Lack of metabolic and behavioral adaptations in rural Gambian men with low body mass index.

Energy expenditure was measured by means of a respiratory chamber in two groups of adult rural Gambian men. The first group (n = 29) had a low body mass index (BMI; in kg/m2) < 18.5), whereas the control group (n = 29) had a higher BMI (> 22). This study shows that the energy expenditure of Gambian men with low BMI is not different from that of Gambian men with normal BMI when the results are normalized for fat-free mass or for weight by analysis of covariance. In Gambian men the nutritional status thus does not seem to affect energy metabolism notably. No differences in respiratory quotient, diet-induced thermogenesis, net work efficiency, spontaneous physical activity, heart rate, or urinary catecholamine excretion were observed between the two groups. It is, however, interesting to note that the basal metabolic rate of Gambian men, regardless of their nutritional status, is approximately 10% (range 4-12% depending on the reference value used) lower than that predicted for individuals living in industrialized countries.

The lack of effect of insulin on luteinizing hormone pulsatility in healthy male volunteers provides evidence of a sexual dimorphism in the metabolic regulation of reproductive hormones.

BACKGROUND: The activity of the neuroendocrine reproductive axis is closely related to nutritional status. This link is particularly important in healthy women, in whom insulin is a positive signal for the reproductive system. In contrast, very little is known regarding this relation in men. OBJECTIVES: This study was designed to evaluate the effect of insulin on the reproductive axis of young male volunteers and to study the effect of short-term hypercaloric feeding on this modulation. DESIGN: The activity of the neuroendocrine reproductive axis was characterized by the pattern of endogenous luteinizing hormone (LH) secretion on the basis of frequent blood sampling protocols. The effect of insulin was tested by comparing the LH secretion pattern between a baseline study and a hyperinsulinemic euglycemic clamp. These studies were performed first in subjects fed a controlled isocaloric diet for 6 d (calculated as 1.5 times their resting metabolic rate) then in the same subjects fed a controlled hypercaloric diet in which 30% extra calories were provided as fat and fructose (3 g · kg(-1) · d(-1)) before undergoing identical protocols. Serum gonadotropins, sex steroids, glucose, insulin, ghrelin, and leptin concentrations were assessed, and the HOMA-IR was calculated. RESULTS: The LH secretion pattern was not affected by insulin or by hypercaloric feeding. Insulin decreased ghrelin and increased leptin concentrations but had no additional effect of hypercaloric feeding despite significantly lower HOMA-IR indexes. CONCLUSIONS: Our data indicate that neither insulin nor short-term hypercaloric feeding has any effect on the activity of the male reproductive axis. They also further support the association between ghrelin and insulin and glucose metabolism. This trial was registered at clinicaltrials.gov as NCT01058681.

Does metabolic compensation explain the majority of less-than-expected weight loss in obese adults during a short-term severe diet and exercise intervention?

Objective:We investigated to what extent changes in metabolic rate and composition of weight loss explained the less-than-expected weight loss in obese men and women during a diet-plus-exercise intervention.Design:In all, 16 obese men and women (41±9 years; body mass index (BMI) 39±6 kg m(-2)) were investigated in energy balance before, after and twice during a 12-week very-low-energy diet(565-650 kcal per day) plus exercise (aerobic plus resistance training) intervention. The relative energy deficit (EDef) from baseline requirements was severe (74%-87%). Body composition was measured by deuterium dilution and dual energy X-ray absorptiometry, and resting metabolic rate (RMR) was measured by indirect calorimetry. Fat mass (FM) and fat-free mass (FFM) were converted into energy equivalents using constants 9.45 kcal per g FM and 1.13 kcal per g FFM. Predicted weight loss was calculated from the EDef using the '7700 kcal kg(-1) rule'.Results:Changes in weight (-18.6±5.0 kg), FM (-15.5±4.3 kg) and FFM (-3.1±1.9 kg) did not differ between genders. Measured weight loss was on average 67% of the predicted value, but ranged from 39% to 94%. Relative EDef was correlated with the decrease in RMR (R=0.70, P<0.01), and the decrease in RMR correlated with the difference between actual and expected weight loss (R=0.51, P<0.01). Changes in metabolic rate explained on average 67% of the less-than-expected weight loss, and variability in the proportion of weight lost as FM accounted for a further 5%. On average, after adjustment for changes in metabolic rate and body composition of weight lost, actual weight loss reached 90% of the predicted values.Conclusion:Although weight loss was 33% lower than predicted at baseline from standard energy equivalents, the majority of this differential was explained by physiological variables. Although lower-than-expected weight loss is often attributed to incomplete adherence to prescribed interventions, the influence of baseline calculation errors and metabolic downregulation should not be discounted.

Developmental, metabolic and immunological costs of flea infestation in the common vole

Parasites use resources from their hosts, which can indirectly affect a number of host functions because of trade-offs in resource allocation. In order to get a comprehensive view of the costs imposed by blood sucking parasites to their hosts, it is important to monitor multiple components of the development and physiology of parasitized hosts over long time periods. The effect of infestation by fleas on body mass, body length growth, haematocrit, resistance to oxidative stress, resting metabolic rate and humoral immune response were experimentally evaluated. During a 3-month period, male common voles, Microtus arvalis, were either parasitized by rat fleas (Nosopsyllus fasciatus), which are naturally occurring generalist ectoparasites of voles, or reared without fleas. Then voles were challenged twice by injecting Keyhole Limpet Haemocyanin (KLH) to assess whether the presence of fleas affects the ability of voles to produce antibodies against a novel antigen. During the immune challenge we measured the evolution of body mass, haematocrit, resistance to oxidative stress and antibody production. Flea infestation negatively influenced the growth of voles. Moreover, parasitized voles had reduced haematocrit, higher resting metabolic rate and lower production of antibodies against the KLH. Resistance to oxidative stress was not influenced by the presence of fleas. During the immune challenge with KLH, body mass decreased in both groups, while the resistance to oxidative stress remained stable. In contrast, the haematocrit decreased only in parasitized voles. Our experiment shows that infestation by a haematophageous parasite negatively affects multiple traits like growth, energy consumption and immune response. Fleas may severely reduce the survival probability and reproductive success of their host in natural conditions.

Metabolic equivalent: one size does not fit all.

The metabolic equivalent (MET) is a widely used physiological concept that represents a simple procedure for expressing energy cost of physical activities as multiples of resting metabolic rate (RMR). The value equating 1 MET (3.5 ml O2 x kg(-1) x min(-1) or 1 kcal x kg(-1) x h(-1)) was first derived from the resting O2 consumption (VO2) of one person, a 70-kg, 40-yr-old man. Given the extensive use of MET levels to quantify physical activity level or work output, we investigated the adequacy of this scientific convention. Subjects consisted of 642 women and 127 men, 18-74 yr of age, 35-186 kg in weight, who were weight stable and healthy, albeit obese in some cases. RMR was measured by indirect calorimetry using a ventilated hood system, and the energy cost of walking on a treadmill at 5.6 km/h was measured in a subsample of 49 men and 49 women (26-45 kg/m2; 29-47 yr). Average VO2 and energy cost corresponding with rest (2.6 +/- 0.4 ml O2 x kg(-1) x min(-1) and 0.84 +/- 0.16 kcal x kg(-1) x h(-1), respectively) were significantly lower than the commonly accepted 1-MET values of 3.5 ml O2 x kg(-1) x min(-1) and 1 kcal x kg(-1) x h(-1), respectively. Body composition (fat mass and fat-free mass) accounted for 62% of the variance in resting VO2 compared with age, which accounted for only 14%. For a large heterogeneous sample, the 1-MET value of 3.5 ml O2 x kg(-1) x min(-1) overestimates the actual resting VO2 value on average by 35%, and the 1-MET of 1 kcal/h overestimates resting energy expenditure by 20%. Using measured or predicted RMR (ml O2 x kg(-1) x min(-1) or kcal x kg(-1) x h(-1)) as a correction factor can appropriately adjust for individual differences when estimating the energy cost of moderate intensity walking (5.6 km/h).

Comparison of the metabolic and endocrine effects of 3,5,3'-triiodothyroacetic acid and thyroxine.

To test the hypothesis that 3,5,3'-triiodothyroacetic acid (Triac) is more active as a TSH suppressor than on peripheral parameters of thyroid hormone action, the following parameters were studied: basal metabolic rate, sleeping energy expenditure (SEE), sex hormone-binding globulin, and cholesterol. In a double blind trial, 14 subjects received during 3 weeks (phase 1) 180 micrograms T4 or 1700 micrograms Triac daily, divided into 3 doses, to suppress thyroidal secretion. The dosage was doubled for the next 3 weeks (phase 2). Under T4 treatment, TSH reached 0.11 mU/L during phase 1 and less than 0.03 mU/L during phase 2. With Triac, a marked TSH inhibition occurred after 1 week (0.17 mU/L), followed by an escape during the following 2 weeks (0.63 mU/L). During phase 2, an almost complete TSH suppression was obtained (0.03 mU/L). Both Triac doses suppressed endogenous thyroid hormone secretion, as evidenced by T4 and rT3 levels. Both substances induced a 2-fold stimulation of sex hormone-binding globulin during phase 2. Serum cholesterol decreased similarly, without affecting the high/low density lipoprotein ratio. T4 increased SEE by 4.1% and 8.5% during phases 1 and 2. Triac failed to induce the expected peripheral metabolic responses of the thyroid hormones, as demonstrated by an unchanged SEE and basal metabolic rate. These results clearly show a preferential action of Triac on TSH suppression.

Pure amnesia after unilateral left polar thalamic infarct: topographic and sequential neuropsychological and metabolic (PET) correlations.

A 54-year-old patient who had an isolated small polar thalamic infarct and acute global amnesia with slight frontal type dysfunction but without other neurological dysfunction was studied. Memory improved partially within 8 months. At all stages the impairment was more severe for verbal than non-verbal memory. Autobiographic recollections and newly acquired information tended to be disorganised with respect to temporal order. Procedural memory was unaffected. Both emotional involvement and pleasure in reading were lost. On MRI, the infarct was limited to the left anterior thalamic nuclei and the adjacent mamillothalamic tract. The regional cerebral metabolic rate of glucose (measured with PET) was decreased on the left in the thalamus, amygdala, and posterior cingulate cortex 2 weeks after the infarct, and in the thalamus and posterior cingulate cortex 9 months later. These findings stress the specific role of the left anterior thalamic region in memory and confirm that longlasting amnesia from a thalamic lesion can occur without significant structural damage to the dorsomedial nucleus. Furthermore, they suggest that the anterior thalamic nuclei and possibly their connections with the posterior cingulate cortex play a role in emotional involvement linked to ipsilateral hemispheric functions.

Cycle length of spermatogenesis in shrews (mammalia: soricidae) with high and low metabolic rates and different mating systems.

The aim of the present study was to establish and compare the durations of the seminiferous epithelium cycles of the common shrew Sorex araneus, which is characterized by a high metabolic rate and multiple paternity, and the greater white-toothed shrew Crocidura russula, which is characterized by a low metabolic rate and a monogamous mating system. Twelve S. araneus males and fifteen C. russula males were injected intraperitoneally with 5-bromodeoxyuridine, and the testes were collected. For cycle length determinations, we applied the classical method of estimation and linear regression as a new method. With regard to variance, and even with a relatively small sample size, the new method seems to be more precise. In addition, the regression method allows the inference of information for every animal tested, enabling comparisons of different factors with cycle lengths. Our results show that not only increased testis size leads to increased sperm production, but it also reduces the duration of spermatogenesis. The calculated cycle lengths were 8.35 days for S. araneus and 12.12 days for C. russula. The data obtained in the present study provide the basis for future investigations into the effects of metabolic rate and mating systems on the speed of spermatogenesis.

Inhibition of Na(+)-K(+)-ATPase by digoxin and its relation with energy expenditure and nutrient oxidation rate.

This study investigates the effects of digoxin, an inhibitor of the Na+ pump (Na(+)-K(+)-ATPase), on resting metabolic rate (RMR), respiratory quotient (RQ), and nutrient oxidation rate. Twelve healthy male subjects followed a double-blind protocol design and received either 1 mg/day digoxin or a placebo 2 days before indirect calorimetry measurements. Digoxin induced a 0.22 +/- 0.07 kJ/min or 3.8 +/- 1.5% (mean +/- SE, P = 0.01) decrease in RMR and a 0.40 +/- 0.13 kJ/min (P = 0.01) decrease in fat oxidation rate, whereas carbohydrate and protein oxidation rates did not change significantly. A dose-response relationship between serum digoxin and RQ was observed. These results suggest that digoxin reduces not only RMR but also fat oxidation rate by mechanisms that remain to be elucidated. Because a linkage and an association between genes coding the Na(+)-K(+)-ATPase and the RQ have been previously observed, the present demonstration of an effect of Na(+)-K(+)-ATPase inhibition on fat oxidation rate strengthens the concept that the activity of this enzyme may play a role in body weight regulation.

Markedly blunted metabolic effects of fructose in healthy young female subjects compared with male subjects.

OBJECTIVE: To compare the metabolic effects of fructose in healthy male and female subjects. RESEARCH DESIGN AND METHODS: Fasting metabolic profile and hepatic insulin sensitivity were assessed by means of a hyperglycemic clamp in 16 healthy young male and female subjects after a 6-day fructose overfeeding. RESULTS: Fructose overfeeding increased fasting triglyceride concentrations by 71 vs. 16% in male vs. female subjects, respectively (P &lt; 0.05). Endogenous glucose production was increased by 12%, alanine aminotransferase concentration was increased by 38%, and fasting insulin concentrations were increased by 14% after fructose overfeeding in male subjects (all P &lt; 0.05) but were not significantly altered in female subjects. Fasting plasma free fatty acids and lipid oxidation were inhibited by fructose in male but not in female subjects. CONCLUSIONS: Short-term fructose overfeeding produces hypertriglyceridemia and hepatic insulin resistance in men, but these effects are markedly blunted in healthy young women.

Effects of beta-blockade on energy metabolism following burns.

The purpose of this study was to compare the effects of propranolol administered either by i.v. infusion or by prolonged oral administration (4 days) during the first 3 weeks following burns. The resting metabolic rate (RMR) of 10 non-infected fasting burned patients (TBSA: 28 per cent, range 18-37 per cent) was determined four times consecutively by indirect calorimetry (open circuit hood system) following: (1) i.v. physiological saline; (2) i.v. propranolol infusion (2 micrograms/kg/min following a bolus of 80 micrograms/kg); (3) oral propranolol (40 mg q.i.d. during 4 +/- 1 days); and (4) in control patients. All patients showed large increases in both RMR (144 +/- 2 per cent of reference values) and in urinary catecholamine excretion (three to four times as compared to control values). The infusion of propranolol induced a significant decrease in RMR to 135 +/- 2 per cent and oral propranolol to 129 +/- 3 per cent of reference values. A decrease in lipid oxidation but no change in carbohydrate and protein oxidation were observed during propranolol administration. It is concluded that the decrease in RMR induced by propranolol was not influenced by the route of administration. The magnitude of the decrease in energy expenditure suggests that beta-adrenergic hyperactivity represents only one of the mediators of the hypermetabolic response to burn injury.

Markedly blunted metabolic effects of fructose in healthy young females compared to males

ABSTRACT : Objective: to compare the metabolic effects of fructose in healthy males and females Research Design And Methods: Fasting metabolic profile and hepatic insulin sensitivity were assessed by means of a hyperglycemic clamp in 16 healthy young males and female subjects after a 6-day fructose overfeeding Results: Fructose overfeeding increased fasting triglyceride concentrations by 71 % in males vs 16% in females (p<0.05). Endogenous glucose production was increased by 12%, alanin aminotransferase concentration was increased by 38%, and fasting insulin concentrations was increased by 14% after fructose overfeeding in males (all p<0.05), but were not significantly altered in females. Fasting plasma free fatty acids and lipid oxidation were inhibited by fructose in males, but not in females Conclusions: Short term fructose overfeeding produces hypertriglyceridemia and hepatic insulin resistance in males, but these effects are markedly blunted in healthy young females. Rapport de synthèse : Objectif : De récentes études ont démontré que l'ingestion de hautes doses de fructose modifie certains paramètres métaboliques. Peu d'entre elles se sont cependant intéressées à déterminer si les effets métaboliques du fructose étaient dépendants du sexe. L'objectif de la présente étude était donc de comparer les effets du fructose chez des volontaires sains, hommes et femmes. Méthode : Le profil métabolique à jeun et la sensibilité hépatique à l'insuline ont été déterminés au moyen d'un clamp hyperglycémique chez un collectif de 16 jeunes hommes et femmes après une période de 6 jours de régime riche en fructose. Résultats : La concentration de triglycérides à jeun après ce régime était augmentée de 71% chez les hommes contre 16% chez les femmes (p<0.05). La production endogène de glucose était augmentée de 12%, l'alanine aminotransférase de 38% et la concentration d'insuline à jeun de 14% chez les hommes (p<0.05 pour tous). Chez les femmes, ces paramètres n'étaient au contraire pas significativement modifiés. L'oxydation des acides gras libres et des lipides à jeun était inhibée par le fructose chez les hommes, mais pas chez les femmes. Conclusion : Ces résultats indiquent qu'une suralimentation de courte durée en fructose induit chez l'homme une hypertriglycéridémie et une résistance hépatique à l'insuline, alors que chez la femme jeune, ces effets sont nettement atténués. Il reste à éclaircir de manière plus approfondie les mécanismes sous-tendant ces différences.

Macronutrients and energy balance in obesity.

Energy balance is the difference between metabolizable energy intake and total energy expenditure. Energy intake is difficult to measure accurately; changes in body weight, for example, are not a good measure of the adequacy of energy intake, because fluctuations in body weight are common even if the overall trend is toward weight loss. It is now customary to assess energy requirements indirectly from total energy expenditure. Total energy expenditure consists of basal metabolism, postprandial thermogenesis, and physical activity. Energy expenditure is related to both body weight and body composition. A reduction in total energy expenditure accompanies weight loss, because basal metabolic rate decreases with the loss of lean tissue mass. Similarly, with weight gain, there is an increase in basal metabolic rate, because lean tissue mass grows to support the increase in fat tissue mass. Excess energy intake over energy expenditure causes weight gain and an accompanying increase in total energy expenditure. Following a period of adaptation, total energy expenditure will match energy intake and body weight will stabilize at a higher level. This same relationship holds for weight loss. Respiratory quotient (measured in steady state) is an indication of the proportion of energy expenditure derived from fat and carbohydrate oxidation. Over long periods of time, fat balance is equivalent to energy balance, as an excess of fat intake over fat oxidation causes fat storage.

Thermogenic effect of amrinone in healthy men.

OBJECTIVES: The thermogenic effect of amrinone is unknown and its utilization in patients with severe cardiac failure could potentially increase oxygen requirements and therefore aggravate oxygen debt. Consequently, the present study was undertaken to assess the thermogenic response to amrinone at three different plasma concentrations under controlled conditions and to analyze amrinone's effects on various biochemical variables. DESIGN: A prospective, unblinded, controlled study. The initial control period was followed by three sequential, experimental treatments. SUBJECTS: Ten young, healthy, male volunteers with normal body weight. INTERVENTIONS: Three experimental periods. Amrinone was administered intravenously in progressive doses: a) 0.5 mg/kg followed by 5 micrograms/kg/min; b) 0.5 mg/kg followed by 10 micrograms/kg/min; and c) 1.0 mg/kg followed by 10 micrograms/kg/min. MEASUREMENTS AND MAIN RESULTS: Oxygen consumption (VO2) and CO2 production were continuously measured by means of a computerized indirect calorimeter. At the highest dose, amrinone produced a slight and significant (p < .01) increase in VO2 and in resting metabolic rate (+4.5% and +3.7%, respectively), while no change in CO2 production or in respiratory quotient occurred throughout the study. At the medium and high doses, amrinone increased plasma free fatty acid concentrations by 38% and 53%, respectively (p < .05). No variation in plasma glucose, lactate, insulin, norepinephrine, or epinephrine concentrations was observed during the study. CONCLUSIONS: Amrinone administered intravenously at therapeutic doses has minimal thermogenic and metabolic effects in humans without cardiac failure.

Increased 24-hour energy expenditure in cigarette smokers.

We studied the effect of smoking on energy expenditure in eight healthy cigarette smokers who spent 24 hours in a metabolic chamber on two occasions, once without smoking and once while smoking 24 cigarettes per day. Diet and physical exercise (30 minutes of treadmill walking) were standardized on both occasions. Physical activity in the chamber was measured by use of a radar system. Smoking caused an increase in total 24-hour energy expenditure (from a mean value [+/- SEM] of 2230 +/- 115 to 2445 +/- 120 kcal per 24 hours; P less than 0.001), although no changes were observed in physical activity or mean basal metabolic rate (1545 +/- 80 vs. 1570 +/- 70 kcal per 24 hours). During the smoking period, the mean diurnal urinary excretion of norepinephrine (+/- SEM) increased from 1.25 +/- 0.14 to 1.82 +/- 0.28 micrograms per hour (P less than 0.025), and mean nocturnal excretion increased from 0.73 +/- 0.07 to 0.91 +/- 0.08 micrograms per hour (P less than 0.001). These short-term observations demonstrate that cigarette smoking increases 24-hour energy expenditure by approximately 10 percent, and that this effect may be mediated in part by the sympathetic nervous system. The findings also indicate that energy expenditure can be expected to decrease when people stop smoking, thereby favoring the gain in body weight that often accompanies the cessation of smoking.