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Biomedical subjects

A G Dulloo

Publications and source records attributed to A G Dulloo.

82 records · Page 5Linked to original sources
PubMed1986

The effect of parasympathetic drugs on energy expenditure: relevance to the autonomic hypothesis.

The influence of the parasympathetic nervous system in the control of energy expenditure was investigated in obese and lean rodents during chronic administration of drugs that alter parasympathetic transmission. In the genetically obese ob/ob mice and fa/fa rats and in monosodium glutamate induced hypothalamic obese mice, administration of the parasympathetic inhibitors hyoscine, benztropine, and mecamylamine either had no effect on energy balance or caused losses in body weight that could entirely be accounted for by a reduction in food intake; 24-h oxygen consumption in drug-treated animals was no different from that of the nontreated controls. In the lean animals, both the parasympathetic inhibitors (hyoscine, benztropine, and mecamylamine) and stimulators (bethanecol and neostigmine) had no influence on energy balance nor on body composition. These studies refute the concept that an overactive parasympathetic tone underlies the elevated energetic efficiency of obese models and suggests that the parasympathetic nervous system is unlikely to play an important role in the long-term control of energy expenditure.

Animals↗
PubMed1986

Genetic and dietary influences on the levels of diet-induced thermogenesis and energy balance in adult mice.

Genetic and dietary influences on energy balance and diet-induced thermogenesis were investigated in 5 strains of adult mice fed either a stock diet or a varied and palatable cafeteria diet for 4 weeks. Compared to their stock-fed controls, the total metabolisable energy intake of mice fed a cafeteria diet increased by 60, 45, 28, 50 and 35% in the ob/+ or +/+, C57BL/6, DBA/2, BALB/C and CFLP strains, respectively, while energy expenditure, over the entire period, was increased by 53, 21, 24, 53 and 34%, respectively. The results show the presence of diet-induced thermogenesis in most strains studied, and also indicate that variations in food intake were more strongly determined by diet, whereas variations in energy efficiencies were more strongly influenced by genetics.

Animals↗
PubMed1986

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

The thermogenic effect of an over-the-counter preparation containing 22 mg ephedrine, 30 mg caffeine and 50 mg theophylline was investigated in human volunteers with a predisposition to obesity and also in the lean. The ephedrine/methylxanthines mixture was twice as effective as ephedrine alone in increasing the fasting metabolic rate of both subject groups, and it normalized the reduced thermogenic response to a 1.25-MJ meal observed in those predisposed to obesity. Measurements of 24-h energy expenditure in a respirometer indicate that the mixture had no effect on the daily metabolic rate of the lean, but was effective in causing a significant 8 percent increase in the 24-h energy expenditure of those subjects predisposed to obesity. These studies indicate that relatively mild doses of dietary methylxanthines in combination with ephedrine can raise daily energy expenditure of those predisposed to obesity, mainly by correcting their defective thermogenic response to food. Such ephedrine/methylxanthine preparations could be useful as aids in the treatment of obesity.

Adult↗
PubMed1985

Increased body fat due to elevated energetic efficiency following chronic administration of inhibitors of sympathetic nervous system activity.

The effects on energy balance of drugs known to inhibit the sympathetic nervous system at different sites and with various modes of action were studied in lean mice of the CFLP strain. Metabolizable energy intake was monitored continuously over seven-week experimental periods and energy expenditure was determined by the comparative carcass method as well as by measurements of 24-hour oxygen consumption. Administration of either propranolol, phenoxybenzamine, clonidine, or mecamylamine had no influence on energy balance nor on body composition. On the other hand, administration of alpha-methyl para tyrosine, reserpine, and bethanidine, ie, drugs capable of reducing the levels of noradrenaline at sympathetic terminals, resulted in significant increases in body fat by 38%, 24%, and 46% respectively: this effect was brought about by a reduction in the metabolic rate of these drug-treated groups and the efficiency of energy utilization (both gross and net) was increased by three to nine times. These studies indicate that chronic administration of drugs that act at the receptor level to inhibit sympathetic activity fail to influence metabolic rate, thereby suggesting that thermogenesis under noradrenaline control may involve mechanisms other than the alpha and beta classification of adrenergic receptors. Nonetheless, the ability of some drugs which both reduce noradrenaline levels and decrease metabolic rate would support the concept of an important role of the sympathetic nervous system in the overall control of thermogenesis and in energy balance regulation.

Adipose Tissue↗
PubMed1985

A comparative study of the effects of white sugar, unrefined sugar and starch on the efficiency of food utilization and thermogenesis.

Energy balance studies with weanling rats and mice were carried out to investigate the chronic effects of diets containing white sugar, unrefined sugar, and starch as sole carbohydrate on body composition and energetic efficiency. The results show no significant differences in energetic efficiency and in body composition of both rats and mice fed the different carbohydrate diets. However, there is a tendency for the sugar-fed animals to have higher metabolizable energy intakes, but rarely was this sufficient to increase body energy since there were corresponding increases in metabolic rate. These studies indicate that differences in energy balance between sugar and starch are small and that any increase in thermogenesis that occurred in some of the groups fed sugar-rich diets was in response to the higher energy intake rather than due to a lower efficiency of utilization of sucrose per se.

Animals↗
PubMed1984

Thermogenic drugs for the treatment of obesity: sympathetic stimulants in animal models.

Thirty-three drugs known to stimulate the sympathetic nervous system have been screened for thermogenic properties. The results presented are for seven of them. The drugs were tested in five animal models of obesity (genetic (mice and rats), hypothalamic (mice) and dietary (mice and rats] as well as in lean mice. Energy-balance studies were undertaken using the comparative-carcass technique as well as by measurement of daily oxygen consumption. All seven drugs in obese animals tended to reduce body-weight and fat without loss of body protein: they acted by increasing metabolic rate without increasing food intake. They were much less effective in lean animals. These findings lend support to the concept that obesity is due to a diminished activity of the sympathetic nervous system. Differences in the effectiveness of the drugs are discussed in relation to differences between the animal models of obesity. Ephedrine and tranylcypromine were found to be the most effective drugs in this series of experiments and a prima facie case is made for human clinical trials.

Animals↗
PubMed1984

Energy balance following sympathetic denervation of brown adipose tissue.

The effects of sham, bilateral surgical denervation or excision of interscapular brown adipose tissue on body composition and energetic efficiency were studied in young CFLP mice kept at 25 degrees C and fed a laboratory stock diet. A preliminary experiment showed that 15 weeks following surgery, total body fat was increased by 42% in the denervated group and by 72% in the excised group while body protein was unchanged. In another 7-week energy balance experiment, body fat was also significantly higher by 15 and 18% in the denervated and excised group, respectively, but metabolizable energy intake was slightly lower than that of sham controls. Determination of energy expenditure both by the comparative carcass slaughter technique and by measurement of daily oxygen consumption showed that the metabolic rate was reduced in the denervated nd excised groups. The capacity for thermogenesis, as measured by an increase in oxygen consumption following injections of noradrenaline (600 micrograms/kg body weight) was similar in energetic efficiency, and indicates an important role of the sympathetic nervous system in the regulation of animal heat production by brown adipose tissue and in the overall control of thermogenesis.

Adipose Tissue, Brown↗
PubMedDate not supplied

Role of cytokines in AIDS wasting.

There is now a large literature implicating cytokines in the development of wasting and cachexia commonly observed in a variety of pathophysiologic conditions. In the acquired immunodeficiency syndrome (AIDS), cytokines elicited by primary and secondary infections seem to exert subtle and sustained effects on behavioral, hormonal, and metabolic axes, and their combined effects on appetite and metabolism have been postulated to drive wasting. However, correlations of increased blood levels of a particular cytokine with wasting in AIDS have not been consistent observations, perhaps because cytokines act principally as paracrine and autocrine hormones, as well as indirectly by activating other systems. A better understanding of the mechanisms underlying the catabolic effects of cytokines in clearly needed if more efficacious strategies are to be developed for the prevention and treatment of wasting in AIDS. In this review we first examine the interacting factors contributing to the AIDS wasting syndrome. We then analyze the complex and overlapping role of cytokines in the pathophysiology of this condition, and put forward a number of hypotheses to explain some of the most important features of this syndrome.

Cachexia↗