Noradrenaline-induced calorigenesis in warm- and in cold-acclimated rats: relations between concentration of noradrenaline in arterial plasma, blood flow to differently located masses of brown adipose tissue, and calorigenic response

1980 ◽  
Vol 58 (8) ◽  
pp. 915-924 ◽  
Author(s):  
David O. Foster ◽  
Florent Depocas ◽  
M. Lorraine Frydman

Barbital-sedated, warm-acclimated (WA) or cold-acclimated (CA) rats were infused intravenously with noradrenaline (NA) at doses that elicited graded calorigenic responses. Blood flow (Q) to the various bodies of brown adipose tissue (BAT), the major sites of the NA-induced calorigenesis, was measured with labeled microspheres. The O2 content of arterial blood and of venous blood from interscapular BAT and the concentration of NA in arterial plasma (ANA) were also determined. ANA was linearly related to the dose of NA. Calorigenic response and the Q of total BAT and of separate bodies of BAT were sigmoid functions of ANA. The threshold for calorigenic response or for increased flow to BAT was an ANA of about 2 ng/mL (12 nM), except for some bodies of BAT in CA rats where it was closer to 4 ng/mL. Delivery of O2 to total BAT and calorigenic response were related linearly. The bodies of BAT were heterogeneous in Q per gram and in CA rats the hierarchy in Q per gram changed markedly as ANA and calorigenic response increased. The analysis of these results takes into account that calorigenesis in BAT normally is not mediated by circulating NA, that in NA-infused rats neuronal and extraneuronal uptakes of NA would effect a lower concentration of NA at the adrenoceptors of BAT than in the circulation, and that many factors such as organization and density of adrenergic innervation and the number and efficacy of receptors must have contributed to determining the measured responses of BAT. It is concluded that the differently located bodies of BAT in rats may have significant differences in composition and structure and that they may undergo differential development during cold acclimation.

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.


1985 ◽  
Vol 63 (6) ◽  
pp. 595-598 ◽  
Author(s):  
W. H. Harris ◽  
D. O. Foster ◽  
B. E. Nadeau

This study was undertaken to determine if brown adipose tissue was involved in heat production during fever produced by S. abortus equi (1 μg) in unanesthetized rabbits aged 19–26 days. The fever (0.9–1.6 °C) occurred after a delay of 20–30 min and was frequently biphasic. Radiolabelled microspheres for measuring tissue blood flow were injected intraventricularly into three groups of animals: rabbits not given pyrogen, rabbits in which the febrile response to pyrogen was developing, and rabbits in which the febrile response had peaked. Blood flow to brown fat deposits and other organs was calculated from the fractional distribution of the microspheres and the recovery of microspheres in a reference arterial blood sample. At the fever peak, blood flow to brown fat was not significantly different (p > 0.05) from the control value (0.9 ± 0.2), but during the rising phase of the fever the flow increased significantly (p < 0.01) to 2.6 ± 0.4 mL min−1 g−1. The blood flow to muscles of the forelimbs and hind limbs was also increased significantly (p < 0.05) during the rising phase of the fever. No significant change in blood flow to other organs or tissues was found during the rising phase of the fever. These results indicate that both nonshivering as well as shivering thermogenesis contribute to heat production during development of fever in the young rabbit. However, nonshivering thermogenesis was not involved in the maintenance of the elevated body temperature after the fever had peaked.


1984 ◽  
Vol 62 (8) ◽  
pp. 949-956 ◽  
Author(s):  
Stephanie W. Y. Ma ◽  
David O. Foster

During norepinephrine (NE) induced thermogenesis in the adipocytes of brown adipose tissue (BAT), the blood flow of the tissue, and thus its oxygen supply, seems to be controlled by the adipocytes, possibly through their production of a vasodilator. This study sought to discover a metabolic parameter of the adipocytes that might account for modulation of vasodilator production and BAT blood flow. The blood flow of the interscapular BAT (IBAT) of anesthetized, cold-acclimated rats was varied by infusing NE and by altering the concentration of oxygen in arterial blood [Formula: see text]. Flow was measured with radiolabeled microspheres. IBAT was freeze fixed in situ for determination of its levels of adenine nucleotides and its cytosolic redox state; the latter was measured in terms of the concentration ratios, lactate/pyruvate (L/P) and glycerol-3-phosphate/dihydroxy-acetone phosphate (GP/DHAP) in the tissue. The increase in IBAT blood flow with dose of NE was associated with a progressive decline in tissue ATP, increases in ADP and AMP at high doses of NE, and progressive increases in L/P and GP/DHAP, the latter increases indicating increased reduction of the cytosolic NAD+–NADH system. Reducing [Formula: see text] by hemodilution raised the blood flow, L/P, and GP/DHAP of IBAT to values significantly above those measured in rats of normal [Formula: see text] given the same doses of NE; whereas, elevating [Formula: see text] by hemoconcentration had the opposite effects on these values. For rats of normal or altered [Formula: see text] together, a correlation coefficient of 0.94 was obtained for the relation between IBAT blood flow and L/P and one of 0.85 for that between flow and GP/DHAP. The coefficients for these relations were 0.98 when data from rats of normal [Formula: see text] only were used. Changes in the levels of ATP, ADP, and AMP or in the ratios of these nucleotides in IBAT did not correspond well with changes in blood flow. The results indicate that the cytosolic redox state of BAT may be the metabolic parameter underlying the control of BAT blood flow.


1980 ◽  
Vol 58 (9) ◽  
pp. 1072-1077 ◽  
Author(s):  
Florent Depocas ◽  
Gloria Zaror-Behrens ◽  
Suzanne Lacelle

Desmethylimipramine (DMI, 1 mg DMI∙HCl kg−1) and normetanephrine (NMN, 1 μg min−1 g−0.74) were used to inhibit, respectively, neuronal and extraneuronal uptakes of noradrenaline (NA) during calorigenesis induced in barbital-sedated warm-acclimated (WA) or cold-acclimated (CA) rats by infusion of NA, a procedure which mimics the effects of NA released within calorigenic tissues in response to cold exposure. The doses of the inhibitors were selected for maximal effectiveness in potentiating calorigenic response and for minimal side effects. For rats of either acclimation group treated with DMI and NMN, with DMI only, or with neither inhibitor the doses of NA required to evoke approximately half-maximal calorigenic responses were, respectively, 0.5, 1.0, and 3.5 ng min−1 g−0.74. The corresponding steady-state concentrations of NA in arterial plasma averaged 14.3, 21.7, and 43.2 nM in the three groups of WA rats and 10.0, 14.8, and 31.9 nM in the three groups of CA rats. Reduction by NA uptake inhibitors of the circulating levels of NA necessary to stimulate calorigenesis, half-maximally, presumably in brown adipose tissue, indicates a reduction in the steepness of the NA concentration gradient between capillary plasma and synaptic clefts in that tissue. The steady-state concentration of NA in blood plasma of rats treated with DMI and NMN and infused with NA at a dose of 0.5 ng min−1 g−0.74 (~1 × 10−8 M) is a good estimate of the NA concentration required at calorigenic adrenoceptors to effect half-maximal activation. Presumably, this concentration is also an estimate of that resulting from NA released at nerve endings during cold-induced activation of nonshivering thermogenesis at half-maximal rates in brown adipose tissue.


Life Sciences ◽  
1994 ◽  
Vol 54 (1) ◽  
pp. 17-25 ◽  
Author(s):  
Tomoaki Nagashima ◽  
Hiroshi Ohinata ◽  
Akihiro Kuroshima

Sign in / Sign up

Export Citation Format

Share Document