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Biomedical subjects

A G Dulloo

Publications and source records attributed to A G Dulloo.

At least 55 records · Page 3Linked to original sources
PubMed1997

Altered energy balance and cytokine gene expression in a murine model of chronic infection with Toxoplasma gondii.

The temporal pattern of changes in energy balance and cytokine mRNA expression in spleen and brain were examined in a mouse model of infection with Toxoplasma gondii. During days 1-7 postinfection, food intake was unaltered, but energy expenditure was significantly increased, and this was associated with elevated tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1, IL-5, and interferon (IFN)-gamma. The hypermetabolic state persisted during subsequent anorexia, whose onset coincided with elevated IL-2, and at the end of the acute phase of cachexia, the dual anorexic and hypermetabolic states were associated with the cytokines examined: TNF-alpha, IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-10, and IFN-gamma. In the chronic phase of the infection, the mice showed either partial weight recovery (gainers) or no weight regain (nongainers). The infected gainers, though still hypophagic, were no longer hypermetabolic, and their cytokine mRNA was no longer elevated, except for TNF-alpha and IL-10. In contrast, the infected nongainers continued to show both anoroxia and hypermetabolism, which were associated with elevations in all cytokines examined and particularly those of the TH2 profile (IL-4 and IL-5) and IL-6. Taken together, these studies reveal a distinct pattern of cytokine mRNA expression underlying 1) hypermetabolism vs. anorexia, 2) acute vs. chronic cachexia, and 3) stable weight loss vs. partial weight recovery.

Acute Disease↗
PubMed1996

Twenty-four-hour energy expenditure and urinary catecholamines of humans consuming low-to-moderate amounts of medium-chain triglycerides: a dose-response study in a human respiratory chamber.

OBJECTIVE: To determine whether medium-chain triglycerides, in low-to-moderate amounts consumed with meals (at breakfast, lunch and dinner), can increase daily energy expenditure (EE) and 24-h urinary excretion of catecholamines in humans. DESIGN: Dose-response study conducted under double-blind randomised design. SETTING: Respiratory chamber at the Faculty of Medicine, University of Geneva. SUBJECTS: Eight healthy young men were recruited from the student population by advertisement in our Faculty. METHODS: 24-h EE and urinary catecholamines were measured in each subject during stay in a respiratory chamber on four separate occasions. These were randomised between four different combinations of medium-chain triglycerides (MCT) and long-chain triglycerides (LCT), a total 30g/day, which was consumed with their habitual diet in three equal parts (10g each) at breakfast, lunch, and dinner in the following ratio of MCT: LCT (g/g) 0:30, 5:25, 15:15 and 30:0. RESULTS: 24-h EE increased significantly with increasing MCT:LCT ratio (ANOVA, P < 0.001), with the diet providing a total of 15-30 g MCT per day stimulating 24-h EE by 5%: this corresponds to a mean absolute increase in daily EE of approximately 500kJ, with individual values varying between 268 kJ and 756 kJ. No significant differences were observed in respiratory quotient nor in urinary nitrogen losses across diets, but 24-h urinary noradrenaline was significantly increased (ANOVA, P < 0.025), whereas adrenaline and dopamine were unaltered. CONCLUSIONS: This study suggests that relatively low-to-moderate intake of MCT (15-30 g per day) as part of habitual diet may play a role in the control of human body composition by enhancing daily EE, and that this effect is mediated at least in part through activation of the sympathetic nervous system.

Adult↗
PubMed1996

Autoregulation of body composition during weight recovery in human: the Minnesota Experiment revisited.

OBJECTIVES: To gain insights into the control systems underlying human variability in the regulation of body composition during weight recovery, as well as the disproportionate recovery of fat relative to lean tissue, the classical Minnesota Experiment conducted on 32 men subjected to long-term semi-starvation and refeeding was revisited with the following objectives: (1) to determine whether the control of energy-partitioning between lean and fat tissues during weight loss and weight recovery is an individual characteristic, and if a predictor can be statistically identified, (2) to determine whether the reduction in thermogenesis during weight loss persists during weight recovery, and underlies the disproportionate recovery of fat tissue and (3) to integrate the control of energy-partitioning and that of thermogenesis in order to explain the pattern of lean and fat tissue mobilisation and deposition during weight loss and weight recovery. METHODS: Individual data on body weight, body fat, fat-free-mass (FFM), and basal metabolic rate (BMR), assessed during the control baseline period (i.e. prior to weight loss), at the end of 24 weeks of semi-starvation, and at the end of a 12 week period of restricted refeeding, were used to calculate the following parameters: (i) a quantitative index of energy-partitioning, the P-ratio, defined as the proportion of body energy mobilised as protein during weight loss, or as the proportion of body energy deposited as protein during weight recovery, (ii) a quantitative index of changes in thermogenesis, defined as the change in BMR adjusted for FFM (or for both FFM and fat mass) and (iii) the degree of replenishment of fat and FFM compartments, defined as the recovery of body fat and FFM (during refeeding) as a percentage of that lost during semi-starvation. RESULTS: This re-analysis indicates the following: (i) a large inter-individual variability in P-ratio during both weight loss and weight recovery, but for a given individual, the P-ratio during refeeding is strongly correlated with the P-ratio during semi-starvation, (ii) body composition during the control period is the most important predictor of variability in P-ratio, such that the higher the initial % body fat, the lower the proportion of energy mobilised as protein, and hence the greater the propensity to mobilise fat during semi-starvation and to subsequently deposit fat during refeeding and (iii) at week 12 of refeeding, the change in adjusted BMR is found to be reduced by a magnitude which is inversely proportional to the degree of fat recovery, but is unrelated to the degree of FFM recovery. A quantitative relationship is derived between the P-ratio during refeeding, the % fat recovery, and the P-ratio during semi-starvation. CONCLUSIONS: Evidence is presented here suggesting that (i) human variability in the pattern of lean and fat tissue deposition during weight recovery is to a large extent determined by individual variations in the control of energy-partitioning, for which the initial % body fat is the most important predictor and (ii) the disproportionate gain in fat relative to lean tissue during weight recovery is contributed by a reduction in thermogenesis (i.e. increased efficiency of food utilization) for accelerating specifically the replenishment of the fat stores. These control systems, operating via energy-partitioning and thermogenesis, have been integrated into a compartmental model for the regulation of body composition during underfeeding/refeeding, and can be used to explain the individual pattern of lean and fat tissue deposition during weight recovery in situations ranging from the rehabilitation after malnutrition to the relapse of obesity.

Adipose Tissue↗
PubMed1996

Dissociation of systemic GH-IGF-I axis from a genetic basis for short stature in African Pygmies.

OBJECTIVES: To test the hypothesis that the primary cause of short stature in African Pygmies resides in low levels of insulin-like growth factor I (IGF-I), and to evaluate whether any observed alterations in their systemic IGF-I status can be dissociated from the effects of malnutrition and/or altered immune status. SETTING: Expedition to camps of partially sedentarized African Pygmies and neighbouring Bantu farmers living in the equatorial rain forest of Eastern Cameroon. DESIGN: Serum assays for hormonal and immune status were conducted for individuals (children, adolescents, young and old adults) showing no overt clinical nor biochemical signs of malnutrition, as judged from anthropometry, clinical examinations and serum assays of albumin, pre-albumin, retinol-binding protein, transferrin, iron, zinc, magnesium and calcium. RESULTS: African Pygmies did not differ from Europeans or Bantus in mean serum IGF-I concentrations, nor in the relationship between serum IGF-I and its major binding protein (IGFBP-3). However, although in both African groups the immunoglobulins IgG, IgM and IgE as well as the C-reactive protein and ceruloplasmin were above the normal range of European references, the Pygmies differed from their Bantu neighbours in their much higher IgG and IgM serum levels. A plot of serum IGF-I against these immunoglobulins in Pygmies revealed a reverse sigmoidal relationship, with the low IGF-I values associated with serum levels of IgG and IgM which clearly exceeded those found in the Bantus. CONCLUSIONS: This study indicates that in growing and adult African Pygmies showing no clinical nor biochemical signs of nutritional deficiency, serum IGF-I and IGFBP-3 (hence IGF-I bioavailability to its receptors) are essentially normal, and that low circulating levels of IGF-I in Pygmies reside in differential exposure and/or responsiveness to environmental challenge (e.g. infections) rather than in an inherited defect in the systemic growth-hormone (GH)-IGF-I axis.

Adolescent↗
PubMed1995

Modulation of obese gene expression in rat brown and white adipose tissues.

The ob gene mRNA expression in rat brown adipose tissue (BAT) and epididymal white adipose tissue (WAT) was measured on Northern blots hybridized with a rat ob gene probe. The level of ob gene mRNA in BAT was about 40% of that in WAT. Fasting (36 h) or semi-starvation (10 days) decreased the ob gene mRNA level in both tissues by 62-68%, and cold exposure at 6 degrees C (24 h) decreased it in BAT (-84%) but not in WAT. Acute administration of the beta 3-adrenergic agonist Ro 16-8714 decreased the ob gene mRNA level in BAT (-51%) and WAT (-28%) of lean Zucker rats and only in BAT (-74%) of obese falfa rats. This study demonstrates that, in the rat, the ob gene is not only expressed in WAT but also in BAT, and suggests that in these two tissues, the modulation of the ob gene expression might be more closely associated with known alterations in cell lipid content than with changes in sympathetic activity.

Adipose Tissue↗
PubMed1995

Fish oil enhances macrophage tumor necrosis factor-alpha mRNA expression at the transcriptional level.

Dietary supplementation with fish oil has previously been shown to enhance in vivo and in vitro (macrophage) synthesis of tumor necrosis factor-alpha (TNF-alpha) in response to bacterial lipopolysaccharide (LPS) stimulation. The studies reported here were conducted to gain insight into the molecular mechanisms of this nutrient-immune interaction by comparing the concentration, rate of synthesis, and rate of decay of TNF-alpha mRNA upon LPS stimulation of macrophages obtained from mice fed high-fat diets, rich in either fish oil, corn oil, or coconut oil, or a low-fat diet for a period of 4 weeks. The results indicate that compared with the other diet groups, LPS stimulation of macrophages from mice fed fish oil resulted in (1) enhanced levels of mRNA and protein for TNF-alpha, and (2) increased transcription of TNF-alpha mRNA as assessed by nuclear run-on assays. Posttranscriptional studies showed that the rate of decay of TNF-alpha mRNA did not vary significantly for macrophages from mice fed with fish oil as compared with corn oil. Further studies using actinomycin D and cycloheximide suggested that RNA synthesis, but not protein synthesis, was necessary for TNF-alpha mRNA accumulation. Taken together, the present studies suggest that fish oil enhances macrophage TNF-alpha mRNA expression at the transcriptional level. Although such TNF-alpha upregulation may provide a mechanism for the beneficial effects of fish oil in certain inflammatory and immune disorders, it can also underlie its potential deleterious effects if the degree of upregulation leads to exaggerated TNF-alpha production that exceeds the limits of benefit to reach toxic levels.

Animals↗
PubMed1995

Differential effects of high-fat diets varying in fatty acid composition on the efficiency of lean and fat tissue deposition during weight recovery after low food intake.

The energetics of body weight recovery after low food intake was examined in the rat during refeeding for 2 weeks with isocaloric amounts of high-fat (HF) diets providing 50% of energy as either lard, coconut oil, olive oil, safflower oil, menhaden fish oil, or a mixture of all these fat types. The results indicate that for both body fat and protein, the efficiency of deposition was dependent on the dietary fat type. The most striking differences were found (1) between diets rich in n-3 and n-6 polyunsaturated fatty acids (PUFA), with the diet high in fish oil resulting in a greater body fat deposition and lower protein gain than the diet high in safflower oil; and (2) between diets rich in long-chain (LCT) and medium-chain triglycerides (MCT), with the diet high in lard resulting in a greater gain in both body fat and protein than the diet high in coconut oil. Furthermore, the diet high in olive oil (a monounsaturated fat) and the mixed-fat diet (containing all fat types) were found to be similar to the fish oil diet in that the efficiency of fat deposition was greater (and that of protein gain lower) than with the diet high in safflower oil. Neither the efficiency of fat gain nor that of protein gain were found to correlate with fasting plasma insulin, the insulin to glucose ratio, or plasma lipids.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1995

Dissociation of enhanced efficiency of fat deposition during weight recovery from sympathetic control of thermogenesis.

Studies reported here examined the extent to which conditions known to suppress or markedly increase the sympathetic control of thermogenesis influence enhanced efficiency of fat deposition during weight recovery after caloric restriction. To this end, measurements of energy balance and changes in body energy compartments during refeeding of rats pair fed with weight-matched controls were conducted over a 2-wk period at 22 degrees C, at thermoneutrality (29 degrees C), or in the cold (6 degrees C). The results indicate that, despite identical (or slightly lower) energy intake relative to the respective controls, the refed animals showed greater gain in body fat (by 2- to 2.5-fold), 10-12% lower energy expenditure, and higher energetic efficiency (60-80%) than the controls at all three environmental temperatures. In contrast, protein gain was not different between the refed and control groups. Thus the energy-conserving mechanism specific to acceleration of fat deposition during weight recovery persists when sympathetically driven thermogenesis is shifted from very low to very high intensity. These findings raise the possibility that this energy-conserving mechanism during refeeding may be distinct from sympathetic-dependent mechanisms underlying adaptive reduction in thermogenesis during severe energy deficit and weight loss.

Adipose Tissue↗
PubMed1994

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.

Analysis of Variance↗
PubMed1994

Paraxanthine (metabolite of caffeine) mimics caffeine's interaction with sympathetic control of thermogenesis.

The notion that paraxanthine (the major dimethylated by-product of caffeine) may be a biologically active metabolite that could mediate some of the effects of caffeine was tested in relation to the well-established property of caffeine as a thermogenic stimulant. From studies measuring the in vitro respiration rates of rat brown adipose tissue in the basal state and in response to ephedrine (an enhancer of norepinephrine release from sympathetic nerve endings), it is shown that paraxanthine has the same potency as its parent compound, caffeine, in interacting with the adrenergic system to potentiate thermogenesis. These data provide the first direct demonstration of a physiological effect of the main metabolite of caffeine and raise the possibility that paraxanthine may contribute importantly to the ability of caffeine to potentiate the thermogenic effects of well-known stimuli of the sympathetic nervous system such as cold exposure, moderate exercise, and sympathomimetic drugs.

Adipose Tissue, Brown↗
PubMed1993

Adaptive role of energy expenditure in modulating body fat and protein deposition during catch-up growth after early undernutrition.

After 10 or 30 d of growth arrest due to undernutrition during the early weaning period, rehabilitated rats fed ad libitum showed the phenomenon of catch-up growth, ie, gains in body weight and body protein were greater by 50% and 25%, respectively, (P < 0.001) than those of controls with similar starting body weight [ie, weight-matched (WM) controls]. These increases, however, were entirely dependent on the higher food intake because they failed to occur when food intakes were maintained at similar amounts to those for WM controls. In contrast, independent of whether the rehabilitated groups were spontaneously hyperphagic relative to WM controls or made normophagic by pair-feeding to WM controls, the gross energetic efficiency was increased (P < 0.01) and body fat gain was more elevated (2-2.5 fold, P < 0.001) during the first 2 wk of refeeding compared with WM controls--differences that were uninfluenced by the duration of growth arrest. Taken together, these studies suggest that the often reported impressive gains in body fat during recovery from malnutrition may result not only from unbalanced diets or excess dietary intake, but also from a transitory enhancement in the efficiency of food utilization and a shift in energy partitioning in favor of an acceleration for the replenishment of fat stores.

Animals↗
PubMed1993

24 hour energy expenditure several months after weight loss in the underfed rat: evidence for a chronic increase in whole-body metabolic efficiency.

The existence and quantitative contribution of an adaptive increase in whole-body metabolic efficiency in response to low caloric intake was examined after prolonged underfeeding in the rat. 24h energy expenditures (EE) and body composition were measured in chronically underfed rats which had been maintaining a stable body weight for several months after an initial period of substantial weight loss. Comparisons were made with ad libitum fed controls. The mean coefficient of variation for daily EE, assessed over three consecutive days, was 3% (range 1.7-4.0%) in the control group and 1.6% (range 0.7-2.1%) in the chronically underfed group, and hence reflect steady state conditions. Body composition was determined by chemical analysis, and as a proportion of body weight (BW), the fat content in the underfed group was reduced by 40% whereas lean body mass was significantly higher by 8%. Independently of the criteria utilized for metabolically active mass, 24h EE was lower in the underfed group than in controls, by 17%, 14% and 8% as a function of BW0.66, BW0.75 and lean body mass respectively (P < 0.01). Underfeeding was also associated with a substantial reduction in the level of external work, but in ad libitum fed animals similar reductions in external work (induced by limiting locomotion) failed to alter 24h EE significantly. Taken together, these studies provide evidence for an increased metabolic efficiency in response to low calorie intake well beyond the period of dynamic weight loss.

Adipose Tissue↗
PubMed1993

Ephedrine, xanthines and prostaglandin-inhibitors: actions and interactions in the stimulation of thermogenesis.

The pivotal role of the sympathoadrenal system in the defense of le milieu interieur has, in the last 15 years, been extended to include the fat stores-a notion that forms the basis of current strategies for thermogenic stimulation in obesity therapy. The search for effective and safe sympathetic stimulants has been directed at two main levels: (i) the development of novel beta-agonists selective for thermogenesis, and (ii) the evaluation of drugs already in clinical use for other purposes (e.g. ephedrine) which could conceivably increase the release of catecholamines to levels that enhance thermogenesis without significant cardiovascular effects. A re-direction of these strategies seem inevitable because at therapeutic doses, the thermogenic effects of these sympathomimetics seem to be considerably dampened by negative feedback mechanisms that operate both extracellularly (e.g. via adenosine & prostaglandins) as well as inside the cells (via cAMP phosphodiesterases). Such a contention is supported by studies both in man and in animals showing that methylxanthines and aspirin, drugs known to be capable of interfering with these modulators, potentiate the thermogenic effects of ephedrine. Future research aimed at clarifying the types and subtypes of these negative modulators of sympathomimetic-induced thermogenesis and their targeting by more selective antagonists would no doubt be pivotal in providing the safe drug combination with the necessary thermogenic properties to assist the management of obesity.

Animals↗
PubMed1993

Ephedrine, caffeine and aspirin: safety and efficacy for treatment of human obesity.

The safety and efficacy of a mixture of ephedrine (75-150mg), caffeine (150mg) and aspirin (330mg), in divided premeal doses, were investigated in 24 obese humans (mean BMI 37.0) in a randomized double blind placebo-controlled trial. Energy intake was not restricted. Overall weight loss over 8 weeks was 2.2kg for ECA vs. 0.7 kg for placebo (p < 0.05). 8 of 13 placebo subjects returned 5 months later and received ECA in an unblinded crossover. After 8 weeks, mean weight loss with ECA was 3.2 kg vs 1.3 kg for placebo (p = 0.036). 6 subjects continued on ECA for 7 to 26 months. After 5 months on ECA, average weight loss in 5 of these was 5.2 kg compared to 0.03 kg gained during 5 months between studies with no intervention (p = 0.03). The sixth subject lost 66 kg over 13 months by self-imposed caloric restriction. In all studies, no significant changes in heart rate, blood pressure, blood glucose, insulin, and cholesterol levels, and no differences in the frequency of side effects were found. ECA in these doses is thus well tolerated in otherwise healthy obese subjects, and supports modest, sustained weight loss even without prescribed caloric restriction, and may be more effective in conjunction with restriction of energy intake.

Adult↗
PubMed1992

Potentiation of the thermogenic antiobesity effects of ephedrine by dietary methylxanthines: adenosine antagonism or phosphodiesterase inhibition?

Current concepts about the mechanisms underlying the therapeutic effects of dietary methylxanthines (caffeine, theophylline, and theobromine) favor their actions as antagonists of adenosine receptors, and attribute their other possible modes of action, namely those associated with translocation of intracellular calcium, inhibition of phosphodiesterase enzyme (PDE) activity, or the release of catecholamines, to high (near-toxic) doses. From studies measuring the respiration rate of brown adipose tissue (BAT), evidence is provided here that at concentrations compatible with therapeutic doses, the ability of methylxanthines (25 to 50 mumol/L) to potentiate the thermogenic effect of the sympathomimetic drug, ephedrine (0.25 mumol/L), particularly under conditions of caloric restriction, involves a minor contribution of adenosine antagonism, but could mainly be explained by the inhibition of PDE activity. In view of current interest in the pharmacological stimulation of metabolic rate to assist the management of obesity with low-calorie regimens, the targeting of PDE activity is therefore a rational approach in the search for drugs that could potentiate sympathomimetic stimulation of metabolic rate.

Adenosine↗
PubMed1992

Influence of dietary composition on energy expenditure during recovery of body weight in the rat: implications for catch-up growth and obesity relapse.

The influence of dietary composition on whole-body energetics was examined during the first 2 weeks of isocaloric refeeding after low food intake in a rat model. The high energetic efficiency and energy partitioning toward fat accretion characteristic of this refeeding period were unaltered by (1) dietary fat levels varying between 6% and 30% of energy intake; (2) protein levels between 15% and 40%; (3) carbohydrate types (glucose v fructose v sucrose v starch v unrefined carbohydrate); and (4) diets containing 30% fat but differing in fatty acid composition (long-chain triglycerides [LCT] v medium-chain triglycerides [MCT] v oleic v linoleic v alpha-linolenic metabolites eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA] omega-3 fatty acids). Changes were only observed for extreme diets, ie, those deficient in protein or very high in fat. Low-protein diet was the only condition in which the high metabolic efficiency characteristic of the refeeding period was partially suppressed, and this occurred despite a lack of concomitant reduction in body fat deposition. On the contrary, with high-fat diets (> 30% of dietary energy consumption) the elevated efficiency was further increased, an effect that was only partially accounted for by the lower energy cost of body fat gain from high-fat diets. These studies indicate that during body weight recovery, the mechanisms underlying the adaptive increase in metabolic efficiency favoring the replenishment of body fat stores override any effect of food type on thermogenesis, and suggest some convergence in the controlling neural pathway. The implications of these findings vis-a-vis nutritional rehabilitation (catch-up growth) and obesity relapse are discussed.

Animals↗
PubMed1992

Fish oil decreases natural resistance of mice to infection with Salmonella typhimurium.

Mortality rate in mice fed fish oil for 4 weeks was remarkably higher after a very low peroral (PO) challenge with Salmonella typhimurium, as compared with those fed diets rich in either corn oil or hydrogenated coconut oil, or a low fat (chow) diet. None of the surviving mice fed the fish oil diet showed bacterial counts in their spleens, unlike 45.4% to 66.6% of surviving mice fed high fat or low fat diets. The spleens of mice fed fish oil presented the highest number of bacteria 7 days after intraperitoneal infection with the same bacterial strain. Thus, the current studies demonstrate that a diet rich in fish oil decreases host resistance to infection.

Adipose Tissue↗