Effects of rate of blood flow on fractional extraction and on uptake of infused noradrenaline by brown adipose tissue in vivo

1980 ◽  
Vol 58 (10) ◽  
pp. 1212-1220 ◽  
Author(s):  
David O. Foster ◽  
Florent Depocas ◽  
Gloria Zaror-Behrens ◽  
M. Lorraine Frydman ◽  
Suzanne Lacelle
Keyword(s):  
Blood Flow ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Major Influence ◽  
Interscapular Brown Adipose Tissue ◽  
Diffusion Limited ◽  
Brown Adipose ◽  
Arterial Plasma ◽  
Response Percentage

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.

Noradrenaline-induced calorigenesis in warm- or cold-acclimated rats. In vivo estimation of adrenoceptor concentration of noradrenaline effecting half-maximal response

1980 ◽  
Vol 58 (9) ◽  
pp. 1072-1077 ◽  
Author(s):  
Florent Depocas ◽  
Gloria Zaror-Behrens ◽  
Suzanne Lacelle
Keyword(s):  
Adipose Tissue ◽  
Steady State ◽  
Brown Adipose Tissue ◽  
Maximal Response ◽  
Brown Adipose ◽  
Acclimation Group ◽  
Arterial Plasma ◽  
State Concentration ◽  
Na Uptake

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.

Transient upregulation of IGF-I gene expression in brown adipose tissue of cold-exposed rats

1997 ◽  
Vol 272 (3) ◽  
pp. E453-E460 ◽  
Author(s):  
C. Duchamp ◽  
K. A. Burton ◽  
A. Geloen ◽  
M. J. Dauncey
Keyword(s):  
Adipose Tissue ◽  
Food Intake ◽  
Brown Adipose Tissue ◽  
Unit Weight ◽  
Mrna Levels ◽  
Interscapular Brown Adipose Tissue ◽  
Total Rna ◽  
Brown Adipose ◽  
Igf I

The possible involvement of locally produced insulin-like growth factor I (IGF-I) in the cold-induced hyperplasia of interscapular brown adipose tissue (BAT) was investigated in 2-, 4-, and 7-day cold-exposed (CE, 4 degrees C) rats by measuring BAT IGF-I expression at a time when extensive BAT cell proliferation occurs. By comparison with thermoneutral (25 degrees C) controls, plasma IGF-I decreased in CE rats despite an increased food intake, whereas BAT IGF-I peptide increased markedly to peak after 4 days at 4 degrees C. The ratio of class 1 to class 2 IGF-I mRNA was much higher in BAT than in liver. BAT IGF-I mRNA levels per unit weight total RNA doubled after 2 days at 4 degrees C but decreased thereafter to the level in controls. Upregulation of BAT IGF-I mRNA also occurred in CE rats with a food intake restricted to the level of controls. The transient cold-induced upregulation of BAT IGF-I (per unit weight total RNA) suggests that IGF-I plays a role in the early cold-induced BAT hyperplasia that occurs in vivo.

Sympathetic denervation impairs responses of brown adipose tissue to VMH stimulation

1986 ◽  
Vol 251 (5) ◽  
pp. R1005-R1008 ◽  
Author(s):  
Y. Minokoshi ◽  
M. Saito ◽  
T. Shimazu
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Temperature Response ◽  
Sympathetic Denervation ◽  
Nerve Supply ◽  
Rapid Rise ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose ◽  
Stimulation Of

Effects of unilateral surgical denervation of the interscapular brown adipose tissue (IBAT) on its thermogenic and lipogenic responses to electrical stimulation of the ventromedial hypothalamic (VMH) nucleus were studied in anesthetized rats. The rapid rise in IBAT temperature in response to VMH stimulation was greatly suppressed in the denervated IBAT, whereas the temperature response was not impaired in the contralateral innervated IBAT in the same animals. Similarly, the increased rates of conversion of [14C] glucose and [3H]H2O to fatty acids and glyceride glycerol in vivo in IBAT after VMH stimulation were almost completely inhibited by sympathetic denervation. These results indicate clearly that the increases in lipogenic and thermogenic activities in IBAT in response to VMH stimulation are mediated by the sympathetic nerve supply of this tissue.

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
Keyword(s):  
Blood Flow ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Venous Blood ◽  
Adrenergic Innervation ◽  
Arterial Blood ◽  
Composition And Structure ◽  
Brown Adipose ◽  
Arterial Plasma ◽  
Sigmoid Functions

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.

scholarly journals Glucose utilization by interscapular brown adipose tissue in vivo during nutritional transitions in the rat

1991 ◽  
Vol 273 (1) ◽  
pp. 233-235 ◽  
Author(s):  
M J Holness ◽  
Y L Liu ◽  
J S Beech ◽  
M C Sugden
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Glucose Utilization ◽  
Fold Increase ◽  
Interscapular Brown Adipose Tissue ◽  
Overall Response ◽  
Brown Adipose ◽  
Control Post

Glucose utilization indices (GUI) of interscapular brown adipose tissue (IBAT) declined by 84% after 48 h starvation. Two-thirds of the overall response was observed within 6 h, correlating with decreased insulin concentrations. Re-feeding 48 h-starved rats restored insulin concentrations and evoked a rapid 15-fold increase in IBAT GUI. GUI values after re-feeding were markedly higher than those observed at equivalent insulin concentrations in control post-absorptive rats.

Recovery of function in sympathetic nerves of interscapular brown adipose tissue of rats treated with 6-hydroxydopamine

1984 ◽  
Vol 62 (10) ◽  
pp. 1327-1332 ◽  
Author(s):  
Florent Depocas ◽  
David O. Foster ◽  
Gloria Zaror-Behrens ◽  
Suzanne Lacelle ◽  
B. Nadeau
Keyword(s):  
Blood Flow ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Recovery Of Function ◽  
Subcutaneous Administration ◽  
Acclimation Temperature ◽  
Noradrenaline Content ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose ◽  
6 Hydroxydopamine

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.

scholarly journals Evidence for a high fatty acid synthesis activity in interscapular brown adipose tissue of genetically obese Zucker rats

1982 ◽  
Vol 204 (2) ◽  
pp. 503-507 ◽  
Author(s):  
M Lavau ◽  
R Bazin ◽  
Z Karaoghlanian ◽  
C Guichard
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Brown Adipose Tissue ◽  
Fatty Acid Synthetase ◽  
High Fatty Acid ◽  
Acid Synthesis ◽  
Zucker Rats ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose

Obese (fa/fa) rats (30 days old) exhibited a 50% increase in the weight of interscapular brown adipose tissue compared with their lean (Fa/fa) littermates. The tissue weight increase was accounted for by an increased fat content. Lipogenesis in vivo, as assessed by the incorporation of 3H from 3H2O into lipid, was increased 5-fold in brown adipose tissue of obese as compared with lean rats. Accordingly, acetyl-CoA carboxylase, fatty acid synthetase, citrate-cleavage enzyme and malic enzyme in this tissue were 4-8 times more active in obese than in lean rats.

scholarly journals Developmental changes in fatty acid synthesis in interscapular brown adipose tissue of lean and genetically obese (ob/ob) mice

1983 ◽  
Vol 212 (2) ◽  
pp. 393-398 ◽  
Author(s):  
S W Mercer ◽  
P Trayhurn
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Brown Adipose Tissue ◽  
Fatty Acid Synthesis ◽  
Acid Synthesis ◽  
Obese Mice ◽  
Carbohydrate Diet ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose

Fatty acid synthesis was measured in vivo with 3H2O in interscapular brown adipose tissue of lean and genetically obese (ob/ob) mice. At 26 days of age, before the development of hyperphagia, synthesis in brown adipose tissue was higher in the obese than in the lean mice; synthesis was also elevated in the liver, white adipose tissue and carcass of the obese mice. At 8 weeks of age, when hyperphagia was well established, synthesis remained elevated in all tissues of the obese mice, with the exception of brown adipose tissue. Elevated synthesis rates were not apparent in brown adipose tissue of the obese mice at 14 days of age, nor at 35 days of age. These results demonstrate that brown adipose tissue in ob/ob mice has a transitory hyperlipogenesis at, and just after, weaning on to a low-fat/high-carbohydrate diet. Once hyperphagia has developed, by week 5 of life, brown adipose tissue is the only major lipogenic tissue in the obese mice not to exhibit elevated rates of fatty acid synthesis; this suggests that insulin resistance develops much more rapidly in brown adipose tissue than in other lipogenic tissues of the ob/ob mouse.

scholarly journals Relationship of brown adipose tissue perfusion and function: a study through β2-adrenoreceptor stimulation

2016 ◽  
Vol 120 (8) ◽  
pp. 825-832 ◽  
Author(s):  
Laura Ernande ◽  
Kristin I. Stanford ◽  
Robrecht Thoonen ◽  
Haihua Zhang ◽  
Maëva Clerte ◽  
...  
Keyword(s):  
Blood Flow ◽  
Adipose Tissue ◽  
Oxygen Consumption ◽  
Brown Adipose Tissue ◽  
Glucose Uptake ◽  
Direct Effect ◽  
Brown Adipocytes ◽  
Bat Activity ◽  
Brown Adipose

Brown adipose tissue (BAT) activation increases glucose and lipid consumption; as such, it is been considered as a potential therapy to decrease obesity. BAT is highly vascularized and its activation is associated with a necessary increase in blood flow. However, whether increasing BAT blood flow per se increases BAT activity is unknown. To examine this hypothesis, we investigated whether an isolated increase in BAT blood flow obtained by β2-adrenoreceptor (β2-AR) stimulation with salbutamol increased BAT activity. BAT blood flow was estimated in vivo in mice using contrast-enhanced ultrasound. The absence of direct effect of salbutamol on the function of isolated brown adipocytes was assessed by measuring oxygen consumption. The effect of salbutamol on BAT activity was investigated by measuring BAT glucose uptake in vivo. BAT blood flow increased by 2.3 ± 0.6-fold during β2-AR stimulation using salbutamol infusion in mice ( P = 0.003). β2-AR gene expression was detectable in BAT but was extremely low in isolated brown adipocytes. Oxygen consumption of isolated brown adipocytes did not change with salbutamol exposure, confirming the absence of a direct effect of β2-AR agonist on brown adipocytes. Finally, β2-AR stimulation by salbutamol increased BAT glucose uptake in vivo (991 ± 358 vs. 135 ± 49 ng glucose/mg tissue/45 min in salbutamol vs. saline injected mice, respectively, P = 0.046). In conclusion, an increase in BAT blood flow without direct stimulation of the brown adipocytes is associated with increased BAT metabolic activity. Increasing BAT blood flow might represent a new therapeutic target in obesity.

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