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

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.

2002 ◽  
Vol 282 (3) ◽  
pp. E714-E720 ◽  
Author(s):  
Dana Dawson ◽  
Michelle A. Vincent ◽  
Eugene J. Barrett ◽  
Sanjiv Kaul ◽  
Andrew Clark ◽  
...  

The purpose of this study was to noninvasively quantify the effects of insulin on capillary blood volume (capBV) and RBC velocity ( V RBC) in skeletal muscle in vivo with the use of contrast-enhanced ultrasound. We performed contrast ultrasound of the rat hindlimb adductor muscles at baseline and after 2-h infusions of either insulin (3 or 40 mU · kg−1 · min−1) or saline. Saline-treated animals were also studied during contractile exercise. V RBC and capBV were calculated from the relation between pulsing interval and video intensity. Femoral artery blood flow, measured by a flow probe, increased with both contractile exercise and insulin. Contractile exercise increased capBV more than twofold and V RBC fivefold. Insulin also increased capBV more than twofold in a dose-dependent fashion but did not significantly alter V RBC. Saline infusion did not significantly alter capBV, V RBC, or femoral artery blood flow. We conclude that physiological changes in skeletal muscle capillary perfusion can be assessed in vivo with the use of contrast-enhanced ultrasound. Exercise increases both V RBC and capBV, whereas hyperinsulinemia selectively increases only capBV, which may enhance skeletal muscle glucose uptake.


2005 ◽  
Vol 99 (2) ◽  
pp. 683-690 ◽  
Author(s):  
Nicole D. Paterson ◽  
John M. Kowalchuk ◽  
Donald H. Paterson

It has been suggested that, during heavy-intensity exercise, O2 delivery may limit oxygen uptake (V̇o2) kinetics; however, there are limited data regarding the relationship of blood flow and V̇o2 kinetics for heavy-intensity exercise. The purpose was to determine the exercise on-transient time course of femoral artery blood flow (Q̇leg) in relation to V̇o2 during heavy-intensity, single-leg, knee-extension exercise. Five young subjects performed five to eight repeats of heavy-intensity exercise with measures of breath-by-breath pulmonary V̇o2 and Doppler ultrasound femoral artery mean blood velocity and vessel diameter. The phase 2 time frame for V̇o2 and Q̇leg was isolated and fit with a monoexponent to characterize the amplitude and time course of the responses. Amplitude of the phase 3 response was also determined. The phase 2 time constant for V̇o2 of 29.0 s and time constant for Q̇leg of 24.5 s were not different. The change (Δ) in V̇o2 response to the end of phase 2 of 0.317 l/min was accompanied by a ΔQ̇leg of 2.35 l/min, giving a ΔQ̇leg-to-ΔV̇o2 ratio of 7.4. A slow-component V̇o2 of 0.098 l/min was accompanied by a further Q̇leg increase of 0.72 l/min (ΔQ̇leg-to-ΔV̇o2 ratio = 7.3). Thus the time course of Q̇leg was similar to that of muscle V̇o2 (as measured by the phase 2 V̇o2 kinetics), and throughout the on-transient the amplitude of the Q̇leg increase achieved (or exceeded) the Q̇leg-to-V̇o2 ratio steady-state relationship (ratio ∼4.9). Additionally, the V̇o2 slow component was accompanied by a relatively large rise in Q̇leg, with the increased O2 delivery meeting the increased V̇o2. Thus, in heavy-intensity, single-leg, knee-extension exercise, the amplitude and kinetics of blood flow to the exercising limb appear to be closely linked to the V̇o2 kinetics.


2012 ◽  
Vol 303 (10) ◽  
pp. R1071-R1079 ◽  
Author(s):  
Scott D. Clarke ◽  
Kevin Lee ◽  
Zane B. Andrews ◽  
Robert Bischof ◽  
Fahri Fahri ◽  
...  

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.


1997 ◽  
Vol 83 (4) ◽  
pp. 1383-1388 ◽  
Author(s):  
G. Rådegran

Rådegran, G. Ultrasound Doppler estimates of femoral artery blood flow during dynamic knee extensor exercise in humans. J. Appl. Physiol.83(4): 1383–1388, 1997.—Ultrasound Doppler has been used to measure arterial inflow to a human limb during intermittent static contractions. The technique, however, has neither been thoroughly validated nor used during dynamic exercise. In this study, the inherent problems of the technique have been addressed, and the accuracy was improved by storing the velocity tracings continuously and calculating the flow in relation to the muscle contraction-relaxation phases. The femoral arterial diameter measurements were reproducible with a mean coefficient of variation within the subjects of 1.2 ± 0.2%. The diameter was the same whether the probe was fixed or repositioned at rest (10.8 ± 0.2 mm) or measured during dynamic exercise. The blood velocity was sampled over the width of the diameter and the parabolic velocity profile, since sampling in the center resulted in an overestimation by 22.6 ± 9.1% ( P< 0.02). The femoral arterial Doppler blood flow increased linearly ( r = 0.997, P < 0.001) with increasing load [Doppler blood flow = 0.080 ⋅ load (W) + 1.446 l/min] and was correlated positively with simultaneous thermodilution venous outflow measurements ( r = 0.996, P < 0.001). The two techniques were linearly related (Doppler = thermodilution ⋅ 0.985 + 0.071 l/min; r = 0.996, P < 0.001), with a coefficient of variation of ∼6% for both methods.


2006 ◽  
Vol 38 (Supplement) ◽  
pp. S196-S197
Author(s):  
Allison J. Harper ◽  
Leonardo F. Ferreira ◽  
Barbara J. Lutjemeier ◽  
Dana K. Townsend ◽  
Thomas J. Barstow

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