Tissue distribution of cold-induced thermogenesis in conscious warm- or cold-acclimated rats reevaluated from changes in tissue blood flow: The dominant role of brown adipose tissue in the replacement of shivering by nonshivering thermogenesis

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.

1978 ◽  
Vol 56 (1) ◽  
pp. 110-122 ◽  
Author(s):  
David O. Foster ◽  
M. Lorraine Frydman

Cardiac output (CO) and the fractional distribution (FD) of γ-labeled plastic microspheres (15 ± 5 μm) injected into the left ventricle were used to calculate blood flow to organs and tissues of barbital-sedated warm-acclimated (WA) or cold-acclimated (CA) white rats at rest and then during their maximal calorigenic response to infused noradrenaline (NA). Flow to the major masses of brown adipose tissue (BAT) increased in WA rats from a mean of 0.81 ml/min (0.92% of CO) at rest to 13.5 ml/min (11.4% of CO) during calorigenesis; it increased in CA rats from 2.3 ml/min (2.6% of CO) to 57.2 ml/min (33.5% of CO). Flow to skeletal muscle increased in WA rats from 12.0 ml/min at rest to 15.1 ml/min during calorigenesis; it increased in CA rats from 9.9 ml/min to 14.5 ml/min. Flow to heart and to muscles involved in respiratory movements was two to five times greater during calorigenesis. Flow to most other tissues and organs increased or decreased by less than 40%.Arteriovenous differences in blood oxygen [Formula: see text] across interscapular BAT (IBAT) during rest and during calorigenesis together with measurements of blood flow established that IBAT alone accounted for 14% of the extra O2 used by CA rats during NA-induced calorigenesis. If during calorigenesis other masses of BAT have an [Formula: see text] as great as that for IBAT, the major masses of BAT together would account for 60% of the calorigenic response of the CA rat. In contrast, even if the skeletal muscle of the CA rat used all the O2 in the blood flowing through it during calorigenesis, it could not have been responsible for more than 12% of the calorigenic response.The rat, long considered to exemplify major participation of skeletal muscle in nonshivering thermogenesis (NST), now becomes just one of a growing list of species for which there is explicit or circumstantial evidence that NST occurs principally in BAT. It thus becomes reasonable to propose as a general principle that BAT is the primary anatomical site of the NST that is characteristic of many small mammals: CA adults, newborns, and hibernators alike.


2014 ◽  
Vol 307 (11) ◽  
pp. E1020-E1029 ◽  
Author(s):  
Ruy A. Louzada ◽  
Maria C. S. Santos ◽  
João Paulo A. Cavalcanti-de-Albuquerque ◽  
Igor F. Rangel ◽  
Andrea C. F. Ferreira ◽  
...  

During cold acclimation, shivering is progressively replaced by nonshivering thermogenesis. Brown adipose tissue (BAT) and skeletal muscle are relevant for nonshivering thermogenesis, which depends largely on thyroid hormone. Since the skeletal muscle fibers progressively adapt to cold exposure through poorly defined mechanisms, our intent was to determine whether skeletal muscle type 2 deiodinase (D2) induction could be implicated in the long-term skeletal muscle cold acclimation. We demonstrate that in the red oxidative soleus muscle, D2 activity increased 2.3-fold after 3 days at 4°C together with the brown adipose tissue D2 activity, which increased 10-fold. Soleus muscle and BAT D2 activities returned to the control levels after 10 days of cold exposure, when an increase of 2.8-fold in D2 activity was detected in white glycolytic gastrocnemius but not in red oxidative gastrocnemius fibers. Propranolol did not prevent muscle D2 induction, but it impaired the decrease of D2 in BAT and soleus after 10 days at 4°C. Cold exposure is accompanied by increased oxygen consumption, UCP3, and PGC-1α genes expression in skeletal muscles, which were partialy prevented by propranolol in soleus and gastrocnemius. Serum total and free T3 is increased during cold exposure in rats, even after 10 days, when BAT D2 is already normalized, suggesting that skeletal muscle D2 activity contributes significantly to circulating T3 under this adaptive condition. In conclusion, cold exposure is accompanied by concerted changes in the metabolism of BAT and oxidative and glycolytic skeletal muscles that are paralleled by type 2 deiodinase activation.


1987 ◽  
Vol 243 (1) ◽  
pp. 281-284 ◽  
Author(s):  
J A Fernandez ◽  
T Mampel ◽  
F Villarroya ◽  
R Iglesias

Tri-iodothyronine (T3)production by interscapular brown fat was studied by measurements of arterio-venous differences and blood flow across the tissue in rats exposed to the following situations: controls, acute cold, chronic cold and starvation. Results demonstrate that brown adipose tissue is a source of systemic T3 in the rat and that the T3 release is modulated according to the physiological situation of the animal: increased in cold exposure and inhibited in starvation.


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.


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

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.


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.


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