Exercise training and calorie restriction increase SREBP-1 expression and intramuscular triglyceride in skeletal muscle

2006 ◽  
Vol 291 (1) ◽  
pp. E90-E98 ◽  
Author(s):  
Kristen J. Nadeau ◽  
Lindsay B. Ehlers ◽  
Lina E. Aguirre ◽  
Russell L. Moore ◽  
Korinne N. Jew ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Exercise Training ◽  
Calorie Restriction ◽  
Fatty Acid Synthase ◽  
Regulatory Element ◽  
Vastus Lateralis ◽  
Vastus Lateralis Muscle ◽  
Sprague Dawley ◽  
Intramuscular Triglyceride

Intramuscular triglyceride (IMTG) deposition in skeletal muscle is associated with obesity and type 2 diabetes (T2DM) and is thought to be related to insulin resistance (IR). Curiously, despite enhanced skeletal muscle insulin sensitivity, highly trained athletes and calorie-restricted (CR) monkeys also have increased IMTG. Sterol regulatory element-binding proteins (SREBPs) are transcription factors that regulate the biosynthesis of cholesterol and fatty acids. SREBP-1 is increased by insulin in skeletal muscle in vitro and in skeletal muscle of IR subjects, but SREBP-1 expression has not been examined in exercise training or calorie restriction. We examined the relationship between IMTG and SREBP-1 expression in animal models of exercise and calorie restriction. Gastrocnemius and soleus muscle biopsies were obtained from 38 Sprague-Dawley rats (18 control and 20 exercise trained). Triglyceride content was higher in the gastrocnemius and soleus muscles of the trained rats. SREBP-1c mRNA, SREBP-1 precursor and mature proteins, and fatty acid synthase (FAS) protein were increased with exercise training. Monkeys ( Macaca mulatta) were CR for a mean of 10.4 years, preventing weight gain and IR. Vastus lateralis muscle was obtained from 12 monkeys (6 CR and 6 controls). SREBP-1 precursor and mature proteins and FAS protein were higher in the CR monkeys. In addition, phosphorylation of ERK1/ERK2 was increased in skeletal muscle of CR animals. In summary, SREBP-1 protein and SREBP-1c mRNA are increased in interventions that increase IMTG despite enhanced insulin sensitivity. CR and exercise-induced augmentation of SREBP-1 expression may be responsible for the increased IMTG seen in skeletal muscle of highly conditioned athletes.

scholarly journals Skeletal muscle phosphatidylcholine and phosphatidylethanolamine are related to insulin sensitivity and respond to acute exercise in humans

2016 ◽  
Vol 120 (11) ◽  
pp. 1355-1363 ◽  
Author(s):  
Sean A. Newsom ◽  
Joseph T. Brozinick ◽  
Katja Kiseljak-Vassiliades ◽  
Allison N. Strauss ◽  
Samantha D. Bacon ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Acute Exercise ◽  
Contractile Function ◽  
Vastus Lateralis ◽  
Mass Spectrometry Analysis ◽  
Vastus Lateralis Muscle ◽  
Intravenous Glucose ◽  
Exercise In Humans

Several recent reports indicate that the balance of skeletal muscle phosphatidylcholine (PC) and phosphatidylethanolamine (PE) is a key determinant of muscle contractile function and metabolism. The purpose of this study was to determine relationships between skeletal muscle PC, PE and insulin sensitivity, and whether PC and PE are dynamically regulated in response to acute exercise in humans. Insulin sensitivity was measured via intravenous glucose tolerance in sedentary obese adults (OB; n = 14), individuals with type 2 diabetes (T2D; n = 15), and endurance-trained athletes (ATH; n = 15). Vastus lateralis muscle biopsies were obtained at rest, immediately after 90 min of cycle ergometry at 50% maximal oxygen consumption (V̇o2 max), and 2-h postexercise (recovery). Skeletal muscle PC and PE were measured via infusion-based mass spectrometry/mass spectrometry analysis. ATH had greater levels of muscle PC and PE compared with OB and T2D ( P < 0.05), with total PC and PE positively relating to insulin sensitivity (both P < 0.05). Skeletal muscle PC:PE ratio was elevated in T2D compared with OB and ATH ( P < 0.05), tended to be elevated in OB vs. ATH ( P = 0.07), and was inversely related to insulin sensitivity among the entire cohort ( r = −0.43, P = 0.01). Muscle PC and PE were altered by exercise, particularly after 2 h of recovery, in a highly group-specific manner. However, muscle PC:PE ratio remained unchanged in all groups. In summary, total muscle PC and PE are positively related to insulin sensitivity while PC:PE ratio is inversely related to insulin sensitivity in humans. A single session of exercise significantly alters skeletal muscle PC and PE levels, but not PC:PE ratio.

Exercise adaptation attenuates VEGF gene expression in human skeletal muscle

2000 ◽  
Vol 279 (2) ◽  
pp. H772-H778 ◽  
Author(s):  
R. S. Richardson ◽  
H. Wagner ◽  
S. R. D. Mudaliar ◽  
E. Saucedo ◽  
R. Henry ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Human Skeletal Muscle ◽  
Acute Exercise ◽  
Vastus Lateralis ◽  
Northern Analysis ◽  
Endothelial Cell Proliferation ◽  
Vastus Lateralis Muscle ◽  
Mrna Levels ◽  
Exercise Adaptation

Angiogenesis is a component of the multifactoral adaptation to exercise training, and vascular endothelial growth factor (VEGF) is involved in extracellular matrix changes and endothelial cell proliferation. However, there is limited evidence supporting the role of VEGF in the exercise training response. Thus we studied mRNA levels of VEGF, using quantitative Northern analysis, in untrained and trained human skeletal muscle at rest and after a single bout of exercise. Single leg knee-extension provided the acute exercise stimulus and the training modality. Four biopsies were collected from the vastus lateralis muscle at rest in the untrained and trained conditions before and after exercise. Training resulted in a 35% increase in muscle oxygen consumption and an 18% increase in number of capillaries per muscle fiber. At rest, VEGF/18S mRNA levels were similar before (0.38 ± 0.04) and after (1.2 ± 0.4) training. When muscle was untrained, acute exercise greatly elevated VEGF/18S mRNA levels (16.9 ± 6.7). The VEGF/18S mRNA response to acute exercise in the trained state was markedly attenuated (5.4 ± 1.3). These data support the concept that VEGF is involved in exercise-induced skeletal muscle angiogenesis and appears to be subject to a negative feedback mechanism as exercise adaptations occur.

scholarly journals Changes Induced by Physical Activity and Weight Loss in the Morphology of Intermyofibrillar Mitochondria in Obese Men and Women

2006 ◽  
Vol 91 (8) ◽  
pp. 3224-3227 ◽  
Author(s):  
Frederico G. S. Toledo ◽  
Simon Watkins ◽  
David E. Kelley
Keyword(s):  
Physical Activity ◽  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Weight Loss ◽  
Insulin Sensitivity ◽  
Lifestyle Modification ◽  
Vastus Lateralis ◽  
Vastus Lateralis Muscle ◽  
Mitochondrial Content ◽  
The Mean

Abstract Context: In obesity, skeletal muscle insulin resistance may be associated with smaller mitochondria. Objective: Our objective was to examine the effect of a lifestyle-modification intervention on the content and morphology of skeletal muscle mitochondria and its relationship to insulin sensitivity in obese, insulin-resistant subjects. Design: In this prospective interventional study, intermyofibrillar mitochondrial content and size were quantified by transmission electron microscopy with quantitative morphometric analysis of biopsy samples from vastus lateralis muscle. Systemic insulin sensitivity was measured with euglycemic hyperinsulinemic clamps. Setting: The study took place at a university-based clinical research center. Participants: Eleven sedentary, overweight/obese volunteers without diabetes participated in the study. Intervention: Intervention included 16 wk of aerobic training with dietary restriction of 500-1000 kcal/d. Main Outcome Measures: We assessed changes in mitochondrial content and size and changes in insulin sensitivity. Results: The percentage of myofiber volume occupied by mitochondria significantly increased from 3.70 ± 0.31 to 4.87 ± 0.33% after intervention (P = 0.01). The mean individual increase was 42.5 ± 18.1%. There was also a change in the mean cross-sectional mitochondrial area, increasing from a baseline of 0.078 ± 0.007 to 0.091 ± 0.007 μm2 (P &lt; 0.01), a mean increase of 19.2 ± 6.1% per subject. These changes in mitochondrial size and content highly correlated with improvements in insulin resistance (r = 0.68 and 0.72, respectively; P = 0.01). Conclusions: A combined intervention of weight loss and physical activity in previously sedentary obese adults is associated with enlargement of mitochondria and an increase in the mitochondrial content in skeletal muscle. These findings indicate that in obesity with insulin resistance, ultrastructural mitochondrial plasticity is substantially retained and, importantly, that changes in the morphology of mitochondria are associated with improvements in insulin resistance.

Effect of short-term exercise training on insulin-stimulated PI 3-kinase activity in human skeletal muscle

1999 ◽  
Vol 277 (6) ◽  
pp. E1055-E1060 ◽  
Author(s):  
Joseph A. Houmard ◽  
Christopher D. Shaw ◽  
Matthew S. Hickey ◽  
Charles J. Tanner
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Exercise Training ◽  
Kinase Activity ◽  
Vastus Lateralis ◽  
Maximal Oxygen Consumption ◽  
Exercise Bout ◽  
Phosphatidylinositol 3 Kinase ◽  
Insulin Signal Transduction ◽  
Before And After

The purpose of this study was to determine if the improvement in insulin sensitivity with exercise training is associated with enhanced phosphatidylinositol 3-kinase (PI 3-kinase) activity. Nine sedentary men were studied before and after 7 days of exercise training (1 h/day, ≈75% maximal oxygen consumption). Insulin sensitivity was determined with a euglycemic-hyperinsulinemic glucose clamp in the sedentary state and 15–17 h after the final exercise bout. PI 3-kinase activity was determined from samples (vastus lateralis) obtained in the fasted condition and after 60 min of submaximal insulin stimulation during the clamp. After exercise, glucose infusion rate increased ( P < 0.05) significantly (means ± SE, 7.8 ± 0.5 vs. 9.8 ± 0.8 mg ⋅ kg−1 ⋅ min−1), indicating improved insulin sensitivity. Insulin-stimulated (insulin stimulated/fasting) phosphotyrosine immunoprecipitable PI 3-kinase activity also increased significantly ( P < 0.05) with exercise (3.1 ± 0.8-fold) compared with the sedentary condition (1.3 ± 0.1-fold). There was no change in fasting PI 3-kinase activity. These data suggest that an enhancement of insulin signal transduction in skeletal muscle may contribute to the improvement in insulin action with exercise.

Exercise training increases lipid metabolism gene expression in human skeletal muscle

2002 ◽  
Vol 283 (1) ◽  
pp. E66-E72 ◽  
Author(s):  
Rebecca J. Tunstall ◽  
Kate A. Mehan ◽  
Glenn D. Wadley ◽  
Gregory R. Collier ◽  
Arend Bonen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Plasma Membrane ◽  
Exercise Training ◽  
Lipid Oxidation ◽  
Binding Protein ◽  
Regulatory Element ◽  
Vastus Lateralis ◽  
Vastus Lateralis Muscle ◽  
Peroxisome Proliferator ◽  
Cpt I

The effects of a single bout of exercise and exercise training on the expression of genes necessary for the transport and β-oxidation of fatty acids (FA), together with the gene expression of transcription factors implicated in the regulation of FA homeostasis were investigated. Seven human subjects (3 male, 4 female, 28.9 ± 3.1 yr of age, range 20–42 yr, body mass index 22.6 kg/m2, range 17–26 kg/m2) underwent a 9-day exercise training program of 60 min cycling per day at 63% peak oxygen uptake (V˙o 2 peak; 104 ± 14 W). On days 1 and 9 of the program, muscle biopsies were sampled from the vastus lateralis muscle at rest, at the completion of exercise, and again 3 h postexercise. Gene expression of key components of FA transport [FA translocase (FAT/CD36), plasma membrane-associated FA-binding protein], β-oxidation [carntine palmitoyltransferase(CPT) I, β-hydroxyacyl-CoA dehydrogenase] and transcriptional control [peroxisome proliferator-activated receptor (PPAR)α, PPARγ, PPARγ coactivator 1, sterol regulatory element-binding protein-1c] were unaltered by exercise when measured at the completion and at 3 h postexercise. Training increased total lipid oxidation by 24% ( P < 0.05) for the 1-h cycling bout. This increased capacity for lipid oxidation was accompanied by an increased expression of FAT/CD36 and CPT I mRNA. Similarly, FAT/CD36 protein abundance was also upregulated by exercise training. We conclude that enhanced fat oxidation after exercise training is most closely associated with the genes involved in regulating FA uptake across the plasma membrane (FAT/CD36) and across the mitochondrial membrane (CPT I).

scholarly journals Impaired exercise training-induced muscle fiber hypertrophy and Akt/mTOR pathway activation in hypoxemic patients with COPD

2015 ◽  
Vol 118 (8) ◽  
pp. 1040-1049 ◽  
Author(s):  
Frédéric Costes ◽  
Harry Gosker ◽  
Léonard Feasson ◽  
Marine Desgeorges ◽  
Marco Kelders ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Muscle Fiber ◽  
Citrate Synthase ◽  
Vastus Lateralis ◽  
C2c12 Myotubes ◽  
Chronic Obstructive ◽  
Vastus Lateralis Muscle ◽  
Cross Sectional ◽  
Gsk 3Β

Exercise training (ExTr) is largely used to improve functional capacity in patients with chronic obstructive pulmonary disease (COPD). However, ExTr only partially restores muscle function in patients with COPD, suggesting that confounding factors may limit the efficiency of ExTr. In the present study, we hypothesized that skeletal muscle adaptations triggered by ExTr could be compromised in hypoxemic patients with COPD. Vastus lateralis muscle biopsies were obtained from patients with COPD who were either normoxemic ( n = 15, resting arterial Po2 = 68.5 ± 1.5 mmHg) or hypoxemic ( n = 8, resting arterial Po2 = 57.0 ± 1.0 mmHg) before and after a 2-mo ExTr program. ExTr induced a significant increase in exercise capacity both in normoxemic and hypoxemic patients with COPD. However, ExTr increased citrate synthase and lactate dehydrogenase enzyme activities only in skeletal muscle of normoxemic patients. Similarly, muscle fiber cross-sectional area and capillary-to-fiber ratio were increased only in patients who were normoxemic. Expression of atrogenes (MuRF1, MAFbx/Atrogin-1) and autophagy-related genes (Beclin, LC3, Bnip, Gabarapl) remained unchanged in both groups. Phosphorylation of Akt (Ser473), GSK-3β (Ser9), and p70S6k (Thr389) was nonsignificantly increased in normoxemic patients in response to ExTr, but it was significantly decreased in hypoxemic patients. We further showed on C2C12 myotubes that hypoxia completely prevented insulin-like growth factor-1-induced phosphorylation of Akt, GSK-3β, and p70S6K. Together, our observations suggest a role for hypoxemia in the adaptive response of skeletal muscle of patients with COPD in an ExTr program.

Aging and exercise training in skeletal muscle: responses of glutathione and antioxidant enzyme systems

1994 ◽  
Vol 267 (2) ◽  
pp. R439-R445 ◽  
Author(s):  
C. Leeuwenburgh ◽  
R. Fiebig ◽  
R. Chandwaney ◽  
L. L. Ji
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Antioxidant Enzyme ◽  
Enzyme Activities ◽  
Vastus Lateralis ◽  
Antioxidant Systems ◽  
Antioxidant Enzyme Activities ◽  
Vastus Lateralis Muscle ◽  
Adult Rats ◽  
Young Rats

Glutathione (GSH) content and antioxidant enzyme activities were investigated in skeletal muscle of young, adult, and old male Fischer 344 rats. Furthermore, the effect of 10 wk of exercise training on these antioxidant systems was evaluated at all ages. In the soleus muscle, GSH concentration increased markedly with age, with no significant change in glutathione disulfide (GSSG) content. Training caused a 30% decrease of GSH (P < 0.05) in the soleus of young rats and a reduction of the GSH-to-GSSG ratio at all ages. Activity of gamma-glutamyl transpeptidase (GGT), a key enzyme for GSH uptake by muscle, was also significantly decreased with training. GSH, GSSG, and the GSH-to-GSSG ratio were not altered with aging or training in the deep portion of vastus lateralis muscle (DVL). Activities of GSH peroxidase (GPX), GSSG reductase (GR), superoxide dismutase (SOD), catalase (CAT), and GSH sulfur-transferase were increased significantly with aging in both soleus and DVL. In DVL, training increased GPX and SOD activities in the young rats, whereas in soleus, training decreased GR and CAT activities in the adult rats and GGT and CAT activities in the old rats. Muscle lipid peroxidation was significantly increased with aging in both DVL and soleus but was not affected by training. These data indicate that aging may cause not only an overall elevation of antioxidant enzyme activities but also a fiber-specific adaptation of GSH system in skeletal muscle. Exercise training, although increasing selective antioxidant enzymes in the young rats, does not offer additional protection against oxidative stress in the senescent muscle.

scholarly journals High Incomplete Skeletal Muscle Fatty Acid Oxidation Explains Low Muscle Insulin Sensitivity in Poorly Controlled T2D

2017 ◽  
Vol 103 (3) ◽  
pp. 882-889 ◽  
Author(s):  
Timothy P Gavin ◽  
Jacob M Ernst ◽  
Hyo-Bum Kwak ◽  
Sarah E Caudill ◽  
Melissa A Reed ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Insulin Sensitivity ◽  
Fatty Acid Oxidation ◽  
Mitochondrial Respiration ◽  
Vastus Lateralis ◽  
Acid Oxidation ◽  
Vastus Lateralis Muscle ◽  
Intravenous Glucose ◽  
Mitochondrial Respiratory

Abstract Context Almost 50% of type 2 diabetic (T2D) patients are poorly controlled [glycated hemoglobin (HbA1c) ≥ 7%]; however, the mechanisms responsible for progressively worsening glycemic control are poorly understood. Lower skeletal muscle mitochondrial respiratory capacity is associated with low insulin sensitivity and the development of T2D. Objective We investigated if skeletal muscle insulin sensitivity (SI) was different between well-controlled T2D (WCD) and poorly controlled T2D (PCD) and if the difference was associated with differences resulting from mitochondrial respiratory function. Design Vastus lateralis muscle mitochondrial respiration, mitochondrial content, mitochondrial enzyme activity, and fatty acid oxidation (FAO) were measured. SI and the acute response to glucose (AIRg) were calculated by MINMOD analysis from glucose and insulin obtained during a modified, frequently sampled, intravenous glucose tolerance test. Results SI and AIRg were lower in PCD than WCD. Muscle incomplete FAO was greater in PCD than WCD and greater incomplete FAO was associated with lower SI and higher HbA1c. Hydroxyacyl-coenzyme A dehydrogenase expression and activity were greater in PCD than WCD. There was no difference in maximal mitochondrial respiration or content between WCD and PCD. Conclusion The current results suggest that greater skeletal muscle incomplete FAO in poorly controlled T2D is due to elevated β oxidation and is associated with worsening muscle SI.

scholarly journals Associations of Serum Adiponectin with Skeletal Muscle Morphology and Insulin Sensitivity

2009 ◽  
Vol 94 (3) ◽  
pp. 953-957 ◽  
Author(s):  
Erik Ingelsson ◽  
Johan Ärnlöv ◽  
Björn Zethelius ◽  
Ramachandran S. Vasan ◽  
Allan Flyvbjerg ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Confidence Interval ◽  
Vastus Lateralis ◽  
Muscle Fibers ◽  
Capillary Density ◽  
Serum Adiponectin ◽  
Vastus Lateralis Muscle ◽  
Type I ◽  
Muscle Morphology

Abstract Context: Skeletal muscle morphology and function are strongly associated with insulin sensitivity. Objective: The objective of the study was to test the hypothesis that circulating adiponectin is associated with skeletal muscle morphology and that adiponectin mediates the relation of muscle morphology to insulin sensitivity. Design, Settings, and Participants: This was a cross-sectional investigation of 461 men aged 71 yr, participants of the community-based Uppsala Longitudinal Study of Adult Men study. Main Outcome Measures: Measures included serum adiponectin, insulin sensitivity measured with euglycemic insulin clamp technique, and capillary density and muscle fiber composition determined from vastus lateralis muscle biopsies. Results: In multivariable linear regression models (adjusting for age, physical activity, fasting glucose, and pharmacological treatment for diabetes), serum adiponectin levels rose with increasing capillary density (β, 0.30 per 50 capillaries per square millimeter increase; P = 0.041) and higher proportion of type I muscle fibers (β, 0.27 per 10% increase; P = 0.036) but declined with a higher proportion of type IIb fibers (β, −0.39 per 10% increase; P = 0.014). Using bootstrap methods to examine the potential role of adiponectin in associations between muscle morphology and insulin sensitivity and the associations of capillary density (β difference, 0.041; 95% confidence interval 0.001, 0.085) and proportion of type IIb muscle fibers (β difference, −0.053; 95% confidence interval −0.107, −0.002) with insulin sensitivity were significantly attenuated when adiponectin was included in the models. Conclusions: Circulating adiponectin concentrations were higher with increasing skeletal muscle capillary density and in individuals with higher proportion of slow oxidative muscle fibers. Furthermore, our results indicate that adiponectin could be a partial mediator of the relations between skeletal muscle morphology and insulin sensitivity.

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.

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