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Biomedical subjects

A Astrup

Publications and source records attributed to A Astrup.

At least 217 records · Page 12Linked to original sources
PubMed1987

Impaired glucose-induced thermogenesis in skeletal muscle in obesity. The role of the sympathoadrenal system.

From a 7-day food recording in 29 morbidly obese patients two groups of six patients each were selected: a high-energy-intake group (HEI) and a low-energy-intake group (LEI). The groups were otherwise comparable. Five lean subjects served as controls for some observations. Oral glucose tolerance tests showed that all patients in the HEI group and the lean controls had normal glucose tolerance, whereas it was abnormal in all subjects in the LEI group. The fasting metabolic rate did not differ between the obese groups but was significantly lower in the lean group. The glucose-induced thermogenesis during 180 min expressed as a percentage of the energy content of the glucose load was lower in both obese groups compared with the lean controls (lean: +11.5 per cent, HEI: +5.3 per cent and LEI: -4.2 per cent, HEI vs lean: P = 0.04 and LEI vs lean: P = 0.005), and lower in the LEI group compared with the HEI group (P = 0.02). The integrated increase in leg oxygen consumption after glucose was also smaller in the LEI group than in the HEI group (15 +/- 269 vs 987 +/- 356 ml, P less than 0.05). The arterial noradrenaline response to glucose was significantly diminished in both obese groups compared with the lean controls. Glucose induced a similar increase in leg noradrenaline release in both obese groups, whereas the arterial adrenaline level was lower in the LEI group compared with the HEI group and with the lean controls (P = 0.04). Among the obese subjects the degree of glucose intolerance was inversely correlated with the post-glucose arterial adrenaline level (r = -0.55, and P = 0.04), and positively correlated with the fractional leg adrenaline extraction (r = 0.71, and P = 0.003). The results suggest that patients who are obese in spite of a fairly low energy intake have a reduced glucose-induced facultative thermogenesis, and that the defect is at least in part located in skeletal muscle. Since the sympathetic nervous system is partly responsible for the glucose-induced thermogenesis, the reduced thermogenic response in the obese patients may be due to an impaired activation of the sympathetic nervous system. It is hypothesized that the reduced arterial adrenaline level in the LEI group is caused by hyperglycaemic suppression of the adrenomedullary secretion and further that this may be a link connecting deterioration of glucose tolerance and a thermogenic defect in obesity.

Adrenal Glands↗
PubMed1986

The effect of chronic ephedrine treatment on substrate utilization, the sympathoadrenal activity, and energy expenditure during glucose-induced thermogenesis in man.

Chronic ephedrine treatment of man has recently been found to enhance the thermogenic response to an acute dose of ephedrine. Conceivably, this sensitization to beta-adrenergic stimulation might also affect the facultative component of diet-induced thermogenesis. The glucose-induced thermogenesis (GIT) was studied in five healthy female subjects after 3 months of chronic peroral ephedrine treatment. Similar experiments 3 months after cessation of treatment served as controls. During chronic ephedrine treatment a sustained 10% elevation of the metabolic rate was found compared to that in the control study. Plasma epinephrine levels were increased 87% during treatment. These increases tended to be positively correlated (r = 0.54, P less than 0.07). GIT expressed as a percentage of the ingested energy load was unaltered during chronic ephedrine treatment compared with that in the control study (9.0% v 8.9%). The respiratory quotient (RQ) indicate that relatively more lipid was oxidized during chronic ephedrine treatment than in the control study. This change was observed in the fasting state as well as after glucose administration. Certain effects of ephedrine seems to be appropriate to a thermogenic drug for the treatment of obesity: A single dose of ephedrine stimulates thermogenesis, an effect that is enhanced during chronic treatment; Chronic treatment elevates the metabolic rate; and The substrate utilization is changed in favor of lipid oxidation.

Adult↗
PubMed1986

Facultative thermogenesis induced by carbohydrate: a skeletal muscle component mediated by epinephrine.

In addition to the obligatory thermogenesis due to processing and storage, carbohydrate ingestion is accompanied by a facultative thermogenesis mediated by catecholamines via beta-adrenoceptors. The anatomical origin of facultative thermogenesis has hitherto not been determined. The possible involvement of skeletal muscle was examined in lean, healthy subjects by measuring the response in forearm oxygen consumption to an oral glucose load. The study demonstrates an early component of skeletal muscle thermogenesis coinciding with the local glucose uptake, followed by a late facultative thermogenesis. The arterial epinephrine concentration increased to a maximum of 200% above base-line values 4 h after glucose. This value greatly exceeds the physiological threshold for the thermogenic action of epinephrine. In forearm venous blood the corresponding increase in epinephrine was only approximately 50% due to enhanced peripheral extraction, which accompanies an increase in arterial epinephrine levels. Due to venous sampling previous studies have overlooked the magnitude of the late postglucose increase in arterial epinephrine, and its potential thermogenic effect has been disregarded. The facultative thermogenesis in skeletal muscle may be of importance for the regulation of body weight in humans.

Adult↗
PubMed1986

Cardiovascular and endocrine responses to head-up tilt and vasopressin infusion in humans.

The effects of passive tilt on arterial and central venous pressures (MAP and CVP), heart rate (HR), arterial concentrations of vasopressin (AVP) and aldosterone (ALDO), osmolality, and hematocrit were studied in eight healthy young men. Tilting was performed at 30 degrees/min to 20 or 40 degrees and maintained for 45 min. The 20 degrees tilt did not change MAP while CVP fell by 5.9 mmHg (P less than 0.01) and HR increased by 5 beats/min (51-56 beats/min, P less than 0.05). AVP and ALDO concentrations were unchanged. At 40 degrees, MAP increased by 5.7 mmHg (86.0-91.7 mmHg, P less than 0.01), CVP decreased by 7.4 mmHg (P less than 0.01), HR rose by 8 beats/min (55-63 beats/min, P less than 0.01), and pulse pressure fell by 6 mmHg (P less than 0.05). ALDO increased fivefold (P less than 0.05), but AVP did not change. Infusions of AVP at 0.25 or 1.0 ng X min-1 X kg body wt-1 elevated plasma AVP to 11 +/- 1 and 52 +/- 8 pg/ml. Only the larger dose caused a small increase in MAP while CVP and HR remained unchanged; however, washout of a subcutaneous depot of Xe was reduced greater than 60% even by the lower dose. It is concluded that small-angle nonhypotensive passive tilt does not affect AVP measurably despite substantial reductions of CVP and a marked increase in ALDO. Elevations of AVP elicit marked subcutaneous vasoconstriction also in the absence of changes in CVP, HR, and MAP.

Adult↗
PubMed1986

Hypotension induced by passive head-up tilt: endocrine and circulatory mechanisms.

Circulatory changes and arterial plasma hormone concentrations were measured in seven healthy young adults during 30 and 60 degrees passive head-up tilt with the subjects supported by a saddle. The 30 degrees tilt induced a decrease in pulse pressure (Pp) from 45 +/- 2 to 35 +/- 4 (mean +/- SE) mmHg concomitant with an increase in heart rate (HR) from 58 +/- 4 to 78 +/- 8 beats/min and a marginal increase in mean arterial pressure (MAP). Norepinephrine increased from 180 +/- 20 to 310 +/- 40 pg/ml, aldosterone increased fivefold, and angiotensin II increased from 8 +/- 2 to 22 +/- 7 pg/ml. The 60 degrees tilt initially produced changes, which were qualitatively similar to the 30 degrees tilt. However, after 19 +/- 3 min sudden decreases were seen in MAP (94 +/- 3 to 50 +/- 8 mmHg), in Pp (38 +/- 5 to 18 +/- 4 mmHg), and in HR (90 +/- 7 to 57 +/- 6 beats/min). Concomitantly, epinephrine doubled while norepinephrine remained unchanged; the vagally controlled hormone pancreatic polypeptide increased from 29 +/- 3 to 51 +/- 8 pmol/l, vasopressin from 4 +/- 1 to 126 +/- 58 pg/ml, and angiotensin II from 23 +/- 9 to 35 +/- 12 pg/ml. The hypotensive bradycardiac episode was immediately reversible on termination of the head-up tilt.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Thermogenesis in human brown adipose tissue and skeletal muscle induced by sympathomimetic stimulation.

The aim of the present work was to elucidate the importance of brown adipose tissue (BAT) and skeletal muscle for ephedrine-induced thermogenesis, and to examine the effect of chronic ephedrine treatment on energy expenditure. The investigations were carried out in vivo on humans, as well as on rats and dogs. In rodents BAT is the major site of cold-induced nonshivering thermogenesis and of facultative thermogenesis: the component of food-induced thermogenesis storage of nutrients. BAT thermogenesis is mediated through an activation of the sympathetic nervous system. Via a sustained stimulation of the sympathetic nervous system, acclimation to cold and overfeeding induces hyperplasia of BAT, and subsequently an increased thermogenic capacity. In a number of obesity syndromes in rodents the sympathetic mediation is defective, and this leads to extreme sensitivity to cold and to obesity. BAT has been reported to be present also in humans, and there has been focused mainly on the interscapular subcutaneous tissue. An ephedrine-induced increase of the interscapular skin temperature has been interpreted as evidence of the presence of thermogenic BAT. This lead to the assumption that BAT, also in humans, plays a significant role in the regulation of energy balance. Likewise, the hypothesis has been advanced that a diminished thermogenesis in BAT may be the cause of some types of human obesity. After validation of the xenon clearance method in rats for blood flow measurements in BAT, the method was applied on humans to examine the ephedrine-induced increase in the interscapular temperature. The warmest interscapular skin area was localized by thermography during ephedrine stimulation. In a second study subcutaneous blood flow and temperature were measured in this area during ephedrine stimulation and compared to the response of white adipose tissue in the lumbar area. The results showed that the increases in blood flow and temperatures were of similar magnitude in the two locations. Biopsies taken from the warmest interscapular spots did not contain brown adipocytes. A histological study on human autopsies confirmed that BAT is rare in the interscapular tissue, but frequently occurring in the perirenal depot. In the next study, the thermogenic function of the perirenal BAT was examined by measurements of blood flow and local temperature. Perirenal BAT thermogenesis was uninfluenced by ephedrine in 4 of 5 subjects. It was estimated that BAT thermogenesis in the single responding subject could account for maximally 15% of the ephedrine-induced increase in whole body oxygen consumption.(ABSTRACT TRUNCATED AT 400 WORDS)

Adipose Tissue, Brown↗
PubMed1985

Enhanced thermogenic responsiveness during chronic ephedrine treatment in man.

The thermogenic effect of a single oral dose of ephedrine (1 mg/kg body weight) was studied by indirect calorimetry in five women with 14% overweight before, during and 2 mo after 3 mo of chronic ephedrine treatment (20 mg, perorally, three times daily). Before treatment and 2 mo after its cessation a similar thermogenic response to ephedrine was observed. The total extra consumption of oxygen was 1.3 1 before and 1.2 1 after cessation of the chronic treatment. After 4 and 12 wk of treatment ephedrine elicited a more sustained response, the extra oxygen consumption in the 3 h following ephedrine intake being 7.0 and 6.9 1, respectively. The ratio of serum T3 to T4 increased significantly after 4 wk of treatment (15.6 +/- 1.3 vs 19.4 +/- 2.4; p less than 0.05), but decreased below the initial value after 12 wk treatment. The mean body weight was significantly reduced after 4 and 12 wk of treatment (2.5 and 5.5 kg, respectively). An improved capacity for beta-adrenergic induced thermogenesis may be useful in the treatment of obesity.

Adipose Tissue, Brown↗
PubMed1985

The effect of non-esterified long-chain fatty acids on blood flow and thermogenesis in brown adipose tissue in the young dog.

In vitro experiments have demonstrated that increasing the molar ratio of extracellular non-esterified fatty acids (NEFA) to albumin stimulates thermogenesis in brown adipocytes. To test these results, in vivo blood flow and local temperature were measured in perirenal brown adipose tissue (BAT) in puppies during thermogenesis induced by increasing the plasma NEFA: albumin ratio by injection of intralipid and heparin. Plasma NEFA concentration increased to 1.5 mmol X 1-I and plasma NEFA:albumin ratio to 4. Concomitantly, the whole body oxygen consumption rose on average about 100% above baseline level. Plasma noradrenaline concentration increased about three-fold and plasma adrenaline concentration about six-fold. The BAT temperature increased by an average of 0.9 degrees C. However, since BAT blood flow was simultaneously reduced by about 50%, it can be calculated that the local heat production was also reduced. Consequently, the increase in whole body oxygen consumption was not due to stimulation of BAT thermogenesis. It is concluded that in vivo assessment of BAT thermogenesis requires concomitant measurements of both local BAT temperature and blood flow.

Adipose Tissue↗
PubMed1985

Vasoconstrictor effect of high FFA/albumin ratios in adipose tissue in vivo.

Subcutaneous or perirenal adipose tissue blood flow was measured with the 133Xe-washout technique before and after intravenous injection or infusion of Intralipid in six anesthetized, otherwise intact mongrel dogs. In four anesthetized mongrel puppies adipose tissue blood flow was measured with the radioactive microsphere method in seven different adipose tissue depots before a bolus injection of Intralipid and at the time after the injection when the thermogenic effect of the Intralipid was maximal. The results showed that the vascular resistance increased in all the examined adipose depots in adult as well as in young dogs after this treatment. The administration of Intralipid did not per se induce the vasoconstriction. The vasoconstriction took place simultaneously with increasing FFA/albumin molar ratios. The results support our previous findings in perfused fat pads that high molar FFA/albumin ratios increase vascular resistance in adipose tissue and they give further support to our suggestion that this vasoconstriction may be a link in a negative-feedback mechanism regulating FFA-mobilization in relation to FFA utilization.

Adipose Tissue↗
PubMed1985

Contribution of BAT and skeletal muscle to thermogenesis induced by ephedrine in man.

This investigation was performed to examine the role of brown adipose tissue (BAT) in thermogenesis induced by ephedrine in man. Light microscopy of biopsies from necropsy cases showed BAT to occur most frequently in the perirenal fat. Perirenal BAT thermogenesis was investigated in five lean men before and during stimulation with 1 mg ephedrine orally X kg body wt-1. Perirenal BAT thermogenesis was assessed by continuous measurements of local temperature and blood flow with the 133xenon clearance method. In the same study the effect of ephedrine on skeletal muscle oxygen consumption was estimated by measurements of leg blood flow and arteriovenous oxygen difference. The perirenal adipose tissue blood flow increased approximately twofold, whereas the local temperature increased approximately 0.1 degrees C on an average. Assuming that man possesses 700 g of BAT with a similar thermogenic capacity, this tissue contributed only 10 ml X min-1 to the 40 ml X min-1 increase in oxygen consumption in the subject whose perirenal BAT showed the most pronounced response to ephedrine. The leg oxygen consumption increased on an average 60% after ephedrine. By extrapolation of this value to whole body skeletal muscle, approximately 50% of the increase in oxygen consumption induced by ephedrine may take place in skeletal muscle. It is concluded that skeletal muscle is a tissue of importance with respect to the thermogenic effect of sympathomimetics in man, whereas the results do not support a major role for perirenal BAT.

Adipose Tissue, Brown↗
PubMed1985

Determination of the tissue-to-blood partition coefficient for 131iodo-antipyrine in human subcutaneous adipose tissue.

131Iodo-antipyrine (131I-AP) is commonly used for blood flow measurements in adipose tissue. These estimations have been based on the assumption of the tissue-to-blood partition coefficient being 1 ml g-1. No exact determination of the tissue-to-blood partition coefficient for 131I-AP in adipose tissue has been carried out. In the present study a partition coefficient of 1.12 +/- 0.06 (mean +/- S.D.) for 131I-AP in adipose tissue has been determined based on the partition coefficient for 131I-AP between lipid-saline (1.24 ml g-1), red blood cells-plasma (0.64 ml g-1), protein-saline (0.19 ml g-1) and plasma-saline (0.84 ml ml-1).

Adipose Tissue↗
PubMed1985

The double isotope technique for in vivo determination of the tissue-to-blood partition coefficient for xenon in human subcutaneous adipose tissue--an evaluation.

Local subcutaneous 133xenon (133Xe) elimination was registered in the human forefoot in 34 patients. The tissue/blood partition coefficient for Xe was estimated individually by simultaneous registration of 133Xe and [131I]antipyrine ([131I]AP) washout from the same local depot. When measured in this way, an average partition coefficient for Xe was found to be 4.3 +/- 1.23 ml g-1. This value is significantly lower than the partition coefficient found in a previous in vitro study in which a Xe partition coefficient of 7.5 +/- 1.57 ml g-1 was found. Thus, if the local blood flow is calculated using the partition coefficient found by the double isotope technique, significantly lower values are obtained than if the in vitro determined coefficient is used. This difference is explained mainly by local dilution when injecting xenon subcutaneously. In short-term studies, utilization of the double isotope technique reduces the coefficient of variation on average flow determinations, thus an improvement in accuracy of local blood flow estimation can be obtained compared to the method in which an average partition coefficient is used. For long-term studies a partition coefficient of 7.5 ml g-1 seems valid.

Adipose Tissue↗