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.
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.
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 mumol/min) and release of glycerol (0.9 and 1.2 mumol/min), but only at maximal stimulation was there significant release of fatty acids (1.9 mumol/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.(ABSTRACT TRUNCATED AT 250 WORDS)
The net rates of uptake of the natural (2R,4'R,8'R) diastereoisomer of alpha-tocopherol (alpha-T) and the biodiscrimination relative to its 2S-epimer (2S,4'R,8'R) have been measured, in two experiments, for the blood and 21 tissues of male Sprague-Dawley rats fed over a period of several months diets containing deuterium-substituted forms of the alpha-T acetates. Gas chromatography-mass spectrometry was used to measure the amount of deuterated tocopherols taken up relative to the amount of nondeuterated tocopherol remaining. The measurements were performed at different times after the rats, placed for one month on a basal diet containing nondeuterated, natural alpha-T acetate, were switched to a diet containing the same total quantity of deuterated forms of either natural alpha-T acetate or a mixture of the acetates of the 2R- and 2S-epimers (i.e., ambo-alpha-T acetate). In experiment 1 the source of vitamin E in the replacement diet was trideuterio-2R,4'R,8'R-alpha-T acetate. The data obtained provide the first direct measure of the rate at which natural vitamin E is replaced and augmented in the tissues of growing animals under normal laboratory dietary conditions. There are dramatic differences in the tissue kinetics; for example, the apparent half-life of vitamin E, i.e., the time at which the total amount of ingested trideuterio-alpha-T taken up is the same as the amount of nondeuterated alpha-T remaining, varies from ca. 1 wk for the lung to ca. 11 wk for the spinal cord. In experiment 2 the vitamin E in the replacement diet was an equimolar mixture of trideuterio-2S,4'R,8'R- and hexadeuterio-2R,4'R,8'R-alpha-T acetates. The results show that there is a preferential uptake of the natural diastereoisomer of alpha-T by all tissues (except the liver during the first month). Examination of fecal material reveals that the biodiscrimination begins in the gut; the incomplete hydrolysis of the acetates shows clearly that this reaction proceeds to a greater extent with the natural diastereoisomer. The greatest discrimination of all the tissues examined was found to occur in the brain. After five months, the level of the deuterated natural diastereoisomer was more than five times that of the deuterated 2S-epimer. These results have potential implications for human nutrition.
Starvation results in an energy-conserving reduction in metabolic rate that has features of an adaptive response. Tissue and organ sites of this response were investigated by examining the effects of starvation for 5 d on tissue blood flow (microsphere method) and regional arteriovenous O2 differences ((a-v)O2) in conscious rats resting quietly at 28 degrees C. Comparison was with fed and overnight-fasted animals. Whole body resting metabolic rates (MR), colonic temperatures (Tc), and tissue weights were also determined. Quantitative changes in energy expenditure (as O2 consumption) were obtained for two regions: the portal-drained viscera (PDV) and the hindquarters (HQ). Fasting overnight resulted in increased blood flow to white adipose tissue (WAT) and decreased flow to the brain, PDV, testes, and skin; however, MR, Tc, the two regional ((a-v)O2, and the weights of most tissues were not significantly altered. In comparison with overnight fasting, starvation for 5 d resulted in a 13% reduction in body weight, weight loss in many tissues and organs, a 26% reduction in MR, a decline of 0.5 degree C in Tc, decreased (a-v)O2 across both the PDV and HQ, reduced cardiac output, and decreased blood flow to the heart, PDV, skin, WAT, leg muscle, HQ, and the musculoskeletal body as a whole. Utilization of O2 by the PDV and HQ (flow X (a-v)O2) declined by amounts that accounted for 22 and 18%, respectively, of the reduction in MR. The reductions in cardiac output (18%) and heart blood flow (36%) indicate that the heart also made a contribution to energy conservation (roughly estimated as 5%).(ABSTRACT TRUNCATED AT 250 WORDS)
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