PubMed Health⌕ Search

Biomedical subjects

A G Dulloo

Publications and source records attributed to A G Dulloo.

At least 73 records · Page 4Linked to original sources
PubMed1992

Dietary supplementation with fish oil enhances in vivo synthesis of tumor necrosis factor.

Studies reported here investigate the influence of dietary fat types on cytokine production in response to endotoxin (LPS) challenge. Tumor necrosis factor (TNF) serum levels were markedly higher (by 10-fold) in mice fed chronically a diet rich in fish oil rather than either a diet rich in corn or coconut oil or a low fat diet. This in vivo hyper-responsiveness in LPS-induced TNF production following fish oil consumption concorded with similar exaggerated in vitro TNF release from macrophages exposed to LPS. These data suggest that high consumption of fish oils, by virtue of their high content of omega-3 polyunsaturated fatty acids, can lead to an exaggerated production of mediators of inflammation with potentially adverse consequences on the outcome and severity of infectious diseases.

Animals↗
PubMed1991

Effects of monosodium glutamate and gold thioglucose on dietary regulation of sympathetic nervous system activity in rodents.

Neonatal administration of monosodium glutamate (MSG) disrupts hypothalamic regulation of a number of neuroendocrine systems. Studies described in this report using techniques of norepinephrine (NE) turnover examined sympathetic nervous system (SNS) activity in heart and interscapular brown adipose tissue (IBAT) of animals given MSG as neonates. Although in every experiment overall rates of NE turnover were lower in MSG-treated mice and rats, the differences were due exclusively to diminished tissue NE content, especially in IBAT. Fractional rates of NE turnover did not differ between groups. In contrast to animals with lesions in the ventromedial hypothalamus produced by gold thioglucose (AuTG) or electric current, MSG-treated mice and rats varied SNS activity in heart and IBAT in accord with changes in nutrient intake. Thus, SNS activity, both at baseline and in response to dietary manipulation, is probably not affected by neonatal MSG administration.

Adipose Tissue, Brown↗
PubMed1991

Peripheral mechanisms of thermogenesis induced by ephedrine and caffeine in brown adipose tissue.

The peripheral mechanisms by which ephedrine and caffeine influence thermogenesis were investigated in innervated rat interscapular brown adipose tissue (IBAT) by assessing its rate of oxygen consumption (MO2) in vitro. Dose-response measurements with tissues from intact or sympathectomized (6-OHDA) animals indicate that the thermogenic effects of low concentrations of ephedrine and also of caffeine are entirely dependent upon the presence of intact sympathetic nerve endings, and thus depend on presynaptic mechanisms. Direct postsynaptic stimulation of thermogenesis is only apparent at much higher concentrations, namely greater than 1 microM for ephedrine and greater than 2mM for caffeine. At subminimal concentrations that neither ephedrine nor caffeine influenced basal tissue respiration, they induced a 4-5-fold increase in basal MO2 when administered in combination, a synergistic response prevented by pre-treatment of the rat with 6-OHDA. Synergistic increases in IBAT respiration were also obtained when subminimal concentration of ephedrine was added to 3-propylxanthine (a specific inhibitor of phosphodiesterase), to 8-phenyltheophylline (a potent adenosine receptor antagonist) or to adenosine deaminase (for enzymatic inactivation of endogenous adenosine). Conversely, the marked synergism in thermogenic response with ephedrine + caffeine was reduced in the presence of 2-chloroadenosine (an adenosine analogue). In tissues from fasted rats, the ephedrine + caffeine synergism in thermogenic response, although attenuated, was nevertheless present. These studies therefore demonstrate that ephedrine, at doses comparable with therapeutic use, stimulates thermogenesis in BAT via sympathetically released NA. In addition, a synergistic interaction between caffeine and ephedrine on BAT thermogenesis is explained by ephedrine's enhancement of sympathetic neuronal release of NA, together with caffeine's dual ability to antagonize adenosine and to inhibit cellular phosphodiesterase activity.

2-Chloroadenosine↗
PubMed1991

Adaptation to low calorie intake in obese mice: contribution of a metabolic component to diminished energy expenditures during and after weight loss.

Adaptive changes in energy expenditure (EE) in response to low calorie intake were assessed quantitatively in obese mice using techniques that measure EE chronically over weeks (by the comparative carcass method), and also over 24 h (by indirect calorimetry). Grossly obese mice were slimmed (by restricting food to 50 per cent of normal intake) until their body weight reached that of the lean. They were subsequently either maintained in the post-obese state by continued food restriction at 25 per cent below the obese controls, or refed at the same calorie intake as controls. Total EE (assessed over 3 week periods) fell by 30 per cent during weight loss (obese controls 1356 kJ vs obese-slimmed 966 kJ, P less than 0.001), by 25 per cent during maintenance of the post-obese weight (obese control 1443 kJ vs post-obese 1062 kJ, P less than 0.001), and remained diminished by 17 per cent during weight regain upon refeeding (obese control 1443 kJ vs slimmed/refed 1176 kJ, P less than 0.001). Similar reductions in daily oxygen consumption were also obtained by indirect calorimetry, and as a function of lean body mass, 24 h VO2 were lower than controls by 17 per cent, 9 per cent and 10 per cent respectively (P less than 0.01 at least), and remained so under conditions of locomotory restraint. It is calculated that in these obese mice, a metabolic component (unassociated with changes in lean body mass and activity) comprised nearly two-thirds of the adaptive fall in EE during weight loss, and one-half of the change in EE during both phases of post-obese weight maintenance and during weight regain. These studies therefore support the notion that in response to low calorie intake, adaptive changes in the efficiency of cellular energy utilization are of considerable quantitative importance in the resistance to weight loss and in the ease with which the obese condition is rapidly regained after slimming.

Adaptation, Physiological↗
PubMed1990

Adaptive changes in energy expenditure during refeeding following low-calorie intake: evidence for a specific metabolic component favoring fat storage.

Studies in this report investigate the existence and quantitative contribution of a metabolic component to an apparently elevated efficiency of energy utilization during refeeding following low-calorie consumption. Energy balance during a 25-d refeeding period was assessed in rats that had been food restricted (at 50% of normal intake) for either 30 or 10 d. Relative to weight-matched controls (with comparable lean tissue mass and similar food intake), refeeding following both periods of low food consumption (30 or 10 d) was associated with a 10% reduction in energy expenditure (p less than 0.001). Analysis of body composition revealed that virtually all the energy saved as a result of this metabolic (as opposed to tissue mass) adaptation was deposited as fat rather than protein. After the energy cost for depositing the extra fat is accounted for, the metabolic component represents a net 15% lower energy expenditure when normal food intake is resumed. These adaptive changes in energy expenditure may thus constitute an important mechanism for the rapid replenishment of energy stores in preparation for recurring food shortages and may also underlie the ease with which the obese condition is rapidly reachieved after weight loss.

Adaptation, Biological↗
PubMed1990

Role of corticosterone in adaptive changes in energy expenditure during refeeding after low calorie intake.

We examined the importance of corticosterone in elevated efficiency of energy utilization during refeeding after low food consumption. Energy balance studies during refeeding (over periods of 14 or 16 days) were conducted in rats previously food restricted for 16 days at 50% of normal food intake. Comparisons made with nonrestricted weight-matched controls after validation studies indicated that 2-wk-younger weight-matched controls had similar maintenance energy requirements and similar efficiency of energy utilization above maintenance (i.e., net efficiency) to nonrestricted age-matched controls. Results indicate that relative to controls refeeding after low food consumption was associated with enhanced energy conservation underlain by a 16-18% reduction (P less than 0.001) in total energy expenditure over a 14-day period. This metabolic adaptation for energy conservation resulted in a threefold increase (P less than 0.001) in body fat accretion but no difference in body protein deposition. Bilateral adrenalectomy (ADX) 2 days before refeeding reduced differences in energy expenditure between refed group and controls from 18 to 8% (P less than 0.01) and attenuated body fat gain from a three- to twofold increase (P less than 0.001) above control group. Effects of ADX were prevented by daily corticosterone replacement. Data suggest that after a period of low calorie intake an adaptive neurohormonal switching mechanism facilitates replenishment of fat stores during refeeding. This metabolic reorientation (characterized by an adaptive fall in energy expenditure) has both an adrenal as well as a nonadrenal component, because it is partially reversed by prior bilateral ADX, an effect attributed to removal of corticosterone-induced inhibition of thermogenesis.

Adrenalectomy↗
PubMed1990

Reduced adipsin expression in murine obesity: effect of age and treatment with the sympathomimetic-thermogenic drug mixture ephedrine and caffeine.

Adipsin gene expression is greatly diminished in certain forms of genetic and acquired obesity. In the present study we evaluate the time course for the development of adipsin deficiency in obesity and its regulation by the sympathomimetic-thermogenic drug mixture ephedrine and caffeine. Previously, it was unknown whether adipsin deficiency occurred before or after the development of massive obesity. In the first series of experiments in which mice were treated with monosodium glutamate (MSG) for the first week of life, we demonstrate that adipsin deficiency occurs early in the development of MSG-induced obesity as evidenced by decreased circulating adipsin concentrations by 1 week of age and deficient adipsin mRNA levels in white adipose tissue (WAT) by 2 weeks. In db/db mice, diminished circulating adipsin was noted at 2 weeks of age. In both models, decreased adipsin gene expression precedes the development of marked obesity. Little is known about the factors which regulate adipsin gene expression in obesity. Common to the ob/ob, db/db and MSG models is diminished thermogenesis and sympathetic nervous system activity. In a second series of experiments we sought to determine whether adipsin deficiency in obesity could be corrected by treatment with ephedrine and caffeine (E+C), a sympathomimetic-thermogenic mixture previously shown to increase thermogenesis and reverse obesity in some models. In the present study, E+C treatment of MSG obese mice reversed obesity and markedly increased serum adipsin and adipsin mRNA levels in WAT and brown adipose tissue (BAT). In ob/ob mice, however, E+C treatment produced a negligible increase in adipsin mRNA levels in WAT and BAT as well as serum adipsin concentrations and this correlated with only a very small decrease in obesity. Thus, the ability of E+C to increase adipsin gene expression correlated with its ability to reverse obesity in these two models. Finally, the effect of E+C on adipsin gene expression may not be exerted directly on the fat cell since treatment of cultured 3T3-F442A adipocytes and isolated rat adipocytes in primary culture produced no effect on adipsin mRNA or secreted protein despite a lipolytic effect as measured by increased glycerol release. In summary, decreased adipsin gene expression occurs early in the development of MSG and db/db obesity and is markedly increased in the MSG model by the sympathomimetic-thermogenic drug mixture, E+C, which also reverses obesity. Elucidation of the factors responsible for these effects may enhance our understanding of fat cell gene regulation and obesity.

Adipose Tissue, Brown↗
PubMed1989

Normal caffeine consumption: influence on thermogenesis and daily energy expenditure in lean and postobese human volunteers.

Single-dose oral administration of 100 mg caffeine increased the resting metabolic rate of both lean and postobese human volunteers by 3-4% (p less than 0.02) over 150 min and improved the defective diet-induced thermogenesis observed in the postobese subjects. Measurements of energy expenditure (EE) in a room respirometer indicate that repeated caffeine administration (100 mg) at 2-h intervals over a 12-h day period increased the EE of both subject groups by 8-11% (p less than 0.01) during that period but had no influence on the subsequent 12-h night EE. The net effect was a significant increase (p less than 0.02) in daily EE of 150 kcal in the lean volunteers and 79 kcal in the postobese subjects. Caffeine at commonly consumed doses can have a significant influence on energy balance and may promote thermogenesis in the treatment of obesity.

Adult↗
PubMed1989

Energy expenditure and diet-induced thermogenesis in presence and absence of hyperphagia induced by insulin.

The influence of experimental hyperinsulinemia on energy intake, energy expenditure, and body composition was investigated in rats treated chronically with high doses of insulin. Energy balance studies, each of 2-wk duration, were conducted with two different long-acting insulins (Protamine and Monotard), administered in the morning (IM), the late afternoon (IA), or both (IMA) and in animals of three different ages, namely in 4-, 8-, and 12-wk-old rats. The results indicate that the level of hyperphagia induced by insulin was markedly influenced by the type of long-acting insulin (P less than 0.001; Protamine greater than Monotard), by age (P less than 0.001; 12 greater than 8 greater than 4 wk), as well as by the timing of insulin administration (P less than 0.002, IMA greater than IM or IA). Body protein deposition was unaltered, but body fat and energy expenditure increased in parallel to the level of hyperphagia. Regression analysis shows a strong linear correlation (r = 0.963) between the change in energy expenditure and the change in energy intake in response to insulin and indicates that approximately 50% of the excess calories consumed was dissipated as heat. In the absence of hyperphagia, however, insulin administration had no effect on energy expenditure nor on energy partitioning. Similarly, the influence of altered meal pattern, induced by administering insulin at different times of the day, was also found to have no impact on energy expenditure. The current investigations therefore refute the notion that high doses of insulin via hyperinsulinemia and/or altered meal pattern have an inhibitory influence on whole body thermogenesis. In contrast, our data demonstrate that the adaptive phenomenon that tends to minimize the accumulation of excess caloric intake, i.e., diet-induced thermogenesis, persists in the hyperinsulinemic state.

Animals↗
PubMed1988

A low-budget and easy-to-operate room respirometer for measuring daily energy expenditure in man.

Accurate assessment of energy requirements of humans under various physiological, pathological, and environmental conditions is hampered by the high cost of techniques for measuring daily energy expenditure. A room respirometer novel in its novel in its low cost of construction and simplicity of operation is described, together with an appreciation of errors and assumptions. It is suitable for measurements of daily energy expenditure in humans with an accuracy of +/- 1.5% and can be reproduced without difficulty in both developed and developing countries.

Adult↗
PubMed1988

Sympathetic nervous system responses to cold exposure and diet in rat skeletal muscle.

Norepinephrine (NE) turnover measured in individual skeletal muscles of the rat assessed sympathetic responses to cold (4 degrees C) and diet. Acute cold exposure increased NE turnover slightly (15-50%) in all muscles examined, including gastrocnemius, tibialis anterior, tensor fascia lata, and soleus, in contrast, cold-accelerated NE turnover in heart by one- to twofold and in interscapular brown adipose tissue (IBAT) by more than threefold. Similar results in skeletal muscle and heart were obtained after 1 wk of cold exposure. Examination of dietary effects on NE turnover, comparing rats fed a sucrose-supplemented diet for 3 days with those fasted for 2 days, indicated that sympathetic activity in skeletal muscle was unresponsive to dietary intake. In heart and IBAT, on the other hand, NE turnover in sucrose-fed rats was twice that obtained in fasted animals. Taken together, the lesser effect of cold and the undetectable response to diet indicate that sympathetic outflow to skeletal muscle is regulated differently than that to heart or IBAT and imply that skeletal muscle is not a major site for sympathetically mediated thermogenic responses to cold exposure or to dietary alteration, such as fasting and sucrose feeding.

Acclimatization↗
PubMed1987

Aspirin as a promoter of ephedrine-induced thermogenesis: potential use in the treatment of obesity.

Chronic administration of aspirin to obese mice had no effect on energy balance and body composition. In contrast, ephedrine increased energy expenditure by 9% and reduced body weight and body fat by 18% and 50%, respectively: obesity, however, was reduced but not reversed. In the presence of both ephedrine and aspirin, increase in energy expenditure found during treatment with ephedrine alone was doubled, and the obese group lost greater than 75% of body fat: obesity was reversed. These studies indicate that although aspirin administered alone has no influence on energy balance it can markedly potentiate thermogenic properties of ephedrine, effects which led to a normalization of body composition of the obese to that of the lean. Such ephedrine-aspirin mixtures, often found in over-the-counter preparations for asthma and bronchial disorders, could be put to new use as aids for treatment of human obesity.

Adipose Tissue↗
PubMed1987

Reversal of obesity in the genetically obese fa/fa Zucker rat with an ephedrine/methylxanthines thermogenic mixture.

Administration of a thermogenic mixture of ephedrine, caffeine and theophylline to grossly obese (11-12 mo old) fa/fa Zucker rats led to a rapid decline in their body weight, which reached lean levels within 9-10 wk, and this postobese weight was maintained for another 5-6 wk. Compared to the no-drug obese controls (O-ND), food intake was reduced by 70% during the dynamic phase of weight loss and by 50% during the postobese period in the food-restricted animals (O-FR) and by about 40% during both phases in the ephedrine/methylxanthines (O-E/Mx) animals. Energy expenditure in the O-FR group was lower than in the O-E/Mx group by 25-33%. Analysis of body composition showed that body fat in both O-FR and O-E/Mx groups was much lower than in the O-ND group, by 2.5- and 4-fold, respectively, and body protein was lower by 50 and 28%, respectively. Thus, compared to the O-ND group, the fat:protein ratio was only 25% lower in the O-FR animals but was three times less in the O-E/Mx group. These findings demonstrate that in the fa/fa rat a mixture of ephedrine and methylxanthines reduces food intake but also minimizes the fall in metabolic rate that usually accompanies such an energy deficit, effects that led to a reversal of their gross obesity. The ability of ephedrine alone or in combination with methylxanthines to reverse obesity in animal models with dietary and hypothalamic etiologies is thus extended to the obesity resulting from the inheritance of a single-gene recessive defect.

Animals↗
PubMed1987

Prevention of genetic fa/fa obesity with an ephedrine-methylxanthines thermogenic mixture.

A thermogenic mixture containing ephedrine and methylxanthines was administered to 8-wk-old genetically obese fa/fa rats (O-E/Mx group) for a period of 15 wk. Their energy balance and the final body composition were compared with an untreated ad libitum-fed (O-AL) group, as well as to other fa/fa obese animals that were either pair fed to lean controls (O-PF group), or that were food restricted to such an extent they maintained a similar body weight to that of lean animals (O-WF group). Energy intake was elevated above lean or O-PF levels by approximately 27 and 10% in the O-AL and O-E/Mx groups, respectively, but lower by 18% in the O-WF group. Energy expenditure, compared with the lean values, was 10% higher in both the O-AL and O-E/Mx groups, but reduced by 13 and 30% in the O-PF and O-WF groups, respectively. The gain in body energy and the efficiency of energy deposition remained elevated above the lean values by 2.3- to 3.5-fold in the O-AL, O-PF, and O-WF groups but were reduced to lean levels in the O-E/Mx groups. These studies indicate that, unlike food restriction, the ephedrine-methylxanthine mixture prevents or arrests the development of the obesity in the fa/fa mutant by normalizing their energetic efficiency to that of the lean.

Animals↗
PubMed1987

Screening of drugs for thermogenic anti-obesity properties: antidepressants.

Twelve antidepressant drugs, currently in clinical use, were screened for thermogenic properties on the basis of their ability to stimulate the activity of the sympathetic nervous system via an inhibitory effect on noradrenaline reuptake into the sympathetic neurons. Drug screening was carried out on mice made obese by hypothalamic lesioning using monosodium glutamate. Preliminary experiments, based on changes in body weight and food intake in response to increased doses of the drugs, indicate that most of the twelve antidepressants possess thermogenic potential. In particular, butriptyline, protriptyline and nortriptyline were most effective in causing marked losses in body weight without altering the food intake of the mice. The potent anti-obesity thermogenic properties of these three antidepressants were confirmed during a 10-week energy balance study involving measurements of energy expenditure over the entire period by the comparative carcass method, as well as by measurement of 24 h oxygen consumption. These studies indicate that the methodology employed in the preliminary screening is valid for identifying drugs with thermogenic potential, and demonstrate that many antidepressants currently in clinical use have marked thermogenic properties, and could therefore influence the nutritional status of patients under drug therapy.

Animals↗
PubMed1986

The thermogenic properties of ephedrine/methylxanthine mixtures: animal studies.

An over-the-counter preparation containing ephedrine, caffeine, and theophylline was examined for thermogenic anti-obesity properties. Administration of the methylxanthines to MSG-induced obese mice for 6 wk had no effect on energy balance or body composition. In contrast, treatment with ephedrine alone caused losses of 14% in body weight and 42% in body fat, effects brought about mainly by a 10% increase in energy expenditure. These changes were accentuated when ephedrine was administered together with one or both methylxanthines: energy expenditure was increased by a further 10%, and led to a reduction of about 25% in body weight and 75% in body fat, while the total food intake and body protein were unaltered. These results indicate that dietary methylxanthines like caffeine and theophylline, although alone have little effect on energy balance, can nevertheless markedly potentiate the thermogenic anti-obesity effect of ephedrine and normalize the body composition of the obese to the lean levels.

Administration, Oral↗