Ephedrine-Induced Thermogenesis in Man: No Role for Interscapular Brown Adipose Tissue

1984 ◽  
Vol 66 (2) ◽  
pp. 179-186 ◽  
Author(s):  
A. Astrup ◽  
J. Bülow ◽  
N. J. Christensen ◽  
J. Madsen

1. The warmest interscapular skin areas were located by thermography in six healthy subjects during ephedrine-induced thermogenesis. 2. In these interscapular areas, and in lumbar control areas, the skin temperature, subcutaneous temperature and adipose tissue blood flow were measured before and during ephedrine-induced thermogenesis. 3. The skin and subcutaneous temperatures increased in the interscapular area as well as in the lumbar area, by about 0.7-1.2°C. The interscapular skin temperature remained about 1°C higher than the lumbar; the subcutaneous temperatures in the two areas were identical during the experiments. 4. Although the interscapular subcutaneous adipose tissue blood flow increased about sixfold and the lumbar increased twofold, the absolute flows were higher in the lumbar area. 5. The oxygen uptake increased to a maximum of 30% above control level. 6. Plasma glucose and glycerol concentrations remained unchanged, and plasma non-esterified fatty acids, lactate and noradrenaline concentrations increased slightly but significantly. 7. Biopsies taken from the hot interscapular areas did not contain brown adipose tissue. 8. It is concluded that the high interscapular skin temperature may be due to a lower insulating fat thickness and that the increases in skin and subcutaneous temperatures during ephedrine-induced thermogenesis are caused by an increased blood flow. These observations weigh against the hypothesis that the interscapular temperature increase is due to functional, interscapular brown adipose tissue.

2013 ◽  
Vol 26 (12) ◽  
pp. 1465-1473 ◽  
Author(s):  
Maëva Clerte ◽  
David M. Baron ◽  
Peter Brouckaert ◽  
Laura Ernande ◽  
Michael J. Raher ◽  
...  

2012 ◽  
Vol 5 (5) ◽  
pp. 652-659 ◽  
Author(s):  
David M. Baron ◽  
Maeva Clerte ◽  
Peter Brouckaert ◽  
Michael J. Raher ◽  
Aidan W. Flynn ◽  
...  

1984 ◽  
Vol 62 (10) ◽  
pp. 1327-1332 ◽  
Author(s):  
Florent Depocas ◽  
David O. Foster ◽  
Gloria Zaror-Behrens ◽  
Suzanne Lacelle ◽  
B. Nadeau

Twenty-four hours after subcutaneous administration of 6-hydroxydopamine (6-OHDA) at a dose of 10 mg/kg body weight in warm-acclimated rats, noradrenaline (NA) content and dopamine β-hydroxylase (DBH) activity of interscapular brown adipose tissue (IBAT) were reduced to about 10 and 35% of control values. Corresponding values for cold-acclimated rats, similarly treated, were 12 and 32%. In both groups of animals, calorigenic function in IBAT assessed by measurement of the effect of cold exposure on rate of blood flow through the tissue was lost almost completely. Twenty-four hours after treatment of rats with various doses of 6-OHDA, calorigenesis in IBAT was directly related to residual NA. Measurements of noradrenaline content and DBH activity from 1 to 10 days after 6-OHDA and the increase in IBAT blood flow of cold-exposed animals from 1 to 7 days after 6-OHDA indicated marked differences in the extent to which each of these indicators of the integrity and function of sympathetic nerve endings recovered with time and with the acclimation temperature of the animals. Regeneration of macromolecuiar components of noradrenergic vesicles in IBAT appeared to occur more rapidly in cold than in warm-acclimated animals. Thus, moderate doses of 6-OHDA may acutely sympathectomize IBAT, but as previously reported for other tissues, full recovery of function of IBAT occurs long before noradrenaline stores are replenished.


1980 ◽  
Vol 58 (10) ◽  
pp. 1212-1220 ◽  
Author(s):  
David O. Foster ◽  
Florent Depocas ◽  
Gloria Zaror-Behrens ◽  
M. Lorraine Frydman ◽  
Suzanne Lacelle

The rate of blood flow (Q) to interscapular brown adipose tissue (IBAT) and the arteriovenous difference in plasma noradrenaline (NA) across the tissue were measured in warm-acclimated (WA) or cold-acclimated (CA) rats during infusion of NA at doses of 1–12.5 ng min−1 g−0.74 (approximately 0.2–2.7 μg min−1 kg−1) and in the period of steady calorigenic response associated with steady concentration of NA in arterial plasma (ANA). ANA was linearly related to the dose of NA. Calorigenic response, percentage of cardiac output to IBAT, and Q per gram of IBAT were sigmoid functions of ANA and at their maxima were about 2.5 times greater in CA than in WA rats. The rate of uptake of NA by IBAT increased with ANA and Q, each of which had a major influence on rate, but the coefficient of extraction of NA by the tissue (ENAIBAT) declined. Measurements in rats given a dose of propranolol that partially inhibited the NA-induced increase in Q to IBAT indicated that the decline in ENAIBAT was attributable primarily to the increase in Q rather than to increasing saturation of uptake mechanisms. Diffusion-limited extraction of NA is the probable basis for the effect of Q on ENAIBAT. Possible implications of flow-dependent extraction of NA in studies involving measurements of the uptake of exogenous NA by tissues or organs are discussed.


1989 ◽  
Vol 67 (4) ◽  
pp. 376-381 ◽  
Author(s):  
Stephanie W. Y. Ma ◽  
David O. Foster

Diet-induced thermogenesis (DIT) in young rats overeating a "cafeteria" (CAF) diet of palatable human foods is characterized by a chronic, propranolol-inhibitable elevation in resting metabolic rate [Formula: see text] and is associated with various changes in brown adipose tissue (BAT) that have been taken as evidence for BAT as the effector of DIT. But direct evidence for participation of BAT in DIT has been lacking. By employing a nonocclusive cannula to sample the venous effluent of interscapular BAT (IBAT) for analysis of its O2 content and measuring tissue blood flow with microspheres, we accomplished direct determination (Fick principle) of the O2 consumption of BAT in conscious CAF rats. In comparison with normophagic controls fed chow, the CAF rats exhibited a 43% increase in metabolizable energy intake, reduced food efficiency, a 22% elevation in resting [Formula: see text] at 28 °C (thermoneutrality) or 24 °C (housing temperature), and characteristic changes in the properties of their BAT (e.g., increased mass, protein content and mitochondrial GDP binding). They also exhibited the greater metabolic response to exogenous noradrenaline characteristic of CAF rats and the near elimination by propranolol of their elevation in [Formula: see text]. By the criterion of their elevated [Formula: see text], the CAF rats were exhibiting DIT at the time of the measurements of BAT blood flow and blood O2 levels. However, BAT O2 consumption was found to be no greater in the CAF rats than in the controls at either 28 or 24 °C. At 28 °C it accounted for less than 1% of whole body [Formula: see text]; at 24 °C it increased to about 10% of overall [Formula: see text] in both diet groups. Direct measurements of BAT O2 consumption during expression of the thermic response to a tube-fed meal were also made in conscious CAF and control rats. Both diet groups exhibited an approximately 15% increase in whole body [Formula: see text] at 90–120 min after the meal. The contribution by BAT to this increase was only 2–3% and did not differ significantly between groups. Thus, the results of these direct measurements of BAT O2 consumption in vivo do not support the theory that DIT in CAF rats is mainly due to increased BAT thermogenesis occurring either chronically or during assimilation of a meal. In further studies of the effector(s) of DIT in CAF rats, partial hepatectomy (two-thirds of the liver removed) was found to acutely reduce the resting [Formula: see text] of CAF rats by 1.85 mL/min, 2.3 times as much as in chow-fed controls. From this difference in response, it was estimated that in the CAF rats liver O2 consumption before hepatectomy exceeded that of the controls by about 1.5 mL/min, an amount that would be sufficient to fully account for the elevation in resting [Formula: see text] of the former. A major role for the liver in the DIT of CAF rats is thus suggested.Key words: cafeteria feeding, diet-induced thermogenesis, thermic effect of food, brown fat, liver.


1988 ◽  
Vol 66 (1) ◽  
pp. 61-65 ◽  
Author(s):  
Nancy J. Rothwell ◽  
Michael J. Stock ◽  
Alison E. Tedstone

The object of this study was to assess the effects of dihydrocodeine on thermogenesis and brown adipose tissue activity in the rat from measurements of oxygen consumption and blood flow. Acute injection of dihydrocodeine tartrate (s.c.) stimulated resting oxygen consumption [Formula: see text] in Sprague–Dawley rats in a dose-dependent manner (0.5–50 mg/kg), with a peak response (40–45% increase) occurring at 10–25 mg/kg. This effect was also observed in urethane-anaesthetized rats (although the effect was reduced) and in conscious animals following gastric intubation with the drug. Pretreatment of rats with either a β-adrenergic antagonist (propranolol, 20 mg/kg), ACTH (4 g/kg), or an opiate antagonist (WIN44441-1, 2 mg/kg) significantly reduced the response to dihydrocodeine, whereas corticosterone injection (5 mg/kg) enhanced the effect. Surgical adrenalectomy or hypophysectomy (HYPX) almost completely abolished the thermogenic effect of dihydrocodeine. Dihydrocodeine also stimulated [Formula: see text] in lean (58% increase) and genetically obese Zucker rats (69% increase), and in both Zucker genotypes these responses were only slightly affected by HYPX, but enhanced in HYPX rats treated daily with corticosterone (1 mg/kg). Tissue blood flow, assessed from the distribution of radiolabelled microspheres, was unaffected in white adipose tissue, skeletal muscle, testes, kidney, brain, and liver (arterial supply) after a single injection of dihydrocodeine (25 mg/kg), but flow to interscapular and perirenal brown adipose tissue was increased by 9- to 10-fold. Surgical sympathectomy of brown adipose tissue prevented the increase in blood flow. These potent thermogenic effects of dihydrocodeine in the rat appear to result from sympathetic activation of heat production in brown fat and to involve opiate receptors, but can also be modified by pituitary and (or) adrenal hormones.


2009 ◽  
Vol 297 (2) ◽  
pp. E490-E494 ◽  
Author(s):  
U. S. Pettersson ◽  
J. Henriksnäs ◽  
L. Jansson

Previous studies have shown that the Goto-Kakizaki (GK) rat, a nonobese type 2 diabetes model, has an increased white adipose tissue (WAT) and islet blood flow when compared with control rats. The aim of the study was to examine if these increased blood flow values in GK rats could be affected by the β3-adrenoceptor antagonist SR-59230A. We measured organ blood flow with a microsphere technique 10 min after administration of SR-59230A (1 mg/kg body wt), or the corresponding volume of 0.9% NaCl solution (1 ml/kg body wt) in rats anaesthetized with thiobutabarbital. The GK rat had an increased blood flow in all intra-abdominal adipose tissue depots except for the sternal fat pad compared with Wistar-Furth (WF) rats. However, no differences were seen in the blood perfusion of subcutaneous white or brown adipose tissue. The blood flow was also increased in both the pancreas and in the islets in the GK rat compared with WF rats. SR-59230A treatment affected neither WAT nor pancreatic blood flow in WF rats. In GK rats, on the other hand, SR-59230A decreased both WAT and islet blood flow values to values similar to those seen in control WF rats. The whole pancreatic blood flow was not affected by SR-59230A administration in GK rats. Interestingly, the brown adipose tissue blood flow in GK rats increased after SR-59230A administration. These results suggest that β3-adrenoceptors are involved in regulation of blood flow both in islet and in adipose tissue.


1979 ◽  
Vol 57 (3) ◽  
pp. 257-270 ◽  
Author(s):  
David O. Foster ◽  
M. Lorraine Frydman

Radioactive microspheres (12–16 μm) were used to measure cardiac output (CO), its fractional distribution, and hence tissue blood flow in conscious, warm-acclimated (WA) or cold-acclimated (CA) white rats exposed to temperatures of 25, 21, 6, −6, and −19 °C, the objective being to assess the tissue distribution of cold-induced thermogenesis. Total oxygen consumption was also measured. CA rats at 25 °C (CA25) had elevated arteriovenous shunting and other signs of heat stress. CA21 proved more suitable controls for the CA group. The cold-induced changes in blood flow to total skeletal muscle not involved in respiratory movements (M) and to the major masses of brown adipose tissue (BAT) were quantitatively very different in the two acclimation groups: in WA25 and CA21 flows to M were 31 (0.24 CO) and 27 (0.17 CO) mL/min, respectively, while flows to BAT were 2.1 and 9.7 mL/min; in WA−19 and CA−19 flows to M were 62 (0.32 CO) and 35 (0.16 CO) mL/min, respectively, while flows to BAT were 25 and 56 mL/min. In contrast, the effects of cold exposure on flows to other tissues and organs were remarkably alike in the two acclimation groups: e.g., flows to heart, ribcage, and diaphragm increased about three times between 25 and −19 °C, flow to the skin fell about 50%, and flows to the hepatosplanchnic region and kidneys were little or not at all affected by cold exposure. Estimates of the contributions of different tissues and organs to cold-induced thermogenesis were made on the basis of the relative changes in blood flow. It is concluded that BAT is by far the dominant anatomical site of the increased heat production of cold-exposed CA rats, and that nonshivering thermogenesis in BAT supplements considerably the shivering thermogenesis of cold-exposed WA rats.


1982 ◽  
Vol 60 (6) ◽  
pp. 747-754 ◽  
Author(s):  
David O. Foster ◽  
Florent Depocas ◽  
Michael Zuker

The interscapular brown adipose tissue (IBAT) of cold-acclimated white rats was partially denervated by cutting in most cases four of the five intercostal nerves going to one of its two bilaterally located, lobular pads. After 24 h the functional ability and the degree of residual sympathetic innervation of the pads and of their lobes were assessed (in separate groups of rats): the former by measuring tissue blood flow as an index of sympathetically mediated calorigenesis during exposure of the animals to −6 °C, the latter by measuring the residual noradrenaline (NA) content of the tissue. Only the four anterior intercostal nerves contributed significantly to the sympathetic innervation of IBAT pads. On average their contributions were unequal, but there was considerable variation between rats in the relative contribution of each nerve. The measurements on lobes of the pads indicated that the sympathetic fibers supplied by a given intercostal nerve were not distributed uniformly throughout the pad. For example, measurements of NA indicated that on average the fibers of the fourth nerve were four times as abundant in the lateral lobe as in the posterior lobe. But at this level of analysis also there was wide variation between rats. The variation in the participation of each intercostal nerve in the sympathetic innervation of rat IBAT and in the distribution of each nerve's fibers to different parts of the IBAT pad could be of genetic origin or it could reflect a considerable degree of flexibility during development of the innervation of IBAT. Because of the observed variation, it is suggested that if functional responses of IBAT evoked by electrical stimulation of intercostal nerves are to be recorded from a highly localized area of the tissue, stimulation of all the nerves probably would be required to obtain responses that are consistent between animals.


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