The regulation of energy metabolism and van't Hoff's rule in the homeotherm animal

Helgoland Marine Research, Dec 1966

Kurzfassung Gegenüber der älteren Ansicht, daß sich der Sauerstoffverbrauch von Geweben großer und kleiner Tiere in vitro nicht unterscheide und daher der Unterschied in vivo auf einer zentralen Regulation beruhe, wird heute ziemlich allgemein angenommen, daß dies nicht der Fall sei, sondern der Sauerstoffverbrauch in vivo keiner regulativen Dämpfung unterliege. Bei homoiothermen Tieren läßt sich die Frage der Regulation des Energiestoffwechsels im Zusammenhang mit der thermoregulatorischen Wärmeproduktion sowie bei Änderungen des Energiestoffwechsels nichtthermoregulatorischer Natur untersuchen. Bei thermoregulatorischen Änderungen des Energiestoffwechsels der Ratte konnte eine integrative Regulation der Wärmeproduktion nachgewiesen werden: bei Änderung der Beteiligung einzelner Teilprozesse (shivering und non-shivering thermogenesis) kann die Gesamtwärmebildung unverändert bleiben. Außerdem konnte gezeigt werden, daß der erhöhte Energiestoffwechsel mit Thyroxin behandelter Tiere in die thermoregulatorische Wärmeproduktion voll einbezogen wird. Versuche an Ratten mit bilateralen elektrolytischen Hypothalamus- und Epithalamusläsionen in niedrigen und hohen Umgebungstemperaturen sowie Ergebnisse über die Größe des Sauerstoffverbrauchs und der Körpertemperatur nach epithalamischen Läsionen bei niedrigen Sauerstoffdrucken erbrachten den Nachweis einer Regulation des Energiestoffwechsels nichtthermoregulatorischer Natur. Durch Ausbleiben einer Erhöhung des Energiestoffwechsels bei Hyperthermie nach Hypophysektomie, epithalamischen Läsionen etc. sowie anhand einer Analyse der Störungen der Regulation der Körpertemperatur und der Wärmeproduktion bei Hypothalamus- und Epithalamusläsionen konnte gezeigt werden, daß bestimmte Änderungen der Wärmeproduktion, die üblicherweise mit der van't Hoffschen Regel erklärt werden, durch zentralnervöse Mechanismen ausgelöst sind.

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The regulation of energy metabolism and van't Hoff's rule in the homeotherm animal

0 Institute of Pathophysiology, University MedicalSchool , P~cs , Hungary T h e regulation of energy m e t a b o l i s m and van't Hoff's rule in the h o m e o t h e r m animal KURZFASSUNG: Die Regulation des Energiestoffwechsels und die van't Hoffsche Regel beim homoiothermen Tier. Gegenliber der iilteren Ansicht, daf~ sich der Sauerstoffverbrauch yon Geweben grof~er und kleiner Tiere in vitro nicht unterscheide und daher der Unterschied in vivo auf einer zentralen Regulation beruhe, wird heute ziemlich allgemein angenommen, dai~ dies nicht der Fall sei, sondern der Sauerstoffverbrauch in vivo keiner regulativen D~impfung unterliege. Bei homoiothermen Tieren l~l~t sich die Frage der Regulation des Energiestoffwechsels im Zusammenhang mit der thermoregulatorischen W~irmeproduktion sowie bei F.nderungen des Energiestoffwechsels nichtthermoregulatorischer Natur untersuchen. Bei thermoregulatorischen F_nderungen des Energiestoffwechsels der Ratte konnte eine integrative Regu= iatlon der W~irmeproduktion nachgewiesen werden: bei Yinderung der Beteiligung einzelner Teilprozesse (shivering und non-shivering thermogenesis) kann die Gesamtw~irmebildung unver~.ndert bleiben. Auf~erdem konnte gezeigt werden, daf~ der erh/Shte Energiestoffwechsel mit Thyroxin behandelter Tiere in die thermoregulatorische W~irmeproduktion roll einbezogen wird. Versuche an Ratten mit bilateralen elektrolytischen Hypothalamus- und Epithalamusl~.sionen in niedrigen und hohen Umgebungstemperaturen sowie Ergebnisse tiber die Gr/Si~e des Sauerstoffverbrauchs und der K/Srpertemperatur nach epithalamischen L~isionen bei niedrigen Sauerstoffdrucken erbrachten den Nachweis einer Regulation des Energiestoffwech= sels nichtthermoregulatorischer Natur. Dutch Ausbteiben einer Erh/Shung des Energiestoffwechsels bei Hyperthermie nach Hypophysektomie, epithalamischen L~isionen etc. sowie anhand einer Analyse der St/Srungen der Regulation der K/Srpertemperatur und der W~irmeproduktion bei Hypothalamus= und Epithalamusl~isionen konnte gezeigt werden, dai~ bestimmte _Knderungen der W~irmeprodnktion, die iiblicherweise mit der van't I-IoffschenRegel erkl~rt werden, durch zentralnerv&e Mechanismen ausgel&t sind. - (FIELD, BELDING& MARTIN 1939, KLEIt3ER1941, WEYMOUTH~x~FIELD 1942, KREI3S 1950, V. BERTALANFFY& PIKOZYNSKI1951, V. BEKTALANFFY& ESTWICK1953, V. BERTALANFFY& PIROZYNSKI1953, FUHRMAN& FUHRMAN 1951, LOCKER 1959) and, on the other hand, interpretation of the older results changed also by taking into account .c E 1.5 E SUBCUTIS Fig. I: Oxygen consumption, colonic temperature (9 to 10 cm from anus), lumbar muscle temperature and subcutaneous temperature in the lumbar region in a rat (0.6 g urethane per kg body weight).Temperatures were measured with thermocouples,oxygen consumption with a modifiedNoyons-Kipp diaferometer.(AEer Sz~Gv.&~, VgRNAI & DON~OFFER 1963) c rn E n e r g y m e t a b o l i s m a n d v a n ' t Hoff's rule Oe ml/dm2/min Fig. 2: Electrical activity of lumbar (upper record) and thigh muscles (lower record) in the rat (0.5 g urethane per kg body weight). No change occurred in oxygen consumption and in electrical activity during at least 4 minutes preceding the segments of records represented; no significant change in oxygen consumption with electrical activity of widely varying intensity. (After SZEGV~IRI,V~.RNAI& [DoNHOFFER1963) Fig. 3: Average oxygen consumption of I0 to 15 rats exposed to different environmental temperatures. Both control rats (white columns) and rats having received 150 to 200 /~g thyroxine per day for 6 to 8 weeks (striped columns) had been kept at room temperature. At 290 C - the indifferent temperature for normal rats - metabolic rates of thyroxinetreated individuals were more than 100 per cent higher. At lower temperatures metabolic rates of controls increased, whereas oxygen consumption of thyroxine-treated rats decreased until - between 10° and 15° C - the difference between metabolic rates of controls and thyroxine-treated rats disappeared. (After ANDIK,NAGY& TdTH 1955) cific dynamic action (SDA) of food disappears, i. e. is being integrated into thermoregulatory heat production, has also been questioned recently, and SDA and thermoregulatory heat production were shown to be additive (Bus~mK et al. 1960). No doubt, energy metabolism responds predictably to various stimuli, but the same might be the "~"\oo>\B%~-~o/ ,° o"o"o-O-~So~ MUSCLE ~-~,-a-A Fig. 4: Oxygen consumption of rat (0.07 g hexobarbital per kg body weight); temperature of colon, interscapular brown fat and of muscle under the brown fat. In a thermoneutrat environment (300 C). colonic- interscat~ular brown fat and muscle temperature are practically identical. A~er transfer into an ambient temperature of 180 C, temperatures of all three sites fall together for about 4 minutes; thereaiter - simultaneously with a marked increase in oxygen consumption - brown fat temperature increases sharply above the other two and maintains this level throughout cold exposure. (Atier DONHOFF~R& SZ~LI~NW1965) case in the absence of central regulation if only processes participating in oxygen consumption responded in a strictly determinate manner. In the homeotherm animal regulation of thermoregulatory heat production and of non-thermoregulatory changes in energy metabolism offer themselves for investigating the problem. Demonstration of non-shivering thermogenesls in the cold-adapted (CoTTLE & CAr~LSON1956, DEVOCAS1960) and the non cold-adapted rat (DoNHOFFER et al. 1957a) furnished the basis for analysing regulation of thermoregutatory heat Methodical details of these and of the following experimental observations can be omitted since they have been published elsewhere (DoN~IOFFZr,et aL 1958, MESTXAN et al. 1958, 1959a, b, SZEGVkl{I,VARNAI& DON~iOFFEt{1963, DONHOFF~I~& SZeL~NYt Energy metabolism and van't HoE's rule In the rat, processes associated with electrical activity of muscle may participate to a widely varying degree in thermoregulatory heat production without any change in total energy metabolism. Figure 1 illustrates an observation in which thermoregulatory heat production was not accompanied by electrical activity of muscle for several minutes, and thereaEer the onset of electrical activity failed to increase the metabolic rate further. Figure 2 demonstrates the electrical activity of the lumbar and femoral musculature aiter thermal balance had been established in an environment of 21 ° C. Evidently, electrical activity of very variable intensity was associated with a fairly steady level of total heat production. Since electrical activity in muscle is associated with an increase in local oxygen consumption, unchanged total heat production indicates that heat production has been o ° ° ' ° o A ° ~ ° ' ° / "o-o \ o \ COLON._. .37,5 O~ O , %_o.o%_o/~o°-o-o-o ~ --g I I I I I I I I I 1 I I I I I I I 1,,] i I I I, P q I I ! I I I I I 130 140 150 min Fig. 5: Oxygen consumption of rat (0.10 g hexobarbital per kg body weight); temperature of colon, interscapular brown fat and of muscle under the brown fat. At an ambient temperature of 180 C, interscapular brown fat temperature was considerably higher than either colonic or muscle temperature. When the rat had been transferred from the cold to the thermoneutral environment (300 C), oxygen consumption decreased immediately, and concurrently, temperature of the interscapular brown adipose tissue declined sharply, while deep colonic temperature and temperature of muscle underlying the brown fat pad showed no change. Evidently, concurrently with the decrease in oxygen consumption in the whole animal, heat production decreased sharply in the brown adipose tissue. (Al%r DON~OFF~R& SZ~L~NYI1965) reduced by a similar amount elsewhere, demonstrating integrative regulation of thermoregutatory heat production. The thyroxine-induced increase in heat production is also completely integrated into thermoregulatory heat production. The metabolic Fig. 6: Unanaesthetized rat, 48 hours after placing bilateral electrolytic lesions into the hypothalamus. Oxygen consumption (]el~) and colonic temperature (right) at an environmental temperature of 30° C (white columns) and of 20° C (striped columns). Oxygen consumption has been measured in three 15 minute periods; colonic temperature has been taken at the end of the third period when the rat had been exposed for 75 to 90 minutes to the experimental temperature. (After MEsTY~N et al. 1958) Fig. 7: Unaesthetized rat, thyroidectom.ized some weeks before, The experiment was performed 48 hours after the electrolytic lesions. Oxygen consumption (left) and colonic temperature (right) at 290 C (white columns) and at 200 C (striped columns). (After MEs-rxRN et at. 1958) rate of rats with severe hypermetaboIism in warmer environments does not exceed, and may even be somewhat lower than the metabolic rate of control rats in the same cold environment (Fig. 3). The discovery of the thermogenic role of brown fat (SMITH 1962, SMITH 1964, SMITt~ & HOCK 1963, SMITH & ROOtleTS 1964) and its dynamic thermoregulatory response, revealed at least one of the principal mechanisms of nonshivering thermogenesis (Figs. 4, 5). The reduction in the BMR (in a thermoneutral environment) observed not unfrequently aider bilateral hypothatamic lesions (GRAFE & GR/ONTHAL1929, M~STYkN et al. 1959b) might also be interpreted to indicate regulation of energy metabolism " - - ' ~ - ~ . / ' ' - ~ ' ~ t t t * I I I I I ! l ~ I t I 1 50 I00 150 min independently of thermoregulatory heat production. Such an interpretation would not be, however, quite convincing. The same applies even more to the frequent increases in the BMR aPcer hypothalamic and epithalamic lesions, which may, or may not, be associated with febrile body temperatures (M~sTYkN et al. 1958, M~sTYKN et al. i959a, b, DONHOFFERet al. 1959b). Regulation of energy metabolism of non-thermoregulatory origin might be investigated (a) after abolition of thermoregulation and (b) in the course of responses independent of thermoregulatory mechanisms. In the absence of thermoregulation, resting energy metabolism of the animal is generally held to follow van't Hoff's rule, i. e. to vary with body temperature with a Q10 between 2 and 3. Deviations from van't Hoff's rule, considered to originate in the peripheral tissues, have been observed by O'CONNOR (1949) in both poikilotherm and homeotherm animals. Nevertheless, any deviations from van't Hoff's rule of central origin in non-thermoregulatory responses, or a~er abolition of thermoregulation might furnish evidence for central regulation of energy metabolism independently of thermoregulatory heat production. Three types of observations seemed to offer p r o m i s i n g hints: (a) the relationship of b o d y t e m p e r a t u r e a n d o x y g e n c o n s u m p t i o n at e n v i r o n m e n t a l temperatures below the t h e r m o n e u t r a l zone aflcer h a v i n g abolished t h e r m o r e g u l a t o r y h e a t p r o d u c t i o n ; Fig. 9: Means and standard errors of oxygen consumption (leh) and colonic temperature (right) of intact rats (I) and rats with bilateral epithalamic lesions (L) which had abolished the response to hypoxia without irnparing the thermoregulatory increase in heat production in response to cold. Oxygen consumption and body temperature at 220 C and atmospheric pressure (white columns) and a pressure of 420 Hg mm (striped columns). At atmospheric pressure both oxygen consumption and body temperature are identical in the intact and the lesioned group, demonstrating that thermoregulation has not been impaired by the lesions. (A~er DONttOFFEt~et al. 1957b) o~ /// / 3z, Fig. 10: Unaesthetized rat with bilateral electrolytic lesions in the epithalamus. Oxygen consumption (left) and colonic temperature (right) at 30° C and atmospheric pressure (longitudinal stripes), at 23° C and atmospheric pressure (oblique str!pes), and at 23° C at a pressure of 420 mm Hg (white columns). That the response to hypoxla was a specific one is demonstrated convincingly by the fact that after restoring atmospheric pressure without any change in the ambient temperature, oxygen consumption and body temperature approached the level observed prior to exposure to hypoxia. (After DONHO~F~ et al. 1957) Energy metabolism and v a n ' t H o E ' s rule (b) analysis of the response of b o d y temperature and energy metabolism to h y p o x i a ; a n d (c) anaiysis of the increase in heat p r o d u c t i o n in response to hyperthermia. Rats in which t h e r m o r e g u l a t o r y heat p r o d u c t i o n h a d been abolished b y b i l a t e r a l electrolytic lesions in the hypothalamus, showed clearly t h a t although oxygen conFig. 11: Unanaesthetized rat with bilateral epithalamic lesions. Oxygen consumption (lelt) and rectal temperature (right) at an ambient temperature of 220 C and atmospheric pressure (white columns) and at the same temperature at 420 mm Hg (striped columns). The lesions had abolished the thermoregulatory increase in heat production; the metabolic rate was the same in an environment of 220 C as in a thermoneutrat one, but no hypothermla developed. Oxygen consumption failed to decline in response to exposure to an ambient pressure of 420 mm Hg; body temperature, however, declined by 30 C during the exposure to the reduced pressure. The specificity of this response is demonstrated by the fact that a&er restoring atmospheric pressure, body temperature reached again the pre-hypoxic level although there was no change in ambient temperature. (AflcerDONHOFFEt<et al. 1957b) Fig. 12: Oxygen consumption of intact rats exposed to various ambient temperatures in an environment practically saturated with water vapour. AlI differences, except for that between 100 and 70 C, are statistically significant. The increase in heat production at environmental temperatures leading to hyperthermia has never been missed in the intact animal sumption m a y fail to increase subsequent to exposure to a cool environment, it m a y be m a i n t a i n e d at the same level in spite of a fall in b o d y temperature of several centigrades (Figs. 6, 7). Somewhat similar observations were m a d e b y Mt~STYKN et al. (1962) on premature neonates showing no signs of thermoregulation. B o d y temperature v a r i e d by more than 6o C, yet oxygen consumption remained u n & a n g e d (Fig. 8). Fig. I3: Oxygen consumption (left) and colonic temperature (right) of an unanaesthetized rat, hypophysectomized five months earlier, at an ambient temperature of 29° C (white columns) and during exposure to: (a) 35.0o C, (b) 37.5 ° C, (c) 38.5° C, (d) 39.50 C, respectively (longitudinal stripes). Despite hyperthermia no increase in heat production. (AEer BALOGI~ et al. 1952~ Fig. 14: Unanaesthetized rat having received 0A per cent of methylthiouracil in the food for five weeks. Oxygen consumption (Ief~) and colonic temperature (right) in an environment of 29.4o C (white columns), exposed to an ambient temperature of 22.9°.C (obI.i.que stripes) and in the course of exposure to: (a) 35.2o C, (b) 37.3o C and (c) 38.6o C (long, tudmal stripes). Methylthiouracil had abolished the metabolic response to hyperthermia, whereas the metabolic response to cotd was not impaired. (After BALOGHet al. 1952) These observations u n d o u b t e d l y indicate that even in the absence of thermoregulatory responses energy metabolism is not governed b y v a n ' t H o f t ' s rule. H o w ever, since heat p r o d u c t i o n remained unchanged, they do not demonstrate unequivocally that the metabolic rate is being integratively regulated. A t ambient temperatures below the thermoneutral zone the rat responds even to a moderate reduction of oxygen tension i n v a r i a b l y with a fall in oxygen consumption and body temperature (LINTZEL1931). It was possible to show that reduction of heat production and o f body temperature are both mediated by central nervous mechanisms, since the response could be abolished completely by epithalamic lesions Fig. 15: Oxygen consumption of rat (left) and colonic temperature (right) in a thermoneutral environment of 29° C (white columns) and at ambient temperatures of 35° C (longitudinal stripes) and 36° C (oblique stripes) before and after subcutaneous administration of urethane (arrow). Urethane abolished the response of oxygen consumption to hyperthermia completely. (After DONHOFF~Ret al. 1953a) ~38 Fig. 16: Oxygen consumption of rat (left) and colonic temperature (right) at an ambient temperature of 290 C (white columns) and at one of 36o C (longitudinal stripes) before and after subcutaneous administration of chloralhydrate (arrow). Chloralhydrate abolished the hyperthermic increase in heat production completely. (At°cerDONHOFFrRet al. 1953a) w i t h o u t necessarily impairing thermoreguIatory responses at normal atmospheric oxygen tension (Fig. 9). The high degree o f independence o f thermoregulatory and hypoxic responses has been pointed out also by observations in which thermoregulation had been severely impaired in the animal and yet the response to hypoxia has been maintained (DoNHOVFER et al. 1957b). Figure 10 illustrates an experiment conducted on a rat in which the lesions abolished the thermoregulatory response. At an ambient temperature of 230 C heat production failed to increase and body temperature decreased by 40 C. When oxygen tension was reduced to 420 mm Hg, oxygen consumption decreased by almost 50 per cent and body temperature fell an additional 30 C. The regulatory nature of the response is revealed by the fact that, without any change in ambient temperature, heat production rose to the initial level after atmospheric oxygen tension had been restored. In addition, the responses of body temperature and energy metabolism are not strictly Fig. 17: Unanaesthetized rat with bilateral electrolytic lesions in the epithalamus involving the ganglia habenulae. Oxygen consumption (lett) and colonic temperature (right) in a thermoneutraI environment (white columns) and at an ambient temperature of 360 C (longitudinal stripes). No increase in heat production despite very marked hyperthermia. (After DON~OFF~;Ret al. 1953a) linked. Figure 11 demonstrates the responses of a rat in which reactions of energy metabolism to hypoxia had been completely abolished by the epithalamic lesion, whereas body temperature dropped more than 3° C. Abolition of the hypoxic response of energy metabolism without impairment of the thermoregulatory response represents strong evidence for the existence of a central regulation of energy metabolism independent of the regulation of heat production. Evidence is strengthened further by observations in which the response to hypoxia persisted although thermoregulatory heat production had been abolished by the epithalamic lesions. The fact that the metabolic response to hypoxia and the thermoregulatory increase in heat production may be both abolished and body temperature may nevertheless fall by several centigrades during hypoxia, demonstrates that the hypoxic fall in heat production is not dependent on a mechanism governed by van't Hofl~'s rule. The mechanism of the increase in metabolic rate in response to hyperthermia has received little attention. According to the the generally held view, it finds a satisfactory explanation in the operation of van't Hoff's rule. The increase in oxygen consumption in hyperthermia represents a 100 per cent response; no exceptions were found in intact animals (Fig. 12). In addition, the increase in the metabolic rate is compatible with a Q~0 between 2 and 3. The generality of the phenomenon and the °C ~- 60 E o" Fig. 18: Unanaesthetized rat with bilateral lesions in the tuberal region of the hypothalamus. Oxygen consumption (leE) and colonic temperature (right) in a thermoneutral environment (white columns) at an ambient temperature of 350 C (longitudinal stripes) and at 200 C (oblique stripes). The lesions had abolished the thermoregulatory increase in heat production in response to cold, whereas the metabolic response to hyperthermia had been preserved. (ARer MESTYkNet al. 1959a) Fig. 19: Unanaesthetized rat with bilateral epithalamic lesions involving both ganglia habenulae. Oxygen consumption (ICE) and colonic temperature (right) at an ambient temperature of 290 C (white columns), 360 C (longitudinal stripes) and 230 C (oblique stripes). The increase in heat production in response to hyperthermia had been abolished by the lesions, whereas the metabolic response to cold was not impaired. (Ai%r DONHOFFERet al. 1953a) compatibility of the Q10 with v a n ' t Hoff's rule represent all the evidence for the ruling assumption. With some benevolence this evidence might perhaps be called circumstantial, however, it has been almost unanimously accepted. It can be demonstrated convincingly in several ways, that this generally held Oxygen consumption and colonic temperature of thyroidectomized, hypophysectomized and methylthiouracil treated rats in response to hyperthermia; means and standard errors. (ARer DONnOFFEt~et aI. 1953b) 02 consumption ml/dm2/h Body temperature Indifferent temperature: 29°C High temperature: 35° to 37° C Before thyroxin After thyroxin Before thyroxin Aiderthyroxin Oxygen consumption and colonic temperature of rats with bilateral hypothalamic lesions at ambient temperatures of 29° and 35° C in the presence and absence of metabolic response to hyperthermia; means and standard errors. (After DONUOFFE~et al. 1959a) Hyperthermic increase maintained n = 36 Hyperthermic increase absent n = 30 Table 2 demonstrates the same situation in animals with hypothalamic lesions. Body temperature rose in the w a r m environment to the same level whether the increase in oxygen consumption had been abolished by the lesion or not. These results suggest that the metabolic response to hyperthermia is not linked to thermoregulatory mechanisms and, of course, show also that hyperthermia is not simply the consequence of passive heat storage but represents a b o d y temperature regulated at a higher level. 1. Shivering and non-shivering thermoregulatory heat production in response to cold as well as exposure of thyroxine~treated rats to low temperatures demonstrate the existence of an integrative regulation of energy metabolism. 2. Responses of rats with hypothalamic and epithalamic lesions to cold and heat, and with epithalamic lesions to hypoxia furnished evidence for central regulation of energy metabolism independently of thermoregulation. 3. By abolishing the increase in heat production in response to hyperthermia and by analysis of observations on animals with hypothalamic and epithalamic lesions, it could be demonstrated convincingly that responses of energy metabolism, apparently compatible with v a n ' t Hoff's rule, are actually mediated by central nervous mechanisms. Diskussion irn Anschlufl an den Vortrag DONHOFFER BaOCK: L~iflt si& aus Ihren Befunden s&on erkennen, ob der Anteil der O2-Aufnahme, der ha& Hypothatamusl~isionen die ha& der RGT-Regel zu erwartende O2-Aufnahme iibersteigt, auf Muskelaktivit~it oder auf Stoffwechselsteigerungen in anderen Organen - wie etwa im braunen Fett - zurii&zufiihren sind? DONHOFFEe: Ihre Frage ist ni&t leicht zu beantworten. Eine gewisse Regulation mug man voraussetzen. Setzt man die Tiere der K~ilte aus, so erhiilt man die gezeigten Resultate. Setzt man die Tiere der Wilrme aus, so finder man dieses Herausspringen des braunen Fettes iiberhaupt nicht. DO~HOFFE~:Nattirlich gibt es diese Me&anismen. Die Veritnderungen treten abet je na& den L~isionens&lagartlg ein und kommen nach einer gewissen Zeit zur vollkommenen Restitution. Es handelt si& bei den Versu&en um die vers&iedenartigsten Folgen, die wir anatomisch auch nicht scharf lokalisieren konnten. STt~m3ELT:Hubert Sie den Sauerstoffverbrauch integral tiber einen gr6geren Zeitraum gemessen oder blieb er yon vornherein konstant? DONHOFVE: Der O~-Verbrauch wurde fiber drei 15-min-Perioden gemessen, nachdem sich das Tier 25 his 30 min bei einer bestimmten Temperatur befunden hatte. Viele L~/sionenbedingen eine glei&zeitige St6rung der chemischen Regulation und der Regulation der K/Srpertemperatur; ich wollte solche F~illezeigen, in denen diese Reaktionen dissoziieren. S'rRuBELT:Wenn Sie den Sauerstoffverbrau& mit einer Apparatur messen, die ihn kontinuierli& ffir jede Minute registriert, erhalten sie einen initialen AbfalI und nach 10 min eine gegenregulatorische Steigerung. Messen Sie integral iiber 15 min, entsteht der Eindru&, als ob der O~-Verbrauch konstant geblieben sei. In Wirkli&keit handelt es si& um zwei voneinander getrennt ablaufende Vorg~/nge. DONI~OFFER: Auch bei kurzfristigen Messungen haben wir keinen vorfibergehenden Abfall des Sauerstoffverbrauches gesehen. ZEISBERCgI~:(t) Were the animals used in your experiment adapted to a certain temperature? According to our experiments a correlation exists between the acclimation temperature and the amount of nonshivering heat production. The rats acclimated to 0° and - 40 C respectively had the greatest nonshivering heat production. Animals adapted to + 300 did not use the nonshivering heat production of noradrenaline type and used the shivering heat production instantaneously after cold exposition. (2) Did you measure the colonic temperature? At what time was the temperature &ange presented in your pictures measured? DONHOFFER: Our animals were adapted to room temperature. In part of the experiments colonic temperature was measured continuously, in other experiments we measured at the end of the Os-consumption measurements, that is, about IV-2hour aiter the animals became adapted. WIESER: Ihre Versu&e lassen si& so deuten, daf~ es eine Ums&aItung yon zentraler zu peripherer Thermogenese gibt, ohne daft es hierbei zu einer Verminderung des Sauerstoffverbrauchs kommt. Erg~inzend m6&te i& auf den Befund yon H. ROttXACHER(Wien) hinweisen, der die Mikroschwingungen yon Muskeln untersu&te. Er land, dug deren Frequenz bei Transferierung der Tiere yon der KS.lte in die WS.rmeunerwarteterweise zunimmt. Eine Erkl~irung w~ire mgglich, wenn man eine zentrai gesteuerte Verlagerung yon zentraler zu peripherer Thermogenese annimmt und wenn bei letzterer mehr WS.rmeabgestrahlt wird als bei ersterer. DONHOFFeR:Sicher spielt bei der Thermogenese die elektris&e Aktivit~it der Muskeln eine Rolle. SCHARF: Experimentell zu unters&eiden sind Auskiinite fiber das s&nelle (sec, min), das mittelschnelle (Std., Tage) und das tr~ige (Tage, Wo&en) arbeitende System der Stoffwe&selregulationen. Rasch reagierende Regulationen ktinnen nur mit automatischen Dauerregistrierungen zu sinnvollen Ergebnissen fiihren, am geeignetsten sind Meg-Registrierverfahren na& dem Prinzip der Leitf~ihigkeitsmessung. Fiir mittelschnell und tr~ige arbeitende Regulationen ist die integrative Messung bequemer und billiger. DONHOFFeR: Wir haben mit einer neuen Methode gearbeitet, die sehr s&nelle, zugleich abet auch Iangfristige Messungen gestattet. AND~K, I., NAGY, L. & T6TH , I. , 1955 . Uber die Wirkung der Umgebungstemperatur auf den Stoffwechsel normaier und mit Thyroxin behandelter Ratten . Acta physiol , hung. 8 , 399 - 404 . BALOGH, L., DONHOEEER, Sz., MESTYX~V ,GY., PAl', T. & T6TEt , I. , 1952 . The response of oxygen consumption of thyroidectomized, hypophysectomized and methylthiouracil treated rats to high environmental temperatures and the action of thyroxine thereon . Acta physiol. hung . 3 , 395 - 403 . BE ~TALANFFY,L. & EsTwmi % R. R. , 1953 . Tissue respiration of musculature and body size . Am. J. Physiol . 173 , 58 - 60 . - - & PItiOZYNSXI , W. J. , 1951 . Tissue respiration and body size . Science , N. Y . 118 , 599 - 600 . - - - - 1953 . Tissue respiration, growth, and basal metabolism . Biol. Bull. mar. biol. Lab ., Woods Hole 105 , 240 - 256 . BUSK1RK , E. R. , THOMPSON,R. 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Szilard Donhoffer. The regulation of energy metabolism and van't Hoff's rule in the homeotherm animal, Helgoland Marine Research, 1966, 541-558, DOI: 10.1007/BF01611644