Smooth muscle energetic in the pig coronary artery during a calcium-dependent and a calcium-independent isometric contraction.

Heat production by resting smooth muscle, was measured with a heat-flux micro calorimeter on cut-open segments of pig coronary artery superfused at 30 degrees C, was 0.93+/-0.06 (n=16) mW/g wet weight. Time courses of the increases in isometric tension and heat production with respect to basal during sustained supra maximal acetylcholine stimulation were qualitatively similar: initial peak tapering down to a supra basal plateau. Mean tension-associated heat production over 1 h was 0.16 J/g. During sustained exposure to phorbol 12,13-dibutyrate, supra basal tension and--with a 5-10 min initial delay--supra basal heat progressively increased to a plateau in about 40 min. Mean tension-associated heat production over 1 h was only 0.02 J/g with normal extracellular and intracellular mobilizable Ca2+ pools, and it was further reduced to 0.01 J/g with depleted Ca2+ pools. These results show that the maintenance--if not necessarily the building up--of tension under phorbol 12,13-dibutyrate does not entail any large dissipation of energy and is not dependent on the presence of normal Ca2+ pools.

Components of energy expenditure in the mdx mouse model of Duchenne muscular dystrophy.

Previous observations showing that basal heat production rates and glucose metabolism were reduced in mdx mouse skeletal muscles incubated in vitro led us to study the components of total energy expenditure by open-circuit indirect calorimetry in the intact, free-moving mdx mouse. Our purpose was to verify if the mdx mouse exhibited whole-body alterations in energy metabolism. The results revealed that total and basal energy expenditure, as well as spontaneous activity, energetic cost of activity, and, therefore, energy expended in relation to activity were not significantly different in C57B1/10 (control) and in dystrophic (mdx) mice. In contrast, the thermic effect of food was 32% larger in mdx than in control mice and was accompanied by significant differences in post-prandial glucose and lipid oxidation. The present in vivo study could not show a direct demonstration that impaired glucose metabolism by skeletal muscles participated in this phenomenon. However, since post-prandial glucose metabolism by skeletal muscles contributes a significant part of the thermic effect of food, the present data are in line with previous studies in vitro that show that mdx mouse skeletal muscles probably suffer an impaired control of their energy metabolism.

Defective regulation of energy metabolism in mdx-mouse skeletal muscles.

Our previous finding of a reduced energy metabolism in slow- and fast-twitch skeletal muscle fibres from the murine model of Duchenne muscular dystrophy (the mdx mouse) led us to examine the importance of intracellular glucose availability for a normal energy turnover. To this end, basal and KCl-stimulated (20.9 mM total extracellular K+) rates of glucose uptake (GUP) and heat production were measured in isolated, glucose-incubated (5 mM) soleus and extensor digitorum longus muscles from mdx and control C57B1/10 mice, in the presence and in the absence of insulin (1.7 nM). Under all conditions and for both muscle types, glucose uptake values for mdx and control muscles were similar although heat production was lower in mdx muscles. The marked stimulation of GUP by insulin in both mdx and control muscles had only minor effects on heat production. In contrast, glucose deprivation or inhibition of glycolysis with 2-deoxy-D-glucose (5 mM) significantly decreased heat production in control muscles only, which attenuated, although did not suppress, the difference in basal heat production between mdx and control muscles. Stimulation of heat production by a short-chain fatty acid salt (octanoate, 2 mM) was significantly less marked in mdx than in control muscles. Increased cytoplasmic synthesis of CoA by addition of 5 mM pantothenate (vitamin B5) increased the thermogenic response to glucose more in mdx than in control muscles. We conclude that the low energy turnover in mdx-mouse muscle fibres is not due to a decrease of intracellular glucose availability, but rather to a decreased oxidative utilization of glucose and free fatty acids. We suggest that some enzyme complex of the tricarboxylic acid cycle or inefficiency of CoA transport in the mitochondria could be involved.

Suppression of Ca(2+)-dependent heat production in mouse skeletal muscle by high fish oil consumption.

The energy dissipation associated with calcium homeostasis amounts to more than 20% of muscle energy expenditure (EE) at rest and can be quantified from microcalorimetric measurements of heat production in response to chemical modulators of sarcoplasmic reticulum (SR) Ca2+ release. Using this approach, Ca(2+)-dependent heat production in both red- and white-fiber muscles from mice fed a high-fat (HF) diet rich in fish oil was found to be significantly lower than in other groups fed HF diets rich in saturated fat (hydrogenated coconut oil) or n-6 polyunsaturated fats corn oil) and in a group fed a low-fat diet. These findings reveal a potentially specific effect of fish oil on muscle-cell energy metabolism via interference with sarcoplasmic calcium homeostasis, and raise the possibility that modification of the energy cost for intracellular calcium homoeostasis may be a cellular mechanism by which diet could modulate skeletal muscle thermogenesis and whole-body EE.

Dystrophin-dependent efficiency of metabolic pathways in mouse skeletal muscles.

Muscles from the mdx mouse (X-linked genetic disorder similar to Duchenne muscular dystrophy) lack dystrophin-associated transsarcolemmal proteins and show reduced maintenance metabolic rates. Here, microcalorimetric comparisons of metabolic stimulation by exogenous substrates in isolated muscles revealed substrate-selective limitation of chemical reaction rates through both glycolytic and TCA-cycle pathways, identical in slow- and fast-twitch mdx muscles. This systemic approach, as opposed to comparisons of single-enzyme activities, sheds new light on the function of dystrophin and associated proteins. The in vivo efficiency of metabolic pathways may depend on stabilization of enzyme complexes by dystrophin-associated elements of the cytoskeleton.

Decreased rates of Ca(2+)-dependent heat production in slow- and fast-twitch muscles from the dystrophic (mdx) mouse.

Using a newly developed microcalorimetric approach to assess the rate of energy expenditure for intracellular [Ca2+] homeostasis in isolated muscles at rest, we found this was lower in mdx than in control mouse muscles, by 62% and 29% in soleus and extensor digitorum longus, respectively. Differences in total and Ca(2+)-dependent rates of specific heat production between mdx and control were enhanced during sustained, KCl-induced stimulation of energy dissipation. These results suggest that the low sarcoplasmic energy status of dystrophic muscles is not due to any excessive energy expenditure for intracellular [Ca2+] homeostasis.

Ca(2+)-dependent heat production by rat skeletal muscle in hypertonic media depends on Na(+)-Cl- co-transport stimulation.

1. The rate of energy dissipation (E) in isolated, superfused soleus muscles from young rats was continuously measured under normosmotic and 100-mosM hyperosmotic conditions. The substantial increase of E with respect to basal level in hyperosmolarity (excess E), which is entirely dependent on the presence of extracellular sodium, was largely prevented or inhibited by bumetanide, a potent inhibitor of Na(+)-Cl- co-transport system, or by the removal of chloride from the superfusate (isethionate substitution). Bumetanide or the removal of chloride also acutely decreased basal E, by about 7%. 2. Bumetanide almost entirely suppressed the major, Ca(2+)-dependent part of excess E in hyperosmolarity, as well as the concomitant increase of 45Ca2+ efflux and small increase in resting muscle tension; in contrast, the part of excess E associated with stimulation of Na(+)-H+ exchange in hyperosmolarity was left unmodified. 3. Reduction of 22Na+ influx by bumetanide was more marked in hyperosmolarity than under control conditions, although stimulation of total 22Na+ influx by a 100-mosM stress was not statistically significant. Inhibition of Ca2+ release into the sarcoplasm using dantrolene sodium did not prevent the stimulation of bumetanide-sensitive 22Na+ influx, but rather increased it about fourfold. 4. It is concluded that the largest part of excess E in hyperosmolarity, which is Ca(2+)-dependent energy expenditure, is suppressed when steady-state stimulation of a Na(+)-Cl- co-transport system is inhibited either directly by bumetanide or the removal of extracellular chloride, or indirectly by the blocking of active Na(+)-K+ transport. How the stimulation of Na(+)-Cl- co-transport, by as little as 1 nmol s-1 (g wet muscle weight)-1 during a 100-mosM stress, enhances Ca(2+)-dependent heat by as much as 2.5 mW (g wet muscle weight)-1 remains to be clarified.

Energetics of ionic contracture in rat-heart papillary muscles.

Energy dissipation and the bearing of tension during ionic contracture in myocardium may not result from one and the same process. To test this, comparative indirect and direct microcalorimetry determinations were made in non-perfused tissue-cell preparations under optimal oxygenation conditions (right papillary muscles, high-pO2 superfusion, 30 degrees C) before, during and after exposure to low-Na, high-K solutions. Over a 15-min contracture plus 45-min recovery cycle, both heat production rate (E), and the indirectly determined heat production rate (EO2) which is oxygen uptake multiplied by the overall energetic equivalent of O2 for nutrient oxidations, were constantly larger than basal rates. The two 60-min time integrals of this increase in metabolic rate were equal [30.3 +/- 3.7 and 31.0 +/- 3.9 (SE) J/g muscle wet weight (n = 9) for E and EO2 respectively]. During contracture however, E exceeded EO2 by 24% (4.7 +/- 1.7 J/g), and during the recovery period EO2 exceeded E by 21% (5.4 +/- 2.6 J/g). Whereas oxidative recovery of the energy lost by the preparation during 15-min contractures was complete, after longer contractures recovery did not occur or was incomplete. In keeping with the now prevalent idea that ion--namely Ca--transport activities are maintained foremost among cellular ATP-dependent processes and consume significant amounts of energy, the present finding that in a 15-min ionic contracture myocardium incurs not only some, but the maximum oxygen debt still compatible with complete oxidative recovery suggests that contracture tension is maintained at low energy cost, essentially by slow-cycling or "rigor" bridges as in hypoxic contractures, whereas heat is mainly related to intracellular calcium homeostasis.

Ca(2+)-dependent heat production under basal and near-basal conditions in the mouse soleus muscle.

1. The rate of energy expended for the clearance of sarcoplasmic Ca2+ by sarcoreticular Ca2+ uptake process(es), plus the concomitant metabolic reactions, was evaluated from measurements of resting heat production by mouse soleus muscle before and after indirect inhibition of Ca2+ uptake by sarcoplasmic reticulum (SR). 2. Direct inhibition of the Ca2+, Mg(2+)-ATPase of SR membrane in intact muscle preparations exposed to the specific inhibitor 2,5-di(tert-butyl-1,4-benzohydroquinone (tBuBHQ) slowly increased the rate of heat production (E). Indirect inhibition of SR Ca2+ uptake was obtained by reducing sarcoplasmic Ca2+ concentration (Ca2+i) as a consequence of reducing Ca2+ release from the SR using dantrolene sodium. This promptly decreased E by 12%. Exposure of the preparations to an Mg(2+)-enriched environment (high Mg2+) or to the chemical phosphatase 2,3-butanedione monoxime (BDM), two other procedures aimed at decreasing SR Ca2+ release, also acutely decreased E, by 20 and 24%, respectively. 3. Subthreshold-for-contracture depolarization of the sarcolemma achieved by increasing extracellular K+ concentration to 11.8 mM induced a biphasic increase of E: an initial peak to 290% of basal E, followed by a plateau phase at 140% of basal E during which resting muscle tension was increased by less than 3%. Most, if not all, of the plateau-phase metabolic response was quickly suppressed by dantrolene or high Mg2+ or BDM. Another means of increasing SR Ca2+ cycling was to partially remove the calmodulin-dependent control of SR Ca2+ release using the calmodulin inhibitor W-7. The progressive increase in E with 30 microM-W-7 was largely reduced by dantrolene or high Mg2+ or BDM. 4. In the presence of either dantrolene or BDM to prevent the effect of W-7 on SR Ca2+ release, exposure of the muscle to W-7 acutely suppressed about 3% of E. This and the above results confirm that the plasmalemmal, calmodulin-dependent Ca(2+)-ATPase, although a qualitatively essential part of the Ca2+i homeostatic system of the cell, can only be responsible for a very minor part of the energy expenditure devoted to the homeostasis of Ca2+i. Active Ca2+ uptake by SR which, at least in the submicromolar range of Ca2+i, is expected to be responsible for most of this Ca(2+)-dependent energy expenditure, might dissipate up to 25-40% of total metabolic energy in the intact mouse soleus under basal and near-basal conditions.

Control of respiration in skeletal muscle at rest.

The suggestion is made that, under resting conditions in situ, muscle cell respiration is dependent on the way O2 and substrates are distributed to the cells by the microcirculation. (Delivery is measured as arterial-blood concentration multiplied by flow to the organ.) Microscale heterogeneity of this distribution, which is more marked but less stable than the more easily demonstrated larger-scale heterogeneity (0.1 to 0.5-g sampling grain), might indeed ration O2 and substrates in a large population of the cells of a resting organ at any given moment, and microscale heterogeneity of distribution may thus take part in the normal control of cell respiration.

[Components and control of cellular energy expenditures in endothermy]. / Composantes et contrôle de la dépense énergétique cellulaire chez l'endotherme.

Attempts to predict and to measure the energy cost of ionic homeostasis in tissue cells are briefly reviewed and attention is drawn to the importance of ion-flux--as well as ion-gradient--maintenance for the preservation of cell structure and function. The energetic consequences of acute and chronic adjustments of two primary-active transport processes, Na-K transport across plasma(sarco) lemma and Ca transport across the endo(sarco)plasmic-reticular membrane, are illustrated. The question of the contribution of protein turnover to the energy expenditure of cell maintenance is raised, but not answered. After looking back on the now well-established concepts of the "intrinsic" cellular control of energy expenditure and the so-called "extrinsic" cellular control by intracellular calcium ion activities, it is suggested that the organ may also control cell metabolism under non-ischemic conditions, through heterogeneous distribution of arterial blood and erythrocytes to cells.

Chest-lung statics: a realistic analog for student laboratory.

A mechanical analog of the human lung-chest wall system was developed in Fribourg and Geneva Universities, Switzerland, to help students understand chest-lung statics. The equipment comprises a lung bellows, with upper airway connected to a three-way manifold, and a transparent chest whose lower part is another bellows that can be mobilized manually. Two water manometers measure intrapulmonary and intrathoracic pressures. The pressure-volume relationships of the lung-chest wall analog, which are essentially determined by the diameters of the bellows and the strains imposed by steel coils, closely parallel those of the human respiratory system. The chest can be opened to demonstrate pneumothorax. A first, guided manipulation of the model at the physiology laboratory provides excellent preparation for--or useful complement to--a human subject experiment on chest-lung statics. Unguided, further use of the model provides an opportunity for students to teach each other. Since the model is used, mean score on chest-lung statics at the practical examination is as good as that on other, more easy subjects.

Evidence by calorimetry for an activation of sodium-hydrogen exchange of young rat skeletal muscle in hypertonic media.

1. The rate of energy dissipation associated with Na(+)-H+ exchange in isolated, superfused soleus muscles from young rats was measured with an isothermal microcalorimeter during quasi-stationary states of oxidative metabolism. 2. Under normal physiological conditions, amiloride, an inhibitor of the Na(+)-H+ exchange across plasma membranes, had no measurable effect on the specific rate of muscle heat production (E); the ouabain-suppressible part of E was identical whether amiloride was absent or present. 3. E was increased under hyperosmotic conditions and the difference with respect to control (excess E) was proportional to the degree of hyperosmolarity of the superfusate. It was 48% of basal E during a +100 mosM stress (with no change of extracellular Na+ concentration, Na+o). Inhibition of Ca2+ release into the sarcoplasm with sodium dantrolene (10(-5) M) or tetracaine (5 x 10(-5) M) suppressed a substantial part (65 and 53%, respectively) of the steady-state excess E (1.2 mW (g wet weight)-1) induced by the +100 mosM stress. Practically 100% of excess E was suppressed in the nominal absence of extracellular sodium (Na+o = 0, Li+ substitution) or under 15 mM-Na+o, and excess E was enhanced when Na+o was increased (hyperosomolarity by addition of Na2SO4 instead of sucrose). 4. Under hyperosmotic conditions, amiloride at the 5 x 10(-7) M concentration had no effect on excess E whereas at 10(-4) M it induced a significant decrease of excess E. The absolute effect of 10(-4) M-amiloride was -0.34 mW (g wet weight)-1 (equal to 28% of the excess E due to a +100 mosM-sucrose stress and to 14% of the excess E due to a +100 mosM-Na2SO4 stress). It was left unaltered in the presence of dantrolene and was independent of the way the +100 mosM stress was obtained (i.e. 100 mM-sucrose or 50 mM-Na2SO4). It was suppressed at Na+o = 0-15 mM and could be mimicked by guanochlor, another potent inhibitor of Na(+)-H+ exchange. In the presence of 10(-4) M-amiloride, the ouabain-suppressible E was significantly reduced. In the presence of ouabain, amiloride had no effect. 5. Muscle tissue space available to [3H]inulin was measured in parallel experiments. It was 23.3% under control conditions and 30.6% after a 2 h exposure of the muscle to a +100 mosM-Na2SO4 stress.(ABSTRACT TRUNCATED AT 400 WORDS)

Is resting muscle oxygen uptake controlled by oxygen availability to cells?

To estimate oxidative capacity of noncontracting rat skeletal muscle, the isolated gracilis muscle was perfused at various high flow rates with high-PO2 (88 kPa) saline-albumin solution and simultaneously perifused at either low (6.3 kPa) or high PO2 in a calorimeter at 28 degrees C. Under low-PO2 perifusion, specific O2 consumption and heat production rates (MO2 and E, respectively) were flow-rate dependent. E values were all larger than those obtained on blood-perfused preparations at 28 degrees C. MO2 reached 0.47 mumol.min-1.g muscle-1 and E reached 4 mW/g. Normalized to 36 degrees C by means of activation energies determined from 30 and 36 degrees C measurements on nonperfused gracilis strips, these maxima correspond to three times the largest MO2 measured by other authors in blood-autoperfused gracilis. Increasing perifusion PO2 from 6.3 to 88 kPa sharply decreased MO2. These results confirm that MO2 of blood-perfused skeletal muscles in vitro (and a fortiori in vivo) is kept much below its maximum for a noncontracting organ; they also suggest that this maximum MO2 is not necessarily an effect of unphysiologically high PO2 in the tissue cells.

Thyroid status and noradrenaline-induced regulatory thermogenesis in heat acclimated rats.

Adjustments of the obligatory and regulatory thermogenesis upon heat acclimation (34 degrees C) and perchlorate treatment were observed in male rats. Resting oxygen consumption measured at neutral temperature was reduced, with respect to control, by 23, 27, and 34% in heat acclimated, perchlorate treated, and heat acclimated-perchlorate treated rats, respectively. Administration of 0.4 mg NA/kg increased oxygen consumption by 40, 30, 5 and 1% above resting level in control, heat acclimated, perchlorate treated, and heat acclimated-perchlorate treated rats, respectively. Whereas significant interaction was found between the effects of thyroid hormones and acclimation temperature on obligatory thermogenesis, the interaction of these factors on regulatory thermogenesis was not statistically significant. Still, hypothyroidism may be considered a thermoregulatory advantage during chronic heat exposure.

Triiodothyronine (T3)-induced thermogenesis: altered T3-efficiency in tissues from fed, starved, and refed hypothyroid rats.

A microcalorimetric study of perifused tissue samples obtained from hypothyroid thyroidectomized rats killed 15 h after a single injection of T3 was conducted in order to observe at the tissue level, and in a constant environment, the T3-dependent thermogenesis induced in fed, starved, and refed states. When 9 micrograms T3/100 g BW had been administered to fed animals, tissue heat production rate (E) increased in liver, soleus muscle, and myocardium. In kidney cortex an increase in E was observed only after 90 micrograms T3. A dose-response study was performed with liver samples, in which both oxygen consumption and heat production rates were measured. Liver and soleus muscle were then further investigated. T3-dependent thermogenesis could not be demonstrated in tissues obtained from rats which had been starved for 3 days before receiving 9 micrograms T3/100 g BW. After a small carbohydrate intake corresponding to about 60 kJ/rat (refed state; 1 kJ congruent to 0.4 kcal) given over a 3-h period preceding the injection of T3, T3-dependent thermogenesis was again present. It is concluded that differences in T3 dependent thermogenesis similar to those previously observed in animals under different nutritional states continue to exist in vitro, when tissues are no longer exposed to differing levels of humoral factors.

Brown adipose tissue heat production in heat acclimated and perchlorate treated rats.

The noradrenaline-induced energy dissipation rate was measured with a direct microcalorimeter in brown adipose tissue taken from rats acclimated to 34 degrees C (HA), perchlorate treated (PC) and heat acclimated-perchlorate treated (HAPC). The response to 10(-7) M NA was reduced by 45%, 47% and 86% in HA, PC and HAPC groups, respectively, as compared to a control group kept at 24 degrees C. In the same groups, the response to 10(-6) M NA was reduced by 34%, 7% and 64%, respectively. The specific activity of the soluble alpha-glycerophosphate dehydrogenase in brown fat from HA rats was reduced by 50%, whereas it was not altered in the PC animals. It is concluded that the sensitivity to noradrenaline of the brown adipose tissue thermogenic mechanisms is decreased in hypothyroidism, and that the acclimation temperature and the thyroid status per se each have a different influence on brown adipose tissue function.

Energetics of active sodium-potassium transport following stimulation with insulin, adrenaline or salbutamol in rat soleus muscle.

The total metabolic energy expenditure associated with active Na-K-transport over the first 20 min of stimulation with insulin, adrenaline or salbutamol (delta HmNa-K) was determined from direct calorimetric and tracer ion flux measurements in isolated muscles at rest. The reversible work performed by the Na-K-pump during the same interval of time (WrevNa-K- was calculated as the product of the ouabain-suppressible Na-K transfers and the mean free energy increase imparted to the two ions as they are transported against their electrochemical gradients across the plasma membrane. Comparison of membrane potential and intracellular Na and K concentrations before and after the stimulation indicated that part of WrevNa-K had contributed to increase in ion electrochemical gradients in the preparation (i.e. had not been lost as heat) during the 20 min period. Accordingly, the maximum value of delta HmNa-K was taken as the sum of the ouabain-suppressible heat production and WrevNa-K. Following stimulation with insulin, adrenaline or salbutamol this maximum corresponded to 10, 10 and 12% respectively, of basal metabolism. Under the same three conditions, the minimum "energetic efficiency" of the active Na-K-transport process, defined as the ratio between WrevNa-K and maximum delta HmNa-K, was 35, 41 and 38%, respectively.

Brown adipose tissue metabolism in streptozotocin-diabetic rats.

Defects of both diet-induced thermogenesis and cold tolerance have been reported for streptozotocin-diabetic rats. Since brown adipose tissue (BAT) is a major effector of both diet- and cold-induced thermogenesis in the rat, the possible cause of these defects was investigated by comparing BAT metabolism under basal conditions and during activation by nerve stimulation, norepinephrine (NE), or octanoate addition in both streptozotocin-diabetic rats and in controls. The following metabolic indices were measured in rat interscapular BAT (IBAT): 1) tissue composition, 2) heat production rate as measured by direct microcalorimetry, 3) redox state of flavoproteins linked to the acyl-coenzyme A dehydrogenase pathway as measured by reflection spectrometry, 4) redox state of NAD(P) as measured by surface-emitted fluorescence, and 5) fatty acid activation and beta-oxidation activities in IBAT homogenate. In streptozotocin-diabetic rats, IBAT was atrophied (DNA content unmodified, protein and lipid content decreased). The basal and NE-stimulated total heat production rates showed a 75% and 56% decrease, respectively. The specific activity of fatty acid beta-oxidation as measured by flavoprotein redox state or enzymatically was decreased by 52% and 59%, respectively. The basal redox level of NAD(P) was about 3 times higher than in the controls and NE stimulation resulted in oxidation in contrast to the reduction observed in control tissues. These results show that the metabolic capacity of IBAT from streptozotocin-diabetic rats is decreased and further suggest that the reduced capacity for beta-oxidation contributes significantly to the metabolic alteration.

Defective diet-induced but normal cold-induced brown adipose tissue adaptation in hypothalamic obesity in rats.

our weeks after bilateral ventromedial hypothalamic (VMH) lesions in the female rat reared at 23 degrees C, the weight of the interscapular brown adipose tissue (IBAT) was doubled as compared to appropriate controls. Tested in vitro, the tissue of the lesioned animals showed, per unit weight, a basal and a noradrenaline--or octanoate--stimulated heat output about half of that of the tissue from the controls. However, basal and stimulated heat outputs as well as beta-oxidative capacity of IBAT from lesioned animals and their appropriate controls were the same when calculated per whole fat pad. The lesioned animals were hyperphagic, with a gross energy intake 70% larger than that of the controls. Cold acclimation at 5 degrees C for 3 weeks was found to restore the basal and stimulated heat outputs per unit weight of IBAT of the lesioned animals to the level of that of their cold acclimated controls. The weight of the tissue did not change significantly in lesioned animals upon cold exposure whereas controls exhibited the expected hypertrophy. Calculated per whole fat pad, the stimulated heat output became 33% larger in lesioned animals than in appropriate controls. The total beta-oxidative capacity increased by 3 fold in controls and 4.8 fold in lesioned animals. Cold exposure was followed by a mean increase of gross energy intake of 43% in the controls and 31% in the lesioned animals as compared to their gross energy intake at 23 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)