scholarly journals Aberrant REDD1-mTORC1 responses to insulin in skeletal muscle from Type 2 diabetics

2015 ◽  
Vol 309 (8) ◽  
pp. R855-R863 ◽  
Author(s):  
David L. Williamson ◽  
Cory M. Dungan ◽  
Abeer M. Mahmoud ◽  
Jacob T. Mey ◽  
Brian K. Blackburn ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Vastus Lateralis ◽  
Glycosylated Hemoglobin ◽  
Whole Body ◽  
Glucose Disposal ◽  
Control Group ◽  
Vastus Lateralis Muscle ◽  
Percent Change ◽  
Phosphorylated Akt

The objective of this study was to establish whether alterations in the REDD1-mTOR axis underlie skeletal muscle insensitivity to insulin in Type 2 diabetic (T2D), obese individuals. Vastus lateralis muscle biopsies were obtained from lean, control and obese, T2D subjects under basal and after a 2-h hyperinsulinemic (40 mU·m−2·min−1)-euglycemic (5 mM) clamp. Muscle lysates were examined for total REDD1, and phosphorylated Akt, S6 kinase 1 (S6K1), 4E-BP1, ERK1/2, and MEK1/2 via Western blot analysis. Under basal conditions [(-) insulin], T2D muscle exhibited higher S6K1 and ERK1/2 and lower 4E-BP1 phosphorylation ( P < 0.05), as well as elevations in blood cortisol, glucose, insulin, glycosylated hemoglobin ( P < 0.05) vs. lean controls. Following insulin infusion, whole body glucose disposal rates (GDR; mg/kg/min) were lower ( P < 0.05) in the T2D vs. the control group. The basal-to-insulin percent change in REDD1 expression was higher ( P < 0.05) in muscle from the T2D vs. the control group. Whereas, the basal-to-insulin percent change in muscle Akt, S6K1, ERK1/2, and MEK1/2 phosphorylation was significantly lower ( P < 0.05) in the T2D vs. the control group. Findings from this study propose a REDD1-regulated mechanism in T2D skeletal muscle that may contribute to whole body insulin resistance and may be a target to improve insulin action in insulin-resistant individuals.

scholarly journals Obesity, type 2 diabetes, and impaired insulin-stimulated blood flow: role of skeletal muscle NO synthase and endothelin-1

2017 ◽  
Vol 122 (1) ◽  
pp. 38-47 ◽  
Author(s):  
Leryn J. Reynolds ◽  
Daniel P. Credeur ◽  
Camila Manrique ◽  
Jaume Padilla ◽  
Paul J. Fadel ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Blood Flow ◽  
Vastus Lateralis ◽  
Glucose Disposal ◽  
Endothelin 1 ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Increased endothelin-1 (ET-1) and reduced endothelial nitric oxide phosphorylation (peNOS) are hypothesized to reduce insulin-stimulated blood flow in type 2 diabetes (T2D), but studies examining these links in humans are limited. We sought to assess basal and insulin-stimulated endothelial signaling proteins (ET-1 and peNOS) in skeletal muscle from T2D patients. Ten obese T2D [glucose disposal rate (GDR): 6.6 ± 1.6 mg·kg lean body mass (LBM)−1·min−1] and 11 lean insulin-sensitive subjects (Lean GDR: 12.9 ± 1.2 mg·kg LBM−1·min−1) underwent a hyperinsulinemic-euglycemic clamp with vastus lateralis biopsies taken before and 60 min into the clamp. Basal biopsies were also taken in 11 medication-naïve, obese, non-T2D subjects. ET-1, peNOS (Ser1177), and eNOS protein and mRNA were measured from skeletal muscle samples containing native microvessels. Femoral artery blood flow was assessed by duplex Doppler ultrasound. Insulin-stimulated blood flow was reduced in obese T2D (Lean: +50.7 ± 6.5% baseline, T2D: +20.8 ± 5.2% baseline, P < 0.05). peNOS/eNOS content was higher in Lean under basal conditions and, although not increased by insulin, remained higher in Lean during the insulin clamp than in obese T2D ( P < 0.05). ET-1 mRNA and peptide were 2.25 ± 0.50- and 1.52 ± 0.11-fold higher in obese T2D compared with Lean at baseline, and ET-1 peptide remained 2.02 ± 1.9-fold elevated in obese T2D after insulin infusion ( P < 0.05) but did not increase with insulin in either group ( P > 0.05). Obese non-T2D subjects tended to also display elevated basal ET-1 ( P = 0.06). In summary, higher basal skeletal muscle expression of ET-1 and reduced peNOS/eNOS may contribute to a reduced insulin-stimulated leg blood flow response in obese T2D patients. NEW & NOTEWORTHY Although impairments in endothelial signaling are hypothesized to reduce insulin-stimulated blood flow in type 2 diabetes (T2D), human studies examining these links are limited. We provide the first measures of nitric oxide synthase and endothelin-1 expression from skeletal muscle tissue containing native microvessels in individuals with and without T2D before and during insulin stimulation. Higher basal skeletal muscle expression of endothelin-1 and reduced endothelial nitric oxide phosphorylation (peNOS)/eNOS may contribute to reduced insulin-stimulated blood flow in obese T2D patients.

scholarly journals In vivo activation of ROCK1 by insulin is impaired in skeletal muscle of humans with type 2 diabetes

2011 ◽  
Vol 300 (3) ◽  
pp. E536-E542 ◽  
Author(s):  
Kwang-Hoon Chun ◽  
Kang-Duk Choi ◽  
Dae-Ho Lee ◽  
YoonShin Jung ◽  
Robert R. Henry ◽  
...  
Keyword(s):  
Vastus Lateralis ◽  
Kinase Domain ◽  
Glucose Disposal ◽  
Vastus Lateralis Muscle ◽  
Protein Levels ◽  
Resistance To Insulin ◽  
Obese Subjects ◽  
Type 2 Diabetic

To determine whether serine/threonine ROCK1 is activated by insulin in vivo in humans and whether impaired activation of ROCK1 could play a role in the pathogenesis of insulin resistance, we measured the activity of ROCK1 and the protein content of the Rho family in vastus lateralis muscle of lean, obese nondiabetic, and obese type 2 diabetic subjects. Biopsies were taken after an overnight fast and after a 3-h hyperinsulinemic euglycemic clamp. Insulin-stimulated GDR was reduced 38% in obese nondiabetic subjects compared with lean, 62% in obese diabetic subjects compared with lean, and 39% in obese diabetic compared with obese nondiabetic subjects (all comparisons P < 0.001). Insulin-stimulated IRS-1 tyrosine phosphorylation is impaired 41–48% in diabetic subjects compared with lean or obese subjects. Basal activity of ROCK1 was similar in all groups. Insulin increased ROCK1 activity 2.1-fold in lean and 1.7-fold in obese nondiabetic subjects in muscle. However, ROCK1 activity did not increase in response to insulin in muscle of obese type 2 diabetic subjects without change in ROCK1 protein levels. Importantly, insulin-stimulated ROCK1 activity was positively correlated with insulin-mediated GDR in lean subjects ( P < 0.01) but not in obese or type 2 diabetic subjects. Moreover, RhoE GTPase that inhibits the catalytic activity of ROCK1 by binding to the kinase domain of the enzyme is notably increased in obese type 2 diabetic subjects, accounting for defective ROCK1 activity. Thus, these data suggest that ROCK1 may play an important role in the pathogenesis of resistance to insulin action on glucose disposal in muscle of obese type 2 diabetic subjects.

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

2013 ◽  
Vol 114 (11) ◽  
pp. 1527-1535 ◽  
Author(s):  
Desy Salvadego ◽  
Rossana Domenis ◽  
Stefano Lazzer ◽  
Simone Porcelli ◽  
Jörn Rittweger ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Resistance Training ◽  
Muscle Mass ◽  
Body Mass ◽  
Mitochondrial Respiration ◽  
Ex Vivo ◽  
Vastus Lateralis ◽  
Whole Body ◽  
Vastus Lateralis Muscle ◽  
Oxidative Function

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 ± 7.3 kg, mean ± SD) and 11 controls (CTRL; body mass 77.8 ± 6.0 kg). Pulmonary O2 uptake (V̇o2) 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 ∼40%, ∼33%, and ∼20%, respectively). V̇o2peak during CE was higher in RTA vs. CTRL (4.05 ± 0.64 vs. 3.56 ± 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), V̇o2 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 ± 23.7 pmol O2·s−1·mg−1 ww) vs. CTRL (35.7 ± 10.2 pmol O2·s−1·mg−1 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 O2 cost at submaximal exercise, despite a much greater body mass.

scholarly journals New records in aerobic power among octogenarian lifelong endurance athletes

2013 ◽  
Vol 114 (1) ◽  
pp. 3-10 ◽  
Author(s):  
Scott Trappe ◽  
Erik Hayes ◽  
Andrew Galpin ◽  
Leonard Kaminsky ◽  
Bozena Jemiolo ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Aerobic Capacity ◽  
Citrate Synthase ◽  
Vastus Lateralis ◽  
Endurance Athletes ◽  
Whole Body ◽  
Oxidative Enzymes ◽  
Vastus Lateralis Muscle ◽  
Peroxisome Proliferator ◽  
Mrna Targets

We examined whole body aerobic capacity and myocellular markers of oxidative metabolism in lifelong endurance athletes [ n = 9, 81 ± 1 yr, 68 ± 3 kg, body mass index (BMI) = 23 ± 1 kg/m2] and age-matched, healthy, untrained men ( n = 6; 82 ± 1 y, 77 ± 5 kg, BMI = 26 ± 1 kg/m2). The endurance athletes were cross-country skiers, including a former Olympic champion and several national/regional champions, with a history of aerobic exercise and participation in endurance events throughout their lives. Each subject performed a maximal cycle test to assess aerobic capacity (V̇o2max). Subjects had a resting vastus lateralis muscle biopsy to assess oxidative enzymes (citrate synthase and βHAD) and molecular (mRNA) targets associated with mitochondrial biogenesis [peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) and mitochondrial transcription factor A (Tfam)]. The octogenarian athletes had a higher ( P < 0.05) absolute (2.6 ± 0.1 vs. 1.6 ± 0.1 l/min) and relative (38 ± 1 vs. 21 ± 1 ml·kg−1·min−1) V̇o2max, ventilation (79 ± 3 vs. 64 ± 7 l/min), heart rate (160 ± 5 vs. 146 ± 8 beats per minute), and final workload (182 ± 4 vs. 131 ± 14 W). Skeletal muscle oxidative enzymes were 54% (citrate synthase) and 42% (βHAD) higher ( P < 0.05) in the octogenarian athletes. Likewise, basal PGC-1α and Tfam mRNA were 135% and 80% greater ( P < 0.05) in the octogenarian athletes. To our knowledge, the V̇o2max of the lifelong endurance athletes is the highest recorded in humans >80 yr of age and comparable to nonendurance trained men 40 years younger. The superior cardiovascular and skeletal muscle health profile of the octogenarian athletes provides a large functional reserve above the aerobic frailty threshold and is associated with lower risk for disability and mortality.

Increased skeletal muscle capillarization enhances insulin sensitivity

2014 ◽  
Vol 307 (12) ◽  
pp. E1105-E1116 ◽  
Author(s):  
Thorbjorn Akerstrom ◽  
Lasse Laub ◽  
Kenneth Vedel ◽  
Christian Lehn Brand ◽  
Bente Klarlund Pedersen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
Glycogen Synthesis ◽  
Blood Stream ◽  
Whole Body ◽  
Glucose Disposal ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

Increased skeletal muscle capillarization is associated with improved glucose tolerance and insulin sensitivity. However, a possible causal relationship has not previously been identified. Therefore, we investigated whether increased skeletal muscle capillarization increases insulin sensitivity. Skeletal muscle-specific angiogenesis was induced by adding the α1-adrenergic receptor antagonist prazosin to the drinking water of Sprague-Dawley rats ( n = 33), whereas 34 rats served as controls. Insulin sensitivity was measured ≥40 h after termination of the 3-wk prazosin treatment, which ensured that prazosin was cleared from the blood stream. Whole body insulin sensitivity was measured in conscious, unrestrained rats by hyperinsulinemic euglycemic clamp. Tissue-specific insulin sensitivity was assessed by administration of 2-deoxy-[3H]glucose during the plateau phase of the clamp. Whole body insulin sensitivity increased by ∼24%, and insulin-stimulated skeletal muscle 2-deoxy-[3H]glucose disposal increased by ∼30% concomitant with an ∼20% increase in skeletal muscle capillarization. Adipose tissue insulin sensitivity was not affected by the treatment. Insulin-stimulated muscle glucose uptake was enhanced independent of improvements in skeletal muscle insulin signaling to glucose uptake and glycogen synthesis, suggesting that the improvement in insulin-stimulated muscle glucose uptake could be due to improved diffusion conditions for glucose in the muscle. The prazosin treatment did not affect the rats on any other parameters measured. We conclude that an increase in skeletal muscle capillarization is associated with increased insulin sensitivity. These data point toward the importance of increasing skeletal muscle capillarization for prevention or treatment of type 2 diabetes.

Abstract 3795: Readjusting The Catabolic-anabolic Balance In Heart Failure: Beneficial Effects Of Physical Exercise On Protein Catabolism In The Skeletal Muscle

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Stephan Gielen ◽  
Marcus Sandri ◽  
Volker Adams ◽  
Norman Mangner ◽  
Sandra Erbs ◽  
...  
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Molecular Mechanisms ◽  
Vastus Lateralis ◽  
E3 Ligase ◽  
Tnf Alpha ◽  
Control Group ◽  
Vastus Lateralis Muscle ◽  
List Type ◽  
Ubiquitin Proteasome

Background: Progressive muscle wasting frequently occurs in the course of chronic heart failure (CHF) and has recently been identified as independent predictor of mortality in clincal studies. However, the molecular mechanisms that mediate muscle catabolism are still largely unknown and no specific pharmacological agents are available to antagonize the loss of muscle mass. We therefore tested the potential of an established anabolic intervention, i.e. exercise training, to prevent cytokine-induced ubiquitin-proteasome-mediated protein degradation in the skeletal muscle of stable patients with advanced CHF. Methods: 43 CHF-patients and 41 healthy subjects (HS) were prospectively randomized to 4 weeks of supervised bicycle ergometer training at 70% of the heart rate reserve 4 times 20 min/day or to a control group (C). Before and after the intervention a spiroergometry, echocardiography, and skeletal muscle biopsy from the vastus lateralis muscle were performed. Expression of TNF-alpha and the E3 ligase Murf-1, which tags proteins for degradation via the ubiquitin-proteasome system, were quantified by real-time PCR standardized for 18S-rRNA. Results: In CHF patients (age 60.3 ± 2.9 years, BMI 28.9 ± 1.7, LV-EF 27.4 ± 1.7%): training increased VO2max from 14.9 ± 3.3 to 18.1 ± 4.7 mL/min/kg (p<0.01 vs. C), and LV-EF from 26.8 ± 4.6 to 33.1 ± 5.5% (p=0.001 vs. C). At baseline Murf-1 expression was significantly higher as compared to HS. Training decreased Murf-1 expression from 0.49 ± 0.21 to 0.22 ± 0.07 rel. units (p<0.05) and TNF-alpha expression from 79 ± 7.1 to 44.7 ± 5.9 rel. units (p<0.001). In HS (age 64.7 ± 2.7 years, BMI 26.2 ± 0.5, LV-EF 63 ± 0.8%) training increased VO2 max from 20.3 ± 2.1 to 27.9.2 ± 1.3 mL/kg min (p=0.01 vs. C). Murf-1 and TNF-alpha expression remained unchanged versus untrained HS. Conclusions: CHF is associated with local inflammatory and catabolic activation in the skeletal muscle as indicated by higher baseline TNF-alpha and Murf-1 levels. Training cuts the elevated TNF-alpha and E3-ligase expressions by half within only four weeks of intervention. These findings emphasize the role of training for the prevention of muscle atrophy and may provide a novel explanation for the prognostic benefits of exercise in CHF.

Similar changes of gene expression in human skeletal muscle after resistance exercise and multiple fine needle biopsies

2012 ◽  
Vol 112 (2) ◽  
pp. 289-295 ◽  
Author(s):  
Birgit Friedmann-Bette ◽  
Fides Regina Schwartz ◽  
Holger Eckhardt ◽  
Rudolf Billeter ◽  
Gabriel Bonaterra ◽  
...  
Keyword(s):  
Gene Expression ◽  
Resistance Exercise ◽  
Glucose Transporter ◽  
Vastus Lateralis ◽  
Whole Body ◽  
Control Group ◽  
Marker Genes ◽  
Vastus Lateralis Muscle ◽  
Fine Needle ◽  
Lateralis Muscle

Repeated biopsy sampling from one muscle is necessary to investigate muscular adaptation to different forms of exercise as adaptation is thought to be the result of cumulative effects of transient changes in gene expression in response to single exercise bouts. In a crossover study, we obtained four fine needle biopsies from one vastus lateralis muscle of 11 male subjects (25.9 ± 3.8 yr, 179.2 ± 4.8 cm, 76.5 ± 7.0 kg), taken before (baseline), 1, 4, and 24 h after one bout of squatting exercise performed as conventional squatting or as whole body vibration exercise. To investigate if the repeated biopsy sampling has a confounding effect on the observed changes in gene expression, four fine needle biopsies from one vastus lateralis muscle were also taken from 8 male nonexercising control subjects (24.5 ± 3.7 yr, 180.6 ± 1.2 cm, 81.2 ± 1.6 kg) at the equivalent time points. Using RT-PCR, we observed similar patterns of change in the squatting as well as in the control group for the mRNAs of interleukin 6 (IL-6), IL-6 receptor, insulin-like growth factor 1, p21, phosphofructokinase, and glucose transporter in relation to the baseline biopsy. In conclusion, multiple fine needle biopsies obtained from the same muscle region can per se influence the expression of marker genes induced by an acute bout of resistance exercise.

Pre- and posttranslational upregulation of muscle-specific glycogen synthase in athletes

1994 ◽  
Vol 266 (1) ◽  
pp. E92-E101 ◽  
Author(s):  
H. Vestergaard ◽  
P. H. Andersen ◽  
S. Lund ◽  
O. Schmitz ◽  
S. Junker ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Glycogen Synthase ◽  
Vastus Lateralis ◽  
Glycogen Synthesis ◽  
Whole Body ◽  
Glucose Disposal ◽  
Synthesis Rate ◽  
Vastus Lateralis Muscle ◽  
Protein Activity ◽  
Control Subjects

Expression of muscle-specific glycogen synthase (GS) and phosphofructokinase (PFK) was analyzed in seven athletes and eight control subjects who were characterized using the euglycemic, hyperinsulinemic (2 mU.kg-1.min-1) clamp technique in combination with indirect calorimetry and biopsy sampling of vastus lateralis muscle. In the basal state, total GS activity and half-maximal GS activation by glucose 6-phosphate (G-6-P) were respectively 34% (P < 0.03) and 50% (P < 0.005) higher in athletes than in control subjects. In parallel, GS mRNA/microgram total RNA in athletes was 40% (P < 0.005) higher. No difference in GS immunoreactive protein abundance was found between the groups. PFK activity and protein levels were respectively 15% (P < 0.05) and 20% (P < 0.02) lower in athletes, whereas no differences was found in the level of PFK mRNA. After 4 h of hyperinsulinemia, total glucose disposal rate (P < 0.005) and both nonoxidative (P < 0.02) and oxidative (P < 0.03) glucose metabolism were significantly higher in athletes. In parallel, after hyperinsulinemia, the relative activation of GS by G-6-P was significantly higher in athletes, whereas total activity and gene expression of both GS and PFK were unaffected by insulin. We conclude that athletes have increased whole body insulin-stimulated nonoxidative glucose metabolism associated with both pretranslational (mRNA) and posttranslational (enzyme activity) upregulation of GS. However, the immunoreactive mass of GS is normal, emphasizing that posttranslational regulation of the GS protein activity is important for the increased glycogen synthesis rate of muscle in endurance-trained individuals.

scholarly journals Genes and biochemical pathways in human skeletal muscle affecting resting energy expenditure and fuel partitioning

2011 ◽  
Vol 110 (3) ◽  
pp. 746-755 ◽  
Author(s):  
Xuxia Wu ◽  
Amit Patki ◽  
Cristina Lara-Castro ◽  
Xiangqin Cui ◽  
Kui Zhang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Energy Expenditure ◽  
Vastus Lateralis ◽  
Resting Energy Expenditure ◽  
Whole Body ◽  
Cellular Respiration ◽  
Vastus Lateralis Muscle ◽  
Peptidase Activity ◽  
The Metabolic Syndrome ◽  
Resting Energy

Genes influencing resting energy expenditure (REE) and respiratory quotient (RQ) represent candidate genes for obesity and the metabolic syndrome because of the involvement of these traits in energy balance and substrate oxidation. We aim to explore the molecular basis for individual variation in REE and fuel partitioning as reflected by RQ. We performed microarray studies in human vastus lateralis muscle biopsies from 40 healthy subjects with measured REE and RQ values. We identified 2,392 and 1,115 genes significantly correlated with REE and RQ, respectively. Genes correlated with REE and RQ encompass a broad array of functions, including carbohydrate and lipid metabolism, gene expression, mitochondrial processes, and membrane transport. Microarray pathway analysis revealed that REE was positively correlated with upregulation of G protein-coupled receptor signaling (meet criteria/total genes: 65 of 283) involved in autonomic nervous system functions, including those receptors mediating adrenergic, dopamine, γ-aminobutyric acid (GABA), neuropeptide Y (NPY), and serotonin action (meet criteria/total genes: 46 of 176). Reduced REE was associated with an increase in genes participating in ubiquitin-proteasome-dependent proteolytic pathways (58 of 232). Serine-type peptidase activity (9 of 76) was positively correlated with RQ, while genes involved in the protein phosphatase type 2A complex (4 of 9), mitochondrial function and cellular respiration (38 of 315), and unfolded protein binding (19 of 97) were associated with reduced RQ values and a preference for lipid fuel metabolism. Individual variations in whole body REE and RQ are regulated by differential expressions of specific genes and pathways intrinsic to skeletal muscle.

Sign in / Sign up

Export Citation Format

Share Document