Redox state of brown adipose tissue as a possible determinant of its blood flow

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 (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.


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.


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

2011 ◽  
Vol 301 (4) ◽  
pp. R987-R994 ◽  
Author(s):  
Youichirou Ootsuka ◽  
Keerthi Kulasekara ◽  
Rodrigo Cunha de Menezes ◽  
William W. Blessing

Brown adipose tissue (BAT) thermogenesis occurs episodically in an ultradian manner approximately every 80–100 min during the waking phase of the circadian cycle, together with highly correlated increases in brain and body temperatures, suggesting that BAT thermogenesis contributes to brain and body temperature increases. We investigated this in conscious Sprague-Dawley rats by determining whether inhibition of BAT thermogenesis via blockade of beta-3 adrenoceptors with SR59230A interrupts ultradian episodic increases in brain and body temperatures and whether SR59230A acts on BAT itself or via sympathetic neural control of BAT. Interscapular BAT (iBAT), brain, and body temperatures, tail artery blood flow, and heart rate were measured in unrestrained rats. SR59230A (1, 5, or 10 mg/kg ip), but not vehicle, decreased iBAT, body, and brain temperatures in a dose-dependent fashion (log-linear regression P < 0.01, R2 = 0.3, 0.4, and 0.4, respectively, n = 10). Ultradian increases in BAT, brain, and body temperature were interrupted by administration of SR59230A (10 mg/kg ip) compared with vehicle, resuming after 162 ± 24 min (means ± SE, n = 10). SR59230A (10 mg/kg ip) caused a transient bradycardia without any increase in tail artery blood flow. In anesthetized rats, SR59230A reduced cooling-induced increases in iBAT temperature without affecting cooling-induced increases in iBAT sympathetic nerve discharge. Inhibition of BAT thermogenesis by SR59230A, thus, reflects direct blockade of beta-3 adrenoceptors in BAT. Interruption of episodic ultradian increases in body and brain temperature by SR59230A suggests that BAT thermogenesis makes a substantial contribution to these increases.


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