In Vivo Noninvasive Characterization of Brown Adipose Tissue Blood Flow by Contrast Ultrasound in Mice

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.

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Functional characterization of human brown adipose tissue metabolism

Biochemical Journal ◽

10.1042/bcj20190464 ◽

2020 ◽

Vol 477 (7) ◽

pp. 1261-1286 ◽

Cited By ~ 3

Author(s):

Marie Anne Richard ◽

Hannah Pallubinsky ◽

Denis P. Blondin

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Functional Characterization ◽

Human Infants ◽

Positron Emission ◽

Brown Adipose ◽

Treatment Of Obesity ◽

And Function

Brown adipose tissue (BAT) has long been described according to its histological features as a multilocular, lipid-containing tissue, light brown in color, that is also responsive to the cold and found especially in hibernating mammals and human infants. Its presence in both hibernators and human infants, combined with its function as a heat-generating organ, raised many questions about its role in humans. Early characterizations of the tissue in humans focused on its progressive atrophy with age and its apparent importance for cold-exposed workers. However, the use of positron emission tomography (PET) with the glucose tracer [18F]fluorodeoxyglucose ([18F]FDG) made it possible to begin characterizing the possible function of BAT in adult humans, and whether it could play a role in the prevention or treatment of obesity and type 2 diabetes (T2D). This review focuses on the in vivo functional characterization of human BAT, the methodological approaches applied to examine these features and addresses critical gaps that remain in moving the field forward. Specifically, we describe the anatomical and biomolecular features of human BAT, the modalities and applications of non-invasive tools such as PET and magnetic resonance imaging coupled with spectroscopy (MRI/MRS) to study BAT morphology and function in vivo, and finally describe the functional characteristics of human BAT that have only been possible through the development and application of such tools.

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Uptake of glucose and release of fatty acids and glycerol by rat brown adipose tissue in vivo

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y86-101 ◽

1986 ◽

Vol 64 (5) ◽

pp. 609-614 ◽

Cited By ~ 109

Author(s):

Stephanie W. Y. Ma ◽

David O. Foster

Keyword(s):

Fatty Acids ◽

Adipose Tissue ◽

Fatty Acid ◽

Brown Adipose Tissue ◽

Tissue Blood Flow ◽

Glycerol Release ◽

Maximal Stimulation ◽

Brown Adipose ◽

Lactate And Pyruvate

The net in vivo uptake or release of free fatty acids glycerol, glucose, lactate, and pyruvate by the interscapular brown adipose tissue (IBAT) of barbital-anesthetized, cold-acclimated rats was determined from measurements of plasma arteriovenous concentration differences across IBAT and tissue blood flow. Measurements were made without stimulation of the tissue and also during submaximal and maximal stimulation by infused noradrenaline (NA), the physiological activator of BAT thermogenesis. There was no appreciable uptake of glucose or release of fatty acids and glycerol by the nonstimulated tissue. At both levels of stimulation there was significant uptake of glucose (1.7 and 2.0 μmol/min) and release of glycerol (0.9 and 1.2 μmol/min), but only at maximal stimulation was there significant release of fatty acids (1.9 μmol/min). Release of lactate and pyruvate accounted for 33% of the glucose taken up at submaximal stimulation and 88% at maximal stimulation. By calculation, the remainder of the glucose taken up was sufficient to have fueled about 12% of the thermogenesis at submaximal stimulation, but only about 2% at maximal stimulation. As estimated from the rate of glycerol release, the rate of triglyceride hydrolysis was sufficient at submaximal stimulation to fuel IBAT thermogenesis entirely with the resulting fatty acids, but it was not sufficient to do so at maximal stimulation when some of the fatty acid was exported. It is suggested that at maximal NA-induced thermogenesis a portion of lipolysis proceeded only to the level of mono- and di-glycerides with the result that glycerol release did not fully reflect the rate of fatty acid formation. Both in absolute terms and in relation to the export of glycerol the in vivo export of fatty acids from the adipocytes of IBAT was much less than is observed with brown adipocytes in vitro.

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Macronutrient metabolism of adipose tissue at rest and during exercise: a methodological viewpoint

Proceedings of The Nutrition Society ◽

10.1017/s0029665199001184 ◽

1999 ◽

Vol 58 (4) ◽

pp. 877-886 ◽

Cited By ~ 10

Author(s):

Keith N. Frayn

Keyword(s):

Fatty Acids ◽

Blood Flow ◽

Adipose Tissue ◽

Human Subjects ◽

Tissue Blood Flow ◽

Adipose Tissue Metabolism ◽

Tissue Metabolism ◽

Fat Mobilization ◽

Adipose Tissue Blood Flow

The metabolism of white adipose tissue is regulated by many factors, including hormones and substrates delivered in the blood, the activity of the autonomic nervous system and the rate of flow of blood through the tissue. An integrated view of adipose tissue metabolism can only be gained, therefore, from studies in vivo. Of the various techniques available for studying adipose tissue metabolism in vivo, the measurement of arterio-venous differences offers some unique possibilities. In human subjects this technique has been performed mostly by catheterization of the venous drainage of the subcutaneous abdominal depot. Studies using this technique indicate that adipose tissue has an active pattern of metabolism, responding rapidly to meal ingestion by suppressing the release of non-esterified fatty acids, or to exercise with an increase in fat mobilization. Adipose tissue blood flow may also change rapidly in these situations; for instance, it increases markedly after a meal, potentially increasing the delivery of triacylglycerol to the enzyme lipoprotein lipase (EC 3.1.1.34) for hydrolysis. During exercise, there is evidence that adipose tissue blood flow does not increase sufficiently to allow delivery of all the fatty acids released into the systemic circulation. The various adipose tissue depots have their own characteristic metabolic properties, although in human subjects these are difficult to study with the arterio-venous difference technique. A combination of tracer infusion with selective catheterization allows measurements of leg, splanchnic and non-splanchnic upper-body fat mobilization and triacylglycerol clearance. Development of such techniques may open up new possibilities in the future for obtaining an integrated picture of adipose tissue function and its depot-specific variations.

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

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y80-184 ◽

1980 ◽

Vol 58 (10) ◽

pp. 1212-1220 ◽

Cited By ~ 3

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.

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

Journal of Applied Physiology ◽

10.1152/japplphysiol.00634.2015 ◽

2016 ◽

Vol 120 (8) ◽

pp. 825-832 ◽

Cited By ~ 10

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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Brown adipose tissue, liver, and diet-induced thermogenesis in cafeteria diet-fed rats

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y89-061 ◽

1989 ◽

Vol 67 (4) ◽

pp. 376-381 ◽

Cited By ~ 30

Author(s):

Stephanie W. Y. Ma ◽

David O. Foster

Keyword(s):

Blood Flow ◽

Adipose Tissue ◽

Brown Adipose Tissue ◽

Direct Determination ◽

Metabolizable Energy ◽

Whole Body ◽

Tissue Blood Flow ◽

Direct Measurements ◽

Brown Adipose ◽

Diet Induced Thermogenesis

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.

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Thermogenic effects of dihydrocodeine in the rat

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y88-011 ◽

1988 ◽

Vol 66 (1) ◽

pp. 61-65 ◽

Cited By ~ 1

Author(s):

Nancy J. Rothwell ◽

Michael J. Stock ◽

Alison E. Tedstone

Keyword(s):

Blood Flow ◽

Adipose Tissue ◽

Oxygen Consumption ◽

Brown Adipose Tissue ◽

Opiate Receptors ◽

Zucker Rats ◽

Tissue Blood Flow ◽

Dependent Manner ◽

Brown Adipose ◽

Adrenergic Antagonist

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.

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