Ji-Ming Ye

Nonshivering Thermogenesis in a Marsupial (the Tasmanian Bettong Bettongia gaimardi ) Is Not Attributable to Brown Adipose Tissue

The Tasmanian bettong (Bettongia gaimardi, a marsupial) is a rat‐kangaroo that increases nonshivering thermogenesis (NST) in response to norepinephrine (NE). This study attempted to assess whether brown adipose tissue (BAT), a specialized thermogenic effector, is involved in NST in the bettong. Regulatory NST, indicated by resting oxygen consumption (Vo2) of the whole body, was measured under conscious conditions at 20°C with various stimuli: cold (4°–5°C) or warm (25°C) acclimation, NE injection, and the β3‐adrenoceptor agonist (BRL) 37344. In line with the functional studies in vivo, the presence of BAT was evaluated by examining the expression of the uncoupling protein 1 (UCP1) with both rat cDNA and oligonucleotide probes. Both NE and BRL 37344 significantly stimulated NST in the bettong. After cold acclimation of the animals (at 4°–5°C for 2 wk), the resting Vo2 was increased by 15% and the thermogenic effect of NE was enhanced; warm‐acclimated animals showed a slightly depressed response. However, no expression of UCP1 was detected in bettongs either before or after cold exposure (2 wk). These data suggest that the observed NST in the marsupial bettong is not attributable to BAT.

Inhibition by vasodilators of noradrenaline and vasoconstrictor-mediated, but not skeletal muscle contraction-induced oxygen uptake in the perfused rat hindlimb; implications for non-shivering thermogenesis in muscle tissue.

1. The effect of noradrenaline as well as of vasopressin and angiotensin II to increase oxygen uptake and perfusion pressure by the isolated perfused rat hindlimb were completely inhibited by the vasodilators, nitroprusside (0.5 mM), nifedipine (2.5 microM) and isoprenaline (50 nM). 2. Oxygen uptake due to sciatic nerve stimulation of skeletal muscle contraction was not inhibited by 0.5 mM nitroprusside but was found to increase further that produced by a maximum dose of either noradrenaline or angiotensin II. 3. Analysis of high energy phosphates in samples of freeze-clamped hindlimb muscle showed no difference before and after vasoconstrictor addition or with muscle sampled in vivo. 4. It is concluded that norepinephrine mediated increase in oxygen uptake by the perfused rat hindlimb results from its vasoconstrictor action.

A comparison of vasopressin and noradrenaline on oxygen uptake by perfused rat hindlimb, kidney, intestine and mesenteric arcade suggests that it is in part due to contractile work by blood vessels

1. The rat hindlimb, kidney and intestine were each perfused in a nonrecirculating mode at 25 degrees C using an artificial perfusate (initial pressure 85 +/- 5 mmHg) and the effects of vasopressin and noradrenaline on oxygen uptake and perfusion pressure determined. 2. Both vasopressin (K0.5 = 0.1 nM) and noradrenaline (K0.5 = 2 nM) increased oxygen uptake as well as perfusion pressure by the perfused hindlimb; changes in oxygen uptake were closely matched by changes in pressure. The maximum increase in oxygen uptake was approx. 9 mumol/hr per g wet wt of hindlimb. 3. The perfused kidney also responded to vasopressin and noradrenaline with parallel increases in oxygen uptake and perfusion pressure for each agent. The largest increase in oxygen uptake was approx. 30 mumol/hr per g wet wt but this was not maximal. 4. Vasopressin increased oxygen uptake and pressure by the perfused intestine over the range 0.01-2 nM, but the changes in pressure only became significant at doses greater than 0.1 nM. 5. Noradrenaline inhibited oxygen uptake and increased perfusion pressure in a dose-dependent manner at pharmacological concentrations (greater than 30 nM) when shunting of perfusate may have contributed to unperfused regions. 6. A network of mesenteric blood vessels estimated to contain approx. 6% vascular tissue by weight, with the remainder white fat cells, lymphatics and connective tissue, was also perfused. 7. Vasopressin (K0.5 = 0.3 nM) and noradrenaline (K0.5 = 30 nM) each increased oxygen uptake and perfusion pressure in a dose-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Potential for non-shivering thermogenesis in perfused chicken (Gallus domesticus) muscle

The humoral modulation of resting muscle heat production of chickens (Gallus domesticus) was investigated in vitro. The resting distal lower limb was perfused via the popliteal artery at 25 degrees C without erythrocytes at constant flow. The preparation was stable for at least 3 hr, showing a constant oxygen uptake (MO2) and perfusion pressure as well as adequately maintaining muscle energy charge and creatine phosphate: creatine ratio. Noradrenaline (NOR), adrenaline (ADR) and serotonin (5-HT) each caused a dose-dependent rise in perfusion pressure. NOR and ADR evoked increased MO2 at low doses eventually followed by decreased MO2 at higher agonist concentrations. 5-HT gave smaller but qualitatively similar MO2 effects. The actions of 50 nM NOR were blocked by prazosin (10 microM) and nitroprusside (0.5 mM), but not altered by propranolol (10 microM). NOR-induced stimulatory MO2 changes in the presence of pharmacological concentrations (1 microM) of glucagon were more pronounced and the thermogenic concentration range of NOR was increased. Taken together, these in vitro findings demonstrate a potential for vasoconstrictor-controlled muscle nonshivering thermogenesis in birds as in marsupials and mammals, suggesting that vascular control of muscle MO2 may be a widespread biological mechanism. The possible implications of these findings for avian nonshivering thermogenesis are discussed.

Resting Muscle: A Source of Thermogenesis Controlled by Vasomodulators

Perfused, but neither incubated nor perifused, hindlimb muscle responds to a variety of vasomodulators, including noradrenaline, by rapidly altering the rate of oxygen consumption and metabolite release. The vascular tissue of muscle is identified as highly energetic and may be the major contributor to hindlimb thermogenesis. In addition, vasomodulators may control the delivery of nutrients to specialized skeletal muscle mitochondria by altering the microvascular distribution of flow. We propose that resting skeletal muscle contributes to whole body thermogenesis of endotherms and that it is controlled by total, as well as zonal (within muscle), nutrient delivery.

Altered muscle metabolism associated with vasoconstriction in spontaneously hypertensive rats

In the rat muscle vascular bed, vasoconstrictors either increase or decrease oxygen consumption (V˙o 2). The present study compared the effects of norepinephrine (NE), angiotensin II (ANG II), and 5-hydroxytryptamine (5-HT) on vasoconstriction-associated metabolism in the constant-flow perfused hindlimb of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) in the absence of insulin. Basal perfusion pressure,V˙o 2, glucose uptake, and lactate production were increased by 21.4, 11.9, 46.4, and 44.9% ( P < 0.05 for all), respectively, in SHR, which also had higher blood pressure and metabolic rate ( P < 0.05) in vivo. Dose-response curves for NE-induced perfusion pressure,V˙o 2, and lactate production in SHR were shifted to the left compared with WKY. Associated with the increased perfusion pressure, NE-inducedV˙o 2 and glucose uptake were both decreased ( P < 0.01), particularly at high concentrations. These differences were unaffected by 10 μM propranolol but were all diminished by further addition of prazosin (2.5 nM). ANG II stimulatedV˙o 2, glucose uptake, and lactate production in both strains, but the increased lactate production was smaller in SHR ( P < 0.05) with a proportional decrease ( P< 0.05) in glucose uptake. Conversely, 5-HT decreasedV˙o 2 in both strains ( P < 0.01), and this effect was greater in SHR ( P < 0.01). These data suggest that SHR muscle thermogenesis and glucose uptake are impaired during vasoconstriction, especially in response to NE.In the rat muscle vascular bed, vasoconstrictors either increase or decrease oxygen consumption (VO2). The present study compared the effects of norepinephrine (NE), angiotensin II (ANG II), and 5-hydroxytryptamine (5-HT) on vasoconstriction-associated metabolism in the constant-flow perfused hindlimb of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) in the absence of insulin. Basal perfusion pressure, VO2, glucose uptake, and lactate production were increased by 21.4, 11.9, 46.4, and 44.9% (P < 0.05 for all), respectively, in SHR, which also had higher blood pressure and metabolic rate (P < 0.05) in vivo. Dose-response curves for NE-induced perfusion pressure, VO2, and lactate production in SHR were shifted to the left compared with WKY. Associated with the increased perfusion pressure, NE-induced VO2 and glucose uptake were both decreased (P < 0.01), particularly at high concentrations. These differences were unaffected by 10 microM propranolol but were all diminished by further addition of prazosin (2.5 nM). ANG II stimulated VO2, glucose uptake, and lactate production in both strains, but the increased lactate production was smaller in SHR (P < 0.05) with a proportional decrease (P < 0.05) in glucose uptake. Conversely, 5-HT decreased VO2 in both strains (P < 0.01), and this effect was greater in SHR (P < 0.01). These data suggest that SHR muscle thermogenesis and glucose uptake are impaired during vasoconstriction, especially in response to NE.