Postprandial heat production in skeletal muscle is associated with altered mitochondrial function and altered futile calcium cycling

2012 ◽  
Vol 303 (10) ◽  
pp. R1071-R1079 ◽  
Author(s):  
Scott D. Clarke ◽  
Kevin Lee ◽  
Zane B. Andrews ◽  
Robert Bischof ◽  
Fahri Fahri ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Femoral Artery ◽  
Heat Production ◽  
Mitochondrial Function ◽  
Uncoupling Protein ◽  
Vastus Lateralis Muscle ◽  
Muscle Temperature ◽  
Calcium Cycling ◽  
Doppler Flowmetry

This study aimed to determine whether postprandial temperature excursions in skeletal muscle are consistent with thermogenesis or altered blood flow. Temperature probes were implanted into the vastus lateralis muscle of ovariectomized ewes, and blood flow was assessed using laser-Doppler flowmetry (tissue flow) and transit-time ultrasound flowmetry (femoral artery flow). The animals were program-fed between 1100 and 1600, and temperature and blood flow were measured during intravenous administration of either isoprenaline or phenylephrine and during feeding and meal anticipation. In addition, muscle biopsies were collected prefeeding and postfeeding to measure uncoupling protein (UCP) expression and mitochondrial function, as well as indices of calcium cycling (ryanodine 1 receptor: RyR1 and sarcoendoplasmic calcium-dependent ATPases SERCA1/ SERCA2a). Isoprenaline increased femoral artery blood flow, whereas phenylephrine reduced blood flow. At high doses only, isoprenaline treatment increased heat production in muscle. Phenylephrine treatment did not alter muscle temperature. Meal anticipation was evoked in fasted animals (previously program-fed) that were housed beside animals that were fed. Increases in muscle temperature were elicited by feeding and meal anticipation, without changes in blood flow during either paradigm. Analyses of respiration in isolated mitochondria indicated that the postprandial increase in heat production was associated with an increase in state 4 respiration, without increased UCP1, UCP2, or UCP3 expression. Feeding increased the expression of RyR1 and SERCA2a. We conclude that excursions in muscle temperature may occur independent of blood flow, suggesting that postprandial heat production is driven by altered mitochondrial function and changes in calcium cycling.

scholarly journals Differential Effects of Acute and Chronic Estrogen Treatment on Thermogenic and Metabolic Pathways in Ovariectomized Sheep

Endocrinology ◽  
2013 ◽  
Vol 154 (1) ◽  
pp. 184-192 ◽  
Author(s):  
Scott D. Clarke ◽  
Iain J. Clarke ◽  
Alexandra Rao ◽  
Roger G. Evans ◽  
Belinda A. Henry
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Protein Kinase ◽  
Food Intake ◽  
Femoral Artery ◽  
Heat Production ◽  
Artery Blood Flow ◽  
Femoral Artery Blood Flow ◽  
Amp Activated Protein Kinase ◽  
Estradiol 17Β

Estrogen is protective against weight gain, but the underlying mechanisms are not fully elucidated. We sought to characterize the effects of estrogen on energy expenditure in skeletal muscle and adipose tissue in ovariectomized sheep. Temperature probes were implanted into sc (gluteal) and visceral (retroperitoneal) fat depots and skeletal muscle of the hind limb (vastus lateralis). Food was available from 1100–1600 h to entrain postprandial thermogenesis. We characterized the effects of single (50 μg estradiol benzoate, im) and repeated (25 μg estradiol-17β, iv) injections as well as chronic (3 × 3 cm estradiol-17β implants for 7 d) treatment on heat production. A single injection of estrogen increased heat production in visceral fat and skeletal muscle, without an effect on food intake. Increased heat production in skeletal muscle was sustained by repeated estradiol-17β injections. On the other hand, continuous treatment reduced food intake but had no effect on thermogenesis. To determine possible mechanisms that underpin estradiol-17β-induced heat production, we measured femoral artery blood flow, the expression of uncoupling protein (UCP) mRNA and the phosphorylation of AMP-activated protein kinase and Akt in fat and muscle. There was little effect of either single or repeated injections of estradiol-17β on the expression of UCP1, -2, or -3 mRNA in visceral fat or skeletal muscle. Acute injection of estradiol-17β increased the phosphorylation of AMP-activated protein kinase and Akt in muscle only. Estradiol-17β treatment did not alter femoral artery blood flow. Thus, the stimulatory effect of estradiol-17β on thermogenesis in female sheep is dependent upon a pulsatile pattern of treatment and not constant continuous exposure.

Microdialysis ethanol removal reflects probe recovery rather than local blood flow in skeletal muscle

1998 ◽  
Vol 85 (2) ◽  
pp. 751-757 ◽  
Author(s):  
G. Rådegran ◽  
H. Pilegaard ◽  
J. J. Nielsen ◽  
J. Bangsbo
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Femoral Artery ◽  
Vastus Lateralis ◽  
Molecular Transport ◽  
Thigh Muscle ◽  
High Dose ◽  
Vastus Lateralis Muscle ◽  
Acetate Solution ◽  
Induced Changes

The present study compared the microdialysis ethanol outflow-inflow technique for estimating blood flow (BF) in skeletal muscle of humans with measurements by Doppler ultrasound of femoral artery inflow to the limb (BFFA). The microdialysis probes were inserted in the vastus lateralis muscle and perfused with a Ringer acetate solution containing ethanol, [2-3H]adenosine (Ado), andd-[14C(U)]glucose. BFFA at rest increased from 0.16 ± 0.02 to 1.80 ± 0.26 and 4.86 ± 0.53 l/min with femoral artery infusion of Ado (AdoFA,i) at 125 and 1,000 μg ⋅ min−1 ⋅ l−1thigh volume (low dose and high dose, respectively; P < 0.05) and to 3.79 ± 0.37 and 6.13 ± 0.65 l/min during one-legged, dynamic, thigh muscle exercise without and with high AdoFA,i, respectively ( P < 0.05). The ethanol outflow-to-inflow ratio (38.3 ± 2.3%) and the probe recoveries (PR) for [2-3H]Ado (35.4 ± 1.6%) and ford-[14C(U)]glucose (15.9 ± 1.1%) did not change with AdoFA,i at rest ( P = not significant). During exercise without and with AdoFA,i, the ethanol outflow-to-inflow ratio decreased ( P < 0.05) to a similar level of 17.5 ± 3.4 and 20.6 ± 3.2%, respectively ( P = not significant), respectively, while the PR increased ( P < 0.05) to a similar level ( P = not significant) of 55.8 ± 2.8 and 61.2 ± 2.5% for [2-3H]Ado and to 42.8 ± 3.9 and 45.2 ± 5.1% ford-[14C(U)]glucose. Whereas the ethanol outflow-to-inflow ratio and PR correlated inversely and positively, respectively, to the changes in BF during muscular contractions, neither of the ratio nor PR correlated to the AdoFA,i-induced BF increase. Thus the ethanol outflow-to-inflow ratio does not represent skeletal muscle BF but rather contraction-induced changes in molecular transport in the interstitium or over the microdialysis membrane.

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 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.

Periodic hemodynamics in skeletal muscle during local arterial pressure reduction

1992 ◽  
Vol 73 (3) ◽  
pp. 1077-1083 ◽  
Author(s):  
J. A. Schmidt ◽  
M. Intaglietta ◽  
P. Borgstrom
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Arterial Pressure ◽  
Slow Wave ◽  
Control Period ◽  
Wave Flow ◽  
Median Frequency ◽  
Doppler Flowmetry ◽  
Arterial Blood ◽  
Flow Motion

The time-dependent features of red blood cell flow were evaluated with laser-Doppler flowmetry (LDF) in the left gastrocnemius muscle of 31 anesthetized New Zealand White rabbits during stepwise arterial occlusion. During the control period with a median femoral pressure of 72 mmHg, 29 animals showed minor irregular fluctuations in LDF blood flow, and only two animals displayed periodic variations of blood flow. Lowering femoral arterial pressure induced maximal periodic blood flow variations at a median pressure of 35 mmHg in all animals with a median frequency of 1.5 cycles/min (termed “slow-wave flow motion”). The median amplitude was 48% of the corresponding average flow. These slow waves disappeared at a median femoral pressure of 20 mmHg. The median LDF flow value was 4.00 arbitrary units (AU) at control pressure and 2.05 AU at maximum slow-wave flow motion. When slow-wave flow motion was seen at several pressure levels, their frequency was identical, which supports the local pacemaker concept. This study promotes a novel concept for the role and physiological significance of periodic hemodynamics in that it is a condition not characteristic for normal control situations but is activated below a specific local arterial blood pressure and flow threshold, which is known to be the lower end of autoregulation in the microcirculation of rabbit skeletal muscle. This also suggests that slow-wave flow motion is primarily under local control mechanisms.

scholarly journals Central Leptin Activates Mitochondrial Function and Increases Heat Production in Skeletal Muscle

Endocrinology ◽  
2011 ◽  
Vol 152 (7) ◽  
pp. 2609-2618 ◽  
Author(s):  
Belinda A. Henry ◽  
Zane B. Andrews ◽  
Alexandra Rao ◽  
Iain J. Clarke
Keyword(s):  
Skeletal Muscle ◽  
Heat Production ◽  
Mitochondrial Function

Estrogen modulates the contribution of neuropeptide Y to baseline hindlimb blood flow control in female Sprague-Dawley rats

2010 ◽  
Vol 298 (5) ◽  
pp. R1351-R1357 ◽  
Author(s):  
Dwayne N. Jackson ◽  
Christopher G. Ellis ◽  
J. Kevin Shoemaker
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Flow Control ◽  
Neuropeptide Y ◽  
Female Rats ◽  
Vastus Lateralis Muscle ◽  
Peptidase Activity ◽  
Vascular Conductance ◽  
Ovx Rats ◽  
Blood Flow Control

The purpose of this study was to determine the role of estrogen in neuropeptide Y (NPY) and Y1 receptor (Y1R)-mediated vascular responses in female rats. Based on earlier work from our laboratory that female rats lacked an NPY contribution to hindlimb vascular conductance relative to males, we tested the hypothesis that estrogen modulates Y1R-mediated hindlimb blood flow control. Thus it was expected that ovariectomy would: 1) increase skeletal muscle Y1R expression, 2) decrease skeletal muscle Y2 receptor (Y2R) expression, 3) decrease peptidase activity, and/or 4) increase overall skeletal muscle NPY concentration. Separate groups of control (CTL), ovariectomized (OVX), and OVX + 17β-estradiol replacement (OVX + E2; 21-day pellet) rats were studied. Animals were anesthetized and given localized hindlimb delivery of BIBP-3226 (Y1R antagonist), while femoral artery blood flow and blood pressure were recorded. Tissue samples from the white and red vastus lateralis muscle were extracted to examine Y1R and Y2R expression, peptidase activity, and NPY concentration. We found that Y1R blockade resulted in increased baseline hindlimb blood flow and vascular conductance in OVX rats, whereas no change was noted in CTL or OVX + E2 groups ( P < 0.05). This enhanced functional effect in the OVX group aligned with greater skeletal muscle Y1R expression in white vastus muscle and a substantial increase in NPY concentration in both white and red vastus muscle compared with CTL and OVX + E2 groups. There was no change in Y2R expression or peptidase activity among the groups. These data support the hypothesis that estrogen blunts Y1R activation in the rat hindlimb through an effect on Y1R expression and NPY concentration.

ATP-induced vasodilation and purinergic receptors in the human leg: roles of nitric oxide, prostaglandins, and adenosine

2009 ◽  
Vol 296 (4) ◽  
pp. R1140-R1148 ◽  
Author(s):  
Stefan P. Mortensen ◽  
José González-Alonso ◽  
Laurids T. Bune ◽  
Bengt Saltin ◽  
Henriette Pilegaard ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Blood Flow ◽  
Human Skeletal Muscle ◽  
Purinergic Receptors ◽  
Vastus Lateralis ◽  
Muscle Blood Flow ◽  
Pcr Analysis ◽  
Receptor Subtypes ◽  
Vastus Lateralis Muscle

Plasma ATP is thought to contribute to the local regulation of skeletal muscle blood flow. Intravascular ATP infusion can induce profound limb muscle vasodilatation, but the purinergic receptors and downstream signals involved in this response remain unclear. This study investigated: 1) the role of nitric oxide (NO), prostaglandins, and adenosine as mediators of ATP-induced limb vasodilation and 2) the expression and distribution of purinergic P2 receptors in human skeletal muscle. Systemic and leg hemodynamics were measured before and during 5–7 min of femoral intra-arterial infusion of ATP [0.45–2.45 μmol/min] in 19 healthy male subjects with and without coinfusion of NG-monomethyl-l-arginine (l-NMMA; NO formation inhibitor; 12.3 ± 0.3 (SE) mg/min), indomethacin (INDO; prostaglandin formation blocker; 613 ± 12 μg/min), and/or theophylline (adenosine receptor blocker; 400 ± 26 mg). During control conditions, ATP infusion increased leg blood flow (LBF) from baseline conditions by 1.82 ± 0.14 l/min. When ATP was coinfused with either l-NMMA, INDO, or l-NMMA + INDO combined, the increase in LBF was reduced by 14 ± 6, 15 ± 9, and 39 ± 8%, respectively (all P < 0.05), and was associated with a parallel lowering in leg vascular conductance and cardiac output and a compensatory increase in leg O2 extraction. Infusion of theophylline did not alter the ATP-induced leg hyperemia or systemic variables. Real-time PCR analysis of the mRNA content from the vastus lateralis muscle of eight subjects showed the highest expression of P2Y2 receptors of the 10 investigated P2 receptor subtypes. Immunohistochemistry showed that P2Y2 receptors were located in the endothelium of microvessels and smooth muscle cells, whereas P2X1 receptors were located in the endothelium and the sacrolemma. Collectively, these results indicate that NO and prostaglandins, but not adenosine, play a role in ATP-induced vasodilation in human skeletal muscle. The expression and localization of the nucleotide selective P2Y2 and P2X1 receptors suggest that these receptors may mediate ATP-induced vasodilation in skeletal muscle.

scholarly journals Withania somnifera Extract Enhances Energy Expenditure via Improving Mitochondrial Function in Adipose Tissue and Skeletal Muscle

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 431 ◽  
Author(s):  
Da-Hye Lee ◽  
Jiyun Ahn ◽  
Young-Jin Jang ◽  
Hyo-Deok Seo ◽  
Tae-Youl Ha ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Oxygen Consumption ◽  
Energy Expenditure ◽  
Mitochondrial Function ◽  
Withania Somnifera ◽  
Uncoupling Protein ◽  
Subcutaneous Fat ◽  
Mitochondrial Activity ◽  
Beige Adipocytes

Withania somnifera (WS), commonly known as ashwagandha, possesses diverse biological functions. WS root has mainly been used as an herbal medicine to treat anxiety and was recently reported to have an anti-obesity effect, however, the mechanisms underlying its action remain to be explored. We hypothesized that WS exerts its anti-obesity effect by enhancing energy expenditure through improving the mitochondrial function of brown/beige adipocytes and skeletal muscle. Male C57BL/6J mice were fed a high-fat diet (HFD) containing 0.25% or 0.5% WS 70% ethanol extract (WSE) for 10 weeks. WSE (0.5%) supplementation significantly suppressed the increases in body weight and serum lipids, and lipid accumulation in the liver and adipose tissue induced by HFD. WSE supplementation increased oxygen consumption and enhanced mitochondrial activity in brown fat and skeletal muscle in the HFD-fed mice. In addition, it promoted browning of subcutaneous fat by increasing mitochondrial uncoupling protein 1 (UCP1) expression. Withaferin A (WFA), a major compound of WS, enhanced the differentiation of pre-adipocytes into beige adipocytes and oxygen consumption in C2C12 murine myoblasts. These results suggest that WSE ameliorates diet-induced obesity by enhancing energy expenditure via promoting mitochondrial function in adipose tissue and skeletal muscle, and WFA is a key regulator in this function.

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