Evidence of a defect in energy expenditure in 7-day-old Zucker rat (fa/fa)

The aim of the investigation was to see whether a defect in energy expenditure could be found in the Zucker rat at the onset of obesity. Obese (fa/fa) and lean (Fa/fa) 7-day-old pups were studied at three ambient temperatures. At 33 degrees C fa/fa pups showed a reduction in oxygen consumption, respiratory CO2 production, in vivo oxidation of injected [1-14C]palmitic acid, as well as in core temperature. When the pups were kept at 28 degrees C, the difference between genotypes was considerably accentuated, thus indicating a subnormal thermogenic response of the fa/fa pups to a mildly cold environment. At 20 degrees C, however, the metabolic rates dropped to the same low level, and the core temperature equilibrated with ambient temperature in both genotypes. The results demonstrate that the 1-wk-old fa/fa pup has a defect in thermoregulatory thermogenesis. The magnitude of the deficit in energy expenditure was more than adequate to account for the 50% greater fat content of 7-day-old fa/fa pups.

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Analysis of energy expenditure at different ambient temperatures in mice lacking DGAT1

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00248.2002 ◽

2003 ◽

Vol 284 (1) ◽

pp. E213-E218 ◽

Cited By ~ 50

Author(s):

Hubert C. Chen ◽

Zuleika Ladha ◽

Steven J. Smith ◽

Robert V. Farese

Keyword(s):

Food Intake ◽

Energy Expenditure ◽

Ambient Temperature ◽

Cold Environment ◽

Normal Surface ◽

Ambient Temperatures ◽

Active Mechanism ◽

Key Enzyme ◽

Secondary Mechanism ◽

Obesity Resistance

Mice lacking acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1), a key enzyme in triglyceride synthesis, have increased energy expenditure and therefore are resistant to obesity. Because ambient temperature can significantly affect energy expenditure in mice, we undertook these studies to determine the effects of different ambient temperatures on energy expenditure, food intake, and thermoregulation in DGAT1-deficient [ Dgat1(−/−)] mice. Dgat1(−/−) mice had increased energy expenditure irrespective of changes in the ambient temperature. Although core temperature was normal, surface temperature was increased in Dgat1(−/−) mice, most likely reflecting an active mechanism to dissipate heat from increased thermogenesis. Dgat1(−/−) mice had increased food intake at baseline, and this hyperphagia became more pronounced upon exposure to cold. When fasted in a cold environment, Dgat1(−/−) mice developed hypothermia, which was associated with hypoglycemia. These results suggest that the hyperphagia in Dgat1(−/−) mice is a secondary mechanism that compensates for the increased utilization of fuel substrates. Our findings offer insights into the mechanisms of hyperphagia and increased energy expenditure in a murine model of obesity resistance.

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Calculation of substrate oxidation rates in vivo from gaseous exchange

Journal of Applied Physiology ◽

10.1152/jappl.1983.55.2.628 ◽

1983 ◽

Vol 55 (2) ◽

pp. 628-634 ◽

Cited By ~ 1244

Author(s):

K. N. Frayn

Keyword(s):

Ketone Bodies ◽

Fat Oxidation ◽

Nitrogen Excretion ◽

Co2 Production ◽

Gaseous Exchange ◽

Oxidation Rates ◽

The Difference ◽

Urinary Nitrogen Excretion ◽

Urinary Nitrogen

This paper reviews the assumptions involved in calculating rates of carbohydrate and fat oxidation from measurements of O2 consumption, CO2 production, and urinary nitrogen excretion. It is shown that erroneous results are obtained in the presence of metabolic processes such as lipogenesis and gluconeogenesis. The apparent rates calculated under these conditions can, however, be interpreted as net rates of “utilization.” Thus the apparent rate of carbohydrate oxidation is the sum of the rates of utilization for oxidation and for lipogenesis minus the rate at which carbohydrate is formed from amino acids. The apparent rate of fat oxidation is the difference between the rates of oxidation and synthesis from carbohydrate, so that the apparently negative rates encountered in patients infused with glucose do quantitatively represent net rates of synthesis. Other processes such as synthesis of ketone bodies or lactate at rates greater than their utilization can also disturb the calculations, but the magnitude of the effect can be estimated from appropriate measurements. Methods of correcting the observed gaseous exchange in these circumstances are given.

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Sweating responses to central and peripheral heating in spinal man

Journal of Applied Physiology ◽

10.1152/jappl.1976.40.5.701 ◽

1976 ◽

Vol 40 (5) ◽

pp. 701-706 ◽

Cited By ~ 34

Author(s):

J. A. Downey ◽

C. E. Huckaba ◽

P. S. Kelley ◽

H. S. Tam ◽

R. C. Darling ◽

...

Keyword(s):

Core Temperature ◽

Rapid Decrease ◽

Central Temperature ◽

Ambient Temperatures ◽

The Core ◽

Central Heating ◽

Temperature Thresholds ◽

Skin Cooling ◽

Skin Temperatures

Studies of central and peripheral heating of a resting spinal man (T6) were performed under various ambient temperatures (20–34 degrees C). It was found that at a constant core temperature, sweating could not be initiated by sentient skin heating alone, but skin cooling alone did produce a rapid decrease in sweating response. Central heating alone induced sweating responses and the central temperature thresholds of sweating were inversely related to the ambient (sentient skin) temperatures. The local and mean sweating rates were found to be linearly related to the core temperature. The slopes of local sweating rates versus the core temperature vary increasingly with the following locations: chest, forearm, and forehead; but the slopes of mean sweating rates versus core temperature were essentially constant.

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Evaluation of the accuracy of body temperature measurement using external radio transmitters

Canadian Journal of Zoology ◽

10.1139/z96-196 ◽

1996 ◽

Vol 74 (9) ◽

pp. 1778-1781 ◽

Cited By ~ 59

Author(s):

Doris Audet ◽

Donald W. Thomas

Keyword(s):

Body Temperature ◽

Core Temperature ◽

Field Conditions ◽

Temperature Sensitive ◽

External Temperature ◽

Ambient Temperatures ◽

Body Temperature Measurement ◽

Radio Transmitters ◽

The Difference ◽

Skin Temperatures

The facultative depression of body temperature represents an important energy strategy for small homeotherms. However, measuring body temperature under field conditions by means other than externally attached temperature-sensitive radio transmitters is problematical. We show that skin temperatures measured by external radio transmitters can accurately reflect core temperature for the bat Carollia perspicillata. We compared body and skin temperatures at three ambient temperatures (Ta; 21, 26, and 31 °C). The difference between skin and body temperature (ΔT) was linearly correlated with Ta and can be predicted by ΔT = 4.396 − 0.118Ta. We argue that external temperature-sensitive radio transmitters can provide a reliable index of core temperature and so permit the study of torpor or facultative hypothermia under field conditions.

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Physiological levels and action of dehydroepiandrosterone in Yucatan miniature swine

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.2001.281.1.r1 ◽

2001 ◽

Vol 281 (1) ◽

pp. R1-R9 ◽

Cited By ~ 5

Author(s):

A. R. Tagliaferro ◽

A. M. Ronan

Keyword(s):

Body Weight ◽

Energy Expenditure ◽

Miniature Swine ◽

Serum Triglycerides ◽

Lipid Utilization ◽

Treatment Conditions ◽

Plasma Insulin Levels ◽

The Difference

The biological role of dehydroepiandrosterone (DHEA) and its less active sulphated conjugate DHEAS was investigated in two experiments using Yucatan miniature swine. In experiment 1, plasma levels of both DHEA(S) among males were greater than female pigs that ranged in age from 0.3 to 84 mo old ( P< 0.0001). In males, DHEA(S) were related inversely to serum triglycerides; DHEA was positively related to triglycerides in females ( P < 0.01). In experiment 2, four 2-yr old male pigs, used as their own control, showed a 5% decrease in body weight, 11% increase in energy expenditure, 88% increase in lipid, and 100% decrease in glucose utilization ( P < 0.0001) in response to DHEA vs. placebo treatments when adjusted for body weight. Plasma DHEA(S) were not different between treatment conditions. Glucose tolerance and plasma insulin levels were not different from controls. In vivo response to norepinephrine indicated β-adrenergic sensitivity was altered by DHEA. Present findings suggest DHEA and/or its hormone products are important in modulating energy expenditure and lipid utilization for energy in male animals. The role of DHEA in energy metabolism and the difference between sexes warrant further investigation.

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Revision of calculations in the doubly labeled water method for measurement of energy expenditure in humans

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1994.267.6.e805 ◽

1994 ◽

Vol 267 (6) ◽

pp. E805-E807 ◽

Cited By ~ 5

Author(s):

W. A. Coward ◽

P. Ritz ◽

T. J. Cole

Keyword(s):

Experimental Study ◽

Energy Expenditure ◽

Recent Work ◽

Isotope Dilution ◽

Rate Constants ◽

Isotope Fractionation ◽

Co2 Production ◽

Doubly Labeled Water ◽

Doubly Labeled Water Method ◽

The Difference

In the doubly labeled water (DLW) method for the measurement of energy expenditure in humans, the basis of the calculation for CO2 production is the difference between the products of the rate constants for the disappearance of 18O and 2H from body water (KO, and KD, respectively) and the matching isotope dilution spaces (NO and ND, respectively). Thus, omitting corrections for isotope fractionation, CO2 production = 0.5 (KONO-KDND). In this calculation, it is also customary to normalize observed NO and ND values to a fixed value for ND/NO. The increasing use of the method has resulted in the generation of substantially more information on the normal value for ND/NO than existed at the time the method was first developed, and recent work has suggested that revisions of the originally used value of 1.03 may now be deemed appropriate. Values of 1.034 or 1.0427 have recently been suggested, but when applied in energy expenditure studies these estimates would lead to significantly different expenditure measurements. It can, however, be shown from published work and direct experimental study that ND/NO values are method dependent, and for these reasons the lower revised value of 1.034 appears to be more acceptable. The possibility that particular populations may ultimately be shown to be different from 1.034 should not, however, be dismissed entirely, and for this reason we suggest that information derived in individual experiments could be used in a Bayesian fashion to generate new ND/NO estimates. The appropriate techniques are described.

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Energy expenditure by doubly labeled water: validation in humans and proposed calculation

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1986.250.5.r823 ◽

1986 ◽

Vol 250 (5) ◽

pp. R823-R830 ◽

Cited By ~ 67

Author(s):

D. A. Schoeller ◽

E. Ravussin ◽

Y. Schutz ◽

K. J. Acheson ◽

P. Baertschi ◽

...

Keyword(s):

Energy Expenditure ◽

Isotope Dilution ◽

Isotope Ratio Mass Spectrometry ◽

Co2 Production ◽

Doubly Labeled Water ◽

Adult Males ◽

Doubly Labeled Water Method ◽

The Difference ◽

Total Body ◽

Atom Percent Excess

To further validate the doubly labeled water method for measurement of CO2 production and energy expenditure in humans, we compared it with near-continuous respiratory gas exchange in nine healthy young adult males. Subjects were housed in a respiratory chamber for 4 days. Each received 2H2(18)O at either a low (n = 6) or a moderate (n = 3) isotope dose. Low and moderate doses produced initial 2H enrichments of 5 and 10 X 10(-3) atom percent excess, respectively, and initial 18O enrichments of 2 and 2.5 X 10(-2) atom percent excess, respectively. Total body water was calculated from isotope dilution in saliva collected at 4 and 5 h after the dose. CO2 production was calculated by the two-point method using the isotopic enrichments of urines collected just before each subject entered and left the chamber. Isotope enrichments relative to predose samples were measured by isotope ratio mass spectrometry. At low isotope dose, doubly labeled water overestimated average daily energy expenditure by 8 +/- 9% (SD) (range -7 to 22%). At moderate dose the difference was reduced to +4 +/- 5% (range 0-9%). The isotope elimination curves for 2H and 18O from serial urines collected from one of the subjects showed expected diurnal variations but were otherwise quite smooth. The overestimate may be due to approximations in the corrections for isotope fractionation and isotope dilution. An alternative approach to the corrections is presented that reduces the overestimate to 1%.

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Enhancement of ADP-induced Platelet Aggregation by Adrenaline in Vivo and Its Prevention

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647788 ◽

1973 ◽

Vol 29 (02) ◽

pp. 490-498 ◽

Cited By ~ 6

Author(s):

Hiroh Yamazaki ◽

Itsuro Kobayashi ◽

Tadahiro Sano ◽

Takio Shimamoto

Keyword(s):

Platelet Count ◽

Platelet Aggregation ◽

Platelet Rich Plasma ◽

The Other ◽

Endothelial Surface ◽

Important Interaction ◽

Blood Coagulability ◽

The Difference

SummaryThe authors previously reported a transient decrease in adhesive platelet count and an enhancement of blood coagulability after administration of a small amount of adrenaline (0.1-1 µg per Kg, i. v.) in man and rabbit. In such circumstances, the sensitivity of platelets to aggregation induced by ADP was studied by an optical density method. Five minutes after i. v. injection of 1 µg per Kg of adrenaline in 10 rabbits, intensity of platelet aggregation increased to 115.1 ± 4.9% (mean ± S. E.) by 10∼5 molar, 121.8 ± 7.8% by 3 × 10-6 molar and 129.4 ± 12.8% of the value before the injection by 10”6 molar ADP. The difference was statistically significant (P<0.01-0.05). The above change was not observed in each group of rabbits injected with saline, 1 µg per Kg of 1-noradrenaline or 0.1 and 10 µg per Kg of adrenaline. Also, it was prevented by oral administration of 10 mg per Kg of phenoxybenzamine or propranolol or aspirin or pyridinolcarbamate 3 hours before the challenge. On the other hand, the enhancement of ADP-induced platelet aggregation was not observed in vitro, when 10-5 or 3 × 10-6 molar and 129.4 ± 12.8% of the value before 10∼6 molar ADP was added to citrated platelet rich plasma (CPRP) of rabbit after incubation at 37°C for 30 second with 0.01, 0.1, 1, 10 or 100 µg per ml of adrenaline or noradrenaline. These results suggest an important interaction between endothelial surface and platelets in connection with the enhancement of ADP-induced platelet aggregation by adrenaline in vivo.

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Reliability of a Single β-Thromboglobulin Measurement in a Diabetic Population : Importance of PGE1 in Anticoagulant Mixture

Thrombosis and Haemostasis ◽

10.1055/s-0038-1651094 ◽

1987 ◽

Vol 57 (02) ◽

pp. 201-204 ◽

Cited By ~ 2

Author(s):

P Y Scarabin ◽

L Strain ◽

C A Ludlam ◽

J Jones ◽

E M Kohner

Keyword(s):

In Vitro Release ◽

Mean Value ◽

Reliable Estimate ◽

Diabetic Patients ◽

Single Measurement ◽

Diabetic Population ◽

The Difference ◽

Vitro Release

SummaryDuring the collection of samples for plasma β-thromboglobulin (β-TG) determination, it is well established that artificially high values can be observed due to in-vitro release. To estimate the reliability of a single β-TG measurement, blood samples were collected simultaneously from both arms on two separate occasions in 56 diabetic patients selected for a clinical trial. From each arm, blood was taken into two tubes containing an anticoagulant mixture with (tube A) and without (tube B) PGE!. The overall mean value of B-TG in tube B was 1.14 times higher than in tube A (p <0.01). The markedly large between-arms variation accounted for the most part of within-subject variation in both tubes and was significantly greater in tube B than in tube A. Based on the difference between B-TG values from both arms, the number of subjects with artifically high B-TG values was significantly higher in tube B than in tube A on each occasion (overall rate: 28% and 14% respectively). Estimate of between-occasions variation showed that B-TG levels were relatively stable for each subject between two occasions in each tube. It is concluded that the use of PGEi decreases falsely high B-TG levels, but a single measurement of B-TG does not provide a reliable estimate of the true B-TG value in vivo.

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Tele-Substitution Reactions in the Synthesis of a Promising Class of Antimalarials

10.26434/chemrxiv.12212927 ◽

2020 ◽

Author(s):

Marat Korsik ◽

Edwin Tse ◽

David Smith ◽

William Lewis ◽

Peter J. Rutledge ◽

...

Keyword(s):

Heterocyclic Ring ◽

Ring System ◽

Substitution Reactions ◽

Laboratory Notebook ◽

Polar Solvents ◽

X Ray ◽

X Ray Crystallography ◽

The Core ◽

Nmr Data

We have discovered and studied a telesubstitution reaction in a biologically important heterocyclic ring system. Conditions that favour the tele-substitution pathway were identified: the use of increased equivalents of the nucleophile or decreased equivalents of base, or the use of softer nucleophiles, less polar solvents and larger halogens on the electrophile. Using results from X-ray crystallography and isotope labelling experiments a mechanism for this unusual transformation is proposed. We focused on this triazolopyrazine as it is the core structure of the in vivo active anti-plasmodium compounds of Series 4 of the Open Source Malaria consortium. Archive of the electronic laboratory notebook with the description of all conducted experiments and raw NMR data could be accessed via following link <a href="https://ses.library.usyd.edu.au/handle/2123/21890">https://ses.library.usyd.edu.au/handle/2123/21890</a> . For navigation between entries of laboratory notebook please use file "Strings for compounds in the article.pdf" that works as a reference between article codes and notebook codes, also this file contain SMILES for these compounds.

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