole R. Guesbeck ◽  
Matthew S. Hickey ◽  
Kenneth G. MacDonald ◽  
Walter J. Pories ◽  
Inge Harper ◽  
...  
Keyword(s):  
Bypass Surgery ◽  
Respiratory Exchange Ratio ◽  
Gastric Bypass Surgery ◽  
Stable Condition ◽  
Substrate Utilization ◽  
Morbidly Obese ◽  
Macronutrient Intake ◽  
Obese Women ◽  
Fat Utilization ◽  
Daily Energy

The purpose of this study was to compare substrate utilization during fasting and submaximal exercise in morbidly obese women after weight loss (WL) with that in weight-matched controls (C). WL were studied in the weight-stable condition ∼24 mo after gastric bypass surgery. Energy intake (self-reported) and expenditure (2H2 18O) were also compared. The respiratory exchange ratio during exercise at the same absolute (15 W) workload was significantly ( P ≤ 0.05) elevated in WL vs. C (0.90 ± 0.02 vs. 0.83 ± 0.03); this was reflected as lower fat utilization in WL (29.7 ± 4.8 vs. 53.2 ± 9.7% of energy from fat). Respiratory exchange ratio during exercise at the same relative (65% of maximal O2 uptake) intensity was also significantly ( P < 0.05) elevated in WL (0.96 ± 0.01 vs. 0.89 ± 0.02), and fat use was concomitantly depressed (12.4 ± 3.0 vs. 34.3 ± 9.9% of energy from fat). Resting substrate utilization, daily energy expenditure, and self-reported relative macronutrient intake did not differ between groups. These data suggest that lipid oxidation is depressed during physical activity in WL. This defect may, at least in part, contribute to a propensity for the development of morbid obesity.

Neural control of glucose uptake by skeletal muscle after central administration of NMDA

1995 ◽  
Vol 268 (2) ◽  
pp. R492-R497 ◽  
Author(s):  
C. H. Lang ◽  
M. Ajmal ◽  
A. G. Baillie
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Glucose Uptake ◽  
Neural Control ◽  
Plasma Insulin ◽  
Regional Blood Flow ◽  
Muscle Blood Flow ◽  
Whole Body ◽  
Glucose Disposal ◽  
Central Administration

Intracerebroventricular injection of N-methyl-D-aspartate (NMDA) produces hyperglycemia and increases whole body glucose uptake. The purpose of the present study was to determine in rats which tissues are responsible for the elevated rate of glucose disposal. NMDA was injected intracerebroventricularly, and the glucose metabolic rate (Rg) was determined for individual tissues 20-60 min later using 2-deoxy-D-[U-14C]glucose. NMDA decreased Rg in skin, ileum, lung, and liver (30-35%) compared with time-matched control animals. In contrast, Rg in skeletal muscle and heart was increased 150-160%. This increased Rg was not due to an elevation in plasma insulin concentrations. In subsequent studies, the sciatic nerve in one leg was cut 4 h before injection of NMDA. NMDA increased Rg in the gastrocnemius (149%) and soleus (220%) in the innervated leg. However, Rg was not increased after NMDA in contralateral muscles from the denervated limb. Data from a third series of experiments indicated that the NMDA-induced increase in Rg by innervated muscle and its abolition in the denervated muscle were not due to changes in muscle blood flow. The results of the present study indicate that 1) central administration of NMDA increases whole body glucose uptake by preferentially stimulating glucose uptake by skeletal muscle, and 2) the enhanced glucose uptake by muscle is neurally mediated and independent of changes in either the plasma insulin concentration or regional blood flow.

scholarly journals Association between hand muscle thickness and whole-body skeletal muscle mass in healthy adults: a pilot study

2017 ◽  
Vol 29 (9) ◽  
pp. 1644-1648 ◽  
Author(s):  
Akio Morimoto ◽  
Tadashi Suga ◽  
Nobuaki Tottori ◽  
Michio Wachi ◽  
Jun Misaki ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Pilot Study ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Muscle Thickness ◽  
Healthy Adults ◽  
Whole Body ◽  
Hand Muscle

Determinants of maximal whole-body fat oxidation in elite cross-country skiers: Role of skeletal muscle mitochondria

2018 ◽  
Vol 28 (12) ◽  
pp. 2494-2504 ◽  
Author(s):  
Sune Dandanell ◽  
Anne-Kristine Meinild-Lundby ◽  
Andreas B. Andersen ◽  
Paul F. Lang ◽  
Laura Oberholzer ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Body Fat ◽  
Fat Oxidation ◽  
Whole Body ◽  
Muscle Mitochondria ◽  
Skeletal Muscle Mitochondria ◽  
Cross Country

scholarly journals Influence of Menstrual Cycle Estradiol-β-17 Fluctuations on Energy Substrate Utilization-Oxidation during Aerobic, Endurance Exercise

2021 ◽  
Vol 18 (13) ◽  
pp. 7209
Author(s):  
Hannah N. Willett ◽  
Kristen J. Koltun ◽  
Anthony C. Hackney
Keyword(s):  
Menstrual Cycle ◽  
Athletic Performance ◽  
Luteal Phase ◽  
Substrate Utilization ◽  
Follicular Phase ◽  
Exercise Session ◽  
Future Research ◽  
Physically Active ◽  
Energy Substrate ◽  
Fat Utilization

This study examined the effect of estradiol-β-17 across the menstrual cycle (MC) during aerobic exercise on energy substrate utilization and oxidation. Thirty-two eumenorrheic (age = 22.4 ± 3.8 y (mean ± SD)), physically active women participated in two steady-state running sessions at 65% of VO2max, one during the early follicular and one during the luteal phase of the MC. Blood samples were collected at rest before each exercise session and analyzed for Estradiol-β-17 to confirm the MC phase. Carbohydrate (CHO) utilization and oxidation values were significantly lower (p < 0.05) in the luteal (utilization: 51.6 ± 16.7%; oxidation: 1.22 ± 0.56 g/min; effect size (ES) = 0.45, 0.27) than follicular phase (utilization: 58.2 ± 15.1%; oxidation: 1.38 ± 0.60 g/min) exercise sessions. Conversely, fat utilization and oxidation values were significantly (p < 0.05) higher in the luteal (utilization: 48.4 ± 16.7%; oxidation: 0.49 ± 0.19 g/min; ES = 0.45,0.28) than follicular phase (utilization: 41.8 ± 15.1%; oxidation: 0.41 ± 0.14 g/min). Estradiol-β-17 concentrations were significantly (p < 0.01) greater during the luteal (518.5 ± 285.4 pmol/L; ES = 0.75) than follicular phase (243.8 ± 143.2 pmol/L). Results suggest a greater use of fat and reduced amount of CHO usage during the luteal versus follicular phase, directly related to the change in resting estradiol-β-17. Future research should investigate the role these changes may play in female athletic performance.

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